bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear Hall Coefficient in Films of a Three-Dimensional Topological Insulator
Authors: Stepina N. P. , Bazhenov A. O. , Shumilin A. V. , Zhdanov E. Yu. , Ishchenko D. V. , Kirienko V. V. , Aksenov M. S. , Tereshchenko O. E.
Published: September 2024

The magnetoresistance and the Hall effect in transistor structures fabricated on films of the three-dimensional topological insulator (Bi,Sb)2(Te,Se)3 are studied. It is shown that the negative magnetoresistance at low magnetic field is described in terms of quantum corrections to the conductivity. The magnitude of these corrections depends on the gate voltage and increases when approaching the charge neutrality point. The Hall coefficient RH is nonlinear at low magnetic fields for any gate voltage, and the RH nonlinearity is the most pronounced at high negative gate voltages. At high fields, the slope of the magnetic field dependence of the Hall coefficient changes its sign at some gate voltage.
Management dilemma: managing bipolar affective disorder in a patient with hereditary angioedema
Authors: Wimalasiri Isuri Upeksha , Jain Nikhil , Jayaram Mahesh
Published: September 2024

Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by the deficiency or dysfunction of C1 esterase inhibitors. We present a case of a female in her 50s with HAE and bipolar affective disorder (BPAD). She has experienced severe depressive and manic episodes with significant disruption to her life. She has also had potentially life-threatening episodes of recurrent angioedema with severe facial and body swelling and post-pharyngeal symptoms.

She presented to us with a depressive episode with suicidal ideation. Her angioedema was flared by both psychological stressors and psychotropic medications. Choosing the correct mood stabiliser without triggering angioedema was a major challenge in her treatment. Also, psychosocial interventions and frequent liaison with her immunology team were necessary to provide her with optimum care in the community. Here, we discuss the challenges we faced and how we overcame them in managing this rare presentation of coexisting BPAD and HAE.
Coccidiomycosis septic arthritis presenting as ankle monoarthritis in a patient with presumed psoriatic arthritis
Authors: Tancer Stephanie , Ressler Adam , Miceli Marisa H , Wallace Beth I
Published: September 2024

A man in his 50s with a history of psoriasis was evaluated for acute on chronic left ankle pain. His symptoms were attributed to psoriatic arthritis, and he tried several immunosuppressive regimens without improvement. Further diagnostic workup confirmedCoccidioides immitis/posadasiiseptic monarthritis thought secondary to a known remote history of Valley fever while residing in Arizona and subsequent reactivation in the setting of immunosuppression. The patient ultimately required prolonged anti-fungal therapy and multiple surgical debridements.

Although psoriatic arthritis can present as monarthritis, it is uncommon, with more likely differential considerations including crystal arthropathies, trauma and both typical and atypical infections. Acute monarthritis should always prompt concern for a septic joint, even in a patient with autoimmune disease. The specific history elicited from the patient, including residence in an endemic region, and known priorCoccidioidesinfection, increased suspicion forCoccidioidesand led to the correct diagnosis and management.
Exploring heterogeneity in coxarthrosis medication use patterns before total hip replacement: a State Sequence Analysis
Authors: Novelli Anna , Frank-Tewaag Julia , Franke Sebastian , Weigl Martin , Sundmacher Leonie
Published: September 2024

Objective

Evidence of geographical variation in total hip replacement (THR) and deviations from treatment guidelines persists. In this exploratory study, we aim to gain an in-depth understanding of patients’ healthcare trajectories by identifying and visualising medication use patterns in coxarthrosis patients before surgery. We examine their association with patient characteristics and THR, and compare them with recommendations on mild analgesics, opioid prescription and exhaustion of conservative therapy.

Methods

In this exploratory study, we apply State Sequence Analysis (SSA) on German health insurance data (2012–2015). We analyse a cohort of coxarthrosis patients, half of whom underwent THR after a 1 year observation period and half of whom did not undergo surgery until at least 1 year after the observation period. Hierarchical states are defined based on prescriptions. We construct sequences, calculate sequence similarity using optimal matching and identify medication use patterns via clustering. Patterns are visualised, descriptive statistics are presented and logistic regression is employed to investigate the association of medication patterns with subsequent THR.

Results

Seven distinct medication use patterns are identified, correlating strongly with patient characteristics and subsequent THR. Two patterns leading to THR demonstrate exhaustion of pharmacological therapy. Opioid use is concentrated in two small patterns with low odds for THR. The most frequent pattern lacks significant pharmacological therapy.

Conclusions

This SSA uncovers heterogeneity in medication use patterns before surgery in coxarthrosis patients. Cautious opioid handling and adherence to a stepped prescription approach are observed, but many patients display low medication therapy usage and lack evidence of exhausting conservative options before surgery.
Qualitative interview study of patient-reported symptoms, impacts and treatment goals of patients with obstructive hypertrophic cardiomyopathy
Authors: Shore Supriya , Ervin Claire , Kosa Katherine , Fehnel Sheri , Salberg Lisa , Butzner Michael , Heitner Stephen B , Jacoby Daniel , Saberi Sara
Published: September 2024

Objective

Hypertrophic cardiomyopathy (HCM), including obstructive HCM (oHCM), is the most common inherited cardiomyopathy causing lifestyle-limiting symptoms. Data are lacking about patients’ perspectives on the daily impact of their symptoms. This qualitative interview study was conducted to better understand patients’ experiences with oHCM.

