julilili42/papers huggingface dataset:
Col1a2 mice exhibit alterations in ossicular bone quality typical of osteogenesis imperfecta but no hearing loss
2025-05-19

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder clinically mainly characterized by skeletal fragility. However, non-skeletal manifestations, some of which do not appear until adulthood, can additionally severely impact the health and quality of life of the affected patients. These include hearing loss that is observed in approximately every second OI patient. While the hearing loss in OI is mainly due to impaired sound transmission (i.e., conductive hearing loss), the underlying mechanisms are currently elusive. Here, we investigated the Oim (Col1a2<sup>oim/oim</sup>) mouse model of classical OI, focusing on bone quality features of the middle ear and hearing function. No osseous morphological changes were observed in the middle or inner ear of male Col1a2<sup>oim/oim</sup> mice compared to wildtype controls. Backscattered electron imaging and Fourier-transform infrared spectroscopy revealed increased matrix mineralization and matrix maturity of the auditory ossicles (malleus, stapes). These changes have previously been described as typical features of OI in other skeletal regions. However, measurement of auditory function by auditory brainstem response revealed no gross hearing pathology and even indicated a slightly improved hearing ability in Col1a2<sup>oim/oim</sup> mice in the 32 kHz range as determined by distortion product otoacoustic emissions (DPOAEs). Taken together, our results indicate that the conductive hearing loss observed in classical OI is not due to the altered bone quality of the middle ear, at least under unchallenged conditions in mice.
Parkin-dependent ubiquitination of TAX1BP1 directs efficient autophagic removal of defective mitochondria
2025-05-19

Abstract In stressed cells, the recessive Parkinson disease (PD) associated gene products PINK1 and parkin mediate the autophagic removal of damaged mitochondria (mitophagy). Upon mitochondrial membrane potential disruption, PINK1 phosphorylation activates the ubiquitin ligase parkin which ubiquitinates various mitochondrial protein substrates. These feed-forward modifications on the mitochondria surface attract ubiquitin-binding autophagy receptors that target ubiquitinated mitochondria to autophagosomes and indirectly contribute to phagophore elongation. Investigating post-translational protein modifications during this process, we detected transient ubiquitination of K549 within the third coiled-coil domain (CC3) of TAX1BP1 in HeLa cells expressing WT but not catalytically inactive parkin. Parkin-dependent ubiquitination did not target TAX1BP1 to proteasomal degradation but was rather indicative of a regulatory modification. In cells with the full complement of autophagy receptors, TAX1BP1 plays only a minor role in mitophagy. However, when expressed as a sole autophagy receptor, both WT and ubiquitination deficient TAX1BP1 were capable of promoting mitophagy, albeit mitochondria degradation was slightly delayed under mutant conditions. Use of the lysosomal inhibitor bafilomycin A indicated classical autophagolysosomal targeting of damaged mitochondria mediated by WT TAX1BP1. However, for the ubiquitination-deficient TAX1BP1, we observed an increased prevalence of enlarged endolysosomal vesicles carrying accumulated TAX1BP1-positive autophagosomes filled with mitochondrial material. Thus, while ubiquitination of the CC3 domain of TAX1BP1 is not essential for complete mitophagy, the lack of CC3 in TAX1BP1 reroutes the degradation flux to a less efficient endolysosmal degradative pathway. Interestingly, the PD gene product VPS35, becomes prominently engaged in this alternative mitophagy pathway.
Dynamics and equilibrium states of infinite systems of lattice bosons
2025-05-19

We consider the dynamics of systems of lattice bosons with infinitely many degrees of freedom. We show that their dynamics defines a group of automorphisms on a --algebra introduced by Buchholz, which extends the resolvent algebra of local field operators. For states that admit uniform bounds on moments of the local particle number, we derive propagation bounds of Lieb--Robinson type. Using these bounds, we show that the dynamics of local observables gives rise to a strongly continuous unitary group in the GNS representation. Moreover, accumulation points of finite-volume Gibbs states satisfy the KMS condition with respect to this group. This, in particular, proves the existence of KMS states.
First Search for Axion Dark Matter with a MADMAX Prototype
2025-05-20

