bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between physical activity and diabetes mellitus: mediation analysis involving Systemic Immune-Inflammatory Index in a cross-sectional NHANES study
Authors: Chen Yongze , Huang Ruixian , Mai Zhenhua , Jin Zhimei , Lai Fengxia , Chen Xueqin , Kong Danli , Ding Yuanlin
Published: February 2025

Objectives

In this study, we aimed to clarify the relationship between physical activity (PA) and diabetes mellitus (DM), as well as the mediating role of Systemic Immune-Inflammatory Index (SII) in the relationship.

Design

A cross-sectional study.

Setting

National Health and Nutrition Examination Survey (NHANES) data collection took place in the USA at participants’ homes and mobile examination centres with specialised equipment.

Participants

The study population consisted of 9493 American adults aged 20 and above from the NHANES 2005 to 2018.

Primary and secondary outcome measures

Information on the specific PA was reported through self-administered questionnaire by participants and we used this information to calculate a metabolic equivalent score for the particular PA. The calculation of SII follows a standard formula: SII=P (platelets)×N (neutrophils)/L (lymphocytes).

Results

A total of 9493 participants were included, with 1672 diagnosed with DM. The participants with DM were more inclined to have lower levels of PA while having higher levels of SII. In all three models, high levels of PA were significantly negatively associated with the risk of DM compared with moderate levels of PA, and a non-linear association between natural logarithm-physical activity (Ln-PA) and DM was observed. Furthermore, there was a significant reduction in DM risk for Ln-PA >6.71 in all models. Mediation analysis showed that SII mediated the relationship between PA and DM, as well as between Ln-PA and DM, with respective mediation proportions of 4.32% and 12.141%, as well as 3.12% and 10.46% after adjusting for covariates.

Conclusion

This study investigated the relationship among PA, SII and DM. We provide robust evidence supporting the inverse association between PA and DM risk while highlighting the mediating role of inflammation, as reflected by SII. These findings contribute valuable insights to inform public health strategies and clinical interventions aimed at reducing the global burden of DM.
Isokinetic muscle strength training combined with proprioceptive neuromuscular facilitation for rehabilitation of patients after anterior cruciate ligament reconstruction: a protocol for a randomised controlled trial
Authors: Wang Bin , Zhang Qiaojun , Li Peng , Xu Yumeng , Li Wenjuan , Lei Xiaohui , Wan Kai , Lu Lei , Gao Xin , Zhang Siduo , Fu Peijia , Qiao Hongfei , Ma Ben
Published: February 2025

Introduction

Anterior cruciate ligament injury seriously affects the motor function of patients. Currently, there are numerous rehabilitation methods after anterior cruciate ligament reconstruction (ACLR). The aim of this study was to investigate the rehabilitation effect of isokinetic muscle strength training combined with proprioceptive neuromuscular facilitation (PNF) technique in postoperative patients. A single-blind randomised controlled trial was conducted to compare the difference between this combined therapy and conventional rehabilitation, and to provide a scientific basis for optimising the rehabilitation strategy after ACLR, to promote faster and better recovery of knee joint function in patients.

Methods and analysis

This study is a randomised controlled, assessor-blind trial. A total of 40 patients after ACLR were randomly divided into a control group and a test group. Conventional rehabilitation and isokinetic muscle strength training will be performed in the control group, while the test group will receive PNF techniques in addition to the interventions of the control group. These interventions were performed three times a week for 6 weeks. All interventions will be completed in the Department of Rehabilitation Medicine of the Second Affiliated Hospital of Xi'an Jiaotong University. The primary outcome measure will be assessed by knee proprioception. Secondary outcome measures will include knee isokinetic strength, balance ability and Lysholm knee function score. The above assessments will include a baseline assessment, an assessment after 6 weeks of intervention, and a follow-up visit at week 24.

Ethics and dissemination

This study was approved by the Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University (Number: 2024059). Study results will be published in open access peer-reviewed journals and may be shared at relevant meetings and research meetings.

Trial registration number

ChiCTR2400085897.
Quality improvement collaborative to increase access to caesarean sections: lessons from Bihar, India
Authors: Mehndiratta Abha , Moharana Prabir Ranjan , Mahapatra Tanmay , Srikantiah Sridhar , Babu Sunil , Simba Sarita , Sanjiv Daulatrao Sanjiv Daulatrao , Pandey Vikas , Shastri Rahul , Kodiyath Srinivas , Mukherjee Sulagna , Sah Pramod , Barker Pierre
Published: February 2025

Background

Countries with resource-poor health systems have struggled to improve access to and the quality of caesarean section (C-section; CS) for women seeking care in public health facilities. Access to C-section in Bihar State remains very low, while access has increased in many other contexts.

Methods

We used quality improvement (QI) combined with targeted resource management to test and implement changes that were designed to increase C-section delivery. We compared C-section delivery percentages after the interventions across eight intervened (QI) hospitals and between QI hospitals and the remaining 22 non-intervened (non-QI) hospitals with baseline CS <10%. We linked patterns of improvement and sustainability to theoretical drivers of improvement and timing of interventions.

Results

In QI hospitals, C-section percentage increased from 2.9% at baseline to 5.9% in the intervention phase and 4.6% in the post intervention phase. In non-QI hospitals, we observed a small change (2.6–3.3%) during the same time period of the interventions in the QI hospitals. Addition of skilled personnel resulted in increased C-section percentage in QI hospitals (3.6–5.9%) but not non-QI hospitals (3.4–3.2%).