Methods

In October 2019, telephone interviews were conducted with 20 US adults with oHCM identified by the Hypertrophic Cardiomyopathy Association. Using a semi-structured interview guide, key symptoms, impacts of oHCM and oHCM treatment goals were discussed.

Results

Median age was 54 years (range 29–78), 55% were women, 85% were white and 15% were Hispanic or Latino. Median time since diagnosis was 3 years. Symptoms included shortness of breath, dizziness/light-headedness, heart palpitations/fluttering (all 95%), fatigue (90%) and chest pain/pressure (80%). All participants reported limitations in physical functioning/activities; most reported additional impacts (emotional stress (80%), fear of dying (55%)). Shortness of breath and fatigue were among their most bothersome symptoms; an effective oHCM treatment would need to improve ≥1 of these symptoms (allowing increased physical/social activity).

Conclusions

Patients with oHCM experience a high symptom burden and psychosocial impacts, affecting health status. Improved shortness of breath, fatigue and physical functioning are highly valued by patients and represent important treatment goals.
Risky sexual behaviour and its determinants among undergraduate students residing in hostels of Kathmandu Metropolitan City, Nepal: a cross-sectional study
Authors: Chaudhary Ram Kumar , Chalise Anisha , Pandey Saloni , Paudel Shishir
Published: September 2024

Objectives

To assess the prevalence of risky sexual behaviour (RSB) and its associated factors among Nepalese undergraduates residing in hostels of Kathmandu Metropolitan City, Nepal.

Design

Cross-sectional study

Setting

Hostels operating inside Kathmandu Metropolitan City were taken as the study setting.

Participant

A total of 361 undergraduate students residing in hostels in the Metropolitan City

Outcome measures

RSB was the outcome measure assessed using nine questions able to trace any risky sexual practice practiced by the participants within the past year prior to data collection. The question included participants’ engagement in sexual activity before the age of consent, having unprotected vaginal sex even when pregnancy is not intended, engaging in vaginal sex with strangers without a condom, risky oral sex with a stranger and/or intimate partner, risky condom use, having multiple sex partners, having sex under the influence of alcohol and having sex with commercial sex workers. A positive response to any of these nine questions was considered indicative of RSB. Pearson’s χ2test and multivariable logistic regression analysis were performed to determine factors associated with RSB at the 5% level of significance.

Results

The prevalence of RSB was found to be 35.7% (95% CI: 30.2 to 40.2). RSB was found to be associated with higher age (≥25 years) (aOR: 3.938; 95% CI: 1.707 to 8.673), male gender (aOR: 3.233; 95% CI: 1.623 to 6.439), being in relationships in the past/current (aOR: 3.914, 95% CI: 2.099 to 7.012), lower education of mother (aOR: 3.655; 95% CI: 1.189 to 9.237) and peer pressure to have a sexual relationship (aOR: 2.356; 95% CI: 1.260 to 4.349). Notably, bivariate analysis illustrated problematic pornographic consumption to have a statistical relation with RSB, which was weakened and became non-significant after accounting for other factors in the adjusted model (aOR:1.213, 95% CI: 0.331 to 4.442).

Conclusion

RSB is a concerning behaviour among undergraduate students and is linked with age, gender, relationship status, parental education and peer pressure. There is a need for comprehensive sex education programmes that equip students with the knowledge and skills needed to navigate healthy relationships, make safe choices and embrace responsible sexual practices.
Exoskeletal-assisted walking combined with transcutaneous spinal cord stimulation to improve bone health in persons with spinal cord injury: study protocol for a prospective randomised controlled trial
Authors: Cirnigliaro Christopher M , Kuo William , Forrest Gail F , Spungen Ann M , Parrott J Scott , Cardozo Christopher P , Pal Saikat , Bauman William A
Published: September 2024

Introduction

Persons with non-ambulatory spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have marked loss of bone mineral density below the level of lesion that is directly associated with increased risk of long-bone fractures. There is a paucity of research that has successfully implemented rehabilitation and/or exercise training interventions to mitigate bone loss after acute SCI or reverse bone loss that has already occurred in chronic SCI. This paper describes a research protocol to compare the effect of exoskeletal-assisted walking (EAW) alone versus EAW plus transcutaneous spinal cord stimulation (EAW+tSCS) on bone density, geometry and strength in a cohort of chronic SCI participants.

Methods and analysis

After meeting eligibility criteria and completing baseline testing, sixteen participants will be block randomised into the EAW alone group or the EAW+tSCS combined group (n=8 each group). Each group will receive a total of 108 overground training sessions (60 min sessions, 3 times a week, for 36 weeks) for the 9-month training period. Imaging for bone density and geometry by dual-energy X-ray absorptiometry and peripheral quantitative CT will be performed prior to starting the intervention (baseline), after 72 training sessions, and again after 108 sessions in each of the intervention arms. CT imaging of both lower extremities will be performed at baseline and at the 9-month time point in each of the intervention arms. Finite element models of bone loading will be generated based on three-dimensional (3D) reconstruction of bone architecture from CT imaging prior to and 9 months after the intervention.

Ethics and dissemination

This study is currently approved by the Kessler Foundation and James J. Peters VA Medical Center Institutional Review Board. A member of the research team will review and explain the study consent form and will have all eligible participants sign prior to participation in the study. Results from this study will be disseminated to clinicians and researchers in the SCI community at national and international conferences.

