HKU Bulletin November 2024 (Vol. 26 No. 1)

SOLITARY LIVES The global epidemic of loneliness Preserving silent voices Efforts to document the endangered Hong Kong Sign Language Towards hepatitis B elimination An all-round battle from community testing to drug development NOV 2024 Volume 26 No.1

24 02 30 42 36 02 04 06 08 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 CONTENTS Cover Story Solitary Lives More than a Feeling A Slippery Slope to Depression A Measure of the Problem Neighbourhood Effects Relief for the Lonesome Research The Fear Factor Hep to a Cure Maternal Instinct Invisible Engineers The Bigger Picture Star Quality Pet Project When Foreign Governments Meddle in Elections Teaching and Learning Easing Clinical Nerves A Year at the Museum Knowledge Exchange Clime and Tide A Bionic Slice of Life Pepping up the Pooch A Voice for the Deaf People Reels of Integrity Books Going Viral Tipping the Scales for Public Health SOLITARY LIVES Late last year, the World Health Organization launched a new commission tasked with assessing loneliness “as a pressing public health threat”. The announcement came on a groundswell of research showing loneliness can worsen mental and physical health. HKU researchers have been studying the scale and nature of the problem, and possible solutions. A BIONIC SLICE OF LIFE STAR QUALITY 14 34 44 EASING CLINICAL NERVES REELS OF INTEGRITY GOING VIRAL CLIME AND TIDE THE FEAR FACTOR

In late 2023, the World Health Organization launched a new commission tasked with assessing loneliness “as a pressing public health threat”. The announcement came on a groundswell of research showing loneliness can worsen mental and physical health. HKU researchers have been studying the scale and nature of the problem, and possible solutions. SOLITARY LIVES COVER STORY HKU BULLETIN | NOV 2024 02 03

“I think we have largely failed so far in dealing with loneliness because our definition is too narrow.” Dr Zohar Lederman When Dr Zohar Lederman was an emergency medicine doctor in Israel, he was struck by how many patients did not want to go home because they had no one to go home to. They often ended up in the hospital longer than their condition warranted, but medical staff were not trained nor evaluated on how to help such people. “It was heartbreaking. These patients were really out of the realm of emergency medicine,” he said. The situation inspired him to delve deeper into the problem of loneliness. The results, in both Bioethicist Dr Zohar Lederman has been exploring the philosophical implications of the individual and social harm caused by loneliness, and practical solutions. MORE THAN A FEELING philosophical and scientific terms, were stark: loneliness puts people at higher risk of stroke, anxiety, dementia, depression, suicide and other diseases, and it is common. “Loneliness makes you sicker and increases your risk of premature death. Basically, it’s a kind of social determinant of health,” he said. Dr Lederman, now Clinical Practitioner in HKU’s Department of Emergency Medicine in the School of Clinical Medicine and Research Fellow in the Centre for Medical Ethics and Law, has been investigating how to mitigate the problem and better understand the implications for society from medical and bioethics perspectives – particularly as surveys show that loneliness affects onethird of people in Hong Kong and Mainland China, about 40 per cent in Japan and one in two in the US. “I believe there is an ethical case to engage more systematically with loneliness, first of all as a public health issue and secondly, as a deeply fundamental issue for human beings that goes beyond human health. I think we have largely failed so far in dealing with loneliness because our definition is too narrow,” he said. Lots of kinds of loneliness Traditionally, loneliness has been considered a distressful mismatch between expected and perceived social relations. But social scientists have proposed that it can come in many forms, he said. Political theorists such as Hannah Arendt talk of political loneliness in which people are deprived of political participation and feel alienated from the process, such as Palestinians in the West Bank and Gaza. There is also ethical loneliness, where someone suffers a great injustice such as the Holocaust but does not feel heard or understood when they talk about the experience. And there are things like a lonely death, sexual loneliness or the loneliness of people with disabilities that hinder their communication with others. Caretakers can also feel lonely. Dr Lederman said these are not simply alienating experiences. Since people have evolved to be social and interdependent, loneliness should be seen within that context. “If one recognises that not being lonely is important to human life and human flourishing, and that people have an entitlement or right not to feel lonely in much the same way they have a right to health, then there are ethical implications for governments and society,” he said. The World Health Organization has recognised some of the implications with the establishment of the Commission on Social Connection in November 2023, which is intended to galvanise countries to act. Some have already started. The UK and Japanese governments both have ministries of loneliness. Examples of government actions include mobile cafes that bring people together, subsidised socialisation classes and investment in social robots. Investigating the problem and solutions Dr Lederman has also been investigating how to mitigate loneliness. One project has focussed on social robots that interact and chat with people, although he thinks these are a far from perfect solution. “Intuitively, it feels wrong that human society should decide to care for the lonely by throwing technology at them. But from an academic perspective, we try to be more generous. We have done some work on them and it’s plausible they can help some people as a last resort or a temporary measure,” he said. He also hopes to dovetail his two interests – emergency medicine and bioethics – to investigate loneliness in the emergency departments of Hong Kong hospitals. The yet-to-befunded project aims to determine whether people coming to the hospital are lonelier than those in the community and whether there are correlations between feeling lonely, hospitalisation, mental health outcomes, recurrent visits and the use of healthcare services. The project also hopes to map the available social services for mitigating loneliness. “Loneliness is not only bad for human beings. It can be bad for the economy. If we want to promote public policies that are effective and cost-effective, that’s another reason to engage more seriously with the problem of loneliness,” he said. COVER STORY HKU BULLETIN | NOV 2024 04 05