Conclusions

C-section availability increased for a population of women giving birth following initiation of QI BTS collaborative in a low-income country public sector setting that has historically struggled to provide this service. Addition of obstetric and operating room resources alone, without interventions to support system changes, may not result in additional increase in C-section delivery. The adaptive implementation model may contribute to efforts to provide more access to C-sections in other very resource-limited settings.
Using emergency department data to reduce late-night alcohol-related presentations in an Australian central business district
Authors: Miller Peter , Taylor Nicholas , Egerton-Warburton Diana , Baker Timothy , Kloot Kate , Shepherd Jonathan , Akhlaghi Hamed
Published: February 2025

Introduction

The Cardiff Model for Violence Prevention is a data sharing approach aiming to reduce violence-related presentations to emergency departments (EDs). This model has not previously been tested with patients attending EDs in a major Australian urban setting, nor has the use of media reporting of results and letters to venues without a local violence prevention board been tested.

Objective

To determine this approach’s effect on alcohol-associated presentation rates during high-alcohol hours (HAHs) in a major ED servicing the nightlife district in central Melbourne.

Design

Between July 2017 and June 2020, this prospective study asked people aged≥18 years attending ED about their alcohol consumption and last drink location. From December 2018, quarterly letters were sent to the top five venues identified as the last drink location and press releases were sent to all media outlets.

Findings

A significant gradual decrease in monthly injury attendance rates during HAH was observed (coefficient = −0.001, p= 0.017), however, no step change was found. Venue-level data highlighted a short-term drop in attributed events.

Discussion

Sharing Last Drinks ED data via stand-alone media reporting and letters to venues was associated with a small but significant reduction in alcohol-related injury presentation rates. However, the impact waned as media stopped reporting findings. This study highlights the importance of including a violence prevention board.

Conclusion

The model continues to have promise for reducing alcohol-related harm, however, engagement from government agencies free from alcohol industry funding is important for long-term success.
Clarithromycin-induced myoclonic status epilepticus
Authors: Biçimveren Mahmut Sami
Published: February 2025

Myoclonus is a sudden brief involuntary activity and is either epileptic or non-epileptic. Myoclonic seizures are common in juvenile myoclonic epilepsy and in the much rarer childhood epilepsies, such as Dravet syndrome and Doose syndrome. However, they also occur at any age in adults. Myoclonic seizures may occur in cortical stroke, Alzheimer’s disease, Lance-Adams syndrome, autoimmune limbic encephalitis and toxic-metabolic disorders. Clarithromycin may also cause myoclonic status epilepticus. We report a patient with myoclonic status epilepticus induced by clarithromycin.
Biopolymer-Modified Bentonite Slurry with Gellan Gum for High Salt Resistance in Marine Geotechnical Engineering
Authors: Cao Hongtao , Sun Honglei , Xu Shanlin , Cui Yujun , Cai Yuanqiang , Xu Tao , Lu Xilin
Published: February 2025

The performance of bentonite slurry in submarine tunnel construction is significantly deteriorated by high-salinity seawater intrusion, increasing the risk of excavation face instability. This study investigates the incorporation of the biopolymer gellan gum (GG) into the bentonite slurry, as a high salt resistant and eco-friendly additive. The mechanisms underlying seawater-induced deterioration and GG-imparted salt resistance were analyzed. Results demonstrate that seawater increases the bleeding rate and API (American Petroleum Institute) fluid loss while reducing the apparent viscosity and yield stress of bentonite slurry, thereby compromising its shear-thinning properties. The addition of GG mitigates these negative effects and improves the colloidal stability, rheological properties, and filter cake quality of the slurry. With 1.2% GG, the 24-hour bleeding rate of slurry was reduced from 86.4% to 0%, and a low-permeability filter cake (5.6 × 10⁻⁹ m/s) was rapidly formed, as confirmed by sand infiltration tests. Scanning Electron Microscopy (SEM) analysis revealed that GG re-disperses seawater-induced bentonite platelet aggregates, while Fourier Transform Infrared Spectroscopy (FTIR) results highlight the synergistic effects of cation consumption and gel filling by GG. This study highlights the potential of GG as a sustainable additive for bentonite slurry in marine geotechnical engineering applications.
Can synchrotron radiation reveal the presence of dark sector around black hole?
Authors: Rogatko Marek , Verma Paritosh
Published: February 2025

We studied synchrotron radiation of a massive charged under visible and hidden sector groups, moving in equatorial plane around spherically symmetric weakly magnetized black hole. As a model of dark matter we choose the one, in which Maxwell field is coupled to the additional U(1)-gauge field envisaging the dark sector, the so-called dark photon model. Magnetization of a black hole also stems from Maxwell-dark photon electrodynamics. One found the radiation power and energy loss of the particle and looked for the imprints of dark matter on those phenomena.
Improving quantitative ventifact analysis for climate investigations using the Dyngjusandur sandsheet in Iceland as a planetary analogue
Authors: Hudziak Samuel X. , Ukstins Ingrid , Peate David , Whelley Patrick , Scheidt Stephen , Hamilton Christopher W.
Published: February 2025

