bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilizing Omic Data to Understand Integrative Physiology
Authors: Knepper Mark A
Published: February 2025

Over the past several decades, physiological research has undergone a progressive shift toward greater-and-greater reductionism, culminating in the rise of ‘molecular physiology.’ The introduction of Omic techniques, chiefly protein mass spectrometry and next-generation DNA sequencing (NGS), has further accelerated this trend, adding massive amounts of information about individual genes, mRNA transcripts, and proteins. However, the long-term goal of understanding physiological and pathophysiological processes at a whole-organism level has not been fully realized. This review summarizes the major protein mass spectrometry and NGS techniques relevant to physiology and explores the challenges of merging data from Omic methodologies with data from traditional hypothesis-driven research to broaden the understanding of physiological mechanisms. It summarizes recent progress in large-scale data integration through: 1) creation of online user-friendly Omic data resources with cross-indexing across data sets to democratize access to Omic data; 2) application of Bayesian methods to combine data from multiple Omic data sets with knowledge from hypothesis-driven studies in order to address specific physiological and pathophysiological questions; and 3) application of concepts from Natural Language Processing to probe the literature and to create user-friendly causal graphs representing physiological mechanisms. Progress in development of so-called “Large Language Models”, e.g. ChatGPT, for knowledge integration is also described along with a discussion of the shortcomings of Large Language Models with regard to management and integration of physiological data.
SCRaMbLE: a versatile tool for genome manipulation
Authors: Cheng Li , Li Jielin , Chen Yaojun , Dai Junbiao
Published: February 2025

Genomic rearrangements play an important role in shaping genetic diversity, as they enable the generation of novel structural variations through specific genome manipulation tools. These variations contribute to phenotypic differences among individuals within a population, thereby serving as the foundation for natural selection and driving evolutionary processes. In recent years, Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) has emerged as a promising tool for studying genomic rearrangements. SCRaMbLE utilizes site-specific recombination mediated by loxPsym sites to induce targeted chromosomal rearrangements in yeast cells. In this review, we provide a comprehensive overview of recent advancements in optimization strategies of the SCRaMbLE system and discuss influential factors that affect its performance based on recent research findings. We demonstrate how the SCRaMbLE system can be employed for pathway engineering, phenotype improvement, genome minimization, and dissection of genotype-to-phenotype relationships. We highlight both the advantages and challenges associated with SCRaMbLE and envision its potential applications beyond yeast genetics.
Synthetic forms most beautiful: engineering insights into self-organization.
Authors: Xu Zhejing , Chang Chih-Chia , Coyle Scott
Published: February 2025

Reflecting on the diversity of the natural world, Darwin famously observed that “from so simple a beginning endless forms most beautiful and most wonderful have been, and are being evolved”. However, the examples that we are able to observe in nature are a consequence of chance, constrained by selection, drift and epistasis. Here we explore how the efforts of synthetic biology to build new living systems can expand our understanding of the fundamental design principles that allow life to self-organize biological form, from cellular to organismal levels. We suggest that the ability to impose a length or timescale onto a biological activity is an essential strategy for self-organization in evolved systems and a key design target that is now being realized synthetically at all scales. By learning to integrate these strategies together, we are poised to expand on evolution’s success and realize a space of synthetic forms not only beautiful but with diverse applications and transformative potential.
Vim3 and Mxi‐2 as Promising New Molecular Biomarkers for the Diagnosis of Sperm Disorders
Authors: Weiten Richard , Herden Jan , Huerta Manuel , Nestler Tim , Denil Johan , Heidenreich Axel , Storz Enno , von Brandenstein Melanie
Published: February 2025

Introduction: Male infertility remains a significant clinical challenge that requires the exploration of new diagnostics strategies. Truncated proteins, such as Vim3, a truncated variant of vimentin, show promise as a new class of biomarkers for diagnosing fertility disorders. Our objective was to assess the potential utility of Vim3 and Mxi‐2, a shortened iteration of mitogen‐activated protein kinase (MAPK) p38, as noninvasive biomarkers for diagnosing sperm disorders.

