Miracle-dz/UniFAR-FTUs huggingface dataset:
ADHERENCE TO A WEB-BASED EXERCISE PROGRAMME: A FEASIBILITY STUDY AMONG PATIENTS WITH HIP OR KNEE OSTEOARTHRITIS

Objectives To describe adherence to a 12-week web-based aerobic exercise programme, to compare characteristics between those who adhere or not, and to identify barriers for exercising in patients with hip or knee osteoarthritis. Design Single-arm feasibility study. Subjects Patients with hip or knee osteoarthritis in specialist healthcare, age 40–80 years, and not candidates for joint surgery. Methods Adherence to a 12-week exercise programme was defined as having completed ≥ 2 exercise sessions a week for at least 8 weeks. Baseline differences between adherent and non-adherent groups in demographics, symptoms, disability, physical activity and fitness were assessed using Mann–Whitney U or χ2 tests. Reasons for not completing exercise sessions were reported in weekly diaries. Results A total of 29 patients (median age 64 years, 72% female) were included. Median baseline pain (numerical rating scale 0–10) was 5. Fifteen patients adhered to the exercise programme, 14 did not. Non-adherent patients were less active (p = 0.032) and had lower cardiorespiratory fitness (p = 0.031). The most frequently reported barrier to exercising was sickness. Less than 10% reported pain as a barrier. Conclusion Half of the patients with hip or knee osteoarthritis adhered to the digitally delivered exercise programme and the most frequently reported barrier for adherence was sickness, while less than 10% reported pain as a reason for not exercising. Trial registration ClinicalTrials.gov, NCT04084834. The Regional Committee for Medical and Health Research Ethics South-East, 2018/2198. LAY ABSTRACT Exercise is a core element in the management of osteoarthritis, and adherence to exercise is important to achieve beneficial health effects. Many patients find it challenging to exercise by themselves and need tight support. However, this need cannot solely be met within the healthcare system, and alternative ways to support patients are needed. The aim of this study was to assess adherence to a web-based aerobic exercise programme and to identify barriers for exercising. This feasibility study included 29 participants. Of these, 15 adhered to the programme (exercised at least 2 times per week for a minimum of 8 weeks). Those who did not adhere had lower activity and fitness levels before the start of the study. Sickness was the most frequently reported barrier to exercising, while few reported pain as a barrier. In conclusion, web-based delivery can be valuable in supporting adherence to exercise in patients with hip or knee osteoarthritis.
Engineered coumarin accumulation reduces mycotoxin‐induced oxidative stress and disease susceptibility

Summary Coumarins can fight pathogens and are thus promising for crop protection. Their biosynthesis, however, has not yet been engineered in crops. We tailored the constitutive accumulation of coumarins in transgenic Nicotiana benthamiana, Glycine max and Arabidopsis thaliana plants, as well as in Nicotiana tabacum BY‐2 suspension cells. We did so by overexpressing A. thaliana feruloyl‐CoA 6‐hydroxylase 1 (AtF6’H1), encoding the key enzyme of scopoletin biosynthesis. Besides scopoletin and its glucoside scopolin, esculin at low level was the only other coumarin detected in transgenic cells. Mechanical damage of scopolin‐accumulating tissue led to a swift release of scopoletin, presumably from the scopolin pool. High scopolin levels in A. thaliana roots coincided with reduced susceptibility to the root‐parasitic nematode Heterodera schachtii. In addition, transgenic soybean plants were more tolerant to the soil‐borne pathogenic fungus Fusarium virguliforme. Because mycotoxin‐induced accumulation of reactive oxygen species and cell death were reduced in the AtF6’H1‐overexpressors, the weaker sensitivity to F. virguliforme may be caused by attenuated oxidative damage of coumarin‐hyperaccumulating cells. Together, engineered coumarin accumulation is promising for enhanced disease resilience of crops.
Identification of high-affinity pyridoxal kinase inhibitors targeting cancer therapy: an integrated docking and molecular dynamics simulation approach.

