julilili42/papers huggingface dataset:
An atypical presentation in a child with propionic acidemia? Better think twice!
2025-03-01

Abstract This report details the case of an infant with confirmed propionic acidemia who presented with progressive neurological deterioration and recurrent episodes of metabolic decompensation with elevated lactate levels, but without hyperammonemia. The child's clinical course and neuroradiological findings increasingly deviated from the known clinical and neuroradiological spectrum of propionic acidemia. A rapid trio exome sequencing identified SLC19A3 ‐related thiamine metabolism dysfunction syndrome 2 as a second genetic disease. The pathomechanisms of both diseases synergize in the impairment of brain energy metabolism, and the associated clinical phenotypes partially overlap, which explains the severe and atypical course of propionic acidemia in the reported case.
Global perspectives on tuberculosis in prisons and incarceration centers - Risk factors, priority needs, challenges for control and the way forward
2025-03-01

Tuberculosis (TB) remains a prominent cause of illness and mortality worldwide. Prisons are hotspots for TB transmission worldwide. We reviewed the literature on TB in prisons worldwide, including TB risk factors, delays in diagnosis including drug resistance, the treatment accorded, and operational and logistical issues of TB care in prison. The quantity and quality of data on TB in prisons varies worldwide. The TB incidence rate in prisons varies by World Health Organization region, with African countries having the highest rates of TB and TB/HIV co-infection. Its incidence rate among inmates is about 10 times higher than that of the general population. The growing prevalence of multidrug-resistant TB is particularly concerning, as it may affect high-risk settings and disproportionately affects vulnerable populations, such as prisoners and incarcerated individuals who go undiagnosed for extended periods of time. Factors that drive the high TB rates in prisons include limited access to health services such as TB care, overcrowding, poor ventilation, malnutrition, HIV, alcohol use disorders, illegal drug use, smoking, and other comorbidities, compounded by limited access to healthcare. Addressing TB in prisons requires a multifaceted approach, that includes improving living conditions, enhancing healthcare services, and developing innovative detection methods. The ongoing conflicts in Europe, the Middle East, Asia, and Africa further complicated TB prevention and control efforts in prisons, emphasizing the need for targeted interventions to address TB in these high-risk settings. Structured interventions tailored to the specific risk factors present in each environment should be investigated to effectively focus measures aimed at diminishing the overall burden of TB in prisons. Electronic record-keeping worldwide will allow for accurate data to be collected and shared.
Refining visceral adipose tissue quantification: Influence of sex, age, and BMI on single slice estimation in 3D MRI of the German National Cohort
2025-03-01

The selection of reference locations should be different depending on BMI groups, with a preference for caudal shifts in location with increasing BMI. For women with obesity (BMI >30 kg/m<sup>2</sup>), the L1 level emerges as the optimal reference location.
Instruments for Measuring Healthcare Professionals’ Medication Safety Competence: A Scoping Review
2025-03-01

Elderly patients with chronic diseases often use several drugs (polypharmacy). The more drugs a patient uses, the greater the risk of medication errors. To ensure a safe medication process, healthcare professionals must have a high level of medication safety competence (MSC). Hence, instruments are needed to measure healthcare professionals' MSC and identify areas where improvement is required. A scoping review was conducted to obtain a comprehensive overview of existing instruments. The scoping review was carried out in accordance with the JBI methodology for scoping reviews and in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). An a priori protocol was registered on Open Science Framework https://osf.io/73dmq. The search, performed in January 2024 in six databases, yielded 3740 results, duplicates were removed and 2499 titles and abstracts were screened. Full text screening of 28 articles resulted in the inclusion and analysis of 15 articles. A total of six instruments were identified, all instruments were designed for nurses or nursing students. However, no instrument to assess, eg physicians' or pharmacists' MSC was identified. Five of the six instruments were used in clinical setting and three in educational setting. The Medication Safety Competence Scale (MSCS) and the Medication Safety Scale cover the multidimensionality of MSC. The MSCS's psychometric properties were considered acceptable. Thus, the MSCS can be used to assess nurses MSC in clinical and educational settings.
NLP-powered quantitative verification of the English Grammar Profile’s structure-level assignment
2025-03-01