We use the Dyngjusandur sandsheet, Iceland, as a testbed to assess the type and number of measurements required to accurately represent ventifact orientations and extract paleowind information through a statistical evaluation of the differences between photogrammetric based and
in situ
measurements of ventifact feature orientations. Forty representative ventifacts were selected for
in situ
measurement, 20 of which were imaged for photogrammetric analysis to produce oriented and scaled virtual 3D models. An additional set of measurements were made on the “synthetic” models to allow for statistical assessment of erosional feature orientation. Despite the similarity between the photogrammetric (1145 measurements), and the
in situ
datasets (500 measurements), there are small, but significant differences in mean feature orientation that become more pronounced as sample size is reduced. Results indicate that
in situ
and photogrammetric methods of measuring feature orientation are comparable (to within 2° ± 2° at 1

σ

[
N
 = 20] for inferring paleowind directions), but photogrammetric analyses require less time for data acquisition (by a factor of 0.36–0.66) and yields over five times (5.16×) as many measurements per ventifact, with additional advantages of being able to examine digital objects under different illumination conditions, magnifications, and from angles that are otherwise not possible in the field.
Retentive Decision Transformer with Adaptive Masking for Reinforcement Learning based Recommendation Systems
Authors: Wang Siyu , Chen Xiaocong , Yao Lina
Published: February 2025

Reinforcement Learning-based Recommender Systems (RLRS) have shown promise across a spectrum of applications, from e-commerce platforms to streaming services. Yet, they grapple with challenges, notably in crafting reward functions and harnessing large pre-existing datasets within the RL framework. Recent advancements in offline RLRS provide a solution for how to address these two challenges. However, existing methods mainly rely on the transformer architecture, which, as sequence lengths increase, can introduce challenges associated with computational resources and training costs. Additionally, the prevalent methods employ fixed-length input trajectories, restricting their capacity to capture evolving user preferences. In this study, we introduce a new offline RLRS method to deal with the above problems. We reinterpret the RLRS challenge by modeling sequential decision-making as an inference task, leveraging adaptive masking configurations. This adaptive approach selectively masks input tokens, transforming the recommendation task into an inference challenge based on varying token subsets, thereby enhancing the agent’s ability to infer across diverse trajectory lengths. Furthermore, we incorporate a multi-scale segmented retention mechanism that facilitates efficient modeling of long sequences, significantly enhancing computational efficiency. Our experimental analysis, conducted on both online simulator and offline datasets, clearly demonstrates the advantages of our proposed method.
Harnessing Implementation Science in Clinical Psychology: Past, Present, and Future
Authors: Beidas Rinad S. , Boyd Meredith , Casline Elizabeth , Scott Kelli , Patel-Syed Zabin , Mills Chynna , Mustanski Brian , Schriger Simone , Williams Faith Summersett , Waller Claire , Helseth Sarah A. , Becker Sara J.
Published: February 2025

Implementation science aspires to equitably accelerate the uptake of clinical research into practice to improve population health. The focus of implementation science includes individual behavior change mechanisms that are similar to those that drive the field of clinical psychology. For this reason, clinical psychologists are well-suited to take up implementation science methods in pursuit of improving the quality of behavioral health care. To do so, clinical psychologists must expand beyond individual behavior change to include a focus on organizations and systems. In this review, we reflect on ways that clinical psychologists can lead in the integration of implementation science principles and approaches into clinical psychology research and practice. We discuss the role clinical psychologists play in closing know–do gaps in behavioral health and describe how clinical psychologists can build implementation science competencies. We end with current controversies and opportunities for innovation to further improve the quality of behavioral health care.
Fast and Slow Subduction Earthquakes in Latin America
Authors: Ruiz S. , Ide S. , Potin B. , Madariaga R.
Published: February 2025

Most seismicity in Latin America is controlled by the subduction process. Different zones have hosted earthquakes of magnitudes larger than Mw 8.5 that repeat every several centuries. Events around Mw 8.0 are more frequent; since the beginning of the twentieth century, some collocated earthquakes have occurred with differences of decades, which allows for comparison of old and modern seismological records. The rupture zones that have hosted mega-earthquakes continue to produce smaller earthquakes after three centuries. Therefore, the process of unlocking in the Latin America subduction zone occurs by giant (≥Mw 9.0), mega- (9.0 > Mw ≥ 8.5), and large (8.5 > Mw ≥ 7.5) earthquakes, and interaction between these events is not yet fully understood. We have less understanding of the earthquakes that occurred in the oceanic plates, which have not been correctly recorded due to poor seismological instrumentation and lack of knowledge about subduction during the first half of the twentieth century in Latin America. Slow earthquakes have been observed in some zones of Latin America, several of them with recurrence periods of a few years, as well as tectonic (nonvolcanic) tremors and low-frequency and very low-frequency earthquakes. How do these slow slip manifestations relate to ordinary earthquakes? This question is still difficult to answer for Latin America given the lack of dense geodetic and seismic networks that allow identification of all the slow earthquakes that likely occur more frequently than currently reported.

▪

Latin America subduction zones share similar seismic characteristics. They can host large-magnitude earthquakes and exhibit a variety of slow earthquakes.

▪

Giant earthquakes, with a magnitude greater than 9, have occurred so far in Chile, and mega-earthquakes have occurred in several Latin American countries.

