A Randomized Evaluation of MoodFX, a Patient-Centred e-Health Tool to Support Outcome Measurement for Depression: Une évaluation randomisée de MoodFX, un outil de santé en ligne centré sur le patient pour soutenir la mesure du résultat dans la dépression.

BACKGROUND: e-Health tools using validated questionnaires to assess outcomes may facilitate measurement-based care for psychiatric disorders. MoodFX was created as a free online symptom tracker to support patients for outcome measurement in their depression treatment. We conducted a pilot randomized evaluation to examine its usability, and clinical utility. METHODS: Patients presenting with a major depressive episode (within a major depressive or bipolar disorder) were randomly assigned to receive either MoodFX or a health information website as the intervention and control condition, respectively, with follow-up assessment surveys conducted online at baseline, 8 weeks and 6 months. The primary usability outcomes included the percentage of patients with self-reported use of MoodFX 3 or more times during follow up (indicating minimally adequate usage) and usability measures based on the System Usability Scale (SUS). Secondary clinical outcomes included the Quick Inventory of Depressive Symptomatology, Self-Rated (QIDS-SR) and Patient Health Questionnaire (PHQ-9). RESULTS: Forty-nine participants were randomized (24 to MoodFX and 25 to the control condition). Of the 23 participants randomized to MoodFX who completed the user survey, 18 (78%) used MoodFX 3 or more times over the 6 months of the study. The mean SUS score of 72.7 (65th-69th percentile) represents good usability. Compared to the control group, the MoodFX group had significantly better improvement on QIDS-SR and PHQ-9 scores, with large effect sizes and higher response rates at 6 months. There were no differences between conditions on other secondary outcomes such as functioning and quality of life. CONCLUSION: MoodFX demonstrated good usability and was associated with reduction in depressive symptoms. This pilot study supports the use of digital tools in depression treatment.

E-health tools may be useful for measuring and tracking symptoms and other outcomes during treatment for depression. This study is a randomized evaluation of MoodFX, a free web-based app that helps patients track their symptoms using validated questionnaires, and also offers depression information and self-management tips. A total of 49 participants with clinical depression were randomized to using MoodFX or a health information website, for 6 months. In a survey, the participants that used MoodFX found it easy and useful to use. In addition, the participants that used MoodFX had greater improvement in depressive symptoms after 6 months, compared to those who used the health information website. These results suggest that MoodFX may be a useful tool to monitor outcomes and support depression treatment.

Crystal structure of (S)-5-(3-acetyl-5-chloro-2-ethoxy-6-fluorophenyl)-2-oxazolidinone.

The structure of (S)-5-(3-acetyl-5-chloro-2-ethoxy-6-fluorophenyl)-2-oxazolidinone, C13H13ClFNO4, at 100 K has monoclinic (P21) symmetry. The compound has a polymeric structure propagated by a screw axis parallel to the b axis with N-H⋯O hydrogen bonding. It is of inter-est with respect to efforts in the synthesis of a candidate anti-cancer drug, parsaclisib.

Systematic review on intentional non-medical fentanyl use among people who use drugs.

Objectives: Fentanyl is a highly potent opioid and has, until recently, been considered an unwanted contaminant in the street drug supply among people who use drugs (PWUD). However, it has become a drug of choice for an increasing number of individuals. This systematic review evaluated intentional non-medical fentanyl use among PWUD, specifically by summarizing demographic variance, reasons for use, and resulting patterns of use. Methods: The search strategy was developed with a combination of free text keywords and MeSH and non-MeSH keywords, and adapted with database-specific filters to Ovid MEDLINE, Embase, Web of Science, and PsychINFO. Studies included were human studies with intentional use of non-medical fentanyl or analogues in individuals older than 13. Only peer-reviewed original articles available in English were included. Results: The search resulted in 4437 studies after de-duplication, of which 132 were selected for full-text review. Out of 41 papers included, it was found that individuals who use fentanyl intentionally were more likely to be young, male, and White. They were also more likely to have experienced overdoses, and report injection drug use. There is evidence that fentanyl seeking behaviours are motivated by greater potency, delay of withdrawal, lower cost, and greater availability. Conclusions: Among PWUD, individuals who intentionally use fentanyl have severe substance use patterns, precarious living situations, and extensive overdose history. In response to the increasing number of individuals who use fentanyl, alternative treatment approaches need to be developed for more effective management of withdrawal and opioid use disorder. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021272111.