Abstract Since its inception, the Common European Framework of Reference (CEFR) has become increasingly influential in the field of second language (L2) education. In an effort to define the grammatical structures that English learners acquire at each CEFR level, the English Grammar Profile (EGP) provides a list of over 1,200 structure-level mappings derived from largely manual analysis of learner corpora. Though highly valuable for the design of didactic materials and examinations, the EGP lacks comprehensive quantitative methods to verify the acquisition levels it proposes for the grammatical structures. This paper presents an approach for revisiting the EGP structure-level mappings with empirical statistics. The approach utilizes automatic grammatical construction extraction, a large learner corpus, and statistical testing to empirically determine the level of each structure. The structure-level mappings resulting from our approach show limited agreement with that of the original EGP proposals, suggesting that frequency data alone does not provide enough evidence for the acquisition of the grammatical structures at the levels presented by the EGP.
Prevalence and course of muscle-specific receptor tyrosine kinase (MuSK) antibodies in myasthenia gravis - A retrospective study
2025-03-02

Myasthenia gravis is a neuromuscular disease typically associated with acetylcholine receptor (AChR) autoantibodies. However, in AChR-negative cases, autoantibodies against muscle-specific receptor tyrosine kinase (MuSK) may be present. Given the rarity of MuSK autoantibodies, there is limited information on their development and significance as biomarkers of disease activity. In a retrospective 10-year study, we tested 749 serum samples from 641 patients for MuSK autoantibodies. For MuSK-positive Myasthenia gravis cases, we extended the observation period to almost 17 years and analyzed the correlation between MuSK titers and clinical severity (Besinger score). We also examined the association between elevated but formally negative MuSK titers and other autoimmune diseases. Of the 749 samples, 21 (3 %, n = 7 patients) were MuSK-positive. In these patients, MuSK titers did not correlate with disease severity or treatment changes. 78 samples (10 %, n = 73 patients) showed elevated but formally negative MuSK titers, with no link to other autoimmune diseases. Our results contradict previous studies suggesting that MuSK autoantibodies could serve as biomarkers of Myasthenia gravis severity, and they shed light on the clinical relevance of elevated but formally negative MuSK titers.
In vivo molecular imaging of breast cancer metabolic heterogeneity using [1-13C]pyruvate-d3 hyperpolarized by reversible exchange with parahydrogen
2025-03-03

Metabolic MRI using hyperpolarized (HP) [1-<sup>13</sup>C]pyruvate is promising for diagnostic medicine, allowing the study of cancer metabolism and early detection of therapy response. However, a possible widespread and routine use requires high-throughput and user-friendly technologies to produce the hyperpolarized media. <b>Methods:</b> Recently, we introduced a fast (6 min) and cost-effective method using Spin-Lock Induced Crossing and Signal Amplification By Reversible Exchange (SLIC-SABRE) at μT fields and a rapid purification to produce biocompatible HP solutions of aqueous pyruvate. In this study, we used SLIC-SABRE to conduct <i>in vivo</i> tumor metabolic imaging in a transgenic breast cancer mouse model (MMTV-PyMT). <b>Results:</b> In agreement with previous HP MRI cancer studies, an elevated lactate metabolism was found in tumors compared to healthy breast tissue, heart, and vasculature, as well as distinct metabolic profiles within different tumor compartments. These findings suggest a potential link between lactate-to-pyruvate ratios and the varying levels of tumor cell proliferation and apoptosis observed by histological analyses. <b>Conclusion:</b> Our results underscore the potential of SABRE to enhance the accessibility and throughput of HP MRI, thereby advancing cancer research and diagnostic oncology.
Breaking Barriers in PROTAC Design: Improving Solubility of USP7-Targeting Degraders
2025-03-03