“We know loneliness is a highrisk factor, so if we can do something to reduce it, it will lower the risk of developing mental health problems.” Professor Tatia Mei-chun Lee As many as 40 per cent of middle-aged and elderly adults may suffer from chronic loneliness, meaning there is a discrepancy between their preferred and actual social relations. That puts them at risk for depression. But what is the mechanism that links the two? Professor Tatia Mei-chun Lee, Chair Professor of Psychological Science and Clinical Psychology and May Professor in Neuropsychology, is a pioneer in researching the problem of loneliness in Chinese populations from behavioural and neuroscience perspectives, with the hope of finding a pathway for helping sufferers. Working with local, national, and international collaborators, Professor Lee has been studying to affective pictures. They also completed a standard loneliness survey to measure their perceived loneliness. The results showed weaker structural connectivity between key parts of the brain among those who reported feeling lonely. They also had stronger brain activity in response to negative emotional images, suggesting loneliness facilitated hypervigilance to emotions that posed a social threat. Depleted resources Professor Lee noted that while the brain typically changes in response to experience, “rarely has this been shown in relation to an intangible experience like loneliness. Feeling lonely leaves marks on the brain.” She also did a study showing how loneliness and late-life depression interact in the brain. The number of depressive episodes was found to increase when a person’s perceived loneliness increased. Initially, that increase activated the striatum in the brain – a neural region responsible for reward sensitivity and reward learning. However, after multiple depressive episodes, this activation decreased. Professor Lee’s explanation is that with the first depressive episodes, the brain may work hard to compensate. “It may be that after repeated depressive episodes, their resources become depleted. That’s why there’s a changing relationship. This is our speculation.” She and her team have also looked at how cognitive status and higher cognitive functions are affected when depressed people feel lonely. Unsurprisingly, there is a negative impact. However, Professor Lee’s team member, Professor Robin Shao Zhengxi, Assistant Professor (Research), was able to tease out the different impacts of depression and loneliness. Among middle-aged adults performing a cognitive task measuring executive control functions, depression was associated with more errors, while loneliness was associated with faster response time, showing that depression and loneliness impact executive control functions in different ways. Correspondingly, depression and loneliness were also associated with opposite patterns of brain functional connectivity during task performance. “The better executive control performance and stronger functional connectivity of the high loneliness individual may imply enhanced top-down cognitive control. Maybe they are using that to try to regulate the very uncomfortable feeling of loneliness. But when they do that in the long term, this upregulation might lead to exhaustion of high-level cognitive resources, and the Professor Tatia Mei-chun Lee and her colleagues have been investigating brain activity to see how loneliness can tip people into depression and what might be done to mitigate the effects. person may then develop a mood disorder,” Professor Lee said, adding that this, too, was speculation. Other risks and possible remedies Professor Lee has also found that loneliness can interact with rumination to exacerbate depression. While negative rumination, or brooding, is known to be associated with depression, her research showed that it is of greatest risk when a person ruminates on being lonely. Another known depression risk factor – childhood experience of emotional neglect – was also found to be mediated through loneliness. Explaining the neural effects of loneliness is not Professor Lee’s only interest. She has also been looking at how to mitigate the problem. One project used a specially designed, eight-week meditation training programme and found a significant causeand-effect relationship, with participants less affected by emotional stimuli after the training. She is also leading a Collaborative Research Fund project on psychological resilience, which relates to how quickly one can recover from psychological challenges and trauma, and how resilience relates to mental health. “We study loneliness to understand how it impacts neural functions and our behaviours so we can then look at how to manage it and promote well-being. We know loneliness is a high-risk factor, so if we can do something to reduce it, it will lower the risk of developing mental health problems,” she said. the patterns in the brain related to loneliness and how these interlink with depression, rumination, and higher cognitive functions. “I became interested in loneliness because number one, it is a significant threat to mental health. And number two, because people now live longer and the risk of feeling lonely also increases,” she said. Her team’s first major study, published in 2016, identified a neural network in the brain associated with feelings of loneliness. Subjects underwent a functional magnetic resonance imaging (fMRI) scan to look at their brain in a resting state and in response A SLIPPERY SLOPE TO DEPRESSION COVER STORY HKU BULLETIN | NOV 2024 06 07

HKU scholars have been investigating the effects of loneliness and social isolation in different cultures and the possibility of having a universal framework to identify people at risk. A MEASURE OF THE PROBLEM “We can only capture how people feel in the moment. We don’t have very concrete concepts or measures beyond things like a self-reporting loneliness scale.” Professor Benjamin Ho Mu-hsing On the surface, determining a person’s sense of loneliness and social isolation should be straightforward: just ask them how they feel and who they are socially connected with. But the reality is much more complicated, says Professor Chen Yu-chih, Assistant Professor of Social Work and Social Administration, who is working with collaborators in the US, UK and South Korea in response to a call from the World Health Organization for a measure that would allow for international comparisons. While standardised questionnaires for loneliness exist, different countries have different ideas about what makes a person socially isolated. “Social isolation is about things like social network size and quality, social participation, social support and proximity to people. In China, living in a rural area is considered an indicator of social isolation. In the UK and US, participation in religious activities, such as attending church, is a measure,” he said. “We are using large datasets of about 20,000 people each from China, the UK, US and South Korea to try to find more general denominators.” The data, collected between 2011 and 2018, is also allowing Professor Chen to test the connections between physical activity, depression, social isolation