Miracle-dz/UniFAR-FTUs huggingface dataset:
Bidirectional regulation of structural damage on autophagy in the C. elegans epidermis

ABSTRACT A variety of disturbances such as starvation, organelle damage, heat stress, hypoxia and pathogen infection can influence the autophagic process. However, how the macroautophagy/autophagy machinery is regulated intrinsically by structural damage of the cell remains largely unknown. In this work, we utilized the C. elegans epidermis as the model to address this question. Our results showed that structural damage by mechanical wounding exerted proximal inhibitory effect and distant promotional effect on autophagy within the same epidermal cell. By disrupting individual mechanical supporting structures, we found that only damage of the basal extracellular matrix or the underlying muscle cells activated a distinct autophagic response in the epidermis. On the contrary, structural disruption of the epidermal cells at the apical side inhibited autophagy activation caused by different stress factors. Mechanistic studies showed that the basal promotional effect of structural damage on epidermal autophagy was mediated by a mechanotransduction pathway going through the basal hemidesmosome receptor and LET-363/MTOR, while the apical inhibitory effect was mostly carried out by activation of calcium signaling. Elevated autophagy in the epidermis played a detrimental rather than a beneficial role on cell survival against structural damage. The results obtained from these studies will not only help us better understand the pathogenesis of structural damage- and autophagy-related diseases, but also provide insight into more generic rules of autophagy regulation by the structural and mechanical properties of cells across species. Abbreviations : ATG: autophagy related; BLI-1: BLIstered cuticle 1; CeHDs: C. elegans hemidesmosomes; COL-19: COLlagen 19; DPY-7: DumPY 7; ECM: extracellular matrix; EPG-5: ectopic PGL granules 5; GFP: green fluorescent protein; GIT-1: GIT1 (mammalian G protein-coupled receptor kinase InTeractor 1) homolog; GTL-2: Gon-Two Like 2 (TRP subfamily); HIS-58, HIStone 58; IFB-1: Intermediate Filament, B 1; LET: LEThal; LGG-1: LC3, GABARAP and GATE-16 family 1; MTOR: mechanistic target of rapamycin; MTORC1: MTOR complex 1; MUP-4: MUscle Positioning 4; NLP-29: Neuropeptide-Like Protein 29; PAT: Paralyzed Arrest at Two-fold; PIX-1: PIX (PAK (p21-activated kinase) Interacting eXchange factor) homolog 1; RFP: red fluorescent protein; RNAi: RNA interference; SQST-1: SeQueSTosome related 1; UNC: UNCoordinated; UV: ultraviolet; VAB-10: variable ABnormal morphology 10; WT: wild type.
Towards a framework for comparing functionalities of multimorbidity clinical decision support: A literature-based feature set and benchmark cases

Multimorbidity, the coexistence of two or more health conditions, has become more prevalent as mortality rates in many countries have declined and their populations have aged. Multimorbidity presents significant difficulties for Clinical Decision Support Systems (CDSS), particularly in cases where recommendations from relevant clinical guidelines offer conflicting advice. A number of research groups are developing computer-interpretable guideline (CIG) modeling formalisms that integrate recommendations from multiple Clinical Practice Guidelines (CPGs) for knowledge-based multimorbidity decision support. In this paper we describe work towards the development of a framework for comparing the different approaches to multimorbidity CIG-based clinical decision support (MGCDS). We present (1) a set of features for MGCDS, which were derived using a literature review and evaluated by physicians using a survey, and (2) a set of benchmarking case studies, which illustrate the clinical application of these features. This work represents the first necessary step in a broader research program aimed at the development of a benchmark framework that allows for standardized and comparable MGCDS evaluations, which will facilitate the assessment of functionalities of MGCDS, as well as highlight important gaps in the state-of-the-art. We also outline our future work on developing the framework, specifically, (3) a standard for reporting MGCDS solutions for the benchmark case studies, and (4) criteria for evaluating these MGCDS solutions. We plan to conduct a large-scale comparison study of existing MGCDS based on the comparative framework.
The Relations between Youth Cannabis Use, School Cannabis Use-Related Disciplinary Approaches and Student Perceptions of School Support