The development of von Hippel–Lindau (VHL) hijacking proteolysis-targeting chimeras (PROTACs) has been hindered by suboptimal physicochemical properties, including high total polar surface area (TPSA), high hydrogen bond donor (HBD) counts, and poor solubility. This study explores a novel approach to enhance the physicochemical characteristics of VHL-recruiting USP7 degraders while maintaining their efficacy. By systematically optimizing the lipophilicity, hydrogen bond donor count, and the TPSA of USP-targeting moieties, we designed a series of VHL-based degraders with improved solubility and target degradation potential. The introduction of a constrained six-membered ring in the VHL-binding scaffold or the incorporation of solubilizing groups in the VHL ligand moiety notably improved aqueous solubility without compromising degradation activity. Among the compounds resulting from the latter approach, the bis-basic piperazine-modified PROTAC 40 showed a remarkable 170-fold increase in solubility compared to its precursor while retaining high target selectivity and degradation efficiency. This study demonstrates that tailored modifications to the VHL-binding scaffold can yield solubility-enhanced PROTACs with broad applicability. The methodology may be extended to other E3 ligases to expand the arsenal of degraders for in vivo studies.
Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing
2025-03-03

Introduction Chitin is a highly abundant polysaccharide in nature and is linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, chitin is absent inmammals and plants and, thus, represents a microbeassociatedmolecular pattern (MAMP). However, highly polymeric chitin is insoluble, which potentially hampers recognition by host immune sensors. In plants, secreted chitinases degrade polymeric chitin into diffusible oligomers, which are “fed to” innate immune receptors and co-receptors. In human and murine immune cells, a similar enzymatic activity was shown for human chitotriosidase (CHIT1), and oligomeric chitin is sensed via an innate immune receptor, Toll-like receptor (TLR) 2. However, a complete system of generating MAMPs from chitin and feeding them into a specific receptor/co-receptor-aided sensing mechanism has remained unknown in mammals. Methods The effect of the secreted chitinolytic host enzyme, CHIT1, on the TLR2 activity of polymeric chitin preparations from shrimps, house dust mites and the fungal pathogen Candida albicans was assessed in vitro using cell lines and primary immune cells. Moreover, the regulation of CHIT1 was analyzed. Results Here, we show that CHIT1 converts inert polymeric chitin into diffusible oligomers that can be sensed by TLR1/TLR2 co-receptor/receptor heterodimers, a process promoted by the lipopolysaccharide binding protein (LBP) and CD14. Furthermore, we observed that Chit1 is induced via the b-glucan receptor Dectin-1 upon direct contact of immortalized human macrophages to the fungal pathogen Candida albicans , whereas the defined fungal secreted aspartyl proteases, Sap2 and Sap6, from C. albicans were able to degrade CHIT1 in vitro . Discussion Our study shows the existence of an inducible system of MAMP generation in the human host that enables contact-independent immune activation by diffusible MAMP ligands with a striking similarity to the plant kingdom. Moreover, this study highlights CHIT1 as a potential therapeutic target for TLR2-mediated inflammatory processes that are fueled by oligomeric chitin.
Rhizosphere-associated bacterial and fungal communities of two maize hybrids under increased nitrogen fertilization
2025-03-03

Introduction The selection and application of nitrogen-efficient maize hybrids have significantly bolstered contemporary food security. Nevertheless, the effects of heightened nitrogen fertilizer demand of these crops on the composition and assembly of soil microbial communities in agricultural production require further elucidation. Methods In this study, the effects of four nitrogen fertilizer managements on rhizosphere bacterial and fungal community assembly, co-occurrence network and function of two maize hybrids (LD981 and DH605) were compared. Results and discussion Findings revealed that the bacterial community was primarily shaped by deterministic processes, while stochastic processes played a pivotal role in fungal community assembly. N-efficient hybrid DH605 had a more stable microbial network than N-inefficient hybrid LD981. At N3 (130 g N/m 2 ) rate, the bacterial and fungal community networks were the most complex but unstable, followed by N2 (87 g N/m 2 ), N0 (0 g N/m 2 ), and N1 (43 g N/m 2 ) rates. Excessive nitrogen rate (N3) increased the relative abundance of denitrification genes nirK and norB by enriching nitrogen-related genus such as Nitrolancea and Nitrosospira . It led to an increase in the relative abundance of pathways such as cysteine and methionine metabolism and pyruvate metabolism. The effects of management practices (i.e. maize hybrids and N rates) on microbial communities were ultimately directly or indirectly reflected in microbial functions. Our findings illustrate the relationship between the appropriate selection of crop hybrids and management measures in optimizing rhizosphere microbial community assembly and promoting nitrogen use, which is necessary for sustainable food security.
Whole-brain volumetric analysis in adult moyamoya patients reveals significant atrophy compared to healthy controls
2025-03-03