and health. While the full results will not be available for at least another year, a couple of interesting early findings have emerged. One is a correlation of sorts between social isolation and loneliness. While people can feel lonely yet not be socially isolated, or vice versa, if they are both lonely and isolated, they have a higher risk of severe mental distress. The other result is a lower reporting of loneliness in China, which Professor Chen said may be attributable to cultural reasons. “Chinese people tend not to share their feelings so that may be why they report a lower rate of loneliness,” he said. He will dig deeper into this as the full results emerge. Reluctance to engage Professor Benjamin Ho Mu-hsing, Assistant Professor of Nursing, has also found that it can be difficult to get lonely people to join qualitative studies and accept interventions. He has been working with data from more than 10,700 older adults in the 2018 China Health and Retirement Longitudinal Study, in which 28 per cent reported feeling lonely. “People who suffer from loneliness won’t usually come to an interview and share what they think, so it is frustrating,” he said. “We can only capture how people feel in the moment. We don’t have very concrete concepts or measures beyond things like a self-reporting loneliness scale.” His attempts to use robots and pets in Taiwan and New Zealand have also shown the limits of interventions when lonely people are unreceptive to outreach – those most lonely or isolated are less willing to interact. Professor Ho thinks it might be better to categorise loneliness as a variable rather than a focus itself and try to treat it alongside depression or other mental health issues with things like cognitive behavioural therapy. The young are lonely, too Medical sociologist Professor Tarani Chandola of the Department of Sociology has also shown how loneliness has effects beyond mental health. He was part of a longitudinal study using data from the UK Biobank that found higher levels of loneliness among those aged over 50 were associated with higher levels of physical ill-health, including mobility and cognitive frailty, and higher mortality. Life events, such as widowhood and the death of friends, were closely associated with feeling lonely. But that did not explain emerging evidence from another group – the 16 to 25 year-olds in Britain are the loneliest group in their society, followed by those over 65. “This is becoming more and more common. Mental health issues, which never used to be too bad for young adults, have increased quite dramatically in the last 10 or 20 years. And that’s correlated with a very large increase in loneliness around the world amongst young people,” he said. Possible causes could be the rise of social media and an increase in online gaming, alongside traditional factors like inadequate sleep. People under 40 are also more susceptible to the negative effects of toxic relationships, which Professor Chandola found in other research he did measuring levels of biological stress. “There tends to be a focus on older people when it comes to loneliness, but perhaps it is even more important to look at what is happening amongst young people,” he said. He is now investigating the different effects of social isolation and loneliness on biological stress markers because these would entail different kinds of interventions. If loneliness is the main factor, then therapy might be the best approach. If social isolation is driving both stress and loneliness, then it may be better to do more work fostering social connections. “We need more research to be done on this gap,” he said. COVER STORY HKU BULLETIN | NOV 2024 08 09

Evidence shows that urban density and planning can have direct effects on social isolation and loneliness. Therein could lie a solution, says urban scientist Professor Chinmoy Sarkar. NEIGHBOURHOOD EFFECTS “With demographic shifts to ageing societies, the way we design and pack our cities will be the key to creating multifunctional and interactive neighbourhoods that promote social well-being and longevity.” Professor Chinmoy Sarkar Cities have been associated with many things – more pollution, crime, inequality and traffic congestion. When they are poorly designed, with high population density, they can also increase social isolation and a sense of loneliness. This insight has been well-embedded in urban planning and design for years. But a study led by HKU was the first to support it with robust evidence, using a dataset of more than 400,000 subjects from the UK Biobank. Professor Chinmoy Sarkar, Associate Professor at the Department of Urban Planning and Design, was part of the team that showed, paradoxically, that being physically close to many people can leave us feeling lonely. “When there are higher densities, there will be more unwanted social contacts. If the quality of social contacts is not good, and there is a lack of privacy and social overload, then people tend to withdraw or confine themselves,” he said. “Unwanted social contacts have been found to cause a loss of social networks and social support and eventually lead to loneliness and social isolation.” Professor Sarkar and his colleagues drew on the UK Biobank, which contains information on people’s self-reported sense of loneliness and their social isolation in terms of engagement with other people, and compared this with their environment, such as residential unit density, walkability and greenness. They looked at one- and two-kilometre buffers around the places where individuals lived. For every increase of 1,000 units in the one-kilometre buffer, the odds of feeling lonely rose by 2.8 per cent while social isolation rose by 11 per cent. When that was broken down further, and the people in the top quartile of density were compared with the lower quartile, the odds increased by 14.4 per cent for loneliness in the upper quartile and 30.4 per cent for social isolation. Perception of safety The researchers also looked at housing types. People living in self-contained flats in high-density areas had the worst outcomes – those in the highestdensity of flats had increased odds of 9.6 per cent for loneliness and 28.9 per cent for social isolation versus those living in the lowest flat density. Conversely, living in detached housing actually had a higher protective or beneficial effect with increasing density – those in the highest density of detached housing had reduced odds of 13.2 per cent for loneliness and 20.2 per cent for social isolation versus the lowest density. There were also protective effects from such attributes as greenness, the density of public transport and walkability, or centrality, of a place. “If you are living in a detached house in the leafy suburbs with a garden or other defensible space, you have the perception of safety. You can sit in your garden and talk to your neighbours, which contributes to a sense of community and cohesion that may reduce your perception of