Miracle-dz/UniFAR-FTUs huggingface dataset:
Model-Based Re-Examination of the Effectiveness of Tumor/Immunohistochemistry and Direct-to-Sequencing Protocols for Lynch Syndrome Case Finding in Endometrial Cancer

PURPOSE: Despite widespread provision of Lynch syndrome (LS) screening programs, questions remain about the most effective and efficient protocol for LS case finding. The purpose of this study was to explore the performance of the two protocols widely shown to be the most efficient and effective, respectively: immunohistochemical (IHC) staining of tumor and direct-to-sequencing (DtS) in endometrial cancer populations. METHODS: Simulation models were developed to explore performance of the IHC and DtS protocols, updated to reflect current evidence. Analyses explicitly account for protocol complexity and failure points, as well as decreased sequencing costs. Key outcomes are percent of LS cases identified, total protocol costs and efficiency, and break-even analyses of sequencing costs. All costs are in 2020 US dollars (USD). RESULTS: Under plausible conditions, the IHC protocol is expected to identify 40%-78% of LS cases and DtS protocol from 49% to 97%. When the key variable success in proceeding to sequencing is fixed for both protocols at 50%, 75%, and 100%, the DtS protocol is 9%, 12%, and 16% better at case finding, respectively, than the IHC protocol. The break-even cost of sequencing is about $488 USD when the outcome is total direct testing protocol costs; it is about $670 USD when the outcome is cost per LS case detected. CONCLUSION: This study quantifies the plausible differences in the clinical effectiveness and cost-effectiveness of the two LS case-finding protocols. We demonstrate the large influence of success in proceeding to sequencing and potential impact of decreasing sequencing prices.
A quasi-experimental study on stethoscopes contamination with multidrug-resistant bacteria: Its role as a vehicle of transmission

Stethoscopes have been suggested to be a possible vector of contact transmission. However, only a few studies have focused on the prevalence of contamination by multidrug-resistant (MDR) bacteria and effectiveness of disinfection training to reduce. This study is to investigate the burden of stethoscope contamination with nosocomial pathogens and multidrug-resistant (MDR) bacteria and to analyze habit changes in disinfection of stethoscopes among healthcare workers (HCWs) before and after education and training. We performed a prospective pre and post quasi-experimental study. A total of 100 HCWs (55 doctors and 45 nurses) were recruited. HCWs were surveyed on their disinfection behavior and stethoscopes were cultured by pressing the diaphragm directly onto a blood agar plate before and after education on disinfection. Pulsed-field gel electrophoresis was performed to determine the relatedness of carbapenem-resistant Enterobacteriaceae. Most of the stethoscopes were contaminated with microorganisms before and after the intervention (97.9% and 91.5%, respectively). The contamination rate of stethoscopes with nosocomial pathogens before and after education was 20.8% and 19.2%, respectively. Stethoscope disinfection habits improved (55.1% vs 31.0%; p<0.001), and the overall bacterial loads of contamination were reduced (median colony-forming units, 15 vs 10; p = 0.019) after the intervention. However, the contamination rate by nosocomial pathogens and MDR bacteria did not decrease significantly. A carbapenemase-producing Klebsiella pneumoniae isolates from a stethoscope was closely related to isolates from the patients admitted at the same ward where the stethoscope was used. Stethoscopes were contaminated with various nosocomial pathogens including MDR bacteria and might act as a vehicle of MDR bacteria. Continuous, consistent education and training should be provided to HCWs using multifaceted approach to reduce the nosocomial transmission via stethoscopes.
An Anatomical Atlas-Based Scaling Study for Quantifying Muscle and Hip Joint Contact Forces in Above and Through-Knee Amputees Using Validated Musculoskeletal Modelling