Trial registration number

NCT03096197.
Systematic scoping review of cluster randomised trials conducted exclusively in low-income and middle-income countries between 2017 and 2022
Authors: Goldstein Cory E , Marouf Yacine , Johri Mira , Shaw Julia F , Sergeant Anand , Nicholls Stuart G , Althabe Fernando , Ferrand Rashida A , van der Graaf Rieke , Hemming Karla , Mbuagbaw Lawrence , Treweek Shaun , Welch Vivian A , Weijer Charles , Taljaard Monica
Published: September 2024

Objective

Cluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time.

Design

A systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews.

Data sources

We searched MEDLINE between 1 January 2017 and 17 August 2022.

Eligibility criteria for selecting studies

We included primary reports of CRTs evaluating health-related interventions, conducted exclusively in LMICs and published in English between 2017 and 2022.

Data extraction and synthesis

Data were extracted by one reviewer; a second reviewer verified accuracy by extracting data from 10% of the reports. Results were summarised overall and categorised by country’s economic level or publication year.

Results

Among 800 identified CRTs, 400 (50.0%) randomised geographical areas and 373 (46.6%) were conducted in Africa. 30 (3.7%) had no authors with an LMIC affiliation, and 246 (30.8%) had neither first nor last author with an LMIC affiliation. The relative frequency of first or last authors holding an LMIC affiliation increases as a country’s economic level increases. Most CRTs focused on reducing maternal and neonatal disorders (106, 13.3%). 670 (83.8%) CRTs reported trial registration, 786 (98.2%) reported research ethics committee review and 757 (94.6%) reported consent statements. Among the 757 CRTs, 46 (6.1%) reported a waiver or no consent and, among these, 10 (21.7%) did not provide a rationale. Gatekeepers were identified in 403 (50.4%) CRTs. No meaningful trends were observed in adherence to trial registration or ethics reporting requirements over time.

Conclusion

Our findings suggest existing inequity in authorship practices. There is high adherence to trial registration and ethics reporting requirements, although greater attention to reporting a justification for using a waiver of consent is needed.
Safety, pharmacokinetics, biomarker response and efficacy of E6742: a dual antagonist of Toll-like receptors 7 and 8, in a first in patient, randomised, double-blind, phase I/II study in systemic lupus erythematosus
Authors: Tanaka Yoshiya , Kumanogoh Atsushi , Atsumi Tatsuya , Ishii Tomonori , Tago Fumitoshi , Aoki Mari , Yamamuro Shintaro , Akira Shizuo
Published: September 2024

Objectives

To evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response and efficacy of E6742 in a phase I/II study in patients with systemic lupus erythematosus (SLE).

Methods

Two sequential cohorts of patients with SLE were enrolled and randomised to 12 weeks of two times per day treatment with E6742 (100 or 200 mg; n=8 or 9) or placebo (n=9). The primary endpoint was safety, the secondary endpoints were PK and interferon gene signature (IGS), and the exploratory endpoints were efficacy and biomarker.

Results

The proportion of patients with any treatment-emergent adverse events (TEAEs) was 58.8% in the E6742 group (37.5% (3/8 patients) for 100 mg; 77.8% (7/9 patients) for 200 mg) and 66.7% (6/9 patients) in the placebo group. No Common Terminology Criteria for Adverse Events≥Grade 3 TEAEs occurred. PK parameters were similar to these in previous phase I studies in healthy adults. The IGS and levels of proinflammatory cytokines after ex-vivo challenge with a Toll-like receptor 7/8 agonist were immediately decreased by E6742 treatment. The response rate of the British Isles Lupus Assessment Group-based Composite Lupus Assessment at week 12 was 37.5% (3/8 patients) for E6742 100 mg, 57.1% (4/7 patients) for E6742 200 mg and 33.3% (3/9 patients) for placebo group.

Conclusions

E6742 had a favourable safety profile and was well tolerated, with suppression of IGS responses and preliminary efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials.

Trial registration number

NCT05278663.
Stimulus-dependent spiking and bursting behavior in memsensor circuits: experiment and wave digital modeling
Authors: Jenderny Sebastian , Gupta Rohit , Madurawala Roshani , Strunskus Thomas , Faupel Franz , Kaps Sören , Adelung Rainer , Ochs Karlheinz , Vahl Alexander
Published: September 2024

Biological information processing pathways in neuron assemblies rely on spike activity, encoding information in the time domain, and operating the highly parallel network at an outstanding robustness and efficiency. One particularly important aspect is the distributed, local pre-processing effectively converting stimulus-induced signals to action potentials, temporally encoding analog information. The field of brain-inspired electronics strives to adapt concepts of information processing in neural networks, e.g., stimulus detection and processing being intertwined. As such, stimulus-modulated resistive switching in memristive devices attracts an increasing attention. This work reports on a three-component memsensor circuit, featuring a UV-sensor, a memristive device with diffusive switching characteristics and a capacitor. Upon application of a DC bias, complex, stimulus-dependent spiking and brain-inspired bursting can be observed, as experimentally showcased using combination of a microstructured, tetrapodal ZnO sensor and a Au/SiOxNy/Ag cross-point memristive device. The experimental findings are corroborated by a wave digital model, which successfully replicates both types of behavior and outlines the relation of temporal variation of switching thresholds to the occurrence of bursting activity.