Pyridoxal kinase (PDXK) is a vitamin B6-dependent transferase enzyme encoded by the PDXK gene, crucial for leukemic cell proliferation. Disruption of its activity causes altered metabolism and reduced levels of nucleotides and polyamines. PDXK and pyridoxal 5'-phosphate (PLP) are overexpressed in various carcinomas, making them promising targets for drug design against cancer. Targeting PDXK may hold promise as a therapeutic approach for cancer treatment. This study focused on discovering potential inhibitors that could selectively interrupt the binding of pyridoxal phosphate (PLP) to pyridoxal kinase (PDXK). A commercially available library of 7,28,747 natural and druglike compounds was virtually screened using a molecular docking approach to target the substrate binding pocket of PDXK. Six promising inhibitors were identified, and all-atom molecular dynamics simulations were conducted on the PDXK-ligand complexes for 100 ns to assess their binding conformational stability. The simulation results indicated that the binding of ZINC095099376, ZINC01612996, ZINC049841390, ZINC095098959, ZINC01482077, and ZINC03830976 induced a slight structural change and stabilized the PDXK structure. This analysis provided valuable information about the critical residues involved in the PDXK-PLP complex formation and can be utilized in designing specific and effective PDXK inhibitors. According to this study, these compounds could be developed as anticancer agents targeting PDXK as a potential candidate for further study.Communicated by Ramaswamy H. Sarma.
Epigenetic insights into colorectal cancer: comprehensive genome-wide DNA methylation profiling of 294 patients in Korea

DNA methylation regulates gene expression and contributes to tumorigenesis in the early stages of cancer. In colorectal cancer (CRC), CpG island methylator phenotype (CIMP) is recognized as a distinct subset that is associated with specific molecular and clinical features. In this study, we investigated the genome-wide DNA methylation patterns among patients with CRC. The methylation data of 1 unmatched normal, 142 adjacent normal, and 294 tumor samples were analyzed. We identified 40,003 differentially methylated positions with 6,933 (79.8%) hypermethylated and 16,145 (51.6%) hypomethylated probes in the genic region. Hypermethylated probes were predominantly found in promoter-like regions, CpG islands, and N shore sites; hypomethylated probes were enriched in open-sea regions. CRC tumors were categorized into three CIMP subgroups, with 90 (30.6%) in the CIMP-high (CIMP-H), 115 (39.1%) in the CIMP-low (CIMP-L), and 89 (30.3%) in the non-CIMP group. The CIMP-H group was associated with microsatellite instability-high tumors, hypermethylation of MLH1, older age, and right-sided tumors. Our results showed that genome-wide methylation analyses classified patients with CRC into three subgroups according to CIMP levels, with clinical and molecular features consistent with previous data.
The concomitant use of paracetamol and flucloxacillin. A rare cause of high anion gap metabolic acidosis in the frail oldest old

ABSTRACT Objectives This article describes the occurrence of a high anion gap metabolic acidosis (HAGMA) in two older, female patients with a methicillin sensitive staphylococcus aureus (MSSA) infection. Both patients received flucloxacillin and paracetamol. Both of them initially improved but declined rapidly after two to three weeks of treatment. They developed a severe HAGMA resulting in their death. The objective of this article is to determine whether old age is a major risk factor for developing HAGMA when combining paracetamol with flucloxacillin. Methods A literature study was conducted using the MEDLINE database, PubMed. The used MeSH terms were ‘flucloxacillin, acetaminophen, glutathione synthetase deficiency and acidosis’. Furthermore, we used two cases to illustrate our findings. Results The origin of the high anion gap metabolic acidosis is the accumulation of 5-oxoproline which is known to occur when combining flucloxacillin with paracetamol due to their interaction with different enzymes of the gamma glutamyl cycle. This leads to the depletion of glutathione and the formation of 5-oxoproline. This phenomenon has a higher risk of occurring in frail older adults as most of them have several predisposing risk factors which result in lower baseline glutathione reserve. These risk factors include old age, malnutrition, assigned female at birth, pre-existing kidney and/or liver dysfunction, uncontrolled diabetes and sepsis. Conclusion The purpose of this article is to raise awareness of this phenomenon and its higher occurrence in frail older adults, which hopefully will lead to an earlier diagnosis with a better outcome for the patient.
Virus world database (VWdb), an API-enabled database of virus taxonomy