Objective: Customisation of musculoskeletal modelling using magnetic resonance imaging (MRI) significantly improves the model accuracy, but the process is time consuming and computationally intensive. This study hypothesizes that linear scaling to a lower limb amputee model with anthropometric similarity can accurately predict muscle and joint contact forces. Methods: An MRI-based anatomical atlas, comprising 18 trans-femoral and through-knee traumatic lower limb amputee models, is developed. Gait data, using a 10-camera motion capture system with two force plates, and surface electromyography (EMG) data were collected. Muscle and hip joint contact forces were quantified using musculoskeletal modelling. The predicted muscle activations from the subject-specific models were validated using EMG recordings. Anthropometry based multiple linear regression models, which minimize errors in force predictions, are presented. Results: All predictions showed excellent (error interval c = 0–0.15), very good (c = 0.15–0.30) or good (c = 0.30–0.45) similarity to the EMG data, demonstrating accurate computation of muscle activations. The primary predictors of discrepancies in force predictions were differences in pelvis width (p < 0.001), body mass index (BMI, p < 0.001) and stump length to pelvis width ratio (p < 0.001) between the respective individual and underlying dataset. Conclusion: Linear scaling to a model with the most similar pelvis width, BMI and stump length to pelvis width ratio results in modelling outcomes with minimal errors. Significance: This study provides robust tools to perform accurate analyses of musculoskeletal mechanics for high-functioning lower limb military amputees, thus facilitating the further understanding and improvement of the amputee's function. The atlas is available in an open source repository.
Dissolution behavior and cell compatibility of alkali-free MgO-CaO-SrO-TiO2-P2O5 glasses for biomedical applications

Abstract Owing to their controlled solubility, phosphate invert glasses are of interest for use as temporary implant materials or tissue engineering scaffolds for controlled ion release.MgO-CaO-SrO-TiO2-P2O5 invert glasses were prepared and their dissolution behavior and cell response were examined.MgO addition to the phosphate invert glass system improved glass formation, owing to the relatively large field strength of Mg2+ ions. In osteoblastlike MC3T3-E1 cell culture tests, cell numbers on the invert glasses were significantly larger compared with the control, possibly caused by the release of Mg2+ ions promoting enhanced cell adhesion and proliferation. Alkaline phosphatase (ALP) activity varied with glass composition, with higher strontium for calcium substitution (33 to 100%) showing highest ALP activity. This effect may be caused by the release of strontium ions from the glasses.
The African urban food environment framework for creating healthy nutrition policy and interventions in urban Africa

This study developed, validated, and evaluated a framework of factors influencing dietary behaviours in urban African food environments, to inform research prioritisation and intervention development in Africa. A multi-component methodology, drawing on concept mapping, was employed to construct a framework of factors influencing dietary behaviours in urban Africa. The framework adapted a widely used socio-ecological model (developed in a high-income country context) and was developed using a mixed-methods research approach that comprised: i. Evidence synthesis consisting of a systematic review of 39 papers covering 14 African countries; ii. Qualitative interview data collected for adolescents and adults (n = 144) using photovoice in urban Ghana and Kenya; and iii. Consultation with interdisciplinary African experts (n = 71) from 27 countries, who contributed to at least one step of the framework (creation, validation/evaluation, finalisation). The final framework included 103 factors influencing dietary behaviours. Experts identified the factors influencing dietary behaviours across all the four levels of the food environment i.e. the individual, social, physical and macro levels. Nearly half (n = 48) were individual-level factors and just under a quarter (n = 26) were at the macro environmental level. Fewer factors associated with social (n = 15) and physical (14) environments were identified. At the macro level, the factors ranked as most important were food prices, cultural beliefs and seasonality. Factors ranked as important at the social level were household composition, family food habits and dietary practices. The type of food available in the neighbourhood and convenience were seen as important at the physical level, while individual food habits, food preferences and socioeconomic status were ranked highly at the individual level. About half of the factors (n = 54) overlap with those reported in an existing socio-ecological food environment framework developed in a high-income country context. A further 49 factors were identified that were not reported in the selected high-income country framework, underlining the importance of contextualisation. Our conceptual framework offers a useful tool for research to understand dietary transitions in urban African adolescents and adults, as well as identification of factors to intervene when promoting healthy nutritious diets to prevent multiple forms of malnutrition.
Plasma Membrane-Associated Receptor-like Kinases Relocalize to Plasmodesmata in Response to Osmotic Stress1[OPEN]