▪

Additional slow earthquakes will be detected in Latin America as seismic and geodetic networks become denser.
Quantitative Stress First-Pass Perfusion Cardiac MRI: State of the Art
Authors: Catania Roberta , Quinn Sandra , Rahsepar Amir A. , Agirlar Trabzonlu Tugce , Bisen Jay B. , Chow Kelvin , Lee Daniel C. , Avery Ryan , Kellman Peter , Allen Bradley D.
Published: February 2025

Quantitative stress perfusion cardiac magnetic resonance (CMR) imaging is an emerging and powerful clinical tool that improves the diagnostic accuracy of stress perfusion CMR for noninvasive assessment of epicardial coronary artery disease, microvascular dysfunction, aortic stenosis, and cardiac allograft vasculopathy.
Body MRI Approach: Guide for Common Indications
Authors: Hoegger Mark J. , Fraum Tyler J. , Stephen Vincent T. , Ludwig Daniel R. , Itani Malak , Lanier Michael H. , Rajput Mohammed Z. , Tsai Richard , Tadavarthi Yasasvi , Zhang Donald , Parwal Utkarsh , Shetty Anup S.
Published: February 2025

The slide presentation demonstrates an approach to body MRI for common indications in the abdomen and pelvis, incorporating clinical information, knowledge of imaging patterns, and various scoring paradigms.
Spatial Radiomic Graphs for Outcome Prediction in Radiation Therapy–treated Head and Neck Squamous Cell Carcinoma Using Pretreatment CT
Authors: Bae Joseph , Mani Kartik , Czerwonka Lukasz , Vanison Christopher , Ryu Samuel , Prasanna Prateek
Published: February 2025

Radiomic graph analysis of pretreatment CT enables holistic analysis of head and neck squamous cell carcinoma tumors and their surrounding environment, showing good performance in local-regional recurrence and distant metastasis prediction and unique model interpretability.
Heat-producing thermoeffector plasticity in response to prolonged iterative exposure to a high heat-loss environment: No indication of thermoregulatory fatigue
Authors: Moes Maaike I. , Elia Antonis , Eiken Ola , Keramidas Michail E.
Published: February 2025

Previous studies have suggested that, during prolonged cold exposure, shivering thermogenesis may gradually be attenuated, supposedly reflecting a state of central fatigue (aka “thermoregulatory fatigue”) provoked by extended shivering activity, that precipitates hypothermia. The purpose of this study was to revisit the validity of this notion. Twelve noncold‐acclimatized men participated in three ∼10‐h sessions, during which they performed repeatedly three 120‐min cold‐water immersions. To induce discrete amounts of heat‐producing thermoeffector output, presumptively leading to distinct levels of fatigue during each session, subjects were submersed, within each session, in either severely (15°C), moderately (20°C), or slightly (28°C) cold water. The cold‐induced elevation in thermogenic rate was similar across the three repeated immersions performed within the 15°C (˜130 W･m2) and 20°C (˜100 W･m2) sessions (P ≥ 0.43). In the 28°C‐session, the metabolic heat production was augmented by ˜7% in the second and third immersions compared to in the first immersion (P=0.01). No intrasession differences were noted with regards to the body‐core cooling rate, the cold‐induced drop in skin temperature and forearm cutaneous vascular conductance, or the stress‐hormone (salivary α‐ amylase and cortisol concentrations) and thermoperceptual responses (P>0.05). The present findings, therefore, demonstrate that the ability to generate heat remains intact during prolonged iterative exposure to a high‐heat loss environment in a single day, regardless of the severity of cold stressor. The intermittent application of slight cold stress (i.e., 28°C water) appears to mediate metabolic sensitization, reflecting either the circadian rhythmicity of heat‐producing thermoeffector activity, or perhaps the rapid induction of metabolic adaptation.
Modeling and Recognition of Retinal Blood Vessels Tortuosity in ROP Plus Disease: A Hybrid Segmentation–Classification Scheme
Authors: Varysova Alice , Kubicek Jan , Penhaker Marek , Augustynek Martin , Oczka David , Marsolkova Kristyna , Timkovic Juraj
Published: February 2025

Retinopathy of prematurity (ROP) remains a significant cause of childhood blindness despite advancements in neonatal care. Identifying the plus form of ROP, characterized by dilated and tortuous blood vessels, is crucial for timely intervention. This study introduces an intelligent segmentation–classification system for the autonomous detection of retinal blood vessels and the classification of ROP plus form. Utilizing Clarity RetCam 3 images, our system employs morphological image processing and convolutional neural networks (CNNs) for segmentation and classification, respectively. Testing on a dataset of premature infants’ retinal images demonstrates high segmentation accuracy (median = 0.974) and superior classification performance (accuracy = 0.975, sensitivity = 0.950, and specificity = 1). In addition, the system exhibits versatility, with successful segmentation in adult retinal images from public databases. These findings highlight the system’s potential for clinical use in retinal vessel identification, feature extraction, and ROP plus form classification. The proposed system is capable of effectively identifying retinal blood vessels from both alternatives including adult and premature born retinal images with a high accuracy in contrast to related studies. Thus, this system has the potential to be used in clinical practice for retinal blood vessels’ identification, retinal blood vessels’ feature extraction, and ROP plus form classification.
Effects of Lee Silverman Voice Treatment‐BIG on Motor, Cognition, Mental Health, Occupational Performance, and Occupational Balance in Patients With Schizophrenia: A Single‐Subject Experimental Study
Authors: Jang Woo-Hyuk , Seo Sang-Min , Kim Si-Hyun
Published: February 2025

Introduction: In this study, we aim to apply BIG to patients with schizophrenia to confirm changes in mental symptoms, task performance, and occupational balance through motor and cognitive enhancement.