loneliness or isolation. Whereas in apartment blocks, at least from my experience in Hong Kong and other high-density cities, you may not even know who your next-door neighbour is; hence the importance of designing functionally interactive public spaces in neighbourhoods,” he said. In all cases, the effects were more pronounced at the two-kilometre buffer, which Professor Sarkar said was due to the urban scaling effect, and among males and older people. Need to optimise density Loneliness and social isolation are both associated with poor mental and physical health, and he said the findings imply that government loneliness strategies need to take into account urban planning and policies, such as densification. “Optimising housing density and the mix of housing should be the cornerstone of any government’s population-wide policy that aims to enhance the social well-being and mental capacity of our population. This should happen alongside the design of neighbourhoods that allow people to interact in ways that help reduce the burden of social isolation and perceived or actual psychosocial stress,” he said. “After all, these policies affect millions of city residents. With demographic shifts to ageing societies, the way we design and pack our cities will be the key to creating multifunctional and interactive neighbourhoods that promote social well-being and longevity.” Professor Sarkar is also looking at the relationship between the living environment in Hong Kong and depression by measuring the build-up of the stress hormone, cortisol, in hair samples. And he is participating in a study looking at the effects of urban design and density on longevity in Hong Kong and the UK. COVER STORY HKU BULLETIN | NOV 2024 10 11

HKU researchers have been investigating interventions to help alleviate loneliness among Hong Kong’s elderly. RELIEF FOR THE LONESOME “We found that technology acceptance and subjective memory loss predict lifespace mobility, and that mobility is a very important mediator of the effect of loneliness.” Professor Doris Yu Sau-fung When the COVID-19 pandemic struck, Professor Doris Yu Saufung of the School of Nursing was overseeing a team of nurses working to identify and engage with ‘hidden elders’ – those who live alone – and bring them to community facilities for health assessments and counselling. The pandemic put a halt to that work, but team members saw a deep need in this group for social contact. They organised a getaround of ‘gate nursing’ where they stood at the gates of people’s homes and did exercises and provided them with psychological support. For Professor Yu, the experience revealed the vulnerability of older people in Hong Kong when it comes to loneliness. It has inspired her to dig deeper into the problem and apply those insights to her other research. In one study, she surveyed more than 10,000 older people in all 18 of Hong Kong’s districts and the results confirmed her concerns: 58 per cent of people aged over 65 reported being lonely. “The high prevalence calls for more attention to be paid to effective interventions for this growing public health problem,” she said. Professor Yu also undertook a detailed and systematic review of the literature on interventions to classify them in a consistent way and determine which had Social robots as companions Professor Vivian Lou Weiqun, Director of the Sau Po Centre on Ageing, has been collaborating with the Singapore University of Social Sciences to see if technology in the form of social robots can help relieve loneliness. These robots offer emotional support and a sense of connectedness, rather than just entertainment. A preliminary study of people aged from 60 to 75 living alone in Hong Kong and Singapore found that they fell into three groups: the practicalists, who wanted the robots to perform specific tasks such as medication reminders; the traditionalists, who were reluctant to acknowledge the robots as pets and wanted human contact; the best results. Psychological intervention, either alone or with other activities such as exercise, was found to be the most effective. “There are a lot of studies about psychological counselling and helping people build up their self-image. They may feel lonely because they don’t feel they are good at socialising. So self-esteem is a very important individualised factor contributing to loneliness,” she said. Loneliness and healthy ageing Professor Yu has incorporated loneliness into her work on healthy ageing. Building on earlier work on sarcopenia (muscle loss) in the elderly, she is looking at the environmental and social demographic factors associated with loneliness. The focus is on life-space mobility which captures ‘real-life mobility’ extending from one’s bedroom to the neighbourhood area and community, as well as technology acceptance and subjective memory loss – all of which can impact or interact with loneliness. “How often a person goes out depends not only on their physical ability but also on their psychological status and the social environment,” she said. “Our preliminary findings are significant. We found that technology acceptance and subjective memory loss predict life-space mobility, and that mobility is a very important mediator of the effect of loneliness.” On technology use, Professor Yu has also found that people who live alone, once trained on digital technology, tend to engage more with apps that have a psychological component, such as a laughing yoga app to boost mood, which supports her finding that psychological interventions could be important for combating loneliness. She has also found that it is best to engage with older adults in person, given many elderly are not familiar or comfortable with digital technology. That insight has been applied in other research she is doing to test apps that help people monitor heart disease – it motivated her to add a component where the app is paired with human interaction. Moving forward, Professor Yu will combine data on the physical environment, socio-economic demographics and loneliness surveys to see which factors are affecting or determining loneliness among Hong Kong’s elderly. She also has a project to train elderly people as health coaches that she hopes can engage people who live alone to become coaches. “I am thinking of how to use interventions that are not labelled as combating loneliness, but can still help older people tackle lonely feelings,” she said. and the enthusiasts, who enjoyed interacting with the robots. But while overall loneliness levels were reduced among subjects in Singapore, in Hong Kong “the loneliness level increased after initial interactions with ‘the robot’, which may be attributed to a desire for human interactions among study participants,” Professor Lou said. “Given the growing ageing trend, it is time to reconceptualise social relationships and companionship. Traditionally, it meant spending time with certain people, in particular family members. But we need to admit that more older adults are spending more time alone and social robots should be designed and introduced properly to them to allow greater acceptance.” COVER STORY HKU BULLETIN | NOV 2024 12 13