Abstract Background: In the school year immediately following cannabis legalization in Canada, this paper investigated youth perceptions of school support for the prevention and cessation of substance use. Scant research has examined student perceptions in relation to school disciplinary approaches. This study was the first to classify school discipline approach styles using school-level measures. Objective: The objective of this study was to examine whether different school cannabis use-related disciplinary approaches are associated with student cannabis use and perceptions of school supportiveness for the prevention and cessation of substance use. Results: School- and student-level survey data from Year 7 (the 2018/2019 school year) of the COMPASS study were used, including 68,037 grade 9–12 (Secondary I–V in Quebec) students attending 131 Canadian secondary schools. Schools were classified as using different cannabis use-related disciplinary styles based on school-administrator reported approaches to student first-offense violations of school cannabis policies. We identified that although none of the cannabis use-related disciplinary approach styles examined were associated with cannabis use, they were associated with student perceptions. Students attending schools classified as using a Permissive/Supportive approach had a higher likelihood of perceiving their school as supportive for substance use prevention/cessation than their peers at Authoritarian schools. Students who perceived their school as supportive for substance use prevention/cessation were less likely to report current cannabis use than their peers who perceived their school as unsupportive. Conclusions: Unlike previous studies using school classification styles that are based on student perceptions, results do not support direct associations between school cannabis use-related disciplinary styles and student cannabis use. Future prospective research should examine whether supportive disciplinary approaches (e.g., counseling referrals, educational programs) promote student perceptions of school supportiveness, and in turn, deter student substance use.
Word Embedding and Clustering for Patient-Centered Redesign of Appointment Scheduling in Ambulatory Care Settings

Background. A key to a more efficient scheduling systems is to ensure appointments are designed to meet patient's needs and to design and simplify appointment scheduling less prone to error. Electronic Health Records (EHR) consist of valuable information about patient characteristics and their healthcare needs. The aim of this study is to utilize information from structured and unstructured EHR data to redesign appointment scheduling in community health clinics. Methods. We used Global Vectors for Word Representation, a word embedding approach, on free text field "scheduler note" to cluster patients into groups based on similarities of reasons for appointment. We then redesigned an appointment scheduling template with new types and durations based on the clusters. We compared the current appointment scheduling system and our proposed system by predicting and evaluating clinic performance measures such as patient time spent in-clinic and number of additional patients to accommodate. Results. We collected 17,722 encounters of an urban community health clinic in 2014 including 102 unique types recorded in the EHR. Following data processing, word embedding implementation, and clustering, appointment types were grouped into 10 clusters. The proposed scheduling template could open space to see overall an additional 716 patients per year and decrease patient in-clinic time by 3.6 minutes on average (p-value<0.0001). Conclusions. We found word embedding, that is an NLP approach, can be used to extract information from schedulers notes for improving scheduling systems. Unsupervised machine learning approach can be applied to simplify appointment scheduling in CHCs. Patient-centered appointment scheduling can be achieved by simplifying and redesigning appointment types and durations that could improve performance measures, such as increasing availability of time and patient satisfaction.
Older adults' personal health information management: The role and perspective of various healthcare providers

The management of personal health information (PHI) by older adults (OAs) takes place within a socio-technical context and requires the support of various stakeholders, including healthcare providers. This study investigates provider roles in supporting OA personal health information management (PHIM), barriers they face, and related design implications for health information technology (HIT). We interviewed 27 providers serving OAs in Seattle, WA. Providers support OA PHIM through medication management, interpreting HI, and providing resources. Barriers to OA PHIM described by providers include (1) challenges with communication between OAs, providers, and caregivers, (2) limited time and resources, and (3) limitations of tools such as secure messaging. Considering these barriers, provider roles, and the socio-technical context for HIT implementation, we recommend the design of HIT that facilitates communication across multiple provider types, integrates caregivers and patient-generated data, supports understanding of OA home environments, and offers credible health resources designed for OAs.
CASC7: a LncRNA with potential clinical application