Competition-driven eco-evolutionary feedback reshapes bacteriophage lambda's fitness landscape and enables speciation.

A major challenge in evolutionary biology is explaining how populations navigate rugged fitness landscapes without getting trapped on local optima. One idea illustrated by adaptive dynamics theory is that as populations adapt, their newly enhanced capacities to exploit resources alter fitness payoffs and restructure the landscape in ways that promote speciation by opening new adaptive pathways. While there have been indirect tests of this theory, to our knowledge none have measured how fitness landscapes deform during adaptation, or test whether these shifts promote diversification. Here, we achieve this by studying bacteriophage [Formula: see text], a virus that readily speciates into co-existing receptor specialists under controlled laboratory conditions. We use a high-throughput gene editing-phenotyping technology to measure [Formula: see text]'s fitness landscape in the presence of different evolved-[Formula: see text] competitors and find that the fitness effects of individual mutations, and their epistatic interactions, depend on the competitor. Using these empirical data, we simulate [Formula: see text]'s evolution on an unchanging landscape and one that recapitulates how the landscape deforms during evolution. [Formula: see text] heterogeneity only evolves in the shifting landscape regime. This study provides a test of adaptive dynamics, and, more broadly, shows how fitness landscapes dynamically change during adaptation, potentiating phenomena like speciation by opening new adaptive pathways.

Imaged capillary isoelectric focusing tandem high-resolution mass spectrometry using nano electrospray ionization (ESI) for protein heterogeneity characterization.

Recombinant monoclonal antibodies (mAbs) have been spurring the rapid growth of commercial biotherapeutics. During production their charge heterogeneity must be assessed as a critical quality attribute to ensure safety, efficacy, and potency. Although imaged capillary isoelectric focusing (icIEF) is a powerful tool for this process, it could be improved further with tandem high-resolution mass spectrometry (HRMS). In this work, a nano-electrospray ionization (nano-ESI) apparatus was constructed to directly couple icIEF to HRMS. The system was evaluated with the standard NISTmAb, as well as more complex mAb, bi-specific antibody, and fusion protein samples. NISTmAb concentrations as low as 0.25 mg/ml demonstrated excellent sensitivity. There were good repeatabilities at 1 mg/ml with 7.58% and 8.01% RSDs for intention time and MS intensity, respectively, and the HRMS signal showed a strong linearity (R = 0.9983) across different concentrations. Meanwhile, the fingerprinting of the complex samples illustrated the versatility and potential of icIEF-HRMS. icIEF-HRMS developed can provide a comprehensive understanding of the underlying structural modifications that impact protein charge heterogeneity. Compared to the traditional ESI, nano-ESI can significantly improve sensitivity while maintaining a reasonable repeatability and throughput. Furthermore, the interface is much easier to connect, and is compatible with many commercial HRMS instruments.

Competition-driven eco-evolutionary feedback reshapes bacteriophage lambda's fitness landscape and enables speciation.

A major challenge in evolutionary biology is explaining how populations navigate rugged fitness landscapes without getting trapped on local optima. One idea illustrated by adaptive dynamics theory is that as populations adapt, their newly enhanced capacities to exploit resources alter fitness payoffs and restructure the landscape in ways that promote speciation by opening new adaptive pathways. While there have been indirect tests of this theory, none have measured how fitness landscapes deform during adaptation, or test whether these shifts promote diversification. Here, we achieve this by studying bacteriophage λ, a virus that readily speciates into co-existing receptor specialists under controlled laboratory conditions. We used a high-throughput gene editing-phenotyping technology to measure λ's fitness landscape in the presence of different evolved-λ competitors and found that the fitness effects of individual mutations, and their epistatic interactions, depend on the competitor. Using these empirical data, we simulated λ's evolution on an unchanging landscape and one that recapitulates how the landscape deforms during evolution. λ heterogeneity only evolved in the shifting landscape regime. This study provides a test of adaptive dynamics, and, more broadly, shows how fitness landscapes dynamically change during adaptation, potentiating phenomena like speciation by opening new adaptive pathways.

A profile of patients' and doctors' perceptions, acceptance, and utilization of e-health in a deprived region in southwestern China.