Method: This study used a single‐subject A‐B‐A design. It consisted of a total of 22 sessions, with 4 sessions in the baseline period, 16 sessions in the intervention period (Lee Silverman Voice Treatment‐BIG), and 2 sessions in the follow‐up period. The subjects were three male patients diagnosed with chronic schizophrenia, all severe cases. During the 22 sessions, the timed up and go test (TUG) and functional reach test (FRT) and the Montreal Cognitive Assessment (MoCA) were used to determine changes in motor function and cognition, and the subjective cognitive and mental score (SS), Canadian Occupational Performance Measure (COPM), and Occupational Balance Questionnaire‐Korean (OBQ‐K) were used to determine changes in psychiatric symptoms, work performance, and work balance satisfaction before and after the intervention. Statistically significant changes were determined using the two standard deviation (2SD) band method.

Results: The TUG, FRT, and MoCA showed significant results in the intervention period compared to the baseline period. The SS, COPM, and OBQ‐K also showed positive changes in scores from pre‐ to postintervention.

Conclusion: In this study, BIG was found to promote improvement in motor and cognitive function in chronic schizophrenia patients, with positive effects on psychiatric symptoms, task performance, and occupational balance satisfaction.
SMURF2 facilitates GAP17 Isoform 1 membrane displacement to promote mutant p53-KRAS oncogenic synergy
Authors: Ray Paramita , Shukla Shirish , Zhang Yaqing , Donahue Katelyn L. , Nancarrow Derek J. , Kasturirangan Srimathi , Shankar Sunita , Cuneo Kyle , Thomas Dafydd , Gadgeel Shirish M. , Lawrence Theodore S. , Pasca di Magliano Marina , Ray Dipankar
Published: February 2025

Cooperativity between mutant p53 and mutant KRAS, although recognized, is poorly understood. In pancreatic cancer, mutant p53 induces splicing factor hnRNPK causing isoform switch producing overexpression of GTPase activating protein 17 isoform 1 (GAP17-1). GAP17-1 is mis-localized in the cytosol, instead of the membrane, due to insertion of exon 17 encoding a PPLP motif, thus allowing mutant KRAS to remain in the GTP bound hyperactive state. However, the role of PPLP in influencing GAP17-1 mis-localization remains unclear. We show that Smad Ubiquitination Regulatory Factor 2 (SMURF2), a known stabilizer of mutant KRAS, interacts with GAP17-1 via the PPLP motif and displaces it from the membrane, facilitating mutant p53 mediated mutant KRAS hyperactivation. We used cell lines with known KRAS and TP53 mutations, characterized Smurf2 expression in multiple pancreatic cancer mouse models (iKras*; iKras*, p53*, and p48-Cre; Kras*) and performed single cell RNAseq and tissue microarray on preclinical and clinical samples. We found that SMURF2 silencing profoundly reduces survival of mutant TP53; KRAS driven cells. We show that a GAP17-1 AALA mutant does not bind to SMURF2, stays in the membrane, and keeps mutant KRAS in the GDP bound state to inhibit downstream signaling. In mouse models, mutant KRAS and SMURF2 upregulation are correlated in pancreatic intraepithelial neoplasia (PanIN) and ductal adenocarcinoma (PDA) lesions. Furthermore, PDA patients who received neoadjuvant therapy and express moderate to high SMURF2 show decreased overall survival (p=0.04). Implications: In TP53 and KRAS double mutated pancreatic cancer, SMURF2 driven GAP17-1 membrane expulsion facilitates mutant p53-KRAS oncogenic synergy.
THE INFLAMMATORY PATHOGENETIC PATHWAYS OF FABRY NEPHROPATHY AND AGALOPATHY; GLA VARIANTS INDUCTION OF ENDOPLASMIC RETICULUM STRESS
Authors: Feriozzi Sandro , Rozenfeld Paula
Published: February 2025

Fabry disease (FD) is a monogenic disease with highly variable clinical features. This variability suggests that additional pathogenetic pathways may exist besides the intra-lysosomal deposition of globotriaosylceramide (Gb3) and its deacylated form globotriaosylsphingosine (LysoGb3) caused by an enzyme deficiency.
Research studies proved that the deposition of Gb3 and LysoGb3 can stimulate inflammatory processes. Mononuclear immune competent cells exposed to Gb3 deposition express adhesion molecules and release proinflammatory and fibrotic cytokines such as interleukin β, tumour necrosis factor-alpha (TNFα), and transforming growth factor beta (TGFβ). These processes determine the activation of inflammation processes associated with chronic inflammation and tissue fibrosis. The pathogenetic mechanisms stimulated by Gb3 and LysoGb3 deposition could become independent from the initial stimulus, causing an irreversible effect, in which Fabry disease-specific therapy can play a limited role.
A new disease mechanism, "Agalopathy", would coexist with the enzyme deficiency. Missense variants in the coding sequence of the GLA gene would generate the misfolding of the altered protein alpha-galactosidase A. Emergence of misfolded proteins may generate stress of the endoplasmic reticulum (ER), leading to induction of the unfolded protein response (UPR). The UPR causes the release of proinflammatory cytokines and contributes to inflammatory status. This mechanism could be activated independently of glycolipid deposition, and its relationship with inflammatory pathways deserves more research. Strikingly, a zebrafish GLA knockout model that naturally lacks the enzyme that synthesizes Gb3 shows many alterations in lysosomal functions. These pieces of evidence suggest the involvement of alternative pathways independent of Gb3 in FD pathogenesis.
This review aims to describe these processes' role in the pathogenesis of renal damage in FD or Agalopathy nephropathies.
The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits.
Authors: Gudura Tariku T. , Sawaf Hanny , Ogbenna Randy , Mehdi Ali , Herlitz Leal , Gebreselassie Surafel K. , Bobart Shane A.
Published: February 2025

Introduction: Proliferative glomerulonephritis with monoclonal immunoglobin (Ig) deposits (PGNMID) is a rare form of kidney disease associated with low monoclonal protein detection rates and poor renal outcomes. The lack of effective therapy is partly due to limited data and understanding of its pathogenesis.