Abstract Aim To explore the novel lncRNA CASC7 and its potential clinical applications. Long non-coding RNAs (IncRNAs) are defined as non-coding genes with a length exceeding 200 nt. As transcripts of RNA polymerase Il, they have limited coding potential due to the lack of an open reading frame in the gene segment. Research has confirmed that lncRNAs are important biological factors that regulate many life processes in the human body through different mechanisms. This work focused on Cancer Susceptibility Candidate 7 (CASC7), a lncRNA with nuclear and cytoplasmic localization. Publicly available databases show that CASC7 is differentially expressed in human organs as well as in tumor tissues. A study confirmed that CASC7 is abnormally expressed in colorectal cancer, glioma, breast cancer, non-small cell lung cancer and thyroid cancer. In male infertility, asthma and heart failure, it may also be a potential therapeutic target and promising biomarker. CASC7 mainly plays a biological effect through direct or indirect effects of promoting or inhibiting the expression of related genes. Currently, only few studies have assessed CASC7, and its mechanisms are not clear. The main purpose of this review was to examine CASC7 and its possible molecular mechanisms and clinical significance in cancer. Conclusion We reviewed the recent research progress of CASC7 and its potential as a diagnostic marker and therapeutic target, and provide an outlook on its future application in terms of mechanism. Key points CASC7 is a novel lncRNA, for which there are few reports. Aberrant expression of CASC7 may be associated with the emergence and treatment of many clinical diseases, including malignancy.
Understanding the Importance of the Lay Responder Experience in Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association

Bystander cardiopulmonary resuscitation (CPR) is critical to increasing survival from out-of-hospital cardiac arrest. However, the percentage of cases in which an individual receives bystander CPR is actually low, at only 35% to 40% globally. Preparing lay responders to recognize the signs of sudden cardiac arrest, call 9-1-1, and perform CPR in public and private locations is crucial to increasing survival from this public health problem. The objective of this scientific statement is to summarize the most recent published evidence about the lay responder experience of training, responding, and dealing with the residual impact of witnessing an out-of-hospital cardiac arrest. The scientific statement focuses on the experience-based literature of actual responders, which includes barriers to responding, experiences of doing CPR, use of an automated external defibrillator, the impact of dispatcher-assisted CPR, and the potential for postevent psychological sequelae. The large body of qualitative and observational studies identifies several gaps in crucial knowledge that, if targeted, could increase the likelihood that those who are trained in CPR will act. We suggest using the experience of actual responders to inform more contextualized training, including the implications of performing CPR on a family member, dispelling myths about harm, training and litigation, and recognition of the potential for psychologic sequelae after the event.
Council tenancies and hoarding behaviours: A study with a large social landlord in England

Abstract Hoarding behaviours are highly stigmatised and often hidden. People with problematic hoarding behaviours have a higher rate of mental health and other healthcare and social services utilisation. Hoarding is a community health problem, one factor being housing insecurity. Hoarding behaviours represent significant burden to housing providers, impact the community and dealing with it involves multiple community agencies. This study with a city council in England with a large housing stock (over 14,000 properties) in summer 2021 sought to understand the nature, circumstances and extent that hoarding presents. We developed a reporting system and conducted 11 interviews with housing officers in which they described a case to explain their involvement. Our report details the nature of 38 people who hoard: 47% had a known disability or vulnerability, 34% presented a fire and environmental risk, 87% lived alone and 60% were resident in flats. Our qualitative themes are: Working with others, Balancing an enforcement approach, Feeling conflicted, Complex needs of people who hoard and Staff needs. The cases described by the housing officers are combined into six case studies and illustrate the complex, multi‐agency circumstances around decision making and risk stratification. Our findings point to housing officers as frontline professionals dealing with a public health and social care issue which is often the manifestation of complex life histories and mental health conditions. We suggest a greater focus on risk stratification and a more holistic approach to hoarding cases to effectively deal with this most complex of community health and social care issues.
Prognostic value of inflammation‐immunity‐nutrition score in patients with hepatocellular carcinoma treated with anti‐PD‐1 therapy