T he number of viruses that are being identified and characterized is growing by the day. However, it is not easy to gather information on the taxonomy of these viruses as the related data at NCBI (https://www.ncbi.nlm.nih.gov/) (1) are too large (hundreds of thousands of lines) and loaded into a single webpage or not up to date at the ICTV (https://ictv.global/) (2). Hence, there is a gap in knowledge and the need for easy access to the taxonomy information in a user-friendly manner. In this work, we created an easy-to-use web interface, entitled Virus World database (VWdb), accessed from the URL: https://viperdb.org/vw, that can be utilized to select viruses according to various aspects of taxonomy and the related information available in other relevant databases: UniProtKB (3), PDB (4), VIPERdb (5, 6), and EMDB (7). In addition, we created an API (Application Programming Interface) that can be used for programmatic access of the metadata available in VWdb. We downloaded all the taxonomy data available in the new format (https://ncbiinsights.ncbi.nlm.nih.gov/2018/02/22/new-taxonomy-files-availablewith-lineage-type-and-host-information/) on all the kingdoms (e.g., bacteria, inverte­ brates, and viruses) from NCBI. We then parsed and stored all the taxonomy data into a temporary MySQL database (Taxo), followed by searching, extracting, and uploading virus-specific information into a virus entry-specific database, VWdb. This was followed by searching and storing virus-related data from various databases (e.g., UniProtKB, PDB, EMDB, AlphaFoldDB), which involved accessing various APIs via Python scripts with multi-threading on to speed up the search significantly. We have used the taxonomy-ID as the primary key in VWdb and to connect to relevant databases. Additionally, we included the information on Baltimore classification system of genomes for virus families available at ViralZone web resource (8). The details of VWdb schema are given in the Supplementary Information (Fig. S1). We then created multiple PHP web services to query and access data from a web interface to select and display the taxonomy data associated with each virus genome/family/genus in a table form. A flow chart depicting the various steps involved in data acquisition and setting up the MySQL database at VWdb is shown in Fig. S2. Furthermore, we have included a table comprising a glossary of technical terms (e.g., JSON, MySQL) and the description of their intended function (Table 1). At the time of writing, there are 231,437 viruses from 233 virus families and 2,578 genera available at VWdb. These viruses are classified to contain eight different types of genomes (e.g., ribovira, monodnaviria, duplodnaviria), including an unclassified class that infect 13 different hosts, as categorized by NCBI (Table 2). Significantly, however, we have also included the Baltimore classification of viral genomes (e.g., ssRNA, dsDNA) gathered from the Viral Zone resource (8) that is not available at NCBI. One can choose to display all the viruses that infect a particular host (e.g., humans, bacteria, and plants)
Financial Advisers’ and Key Informants’ Perspectives on the Australian Industry-Led Moratorium on Genetic Tests in Life Insurance

Introduction: Genetic discrimination (GD) in the context of life insurance is a perennial concern in Australia and internationally. To address such concerns in Australia, an industry self-regulated Moratorium on Genetic Tests in Life Insurance was introduced in 2019 to restrict life insurers from using genetic test results in underwriting for policies under certain limits. Financial advisers (FAs) are sometimes engaged by clients to provide financial advice and assist them to apply for life insurance. They are therefore well-placed to comment on GD and the operation of the Moratorium. Despite this, the financial advising sector in Australia has yet to be studied empirically with regards to GD and the Moratorium. This study aims to capture this perspective by reporting on interviews with the financial advising sector. Methods: Ten semi-structured qualitative interviews were conducted with FAs and key informants and were analysed using thematic analysis. Conclusion(s): Participants’ level of awareness and understanding of the Moratorium varied. Participants reported mixed views on the Moratorium’s effectiveness, how it operates in practice, and perceived industry compliance. Participants also provided reflections on Australia’s current approach to regulating GD, with most participants supporting the concept of industry self-regulation but identifying a need for this to be supplemented with external oversight and meaningful recourse mechanisms for consumers. Our results suggest that there is scope to increase FAs’ awareness of GD, and that further research, consultation, and policy consideration are required to identify an optimal regulatory response to GD in Australia.
A voxel- and source-based morphometry analysis of grey matter volume differences in very-late-onset schizophrenia-like psychosis.

