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Hok Sum Chan,1 Fanny Wai San Ko,2 Johnny Wai Man Chan,3 Kah Lin Choo,4 Loletta Kit Ying So,5 David Chi Leung Lam,6 Kit Man Sin,7 Wei Yin Wong,8 Yuk Lun Cheng,1 Maureen Mo Lin Wong9 1Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 3Department of Medicine, Queen Elizabeth Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 4Department of Medicine, North District Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 5Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 6Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 7Department of Medicine and Geriatrics, Tuen Mun Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 8Department of Medicine, Haven of Hope Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 9Department of Medicine and Geriatrics, Caritas Medical Centre, Hong Kong Special Administrative Region (HKSAR), People’s Republic of ChinaCorrespondence: Hok Sum Chan, Department of Medicine, 6/F, Block J, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, NT, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China, Email chanhs@ha.org.hkBackground: Chronic obstructive pulmonary disease (COPD) is a common cause for hospital admission. This study aims to review the hospital burden of COPD in Hong Kong (HK) and the trend from year 2006 to 2014.Methods: A multi-center, retrospective study of the characteristics of COPD patients discharged from the public hospitals of HK from year 2006 to 2014. Anonymized data retrieval and analysis were performed. The demographic data of the subjects, use of health-care resources, ventilatory support, medications used and mortality of the subjects were analyzed.Results: Total patient headcount (HC) and admission number reduced from 10,425 and 23,362 in year 2006 to 9613 and 19,771, respectively, in 2014. There was a progressive reduction of female COPD HC from 2193 (21%) in year 2006 to 1517 (16%) in 2014. The utilization of non-invasive ventilation (NIV) increased rapidly and peaked in 2010 (29%) and decreased thereafter. There was a rapid increase in the prescription of long-acting bronchodilators (from 15% to 64%). COPD and pneumonia were the top causes of death, but death due to pneumonia was rapidly increasing while death due to COPD was progressively decreasing over the period.Conclusion: COPD HC and admission number (particularly in female patients) decreased progressively from year 2006 to 2014. There was also a decreasing trend of severity of disease as reflected by lower NIV use (after year 2010) and lower mortality rate due to COPD. Reduced smoking prevalence and tuberculosis (TB) notification rate in the community in the past might have reduced the incidence and severity of COPD and the hospital burden of disease. We observed an increasing trend of mortality due to pneumonia in COPD patients. Appropriate and timely vaccination programs are recommended for COPD patients as in the general elderly population.Keywords: hospital burden, mortality, smoking, old tuberculosis, pneumonia

Hok Sum Chan,1 Fanny Wai San Ko,2 Johnny Wai Man Chan,3 Loletta Kit Ying So,4 David Chi Leung Lam,5 Veronica Lee Chan,6 Cheuk Yin Tam,7 Wai Cho Yu8 1Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 3Department of Medicine, Queen Elizabeth Hospital, 4Department of Medicine, Pamela Youde Nethersole Eastern Hospital, 5Department of Medicine, Queen Mary Hospital, University of Hong Kong, 6Department of Medicine and Geriatrics, United Christian Hospital, 7Department of Medicine and Geriatrics, Tuen Mun Hospital, 8Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Background: COPD is a common cause for hospital admission. Conventional studies of the epidemiology of COPD involved large patient number and immense resources and were difficult to be repeated. The present study aimed at assessing the utilization of a computerized data management system in the collection and analysis of the epidemiological and clinical data of a large COPD cohort in Hong Kong (HK). Patients and methods: It was a computerized, multicenter, retrospective review of the characteristics of patients discharged from medical departments of the 16 participating hospitals with the primary discharge diagnosis of COPD in 1 year (2012). Comparison was made between the different subgroups in the use of medications, ventilatory support, and other health care resources. The mortality of the subjects in different subgroups was traced up to December 31, 2014. The top 10 causes of death were analyzed. Results: In total, 9,776 subjects (82.6% men, mean age =78 years) were identified. Of the 1,918 subjects with lung function coding, 85 (4.4%), 488 (25.5%), 808 (42.1%), and 537 (28.0%) subjects had the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 2, 3, and 4 classes, respectively. Patients with higher GOLD classes had higher number of hospital admissions, longer hospital stay, increased usage of noninvasive mechanical ventilation (NIV), combinations of long-acting bronchodilators, and higher mortality. Of the 9,776 subjects, 2,278 (23.3%) received NIV, but invasive mechanical ventilation was uncommon (134 of 9,776 subjects [1.4%]); 4,427 (45.3%) subjects had died by the end of 2014. The top causes of death were COPD, pneumonia, lung cancer, and other malignancies. Conclusion: Patients admitted to hospitals for COPD in HK had significant comorbidities, mortality, and imposed heavy burden on health care resources. It is possible to collect and analyze data of a large COPD cohort through a computerized system. Suboptimal coding of lung function results was observed, and underutilization of long-acting bronchodilators was common. Keywords: noninvasive ventilation, medications, chronic effect of TB, GOLD classification, health care resources