There are no validated biomarkers that can predict the clinical benefit of immune checkpoint blockers against the programmed cell death protein 1 (PD‐1) treatments in hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic value of inflammation‐immunity‐nutrition score (IINS) in patients with HCC treated with anti‐PD‐1 therapy.
Determination of diagnostic threshold in harmonization and comparison of clinical utility for five major antiphospholipid antibody assays used in Japan

Anticardiolipin antibodies (aCL) and anti‐β2‐glycoprotein I antibodies (aβ2GPI) are essential in diagnosing antiphospholipid syndrome (APS) according to the international APS guideline. Five commercial assays for aCL and aβ2GPI are available in Japan, but their test results are quite discordant. For harmonization of diagnosing APS, upper reference limit (URL) and diagnostic accuracy of each assay were evaluated and compared by testing common sets of specimens across all assays.
Degree of adherence to plant-based diet and total and cause-specific mortality: prospective cohort study in the Million Veteran Program

Abstract Objective: To examine the association between adherence to plant-based diets and mortality. Design: Prospective study. We calculated a plant-based diet index (PDI) by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful PDI (hPDI) and an unhealthful PDI (uPDI) by further separating the healthy plant foods from less-healthy plant foods. Setting: The VA Million Veteran Program. Participants: 315 919 men and women aged 19–104 years who completed a FFQ at the baseline. Results: We documented 31 136 deaths during the follow-up. A higher PDI was significantly associated with lower total mortality (hazard ratio (HR) comparing extreme deciles = 0·75, 95 % CI: 0·71, 0·79, P trend < 0·001]. We observed an inverse association between hPDI and total mortality (HR comparing extreme deciles = 0·64, 95 % CI: 0·61, 0·68, P trend < 0·001), whereas uPDI was positively associated with total mortality (HR comparing extreme deciles = 1·41, 95 % CI: 1·33, 1·49, P trend < 0·001). Similar significant associations of PDI, hPDI and uPDI were also observed for CVD and cancer mortality. The associations between the PDI and total mortality were consistent among African and European American participants, and participants free from CVD and cancer and those who were diagnosed with major chronic disease at baseline. Conclusions: A greater adherence to a plant-based diet was associated with substantially lower total mortality in this large population of veterans. These findings support recommending plant-rich dietary patterns for the prevention of major chronic diseases.
Design and Implementation of Substation Equipment Dynamic Capacity-Increase System

As for new bottleneck to limit the transmission capacity of power grid caused by equipment's capacity in substation,the dynamic capacity-increase technology of substation equipments were studied,and the dynamic capacity-increase system was designed for substation equipments. Through collecting condition monitoring parameters such as the temperature and current of transformer,this paper calculated the load capacity of transformer according to the‘Guide for Oil Immersed Power Transformer Load'( GB/T 1094. 7) and the thermal equivalent circuit model of transformer. Then,the load capacities of circuit breaker,transformer and isolating switch in substation circuit after overload were checked by using current shunt algorithm. Combined with the operation mode of pow er grid and the risk assessment value,the running state and capacity-increase ability of substation equipment were analyzed and estimated. The pilot application shows that the calculation results of the system can provide a scientific basis for the operation of scheduling personnel.
The Rcs System Contributes to the Motility Defects of the Twin-Arginine Translocation System Mutant of Extraintestinal Pathogenic Escherichia coli

