Predicting herd immunity achievement: a time-series analysis of vaccination and fatality rates using 1,075 days of COVID-19 data.

Introduction: The COVID-19 pandemic, driven by SARS-CoV-2, has made vaccination a critical strategy for global control. However, vaccine hesitancy, particularly among certain age groups, remains a significant barrier to achieving herd immunity. Methods: This study uses Poisson regression and ARIMA time-series modeling to identify factors contributing to vaccine hesitancy, understand age-specific vaccination preferences, and assess the impact of bivalent vaccines on reducing hesitancy and fatality rates. It also predicts the time required to achieve herd immunity by analyzing factors such as vaccine dosing intervals, age-specific preferences, and changes in fatality rates. Results: The study finds that individuals recovering from COVID-19 often delay vaccination due to perceived immunity. There is a preference for combining BNT162b2 and CoronaVac vaccines. The BNT162b2 bivalent vaccine has significantly reduced vaccine hesitancy and is linked with lower fatality rates, particularly in those aged 80 and above. However, it tends to induce more severe side effects compared to Sinovac. Vaccine hesitancy is most prevalent among the youngest (0-11) and oldest (80+) age groups, posing a challenge to reaching 90% vaccination coverage. Conclusion: Vaccine hesitancy is a major obstacle to herd immunity. Effective strategies include creating urgency, offering incentives, and prioritizing vulnerable age groups. Despite these challenges, the government should have continued to encourage vaccinations while gradually lifting COVID-19 control measures, balancing public health safety with the return to normal life, as was observed in the transition period during the latter stages of the pandemic.

Evaluation of Cost-Effectiveness of a Virtual Multidisciplinary Stroke Care Clinic for Community-Dwelling Survivors of Stroke.

BACKGROUND: A technologically integrated, multidisciplinary approach to stroke rehabilitation service was delivered and embedded into conventional health care practice. This article reports an evaluation of cost-effectiveness analysis of a new Virtual Multidisciplinary Stroke Care Clinic (VMSCC) service for community-dwelling survivors of stroke. METHODS AND RESULTS: A randomized controlled trial was conducted. Adults with a first/recurrent ischemic/hemorrhagic stroke were recruited from 10 hospitals. Eligible participants were randomly assigned to receive the VMSCC service (individual virtual consultations with a registered nurse, home blood pressure telemonitoring, and unlimited access to an online resource platform) plus usual care or usual care alone. Cost-effectiveness analyses were performed based on incremental cost-effectiveness ratios expressed as incremental cost per emergency admission reduced, and day of hospitalization reduced over the study period. A total of 256 participants (intervention group n=141 versus control group n=115) with complete cost and health care use data were included in the cost-effectiveness analyses. The VMSCC service, on average, resulted in a greater reduction in the number of emergency admission (-0.06 [95% bootstrapped CI, -0.14 to 0.01]) and fewer days of hospitalization (-0.08, [95% bootstrapped CI -0.40 to 0.24]) but incurred a higher total cost of HK$375 (95% bootstrapped CI, -2103 to 2743) compared with the usual care. The incremental cost-effectiveness ratios of the VMSCC service compared with the usual care were HK$6070 and HK$4826 per an emergency admission and a day of hospital stay reduced respectively. CONCLUSIONS: The study provides preliminary but not confirmative evidence that the VMSCC service could be more effective but more costly than usual care in reducing health service use. REGISTRATION: URL: https://www.chictr.org.cn. Unique identifier: ChiCTR1800016101.

Admission blood tests predicting survival of SARS-CoV-2 infected patients: a practical implementation of graph convolution network in imbalance dataset.