BACKGROUND Very-late-onset schizophrenia-like psychosis (VLOSLP) is associated with significant burden. Its clinical importance is increasing as the global population of older adults rises, yet owing to limited research in this population, the neurobiological underpinnings of VLOSP remain insufficiently clarified. Here we address this knowledge gap using novel morphometry techniques to investigate grey matter volume (GMV) differences between VLOSLP and healthy older adults, and their correlations with neuropsychological scores. METHODS In this cross-sectional study, we investigated whole-brain GMV differences between 35 individuals with VLOSLP (mean age 76.7, 26 female) and 36 healthy controls (mean age 75.7, 27 female) using whole-brain voxel-based morphometry (VBM) and supplementary source-based morphometry (SBM) on high resolution 3D T1-weighted MRI images. Additionally, we investigated relationships between GMV differences and cognitive function assessed with an extensive neuropsychological battery. RESULTS VBM showed lower GMV in the thalamus, left inferior frontal gyrus and left insula in patients with VLOSLP compared to healthy controls. SBM revealed lower thalamo-temporal GMV in patients with VLOSLP. Processing speed, selective attention, mental flexibility, working memory, verbal memory, semantic fluency and confrontation naming were impaired in patients with VLOSLP. Correlations between thalamic volumes and memory function were significant within the group of individuals with VLOSLP, whereas no significant associations remained in the healthy controls. CONCLUSIONS Lower GMV in the thalamus and fronto-temporal regions may be part of the underlying neurobiology of VLOSLP, with lower thalamic GMV contributing to memory impairment in the disorder.
AI‐based assessments of speech and language impairments in dementia

Recent advancements in the artificial intelligence (AI) domain have revolutionized the early detection of cognitive impairments associated with dementia. This has motivated clinicians to use AI‐powered dementia detection systems, particularly systems developed based on individuals' and patients' speech and language, for a quick and accurate identification of patients with dementia. This paper reviews articles about developing assessment tools using machine learning and deep learning algorithms trained by vocal and textual datasets.
The role of anti-Mullerian hormone and other correlates in patients with polycystic ovary syndrome

ABSTRACT Background Anti-Müllerian hormone (AMH) has recently emerged as a promising biomarker for the detection of polycystic ovarian morphology. In polycystic ovary syndrome (PCOS), an elevated level of AMH has been suggested to add value to the Rotterdam criteria in cases of diagnostic uncertainty. In this study, we evaluated the correlation between AMH and PCOS, and the potential role of AMH in PCOS diagnosis. Methods A case-control study was performed on a total of 200 females, 100 of which were diagnosed with PCOS as per Rotterdam revised criteria (2003) and 100 as the control (non-PCOS group). Patient medical records were therefore retrieved for clinical, biochemical and ultrasound markers for PCOS diagnosis. Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and multivariate linear regression models were applied to analyze our data. Results Mean serum levels of LH and AMH, and LH/FSH ratio were significantly different between compared groups. In the PCOS group, the mean serum AMH level was 6.78 ng/mL and LH/FSH ratio was 1.53 while those of controls were 2.73 ng/mL and 0.53, respectively (p < .001). The most suitable compromise between 81% specificity and 79% sensitivity was obtained with a cutoff value of 3.75 ng/mL (26.78 pmol/L) serum AMH concentration for PCOS prediction, with an AUROC curve of 0.9691. Conclusion Serum AMH cutoff level of 3.75 ng/mL was identified as a convenient gauge for the prediction of PCOS and an adjuvant to the Rotterdam criteria.
Ten years of German benefit assessment: price analysis for drugs with unproven additional benefit.

INTRODUCTION Since 2011, the prices for all new drugs in Germany are negotiated based on a benefit assessment. The purpose of this study was to analyze the price regulation of drugs with unproven additional benefit. METHODS Benefit assessment procedures from 2011 to 2020 were reviewed and selected through AMNOG Monitor and Lauer Taxe. Negotiated annual therapy costs, the annual costs of the most cost-efficient appropriate comparative therapy (ACT) and the potential budget impact for 33 included procedures were calculated. RESULTS 55% of the included drugs achieved a negotiated price higher than the most cost-efficient ACT, 3% were identified as equal and 42% showed lower negotiated prices. The potential savings exceeded expenditures by around EUR 523.5 m. After price flexibility was adopted by the legislator in 2017, the overall potential savings still outweighed the expenditures by around EUR 62 m. CONCLUSIONS Our analysis shows that making price negotiations more flexible by law does not undermine the fundamental aim of the AMNOG, which is to avoid additional expenditure without increased patient benefit. The regulation can thus fulfill the objective provided by the legislature of keeping drugs without proven additional benefits in the German healthcare system.
Empowering Women: Evidence from a Field Experiment in Afghanistan