Methods: Semen samples of 19 fertile males (control group) and 82 infertile males with semen abnormalities and no female factor (n = 28 OAT [oligo–astheno–teratozoospermia] syndrome, n = 8 azoospermia, n = 29 teratozoospermia, n = 11 astheno–teratozoospermia, and n = 6 oligozoospermia) were analyzed using ELISA (enzyme‐linked immunosorbent assay) and flow cytometry. Furthermore, we conducted a lateral flow assay (LFA) specific to Vim3.

Results: Our analysis revealed that Vim3 and endothelin‐1 (ET‐1) expression levels were significantly downregulated in non‐normozoospermic patients (e.g., OAT syndrome), while Mxi‐2 was overexpressed in these patients compared to the control group (p < 0.01). Additionally, we introduced a novel LFA that provides a user‐friendly and effective method for examining Vim3 as a biomarker in clinical settings.

Conclusion: Our results suggest that Vim3 and Mxi‐2 have potential as noninvasive semen biomarkers for diagnosing sperm disorders.
The Computational Modeling of Grid‐Connected Double‐Chamber Microbial Fuel Cell (DCMFC) Bioenergy Utilizing MATLAB Simulink Software
Authors: Shabangu Khaya Pearlman , Mthembu Nhlanhla , Chetty Manimagalay , Bakare Babatunde Femi
Published: February 2025

Owing to the depletion of fossil fuels, rising energy costs, and environmental pollution, there has been a growing focus on exploring and exploiting renewable energy sources. This study aims to demonstrate the modeling of a grid‐connected double‐chamber microbial fuel cell (DCMFC) biomass energy system via MATLAB Simulink software. The experimental measurements obtained from DCMFC outputs served as the basis for developing the inverter‐grid connection model and simulation output in MATLAB Simulink software. Briefly, the DCMFC DC boost voltage was connected to the positive and negative buses of the three‐phase DC‒AC inverter circuit, with switching patterns controlled by gate pulses in each transistor. Full square wave single‐stage PWM pulses are generated by the gate for control. The power generated by the inverter was measured via a three‐phase VI block for analysis, with voltages and currents displayed via a scope. To address potential noise during switching, an LC filter is employed to suppress noise output and stabilize power generation. Another power meter measures power from the grid, with waveforms displayed via scope blocks. Before synchronization between power from the DCMFC and the grid occurs, four requirements must be met: the grid voltage must match the inverter output voltage, the inverter frequency must match the grid frequency, the phase sequence must be the same, and the phase angle of the inverter must match that of the grid. Additionally, Institute of Electrical and Electronics Engineers (IEEE)‐specific requirements were evaluated during the simulation for this study. In addition, this study critically examined whether the DCMFC inverter model conforms to conventional requirements, International Electrotechnical Commission (IEC) standards, and IEEE standards for the integration of inverters into the grid. Compared with previous studies on inverter modeling for grid connections, past studies have emphasized the efficacy of biomass power plants and different inverter topologies for photovoltaic (PV) systems. The current study focuses on optimizing a multilevel inverter‐based model, achieving low total harmonic distortion (THD) below IEEE standards. In this study, the use of a multilevel inverter configuration proved highly effective in reducing the harmonic content, leading to synchronized phase sequences and enhanced coherence between the grid and inverter voltages. With a THD of 4.75% at 50 Hz, supported by a harmonic distortion value of 422.5, the chosen configuration significantly minimized the harmonic distortion. This success underpins the system’s reliability and efficiency, offering promising implications for practical applications.
De Novo ACTB Variant Associated With Juvenile‐Onset Temporal Lobe Epilepsy With Favorable Outcomes
Authors: Yan Hong-Jun , Wang Peng-Yu , Liu Wen-Hui , Gu Yu-Jie , Pan Jia-Cheng , Li Hua , Luo Sheng
Published: February 2025