This Letter presents the first search for dark matter axions with mass in the ranges <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"><a:mrow><a:mn>76.56</a:mn></a:mrow></a:math> to <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" display="inline"><c:mn>76.82</c:mn><c:mtext> </c:mtext><c:mtext> </c:mtext><c:mrow><c:mi mathvariant="normal">μ</c:mi><c:mi>eV</c:mi></c:mrow></c:math> and <f:math xmlns:f="http://www.w3.org/1998/Math/MathML" display="inline"><f:mrow><f:mn>79.31</f:mn></f:mrow></f:math> to <h:math xmlns:h="http://www.w3.org/1998/Math/MathML" display="inline"><h:mn>79.53</h:mn><h:mtext> </h:mtext><h:mtext> </h:mtext><h:mrow><h:mi mathvariant="normal">μ</h:mi><h:mi>eV</h:mi></h:mrow></h:math> using a prototype setup for the MAgnetized Disk and Mirror Axion eXperiment (MADMAX). The experimental setup employs a dielectric haloscope consisting of three sapphire disks and a mirror to resonantly enhance the axion-induced microwave signal within the magnetic dipole field provided by the 1.6 T Morpurgo magnet at CERN. Over 14.5 days of data collection, no axion signal was detected. A 95% CL upper limit on the axion-photon coupling strength down to <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" display="inline"><k:mrow><k:mo stretchy="false">|</k:mo><k:msub><k:mrow><k:mi>g</k:mi></k:mrow><k:mrow><k:mi>a</k:mi><k:mi>γ</k:mi></k:mrow></k:msub><k:mo stretchy="false">|</k:mo><k:mo>∼</k:mo><k:mn>2</k:mn><k:mo>×</k:mo><k:msup><k:mrow><k:mn>10</k:mn></k:mrow><k:mrow><k:mo>−</k:mo><k:mn>11</k:mn></k:mrow></k:msup><k:mtext> </k:mtext><k:mtext> </k:mtext><k:msup><k:mrow><k:mi>GeV</k:mi></k:mrow><k:mrow><k:mo>−</k:mo><k:mn>1</k:mn></k:mrow></k:msup></k:mrow></k:math> is set in the targeted mass ranges, surpassing previous constraints, assuming a local axion dark matter density <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" display="inline"><o:msub><o:mi>ρ</o:mi><o:mi>a</o:mi></o:msub></o:math> of <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" display="inline"><q:mrow><q:mn>0.3</q:mn><q:mtext> </q:mtext><q:mtext> </q:mtext><q:mi>GeV</q:mi><q:mo>/</q:mo><q:msup><q:mrow><q:mi>cm</q:mi></q:mrow><q:mrow><q:mn>3</q:mn></q:mrow></q:msup></q:mrow></q:math>. This study marks the first axion dark matter search using a dielectric haloscope.
Sodium–Glucose Cotransporter 2 Inhibitor Use and Risk of Liver-Related Events in Patients With Type 2 Diabetes: A Meta-analysis of Observational Cohort Studies
2025-05-20

BACKGROUND There is uncertainty regarding effect of sodium–glucose cotransporter 2 (SGLT2) inhibitors on the risk of major adverse liver-related outcomes (MALOs). PURPOSE We performed a meta-analysis of observational cohort studies to quantify the magnitude of the association between SGLT2 inhibitor use and risk of developing MALOs for people with type 2 diabetes mellitus (T2DM). DATA SOURCES We systematically reviewed three large electronic databases from inception to January 2025. STUDY SELECTION We included active-comparator, new-user cohort studies with comparison of SGLT2 inhibitors versus other glucose-lowering medications in patients with T2DM. DATA EXTRACTION The primary outcome was incidence rate of MALOs defined as a composite of hepatic decompensation events, hepatocellular carcinoma, liver transplantation, or liver-related deaths. Secondary outcomes included each of the above as individual events. Meta-analysis was performed with random-effects models. DATA SYNTHESIS We identified eight cohort studies with aggregate data on 626,104 patients with T2DM (397,806 SGLT2 inhibitor new users and 228,298 new users of other glucose-lowering agents). During a median of 2.7 years, SGLT2 inhibitor use was associated with significantly lower risk of MALOs (random-effects hazard ratio 0.83, 95% CI 0.72–0.95; I2 = 83.1%) and liver-related deaths (0.64, 0.50–0.82; I2 = 0%). The significant risk reduction in MALOs was observed in comparisons of SGLT2 inhibitors with dipeptidyl peptidase 4 inhibitors, metformin, or pioglitazone but not glucagon-like peptide 1 receptor agonists. Sensitivity analyses did not modify these results. A funnel plot did not show significant publication bias. LIMITATIONS Observational design of the cohort studies and high level of heterogeneity are the main limitations. CONCLUSIONS SGLT2 inhibitor use was associated with lower risk of MALOs for patients with T2DM.
Characterization of Patients with Lymph Node Only Metastatic Urothelial Carcinoma Treated with Nivolumab Plus Gemcitabine-Cisplatin Versus Gemcitabine-Cisplatin Alone from the CheckMate 901 Trial
2025-05-20