The Tat system is an important protein export system critical for bacterial physiology and pathogenesis. It has been observed for a long time that the Tat system is critical for bacterial motility. ABSTRACT Flagellum-mediated bacterial motility is important for bacteria to take up nutrients, adapt to environmental changes, and establish infection. The twin-arginine translocation system (Tat) is an important protein export system, playing a critical role in bacterial physiology and pathogenesis. It has been observed for a long time that the Tat system is critical for bacterial motility. However, the underlying mechanism remains unrevealed. In this study, a comparative transcriptomics analysis was performed with extraintestinal pathogenic Escherichia coli (ExPEC), which identified a considerable number of genes differentially expressed when the Tat system was disrupted. Among them, a large proportion of flagellar biosynthesis genes showed downregulation, indicating that transcription regulation plays an important role in mediating the motility defects. We further identified three Tat substrate proteins, MdoD, AmiA, and AmiC, that were responsible for the nonmotile phenotype. The Rcs system was deleted in the Δtat, the ΔmdoD, and the ΔamiAΔamiC strains, which restored the motility of ΔmdoD and partially restored the motility of Δtat and ΔamiAΔamiC. The flagella were also observed in all of the ΔtatΔrcsDB, ΔmdoDΔrcsDB, and ΔamiAΔamiCΔrcsDB strains, but not in the Δtat, ΔmdoD, and ΔamiAΔamiC strains, by using transmission electron microscopy. Quantitative reverse transcription-PCR data revealed that the regulons of the Rcs system displayed differential expression in the tat mutant, indicating that the Rcs signaling was activated. Our results suggest that the Rcs system plays an important role in mediating the motility defects of the tat mutant of ExPEC. IMPORTANCE The Tat system is an important protein export system critical for bacterial physiology and pathogenesis. It has been observed for a long time that the Tat system is critical for bacterial motility. However, the underlying mechanism remains unrevealed. In this study, we combine transcriptomics analysis and bacterial genetics, which reveal that transcription regulation plays an important role in mediating the motility defects of the tat mutant of extraintestinal pathogenic Escherichia coli. The Tat substrate proteins responsible for the motility defects are identified. We further show that the Rcs system contributes to the motility suppression. We for the first time reveal the link between the Tat system and bacterial motility, which is important for understanding the physiological functions of the Tat system.
Hidradenitis Suppurativa International Online Community: Patient Characteristics and a Novel Model of Treatment Effectiveness

Treatment for hidradenitis suppurativa is diverse, yet frequently unsatisfactory. The aims of this study were to create a reproducible artificial intelligence-based patient-reported outcome platform for evaluation of the clinical characteristics and comorbidities of patients with hidradenitis suppurativa, and to use this to grade treatment effectiveness. A retrospective patient-reported outcome study was conducted, based on online questionnaires completed by English-speaking patients registered to the hidradenitis suppurativa Stuff-ThatWorks® online community. Data collected included patient characteristics, comorbidities and treatment satisfaction. These were recoded into scalable labels using a combination of machine learning algorithm, manual coding and validation. A model of treatment effectiveness was generated. The cohort included 1,050 patients of mean ± standard deviation age 34.3 ± 10.3 years. Greater severity of hidradenitis suppurativa was associated with younger age at onset (p < 0.001) and male sex (p < 0.001). The most frequent comorbidities were depression (30%), anxiety (26.4%), and polycystic ovary syndrome (16.6%). Hurley stage I patients rated topical agents, dietary changes, turmeric, and pain relief measures more effective than tetracyclines. For Hurley stage II, adalimumab was rated most effective. For Hurley stage III, adalimumab, other biologic agents, systemic steroids, and surgical treatment were rated more effective than tetracyclines. Patients with hidradenitis suppurativa often have comorbid psychiatric and endocrine diseases. This model of treatment effectiveness provides a direct comparison of standard and complementary options.