BACKGROUND: E-health has the potential to promote health accessibility, performance and cost-saving. However, the adoption and penetration of e-health in underprivileged areas remains insufficient. We aim to investigate patients' and doctors' perception, acceptance, and utilization of e-health in a rural, spatially isolated and poverty-stricken county in southwestern China. METHODS: A retrospective analysis based on a cross-sectional survey of patients and doctors in 2016 was conducted. Participants were recruited through convenience and purposive sampling, and questionnaires were self-designed and validated by investigators. The utilization, intention to use and preference of four e-health services were evaluated, including e-appointment, e-consultation, online drug purchase, and telemedicine. Predictors of utilization and intention to use e-health services were investigated by multivariable logistic regression. RESULTS: A total of 485 patients were included. The utilization rate of any type of e-health services was 29.9%, ranging from 6% in telemedicine to 18% in e-consultation. Additionally, 13.9%-30.3% of respondents as non-users revealed their willingness to use such services. Users and potential users of e-health services were inclined to specialized care from county, city or province hospitals, and they were most concerned with the quality, ease of use and price of e-health service. Patients' utilization and intention to use e-health could be associated with education and income level, cohabitants, working location, previous medical utilization, and access to digital device and internet. There remained 53.9%-78.3% of respondents reluctant to use e-health services, mainly due to perceived inability to use them. Of 212 doctors, 58% and 28% had provided online consultation and telemedicine before, and over 80% of county-hospital doctors (including actual providers) indicated their willingness to provide such services. Reliability, quality and ease of use were doctors' major concerns regarding e-health. Doctors' actual provision of e-health was predicted by their professional title, number of years in work, satisfaction with the wage incentive system, and self-rated health. Nevertheless, their willingness to adopt was only associated with the possession of smartphone. CONCLUSIONS: E-health is still in its infancy in western and rural China, where health resources are most scarce, and where e-health could prove most beneficial. Our study reveals the wide gaps between patients' low usage and their certain willingness to use e-health, as well as gaps between patients' moderate attention to use and physician's high preparedness to adopt e-health. Patients' and doctors' perceptions, needs, expectations, and concerns should be recognized and considered to promote the development of e-health in these underprivileged regions.

Exploring the Past, Present, and Future of Anti-Angiogenic Therapy in Glioblastoma.

Glioblastoma, a WHO grade IV astrocytoma, constitutes approximately half of malignant tumors of the central nervous system. Despite technological advancements and aggressive multimodal treatment, prognosis remains dismal. The highly vascularized nature of glioblastoma enables the tumor cells to grow and invade the surrounding tissue, and vascular endothelial growth factor-A (VEGF-A) is a critical mediator of this process. Therefore, over the past decade, angiogenesis, and more specifically, the VEGF signaling pathway, has emerged as a therapeutic target for glioblastoma therapy. This led to the FDA approval of bevacizumab, a monoclonal antibody designed against VEGF-A, for treatment of recurrent glioblastoma. Despite the promising preclinical data and its theoretical effectiveness, bevacizumab has failed to improve patients' overall survival. Furthermore, several other anti-angiogenic agents that target the VEGF signaling pathway have also not demonstrated survival improvement. This suggests the presence of other compensatory angiogenic signaling pathways that surpass the anti-angiogenic effects of these agents and facilitate vascularization despite ongoing VEGF signaling inhibition. Herein, we review the current state of anti-angiogenic agents, discuss potential mechanisms of anti-angiogenic resistance, and suggest potential avenues to increase the efficacy of this therapeutic approach.

What dictates income in New York City? SHAP analysis of income estimation based on Socio-economic and Spatial Information Gaussian Processes (SSIG).