Nivolumab (NIVO) plus gemcitabine-cisplatin (GC) demonstrated deep, durable responses in patients with untreated unresectable or metastatic urothelial carcinoma (mUC) with superior overall (OS) and progression-free (PFS) survival versus GC alone. We report post hoc exploratory analyses with 33.6 mo of median follow-up in patients with lymph node (LN) only disease from CheckMate 901. In this phase 3 randomized trial (n = 608), cisplatin-eligible patients received NIVO 360 mg plus GC every 3 wk (Q3W) for six or fewer cycles followed by NIVO 480 mg every 4 wk for ≤2 yr, or GC Q3W for six or fewer cycles. The primary endpoints were OS and PFS by a blinded independent central review (BICR). The objective response rate (ORR) as per the BICR and safety were exploratory. This post hoc analysis evaluated patients with LN only mUC (n = 110). In this subgroup, OS (hazard ratio [HR], 0.58; 95% confidence interval [CI] 0.34-1.00) and PFS (HR, 0.38; 95% CI 0.22-0.66) improved with NIVO + GC versus GC. The ORR was 81% with NIVO + GC versus 64% with GC; complete response rates were 63% versus 34%. The incidence of treatment-related adverse events was similar between arms. In conclusion, clinically meaningful improvements in OS, PFS, and ORR, including twice the rate of complete response and more patients with treatment-free intervals, were observed with NIVO + GC versus GC in patients with LN only disease, providing additional support for first-line NIVO plus cisplatin-based chemotherapy in mUC.
Neural density functional theory in higher dimensions with convolutional layers
2025-05-20

Based on recent advancements in using machine learning for classical density functional theory for systems with one-dimensional, planar inhomogeneities, we propose a machine learning model for application in two dimensions (2D) akin to density functionals in weighted density forms, as, e.g., in fundamental measure theory. We implement the model with fast convolutional layers only and apply it to a system of hard disks in fully 2D inhomogeneous situations. The model is trained on a combination of smooth and steplike external potentials in the fluid phase. Pair correlation functions from test particle geometry show very satisfactory agreement with simulations although these types of external potentials have not been included in the training. The method should be fully applicable to 3D problems.
Self-assessment of Elbow Mobility as a Reliable Method in the Postoperative Follow-up Examination of Radial Head Fractures
2025-05-20

Abstract Sufficient follow-up of fractures is often difficult, due to age-related, health-related or geographical reasons. Self-assessment of the patient’s functional outcome could be an alternative to a personal medical examination. There is a lack of validated questionnaires to record these parameters for elbow injuries. The aim of the study was to validate the patient’s self-assessment of the range of motion following surgical treatment of complex radial head fractures. 50 patients (42% women) with a mean age of 49.7 ± 13.8 years (range 25–82 years) with a surgically treated radial head fracture (Mason III or IV) were examined, 39.6 ± 23.3 months postoperatively. The fracture was treated with radial head reconstruction (60%) or radial head prosthesis (40%). The follow-up examination included the assessment of elbow mobility using a questionnaire (Elbow Motion Assessment Score) and physical examination using a goniometer. In addition, quality of life was assessed using the SF-36 Health Survey. The agreement of the mobility was recorded as a percentage using Spearman’s correlation. Exact agreement between examiner and patient was achieved at 54% in flexion, 40% in extension, 86% in pronation and 54% in supination. The median deviations in agreement were 10° in extension and flexion and 20° in pronation and supination. The correlations were r = 0.550 (flexion), r = 0.841 (extension), r = 0.808 (pronation) and r = 0.754 (supination). Patients who agreed with the examiner on the movements achieved a higher score in the SF-36 Health Survey than patients who did not agree with the examiner (50.5 to 54.1 vs. 40.0 to 45.5). The survey of the range of motion by the patient using a questionnaire showed a high level of agreement with the measurement by an objective examiner. Such self-assessment can therefore be seen as a suitable, cost-effective alternative in the follow-up examination of surgically treated radial head fractures.
Genome-scale metabolic model of Staphylococcus epidermidis ATCC 12228 matches in vitro conditions
2025-05-21