“Memory is like data in our brain and it affects our behaviour and our personality, but it’s not well understood.” Professor Cora Lai Sau-wan In the Hollywood movie, Eternal Sunshine of the Spotless Mind, characters get their memories erased to help them forget about bad relationships. It is one of Professor Cora Lai Sau-wan’s favourite films and it has inspired her in ways that show how life can imitate art. Using mouse models, Professor Lai and her team discovered new insights on how the brain responds to fear and how animals could be de-conditioned against a learnt fear response – essentially, have that memory erased – particularly during sleep. The animals had listened to a tone that was followed by a physical foot-shock and had developed a fear response – freezing in place – whenever they heard the tone later even without foot-shock. transmitted information is stored in the neuron’s dendrites, which have many little protrusions, like leaves on a branch, called dendritic spines, where memories are stored. During this memory-making process, Professor Lai and her team observed that the dendritic spines of animals undergoing fear learning respond differently depending on their location in the brain. “It was puzzling because when fear learning occurs, there are fewer dendritic spines in the frontal cortex [which controls things like memory, emotions and physical movement], whereas in other cortical regions, there are more dendritic spines,” she said. To examine that further, the team tested fear extinction – as in her favourite movie – by training the mouse to unlearn the fear that had become associated with the tone. They played the tone repeatedly but without a physical shock, and the mouse brain responded differently. It formed more dendritic spines very close to where it had previously eliminated the spines under fear conditioning in the frontal cortex. “Basically, that area is like a hotspot or plug. When there’s a need, the dendritic spine is removed. Once that need is gone, it is re-plugged close to the same spot,” Professor Lai said. “It is believed that memories are not stored randomly on neurons but through memory allocation, so similar memories are stored on the same dendrites. This is exactly what we observed.” She also detected changes in dendritic spines in another area of the brain, the auditory cortex which processed the tone sound, but in reverse. Here, fear conditioning led to more spine formation, but this was eliminated with fear extinction. “Through that study, we basically discovered that we could target a fear memory and erase it. It’s non-invasive, although it’s still experimental at this stage,” she said. “The aim of our laboratory is to get a better understanding of how memory is formed, how it is retrieved, how it is consolidated or reconsolidated. Memory is like data in our brain and it affects our behaviour and our personality, but it’s not well understood.” Branches, leaves and hotspots Professor Lai’s research on fear centres around the synapses of the brain, which change when we experience or learn something. Each of the brain’s neurons has many synapses that communicate with other neurons. The Professor Cora Lai Sau-wan of the School of Biomedical Sciences has deepened our understanding of where and how fear memories are stored in the brain – and shown how these memories could potentially be erased. THE FEAR FACTOR The role of sleep A big question underpinning all of this has been the role of sleep. Sleep is known to enhance memory, but other researchers have produced contradictory evidence when it came to fear learning – some found that sleep enhanced it, others that it inhibited it. Professor Lai and her team decided to look for clues in non-REM [rapid eye movement] sleep in relation to fear learning, but again the results were mixed. So they broke that down into slow-wave non-REM sleep, when the brain oscillation becomes very slow, and other non-REM sleep. “And voilà, we found opposite events. The slow-wave sleep actually enhanced fear consolidation and the other stages inhibited it. We found this effect not only in the animal’s behaviour, but in the dendritic spine plasticity,” she said. The results, recently published in Advanced Science, help explain why earlier evidence was contradictory. Professor Lai is now studying the mechanism to gain a deeper understanding of how and why the brain generates these different responses in fear learning. The research holds promise for psychiatric applications. A number of human studies have shown that specific memories can be reactivated during sleep, in a process called reconsolidation. The hope is her research could be developed to help sufferers of post-traumatic stress disorder by deactivating memories. “Our laboratory is not working on humans but we’re trying to look at the mechanism underlying that. That’s our next target,” Professor Lai said. She added that the current work is not only about excitatory neurons, but also inhibitory interneurons which act like brakes on the input state. A number of psychiatric disorders arise from dysfunctions in the excitatory-inhibitory balance, so there is potential to open pathways to treatments for these conditions, too. Electroencephalogram (EEG), electromyography (EMG) and a miniature microscope are used to observe the calcium responses of neurons in the frontal cortex and their relation to sleep and fear learning in mice. RESEARCH HKU BULLETIN | NOV 2024 14 15

“They think they are fine, they have no symptoms, so therefore they are not hepatitis B patients. But this is not true.” Professor Yuen Man-fung Chronic hepatitis B infection can remain asymptomatic for decades, yet left untreated, it can cause severe damage to the liver and lead to life-threatening conditions such as cirrhosis and liver cancer, the third leading cause of cancer deaths in Hong Kong. About 410,000 people in Hong Kong carry the hepatitis B virus, as do more than 257 million globally. The World Health Organization (WHO) has called for its elimination by 2030. A key contributor towards achieving that goal is Professor Yuen Man-fung, Chair Professor of Gastroenterology and Hepatology, and Li Shu Fan Medical Foundation Professor in Medicine. Professor Yuen is the top hepatitis B researcher in the world, according to Expertscape based on publications between 2013 and 2023. He was one of the first in the world to develop a risk score for hepatocellular carcinoma in hepatitis B patients. Promising early results Bepirovirsen already showed in a phase two trial that it could functionally cure 10 per cent of participants, who had undetectable surface antigen of the virus after six months – this is 10 times higher than occurs naturally. Professor Yuen said they aim to push that rate to as high as 30 per cent within the next couple of