Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide association study analysis of disease severity in acne reveals novel biological insights.

Acne vulgaris is a common skin disease that affects >85% of teenage young adults among which >8% develop severe lesions that leaves permanent scars. Genetic heritability studies of acne in twin cohorts have estimated that the heritability for acne is 80%. Previous genome-wide association studies (GWAS) have identified 50 genetic loci associated with increased risk of developing acne when compared to healthy individuals. However only a few studies have investigated genetic association with disease severity. GWAS of disease progression may provide a more effective approach to unveil potential disease modifying therapeutic targets. Here, we performed a multi-ethnic GWAS analysis to capture disease severity in acne patients by using individuals with normal acne as a control. Our cohort consists of a total of 2,956 participants, including 290 severe acne cases and 930 normal acne controls from FinnGen, and 522 cases and 1,214 controls from BioVU. We also performed mendelian randomization (MR), colocalization analyses and transcriptome-wide association study (TWAS) to identify putative causal genes. Lastly, we performed gene-set enrichment analysis using MAGMA to implicate biological pathways that drive disease severity in Acne. We identified two new loci associated with acne severity at the genome-wide significance level, six novel associated genes by MR, colocalization and TWAS analyses, including genes CDC7, SLC7A1, ADAM23, TTLL10, CDK20 and DNAJA4, and 5 novel pathways by MAGMA analyses. Our study suggests that the etiologies of acne susceptibility and severity have limited overlap, with only 26% of known acne risk loci presenting nominal association with acne severity and none of the novel severity associated genes reported as associated with acne risk in previous GWAS.
An agent-based model to simulate the transmission dynamics of bloodborne pathogens within hospitals

Bloodborne pathogens are a major public health concern as they can lead to a variety of medical conditions, including cirrhosis and cancers with significant mortality and morbidity. Three viruses are of major concern: HCV, HBV and HIV. Their transmission is mostly community-associated but the iatrogenic risk of infection is not negligible, even today. Mathematical models are widely used to describe and assess pathogens transmission, within communities and hospitals. Nevertheless, few are focusing on the transmission of pathogens through blood and even fewer on their transmission within hospital as they usually study the risk of community-associated infection in vulnerable populations such as MSM or drug users. Herein, we propose an agent- based SEI (Susceptible-Exposed-Infected) model to explore the transmission dynamics of bloodborne pathogens within hospitals. This model simulates the dynamics of patients between hospital wards, from their admission to discharge, as well as the dynamics of the devices used during at-risk invasive procedures, considering that patient contamination occurs after exposure to a contaminated device. Multiple parameters of the model, such as HCV prevalence, transition probabilities between wards or ward-specific probabilities of undergoing different invasive procedures, were informed with data collected in the University Hospital of Ain Shams in Cairo, Egypt in 2017. We explored the effect of device shortage as well as the effect of random and systematic screening with associated modification in disinfection practices on the risk of infection for patients. By modifying some parameters of the model, we then explored the case of HBV in Ethiopia. In the future, this model could be used to assess the risk of transmission of other bloodborne pathogens in other contexts.
The association between polypharmacy and health-related quality of life among non-dialysis chronic kidney disease patients