Ka Pang Chan,1 Fanny WS Ko,1 Hok Sum Chan,2 Mo Lin Wong,3 Thomas YW Mok,4 Kah Lin Choo,5 David SC Hui1 1Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, 2Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, 3Department of Medicine and Geriatrics, Caritas Medical Centre, 4Respiratory Medical Department, Kowloon Hospital, 5Department of Medicine, North District Hospital, Hong Kong Background: This study aimed to assess the adherence rate of pharmacological treatment to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline published in 2011 and the prevalence of comorbidities among patients with COPD in Hong Kong (HK).Methods: Patients were recruited from five tertiary respiratory centers and followed up for 12 months. Data on baseline physiological, spirometric parameters, use of COPD medications and coexisting comorbidities were collected. The relationship between guideline adherence rate and subsequent COPD exacerbations was assessed.Results: Altogether, 450 patients were recruited. The mean age was 73.7±8.5 years, and 92.2% of them were males. Approximately 95% of them were ever-smokers, and the mean post-bronchodilator (BD) forced expiratory volume in 1 second was 50.8%±21.7% predicted. The mean COPD Assessment Test and modified Medical Research Council Dyspnea Scale were 13.2±8.1 and 2.1±1.0, respectively. In all, five (1.1%), 164 (36.4%), eight (1.8%) and 273 (60.7%) patients belonged to COPD groups A, B, C and D, respectively. The guideline adherence rate for pharmacological treatment ranged from 47.7% to 58.1% in the three clinic visits over 12 months, with overprescription of inhaled corticosteroids (ICS) and underutilization of long-acting BDs in group B COPD patients. Guideline nonadherence was not associated with increased risk of exacerbation after adjustment of confounding variables. However, this study was not powered to assess a difference in exacerbations. In all, 80.9% of patients had at least one comorbidity.Conclusion: A suboptimal adherence to GOLD guideline 2011, with overprescription of ICS, was identified. The commonly found comorbidities also aligned with the trend observed in other observational cohorts. Keywords: COPD, GOLD guideline, adherence

Abstract Quantum networks typically comprise quantum channels, repeaters, and end nodes. Remote state preparation (RSP) allows one end node to prepare the states of the other end nodes remotely. While quantum discord has recently been recognized as necessary for RSP, it does not guarantee the practical implementation of RSP in quantum networks surpasses any classical method. Herein, we theoretically introduce and experimentally study a quantum resource that we call the RSP capability. This resource validates all the static and dynamic elements required to enable genuine quantum networks where the RSP’s implementation can outperform any classical emulation of entanglement- and qubit-unitaries-free strategies, including the static resources of Einstein-Podolsky-Rosen pairs and the dynamic resources of quantum channels and repeaters. Our experiment measures the RSP capability to demonstrate the transition between classical and nonclassical RSP depending on the photon-pair qualities. It shows that quantum discord does not confirm a nonclassical RSP, but the RSP capability does. These results help reveal the quantum advantages that emerge when networking RSP is in play.

Photoluminescence and electroreflectance (ER) measurements on InN thin films grown by metal-organic chemical vapour deposition were performed at ambient and low temperatures. Franz-Keldysh oscillations (FKO's) were observed in the ER spectra. From the analysis of the FKO's, the bandgap of an as-deposited film is estimated to be 0.66 ± 0.02 eV at 90 K, whereas the low-temperature (8 K) photoluminescence (PL) appears as a broad peak between 0.67 eV and 0.77 eV. When the sample is annealed in air at temperatures below 420 °C, the bandgap energy at 90 K estimated from the FKO redshifts to 0.62 ± 0.02 eV. When the sample is annealed at temperatures of 420 °C or above, the low energy PL disappears, but the FKO signal persists with the same bandgap energy. We interpret that the crystalline quality of InN improves with annealing at lower temperatures but degrades dramatically with higher temperature annealing and conclude that the intrinsic bandgap energy of InN at 90 K is 0.62 ± 0.02 eV. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the effectiveness of an intensive community nurse (CN)-supported discharge program in preventing hospital readmissions of older patients with chronic lung disease (CLD). DESIGN: Randomized, controlled trial. SETTING: Two acute hospitals in the same health region in Hong Kong. PARTICIPANTS: One hundred fifty-seven hospitalized patients aged 60 and older with a primary diagnosis of CLD and at least one hospital admission in the previous 6 months. INTERVENTION: CNs made home visits within 7 days of discharge, then weekly for 4 weeks and monthly until 6 months. CNs coordinated closely with a geriatric or respiratory specialist in hospital. Subjects had telephone access to CNs during normal working hours from Monday to Saturday. MEASUREMENTS: The primary outcome was the rate of unplanned readmission within 6 months. The secondary outcomes were the rate of unplanned readmission within 28 days, number of unplanned readmissions, hospital bed days, accident and emergency room attendance, functional and psychosocial status, and caregiver burden. RESULTS: One hundred forty hospitalized patients completed the trial. Intervention group subjects had a higher rate of unplanned readmission within 6 months than control group subjects (76% vs 62%, P=.080, chi2 test). There was no significant group difference in any of the secondary outcomes except that intervention group subjects did better on social handicap scores. CONCLUSION: There was no evidence that an intensive CN-supported discharge program can prevent hospital readmissions in older patients with CLD. [ABSTRACT FROM AUTHOR]

Using the stochastic frontier analysis (SFA) model, this research measures total-factor energy efficiency (TFEE) and disaggregate input efficiency for 10 countries across the Baltic Sea from 2004 to 2014. Real capital, labor, energy use, and carbon dioxide (CO2) are input variables, real gross domestic product (GDP) is the output variable, and renewable energy consumption and urban population are the environmental variables. The results provide not only the TFEE scores, in which statistical noise is considered, but also the determinants of inefficiency, which show the following. (i) Norway, Sweden, Finland, and Latvia perform better with respect to energy efficiency than other countries in the Baltic Sea Region. (ii) Interestingly, the average energy use efficiency scores from 2004 to 2014 in the 10 Baltic countries exhibit a gradual upward trend except for 2009. (iii) For the inefficiency estimates, higher renewable energy consumption and urban population correspond to higher TFEE scores.