Graphical abstract
AI Should Challenge, Not Obey
Authors: Sarkar Advait
Published: September 2024

Let’s transform our robot secretaries into Socratic gadflies.
Canalis: A Throughput-Optimized Framework for Real-Time Stream Processing of Wireless Communication
Authors: Chen Kuan-Yu , Mason Nelson Thomas , Khadem Alireza , Fayazi Morteza , Singapuram Sanjay Sri Vallabh , Dreslinski Ronald , Talati Nishil , Kim Hun-Seok , Blaauw David
Published: September 2024

Stream processing, which involves real-time computation of data as it is created or received, is vital for various applications, specifically wireless communication. The evolving protocols, the requirement for high-throughput, and the challenges of handling diverse processing patterns make it demanding. Traditional platforms grapple with meeting real-time throughput and latency requirements due to large data volume, sequential and indeterministic data arrival, and variable data rates, leading to inefficiencies in memory access and parallel processing. We present Canalis, a throughput-optimized framework designed to address these challenges, ensuring high-performance while achieving low energy consumption. Canalis is a hardware-software co-designed system. It includes a programmable spatial architecture, Flux Stream Processing Unit (FluxSPU), proposed by this work to enhance data throughput and energy efficiency. FluxSPU is accompanied by a software stack that eases the programming process. We evaluated Canalis with eight distinct benchmarks. When compared to CPU and GPU in mobile SoC to demonstrate the effectiveness of domain specialization, Canalis achieves an average speedup of 13.4

\(\times\)

and 6.6

\(\times\)

, and energy savings of 189.8

\(\times\)

and 283.9

\(\times\)

, respectively. In contrast to equivalent ASICs of the benchmarks, the average energy overhead of Canalis is within 2.4

\(\times\)

, successfully maintaining generalizations without incurring significant overhead.
Political Polarization and Finance
Authors: Kempf Elisabeth , Tsoutsoura Margarita
Published: September 2024

We review an empirical literature that studies how political polarization affects financial decisions. We first discuss the degree of partisan segregation in finance and corporate America, the mechanisms through which partisanship may influence financial decisions, and the available data sources used to infer individuals’ partisan leanings. We then describe and discuss the empirical evidence. Our review suggests an economically large and often growing partisan gap in the financial decisions of households, corporate executives, and financial intermediaries. Partisan alignment between individuals explains team and financial relationship formation, with initial evidence suggesting that high levels of partisan homogeneity may be associated with economic costs. We conclude by proposing several promising directions for future research.
High Throughput Electrochemical Screening of Phosphate-Rich Nonflammable Electrolytes in Lithium-Ion Batteries
Authors: Martin Witness , Job Heather M. , Liang Yangang , Feng Ruozhu , Gao Peiyuan , Liu Dianying , Zhong Lirong , Xiao Jie , Wang Wei , Wu Bingbin
Published: September 2024

Frequent fires and explosions in lithium-ion batteries (LIBs) used in grid energy storage systems (ESS) highlight the necessity of revisiting nonflammable phosphate electrolytes as alternatives to the currently used flammable carbonates. However, previous studies have shown the difficulty of integrating phosphate solvents into LIB electrolytes due to compatibility issues with graphite. In this work, we developed a high-throughput (HTP) electrochemical characterization method, akin to pH test paper, to rapidly screen potential phosphate electrolytes and graphite materials. Through HTP screening, we identified 101 promising combinations out of 1,740. This number was reduced to 26 after testing in Li/Graphite half cells. The optimized phosphate-rich electrolyte (60 v% phosphate) with cosolvents demonstrated 300 stable cycles at 0.1 C in Graphite/LiFePO4 (LFP) full cells with thick electrodes (∼3.0 mAh cm−2), surpassing prior research findings. This unique HTP method provides a powerful tool to expedite the development of safe LIBs for ESS applications.
The effect of exam retakes on future exam performance in a large classroom setting
Authors: Davis James T. , Adams Kristina , Morgan Ashley
Published: September 2024

Exam retakes provide students with an additional opportunity to demonstrate mastery of learning objectives. However, this preparation might adversely affect performance on subsequent exams. This study suggests that students who choose to prepare for and take an exam retake not only improve their original exam score but show a larger improvement on subsequent exam performance than those students who did not take an exam retake.
Teaching the distribution of pulmonary blood flow using a Starling resistor model and turbine flowmeters
Authors: de Melo Felipe Xavier , Melo-Silva César Augusto , Amado Veronica Moreira
Published: September 2024

The understanding of respiratory physiology is a challenge to medical students. To improve the learning of pulmonary blood flow distribution through lung vessels in our physiology course, we modeled a Starling resistor model combined with visible turbine flowmeters. Our model can significantly improve the core concept of flow down gradients teaching and its application to West zones.
Contrast gain control is a reparameterization of a population response curve
Authors: Tring Elaine , Moosavi S. Amin , Dipoppa Mario , Ringach Dario L.
Published: September 2024