Background and objective The United States government spends over $85 billion annually on treating non-dialysis chronic kidney disease (CKD). Patients with CKD are prescribed a multitude of medications to manage numerous comorbidities associated with CKD. Thus, this study aims to investigate the association between polypharmacy and health-related quality of life (HRQoL) in non-dialysis CKD patients. Methods This cross-sectional study utilized data from the Medical Expenditure Panel Survey (MEPS) from 2010 through 2019. We classified polypharmacy into three groups based on the number of medication classes: ≤ 4 (minor polypharmacy), 5 through 9 (major polypharmacy), and ≥ 10 (hyperpolypharmacy). To measure HRQoL, a Physical Component Summary (PCS) and a Mental Component Summary (MCS) were obtained from the 12-item Short-Form Health Survey version 2 and Veteran’s Rand 12 item. We applied multivariable ordinary least squares regression to assess the association between polypharmacy and HRQoL in non-dialysis CKD patients. Results A total of 649 CKD patients (weighted n = 667,989) were included. Patients with minor polypharmacy, major polypharmacy, and hyperpolypharmacy were 22.27%, 48.24%, and 29.48%, respectively. Major polypharmacy and hyperpolypharmacy were significantly and negatively associated with lower PCS scores when compared with minor polypharmacy [Beta = -3.12 (95% CI: -3.62, -2.62), p-value<0.001; Beta = -4.13 (95CI: -4.74, -3.52), p-value<0.001]. Similarly, major polypharmacy and hyperpolypharmacy were significantly and negatively associated with lower MCS scores when compared to minor polypharmacy [Beta = -0.38 (95% CI: -0.55, -0.20), p-value<0.001; Beta = -1.70 (95% CI: -2.01, -1.40), p-value<0.001]. The top 5 classes of medications used by CKD patients were antihyperlipidemic (56.31%), beta-adrenergic blockers (49.71%), antidiabetics (42.14%), analgesics (42.17%), and diuretics (39.65%). Conclusion Our study found that both major polypharmacy and hyperpolypharmacy were associated with lower HRQoL among non-dialysis CKD patients. This study highlights the need for further evaluation of the combination of medications taken by non-dialysis CKD patients to minimize unnecessary and inappropriate medication use.
Acceptability and playability of an organization training videogame for young adolescents with ADHD: The development of ATHEMOS

An estimated 8.7% to 9.8% of school-age children in the United States have attention deficit hyperactivity disorder (ADHD), affecting 4.3 to 4.9 million public school students. ADHD is a costly disorder that often goes untreated, especially among adolescents. Accessible computer-based programs have emerged to address the neurocognitive deficits of ADHD, but results to date have been disappointing. In this study, we tested the acceptability, playability, and user satisfaction of a novel planning/organization skills training game, called “ATHEMOS,” based on an established psychosocial treatment package (i.e., Challenging Horizons Program). We conducted eight focus groups during a three-year development period, using feedback from 72 young adolescents with ADHD to iteratively improve the game. Then, during a pilot study in the fourth year, we collected data from 16 young adolescents who played the game as part of a 6- to 16-week school-based intervention. Our findings suggest that the serious game resulted in acceptability and playability ratings only moderately below that of recreational games (δ = −0.40). Critically, average perceptions remained positive when delivered within a school-based ADHD intervention over several weeks or months, with strong overall user satisfaction. Boys found the game more acceptable than girls, with ratings near that of recreational games (δ = −0.23). We conclude that computer-assisted behavior interventions appeal to adolescents with ADHD and offer a potentially promising treatment delivery method in schools.
The location of an internal focus of attention differentially affects motor performance

Prior research has questioned the appropriateness of internal focus instructions or the juxtaposition to external and control conditions. Moreover, there has been a lack of research conducted to test a variety of internal conditions on motor performance. The purpose of the present study was to address those critiques and add to the attentional focus literature by varying the location of an internal focus while performing a standing long jump. Participants performed a standing long jump during five separate conditions (internal focus: toes, knees, hips, arms; and control). The analysis revealed that all internal focus conditions performed worse than the control condition. Furthermore, the only difference between internal conditions was found between arms and knees, where the knee condition resulted in a significantly shorter jump distance relative to the arms. Regardless of the location specified, all internal focus conditions led to detriments in jump performance when compared to the control condition. These findings add to a large body of work demonstrating the importance of instructional content on motor performance.
Hippocampal diﬀerentiation of competing memories predicts the precision of preparatory coding in visual cortex

Many memories contain overlapping features, causing them to compete. How do we overcome memory competition to guide attention in complex environments? We hypothesized that hippocampal diﬀerentiation of competing memories would inﬂuence the precision of preparatory coding in visual cortex during memory-guided attention. We leveraged fMRI-based pattern similarity, receptive ﬁeld modeling, and eye tracking to test this hypothesis in humans performing a memory-dependent visual search task. In the hippocampus, diﬀerentiation of competing memories predicted the precision of memory-guided eye movements. In visual cortex, preparatory coding of remembered target locations predicted search successes, whereas preparatory coding of competing locations predicted search failures due to interference. These eﬀects were linked: stronger hippocampal memory diﬀerentiation was associated with lower competitor activation in visual cortex, yielding more precise preparatory representations. These results reveal how attention succeeds despite memory competition, highlighting a role for memory systems in shaping the precision of preparatory coding in sensory cortex.
Understanding suicidal ideation–a network analysis of the Interpersonal Needs Questionnaire