Methods: We conducted a retrospective analysis of 18 patients with PGNMID from the Cleveland Clinic Kidney Biopsy Epidemiology Project from January 2015 to March 2023.

Results: PGNMID was more predominant among males (67%), and whites (78%), with median age of 60 years. Over 2/3rd of patients presented with hypertension, renal insufficiency, and hematuria, while 26% of patients had nephrotic syndrome. Mean serum creatinine and proteinuria at biopsy were 3.2 mg/dl and 4.3 gm/gm respectively. A detectable monoclonal (M) protein was detected in 28% of cases, however, only 3 patients had underlying hematologic disorders (Multiple Myeloma, CLL, and B cell lymphoma). An endocapillary hypercellularity/membranoproliferative pattern (72%), IgG/Kappa (83%), and IgG3 (56%) were predominant findings on kidney pathology. Eight patients (44%) progressed to ESKD, with a median onset of 7.5 months after the initial kidney biopsy. While 6 patients achieved complete remission primarily with clone directed therapy.

Conclusion: Despite monoclonal protein deposition on kidney biopsy, 28% patients with PGNMID had a detectable monoclonal protein. Unlike other forms of paraproteinemic kidney diseases, renal outcomes for patients with PGNMID are poor, with 44% progressing to ESKD (median time 7.5 months) after kidney biopsy in our cohort. Clone-directed therapy to improve outcomes remains the mainstay of treatment, despite the absence of detectable clone in most cases. Thus, further investigation into the pathogenesis of PGNMID is warranted to guide future treatment discovery and clinical trials.
The Teixeira Leite sisters and their transatlantic alliances: rebuilding an elite social network from the French Third Republic (1880-1930)
Authors: Soares Cecília Elisabeth Barbosa
Published: February 2025

This article partially rebuilds the social network of Brazilian businesswoman Eufrásia Teixeira Leite (1850-1930) and her sister Francisca (1845-1899), by analyzing a sample of letters, cards, and telegram received by her at different periods of her lifetime. A comprehensive methodology used primary sources, such as correspondence and other documents of Eufrásia’s personal archive, complementary to secondary sources, to identify her interlocutors and, indirectly, explore the personality and interests of a 19th century liberal woman. The results illustrate the role of storytelling in sociohistorical research and women’s studies, based on individual cases and using personal archives as a starting point for a broader analysis.
Servidão e organizações: Uma aproximação de Espinosa dos estudos organizacionais críticos
Authors: Siqueira Marcus Vinicius
Published: February 2025

The objective of this article is to relate Spinoza’s thought to critical organizational studies, using the servitude in organizations as a guide. To accomplish this, we analyze Spinoza’s thought and discuss the relationship between his ontology and political approach to understand relevant themes to critical studies, as freedom and servitude. This article contributes to a discussion, analyzing the oxymoron of voluntary servitude, and it anchors itself in Spinoza’s thought to understand critically the relationship between company and person in contemporary organizations, establishing a resistance to the domination and totalitarianism of neoliberalism.
O governo das paixões: Encontros e desencontros entre Descartes e Espinosa
Authors: Mordoch Daniela
Published: February 2025

This article aims to explore the similarities and differences between Descartes and Spinoza's views on governing the passions. The analysis will draw on articles from the Passions of the Soul to support the Cartesian perspective that the will should control the passions by the guidance of reason. As a counterpoint, this text will focus on propositions 7, 8, and 14 of part IV of Spinoza's Ethics. These propositions suggest moderating the force of the affects based on the power of the mind itself, which is also presented as affectivity. Through a critique of Descartes, Spinoza's innovations will be explored, particularly his studies on the affects and passions.
Development of Zafirlukast Analogues for Improved Antithrombotic Activity Through Thiol Isomerase Inhibition
Authors: Keovilay Justine A. , Howard Kaitlind C. , Taylor Kirk A. , Khan Sabeeya , Wurl Sienna E. , Szahaj Melanie K. , Sage Tanya , Chandrika Nishad Thamban , Hou Caixia , Tsodikov Oleg V. , Gibbins Jonathan M. , Garneau-Tsodikova Sylvie , Kennedy Daniel R.
Published: February 2025

BACKGROUND:

Thiol isomerases play essential and nonredundant roles in platelet activation, aggregation, and thrombus formation. Thiol isomerase inhibitors have the potential to overcome the 2 major drawbacks of current antithrombotic therapies, as they target both arterial and venous thrombosis without enhancing bleeding risks. Recently, a Food and Drug Administration–approved drug, zafirlukast (ZAF), was shown to be a promising pan-thiol isomerase inhibitor. The objective of this study is to develop analogues of ZAF with optimized thiol isomerase inhibition and antithrombotic activity.

METHODS:

Thirty-five ZAF analogues were tested in an insulin turbidometric assay for thiol isomerase inhibition. Analogues were tested for platelet activation, aggregation, P-selectin expression, and laser-induced thrombosis in mice and compared with the parent compound.