The authors study the responses of neural populations in mouse primary visual cortex as a function of stimulus contrast. Measurements are performed in different “environments,” each characterized by a different distribution of contrast values. They find that responses across environments can be viewed as a reparameterization of a single contrast-response curve, offering a simple, geometric account of contrast gain control in neural populations.
Enhanced phasic calf muscle activation with swing resistance enhances propulsion of the paretic leg in people poststroke
Authors: Park Seoung Hoon , Yan Shijun , Dee Weena , Keefer Renee , Roth Elliot J. , Rymer William Z. , Wu Ming
Published: September 2024

Applying targeted motor stimulation to the paretic calf muscle and swing resistance to the nonparetic leg during walking induced significant enhancement in muscle activation of the paretic gastrocnemius and anterior-posterior ground reaction force of the paretic leg, whereas no enhancements were observed after walking with swing resistance only. Furthermore, the enhanced gastrocnemius muscle activation and ground reaction force of the paretic leg were partially retained at the late postadaptation period and 10 min after treadmill walking.
Analysis of Random Difference Equations Using the Differential Transformation Method
Authors: Şişman Şeyma , Merdan Mehmet
Published: September 2024

The differential transformation method (DTM) is one of the best methods easily applied to linear and nonlinear difference equations with random coefficients. In this study, we apply the theorems related to the DTM to the given examples and investigate the behaviour of the approximate analytical solutions. The expected value, variance, coefficient of variation, and confidence intervals of the solutions of random difference equations obtained from discrete probability distributions such as uniform, geometric, Poisson, and binomial distributions will be calculated. Maple and MATLAB software packages are used to plot the solution graphs and also to interpret the solution behaviour.
Data‐Driven Structural Health Monitoring on Shaking Table Tests of a 3‐Story Steel Building with Sliding Slabs
Authors: Huang Yu-Tzu , Chou Daniel Yen-Hsun , Chou Chung-Che , Loh Chin-Hsiung
Published: September 2024

Data‐driven structural health monitoring (SHM) is an approach which relies on the information contained in the data and through signal analysis techniques captures the features, variations, and uncertainties that data contain. This paper presents the response of shaking table tests of a full‐scale, 3‐story building with sliding slabs connected by horizontal buckling‐restrained braces for energy dissipation. First, the global dynamic characteristics of the structure were identified from a series of the building response data under different intensity level of base excitations. The variation of the identified modal parameters, such as the mode frequencies and modal shapes, was discovered. The influence of sliding slabs on the dynamic characteristics of the frame was also investigated through the measured response and the equation of motion with six degree of freedom systems. Comparison on the achieved interstory stiffness due to the implementation of sliding slabs and the fixed (locked up) slab was examined. The mechanism and dynamic characteristics of sliding slabs, including energy dissipation of the friction force, BRB hysteresis behavior, and unintended damping force during strong base excitation were analyzed directly using the ARX/recursive model. The extracted unintended damping force performed like a friction hysteretic response, which needs to be considered for frame modeling in shaking table tests. The findings through the data analysis have clarified the important aspects of sliding slabs and demonstrated the benefits and applicability of sliding slabs on reducing the frame response.
Capnocytophaga canimorsus Septicemia With Sepsis‐Induced Coagulopathy and Endocarditis
Authors: Kühnle Jeannine L. , Leitner Maximilian , Mazuru Vitalie , Borchardt Kai , Becker Sören L. , Roth Franziska , Bals Robert , Lepper Philipp M. , Schäfers Hans-Joachim , Jaumann Isabella T.
Published: September 2024

Capnocytophaga canimorsus is a rare cause of serious infections with a high mortality of 10% to 30%. It is usually found in the oral cavity of cats and dogs and can cause severe sepsis in immunocompromised patients. An 81‐year‐old female Caucasian patient presented with C. canimorsus sepsis after a dog bite in her finger three days before presentation to our emergency department. She initially was presented to us with sepsis, thrombopenia, and schistocytes in her laboratory findings, suggesting the differential diagnoses of the multiple subtypes of thrombotic microangiopathy. She was admitted to the medical intensive care unit of the University Hospital of Saarland because of septic shock with circulatory insufficiency. The patient received plasmapheresis, antibiotics, and dialysis, under which she improved significantly. The fingertip of the affected finger developed necrosis and had to be amputated. Furthermore, the patient was diagnosed with a mitral valve endocarditis, a very rare complication of C. canimorsus infection. It was treated conservatively with antibiotics and was no longer detectable 8 weeks after the diagnosis. Surgical intervention was not needed. The case describes well that it is still difficult to distinguish between thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), and sepsis‐induced coagulopathy (SIC), especially in the early phases of acute disease, especially in C. canimorsus-induced sepsis.
Effects of Various Decellularization Methods for the Development of Decellularized Extracellular Matrix from Tilapia (Oreochromis niloticus) Viscera
Authors: Aron Jemwel , Bual Ronald , Alimasag Johnel , Arellano Fernan , Baclayon Lean , Bantilan Zesreal Cain , Lumancas Gladine , Nisperos Michael John , Labares Marionilo , Valle Kit Dominick Don , Bacosa Hernando
Published: September 2024