Introduction Identifying various interacting risk factors for suicidality is important to develop preventive measures. The Interpersonal-Psychological Theory of Suicidal Behavior (IPTS) postulates suicidal ideation resulting from the occurrence of Perceived Burdensomeness (PB) and Thwarted Belongingness (TB). Suicidal behavior ultimately occurs if people have a Capability for Suicide. In past studies, the validity of TB was often not empirically confirmed, questioning which of the aspects of TB are central and related to suicidal ideation and whether applied measurement methods adequately capture the construct. Method Using a sample of 3,404 individuals from different clinical and nonclinical settings, 30% (1,023) of whom reported suicidal ideation, two network analyses were conducted on the Interpersonal Needs Questionnaire (INQ) and a variable mapping suicidal ideation. Results Analyses revealed that some items of the INQ were not related to suicidal ideation and the most central items did not have the strongest associations to suicidal ideation. Conclusion Based on these results, a shortened version of the INQ with the four items that showed the strongest associations with suicidal ideation in the network analyses was suggested.
The sustainability of lean implementations at the hospitals of Ministry of Health Malaysia: A study protocol

Introduction In Malaysia, lean was initiated in 2012 as part of an effort to reduce waiting time at the Ministry of Health (MOH) hospitals. As of now, there are 52 public hospitals that have officially implemented lean. However, little is known whether lean is sustained within the hospitals and the critical success factors (CSFs) affecting sustainability. Therefore, this study protocol aims to fill the gap by (i) identifying the critical success factors [CSFs] for lean sustainability in the MOH, (ii) developing a validated framework to support hospitals in sustaining lean, (iii) the framework will be adapted into a checklist to measure the level of lean sustainability (iv) interviewing hospitals with the lowest and highest level of lean sustainability to further explore the barriers and boosters in sustaining lean. Methods and analysis This study will employ a mixed-method approach and will be conducted in three phases. The first phase involves a combination of scoping review and interviews with key informants to identify the CSFs known to affect lean sustainability at the MOH hospitals and present them in a validated framework. In the second phase, the framework will be adapted into a checklist to measure the level of lean sustainability in the MOH hospitals. The findings will be used to select the hospital with the lowest and highest level of lean sustainability for an interview in the third phase. Discussion The lean sustainability framework will be able to provide more relevant guidance on how to increase the likelihood of lean sustainability and serve as a validated measurement tool for MOH hospitals. In addition, this study will be able to outline the differences in the contributing factors between health organizations that showed a high level of lean sustainability compared to those struggling to sustain.
Partial replacement of soybean meal with full-fat black soldier fly larvae meal in plant-based nursery diets did not influence fecal Escherichia coli colony forming units or improve fecal consistency when pigs were weaned into non-disinfected pens