Genetic factors are estimated to contribute to 80% of people with epilepsy. However, only four genes were reported to be associated with temporal lobe epilepsy (TLE). This study is aimed at investigating the association between ACTB and TLE. Trio‐based exome sequencing was performed in a patient, and a de novo ACTB variant was identified. The patient presented with TLE featuring by age of onset in juvenile, seizure‐free status in adulthood, complications of memory decline and irritability, epileptic discharges in the bilateral temporal lobes, and bilateral hippocampal sclerosis. The pathogenicity of the identified ACTB variant was supposed by multiple pieces of evidence, including the missense tolerance ratio of 0%, high conservation of the affected residue, predicted to be “damaging” or “conserved” by 17 in silico tools, and classification of likely pathogenic variant by the American College of Medical Genetics and Genomics (ACMG) guidelines. Protein modeling indicated the alteration of protein structure and stability caused by the identified variant. The spatiotemporal expression of ACTB is consistent with the phenotypic features of this patient. This study suggested that ACTB is a novel candidate causative gene of TLE. The correlation between phenotypes and spatial–temporal expression provides a novel perspective for further exploration of the pathogenesis and prognosis of the disease.
Antimicrobial Polymeric Nanoparticles in Endodontics: A Systematic Review
Authors: Orozco Marco Felipe Salas , Montero Idania de Alba , Gonzalez Oscar Lozano , Santana Miguel Angel Casillas , Domínguez Jorge Humberto Luna , Olivares-Acosta Iván , Solis Carlo Eduardo Medina , Marín Nuria Patiño
Published: February 2025

Background: The efficacy of endodontic treatments, essential for managing infections and injuries in dental pulp, heavily relies on completely eradicating microorganisms from the root canal system. Traditional methods often fail to achieve thorough disinfection, prompting the exploration of polymeric nanoparticles for their potential to enhance cleanliness.

Objectives: This systematic review aims to evaluate the use and effectiveness of polymeric nanoparticles in endodontic treatments, with a specific focus on their antimicrobial properties.

Methods: Studies eligible for inclusion involved inoculated root canals, dentine, or endodontic medicaments containing relevant microbial species. The interventions examined included the application of polymeric nanoparticles that contain antimicrobial agents, sometimes enhanced by ultrasound or photodynamic therapy, compared against control groups without treatment. The primary outcome was the reduction in bacterial load. Systematic searches were conducted in databases such as PubMed, Web of Science, Scopus, and Google Scholar and completed by January 31, 2024. The risk of bias was assessed using a modified Cochrane tool, and results were synthesized descriptively due to heterogeneity in methodologies and reporting across the studies.

Results: Nine studies met the inclusion criteria, primarily focusing on bacterial strains like Enterococcus faecalis and Staphylococcus aureus. Results indicated that nanoparticles exhibited significant antimicrobial activity, especially those made of chitosan and poly (lactic‐co‐glycolic acid) (PLGA). This suggests a potential to revolutionize root canal disinfection processes. However, clinical translation faces challenges such as ensuring nanoparticle stability, biocompatibility, and cost‐effective manufacturing processes.

Discussion: The evidence was limited by variability in study designs and microbial strains, the absence of clinical trials, and inconsistent reporting precluded a meta‐analysis. Despite promising in vitro results, several barriers hinder the clinical implementation of nanoparticle‐based therapies. Long‐term safety data are sparse, and the potential for adverse effects like inflammatory responses and antimicrobial resistance remains a concern. Additionally, achieving optimal delivery within the intricate anatomy of the root canal system requires further innovation. Addressing these challenges is critical for transitioning from experimental to practical applications.
Comparison of Myopic Progression and Quality of Life Wearing Either DIMs Lenses or Single‐Vision Myopia Correcting Spectacles
Authors: Li Xiaoying , Ma Wei , Song Yutong , Yap Maurice , Liu Longqian
Published: February 2025

Purpose: To assess the efficacy of the Defocus Incorporated Multiple Segments (DIMS) spectacle lens for myopia control and its impact on vision‐related quality of life in Chinese children over a 1‐year period.

Methods: This randomized double‐blind prospective controlled clinical trial enrolled 176 myopic subjects aged between seven and 14 years who were randomly assigned into the DIMS group or the control single‐vision (SV) group. Refractive error and axial length measurements at baseline, three‐, six‐, nine‐, and 12‐month follow‐up visits were monitored. The Quality of Life Impact of Refractive Correction (QIRC) questionnaire was used to evaluate the vision‐related quality of life at baseline and at 12 months postintervention.