Income inequality presents a key challenge to urban sustainability across the developed economies. Traditionally, accurate high granularity income data are generally obtained from field surveys. However, due to privacy considerations, field subjects are hesitant to provide accurate personal income data. A Socio-economic & Spatial-Information-GP (SSIG) model is thereby developed to estimate district-based high granularity income for New York City (NYC). As compared to the state-of-the-art Gaussian Processes (GP) income estimation model based entirely on spatial information, SSIG incorporates socio-economic domain-specific knowledge into a GP model. For SSIG to be explainable, SHapley Additive exPlanations (SHAP) analysis is undertaken to evaluate the relative contribution of various key individual socio-economic variables to district-based per-capita and median household income in NYC. Differentiating from traditional income inequality studies based predominantly on linear or log-linear regression model, SSIG presents a novel income-based model architecture, capable of modelling complex non-linear relationships. In parallel, SHAP analysis serves an effective analytical tool for identifying the key attributes to income inequality. Results have shown that SSIG surpasses other state-of-the-art baselines in estimation accuracy, as far as per-capita and median household income estimation at the Tract-level and the ZIP-level in NYC are concerned. SHAP results have indicated that having a bachelor or a postgraduate degree can accurately predict income in NYC, despite that between-district income inequality due to Sex/Race remains prevalent. SHAP has further confirmed that between-district income gap is more associated with Race than Sex. Furthermore, ablation study shows that socio-economic information is more predictive of income at the ZIP-level, relative to the spatial information. This study carries significant implications for policy-making in a developed context. To promote urban economic sustainability in NYC, policymakers can attend to the growing income disparity (income inequality) contributed by Sex and Race, while giving more higher education opportunities to residents in the lower-income districts, as the estimated per-capita income is more sensitive to the proportion of adults ≥25 holding a bachelor's degree. Finally, interpretative SHAP analysis is useful for investigating the relative contribution of socio-economic inputs to any predicted outputs in future machine-learning-driven socio-economic analyses.

Fractionation and online mass spectrometry based on imaged capillary isoelectric focusing (icIEF) for characterizing charge heterogeneity of therapeutic antibody.

Imaged capillary isoelectric focusing (icIEF) technology has been proved to be robust for the characterization of protein charge heterogeneity due to its high-resolution pI discrimination and high-throughput. Although high performance liquid chromatography (HPLC) tandem mass spectrometry (MS) and offline fraction collection technologies including isoelectric focusing (IEF), ion exchange chromatography (IEX) and free flow electrophoresis (FFE) have been widely utilized for protein charge variant characterization, there are a few applications of MS coupling with icIEF as a front-separation technique and related fractionation technologies for protein charge heterogeneity. However, the application of icIEF-MS has been much less frequent due to difficulties in MS interface, compatible ampholyte and coated capillary cartridge designation, ultimately impeding the breadth of icIEF applications in protein charge heterogeneity. In this study, a therapeutic monoclonal antibody (mAb-M-AT) was used for its charge variant characterization on an integrated icIEF platform with functions including analytical profiling, MS online coupling and fraction collection for charge heterogeneities. The main protein component and its four charge variants were identified using direct icIEF-MS coupling. Additionally, the two major acidic and basic charge variants were collected using preparative fractionation after the protein focused in the separation capillary. The identity of the fractions was confirmed by LC-MS at intact protein level and the results were consistent with those using icIEF-MS online coupling. The multiple operation modes of the icIEF platform described above can be rapidly and flexibly switched just by changing customized capillary separation cartridges without drastically altering instrument configuration. The whole workflow of icIEF-based profiling, fractionation and MS online coupling for protein heterogeneity is straightforward, reliable, and accurate, thus providing comprehensive solutions for in-depth protein heterogeneity characterization.

Imaged capillary isoelectric focusing (icIEF) tandem high resolution mass spectrometry for charged heterogeneity of protein drugs in biopharmaceutical discovery.

Since the first commercial imaged capillary isoelectric focusing (icIEF) instrument was developed twenty years ago, the technology has become the gold standard of quality and manufacturing process control in the biopharmaceutical industry. This is owing to its high-resolution and high-throughput characterization of protein charge heterogeneity. In addition to a charge variant profiling, mass spectrometry (MS) analyses are also desirable to obtain an in-tact molecular weight (MW) and further identification of these charged species. While offline fractionation technologies including isoelectric focusing (IEF) and free flow electrophoresis (FFE) followed by liquid chromatography (LC)-mass spectrometry (MS) coupling have been employed for this purpose, there have been much fewer reported applications of icIEF-based MS connection and fraction collection. Factors that have impeded the development of these icIEF applications include difficulties with a direct connection to the MS interface as well as high background signal of carrier ampholytes and incompatible coated capillary cartridges. In this work, we developed a robust and flexible icIEF-MS platform which overcomes these challenges to achieve both the rapid icIEF separation and high-resolution MS (HRMS) identification of protein charged variants simultaneously. We demonstrate how this methodology proves highly-sensitive and highly reliable for the characterization of commercial monoclonal antibodies (mAbs) and antibody-drug-conjugates (ADCs). The whole workflow of icIEF-MS for protein heterogeneity is straight forward and accurate and can be performed within 45 min. Furthermore, the developed icIEF-MS configuration can flexibly switch to icIEF-based fraction collection model allowing the user to perform additional in-depth characterization such as peptide mapping by high performance liquid chromatography (HPLC) tandem mass spectrometry (LC-MS/MS).