BACKGROUND: Predicting an individual's risk of death from COVID-19 is essential for planning and optimising resources. However, since the real-world mortality rate is relatively low, particularly in places like Hong Kong, this makes building an accurate prediction model difficult due to the imbalanced nature of the dataset. This study introduces an innovative application of graph convolutional networks (GCNs) to predict COVID-19 patient survival using a highly imbalanced dataset. Unlike traditional models, GCNs leverage structural relationships within the data, enhancing predictive accuracy and robustness. By integrating demographic and laboratory data into a GCN framework, our approach addresses class imbalance and demonstrates significant improvements in prediction accuracy. METHODS: The cohort included all consecutive positive COVID-19 patients fulfilling study criteria admitted to 42 public hospitals in Hong Kong between January 23 and December 31, 2020 (n = 7,606). We proposed the population-based graph convolutional neural network (GCN) model which took blood test results, age and sex as inputs to predict the survival outcomes. Furthermore, we compared our proposed model to the Cox Proportional Hazard (CPH) model, conventional machine learning models, and oversampling machine learning models. Additionally, a subgroup analysis was performed on the test set in order to acquire a deeper understanding of the relationship between each patient node and its neighbours, revealing possible underlying causes of the inaccurate predictions. RESULTS: The GCN model was the top-performing model, with an AUC of 0.944, considerably outperforming all other models (p < 0.05), including the oversampled CPH model (0.708), linear regression (0.877), Linear Discriminant Analysis (0.860), K-nearest neighbours (0.834), Gaussian predictor (0.745) and support vector machine (0.847). With Kaplan-Meier estimates, the GCN model demonstrated good discriminability between low- and high-risk individuals (p < 0.0001). Based on subanalysis using the weighted-in score, although the GCN model was able to discriminate well between different predicted groups, the separation was inadequate between false negative (FN) and true negative (TN) groups. CONCLUSION: The GCN model considerably outperformed all other machine learning methods and baseline CPH models. Thus, when applied to this imbalanced COVID survival dataset, adopting a population graph representation may be an approach to achieving good prediction.

Variability in Antimicrobial Prescribing Across Five Ambulatory Settings Within a Large Integrated Health System.

Background: Lack of access to timely, detailed antibiotic use data has limited ambulatory antibiotic stewardship efforts. Antibiotic utilization is tracked across ambulatory care sites and emergency departments (ED) within a large integrated health system. Methods: This is a retrospective cohort analysis from June 1, 2019 to May 31, 2020 comparing antibiotic prescribing for all patients with ICD-10 diagnosis codes for cystitis, otitis media, pharyngitis, sinusitis, and upper respiratory tract infections (URTIs) among five ambulatory care departments across northeast Ohio and southeast Florida locations: ED, Urgent Care (UC), On-Demand Telehealth (TEL), Pediatrics (PED), and Primary Care (PC). Results: A total of 261,947 encounters were included (ED:56,766, UC:92,749, TEL:8,783, PED:29,151, PC:74,498) for the treatment of cystitis (30,932), otitis media (22,094), pharyngitis (59,964), sinusitis (53,693), or URTI (95,264). The population was 63% female with a median age of 34.2 years [12.8-56.3]. A total of 17% of patients had documented penicillin allergies and 18% of patients with pharyngitis received Group A Streptococcus (GAS) testing. Antibiotics were prescribed in 44% of encounters (ED:21,746 [38%], UC:45,652 [49%], TEL:4,622 [53%], PED:10,909 [37%], PC:33,547 [45%]; P < 0.001). Guideline concordant antibiotics were prescribed in 65% of encounters (ED:14,338 [66%], UC:31,532 [69%], TEL:3,869 [84%], PED:8,212 [75%], PC:17,263 [51%]; P < 0.001). Conclusions: Observed rates of antibiotic and guideline concordant antibiotic prescribing were similar to national published rates of antibiotic prescribing in the ambulatory setting. The variability in antibiotic prescribing demonstrates opportunities for targeted outpatient stewardship efforts. Timely antibiotic tracking tools can facilitate ambulatory antimicrobial stewardship activities.

Development and validation of a health literacy scale for family caregivers of older people with chronic illness.