In societies with widespread gender discrimination, development programs with gender quotas are considered a way to improve women’s economic, political, and social status. Using a randomized field experiment across 500 Afghan villages, we examine the effects of a development program that mandates women’s community participation. We find that even in a highly conservative context like Afghanistan, such initiatives improve female participation in some economic, social, and political activities, including increased mobility and income generation. They, however, produce no change in more entrenched female roles linked to family decision-making or in attitudes towards the general role of women in society.
Empowering Women: The Effect of Schooling on Young Women&Apos;S Knowledge and Use of Contraception

Large differences in fertility between women with high and low levels of education suggest that schooling may have a direct impact on knowledge and use of contraception. We investigate this issue using information on women in Mexico. In order to identify the causal effect of schooling, we exploit temporal and geographic variation in the number of lower secondary schools built following the extension of compulsory education in Mexico from 6th to 9th grade in 1993. We show that raising females&apos; schooling beyond 6th grade increases their knowledge of contraception during their reproductive years and increases their propensity to use contraception at sexual debut. This indicates that the impact of schooling on women&apos;s wellbeing extends beyond improved labor market outcomes and includes greater autonomy over their fertility.
Title : Anti-citrullinated protein antibodies are associated with neutrophil extracellular traps in the sputum in relatives of rheumatoid arthritis patients

traps in the sputum in relatives of rheumatoid arthritis patients Authors: M. Kristen Demoruelle MD; Kylie K. Harrall MS, Linh Ho BS, Monica M. Purmalek BA, Nickie L. Seto BS, Heather M. Rothfuss PhD, Michael H. Weisman MD; Joshua J. Solomon MD, Aryeh Fischer MD, Yuko Okamoto MD, Lindsay B. Kelmenson MD, Mark C. Parish BS, Marie Feser MPH, Chelsie Fleischer MA, Courtney Anderson BS, Michael Mahler PhD, Jill M. Norris PhD, Mariana J. Kaplan MD, Brian D. Cherrington PhD, V. Michael Holers MD, and Kevin D. Deane MD, PhD Author Affiliations: University of Colorado Denver, Division of Rheumatology, Aurora, CO, USA; University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Aurora, CO, USA, and Center for Women’s Health Research, University of Colorado Denver, Department of Medicine, Aurora, CO; 3 Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, University of Wyoming, Department of Zoology and Physiology, Laramie, WY, USA; Cedars-Sinai Medical Center, Division of Rheumatology, Los Angeles, CA, USA; National Jewish Health, Division of Pulmonary and Critical Care Medicine, Denver, CO, USA; Inova Diagnostics, San Diego, CA, USA; Colorado School of Public Health, Department of Epidemiology, Aurora, CO, USA Grants: This work was supported by the National Institutes of Health [grant numbers AR066712, AI101990, HD057022, TR001082, AI103023] and the Intramural Research Program (NIAMS; project ZIAAR041199); Rheumatology Research Foundation [Disease Targeted Research Initiative Programs, Scientist Development Award]; and the Walter S. and Lucienne Driskill Foundation.
ChatGPT: ascertaining the self-evident. The use of AI in generating human knowledge

The fundamental principles, potential applications, and ethical concerns of ChatGPT are analyzed and discussed in this study. Since ChatGPT emerged, it has gained a rapidly growing popularity, with more than 600 million users today. The development of ChatGPT was a significant mile-stone, as it demonstrated the potential of large-scale language models to generate natural language responses that are almost indistinguishable from those of a human. ChatGPT's operational principles, prospective applications, and ability to advance a range of human endeavours are discussed in the paper. However, much of the work discusses and poses moral and other problems that rely on the subject. To document the latter, we submitted 14 queries and captured the ChatGPT responses. ChatGPT appeared to be honest, self-knowledgeable, and careful with its answers. The authors come to the realization that since AI is already a part of society, the pervasiveness of the ChatGPT tool to the general public has once again brought to light concerns regarding AI in general. Still, they have moved from the domain of scientific community collective reflection at a conceptual level to everyday practice this time.