Osmotic stress triggers rapid reorganization of the receptor kinases QSK1 and IMK2 at plasmodesmata and induces callose-mediated plasmodesmata closure. Plasmodesmata act as key elements in intercellular communication, coordinating processes related to plant growth, development, and responses to environmental stresses. While many of the developmental, biotic, and abiotic signals are primarily perceived at the plasma membrane (PM) by receptor proteins, plasmodesmata also cluster receptor-like activities; whether these two pathways interact is currently unknown. Here, we show that specific PM-located Leu-rich-repeat receptor-like-kinases, Qiān Shŏu kinase (QSK1) and inflorescence meristem kinase2, which under optimal growth conditions are absent from plasmodesmata, rapidly relocate and cluster to the pores in response to osmotic stress. This process is remarkably fast, is not a general feature of PM-associated proteins, and is independent of sterol and sphingolipid membrane composition. Focusing on QSK1, previously reported to be involved in stress responses, we show that relocalization in response to mannitol depends on QSK1 phosphorylation. Loss-of-function mutation in QSK1 results in delayed lateral root (LR) development, and the mutant is affected in the root response to mannitol stress. Callose-mediated plasmodesmata regulation is known to regulate LR development. We found that callose levels are reduced in the qsk1 mutant background with a root phenotype resembling ectopic expression of PdBG1, an enzyme that degrades callose at the pores. Both the LR and callose phenotypes can be complemented by expression of wild-type and phosphomimic QSK1 variants, but not by phosphodead QSK1 mutant, which fails to relocalize at plasmodesmata. Together, the data indicate that reorganization of receptor-like-kinases to plasmodesmata is important for the regulation of callose and LR development as part of the plant response to osmotic stress.
Combining payment for crop damages and reward for productivity to address wildlife conflict

Conflict caused by wild herbivores damaging crops is an almost universal problem in conservation. We designed and implemented a game‐theory‐based system for supporting farmers whose crops were being heavily damaged by wild herbivores. In this community‐operated system, farmers self‐report their production, which is endorsed by neighboring farmers. The average deficit in production is compensated for by a payment that is directly proportional to the average deficit in production of the group and to the individual farmer's productivity. As a result, farmers are compensated for the average damage (support) and rewarded for individual productivity (reward) (i.e., support cum reward [SuR]). The design of the game is such that only honest reporting gives maximum returns. Farmers who underreport receive less payment because the SuR amount is proportionate to their self‐reported productivity. The endorsing farmers, in their own self‐interest, prevent overreporting. The system involves multiple game situations, the combined result of which is a stable strategy based on honesty and hard work. In 2 villages along the western boundary of Tadoba Andhari Tiger Reserve in central India, we tested the system with 75 farmers over 6 crop seasons. After a few initial attempts to cheat, honesty prevailed throughout the group. Average crop productivity increased 2.5‐fold, in spite of damage, owing to increased effort by farmers. Apart from wildlife conflict resolution, the model offers a promising alternative to crop insurance and a potential behavioral green revolution in agriculture.
Modeling the spread of fake news on Twitter

Fake news can have a significant negative impact on society because of the growing use of mobile devices and the worldwide increase in Internet access. It is therefore essential to develop a simple mathematical model to understand the online dissemination of fake news. In this study, we propose a point process model of the spread of fake news on Twitter. The proposed model describes the spread of a fake news item as a two-stage process: initially, fake news spreads as a piece of ordinary news; then, when most users start recognizing the falsity of the news item, that itself spreads as another news story. We validate this model using two datasets of fake news items spread on Twitter. We show that the proposed model is superior to the current state-of-the-art methods in accurately predicting the evolution of the spread of a fake news item. Moreover, a text analysis suggests that our model appropriately infers the correction time, i.e., the moment when Twitter users start realizing the falsity of the news item. The proposed model contributes to understanding the dynamics of the spread of fake news on social media. Its ability to extract a compact representation of the spreading pattern could be useful in the detection and mitigation of fake news.
Inducible nitric oxide synthase (iNOS) mediates ethanol-induced redox imbalance and up-regulation of inflammatory cytokines in the kidney.