Abstract At weaning, one hundred pigs (21 d of age; 6.96 ± 0.23 kg BW) were used to determine the effect of partially replacing soybean meal (SBM) in corn- and SBM-based nursery diets on growth performance, fecal scores, Escherichia coli (E. coli) colony forming units (CFU), and cecal mucosal microbial profile when weaned into non-disinfected nursery pens. Pens were randomly assigned to one of four dietary treatments (n = 5): high-complexity (contained highly digestible animal proteins and 10.8% SBM) with and without 3,000 ppm ZnO (HC + and HC−, respectively; representative of commercial diets), low-complexity (corn- and SBM-based; 31.8% SBM; LC), or LC with 30% inclusion of full-fat black soldier fly larvae meal (BSFLM) to partially replace SBM (LCFL; 8.0% SBM). Diets were fed for 14 d (phase I), followed by 4 wk of a common corn-SBM diet (phase II). Fecal E. coli CFU and cecal mucosal microbial 16s rRNA community profiles were assessed 7 d after weaning. During phase I, pigs fed LC and LCFL had lower average daily gains (P < 0.05) than pigs fed HC + and HC−, which were not different. Average daily feed intake was not different for pigs fed LC and LCFL, but lower than for pigs fed HC− (P < 0.001); pigs fed HC + had greater feed intake in phase I vs. all other treatment groups (P < 0.001). Upon nursery exit, only pigs fed LCFL had lower BW than pigs fed HC− (P < 0.05), with intermediate values observed for HC + and LC. Day 3 fecal scores were greater for pigs fed LCFL vs. HC + (P < 0.05) and day 7 E. coli CFU were greater for all treatment groups vs. HC + (P < 0.001). Pigs fed HC− (P < 0.01), LC (P < 0.05), and LCFL (P < 0.05) had lower alpha diversity for cecal mucosal microbiota compared to HC+. At the genus level, pigs fed LC had lower Lactobacillus relative abundance vs. pigs fed HC + (P < 0.01). Therefore, BSFLM can partially replace SBM without sacrificing growth performance vs. nursery pigs fed corn- and SBM-based diets, but both groups had reduced phase I growth performance vs. pigs fed highly digestible diets containing animal proteins when weaned into non-disinfected pens. The BSFLM did not influence fecal E. coli CFU or improve fecal consistency after weaning and therefore, is less effective at minimizing digestive upsets vs. HC + diets.
MetaQA: Enhancing human-centered data search using Generative Pre-trained Transformer (GPT) language model and artificial intelligence

Accessing and utilizing geospatial data from various sources is essential for developing scientific research to address complex scientific and societal challenges that require interdisciplinary knowledge. The traditional keyword-based geosearch approach is insufficient due to the uncertainty inherent within spatial information and how it is presented in the data-sharing platform. For instance, the Gulf of Mexico Coastal Ocean Observing System (GCOOS) data search platform stores geoinformation and metadata in a complex tabular. Users can search for data by entering keywords or selecting data from a drop-down manual from the user interface. However, the search results provide limited information about the data product, where detailed descriptions, potential use, and relationship with other data products are still missing. Language models (LMs) have demonstrated great potential in tasks like question answering, sentiment analysis, text classification, and machine translation. However, they struggle when dealing with metadata represented in tabular format. To overcome these challenges, we developed Meta Question Answering System (MetaQA), a novel spatial data search model. MetaQA integrates end-to-end AI models with a generative pre-trained transformer (GPT) to enhance geosearch services. Using GCOOS metadata as a case study, we tested the effectiveness of MetaQA. The results revealed that MetaQA outperforms state-of-the-art question-answering models in handling tabular metadata, underlining its potential for user-inspired geosearch services.
Impact of Clinical Demands on the Educational Mission in Hospital Medicine at 17 Academic Medical Centers

BACKGROUND Clinical growth is outpacing the growth of traditional educational opportunities at academic medical centers (AMCs). OBJECTIVE To understand the impact of clinical growth on the educational mission for academic hospitalists. DESIGN Qualitative study using semistructured interviews that were analyzed using a mixed inductive and deductive method at the semantic level. SETTING Large AMCs across the United States that experienced clinical growth in the past 5 years. PARTICIPANTS Division heads, section heads, and other hospital medicine (HM) leaders who oversaw and guided academic and clinical efforts of HM programs. MEASUREMENTS Themes and subthemes. RESULTS From September 2021 to January 2022, HM leaders from 17 AMCs participated in the interviews, and 3 key themes emerged. First, AMCs' disproportionate clinical growth highlighted the tension between clinical and educational missions. This included a mismatch in supply and demand for traditional teaching time, competing priorities, and clinical growth being seen as both an opportunity and a threat. Second, amid the shifting landscape of high clinical demands and evolving educational opportunities, hospitalists still strongly prefer traditional teaching. To address this mismatch, HM groups have had to alter recruitment strategies and create innovative solutions to help build academic careers. Third, participants noted a need to reimagine the role and identity of an academic hospitalist, emphasizing tailored career pathways and educational roles spanning well beyond traditional house staff teaching teams. LIMITATION The study focused on large AMCs. CONCLUSION Although HM groups have implemented many creative strategies to address clinical growth and keep education front and center, challenges remain, particularly heavy clinical workloads and a continued dilution of traditional teaching opportunities. PRIMARY FUNDING SOURCE Society of Hospital Medicine Student Scholar Grant.
Vascularized Composite Allograft Versus Prosthetic for Reconstruction After Facial and Hand Trauma