BACKGROUND: Substantial evidence suggests that increased oxidative stress in hemodialysis (HD) patients may contribute to cardiovascular complications. Oxidative modifications of human serum albumin (HSA), the largest thiol pool in plasma, alter its biological properties and may affect its antioxidant potential in HD patients. METHODS: We conducted a long-term follow-up study in a cohort of normoalbuminemic HD patients to examine the impact of redox state of serum albumin on patients' survival by measuring the human nonmercaptoalbumin (HNA) fraction of HSA. RESULTS: After adjusting for potential demographic, anthropometric, and clinical confounders, a positive association of HNA level with the risk of death from cardiovascular disease (CVD) and all-cause mortality was observed in normoalbuminemic HD patients. Using stratified analysis, we found a stronger association between HNA level and the risk of death from CVD and all-cause mortality in patients with pre-existing CVD. CONCLUSIONS: Serum HNA level is a positive predictor of mortality in normoalbuminemic HD patients, especially among those with pre-existing CVD. Increased oxidative stress resulting from biological changes in serum albumin levels could contribute to accelerated atherosclerosis and the development of cardiovascular disease in HD patients.

Abstract Background It is essential to subculture the cells once cultured cells reach confluence. For this, trypsin is frequently applied to dissociate adhesive cells from the substratum. However, due to the proteolytic activity of trypsin, cell surface proteins are often cleaved, which leads to dysregulation of the cell functions. Methods In this study, a triplicate 2D-DIGE strategy has been performed to monitor trypsin-induced proteome alterations. The differentially expressed spots were identified by MALDI-TOF MS and validated by immunoblotting. Results 36 proteins are found to be differentially expressed in cells treated with trypsin, and proteins that are known to regulate cell metabolism, growth regulation, mitochondrial electron transportation and cell adhesion are down-regulated and proteins that regulate cell apoptosis are up-regulated after trypsin treatment. Further study shows that bcl-2 is down-regulated, p53 and p21 are both up-regulated after trypsinization. Conclusions In summary, this is the first report that uses the proteomic approach to thoroughly study trypsin-induced cell physiological changes and provides researchers in carrying out their experimental design.

Tetrandrine, a bioactive active compound mainly found in the roots of Stephania tetrandra, exhibits various pharmacological properties. In vitro hairy root (HR) culture may serve as a promising solution for the extraction of tetrandrine, overcoming the limitations of natural cultivation. The present study describes the consistent production of tetrandrine from S. tetrandra hairy roots induced by different strains of Agrobacterium rhizogenes. Cultivation in woody plant medium (WPM) resulted in the highest HR biomass (0.056 g/petri-dish) and tetrandrine content (7.28 mg/L) as compared to other media. The maximum HR biomass (6.95 g dw/L) and tetrandrine production (68.69 mg/L) were obtained in the fifth week of cultivation. The presence of ammonium nitrate (800 mg/L), calcium nitrate (1156 mg/L), sucrose (20 g/L) and casein (2 g/L) enhanced the tetrandrine production. Moreover, the fed-batch cultivation demonstrated that the NH 4 NO 3 (1200 mg/L) was an important growth limiting factor that yielded the highest tetrandrine amount (119.59 mg/L). The cultivation of hairy roots in a mist trickling bioreactor for eight weeks was less (26.24 mg/L) than in the flask. Despite a lower tetrandrine yield observed in bioreactors compared to flask cultures, refining the growth medium and fine-tuning bioreactor operations hold promise for boosting tetrandrine yield., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Yung-Chuan Liu reports financial support was provided by National Science and Technology Council of Taiwan. Parushi Nargotra reports financial support was provided by National Science and Technology Council of Taiwan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

(1) Objective: to investigate the effectiveness of telephysiotherapy compared with traditional rehabilitation for elderly patients and determine the factors impacting its efficacy. (2) Method: Five online databases (PubMed, Google Scholar, Scopus, Web of Science, and Cochrane) were reviewed up to 31 July 2023. The search included the literature in English from 2014 to 2023, to capture the latest practices in telephysiotherapy for elderly patients. Data from all qualified studies were independently extracted by two authors, quantifying effect size to reflect treatment performance. (3) Results: 222 records from 19 articles were analyzed. The effect size for telephysiotherapy was 0.350 (95% C.I. = 0.283-0.416; p < 0.01). The standardized mean differences for physical and psychological outcomes were 0.406 (95% C.I. = 0.325-0.488; p < 0.01) and 0.223 (95% C.I. = 0.110-0.336; p < 0.01), respectively. (4) Conclusions: Telephysiotherapy was more effective than traditional rehabilitation, significantly improving the physical and psychological status of elderly patients. The factors influencing the effectiveness of telephysiotherapy were intervention type, intervention duration, outcome, and gender.

Conformational properties of intrinsically disordered proteins (IDPs) are governed by a sequence-ensemble relationship. To differentiate the impact of sequence-local versus sequence-nonlocal features of an IDP's charge pattern on its conformational dimensions and its phase-separation propensity, the charge "blockiness" κ and the nonlocality-weighted sequence charge decoration (SCD) parameters are compared for their correlations with isolated-chain radii of gyration ( R g s) and upper critical solution temperatures (UCSTs) of polyampholytes modeled by random phase approximation, field-theoretic simulation, and coarse-grained molecular dynamics. SCD is superior to κ in predicting R g because SCD accounts for effects of contact order, i.e., nonlocality, on dimensions of isolated chains. In contrast, κ and SCD are comparably good, though nonideal, predictors of UCST because frequencies of interchain contacts in the multiple-chain condensed phase are less sensitive to sequence positions than frequencies of intrachain contacts of an isolated chain, as reflected by κ correlating better with condensed-phase interaction energy than SCD.