Results: Of the initial cohort, a total of 151 children successfully completed the study (DIMS n = 72; SV n = 79). Baseline characteristics were similar between both groups. Average axial elongation and myopia progression after 1 year were 0.17 (95% CI 0.13–0.20) mm and −0.27 (95% CI −0.36 to −0.18) D in the DIMS group and 0.30 (95% CI 0.26–0.33) mm and −0.55 (95% CI −0.64 to −0.47) D in the SV group. The mean differences in axial elongation and myopia progression were 0.13 mm (95% CI 0.08–0.18 mm, p < 0.001) and −0.28 D (95% CI −0.41 to −0.15 D, p < 0.001) between the two groups. No significant difference in the QIRC score was found between the DIMS and SV groups (55.30 (95% CI 53.17–56.90) versus 54.20 (95% CI 51.99–56.41), p = 0.854)).

Conclusion: The use of DIMS lenses in children was found to slow down myopia progression compared to SV lenses, without negatively affecting their overall quality of life.

Trial Registration: Clinical Trial Registry identifier: ChiCTR2000037443
Understanding Attitudes Towards Refugees: The Role of Origin and Shared Social Identity
Authors:   Filozofski fakultet, Sveučilište u Zagrebu, Jelić Margareta , Uzelac Ena ,   Filozofski fakultet, Sveučilište u Zagrebu
Published: February 2025

The public’s attitude towards pro-refugee policies and the willingness to help refugees largely depend on the specific context of the receiving country. An important factor behind these various attitudes is the degree of identification with refugees, influenced by the similarity of cultural and ethnic identity, as well as by the degree of identification with their refugee experience. In this regard, Croatia is specific because memories of the 1991–1995 war and the refugee experience are still very vivid and frame intergroup relations. We conducted two online studies in Croatia to examine the perception of refugees among Croats. In Study 1 (N=290), we investigated attitudes towards Middle Eastern refugees, willingness to help them, and support for pro-refugee policies. In Study 2 (N=183), we examined the same constructs but focused on refugees from Ukraine. In both studies, the participants were aged between 18 and 63 years, with a higher proportion of female participants. The results of Study 1 revealed a neutral attitude towards Middle Eastern refugees and a lack of prosocial intentions. However, the results of Study 2 indicated a notably positive attitude towards Ukrainian refugees, fair support for pro-refugee policies, and moderate willingness to personally help them. In both studies, regression analyses confirmed that inclusive victim consciousness and empathy were positive predictors of attitudes and prosocial intentions towards refugees, while prejudice towards refugees was a negative predictor. National identification emerged as a relevant positive predictor only when it comes to helping Ukrainian refugees. The results are discussed from the perspective of social categorisation theory, social identity, and the dominant narrative about past collective experiences and the current refugee situation. We also discuss the importance of media, competent authorities, and public policies throughout the crisis in shaping people’s attitudes and prosocial intentions towards refugees.
AZD8701, an Antisense Oligonucleotide Targeting FOXP3 mRNA, as Monotherapy and in Combination with Durvalumab: Phase I trial in Patients with Advanced Solid Tumors
Authors: Siu Lillian L. , Postel-Vinay Sophie , Villanueva-Vázquez Rafael , de Velasco Guillermo , Castanon Alvarez Eduardo , Kyriakopoulos Christos E. , Johnson Melissa , Ouali Kaïssa , McMorn Stephen , Angell Helen K. , Ng Felicia , Saran Shashank , Bayat Mahdiye , Collins Teresa , Roy Archana , Lambert Arthur W. , Cho Song , Miller Neil , Petruzzelli Michele , Stone John , Massard Christophe
Published: February 2025