RESULTS:

Of the 35 analogues, 12 retained activity, with 1, compound 21, that demonstrated a greater potency than that of ZAF, 5 had a similar potency to that of ZAF, and 6 had a weaker potency. Analogues demonstrated inhibition of platelet aggregation and P-selectin expression as compared with ZAF, consistent with their potencies. ZAF and compound 21 were shown to be reversible inhibitors of thiol isomerases, and not cytotoxic to cultured, lung, liver, and kidney cells. Finally, in an in vivo assessment of thrombus formation, compound 21 was able to significantly inhibit thrombus formation without affecting bleeding times.

CONCLUSIONS:

A ZAF analogue, compound 21, with properties superior to those of ZAF was synthesized, demonstrating improved inhibition of platelet activation, aggregation, and thrombus formation as compared with the parent ZAF. This approach could yield a promising clinical candidate for treatment and prophylaxis of arterial and venous thrombosis.
Characteristics of Patients With the Arrhythmogenic Mitral Valve Prolapse Syndrome and Sudden Cardiac Arrest and Sustained Ventricular Arrhythmias
Authors: Chakrabarti Apurba , Giudicessi John R. , Ezzeddine Fatima M. , Delling Francesca N. , Dixit Shalini , Lee Yoo Jin , Muser Daniele , Magnani Silvia , Van Wijngaarden Aniek , Ajmone Marsan Nina , Miller Marc A. , Gandhi Jonathan , Trivieri Maria G. , Font Jonaz , Martins Raphael , McCaffrey James A. , Santangeli Pasquale , Marchlinski Francis E. , Chapagain Himal , Mathew Don , Kancharla Krishna , Syed Faisal F. , Abid Ahad , Cerbin Lukasz , Tzou Wendy S. , Garg Lohit , Della Rocca Domenico G. , Natale Andrea , Mohanty Sanghamitra , Sheldon Seth H. , Kuo Ling , Haugaa Kristina H. , Aabel Eivind W. , Enriquez Andres , Maeda Shingo , Deshmukh Amrish , Ghannam Michael , Bogun Frank M. , Ackerman Michael J. , Liang Jackson J.
Published: February 2025

BACKGROUND:

Patients with arrhythmogenic mitral valve prolapse syndrome are at increased risk for life-threatening ventricular arrhythmias, but studies have been limited by small sample sizes. We sought to assemble an international arrhythmogenic mitral valve prolapse syndrome registry to delineate the clinical, imaging, and treatment characteristics of patients with arrhythmogenic mitral valve prolapse syndrome who survived sudden cardiac arrest (SCA) or had sustained ventricular tachycardia (VT) or ventricular fibrillation.

METHODS:

In this descriptive registry, we characterized patients with arrhythmogenic mitral valve prolapse syndrome who survived SCA, sustained VT, or ventricular fibrillation. Deidentified data were abstracted locally and combined centrally.

RESULTS:

We included 148 patients who had SCA or VT/ventricular fibrillation. Patients had a mean age of 43.7±15.4 years; 68% were women, 73% had bileaflet prolapse, 65% had mitral annular disjunction, 67% had nonsustained VT, and 59% had inferolateral T-wave inversions. Syncope (n=54, 48%) and anterolateral T-wave inversion (n=26, 22%) were relatively common. Catheter ablation was performed in 50 (35%) patients for premature ventricular complexes and in 18 (17.7%) patients for VT. Sites of origin for arrhythmias were commonly in the papillary muscles, fascicles, mitral annulus, and inferior/inferolateral left ventricle.

CONCLUSIONS:

In this international descriptive registry of patients with arrhythmogenic mitral valve prolapse syndrome and SCA, patients were young, women, and had bileaflet mitral valve prolapse, mitral annular disjunction, inferolateral T-wave inversions, and nonsustained VT. A history of syncope and anterolateral T-wave inversions was relatively common in patients who survived SCA or sustained VT/ventricular fibrillation.
Situating Religious Beliefs
Authors: Ringmar Erik
Published: February 2025

Recent scholarship in cognitive theory emphasizes the situatedness of cognitive processes, which occur not only in minds but in bodies engaging with their environments. This article relies on these insights to rethink the concept of religious beliefs. It argues that to believe in something is more fundamental than to believe that something is the case. Religious beliefs are primarily expressions of trust rather than propositional statements. To believe in God is to trust in God, reflecting cognitive processes rooted in embodied and enacted experiences.
The European Union’s Influence on the Organisation of National Healthcare Systems. Navigating the Trends after the COVID-19 Pandemic
Authors: Zapotoczna Zuzanna
Published: February 2025

The COVID-19 pandemic has hit national healthcare systems on an unprecedented scale. At the same time, European societies are witnessing an ongoing war, growing migration and climate crisis. In order to respond to the global challenges facing national healthcare systems, the European Union (EU) is stepping up its actions to promote resilience of national healthcare systems. This is to ensure adequate availability of healthcare services in times of health crises through numerous actions. Despite limited powers in health, the EU legal system creates a multidimensional order for protection of various health-related interests which touch upon the organisation of the Member States’ healthcare systems. This paper navigates the ongoing trends with regard to the EU’s health policy and presents the perspective on ‘standardisation’ of the Member States’ healthcare systems.
Re-Appraisal of Legal Systems in Sub-Saharan Africa: Questioning the Legal Pluralism Paradigm
Authors: Macarthy Motese Emmanuel , Uhumuavbi Ikpenmosa
Published: February 2025