Background: To achieve suitable diabetes care, understanding the factors that affect self-care behaviors is necessary., Objective: To construct a model of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in people with diabetes., Design and Methods: This cross-sectional study analyzed a convenience sample of 311 people with type 2 diabetes in Taiwan. Data were collected through questionnaires, including the Diabetes Symptoms Checklist, Emotional Distress Scale, Empowerment Process Scale, Interpersonal Communication Scale and Self-Care Behavior scale., Results: Structural equation modeling indicated that a model of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in the patients with diabetes best fit the data. Dispositional mindfulness (β = 0.39), internal environmental factors (β = 0.52), and external environmental factors (β = 0.71) directly influenced self-care behaviors in the patients with diabetes. Dispositional mindfulness significantly indirectly affected self-care behaviors via internal and external environmental factors., Conclusions: To improve self-care behaviors, interventions should consider mindfulness training, and also include internal environmental factors and external environmental factors in the mindfulness training., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: Quality of life (QOL) is frequently utilized in clinical medicine and research to assess a patient's health status and treatment effectiveness., Objectives: This study investigates the impact of vocational training on the QOL of visually impaired individuals., Methods: We employed the brief Taiwan version of the World Health Organization QOL Questionnaire (WHOQOL-BREFTW) to assess four domains: physical, psychological, social, and environmental, using a nonequivalent pretest-posttest control group design. The experimental group participated in 6 months of vocational training, including life and career reconstruction. After completing the vocational training, the average QOL score for the experimental group was 3.34 ± 0.18, while the control group had a score of 3.10 ± 0.85. The generalized estimating equation (GEE) results revealed a notable improvement of 10.81 (1.10) in the posttest overall QOL scores compared to the pretest scores in the control group., Conclusion: Vocational training significantly improves the overall QOL for visually impaired individuals. It is noteworthy that the psychological, social relationship, and physical health domains of WHOQOL-BREF TW exhibited the most significant improvements. This emphasizes the following: 1. professional knowledge and technical learning can enhance the abilities of the visually impaired. 2. The improvement in QOL occurs primarily at physical, psychological, and social levels. These levels involve maintaining physical health, reducing dependence on medical care, and enhancing self-care abilities for life reconstruction. 3. Integrating electronics with directional action can help to mitigate the risks associated with outdoor activities.

Background: Virtual reality is a relatively new intervention that has the potential to be used in the treatment of eye and vision problems. This article reviews the use of virtual reality-related interventions in amblyopia, strabismus, and myopia research., Methods: Sources covered in the review included 48 peer-reviewed research published between January 2000 and January 2023 from five electronic databases (ACM Digital Library, IEEE Xplore, PubMed, ScienceDirect and Web of Science). To prevent any missing relevant articles, the keywords, and terms used in the search included "VR", "virtual reality", "amblyopia", "strabismus," and "myopia". Quality assessment and data extraction were performed independently by two authors to form a narrative synthesis to summarize findings from the included research., Results: Total number of 48 references were reviewed. There were 31 studies published on amblyopia, 18 on strabismus, and 6 on myopia, with 7 studies overlapping amblyopia and strabismus. In terms of technology, smartphone-based virtual reality headset viewers were utilized more often in amblyopia research, but commercial standalone virtual reality headsets were used more frequently in myopia and strabismus-related research. The software and virtual environment were mostly developed based on vision therapy and dichoptic training paradigms., Conclusion: It has been suggested that virtual reality technology offers a potentially effective tool for amblyopia, strabismus, and myopia studies. Nonetheless, a variety of factors, especially the virtual environment and systems employed in the data presented, must be explored before determining whether virtual reality can be effectively applied in clinical settings. This review is significant as the technology in virtual reality software and application design features have been investigated and considered for future reference., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Formation of membraneless organelles or biological condensates via phase separation and related processes hugely expands the cellular organelle repertoire. Biological condensates are dense and viscoelastic soft matters instead of canonical dilute solutions. To date, numerous different biological condensates have been discovered, but mechanistic understanding of biological condensates remains scarce. In this study, we developed an adaptive single-molecule imaging method that allows simultaneous tracking of individual molecules and their motion trajectories in both condensed and dilute phases of various biological condensates. The method enables quantitative measurements of concentrations, phase boundary, motion behavior, and speed of molecules in both condensed and dilute phases, as well as the scale and speed of molecular exchanges between the two phases. Notably, molecules in the condensed phase do not undergo uniform Brownian motion, but instead constantly switch between a (class of) confined state(s) and a random diffusion-like motion state. Transient confinement is consistent with strong interactions associated with large molecular networks (i.e., percolation) in the condensed phase. In this way, molecules in biological condensates behave distinctly different from those in dilute solutions. The methods and findings described herein should be generally applicable for deciphering the molecular mechanisms underlying the assembly, dynamics, and consequently functional implications of biological condensates., Competing Interests: ZS, BJ, YX, JW, TP, HC, SD, MZ No competing interests declared, (© 2023, Shen et al.)

We introduce a unique soft lithographic operation that exploits stamp roof collapse-induced gaps to selectively remove an alkanethiol self-assembled monolayer (SAM) on Au to generate surface patterns that are orders of magnitude smaller than structures on the original elastomer stamp. The smallest achieved feature dimension is 5 nm using a micrometer-scale structured stamp in a chemical lift-off lithography (CLL) process. Molecular patterns retained in the gaps between stamp features and their circumscribed or inscribed circles follow mathematical predictions, and their sizes can be tuned by altering the stamp structure dimensions, including height, pitch, and shape. These generated surface molecular patterns can function as biorecognition arrays or be transferred to the underneath Au layer for metallic structure creation. By combining CLL process with this gap phenomenon, soft material properties that are previously thought as demerits can be used to achieve sub-10 nm features in a straightforward sketch., (Copyright © 2023, Wang et al.)