BACKGROUND: Family caregivers (FCs) encounter a variety of health problems in older people with chronic illness, necessitating a certain level of health literacy to access, understand, appraise and apply health information and services. This study aimed to develop and validate a scale for measuring health literacy among FCs of older people with chronic illness. METHODS: Concept mapping was first employed to develop a conceptual model of health literacy of FCs. Scale domains were derived from the conceptual model, and item generation was performed using deductive and inductive methods. Quantitative methods, including merging scale dimensions and items, expert reviews, cognitive interviews, and item reduction analysis, were used to refine the scale. Confirmatory factor analysis was employed to validate the scale's structure. Concurrent validity, internal consistency, and test-retest reliability were also examined. RESULTS: A 20-dimension conceptual model was developed, and 60 items were generated for the scale. Expert review (content validity index > 0.85) and cognitive interview with FCs confirmed the relevance and clarity of the majority of the generated scale items. Confirmatory factor analysis with 451 FCs of older people with chronic illness supported a 5-factor structure (symptom management, daily personal care and household tasks, care coordination, communication and relationship with the care recipient, and self-care of caregivers) with 42 finalized scale items, including four levels of health literacy skills (accessing, understanding, appraising and applying health information). Concurrent validity with the European Health Literacy Questionnaire (HLS-EU-Q47) was satisfactory (r = 0.67, p < 0.01). The Cronbach's α coefficient of the scale was 0.96, with subscales ranging from 0.84 to 0.91. The two-week test-retest reliability was 0.77 (p < 0.01). CONCLUSION: This study developed a conceptual model explaining the concept and factors of health literacy among FCs of older people with chronic illness that could provide the groundwork for future studies in developing relevant evidence-based interventions. A new Health Literacy Scale-Family Caregiver (HLS-FC) with satisfactory psychometric properties was developed in this study, which can be utilized to identify caregivers with insufficient health literacy and facilitate timely interventions by healthcare professionals.

Psychometric testing of the training needs for advance care planning scale for clinicians and nurses.

BACKGROUND: Studies have shown that Chinese Clinicians and nurses have positive attitudes toward ACP, but no local tools exist to assess their need for ACP knowledge and skills training. resulting in their inability to initiate ACP conversations as well as poor end-of-life care for patients. Therefore, this study aims to assess the needs of Chinese Clinicians and nurses for ACP knowledge and skills training and assess the validity and reliability of a questionnaire on the Training Needs for Advance Care Planning (TNACP) scale. METHODS: From October to November 2021, 170 clinicians and nurses were pre-surveyed using a preliminary draft of the questionnaire. The responses were screened using item analysis, Cronbach's alpha coefficient, and the intraclass correlation coefficient (ICC) to describe the internal consistency and stability of the questionnaire. The Content validity index (CVI), Exploratory factor analysis (EFA) and Confirmatory factor analysis (CFA) were used to test the validity of the questionnaire. RESULTS: After independent samples t-test analysis, Except for the entry "A2", the critical ratio between the two groups of the remaining 23 items was statistically significant (p < 0.05). Based on the above screening methods, the "A2" item was deleted, and the final number of questionnaire items was 23. The I-CVI was 0.79-1.00, and the S-CVI/Ave was 0.90. Three common factors were extracted-the cumulative contribution rate was 69.969%, and the factor loading of all items was 0.506-0.843 (all > 0.40). The results of confirmatory factor analysis showed that the Training Needs for Advance Care Planning (TNACP) scale model fit well(X2/df = 2.504, RMSEA = 0.092, GFI = 0.809, AGFI = 0.745, CFI = 0.931, IFI = 0.932, TLI = 0.916); the Cronbach's α = 0.888 for the total questionnaire, and the three dimensions of Cronbach's α were 0.729 to 0.959; and the ICC for the overall scores between the test-retest evaluations was 0.884 (p < 0.001). CONCLUSIONS: The TNACP scale has good reliability and validity and can be used to assess Chinese Clinicians and nurses' training needs for implementing ACP.

Compliance of healthcare workers in a psychiatric inpatient ward to infection control practices during the COVID-19 pandemic: a participant observation study supplemented with a self-reported survey.

BACKGROUND: As an emerging infectious disease with a heterogenous and uncertain transmission pattern, coronavirus disease 2019 (COVID-19) has created a catastrophe in healthcare-associated infections (HAIs) and posed a significant challenge to infection control practices (ICPs) in healthcare settings. While the unique characteristics of psychiatric patients and clinical settings may make the implementation of ICPs difficult, evidence is lacking for compliance with ICPs among healthcare workers (HCWs) in a psychiatric setting during the COVID-19 pandemic. METHODS: A cross-sectional multi-method study based on participant unobtrusive observation coupled with the completion of a self-administered ICP survey was conducted to assess compliance with ICPs among HCWs in a psychiatric inpatient ward in a regional hospital. An online checklist, called eRub, was used to record the performance of HCWs in hand hygiene (HH) and other essential ICPs. Furthermore, a well-validated questionnaire (i.e., Compliance with Standard Precautions Scale, CSPS) was used to collect the participants' self-reported ICP compliance for later comparison. RESULTS: A total of 2,670 ICP opportunities were observed from January to April 2020. The overall compliance rate was 42.6%. HCWs exhibited satisfactory compliance to the wearing of mask (91.2%) and the handling of clinical waste (87.5%); suboptimal compliance to the handling of sharp objects (67.7%) and linen (72.7%); and poor compliance to HH (3.3%), use of gloves (40.9%), use of personal protective equipment (20%), and disinfection of used surface/area (0.4%). The compliance rates of the nurses and support staff to HH were significantly different (χ2 = 123.25, p < 0.001). In the self-reported survey, the overall compliance rate for ICPs was 64.6%. CONCLUSION: The compliance of HCWs in a psychiatric inpatient ward to ICPs during the COVID-19 pandemic ranged from poor to suboptimal. This result was alarming. Revisions of current ICP guidelines and policies that specifically target barriers in psychiatric settings will be necessary.