Cutting-edge mass spectrometry strategy based on imaged capillary isoelectric focusing (icIEF) technology for characterizing charge heterogeneity of monoclonal antibody.

Imaging capillary isoelectric focusing (icIEF) technology has been becoming the gold criteria of monitoring monoclonal antibody (mAb) charge heterogeneity that is one of the major product-related variants in recombinant biopharmaceuticals, since the first commercial instrument developed twenty years ago. However, the protein identification in icIEF separation is just based on isoelectric point (pI) measurement of protein. Although high resolution mass spectrometry (HRMS) is currently the most powerful means of qualitative protein analysis, traditional icIEF cannot compatibly be used in conjunction with MS due to the use of less volatile reagents. In addition, protein heterogeneity characterization in depth such as peptide mapping by high performance liquid chromatography (HPLC) requires the focused protein bands to be collected as fractions after the icIEF separation, which is a great challenge in biopharmaceutical discovery. In this work, pembrolizumab was employed as targeting mAb (a highly selective anti-PD-1 humanized mAb), an integrated icIEF platform was developed including analytical profiling, MS coupling and fraction collections for charged variant preparation. Multiple operation modes can be rapidly and flexibly switched just by changing customized capillary separation cartridges without more configurations. Main component, four acidic variants (A1-A4) and three basic variants (B1-B3) were baseline separated then directly detected by icIEF-HRMS online coupling for rapid screening of intact protein heterogeneity where reliable and accurate molecular weight of protein charged variants were obtained. Next, by installing preparative capillary separation cartridge, fractions of major charge variants (A2-3 and B1-2) and main component were collected for following LC-MS peptide mapping characterization. The whole workflow of icIEF-based MS strategy for protein heterogeneity is straight forward, reliable and accurate, which provides a comprehensive and revolutionary technology for protein drug quality control (QC) monitoring, MS coupling for fingerprinting intact protein and HPLC-MS peptide mapping in depth.

Equality and social determinants of spatial accessibility, availability, and affordability to primary health care in Hong Kong, a descriptive study from the perspective of spatial analysis.

OBJECTIVE: Primary health care (PHC) is widely perceived to be the backbone of health care systems. Since the outbreak of COVID-19, PHC has not only provided primary medical services, but also served as a grassroots network for public health. Our research explored the accessibility, availability, and affordability of primary health care from a spatial perspective, to understand the social determinants affecting access to it in Hong Kong. METHOD: This constitutes a descriptive study from the perspective of spatial analysis. The nearest neighbor method was used to measure the geographic accessibility of PHC based on the road network. The 2SFCA method was used to measure spatial availability and affordability to primary health care, while the SARAR model, Spatial Error model, and Spatial Lag model were then constructed to explain potential factors influencing accessibility and availability of PHC. RESULTS: In terms of accessibility, 95% of residents in Hong Kong can reach a PHC institution within 15 minutes; in terms of availability, 83% of residents can receive PHC service within a month; while in terms of affordability, only 32% of residents can afford PHC services with the support of medical insurance and medical voucher. In Hong Kong, education status and household income show a significant impact on accessibility and availability of PHC. Regions with higher concentrations of residents with post-secondary education receive more PHC resources, while regions with higher concentrations of high-income households show poorer accessibility and poorer availability to PHC. CONCLUSION: The good accessibility and availability of primary health care reflects that the network layout of existing PHC systems in Hong Kong is reasonable and can meet the needs of most residents. No serious gap between social groups further shows equality in resource allocation of PHC in Hong Kong. However, affordability of PHC is not ideal. Indeed, narrowing the gap between availability and affordability is key to fully utilizing the capacity of the PHC system in Hong Kong. The private sector plays an important role in this, but the low coverage of medical insurance in outpatient services exacerbates the crowding of public PHC and underutilization of private PHC. We suggest diverting patients from public to private institutions through medical insurance, medical vouchers, or other ways, to relieve the pressure on the public health system and make full use of existing primary health care in Hong Kong.