Biomolecular condensates, physically underpinned to a significant extent by liquid-liquid phase separation (LLPS), are now widely recognized by numerous experimental studies to be of fundamental biological, biomedical, and biophysical importance. In the face of experimental discoveries, analytical formulations emerged as a powerful yet tractable tool in recent theoretical investigations of the role of LLPS in the assembly and dissociation of these condensates. The pertinent LLPS often involves, though not exclusively, intrinsically disordered proteins engaging in multivalent interactions that are governed by their amino acid sequences. For researchers interested in applying these theoretical methods, here we provide a practical guide to a set of computational techniques devised for extracting sequence-dependent LLPS properties from analytical formulations. The numerical procedures covered include those for the determination of spinodal and binodal phase boundaries from a general free energy function with examples based on the random phase approximation in polymer theory, construction of tie lines for multiple-component LLPS, and field-theoretic simulation of multiple-chain heteropolymeric systems using complex Langevin dynamics. Since a more accurate physical picture often requires comparing analytical theory against explicit-chain model predictions, a commonly utilized methodology for coarse-grained molecular dynamics simulations of sequence-specific LLPS is also briefly outlined., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The ( E / Z )-ocellenynes are C 15 dibrominated Laurencia natural products whose structures have been subject to several reassignments on the basis of extensive NMR analysis, biosynthetic postulates, and DFT calculations. Herein, we report the synthesis of both ( E )- and ( Z )-ocellenyne, which, in combination with single crystal X-ray diffraction studies, allows their absolute configuration to be established and defines the configuration of the syn -12,13-dibromide as being ( S , S ) in keeping with their proposed biogenesis from the (6 S , 7 S )-laurediols.

A theory for sequence-dependent liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) in the study of biomolecular condensates is formulated by extending the random phase approximation (RPA) and field-theoretic simulation (FTS) of heteropolymers with spatially long-range Coulomb interactions to include the fundamental effects of short-range, hydrophobic-like interactions between amino acid residues. To this end, short-range effects are modeled by Yukawa interactions between multiple nonelectrostatic charges derived from an eigenvalue decomposition of pairwise residue-residue contact energies. Chain excluded volume is afforded by incompressibility constraints. A mean-field approximation leads to an effective Flory-Huggins χ parameter, which, in conjunction with RPA, accounts for the contact-interaction effects of amino acid composition and the sequence-pattern effects of long-range electrostatics in IDP LLPS, whereas FTS based on the formulation provides full sequence dependence for both short- and long-range interactions. This general approach is illustrated here by applications to variants of a natural IDP in the context of several different amino-acid interaction schemes as well as a set of different model hydrophobic-polar sequences sharing the same composition. Effectiveness of the methodology is verified by coarse-grained explicit-chain molecular dynamics simulations.

The relationship between the two sustainable development goals (SDGs)-inequality reduction and carbon emission reduction is critical for governments formulating and implementing environmental and redistribution policies. This study uses micro survey data from the China Family Panel Studies (CFPS) to conduct a counterfactual analysis that decomposes and quantifies the net effects of consumption growth, redistribution, and changing patterns of consumption on household carbon emissions. The counterfactual approach helps to overcome the endogeneity concerns. The findings of our study convey a profoundly important and alarming message: the redistribution measures for inequality reduction may increase household carbon emissions. The findings attest to the need for Chinese policymakers to seriously consider the trade-off between inequality reduction and emission reduction, particularly in certain regions in China. To address the trade-off, one key measure is to encourage low-carbon lifestyles and consumption patterns to ensure that the benefits gained by poorer households from redistribution measures will not translate into higher emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We conducted a statistical study and developed a machine learning model to triage COVID-19 patients affected during the height of the COVID-19 pandemic in Hong Kong based on their medical records and test results (features) collected during their hospitalization. The correlation between the values of these features is studied against discharge status and disease severity as a preliminary step to identify those features with a more pronounced effect on the patient outcome. Once identified, they constitute the inputs of four machine learning models, Decision Tree, Random Forest, Gradient and RUSBoosting, which predict both the Mortality and Severity associated with the disease. We test the accuracy of the models when the number of input features is varied, demonstrating their stability; i.e., the models are already highly predictive when run over a core set of (6) features. We show that Random Forest and Gradient Boosting classifiers are highly accurate in predicting patients' Mortality (average accuracy ∼99%) as well as categorize patients (average accuracy ∼91%) into four distinct risk classes (Severity of COVID-19 infection). Our methodical and broad approach combines statistical insights with various machine learning models, which paves the way forward in the AI-assisted triage and prognosis of COVID-19 cases, which is potentially generalizable to other seasonal flus.

Loneliness is associated with depression, sleep disturbance, and an increased risk of cardiovascular disease, and it is a global public health problem. Since physical and mental health have a great impact on loneliness, middle-aged and elderly people who are blind or visually impaired may be more affected by loneliness. Previous research has confirmed that effective social support can enhance physical and mental health and alleviate the negative effects of life stress. Therefore, in this study, we applied a cross-sectional design where data were collected using questionnaires completed in person, by phone, or online for a total of 456 middle-aged and elderly people with visual impairment. We found that the enrolled participants who were unemployed, lacked a stable source of income, lived alone, or were unable to move independently were prone to experiencing high levels of loneliness and low social support, which highlights the necessity of interventions such as counseling to alleviate the sense of loneliness in such groups. During the COVID-19 pandemic, social support measures to reduce the sense of loneliness should be highly encouraged to ensure that middle-aged and elderly people with visual impairment can continue to live independently, and social support seems to be an important factor.