A qualitative examination of the experiences and perspectives of interprofessional primary health care teams in the distribution of the COVID-19 vaccination in Ontario, Canada.

BACKGROUND: Primary health care (PHC) teams contributed to all phases of the COVID-19 vaccination distribution. However, there has been criticism for not fully utilizing the expertise and infrastructure of PHC teams for vaccination distribution. Our study sought to understand the role PHC teams had in the distribution of the COVID-19 vaccine in Ontario, Canada. The key objective informing this study was to explore the experiences and perspectives of interprofessional PHC teams in the distribution of COVID-19 vaccination across Ontario. METHODS: A qualitative approach was used for this study, which involved 39 participants from the six health regions of the province. Eight focus groups were conducted with a range of interprofessional healthcare providers, administrators, and staff working in PHC teams across Ontario. The sample reflected a diverse range of clinical, administrative, and leadership roles in PHC. Focus groups were audio-recorded and transcribed, while transcriptions were then analyzed using thematic analysis. RESULTS: We identified the following four themes in the data: i) PHC teams know their patients; ii) mobilizing team capacity for vaccination, iii) intersectoral collaborations, and iv) operational challenges. CONCLUSIONS: PHC teams were an instrumental component in supporting COVID-19 vaccinations in Ontario. The involvement of PHC in future vaccination efforts is key but requires additional resourcing and inclusion of PHC in decision-making. This will ensure provider well-being and maintain collaborations established during COVID-19 vaccination.

International assessment results on non-NIOSH approved respirators by the national personal protective technology laboratory (NPPTL): a data note.

OBJECTIVES: Due to the COVID-19 pandemic and the shortage of the National Institute for Occupational Safety & Health (NIOSH)-approved N95 respirators, the Food and Drug Administration granted an Emergency Use Authorization to allow the use of non-NIOSH approved respirators provided that these respirators must undergo tests by a protocol of TEB-APR-STP-0059, similar methods of NIOSH standard testing procedure. This initiative safeguards the quality of respirators and the effectiveness of occupational protection. The dataset of all the testing results could benefit further analysis of COVID-19 infection rates in relation to different types of N95 respirators used and identify potential correlations of various test parameters in the testing system for validation. The analysis enhances understanding of the quality, effectiveness, and performance of N95 respirators in the prevention of respiratory infectious transmission and develops improved occupational safety measures. DATA DESCRIPTION: The dataset was transformed, transcribed, and compiled from the official testing data of non-NIOSH-approved N95 respirators reported in the NIOSH website under the Centers for the Disease Control and Prevention in the United States. The dataset included details of 7,413 testing results of N95 respirators (manufacturer, model, and maximum and minimum filtration efficiency) and test parameters (flow rate, initial filter resistance, and initial percent leakage). Supplementary items were added to increase the availability of data analysis and enhance the interpretability of the assessments of the quality of N95 respirators.

Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS.