Purpose: AZD8701 uses next-generation antisense oligonucleotide (ASO) technology to selectively reduce human forkhead box P3 (FOXP3) expression in regulatory T cells, reversing their immunosuppressive function. FOXP3 ASOs alone or with programmed cell death protein (ligand) 1 (PD-[L]1) inhibition attenuated tumor growth in mice. We report a phase I study of AZD8701 alone or combined with durvalumab in patients with advanced solid tumors. Methods: Eligible patients had solid tumors and had received prior standard-of-care treatment including anti-PD-(L)1 therapy. Patient cohorts were treated with AZD8701 intravenously (IV) weekly at escalating doses, either alone (60–960 mg) or combined (240–720 mg) with durvalumab 1,500 mg IV every 4 weeks. The primary objective was safety and tolerability, with the aim of determining the maximum tolerated dose. Results: Forty-five patients received AZD8701 monotherapy and 18 received AZD8701 with durvalumab. One dose-limiting toxicity (increased alanine aminotransferase [ALT]) occurred with AZD8701 960 mg. The most common adverse events (AEs) related to AZD8701 monotherapy were fatigue (22.2%), asthenia, pyrexia, and increased ALT (20%, each); the safety profile was similar when combined with durvalumab. With AZD8701 monotherapy, 24.4% and 15.6% of patients had stable disease for ≥16 and ≥24 weeks, respectively; one patient treated with AZD8701 720 mg and durvalumab had a partial response. FOXP3mRNA changes were heterogeneous (8/13 patients showed reduction), with no clear dose relationship. ASO accumulated in the tumor epithelium and stroma. Conclusions: This study demonstrates the clinical feasibility of ASO therapy, with generally manageable AEs, FOXP3 knockdown, and ASO delivery to the tumor.
Predicting c-KIT Inhibitor Efficacy in Patient-Derived Models of Sinonasal Mucosal Melanomas through Integrated Histogram Analysis of Whole-Tumor DKI, IVIM, and DCE-MRI
Authors: Wang Cong , Niu Xuewei , Xia Tianyi , Wang Peng , Wang Yuzhe , Zhang Zhongshuai , Zhang Jianyuan , Ju Shenghong , Xiao Zebin
Published: February 2025

Purpose: To evaluate whole-tumor histogram analysis of diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced MRI (DCE-MRI), in predicting the efficacy of imatinib, a c-KIT inhibitor, for treating patient derived models derived from sinonasal mucosal melanomas (MMs). Experimental Design: This study included 38 patients with histologically confirmed sinonasal MM, who underwent DKI, IVIM, and DCE-MRI. Patient-derived tumor xenograft (PDX) models and precision-cut tumor slices (PCTS) were established to evaluate tumor response to imatinib. Whole-tumor histogram analysis was conducted on imaging parameters, and logistic regression models were applied to determine the predictive value of these metrics in differentiating responders from non-responders. Results: Among the 38 sinonasal MM patients, 12 were classified as responders and 26 as non-responders based on PDX and PCTS model responses to imatinib. The DKI model revealed significant differences in mean, median, P10, and P90 values of Dk and K between responders and non-responders (P < 0.05). The IVIM model indicated significant differences in P10 and mean values of D, with kurtosis f being a strong predictor. The DCE-MRI model, using the P90 Ktrans metric, demonstrated robust predictive performance, achieving an AUC of 0.89, with 80.77% specificity and 91.67% sensitivity. The combined logistic model integrating DKI, IVIM, and DCE-MRI metrics produced the highest predictive accuracy, with an AUC of 0.90. Conclusions: Whole-tumor histogram analysis of DKI, IVIM, and DCE-MRI offers a non-invasive method for predicting the efficacy of c-KIT inhibitors in sinonasal MMs, presenting valuable implications for guiding targeted treatment in this rare cancer type.
Supplementary Table 4 from Cytokine-Regulated Phosphorylation and Activation of TET2 by JAK2 in Hematopoiesis
Authors: Jeong Jong Jin , Gu Xiaorong , Nie Ji , Sundaravel Sriram , Liu Hui , Kuo Wen-Liang , Bhagat Tushar D. , Pradhan Kith , Cao John , Nischal Sangeeta , McGraw Kathy L. , Bhattacharyya Sanchari , Bishop Michael R. , Artz Andrew , Thirman Michael J. , Moliterno Alison , Ji Peng , Levine Ross L. , Godley Lucy A. , Steidl Ulrich , Bieker James J. , List Alan F. , Saunthararajah Yogen , He Chuan , Verma Amit , Wickrema Amittha
Published: February 2025

Supp Table 4: Loci that are differentially methylated in IMF with JAK2V617F mutations when compared to controls
Supplementary Figures S1-S7 from Cytokine-Regulated Phosphorylation and Activation of TET2 by JAK2 in Hematopoiesis
Authors: Jeong Jong Jin , Gu Xiaorong , Nie Ji , Sundaravel Sriram , Liu Hui , Kuo Wen-Liang , Bhagat Tushar D. , Pradhan Kith , Cao John , Nischal Sangeeta , McGraw Kathy L. , Bhattacharyya Sanchari , Bishop Michael R. , Artz Andrew , Thirman Michael J. , Moliterno Alison , Ji Peng , Levine Ross L. , Godley Lucy A. , Steidl Ulrich , Bieker James J. , List Alan F. , Saunthararajah Yogen , He Chuan , Verma Amit , Wickrema Amittha
Published: February 2025