Tilapia, a widely farmed aquaculture fish, produces substantial waste, including viscera that contain extracellular matrix (ECM) utilized as a biomaterial for tissue regeneration applications. Extracting ECM from viscera requires a specific decellularization method, as no standardized protocol exists. This study performed three decellularization methods: sonication, orbital shaking at room temperature, and agitation at 4°C, using SDS and TX100 at concentrations of 0.1% and 0.3%. The effectiveness of each method was assessed through H&E staining, dsDNA quantification, and SEM imaging to verify cellular content removal and ECM structure preservation. Additional analyses, including ATR‐FTIR, SDS‐PAGE, protein quantification, HPLC, and detergent residue tests, were performed to examine functional groups, collagen composition, protein content, amino acid profiles, and detergent residues in the decellularized samples. The results of H&E staining showed a significant reduction in cellular components in all samples, which was confirmed through DNA quantification. Sonication with 0.3% SDS achieved the highest DNA removal rate (96.5 ± 1.1%), while SEM images revealed that agitation at 4°C with 0.3% TX100 better preserved ECM structure. Collagen was present in all samples, as confirmed by ATR‐FTIR analysis, which revealed pronounced spectral peaks in the amide I, II, III, A, and B regions. Samples treated with agitation at 4°C using 0.1% SDS exhibited the highest protein content (875 ± 15 µg/mg), whereas those treated with TX100 had lower detergent residue. Overall, the decellularization methods effectively reduced DNA content while preserving ECM structure and components, highlighting the potential of tilapia viscera as bioscaffolds and offering insights into utilizing fish waste for high‐value products.
Solutions of Inhomogeneous Multiplicatively Advanced ODEs and PDEs with a q‐Fredholm Theory and Applications to a q‐Advanced Schrödinger Equation
Authors: Pravica David W. , Randriampiry Njinasoa , Spurr Michael J.
Published: September 2024

For q > 1, a new Green’s function provides solutions of inhomogeneous multiplicatively advanced ordinary differential equations (iMADEs) of form y(N)(t) − Ay(qt) = f(t) for t ∈ [0, ∞). Such solutions are extended to global solutions on ℝ. Applications to inhomogeneous separable multiplicatively advanced partial differential equations are presented. Solutions to a linear free forced q‐advanced Schrödinger equation are obtained, opening an avenue to applications in quantum mechanics. New q‐Mittag‐Leffler functions  qEα,β and ΥN,p govern the allowable decay rate of the inhomogeneities f(t) in the above iMADE. This provides a refinement to standard distribution theory, as we show is necessary for this study of iMADEs. A q‐Fredholm theory is developed and related to the above approach. For f(t) whose antiderivatives provide eigenfuntions of the noncompact integral operator K below, we exhibit solutions of the iMADE. Examples are provided, including a certain class of Dirichlet series.
Design, Manufacturing, and Testing of a Non‐Preload Variable Friction Damper for Seismic Application of Buildings
Authors: Liu Wei , Kong Sihua , Zhao Guifeng , Ma Yuhong , Yang Zhenyu , Guan Qingsong , Chen Jiachuan
Published: September 2024

Friction dampers are widely used due to their simple structure, remarkable energy dissipation capacity, and frequency independence. However, existing friction dampers are prone to relaxing the preload force during long‐term service, which can lead to cold bonding or cold solidification. To overcome this critical shortcoming, a novel non‐preload variable friction damper (NVFD) was firstly proposed. The construction of the proposed NVFD is provided in detail. Furthermore, restoring the force model through the amplification factors of friction force and inertial mass was derived based on the principle of the proposed NVFD. Then, pseudo‐static tests with various parameters were conducted. Finally, a single‐degree‐of‐freedom (SDOF) structure was employed to compare the effectiveness of this paper’s new NVFD with a conventional friction damper (FD) under various earthquake levels. The results show that non‐preload characteristics avoided the problems of large preloads by traditional friction dampers; thus, the NVFD had stable and reliable variable friction performance, which can effectively adapt to different hazard levels.
Inhibition of JNK Signaling Overcomes Cancer-Associated Fibroblast-Mediated Immunosuppression and Enhances the Efficacy of Immunotherapy in Bladder Cancer
Authors: Cui Chengying , Zhang Haojie , Yang Congcong , Yin Mingwei , Teng Xinkun , Yang Miaomiao , Kong Dejie , Zhang Jinzhi , Peng Weidong , Chu Zhimin , Wang Jingjing , Sun Yating , Kang Liping , Lyu Bin , Gao Qian , Wu Mingqing , Wang Yongqiang , Li Yang
Published: September 2024

Currently, only 20% to 40% of patients with cancer benefit from immune checkpoint inhibitors. Understanding the mechanisms underlying the immunosuppressive tumor microenvironment (TME) and characterizing dynamic changes in the immunologic landscape during treatment are critical for improving responsiveness to immunotherapy. In this study, we identified JNK signaling in cancer-associated fibroblasts (CAF) as a regulator of the immunosuppressive TME. Single-cell RNA sequencing of bladder cancer samples treated with a JNK inhibitor revealed enhanced cytotoxicity and effector functions of CD8+ T cells. In untreated tumors, CAFs interacted frequently with CD8+ T cells and mediated their exhaustion. JNK inhibition abrogated the immunosuppression function of CAFs by downregulating the expression of thymic stromal lymphopoietin (TSLP), thereby restoring CD8+ T-cell cytotoxicity. In addition, blockade of CAF-derived TSLP in combination with anti–PD-1 treatment promoted tumor elimination by CD8+ T cells in vivo. Collectively, these results indicate that JNK signaling plays an important immunosuppressive role in the TME by promoting expression of TSLP in CAFs and suggest that inhibiting JNK signaling could be a promising immunotherapeutic strategy for cancer treatment.