Abstract Moyamoya disease (MMD) may lead to perfusion deficits, stroke and brain atrophy in the long term. Our aim was to analyze whole-brain volumetry (WBV) of a large cohort of MMD patients compared to healthy controls. 3D T1w MRI sequences of adult MMD patients treated at our center between 2016-2022 without prior revascularization were analyzed for WBV (AssemblyNet) and compared age-controlled to healthy controls (HC). A total of 133 different regions of interest (ROI) were examined retrospectively for each patient separately by localization, structure and tissue type. All segmentations were subjected to automated and manual quality control (QC). After QC, 149 hemispheres from 80 MMD patients were compared to 258 hemispheres from 129 HC. A significant brain volume loss was observed in MMD patients with increasing age, with the greatest reduction seen in bilaterally affected patients with Suzuki grade &amp;gt;3. As direct signs of brain atrophy, significant differences were seen across all ROIs, emphasized in cortical gray matter (GM) with a reduction of 4.4% (95%CI 2.7%–6.1%; p&amp;lt;.001) in patients aged 30-45y and 3.4% (95%CI 2.1% 4.7%; p&amp;lt;.001) aged 46-60y. As indirect sign for atrophy, external CSF spaces increased by up to 26.4% (95%CI 17.0%–35.9%; p&amp;lt;.001) for 30-45y and 28.4% (95%CI 17.1%–39.7%; p&amp;lt;.001) for 46-60y compared to HC. Infratentorial, significant volume loss was observed for patients aged 46-60y with 11.6% for cerebellar white matter (WM) (95%CI 3.7%–19.5%; p=.0025) and with 8.5% (95%CI 3.5%–13.5%; p=.0006) for the brainstem, likely due to secondary neurodegeneration. MMD patients &amp;gt;45y without ischemia also had significantly less GM and WM volume, with accordingly enlarged CSF spaces. MMD may lead to significant differences in brain volume of local and global ROI as a sign of brain atrophy, even in the absence of infarctions. These findings might be useful for the understanding of the disease burden and in decision making for timely revascularization.
Effects of TrkB-related induced metaplasticity within the BLA on anxiety, extinction learning, and plasticity in BLA-modulated brain regions
2025-03-03

Taken together, these findings reveal the dissociative involvement of BLA function, on the one hand, in anxiety, which is affected by the knockdown of TrkB, and, on the other hand, in extinction learning, which is more significantly affected by the combination of intra-BLA-induced metaplasticity and exposure to emotional trauma.
Undisclosed Conflicts of Interest in Japanese Cancer Clinical Trials: A Cross-Sectional Study of Author-Pharmaceutical Industry Financial Relationships
2025-03-03