years, meaning such patients would no longer need to take drugs every day for the rest of their lives to control the virus. But even with that promise, there is the problem that people often do not know they carry the hepatitis B virus until their liver is damaged – the virus sometimes does not show up on standard blood tests. Professor Yuen is therefore also working to improve detection of these hidden or ‘occult’ cases. He is collaborating on a project that has increased the diagnostic rate of occult hepatitis B infection from less than 20 per cent to 67 per cent. He also identified a treatment target by showing patients who spontaneously lost the surface antigen of the virus before the age of 50 had a significantly lower chance of developing serious liver disease. That discovery led to the development of a new drug, bepirovirsen, that is undergoing a phase three clinical trial in centres around the world and offers hope of a cure for at least some patients. He is also investigating other treatments, including a promising combination of antiviral and immunomodulatory agents, and he has helped develop outreach programmes to offer testing and treatment in the community. “We want to align with the WHO goal of eliminating hepatitis B in the world by 2030. Although this may take a few years longer, at least we need to move in that direction to diagnose and treat patients and decrease mortality related to viral infection,” he said. World-leading hepatitis researcher, Professor Yuen Man-fung, has made serious inroads towards a cure for some hepatitis B patients. He is also working to get more people tested so they can seek treatment for this silent but harmful virus. HEP TO A CURE He has also recently completed a study that confirmed the hepatitis B virus can integrate with a person’s DNA, so even if all viable traces of the virus are killed off in a person’s liver, the liver cancer process can still be triggered because the virus remains in their DNA. “The integration process actually starts early in a person’s lifetime, so we want to emphasise that we need to treat patients as soon as possible – when they are in their 20s or 30s – rather than wait for other indications. Some experts say we should wait until the virus reaches a certain level in the blood before treatment, but we believe it should happen before the integration process becomes more entrenched. Theoretically, this would decrease the chance of developing liver cancer,” he said. Combatting hepatitis C, too An important factor in doing that is to make sure people are aware they are hepatitis B carriers. According to Hong Kong’s Department of Health, nearly 40 per cent of hepatitis B carriers are unaware of their condition. “They think they are fine, Professor Yuen with the liver health screening mobile truck. they have no symptoms, so therefore they are not hepatitis B patients. But this is not true,” Professor Yuen said. He recently teamed up with the Hong Kong Liver Foundation to bring testing into the community through a mobile truck that will spend the next five years travelling to each of Hong Kong’s 18 districts to test people for the virus and make referrals if treatment is needed. He has also been involved in programmes to treat another lifethreatening infection, hepatitis C, in vulnerable populations. In one programme, he worked with different NGOs to screen and treat nearly 400 former intravenous drug users. More recently, he has been working with the Correctional Services Department, the Hospital Authority and the Chinese University of Hong Kong in a programme focussed on prisoners. They are tested at prison and can receive treatment there, too. “Hepatitis C can be cured with a few months of treatment but if untreated, it will also cause liver damage,” he said. RESEARCH HKU BULLETIN | NOV 2024 16 17

“Policymakers should consider extending paid maternity leave to international norms to improve mental health among working mothers and to support workforce retention.” Professor Quan Jianchao Researchers from HKUMed have found that extending Hong Kong’s statutory paid maternity leave led to a significant improvement in maternal mental health. The findings have significant implications at a time when birth rates worldwide are falling and labour force shortages are a significant problem. MATERNAL INSTINCT In July 2020, Hong Kong extended statutory paid maternity leave from 10 to 14 weeks to align with International Labour Organization standards. Not only was this a great day for new mums, but it also provided a rare opportunity to study directly and immediately the implications of such a change on the mothers concerned, with a particular focus on postnatal depression, if any. The research team which undertook the research comprised experts from HKUMed’s School of Public Health and School of Nursing, as well as collaborators from Singapore’s Duke-NUS Medical School and Canada’s University of British Columbia. Their study revealed a 22 per cent decrease in postnatal depressive symptoms among mothers and a 33 per cent reduction in mothers reporting that baby care interfered with their emotional well-being. Significant benefits Professor Quan Jianchao, Clinical Assistant Professor in the School of Public Health, and senior author of the study, said: “Even this modest change in policy, an additional four weeks of paid leave, was associated with significant mental health benefits. Policymakers should consider extending paid maternity leave to international norms to improve mental health among working mothers and to support workforce retention.” For the study, the team used the policy enactment as an observational natural experiment to assess the mental health implications of this policy change on probable postnatal depression – that is, Edinburgh Postnatal Depression Scale (EPDS) scores of 10 or higher – and postpartum emotional well-being. “The EPDS is widely clinically used and has been validated in Hong Kong,” explained Professor Quan. “The reason we use the term ‘potential’ in our findings is that this is a screening tool. Postnatal depression (or indeed depression) is a clinical diagnosis – it can only be diagnosed by a physician, as opposed to diabetes or hypertension that is diagnosed by a laboratory test or measurement.” Using an opportunistic observational study design, the team recruited 1,414 survey respondents who had given birth either before the policy implementation during August to December 2020, or after the implementation, between December 2020 and July 2022. Participants had an average age of 32, for most this was their first child, and the majority had skilled occupations. “Our results show that the policy was associated with a 22 per cent decrease in mothers experiencing postnatal depressive symptoms and a 33 per cent decrease in postpartum emotional well-being interference,” said Professor Quan. “This was somewhat surprising given the modest length of leave extension, though it is hard to attribute the causality definitely