The notion that multiple legal systems autonomously coexist in independent states in sub-Saharan Africa due to the interaction of the continent with foreign legal systems is theoretically flawed, misleading and an incorrect application of the concept of legal pluralism. This article examines the nature of legal pluralism in the context of transitioning independent nation-states. It contends that these nation-states, especially in sub-Saharan Africa, do not operate legally pluralistic legal systems, as often presented in scholastic works. Using system and lifecycle theories, this article argues against the prevailing conceptualization of legal pluralism in African legal systems. We argue that the prevailing conceptualization of pluralistic legal systems in sub-Saharan Africa is based on the fallacy of the undistributed middle, leading to flawed conclusions and disastrous governance outcomes. This widespread orthodoxy in legal and sociopolitical scholarship heightens perceived conflicts between imperial universalism and cultural existentialism, which has been the epicenter of legal discussion in Africa’s transitioning nations.
Lo spazio terzo come dimora interiore: l’esperienza dell’esilio e della costruzione identitaria nella poesia di Ġayāṯ al-Madhūn
Authors: Palmegiani Angelika
Published: February 2025

Poetry has occupied a pivotal role within Arab culture since the pre-Islamic era, and its significance has grown exponentially in the wake of the Arab uprisings in 2011. Despite the revolutions not yielding the anticipated socio-political transformations, they have instigated the emergence of novel modes of expression and stylistic approaches that proffer artists a means to navigate social and personal dilemmas. Poets have redirected their focus from the epicentres of the uprisings toward more introspective and secluded domains. This shift in tone and style is inextricably linked to the circumstances of numerous artists who, compelled by necessity, have departed their countries of origin and sought solace in new lands, even before the outbreak of the revolution, due to the oppressive political, economic, and social conditions. Among those resonating with the enduring sense of flux is Ġayāṯ al-Madhūn (1979), a Palestinian-born Syrian poet who moved to Stockholm in 2008 and now lives in Berlin. His verses convey the persistent condition of displacement, the wistful yearning for his homeland, and the solitude borne of migration. Even as his material circumstances have ameliorated, affording him the latitude for creative expression, his newfound residence is tinged with an ineffable discontent, as it remains an imperfect substitute for the home relinquished. This article scrutinises the enigmatic predicament of the poet, who finds within his new milieu a latent but perpetually unfulfilled sense of belonging, while concurrently remaining tethered to the remembrance of the circumstances compelling his refuge-seeking elsewhere.
New Notes on Ǧubrān’s Education in Boston and Its Effect on His Later Career
Authors: Corrao Francesca Maria
Published: February 2025

Ǧubrān’s cultural training in Boston fostered the young Arab immigrant’s rapid success. The poet’s universalist vision enabled a fruitful dialogue between East and West in the nation-forming years of the Arab states. The dissemination of such ideas through literary journals ferried the renewal of modern poetry from New York to Cairo and Tunis.

Numerous studies have delved into the main elements and indications that emerged from his writings (on the contribution of Christianity, Nietzsche, and the cultural milieu of the Arab Nahḍa), while his American education has been investigated less. Here we shall examine some aspects that prove useful in reconstructing the contribution of Transcendentalism and its epigones in the Boston intellectual milieu.
Depressive symptoms delayed but subsequently led to the diagnosis of transthyretin amyloidosis: a case report
Authors: Knezevic Vladimir , Ratkovic Dragana , Zivanovic Zeljko , Comic Masa , Knezevic Jelena , Ivetic Olga , Radosavkic Radosav
Published: February 2025

Transthyretin amyloidosis is a rare disorder caused by the accumulation of misfolded transthyretin amyloid in organs. The symptoms can include neuropathy, cardiomyopathy, nephropathy, depression and cognitive decline. Because of the non-specificity of symptoms, it usually takes considerable time to diagnose, which delays specific therapy and leads to a worse prognosis. Our case highlights the psychological symptoms of this disorder that initially delayed diagnosis, and later helped to reach the correct diagnosis. We report the case of a man who presented with weakness of limbs, dizziness, vomiting, social withdrawal, loss of interest, reduced energy and difficulty concentrating. Different specialist evaluations failed to identify a cause, and the symptoms were attributed to depressive disorder. After psychiatric hospitalization to rule out depression as a possible cause, the patient was transferred to an internal medicine clinic where additional diagnostics led to a transthyretin amyloidosis diagnosis. Early-stage transthyretin amyloidosis is difficult to diagnose owing to its non-specific symptoms, but timely treatment is necessary to improve the disease course and outcome. With reference to this case, we emphasize that psychological symptoms in somatic illnesses can both delay and facilitate diagnosis of underlying disease.
Beyond the Incident: Examining Criminal and Coronial Court Documents to Explore the Impact of Workplace Fatalities on Coworkers
Authors: Rawlings Jeanette , Muir Carlyn , Ayton Darshini
Published: February 2025

When workplace fatalities occur, the coworkers of the victims are exposed to traumatic experiences that can significantly affect them for years. This retrospective document analysis from criminal and coronial court documents, examined the exposure and impact experienced by coworkers when workplace fatalities occur. The findings identify the experiences coworkers encounter when confronted with a workplace fatality, as well as their peritraumatic and posttraumatic responses to the trauma. This study reveals that some coworkers subsequently develop secondary or associated symptoms such as depression, posttraumatic stress disorder, adjustment disorder, anxiety disorder, suicidal ideation and ongoing difficulties in interpersonal relationships, which lead to long-lasting and debilitating impact on them. This study shows that when a workplace fatality occurs, the elements of exposure and the trauma responses in coworkers are significant.