Abstract In the past decade, vascularized composite allotransplantation (VCA) has become clinical reality for reconstruction after face and hand trauma. It offers patients the unique opportunity to regain form and function in a way that had only been achieved with traditional reconstruction or with the use of prostheses. On the other hand, prostheses for facial and hand reconstruction have continued to evolve over the years and, in many cases, represent the primary option for patients after hand and face trauma. We compared the cost, associated complications, and long-term outcomes of VCA with prostheses for reconstruction of the face and hand/upper extremity. Ultimately, VCA and prostheses represent 2 different reconstructive options with distinct benefit profiles and associated limitations and should ideally not be perceived as competing choices. Our work adds a valuable component to the general framework guiding the decision to offer VCA or prostheses for reconstruction after face and upper extremity trauma.
Clinical study and genetic analysis of Cornelia de Lange syndrome caused by a novel MAU2 gene variant in a Chinese boy

Abstract Background Cornelia de Lange syndrome (CdLS) is mainly characterized by specific facial features, growth retardation, and bone deformities. Seven genes reportedly cause CdLS. Recent research has reported that loss‐of‐function variants affecting MAU2, which encodes a regulator of the cohesin complex, can cause CdLS. Thus far, only one MAU2‐CdLS case has been reported worldwide. Methods We detected a novel variant in MAU2 gene, NM_015329, c.526C>T (p.Arg176Trp) in a Chinese patient with CdLS, constructed a plasmid for in vitro transcriptional and protein level analysis, and analyzed the interaction between the MAU2/NIPBL complex using molecular dynamics (MD). Results The results showed that the level of the exogenous MAU2 mutant protein was significantly reduced compared with that of the exogenous wild‐type protein. However, MD analysis predicted an increased binding free energy between the MAU2 and NIPBL proteins that may impact the structural stability of the complex. Conclusion We investigated a MAU2‐CdLS case in a Chinese family, which strengthens the association between MAU2 variants and CdLS phenotypes. We therefore propose that MAU2 be included in the CdLS gene screening list.
External mechanical loading overrules cell-cell mechanical communication in sprouting angiogenesis during early bone regeneration

Sprouting angiogenesis plays a key role during bone regeneration. For example, insufficient early revascularization of the injured site can lead to delayed or non-healing. During sprouting, endothelial cells are known to be mechano-sensitive and respond to local mechanical stimuli. Endothelial cells interact and communicate mechanically with their surroundings, such as outer-vascular stromal cells, through cell-induced traction forces. In addition, external physiological loads act at the healing site, resulting in tissue deformations and impacting cellular arrangements. How these two distinct mechanical cues (cell-induced and external) impact angiogenesis and sprout patterning in early bone healing remains however largely unknown. Therefore, the aim of this study was to investigate the relative role of externally applied and cell-induced mechanical signals in driving sprout patterning at the onset of bone healing. To investigate cellular self-organisation in early bone healing, an in silico model accounting for the mechano-regulation of sprouting angiogenesis and stromal cell organization was developed. Computer model predictions were compared to in vivo experiments of a mouse osteotomy model stabilized with a rigid or a semirigid fixation system. We found that the magnitude and orientation of principal strains within the healing region can explain experimentally observed sprout patterning, under both fixation conditions. Furthermore, upon simulating the selective inhibition of either cell-induced or externally applied mechanical cues, external mechanical signals appear to overrule the mechanical communication acting on a cell-cell interaction level. Such findings illustrate the relevance of external mechanical signals over the local cell-mediated mechanical cues and could be used in the design of fracture treatment strategies for bone regeneration.