Significance: JNK signaling promotes the secretion of TSLP by bladder cancer–associated fibroblasts to impede CD8+ T-cell activity, which can be circumvented by combination treatment targeting JNK signaling and PD-1.
The Role of Residential Segregation in Treatment and Outcomes of Ductal Carcinoma In Situ of the Breast
Authors: Nabi Oumarou , Liu Ying , Struthers James , Lian Min
Published: September 2024

Background:

It remains unclear whether residential segregation impacts on clinical treatment and outcomes for ductal carcinoma in situ (DCIS), a nonobligate precursor to invasive breast cancer (IBC).

Methods:

This population-based retrospective cohort study included adult non-Hispanic White and Black women diagnosed with unilateral DCIS between January 1990 and December 2015, followed through December 2016, and identified from the Surveillance, Epidemiology, and End Results dataset. County-level racialized economic segregation was measured using the Index of Concentration at the Extremes. Multilevel logistic regression and Cox proportional hazards regression accounting for county-level clustering were used to estimate the ORs of local treatment and HRs of subsequent IBC and mortality.

Results:

Of 103,898 cases, mean age was 59.5 years, 12.5% were non-Hispanic Black, 87.5% were non-Hispanic White, 97.5% underwent surgery, 64.5% received radiotherapy following breast-conserving surgery (BCS), 7.1% developed IBC, and 18.6% died from all causes. Among women living in the least versus most privileged counties, we observed higher odds of receiving mastectomy [vs. BCS; OR = 1.51; 95% confidence interval (CI), 1.35–1.69; Ptrend < 0.001] and radiotherapy following BCS(OR = 1.27; 95% CI, 1.07–1.51; Ptrend < 0.01); the risk was higher in subsequent ipsilateral IBC (HR = 1.16; 95% CI, 1.02–1.32; Ptrend = 0.04), not in breast cancer–specific mortality (HR = 1.04; 95% CI, 0.88–1.23; Ptrend = 0.56).

Conclusions:

The results provide evidence for disparities in clinical treatment for DCIS and prognostic outcomes among women in racially and economically segregated counties.

Impact:

Our findings may inform geographically targeted multilevel interventions to reduce breast cancer burden and improve breast cancer care and equity.
Coexistence of Rare Genetic Disorders in a Consanguineous Family: Case Study of KLHL24-Related Hypertrophic Cardiomyopathy and Char Syndrome
Authors: Linnenkamp Bianca Domit Werner , Pires Lucas Vieira Lacerda , Stephan Bruno de Oliveira , Vilalva Kelvin Henrique , Lombardi Peres de Carvalho Mariana , Vicente Pereira Lipari Layara Fernanda , Fernandes Fabio , Krieger Jose Eduardo
Published: September 2024

Introduction: Physicians often search for a single underlying cause that explains all of a patient’s signs and symptoms. However, evidence from the literature suggests that the concurrent presence of two rare diseases, although uncommon, poses significant diagnostic challenges. Precision medicine is increasingly important in these scenarios, enabling more rapid diagnosis and tailored treatments. Case Presentation: This report discusses a patient involving a consanguineous Brazilian family, where two sisters are diagnosed with autosomal recessive KLHL24-related hypertrophic cardiomyopathy. Additionally, one sister is diagnosed with Char syndrome due to a TFAP2B deletion. Conclusion: This case underscores the possibility that multiple rare genetic disorders can coexist, contributing to complex clinical phenotypes. Whole-exome sequencing proves to be a critical tool in identifying the genetic underpinnings of such complex cases, facilitating precise diagnosis and genetic counseling. The discovery of a homozygous KLHL24 variant further broadens the known mutation spectrum and underscores its significance in autosomal recessive hypertrophic cardiomyopathy.
Evaluating Oxidative Stress Markers in At-Risk Individuals for Bipolar Disorder: A Systematic Review and Meta-Analysis
Authors: Arat-Çelik Hidayet Ece , Eslami Abriz Aysan , Coello Klara , Vinberg Maj , Ceylan Deniz
Published: September 2024