This study sampled 86 community-dwelling older adults to investigate the effect of horticultural activities on their quality of life, perceived stress, and working memory. The results demonstrated that after 8 weeks of horticultural activities, the effect sizes (Cohen's d) of their quality of life, perceived stress, and working memory were 0.92, -1.32, and 0.62, respectively. Among the four domains of quality of life, the social relationships domain improved the most. For perceived stress, the score of the experimental group decreased from 1.70 (0.48) to 1.29 (0.58). For working memory, the score increased from 3.43 (1.13) to 4.14 (1.27), whereas the score of the control group did not change substantially. Statistical analysis conducted using a generalized estimating equation revealed a significant interaction effect between group and time (P < 0.001). This study provides a reference for improving the quality of life, perceived stress, and working memory in older people., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Phase separation of several different overall neutral polyampholyte species (with zero net charge) is studied in solution with two oppositely charged ion species that can form ion pairs through an association reaction. Hereby, a field theory description of the system, which treats polyampholyte charge sequence dependent electrostatic interactions as well as excluded volume effects, is given. Interestingly, analysis of the model using random phase approximation and field theoretic simulation consistently shows evidence of a re-entrant polyampholyte phase separation at high ion concentrations when there is an overall decrease of volume upon ion association. As an illustration of the ramifications of our theoretical framework, several polyampholyte concentration vs ion concentration phase diagrams under constant temperature conditions are presented to elucidate the dependence of phase separation behavior on the polyampholyte sequence charge pattern as well as ion pair dissociation constant, volumetric effects on ion association, solvent quality, and temperature.

This study tested an ecological model of resilience that illustrated the influence of COVID-19-related stressors (i.e., social and health stressors) and various socio-ecological factors at microsystem (i.e., parent-child conflicts and couple relationship) and exo-system levels (i.e., the utilization of community resources) on family functioning among Chinese families during COVID-19. An anonymous telephone survey was conducted using random sampling method. The sample contained 322 respondents who were co-habiting with their child(ren) and their partner. Hierarchical regression analysis and structural equation modelling were used to examine the differential impacts of various levels of factors and the model that were proposed. Results showed that 13.2% of the households were categorized as at-risk of poorer family functioning. Couple relationship and stressors significantly accounted for much of the variance in family functioning. While stressors had a significant direct effect on family functioning, couple relationship, but not parent-child conflicts or utilization of community resources, significantly mediated and moderated the impact of stressors on family functioning. The findings highlighted the impacts of both individual and ecological factors on family functioning under COVID-19. Importantly, cultural and contextual factors should be considered when adopting ecological model of resilience to examine family functioning in diverse cultural groups., Competing Interests: We have no known conflicts of interests to disclose., (© 2022 John Wiley & Sons Ltd.)

The SynGAP/PSD-95 binary protein system serves as a simple mimicry of postsynaptic densities (PSDs), which are protein assemblies based largely on liquid-liquid phase separation (LLPS), that are located underneath the plasma membrane of excitatory synapses. Surprisingly, the LLPS of the SynGAP/PSD-95 system is much more pressure sensitive than typical folded states of proteins or nucleic acids. It was found that phase-separated SynGAP/PSD-95 droplets dissolve into a homogeneous solution at a pressure of tens to hundred bar. Since organisms in the deep sea are exposed to pressures of up to ∼1000 bar, this observation suggests that deep-sea organisms must counteract the high pressure sensitivity of PSDs to avoid neurological impairment. We demonstrate here that the compatible osmolyte trimethylamine- N -oxide (TMAO) as well as macromolecular crowding agents at moderate concentrations can mitigate the deleterious effect of pressure on SynGAP/PSD-95 droplet stability, extending stable LLPS up to almost a kbar level. Moreover, the formation of SynGAP/PSD-95 droplets is a very rapid process that can be switched on and off in seconds. In contrast with the marked effects of the cosolutes on droplet stability, at the cosolutes' respective biologically relevant concentrations, their impact on the phase transformation kinetics is rather small. Only a high TMAO concentration results in a significant kinetic retardation of LLPS. Taken together, these findings offer new biophysical insights into the neurological effects of hydrostatic pressure. In particular, our results indicate how pressure-induced neurological disorders might be alleviated by upregulating certain cosolutes in the cellular milieu.