ABSTRACT Staphylococcus epidermidis , a commensal bacterium inhabiting collagen-rich areas like human skin, has gained significance due to its probiotic potential in the nasal microbiome and as a leading cause of nosocomial infections. While infrequently leading to severe illnesses, S. epidermidis exerts a significant influence, particularly in its close association with implant-related infections and its role as a classic opportunistic biofilm former. Understanding its opportunistic nature is crucial for developing novel therapeutic strategies, addressing both its beneficial and pathogenic aspects, and alleviating the burdens it imposes on patients and healthcare systems. Here, we employ genome-scale metabolic modeling as a powerful tool to elucidate the metabolic capabilities of S. epidermidis . We created a comprehensive computational resource for understanding the organism’s growth conditions within diverse habitats by reconstructing and analyzing a manually curated and experimentally validated metabolic model. The final network, i Sep23, incorporates 1,415 reactions, 1,051 metabolites, and 705 genes, adhering to established community standards and modeling guidelines. Benchmarking with the Metabolic Model Testing suite yields a high score, indicating the model’s remarkable semantic quality. Following the findable, accessible, interoperable, and reusable (FAIR) data principles, i Sep23 becomes a valuable and publicly accessible asset for subsequent studies. Growth simulations and carbon source utilization predictions align with experimental results, showcasing the model’s predictive power. Ultimately, this work provides a robust foundation for future research aimed at both exploiting the probiotic potential and mitigating the pathogenic risks posed by S. epidermidis . IMPORTANCE Staphylococcus epidermidis , a bacterium commonly found on human skin, has shown probiotic effects in the nasal microbiome and is a notable causative agent of hospital-acquired infections. While these infections are typically non-life-threatening, their economic impact is considerable, with annual costs reaching billions of dollars in the United States. To better understand its opportunistic nature, we employed genome-scale metabolic modeling to construct a detailed network of S. epidermidis ’s metabolic capabilities. This model, comprising over a thousand reactions, metabolites, and genes, adheres to established standards and demonstrates solid benchmarking performance. Following the findable, accessible, interoperable, and reusable (FAIR) data principles, the model provides a valuable resource for future research. Growth simulations and predictions closely match experimental data, underscoring the model’s predictive accuracy. Overall, this work lays a solid foundation for future studies aimed at leveraging the beneficial properties of S. epidermidis while mitigating its pathogenic potential.
Capture of Longitudinal Change in Real‐Life Walking in Cerebellar Ataxia Increases Patient Relevance and Effect Size
2025-05-21

ABSTRACT Background With disease‐modifying drugs for degenerative ataxias on the horizon, ecologically valid measures of gait performance that can detect patient‐relevant changes in trial‐like time frames are highly warranted. Objectives In this 2‐year longitudinal study, we aimed to unravel ataxic gait measures sensitive to longitudinal changes in patients' real lives using wearable sensors. Methods We assessed longitudinal gait changes of 26 participants with degenerative cerebellar disease (Scale for the Assessment and Rating of Ataxia [SARA]: 9.4 ± 4.1) at baseline, 1‐year, and 2‐year follow‐up using three body‐worn inertial sensors in two conditions: (1) laboratory‐based walking (LBW); and (2) real‐life walking (RLW). In RLW, a context‐sensitive analysis was performed by selecting comparable walking bouts according to macroscopic gait characteristics. Gait analysis focused on measures of spatio‐temporal variability, particularly stride length variability, lateral step deviation, and a compound measure of spatial variability (SPCmp). Results Gait variability measures showed high test–retest reliability in both walking conditions (intraclass correlation coefficient [ICC], ≥0.82). Cross‐sectional analyses revealed high correlations of gait measures with ataxia severity (SARA, effect size ρ ≥ 0.75); and with patients' subjective balance confidence (Activity‐specific Balance Confidence scale [ABC]: ρ ≥ 0.71). Although SARA showed longitudinal changes only after 2 years, the gait measure SPCmp revealed changes after 1 year with high effect size ( r prb = 0.80). Sample size estimation for the gait measure SPCmp showed a required cohort size of n = 42 participants (n = 38; spinocerebellar ataxias [SCA] 1/2/3 subgroup) to detect a 50% reduction in progression at 1 year with a hypothetical intervention, compared to n = 147 for SARA at 2 years. Conclusions Because of their ecological validity and larger effect sizes, real‐life gait characteristics represent promising performance measures as outcomes for future treatment trials. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Accuracy of extended point-of-care lung ultrasound (EPLUS) for aetiological differentiation of lower respiratory tract infections: a prospective cohort study from India
2025-05-21