PURPOSE Conflicts of interest (COIs) in medical research can introduce biases affecting research integrity. This study investigated the scale and disclosure of COIs among Japanese authors of cancer clinical trials. METHODS Fifty-eight cancer randomized controlled trials from 2020, involving 226 Japanese authors, were systematically abstracted and analyzed. The financial relationships between these authors and pharmaceutical companies were examined using payment data from 56 companies for the years 2018-2019. COI statements were extracted from each publication, and COI declaration rates were calculated by comparing declared companies against those that reported payments. The analysis was conducted at both the author and article levels. For author-level analyses, the declaration rate was calculated per declaration rather than per author. For article-level analyses, payments were aggregated and attributed to their respective articles. RESULTS Phase III trials comprised 82.8% (48/58) of the included studies. Of 226 authors, 202 (89.4%) were medical doctors and 208 (92.0%) received at least one payment. The median number of companies providing at least one payment per author was 9 (IQR, 4-12), with a median total payment of 5,158-$62,534 USD). Among 280 unique disclosures from authors with payments, only 29 (10.4%) accurately reported COIs, whereas 80 (28.6%) reported no COIs. For 58 articles, only two (3.4%) accurately reported COIs, seven (12.1%) reported no COIs, and 49 (84.5%) partially disclosed COI information. CONCLUSION Japanese cancer clinical trial authors frequently received industry payments, yet their COI disclosures were often inadequate. This highlights the need for stricter guidelines and improved education on COI reporting in Japan.
Metacognitive Reactivity and Temporal Perception: The Influence of Confidence Ratings on the Temporal Binding Window
2025-03-03

ABSTRACT The influence of confidence in assessing the perceived timing of sensory events on perceptual decision-making remains poorly understood. Metacognition—the ability to reflect on one’s thought processes — is often assessed through confidence ratings in perceptual tasks. However, accessing metacognitive information can influence task performance, a phenomenon known as the reactivity effect. This study examines metacognitive reactivity by examining the impact of confidence ratings on the temporal binding window (TBW) in two multisensory time perception tasks that use identical stimuli but require different judgments: Temporal Order Judgment (TOJ) and Simultaneity Judgment (SJ). Thirty-five participants (aged 18–39) completed TOJ and SJ tasks with and without confidence ratings via Prolific, an online participant recruitment platform. Psychometric functions were fitted to response and confidence data to determine TBW and the point of subjective simultaneity (PSS). Both tasks exhibited reactivity effects, with the effect being stronger in the SJ task. TBW significantly differed between TOJ and SJ tasks, regardless of confidence ratings. Additionally, TBWs from TOJ and SJ tasks were strongly correlated, as were the width parameters of confidence curves, suggesting shared underlying mechanisms in both perceptual and metacognitive processes. These findings highlight the utility of confidence ratings in evaluating TOJ and SJ performance, revealing both task differences and commonalities. We also discuss the potential for training interventions to enhance temporal perception, particularly in older adults. Finally, we reflect on the advantages and challenges of online data collection via Prolific, including its diverse participant pool and timing precision limitations.
Comprehensive IC-ICP-MS analysis of polyphosphonates and their transformation products
2025-03-04

Polyphosphonates (PPs) are increasingly used in detergents and as antiscalants in Europe, with an estimated 18,600 tons annually entering surface waters. Aminopolyphosphonates (APPs) can be readily transformed by environmental processes, contrary to previous beliefs about PP stability during wastewater treatment. Together with the identification of glyphosate as a minor transformation product (TP) of the widely used diethylenetriamine penta(methylenephosphonate) (DTPMP), this necessitates further detailed APP transformation studies. A novel speciation analysis method for phosphonates and several potential phosphorus-containing TPs was developed using a rapid ion chromatographic (IC) separation and element-specific detection by inductively coupled plasma-triple quadrupole-mass spectrometry (ICP-TQ-MS). Chromatographic separation was optimised with a five-step gradient, allowing the simultaneous analysis of a wide range of analytes with varying sizes and numbers of negative charges within a single chromatographic run. Nine phosphorus species including APPs, PPs, glyphosate, aminomethylphosphonic acid (AMPA) and phosphate can be analysed within a run time of 205 seconds. Excellent species-specific detection limits in the range of 0.06 to 0.73 μg/L of phosphorus were reached. Unidentified TPs could also be quantified by using a species-unspecific calibration approach to close the phosphorus mass balance (PMB). The method's applicability was successfully demonstrated by monitoring DTPMP transformation with MnO<sub>2</sub> under environmentally relevant conditions. DTPMP and its TPs were identified and quantified over the course of the transformation experiment with PMB values ≥73 %. This rapid, straightforward, robust and highly sensitive approach offers an effective means of quantifying (aminopoly)phosphonates and their TPs, contributing to a better understanding of their environmental fate and impact.