The assembly of functional biomolecular condensates often involves liquid-liquid phase separation (LLPS) of proteins with multiple modular domains, which can be folded or conformationally disordered to various degrees. To understand the LLPS-driving domain-domain interactions, a fundamental question is how readily the interactions in the condensed phase can be inferred from interdomain interactions in dilute solutions. In particular, are the interactions leading to LLPS exclusively those underlying the formation of discrete interdomain complexes in homogeneous solutions? We address this question by developing a mean-field LLPS theory of two stoichiometrically constrained solute species. The theory is applied to the neuronal proteins SynGAP and PSD-95, whose complex coacervate serves as a rudimentary model for neuronal postsynaptic densities (PSDs). The predicted phase behaviors are compared with experiments. Previously, a three SynGAP/two PSD-95 ratio was determined for SynGAP/PSD-95 complexes in dilute solutions. However, when this 3:2 stoichiometry is uniformly imposed in our theory encompassing both dilute and condensed phases, the tie-line pattern of the predicted SynGAP/PSD-95 phase diagram differs drastically from that obtained experimentally. In contrast, theories embodying alternate scenarios postulating auxiliary SynGAP-PSD-95 as well as SynGAP-SynGAP and PSD-95-PSD-95 interactions, in addition to those responsible for stoichiometric SynGAP/PSD-95 complexes, produce tie-line patterns consistent with experiment. Hence, our combined theoretical-experimental analysis indicates that weaker interactions or higher-order complexes beyond the 3:2 stoichiometry, but not yet documented, are involved in the formation of SynGAP/PSD-95 condensates, imploring future efforts to ascertain the nature of these auxiliary interactions in PSD-like LLPS and underscoring a likely general synergy between stoichiometric, structurally specific binding and stochastic, multivalent "fuzzy" interactions in the assembly of functional biomolecular condensates., (Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Emerging evidence suggests that breast cancer stem cells (BCSCs), and epithelial-mesenchymal transition (EMT) may be involved in resistance to doxorubicin. However, it is unlear whether the doxorubicin-induced EMT and expansion of BCSCs is related to cancer dormancy, or outgrowing cancer cells with maintaining resistance to doxorubicin, or whether the phenotypes can be transferred to other doxorubicin-sensitive cells. Here, we characterized the phenotype of doxorubicin-resistant TNBC cells while monitoring the EMT process and expansion of CSCs during the establishment of doxorubicin-resistant MDA-MB-231 human breast cancer cells (DRM cells). In addition, we assessed the potential signaling associated with the EMT process and expansion of CSCs in doxorubicin-resistance of DRM cells. DRM cells exhibited morphological changes from spindle-shaped MDA-MB-231 cells into round-shaped giant cells. They exhibited highly proliferative, EMT, adhesive, and invasive phenotypes. Molecularly, they showed up-regulation of Cyclin D1, mesenchymal markers (β-catenin, and N-cadherin), MMP-2, MMP-9, ICAM-1 and down-regulation of E-cadherin. As the molecular mechanisms responsible for the resistance to doxorubicin, up-regulation of EGFR and its downstream signaling, were suggested. AKT and ERK1/2 expression were also increased in DRM cells with the advancement of resistance to doxorubicin. Furthermore, doxorubicin resistance of DRM cells can be transferred by autocrine signaling. In conclusion, DRM cells harbored EMT features with CSC properties possessing increased proliferation, invasion, migration, and adhesion ability. The doxorubicin resistance, and doxorubicin-induced EMT and CSC properties of DRM cells, can be transferred to parental cells through autocrine signaling. Lastly, this feature of DRM cells might be associated with the up-regulation of EGFR.

A territory-wide retrospective observational study was conducted in Hong Kong between January 23 to April 22, 2020 to demonstrate changes in pediatric seizure-related accident and emergency department (A&E) visits during the COVID-19 pandemic. Parallel periods from 2015 to 2019 were used as control. All-cause A&E attendances in all paediatric age groups decreased significantly during the study period. Seizure-related attendances decreased across all pediatric age-groups in 2020 (RR 0.379, 95% CI 0.245-0.588), with a disproportionately large decrease in the 0-6 years age group (RR 0.303, 95% CI 0.174-0.526) compared with the 7-18 years age group (RR 0.534, 95% CI 0.393-0.719). Decrease in RTI-related A&E attendances was also more drastic in the 0-6 age group. The two time trends are congruent in the 0-6 years but not the 7-18 years age group. Such a trend is suggestive of the usefulness of infection control measures in seizure prevention, especially amongst young children., Competing Interests: Declaration of competing interest All authors have nothing to disclose., (Copyright © 2020. Published by Elsevier B.V.)

An accurate account of disordered protein conformations is of central importance to deciphering the physicochemical basis of biological functions of intrinsically disordered proteins and the folding-unfolding energetics of globular proteins. Physically, disordered ensembles of nonhomopolymeric polypeptides are expected to be heterogeneous, i.e., they should differ from those homogeneous ensembles of homopolymers that harbor an essentially unique relationship between average values of end-to-end distance R EE and radius of gyration R g . It was posited recently, however, that small-angle X-ray scattering (SAXS) data on conformational dimensions of disordered proteins can be rationalized almost exclusively by homopolymer ensembles. Assessing this perspective, chain-model simulations are used to evaluate the discriminatory power of SAXS-determined molecular form factors (MFFs) with regard to homogeneous versus heterogeneous ensembles. The general approach adopted here is not bound by any assumption about ensemble encodability, in that the postulated heterogeneous ensembles we evaluated are not restricted to those entailed by simple interaction schemes. Our analysis of MFFs for certain heterogeneous ensembles with more narrowly distributed R EE and R g indicates that while they deviate from MFFs of homogeneous ensembles, the differences can be rather small. Remarkably, some heterogeneous ensembles with asphericity and R EE drastically different from those of homogeneous ensembles can nonetheless exhibit practically identical MFFs, demonstrating that SAXS MFFs do not afford unique characterizations of basic properties of conformational ensembles in general. In other words, the ensemble to MFF mapping is practically many-to-one and likely nonsmooth. Heteropolymeric variations of the R EE - R g relationship were further showcased using an analytical perturbation theory developed here for flexible heteropolymers. Ramifications of our findings for interpretation of experimental data are discussed.