Somatic Mutations and Alzheimer's Disease.

Alzheimer's disease (AD) represents a global health challenge, with an estimated 55 million people suffering from the non-curable disease across the world. While amyloid-ß plaques and tau neurofibrillary tangles in the brain define AD proteinopathy, it has become evident that diverse coding and non-coding regions of the genome may significantly contribute to AD neurodegeneration. The diversity of factors associated with AD pathogenesis, coupled with age-associated damage, suggests that a series of triggering events may be required to initiate AD. Since somatic mutations accumulate with aging, and aging is a major risk factor for AD, there is a great potential for somatic mutational events to drive disease. Indeed, recent data from the Gozes team/laboratories as well as other leading laboratories correlated the accumulation of somatic brain mutations with the progression of tauopathy. In this review, we lay the current perspectives on the principal genetic factors associated with AD and the potential causes, highlighting the contribution of somatic mutations to the pathogenesis of late onset Alzheimer's disease. The roles that artificial intelligence and big data can play in accelerating the progress of causal somatic mutation markers/biomarkers identification, and the associated drug discovery/repurposing, have been highlighted for future AD and other neurodegenerations, with the aim to bring hope for the vulnerable aging population.

Oral microbiota signatures in post-traumatic stress disorder (PTSD) veterans.

Post-traumatic stress disorder (PTSD) represents a global public health concern, affecting about 1 in 20 individuals. The symptoms of PTSD include intrusiveness (involuntary nightmares or flashbacks), avoidance of traumatic memories, negative alterations in cognition and mood (such as negative beliefs about oneself or social detachment), increased arousal and reactivity with irritable reckless behavior, concentration problems, and sleep disturbances. PTSD is also highly comorbid with anxiety, depression, and substance abuse. To advance the field from subjective, self-reported psychological measurements to objective molecular biomarkers while considering environmental influences, we examined a unique cohort of Israeli veterans who participated in the 1982 Lebanon war. Non-invasive oral 16S RNA sequencing was correlated with psychological phenotyping. Thus, a microbiota signature (i.e., decreased levels of the bacteria sp_HMT_914, 332 and 871 and Noxia) was correlated with PTSD severity, as exemplified by intrusiveness, arousal, and reactivity, as well as additional psychopathological symptoms, including anxiety, hostility, memory difficulties, and idiopathic pain. In contrast, education duration correlated with significantly increased levels of sp_HMT_871 and decreased levels of Bacteroidetes and Firmicutes, and presented an inverted correlation with adverse psychopathological measures. Air pollution was positively correlated with PTSD symptoms, psychopathological symptoms, and microbiota composition. Arousal and reactivity symptoms were correlated with reductions in transaldolase, an enzyme controlling a major cellular energy pathway, that potentially accelerates aging. In conclusion, the newly discovered bacterial signature, whether an outcome or a consequence of PTSD, could allow for objective soldier deployment and stratification according to decreases in sp_HMT_914, 332, 871, and Noxia levels, coupled with increases in Bacteroidetes levels. These findings also raise the possibility of microbiota pathway-related non-intrusive treatments for PTSD.

Mobile Health Applications for Depression in China: A Systematic Review.

Mobile health (mHealth) applications (apps) have the potential to increase access to mental health care. In China, there is growing interest in mHealth apps for depression. Our objective was to systematically review research on mHealth for depression in China to identify benefits and challenges. A systematic literature search was conducted using Chinese and English databases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized and nonrandomized clinical studies on mHealth apps and depression in China were included. Study quality was assessed using the Cochrane Risk of Bias tool. Seven studies met the inclusion criteria with three randomized trials, two quasi-randomized trials, one clinical trial with an uncertain grouping method, and one study with a single-group design. All studies used the WeChat platform and included activities such as psychoeducation, self-management, supervised group chats, and/or remote contact with a healthcare team, in comparison to usual care. All studies reported significant and large benefits for outcomes, but the risk of bias was high. There are few rigorous evaluations of mHealth apps for depression in China, with all included studies involving WeChat programs and most using WeChat to extend nursing discharge care for inpatients with depression. While these studies showed significant improvement in health outcomes as compared to usual care, the results remain inconclusive because of the high risk of bias. mHealth holds promise for increasing access to mental health care in China, but issues such as efficacy, scalability, patient and clinician acceptability, and data privacy must be addressed.