in these natural experiments.” The study comes at a time of demographic challenges in East Asia when birth rates are falling, the proportion of elderly in populations is growing and many governments are seeking ways to encourage young people to have children. In Hong Kong, only 52 per cent of women currently participate in the workforce, compared to 64 per cent of men, so retaining female employees is important to address the labour shortage. Women of child-bearing age (25–34 years old) have the highest workforce participation rate (80 per cent), making them the most likely to benefit from an optimal maternity leave policy. Postnatal depression is a serious mental disorder which can affect mothers up to a year after childbirth. About 30 per cent of new mothers in Hong Kong experience postnatal depression, which is markedly higher than the global average of 18 per cent. The figure for Mainland China is 14 per cent and just 3 per cent in Singapore. Maternity leave policy could have important implications for public health, including improved maternal mental and physical health and higher breastfeeding rates. 18 weeks leave “The International Labour Organization, which is part of the United Nations, actually mandates a minimum maternity leave period of 14 weeks and recommends increasing it to at least 18 weeks to ensure an adequate rest and recovery time for the mother,” said Professor Quan. “In 2021, 52 countries met or exceeded this 18-week standard. The US is a notable exception/ outlier with no nationally mandated paid leave. “Longer periods and more flexible arrangements such as shared parental leave (rather than separate maternity/ paternity) can also be considered. Many countries offer shared parental leave – Singapore announced on their National Day in August 2024 an additional 10 weeks of government-paid shared leave to bring it up to 30 weeks by 2026. Flexibility should be beneficial as people tend to make the best decisions for their circumstances but notably, men have higher labour force participation and higher wages so the costs may be higher.” Professor Quan pointed out that the Hong Kong Government has launched other family-friendly initiatives too, for example, a Newborn Baby Bonus. The research findings were published in the healthcare journal Health Affairs. RESEARCH HKU BULLETIN | NOV 2024 18 19

“Policies and scientific initiatives for soil animal conservation need to be more widespread. We anticipate that our study will reveal to the public the immense power of these ‘invisible’ creatures.” Ms Zeng Xiaoyi total of 60 articles, encompassing 476 observations across 93 study sites from all continents except for the polar regions. “Fortunately, the extensive work on the Global Termite Diversity Map by our collaborators – Dr Joel S Woon from the University of Liverpool and Dr Paul Eggleton from the Natural History Museum in London – provided us with an opportunity to analyse the relationship between termite diversity and the effect of invertebrates on forest litter decomposition,” said Ms Zeng. The HKU team’s study showed that invertebrates contributed 31 per cent to global forest litter decomposition, and in tropical and subtropical forests their contribution was 1.4 times higher than in temperate and boreal forests. They also found that termites – often considered pests to humans – contributed to the greater decomposition in tropical and subtropical forests. As well as termites, detritivore invertebrates such as earthworms, woodlice, and millipedes directly consume plant litter, and many invertebrates indirectly drive litter decomposition. “For instance, the activity of detritivores leads to litter fragmentation, thereby increasing the exposure of leaf litter to microbial decomposers,” said Ms Zeng. “Other invertebrates, including beetles, ants, mites and springtails, influence decomposition processes by mediating soil food webs and affecting soil physical and chemical properties, such as moisture and temperature.” Sampling bias Professor Ashton explained that one of the reasons the role of such invertebrates in the subtropics has often been overlooked is due to regional sampling bias. “There is a bias in ecology towards the temperate zone,” she said, adding that a recent study has also observed a significant taxonomic bias in biodiversity conservation research favouring vertebrates, which constitute 89 per cent of the mostMyriad soil organisms beneath our feet play a vital role in supporting ecosystem services and sustaining our lives, but they often receive less attention from scientists and the public compared to the more visible ‘star’ species. A new study has revealed just how crucial invertebrates such as termites are, particularly in the world’s tropical and subtropical areas. “Invertebrates are responsible for about a third of global forest leaf litter decomposition,” said PhD candidate Ms Zeng Xiaoyi from the School of Biological Sciences, of invertebrates for both their direct contributions and their indirect effects stemming from their interactions with microbes, vertebrates and environmental variables,” said Ms Zeng. “Secondly, we advocate for consideration of the regional variation that our study has revealed so as to enhance the precision of model forecasts. Finally, we suggest introducing invertebrates into Earth System Models by developing global invertebrate databases through combining traditional taxonomic and molecular approaches.” Ecosystem services The findings also highlight the importance of conserving invertebrate biodiversity and the valuable ecosystem services they provide. “The decline of many invertebrates, often considered as crop pests [for example, termites], is alarming due to the overuse of pesticides, further emphasising the need for their conservation,” said Ms Zeng. “Policies and scientific initiatives for soil animal conservation need to be more widespread. We anticipate that our study will reveal to the public the immense power of these ‘invisible’ creatures. They are not only an integral part of nature but also a group that urgently requires our protection and conservation efforts.” Moving their focus to the role of the decomposition process as the primary source of available nutrients for plants, the team will next investigate how invertebrates mediate plant growth through this pathway. They aim to employ stable isotope technology to track the nitrogen flux from leaf litter to living plant tissues so as to determine whether such knock-on effects vary across different climatic regions. Implementing this approach will enable them to identify the specific roles that invertebrates play in vegetation development and how these roles are influenced by climatic factors. who led the study supervised by Professor Louise A Ashton. “In particular, those found in tropical and subtropical forests have a more substantial impact on this process compared to their counterparts in forests outside of these regions. As significant ecosystem engineers in the tropics and subtropics, termites play a crucial role in these decomposition processes.” The team conducted a comprehensive literature search on databases like Web of Science and ScienceDirect, and initially yielded 2,278 articles. They finally included a New findings highlight the critical role of invertebrates in breaking down forest litter and thereby helping sustain carbon and nutrient cycling. INVISIBLE ENGINEERS studied species, while invertebrates remain markedly underrepresented. “However, these types of taxonomic bias have become better recognised recently and there are efforts to better understand the ecology of the tropics,” said Professor Ashton. It is hoped the new findings can be used to improve the accuracy of Earth System Models in future. “While existing biogeochemical models typically incorporate climate, vegetation and soil characteristics to predict carbon and nitrogen turnover in terrestrial ecosystems, we are now advocating the inclusion HKU BULLETIN | NOV 2024 20 21 RESEARCH