The nucleoside analogue decitabine (or 5-aza-dC) is used to treat several haematological cancers. Upon its triphosphorylation and incorporation into DNA, 5-aza-dC induces covalent DNA methyltransferase 1 DNA-protein crosslinks (DNMT1-DPCs), leading to DNA hypomethylation. However, 5-aza-dC's clinical outcomes vary, and relapse is common. Using genome-scale CRISPR/Cas9 screens, we map factors determining 5-aza-dC sensitivity. Unexpectedly, we find that loss of the dCMP deaminase DCTD causes 5-aza-dC resistance, suggesting that 5-aza-dUMP generation is cytotoxic. Combining results from a subsequent genetic screen in DCTD-deficient cells with the identification of the DNMT1-DPC-proximal proteome, we uncover the ubiquitin and SUMO1 E3 ligase, TOPORS, as a new DPC repair factor. TOPORS is recruited to SUMOylated DNMT1-DPCs and promotes their degradation. Our study suggests that 5-aza-dC-induced DPCs cause cytotoxicity when DPC repair is compromised, while cytotoxicity in wild-type cells arises from perturbed nucleotide metabolism, potentially laying the foundations for future identification of predictive biomarkers for decitabine treatment.

The mediating effect of dispositional mindfulness on the association between UPPS-P impulsivity traits and gaming disorder among Asia-Pacific young adults.

BACKGROUND: Little evidence is available to verify the mediating effect of dispositional mindfulness on the association between gaming disorder and various impulsivity traits. The present study aimed to investigate the mediating effect of dispositional mindfulness on the association between the five UPPS-P impulsivity traits and the risk of gaming disorder among young adults. METHODS: It was an inter-regional cross-sectional study using online survey in Australia, Japan, The Philippines and China. Impulsivity measured by the UPPS-P Impulsive Behavior Scale-Short version; dispositional mindfulness measured by the Mindfulness Attention Awareness Scale; and the risk of gaming disorder measured by the Internet Gaming Disorder Scale were collected in the focal regions. Structural equation modeling was performed by SPSS AMOS version 26 to verify the study hypotheses. Bootstrapped 95% confidence interval was reported. Statistical significance was indicated by the p-value below 0.05. RESULTS: Among the 1,134 returned questionnaires, about 40% of them aged 18-20 years and 21-23 years, respectively. 53.8% were male. 40.7% had been playing digital and video games for over 10 years. The prevalence of gaming disorder was 4.32%. The model fitness indices reflected that the constructed model had an acceptable model fit (χ2(118) = 558.994, p < 0.001; χ2/df = 4.737; CFI = 0.924; TLI = 0.890; GFI = 0.948; RMSEA = 0.058; SRMR = 0.0487). Dispositional mindfulness fully mediated the effect of positive urgency and negative urgency on the risk of gaming disorder. The effect of lack of premeditation on the risk of gaming disorder was partially mediated by dispositional mindfulness. However, dispositional mindfulness did not mediate the effect of sensation seeking on the risk of gaming disorder. CONCLUSIONS: The varied associations between dispositional mindfulness and the five impulsivity traits hints that improving some impulsive traits may increase dispositional mindfulness and so lower the risk of gaming disorder. Despite further studies are needed to verify the present findings, it sheds light on the need to apply interventions on gamers based on their impulsivity profile. Interventions targeting at emotion regulation and self-control such as mindfulness-based interventions seem to be effective to help gamers with dominant features of urgency and lack of premeditation only. Other interventions shall be considered for gamers with high sensation seeking tendency to enhance the effectiveness of gaming disorder prevention.

Patterns of sedentary behavior among older women with urinary incontinence and urinary symptoms: a scoping review.

BACKGROUND: Independent of physical activity, sedentary behavior has emerged as a significant risk factor for health. Particularly, older adults spent as high as 13 h daily on sedentary activities, which account for 98% of their awake times. Although there is growing evidence revealing the potential association between sedentary behavior and urinary incontinence (UI) across populations of different ages, the relationship between sedentary behavior and urinary symptoms in older women, who are twice as likely to have UI than older men, has not been reviewed. This scoping review aimed to synthesize available evidence of the relationship between sedentary behavior and urinary symptoms in noninstitutionalized older women. METHODS: Six electronic databases (PubMed, Web of Science, SPORTDiscus, Ovid Nursing Database, EMBASE, and MEDLINE) were searched from their inception to April 2023. Observational and experimental studies that measured sedentary behavior using objective and/or self-reported methods in older women aged 60 + years having any type of UI, with English full texts available, were included. Relevant data, including sedentary patterns (types, definitions, measurements, and daily patterns) and UI types were tabulated. A narrative synthesis of the findings was also conducted. RESULTS: A total of seven studies (n = 1,822) were included for review and reporting. Objective measurement showed that older women with UI were engaged in > 8 h sedentary activities daily (493.3-509.4 min/day), which accounted for 73% of their awake times. The duration of self-reported sedentary behavior was lower than the time measured objectively, and the average weekday sitting time was 300-380 min/day. With or without adjustment for confounding factors (e.g., age and number of vaginal deliveries), the daily proportion of sedentary time and average duration of sedentary bouts were positively associated with the prevalence of urgency UI. Notably, sedentary patients with UI were more likely to have lower urinary tract symptoms, including bothersome incontinence, to use incontinence products, and to have nocturia episodes, than their age-matched counterparts who were less sedentary. CONCLUSION: Our findings suggest a potential relationship between sedentary behavior and UI in older women, but the causality of the relationship remains unclear. To further inform the clinical role of sedentary behavior in the context of UI, a greater number of rigorous studies with a prospective study design is urgently needed.