Light-activated molecular machines are fast-acting broad-spectrum antibacterials that target the membrane.

The increasing occurrence of antibiotic-resistant bacteria and the dwindling antibiotic research and development pipeline have created a pressing global health crisis. Here, we report the discovery of a distinctive antibacterial therapy that uses visible (405 nanometers) light-activated synthetic molecular machines (MMs) to kill Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, in minutes, vastly outpacing conventional antibiotics. MMs also rapidly eliminate persister cells and established bacterial biofilms. The antibacterial mode of action of MMs involves physical disruption of the membrane. In addition, by permeabilizing the membrane, MMs at sublethal doses potentiate the action of conventional antibiotics. Repeated exposure to antibacterial MMs is not accompanied by resistance development. Finally, therapeutic doses of MMs mitigate mortality associated with bacterial infection in an in vivo model of burn wound infection. Visible light-activated MMs represent an unconventional antibacterial mode of action by mechanical disruption at the molecular scale, not existent in nature and to which resistance development is unlikely.

Brushed Metals for Rechargeable Metal Batteries.

Battery designs are swiftly changing from metal-ion to rechargeable metal batteries. Theoretically, metals can deliver maximum anode capacity and enable cells with improved energy density. In practice, these advantages are only possible if the parasitic surface reactions associated with metal anodes are controlled. These undesirable surface reactions are responsible for many troublesome issues, like dendrite formation and accelerated consumption of active materials, which leads to anodes with low cycle life or even battery runaway. Here, a facile and solvent-free brushing method is reported to convert powders into films atop Li and Na metal foils. Benefiting from the reactivity of Li metal with these powder films, surface energy can be effectively tuned, thereby preventing parasitic reaction. In-operando study of P2 S5 -modified Li anodes in liquid electrolyte cells reveals a smoother electrode contour and more uniform metal electrodeposition and dissolution behavior. The P2 S5 -modified Li anodes sustain ultralow polarization in symmetric cell for >4000 h, ≈8× longer than bare Li anodes. The capacity retention is ≈70% higher when P2 S5 -modified Li anodes are paired with a practical LiFePO4 cathode (≈3.2 mAh cm-2 ) after 340 cycles. Brush coating opens a promising avenue to fabricate large-scale artificial solid-electrolyte-interphase directly on metals without the need for organic solvent.

Blue-Light Therapy for Seasonal and Non-Seasonal Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To determine the efficacy and safety of blue-light therapy in seasonal and non-seasonal major depressive disorder (MDD), by comparison to active and inactive control conditions. METHODS: We searched Web of Science, EMBASE, Medline, PsycInfo, and Clinicaltrials.gov through January 17, 2022, for randomized controlled trials (RCTs) using search terms for blue/blue-enhanced, light therapy, and depression/seasonal affective disorder. Two independent reviewers extracted data. The primary outcome was the difference in endpoint scores on the Structured Interview Guide for the Hamilton Depression Rating Scale - Seasonal Affective Disorder (SIGH-SAD) or the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) between blue light and comparison conditions. Secondary outcomes were response (≥ 50% improvement from baseline to endpoint on a depression scale) and remission rates (endpoint score in the remission range). RESULTS: Of 582 articles retrieved, we included nine RCTs (n = 347 participants) assessing blue-light therapy. Seven studies had participants with seasonal MDD and two studies included participants with non-seasonal MDD. Four studies compared blue light to an inactive light condition (efficacy studies), and five studies compared it to an active condition (comparison studies). For the primary outcome, a meta-analysis with random-effects models found no evidence for the efficacy of blue-light conditions compared to inactive conditions (mean difference [MD] = 2.43; 95% confidence interval [CI], -1.28 to 6.14, P = 0.20); however, blue-light also showed no differences compared to active conditions (MD = -0.11; 95% CI, -2.38 to 2.16, P = 0.93). There were no significant differences in response and remission rates between blue-light conditions and inactive or active light conditions. Blue-light therapy was overall well-tolerated. CONCLUSIONS: The efficacy of blue-light therapy in the treatment of seasonal and non-seasonal MDD remains unproven. Future trials should be of longer duration, include larger sample sizes, and attempt to better standardize the parameters of light therapy.