Introduction: Bipolar disorder (BD), a mood disorder with recurrent affective episodes and a strong genetic basis is frequently associated with significant comorbidities, both physical and psychiatric, yet its neurobiology remains unclear. Recent evidence underscores oxidative stress as a pivotal factor linking BD to its comorbidities, prompting an investigation into whether this is a sign of a genetic vulnerability or a consequence of the disease. In this study, we systematically reviewed oxidative stress studies conducted on individuals at risk for BD. We performed a meta-analysis on studies examining oxidative DNA damage in these individuals. Methods: The literature was searched across the databases PubMed, Web of Science, Scopus, Ovid MEDLINE, and Cochrane to locate studies of oxidative stress markers in relatives of patients with BD compared with healthy controls (from 1946 to March 2024). Studies were considered for inclusion based on the following criteria: (i) involvement of first- or second-degree relatives of individuals diagnosed with BD, (ii) presence of a healthy control group, (iii) reporting of oxidative stress parameters for relatives, including mean and standard deviation or median and interquartile range (25–75%) values, and (iv) publication in the English language. Studies comparing the levels of 8-hydroxy-2′-deoxyguanosine (8-OH-dG) or its tautomer 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in individuals at risk for BD with healthy controls were evaluated using a meta-analysis with the random-effects method. The risk of bias was evaluated using the Risk of Bias in Non-Randomized Studies of Exposure (ROBINS-E) tool. Results: Eleven studies were included in the systematic review and four studies for the meta-analysis. The meta-analysis included 543 individuals (first-degree relatives of individuals with BD = 238, control = 305). 8-OH-dG levels were found to be increased in first-degree relatives of individuals with BD compared to healthy controls (random effects: Hedges’s g = 0.53, 95% CI = 0.36–0.71, p < 0.001). Findings of oxidative stress markers other than oxidative DNA damage in relatives of individuals with BD are limited and scarce. Conclusion: In this meta-analysis, which consists of a limited number of studies, oxidative DNA damage seems to be a trait marker for BD. This finding could be associated with increased comorbidity and a higher risk of premature aging in individuals at risk for BD. However, further studies with larger sample sizes and longitudinal designs are warranted to confirm findings. Clarifying the changes in these markers from individuals at risk for the disorder throughout the course of the illness would help bridge the gap in understanding the role of oxidative pathways in the risk of BD.
Decreased Phagocytosis and Intracellular Killing of Bacteria in Leukocytes of Geriatric Patients with Clostridioides difficile Infections
Authors: Seele Jana , Heinen Kaya S. , Meier Volker , Ballüer Melissa , Liedtke Ellea , Djukic Marija , Eiffert Helmut , Nau Roland
Published: September 2024

Introduction: Patients suffering from a Clostridioides difficile infection have a higher overall mortality than patients with similar comorbidities. Methods: Whole blood samples of 15 patients with C. difficile enteritis and 15 control patients matched for age and sex were used to analyze the capacity of blood phagocytes to internalize and kill encapsulated Escherichia (E.) coli. The median age of C. difficile patients and control patients was 81 and 82 years, respectively. Blood samples were co-incubated with E. coli for 15 or 30 min. After 15 min of co-incubation, extracellular bacteria were killed by gentamicin for 15–45 min. Then eukaryotic cells were lysed with distilled water, and the number of intracellular bacteria per ml whole blood was determined by quantitative plating on agar plates. Both groups were compared by Mann-Whitney U test. Results: After 15 or 30 min of co-incubation, blood phagocytes from patients with C. difficile enteritis showed a reduced density of phagocytosed or adherent bacteria in comparison to blood phagocytes from control patients (15 min: p = 0.046, 30 min: p = 0.005). The density of intracellular bacteria decreased less rapidly over time in the blood from C. difficile patients (median Δlog CFU/mL × h [25th/75th percentile] −0.893 [−1.893/−0.554] vs. −1.483 [−2.509/−1.028]; p = 0.02). In line with these results, the percentage of intracellularly killed bacteria was decreased in phagocytes from C. difficile-infected patients compared to controls (median intracellular killing rate 64.3% for blood phagocytes from C. difficile patients vs. 81.9% for blood phagocytes from control patients within 30 min of co-incubation, p = 0.048). Conclusion: Blood phagocytes from patients with C. difficile enteritis exhibited a reduced capacity to phagocytose and kill bacteria in comparison to blood phagocytes from age- and sex-matched control patients. Patients with C. difficile infection may have a higher disposition to develop infectious diseases than age- and sex-matched control patients.
EGFR-Tyrosine Kinase Inhibitor Combined with Radiotherapy in 105 Patients of Lung Adenocarcinoma with Brain Metastasis: A Retrospective Study of Prognostic Factor Analysis
Authors: Yu Wenjuan , Xing Yuan , Song Xiao , Li Tian , Zhang Mi
Published: September 2024

Introduction: This study aimed to retrospectively analyse the response and prognosis factors for patients with lung adenocarcinoma exhibiting brain metastasis and epidermal growth factor receptor (EGFR) mutations, who were treated with a combination of EGFR-tyrosine kinase inhibitor (TKI) and brain radiotherapy (RT). Methods: Clinicopathological data of patients with lung adenocarcinoma were collected from January 2021 to January 2024 at the First Affiliated Hospital of Hebei North University. Statistical analysis was performed using SPSS version 26.0, with significance set at p < 0.05. Results: A total of 105 patients were included. The overall survival (OS) rates at 1, 2, and 3 years were 82.9%, 61.2%, and 33.7%, respectively. The progression-free survival 1 (PFS1) rates at 1, 2, and 3 years were 62.7%, 36.6%, and 22.1%, respectively. The progression-free survival 2 (PFS2) rates at 1, 2, and 3 years were 80.8%, 54.6%, and 31.4%, respectively. The median OS, PFS1, and PFS2 were 29.8, 18.0, and 28.1 months, respectively. Cox multivariate analysis identified gene mutation status and brain radiation dose as independent prognostic factors for OS. For PFS1, gene mutation status, brain radiation dose, and initial treatment response were independent prognostic factors. Clinical stage, gene mutation status, brain radiation dose, and initial treatment response were independent prognostic factors for PFS2. Conclusion: The combination of TKIs and brain RT is effective for patients with lung adenocarcinoma with EGFR mutations and brain metastases. Patients with exon 19 Del or exon 21 L858R mutations and brain radiation doses ≥40 Gy exhibit longer OS, PFS1, and PFS2. Additionally, complete remission + partial remission is associated with extended PFS1 and PFS2, while patients in stage IVA show longer PFS2.