Transcription-coupled repair of DNA-protein cross-links depends on CSA and CSB.

Covalent DNA-protein cross-links (DPCs) are toxic DNA lesions that block replication and require repair by multiple pathways. Whether transcription blockage contributes to the toxicity of DPCs and how cells respond when RNA polymerases stall at DPCs is unknown. Here we find that DPC formation arrests transcription and induces ubiquitylation and degradation of RNA polymerase II. Using genetic screens and a method for the genome-wide mapping of DNA-protein adducts, DPC sequencing, we discover that Cockayne syndrome (CS) proteins CSB and CSA provide resistance to DPC-inducing agents by promoting DPC repair in actively transcribed genes. Consequently, CSB- or CSA-deficient cells fail to efficiently restart transcription after induction of DPCs. In contrast, nucleotide excision repair factors that act downstream of CSB and CSA at ultraviolet light-induced DNA lesions are dispensable. Our study describes a transcription-coupled DPC repair pathway and suggests that defects in this pathway may contribute to the unique neurological features of CS.

Effects of exercise interventions on brain-derived neurotrophic factor levels in overweight and obesity: A systematic review and meta-analysis.

Background: /Objective. An explosion in global obesity epidemic poses threats to the healthcare system by provoking risks of many debilitating diseases, including cognitive dysfunction. Physical activity has been shown to alleviate the deleterious effects of obesity-associated cognitive deficits across the lifespan. Given the strong neuroprotective role of brain-derived neurotrophic factor (BDNF) and exercise training as a known modulator for its elevation, this systematic review sought to examine the strength of the association between exercise and BDNF levels in healthy people with overweight and obesity. Methods: Six electronic databases (PubMed, MEDLINE, EMBASE, Web of Science, Ovid Nursing Database, and SPORTDiscus) were searched from their inceptions through December 2022. The primary outcome of interest was BDNF levels. Interventional studies (randomized and quasi-experimental) with English full text available were included. Risk of bias of the included studies was assessed using the Physiotherapy Evidence Database Scale. Data were extracted for meta-analyses by random-effects models. Results: Thirteen studies (n = 750), of which 69.2% (9/13) had low risk of bias, were included. In the meta-analysis, exercise interventions had no significant effect on resting BDNF levels (standardized mean difference: -0.30, 95% CI -0.80 to 0.21, P = 0.25). Subgroup analyses also indicated no effects of age and types of control groups being compared on moderating the association. Conclusion: To further inform the role of BDNF in obesity-related cognitive functioning, rigorous studies with larger samples of participants and raw data available were imperatively deserved.

Drug repositioning for immunotherapy in breast cancer using single-cell analysis.

Immunomodulatory peptides, while exhibiting potential antimicrobial, antifungal, and/or antiviral properties, can play a role in stimulating or suppressing the immune system, especially in pathological conditions like breast cancer (BC). Thus, deregulation of these peptides may serve as an immunotherapeutic strategy to enhance the immune response. In this meta-analysis, we utilized single-cell RNA sequencing data and known therapeutic peptides to investigate the deregulation of these peptides in malignant versus normal human breast epithelial cells. We corroborated our findings at the chromatin level using ATAC-seq. Additionally, we assessed the protein levels in various BC cell lines. Moreover, our in-house drug repositioning approach was employed to identify potential drugs that could positively impact the relapse-free survival of BC patients. Considering significantly deregulated therapeutic peptides and their role in BC pathology, our approach aims to downregulate B2M and SLPI, while upregulating PIGR, DEFB1, LTF, CLU, S100A7, and SCGB2A1 in BC epithelial cells through our drug repositioning pipeline. Leveraging the LINCS L1000 database, we propose BRD-A06641369 for B2M downregulation and ST-4070043 and BRD-K97926541 for SLPI downregulation without negatively affecting the MHC complex as a significantly correlated pathway with these two genes. Furthermore, we have compiled a comprehensive list of drugs for the upregulation of other selected immunomodulatory peptides. Employing an immunotherapeutic approach by integrating our drug repositioning pipeline with single-cell analysis, we proposed potential drugs and drug targets to fortify the immune system against BC.