The study highlights the high sensitivity of LUS for detecting pulmonary changes but revealed low specificity to differentiate pulmonary conditions, especially in the presence of pre-existing comorbidities. Future research should explore the accuracy of combinations of clinical characteristics and ultrasound findings in algorithmic approaches, which may improve diagnostics in resource-limited settings.
Direct Laser Writing of Au Top Contacts on WSe2 for High-Speed Photodetection
2025-05-21

We demonstrate high-speed photodetectors based on bi-, few- and multilayered WSe2 flakes fabricated by high-resolution direct laser writing of Au top contacts from atomically precise gold nanoclusters as an alternative to conventional photolithography. Time-resolved steady-state and transient photoresponse measurements reveal remarkable switching speeds exhibiting response times down to 7 ns and electrical bandwidths up to 250 MHz. Key performance metrics, including responsivity, detectivity and external quantum yield are studied with respect to the applied irradiance and excitation wavelength. By demonstrating high-speed switching in thin-layered WSe2-based devices, this work highlights the potential of laser-written metal-semiconductor interfaces for high-speed optoelectronic applications of 2D materials.
Synergistic treatment of linoleic acid and cefazolin on Staphylococcus aureus biofilm-related catheter infections
2025-05-21

ABSTRACT Staphylococcus aureus is a human pathogen that causes severe infections through biofilm formation. S. aureus biofilm is particularly susceptible to catheters in patients undergoing peritoneal dialysis. Although antibiotics are used to treat catheter infections, high-concentration treatments adversely affect human host immune systems and change the physicochemical properties of the catheters. To improve therapeutic outcomes without side effects, we combined antibiotics and natural products. In this study, we propose a combination of linoleic acid (LA) and cefazolin (CFZ) to treat S. aureus infections synergistically and apply it to catheter environments and in vivo systems. LA is a polyunsaturated fatty acid derived from natural products, and CFZ is a major antibiotic used to treat S. aureus catheter-related infections. The optimum synergistic condition was determined using silicon pad-forming biofilm similar to catheter materials. S. aureus biofilms were considerably inhibited in vitro and in vivo owing to the improved antibacterial effects. Furthermore, the combination negatively regulated the chemokine levels in the peritoneum, kidney, and liver extracted from mouse models. Moreover, it did not affect the cytotoxicity of human omentum mesothelial cells and the functions of the kidney and liver. Therefore, the combination of LA and CFZ could be a potential synergistic therapy for S. aureus catheter infections. IMPORTANCE Catheter contamination is commonly caused by Staphylococcus aureus biofilm formation, primarily in peritoneal dialysis patients. Although antibiotics are used to treat catheter infections, high concentrations of antibiotics impair the immune system of the human host and alter the physicochemical properties of catheters. Therefore, it is crucial to improve therapeutic outcomes while minimizing the side effects of antibiotics. Combined treatments with natural products can be solutions to alleviate these problems. Our study offers a new synergistic combination (linoleic acid and cefazolin) for the control of catheter infections caused by S. aureus biofilms, especially in peritoneal dialysis.
Diagnosis, management and prevention of loiasis: guideline of the German Society for Tropical Medicine, Travel Medicine, and Global Health (DTG)
2025-05-21

Abstract Loiasis is a complex filarial infection endemic in Central Africa and parts of West Africa. Loa loa is transmitted by the deer fly Chrysops dimidiata and C. silacea . The clinical manifestation of the disease is highly variable ranging from asymptomatic infection, symptomatic disease, to life-threatening complications. The diagnosis of L. loa infection is challenging due to a significant proportion of occult infections and a lack of reliable point of care tests. While diethylcarbamazine is the gold standard for curative treatment in many non-endemic countries, its use is limited in endemic regions due to its propensity for severe adverse drug reactions that may occasionally lead to life threatening complications. Alternative treatment regimens have specific indications and limitations in the treatment of loiasis. In this guideline, issued by the German Society for Tropical Medicine, Travel Medicine, and Global Health, recommendations for the diagnosis, management, treatment, and prevention of loiasis are provided based on the currently available best evidence, and gaps in our understanding are highlighted.