This study investigated the effects of an 8-week horticultural activity intervention on attitudes toward aging, sense of hope, and hand-eye coordination in 88 older adults in residential care facilities. In the experimental group, the mean score for "attitudes toward aging" increased from 3.81 before the intervention to 4.74 points after the intervention (standard deviation SD = 0.24 and 0.27, respectively), and the control group dropped from 3.75 to 3.70 (standard deviations, respectively SD = 0.27 and 0.28). The mean score for "sense of hope" increased from 3.28 before the intervention to 3.81 points after the intervention (SD = 0.49 and 0.26, respectively). In contrast to the control group, the mean score gradually declined from 3.26 to 3.16 points (standard deviation SD = 0.54 and 0.48, respectively). In the test of hand-eye coordination, the time required to complete the cup stacking test significantly decreased from 33.56 to 25.38 s in the experimental group but did not significantly change in the control group. Generalized estimating equation analysis revealed a significant interaction between group and time ( p < 0.001). The data trends revealed significant differences in outcomes between the experimental group and the control group. At 3 months after the end of the study, the effect size in the experimental group remained higher than that in the control group.

Biomolecular condensates such as membraneless organelles, underpinned by liquid-liquid phase separation (LLPS), are important for physiological function, with electrostatics, among other interaction types, being a prominent force in their assembly. Charge interactions of intrinsically disordered proteins (IDPs) and other biomolecules are sensitive to the aqueous dielectric environment. Because the relative permittivity of protein is significantly lower than that of water, the interior of an IDP condensate is expected to be a relatively low-dielectric regime, which aside from its possible functional effects on client molecules should facilitate stronger electrostatic interactions among the scaffold IDPs. To gain insight into this LLPS-induced dielectric heterogeneity, addressing in particular whether a low-dielectric condensed phase entails more favorable LLPS than that posited by assuming IDP electrostatic interactions are uniformly modulated by the higher dielectric constant of the pure solvent, we consider a simplified multiple-chain model of polyampholytes immersed in explicit solvents that are either polarizable or possess a permanent dipole. Notably, simulated phase behaviors of these systems exhibit only minor to moderate differences from those obtained using implicit-solvent models with a uniform relative permittivity equals to that of pure solvent. Buttressed by theoretical treatments developed here using random phase approximation and polymer field-theoretic simulations, these observations indicate a partial compensation of effects between favorable solvent-mediated interactions among the polyampholytes in the condensed phase and favorable polyampholyte-solvent interactions in the dilute phase, often netting only a minor enhancement of overall LLPS propensity from the very dielectric heterogeneity that arises from the LLPS itself. Further ramifications of this principle are discussed.

Klebsiella pneumoniae with crude glycerol-utilizing and hydrogen (H 2 )-producing abilities was successfully isolated from return activated sludge from Shatin Sewage Treatment Works. The H 2 production strategy used in this study was optimized with crude glycerol concentrations, and 1,020 μmol of H 2 was generated in 3 h. An organic-microbe hybrid system was constructed with metal-free hydrothermal carbonation carbon (HTCC) microspheres to enhance the H 2 production under visible light (VL) irradiation. Under optimized VL intensity and HTCC concentration, an elevation of 35.3% in H 2 production can be obtained. Electron scavenger study revealed that the photogenerated electrons (e - ) from HTCC contributed to the additional H 2 production. The variation in intercellular intermediates, enzymatic activity, and reducing equivalents also suggested that the photogenerated e - interacted with K. pneumoniae cells to direct the metabolic flux toward H 2 production. This study demonstrated the feasibility of using an organic-microbe hybrid system as a waste-to-energy technology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chan, Xiao, Tsang, Zeng, Wang, Peng and Wong.)

Polyampholyte field theory and explicit-chain molecular dynamics models of sequence-specific phase separation of a system with two intrinsically disordered protein (IDP) species indicate consistently that a substantial polymer excluded volume and a significant mismatch of the IDP sequence charge patterns can act in concert, but not in isolation, to demix the two IDP species upon condensation. This finding reveals an energetic-geometric interplay in a stochastic, "fuzzy" molecular recognition mechanism that may facilitate subcompartmentalization of membraneless organelles.

Background and Aims: Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV-A). HEV species C genotype 1 (HEV-C1) circulates in rats and is highly divergent from HEV-A. It was previously considered unable to infect humans, but the first case of human HEV-C1 infection was recently discovered in Hong Kong. The aim of this study is to further describe the features of this zoonosis in Hong Kong., Approach and Results: We conducted a territory-wide prospective screening study for HEV-C1 infection over a 31-month period. Blood samples from 2,860 patients with abnormal liver function (n = 2,201) or immunosuppressive conditions (n = 659) were screened for HEV-C1 RNA. In addition, 186 captured commensal rats were screened for HEV-C1 RNA. Sequences of human-derived and rat-derived HEV-C1 isolates were compared. Epidemiological and clinical features of HEV-C1 infection were analyzed. HEV-C1 RNA was detected in 6/2,201 (0.27%) patients with hepatitis and 1/659 (0.15%) immunocompromised persons. Including the previously reported case, eight HEV-C1 infections were identified, including five in patients who were immunosuppressed. Three patients had acute hepatitis, four had persistent hepatitis, and one had subclinical infection without hepatitis. One patient died of meningoencephalitis, and HEV-C1 was detected in cerebrospinal fluid. HEV-C1 hepatitis was generally milder than HEV-A hepatitis. HEV-C1 RNA was detected in 7/186 (3.76%) rats. One HEV-C1 isolate obtained from a rat captured near the residences of patients was closely related to the major outbreak strain., Conclusions: HEV-C1 is a cause of hepatitis E in humans in Hong Kong. Immunosuppressed individuals are susceptible to persistent HEV-C1 infection and extrahepatic manifestations. Subclinical HEV-C1 infection threatens blood safety. Tests for HEV-C1 are required in clinical laboratories., (© 2020 by the American Association for the Study of Liver Diseases.)