A longitudinal study on the change in sleep across three waves of the COVID-19 outbreaks in Hong Kong.

In the year 2020, Hong Kong experienced four COVID-19 epidemic waves. The present study aimed to examine the transition of sleep disturbances and explore its associated factors across the later three epidemic waves. Among the 1138 respondents who participated in an online survey at the second wave (T1, April 2020), 338 and 378 participants also completed a follow-up at the third (T2, August 2020) and fourth waves (T3, December 2020), respectively. Participants completed the Insomnia Severity Index and an investigator-designed questionnaire regarding potential factors associated with sleep change such as perceived risk of being infected, economic stress, and confidence in the government and health care professional. Sample of this study were mainly female (67.7%), married (50.3%), young adults (54.2%) with tertiary education (81.6%). Maintaining normal sleep was the most prevalent trajectory of sleep of all three waves (50.5%), followed by persistent insomnia (17.2%) and remitted insomnia (9.0%). Besides female, older-age and lower education level, the results showed that increment in worry about family being infected (adjusted risk ratio, RR = 1.28), perceived interference of daily lives (adjusted RR = 1.19), and economic distress (adjusted RR = 1.24) were significantly associated with the development of clinical insomnia during the three epidemic waves. These factors were also associated with worsening of other sleep parameters. Insomnia being persistent across the three waves of COVID-19 outbreaks was common. Increasing economic distress, daily interference, and worry about family members being infected were associated with an increasing risk of clinical insomnia across the three COVID-19 outbreaks. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00486-w.

A qualitative examination of primary care team's participation in the distribution of the COVID-19 vaccination.

BACKGROUND: Primary health care (PHC) has historically led and implemented successful immunization programs, driven by strong relationships with patients and communities. During the COVID-19 pandemic, Canada began its vaccination strategy with mass immunizations that later included local efforts with PHC providers. This study seeks to understand how PHC contributed to the different phases of the COVID-19 vaccination rollouts in Ontario, Canada's most populous province. METHODS: We conducted a descriptive qualitative study with focus groups consisting of PHC providers, administrators, and staff in Ontario. Eight focus groups were held with 39 participants representing geographic diversity across the six Ontario Health regions. Participants reflected a diverse range of clinical, administrative, and leadership roles. Each focus group was audio-recorded and transcribed with transcriptions analyzed using thematic analysis. RESULTS: With respect to understanding PHC teams' participation in the different phases of the COVID-19 vaccination rollouts, we identified five themes: (i) supporting long-term care, (ii) providing leadership in mass vaccinations, (iii) integrating vaccinations in PHC practice sites, (iv) reaching those in need through outreach activities; and (v) PHC's contributions being under-recognized. CONCLUSIONS: PHC was instrumental in supporting COVID-19 vaccinations in Ontario, Canada across all phases of the rollout. The flexibility and adaptability of PHC allowed teams to participate in both large-scale and small-scale vaccination efforts.

2024 Statement from Asia expert operators on transcatheter pulmonary valve replacement.

Transcatheter pulmonary valve replacement (TPVR), also known as percutaneous pulmonary valve implantation, refers to a minimally invasive technique that replaces the pulmonary valve by delivering an artificial pulmonary prosthesis through a catheter into the diseased pulmonary valve under the guidance of X-ray and/or echocardiogram while the heart is still beating not arrested. In recent years, TPVR has achieved remarkable progress in device development, evidence-based medicine proof and clinical experience. To update the knowledge of TPVR in a timely fashion, and according to the latest research and further facilitate the standardized and healthy development of TPVR in Asia, we have updated this consensus statement. After systematical review of the relevant literature with an in-depth analysis of eight main issues, we finally established eight core viewpoints, including indication recommendation, device selection, perioperative evaluation, procedure precautions, and prevention and treatment of complications.