Overexpression of the inducible isoform of the enzyme nitric oxide synthase (iNOS) has been associated to pathological processes in the kidney. Ethanol consumption induces the renal expression of iNOS. However, the contribution of this enzyme to the deleterious effects of ethanol in the kidney remains elusive. We examined whether iNOS plays a role in the renal dysfunction and oxidative stress induced by ethanol consumption. With this purpose, male C57BL/6 wild-type (WT) or iNOS-deficient (iNOS-/-) mice were treated with ethanol (20% v/v) for 10 weeks. Treatment with ethanol increased the expression of Nox4 as well as the concentration of thiobarbituric acid reactive substances (TBARS) and the levels of tumor necrosis factor (TNF)-α in the renal cortex of WT, but not iNOS-deficient mice. Augmented serum levels of creatinine and increased systolic blood pressure were found in WT and iNOS-deficient mice treated with ethanol. WT mice treated with ethanol showed increased production of reactive oxygen species (ROS) and myeloperoxidase (MPO) activity, but these responses were attenuated in iNOS-deficient mice. We concluded that iNOS played a role in ethanol-induced oxidative stress and pro-inflammatory cytokines production in the kidney. These are mechanisms that may contribute to the renal toxicity induced by ethanol.
Quantitative Resting State Electroencephalography in Patients with Schizophrenia Spectrum Disorders Treated with Strict Monotherapy Using Atypical Antipsychotics

Objective The effect of antipsychotic drugs on quantitative electroencephalography (EEG) has been mainly examined by the administration of a single test dose or among patients using combinations of other psychotropic drugs. We therefore investigated the effects of strict monotherapy with antipsychotic drugs on quantitative EEG among schizophrenia patients. Methods Data from 2,364 medical reports with EEG results from psychiatric patients admitted to the Hokkaido University Hospital were used. We extracted EEG records of patients who were diagnosed with schizophrenia spectrum disorders and who were either undergoing strict antipsychotic monotherapy or were completely free of psychotropic drugs. The spectral power was compared between drug-free patients and patients using antipsychotic drugs. We also performed multiple regression analysis to evaluate the relationship between spectral power and the chlorpromazine equivalent daily dose of antipsychotics in all the patients. Results We included 31 monotherapy and 20 drug-free patients. Compared with drug-free patients, patients receiving antipsychotic drugs demonstrated significant increases in theta, alpha and beta power. When patients taking different types of antipsychotics were compared with drug-free patients, we found no significant change in any spectrum power for the aripiprazole or blonanserin groups. Patients taking risperidone demonstrated significant increases in alpha and beta power. Patients taking clozapine and olanzapine demonstrated significant slow wave increases. Multiple regression analysis revealed that the chlorpromazine equivalent dose was positively associated with theta power. Conclusion Use of any antipsychotic drug by patients was associated with a dose-dependent increase in theta power. However, each type of antipsychotic demonstrated different spectral power changes.
Cervical Cancer Immunotherapy: Facts and Hopes