Our approach is novel in that we have demonstrated, for the first time, that timeseries satellite-based multispectral data is nearly as effective as drone/airborne hyperspectral imaging for high-throughput foliar trait monitoring,” said Professor Wu Jin from the School of Biological Sciences, who led the international team of researchers. Utilising high-resolution imagery from the Sentinel-2 satellite, which captures multispectral data at weekly intervals with a 10-metre resolution, the team recorded the reflections of light from plant leaves, and gained valuable insights into the physical and biochemical properties of the vegetation. They then compared their observations to the timing of phenological (that is, plant life cycle) events. “By integrating the data from satellite imagery and phenological observations, the team gained comprehensive information about plant functional traits across high dimensions,” said Professor Wu. “Further, the free cost and global availability of the input data we used indicates that our successful technique provides the scientific community with a completely novel, freely accessed, and large-scale foliar trait data source, revolutionising conventional ways of monitoring Earth’s surface.” Conventionally, scientists have relied on either field-based methods or drone/airborne hyperspectral imaging systems for plant functional traits monitoring. Field-based approaches are often time-consuming, resource-expensive, labour-intensive, and difficult to scale up to regional, continental, or global levels. ‘Foliar traits’ refer to the key characteristics or features of a plant’s foliage such as leaf morphology, colour, chemical composition and photosynthetic rates, which can reveal a lot about how a plant grows, how it uses water and nutrients, how it photosynthesises and how it might respond to different environmental conditions like drought “We have demonstrated, for the first time, that time-series satellite-based multispectral data is nearly as effective as drone/airborne hyperspectral imaging for high-throughput foliar trait monitoring.” Professor Wu Jin index, although its importance varies considerably among traits.” The new regional plant trait dataset generated by this novel approach will provide scientists with a wealth of information about plant characteristics across a large geographical area, information which could be used to inform conservation strategies and efforts to restore or rehabilitate damaged ecosystems. Additionally, information on plant traits can also be used to model ecosystem processes, such as nutrient cycling and carbon sequestration, processes that play a critical role in mitigating climate change by removing carbon dioxide from the atmosphere. “Through understanding how different plant traits influence these processes, scientists can develop strategies to enhance these natural climate solutions,” said Professor Wu. “The dataset could also help in predicting Using an innovative combination of the Sentinel-2 satellite mission and its dynamic time-series capabilities, along with phenological observations, biological scientists have made a promising advancement in mapping plant functional traits from space. THE BIGGER PICTURE the spread of invasive species or the potential impact of pests and diseases on local vegetation, which can have significant implications for biodiversity, agriculture, and local economies. In essence, this new regional plant trait dataset equips scientists with essential data to inspire and generate novel knowledge needed to tackle environmental problems more effectively and design more sustainable landscapes for the future.” The initial research using Sentinel-2 was done over ecosystem sites across the US, but in theory, the approach can be applied to any region across the globe. “We began our research in the US because readily available data allowed us to verify and refine our approach effectively,” said Professor Wu. “Our next step involves conducting extensive ground truth sampling in China and other regions worldwide. By doing so, we aim to demonstrate the versatility High-resolution satellite-based maps with multispectral data. or high temperatures. In other words, these ‘essential foliar traits’ provide important information about a plant’s health, growth, and overall function in an ecosystem. In addition to the main breakthrough, the team also found evidence suggesting that the leaf economics spectrum (LES) may be the underlying mechanism driving this technical success. Strong correlation “In our research, we found that the satellite-derived seasonal amplitude of the vegetation index, which can be viewed as a proxy for ecosystem-scale leaf turnover rate or leaf lifespan, strongly correlates with multiple essential plant traits of interest,” said Professor Wu. “This finding aligns with previous understandings of the LES theory. Moreover, in our final model that connects satellite-based time-series multispectral data for foliar trait prediction, we observed a significant role for the satellite-derived seasonal amplitude of the vegetation and adaptability of our methodology. Ultimately, our objective is to make our approach globally applicable. “By gathering data and validating our approach in various locations around the world, we can contribute to a more comprehensive understanding of ecosystem health, resilience, and vulnerability. This, in turn, can help inform effective strategies for conservation and sustainable management of ecosystems across the planet.” The team also aim to build upon the technical advances of their current research, which was published in Remote Sensing of Environment, and move forward multiple further research foci that best leverage this technical advance. “Plant traits provide crucial baseline information to further guide effective naturebased solutions for climate change mitigation,” said Professor Wu. RESEARCH HKU BULLETIN | NOV 2024 22 23

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