It is a sad fact that despite being almost completely preventable through human papillomavirus (HPV) vaccination and screening, cervical cancer remains the fourth most common cancer to affect women worldwide. Persistent high-risk HPV (hrHPV) infection is the primary etiologic factor for cervical cancer. Upward of 70% of cases are driven by HPV types 16 and 18, with a dozen other hrHPVs associated with the remainder of cases. Current standard-of-care treatments include radiotherapy, chemotherapy, and/or surgical resection. However, they have significant side effects and limited efficacy against advanced disease. There are a few treatment options for recurrent or metastatic cases. Immunotherapy offers new hope, as demonstrated by the recent approval of programmed cell death protein 1–blocking antibody for recurrent or metastatic disease. This might be augmented by combination with antigen-specific immunotherapy approaches, such as vaccines or adoptive cell transfer, to enhance the host cellular immune response targeting HPV-positive cancer cells. As cervical cancer progresses, it can foster an immunosuppressive microenvironment and counteract host anticancer immunity. Thus, approaches to reverse suppressive immune environments and bolster effector T-cell functioning are likely to enhance the success of such cervical cancer immunotherapy. The success of nonspecific immunostimulants like imiquimod against genital warts also suggest the possibility of utilizing these immunotherapeutic strategies in cervical cancer prevention to treat precursor lesions (cervical intraepithelial neoplasia) and persistent hrHPV infections against which the licensed prophylactic HPV vaccines have no efficacy. Here, we review the progress and challenges in the development of immunotherapeutic approaches for the prevention and treatment of cervical cancer.
Deep-learning-based direct synthesis of low-energy virtual monoenergetic images with multi-energy CT

Abstract. Purpose: We developed a deep learning method to reduce noise and beam-hardening artifact in virtual monoenergetic image (VMI) at low x-ray energy levels. Approach: An encoder–decoder type convolutional neural network was implemented with customized inception modules and in-house-designed training loss (denoted as Incept-net), to directly estimate VMI from multi-energy CT images. Images of an abdomen-sized water phantom with varying insert materials were acquired from a research photon-counting-detector CT. The Incept-net was trained with image patches (64 × 64 pixels) extracted from the phantom data, as well as synthesized, random-shaped numerical insert materials. The whole CT images (512 × 512 pixels) with the remaining real insert materials that were unseen in network training were used for testing. Seven contrast-enhanced abdominal CT exams were used for preliminary evaluation of Incept-net generalizability over anatomical background. Mean absolute percentage error (MAPE) was used to evaluate CT number accuracy. Results: Compared to commercial VMI software, Incept-net largely suppressed beam-hardening artifact and reduced noise (53%) in phantom study. Incept-net presented comparable CT number accuracy at higher-density (P-value [0.0625, 0.999]) and improved it at lower-density inserts (P-value = 0.0313) with overall MAPE: Incept-net [2.9%, 4.6%]; commercial-VMI [6.7%, 10.9%]. In patient images, Incept-net suppressed beam-hardening artifact and reduced noise (up to 50%, P-value = 0.0156). Conclusion: In this preliminary study, Incept-net presented the potential to improve low-energy VMI quality.
Evaluation of cytochrome b sequence to identify Leishmania species and variants: the case of Panama

BACKGROUND The genetic heterogeneity of Leishmania parasites is a major factor responsible for the wide variety of Leishmania-associated manifestations. Consequently, understanding the genetic make-up of Leishmania species using suitable molecular markers is an important component of realising local and regional scale disease risk. The cytochrome b (cytb) is frequently used to type New World Leishmania species. However, its potential to discriminate Leishmania species and variants requires further evaluation. OBJECTIVES To explore the capacity of cytb gene to identify New World Leishmania species and variants and to develop an approach able to type local Leishmania species and variants. METHODS We retrieved 360 partial and complete Leishmania cytb gene sequences publicly available in GenBank database to study all single nucleotide polymorphisms (SNPs) across the cytb gene that differentiate New World Leishmania species. This information was used to develop an approach based upon the polymorphisms found in a DNA segment of 948bp. We also compared the typing results found with this technique with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) profiling obtained using HSP70 gene as target. One hundred Panamanian isolates were used to both typed Leishmania species and assess local genetic variability. FINDINGS We found complete agreement between our cytb approach and the PCR-RFLP profiling method based on HSP70 for Leishmania species identification. Ninety-two isolates were identified as L. panamensis, although other Viannia species were found circulating at a lower frequency. Three L. panamensis haplotypes were identified in Panamanian provinces. We also provide an initial report of L. guyanensis haplotypes circulating in Panama. MAIN CONCLUSIONS Cytb gene sequence encompasses key main SNPs that aid to identify Leishmania species. The cytb approach developed with this information was able to identify and assess genetic variability of local Leishmania species found in this study.