Supplementary Figures S1-S7
SEX DIFFERENCES IN MARKERS OF CEREBRAL SMALL VESSEL DISEASE IN PATIENTS WITH LOBAR INTRACEREBRAL HEMORRHAGE
Authors: Incontri Diego , Marchina Sarah , Wilson Mitchell , Wang Jia-Yi , Losso Merryjean , Andreev Alexander , Lin David , Heistand Elizabeth C. , Carvalho Filipa , Marchal Juliette , Nallaparaju Anusha , Lioutas Vasileios , Selim Magdy H.
Published: February 2025

Introduction: Cerebral small vessel disease (CSVD) is a major cause of primary lobar intracerebral hemorrhage (ICH) due to cerebral amyloid angiopathy (CAA) or hypertensive arteriopathy (HA). Sex differences in CSVD imaging markers and prevalence of CAA vs HA in lobar ICH remain unexplored.

Methods: We performed a retrospective analysis of patients with primary lobar ICH who underwent MRI during hospitalization. We collected demographic, clinical, and outcome data. We reviewed MRIs for CSVD markers and calculated composite CSVD burden score (cCSVDbs). We assigned possible/probable CAA using Boston criteria 2.0. We grouped patients based on their sex and examined associations between sex and CSVD markers, cCSVDbs, or CAA. Kaplan Meier survival analysis was used to determine ICH-onset age among patients with first-ever symptomatic lobar ICH.

Results: 214 patients were included (102 (47.66%) women). Men were more likely to be current alcohol abusers (25.69%vs9.09%, p=0.002), current smokers (24.30%vs12.12%, p=0.024), and have coronary artery disease (26.79%vs15.69%, p=0.048), and hyperglycemia on admission (142.79±59.59vs126.58±37.29, p=0.019). Women were older (74.91±11.69vs69.28±14.53 years, p=0.002), and more likely to have possible/probable CAA in univariate (97.06%vs88.39%; OR 4.33, 95%CI 1.19-15.67; p=0.025) but not multivariate analysis. We found no significant differences in MRI markers of CSVD, cCSVDbs, or CAA. Among patients who presented with their first-ever primary symptomatic lobar ICH (n=187), men were younger than women (73vs77 years, p=0.001).

Conclusions: In our cohort of patients with primary lobar ICH, we found no significant difference in clinical and imaging characteristics between sexes. However, men were more likely to have a younger lobar ICH-onset age compared to women.
Internalized Shame in Treatment-Seeking Adults with Obesity Class II-III and Its Association with Quality of Life, Body Image, and Self-Esteem
Authors: Lagerström Marcus , Johnsson Per , Orrenius Bengt , Järvholm Kajsa , Olbers Torsten , Engström My
Published: February 2025

Introduction: Health-related quality of life (HRQoL) may be impaired in individuals living with obesity, possibly due to exposure to obesity-related stigma which may in turn activate shame. Few studies have been conducted on shame in relation to obesity and its potential association with other constructs such as HRQoL, self-esteem, and body image. In this study, internalized shame and the potential association with HRQoL, self-esteem, and body image were investigated in treatment-seeking patients with obesity class II-III. Methods: In total, 228 patients referred for obesity treatment at a tertiary clinic in Sweden participated in the study. The cohort was stratified into two groups using a clinical cutoff (≥50) indicating pathological levels of shame as reported on the Internalized Shame Scale (ISS): a high shame group (HSG) and low shame group (LSG). Results: The mean ISS score for the overall cohort was 41.6, with a mean of 28.1 for the LSG and 66.5 for the HSG. Compared to the LSG, the HSG reported a lower quality of life in seven of eight HRQoL domains as well as a lower obesity-specific health-related quality of life. Furthermore, a higher shame score was associated with poorer body image and lower self-esteem. Conclusion: Taken together, these findings indicate that a substantial number of patients with obesity report high internalized shame and that these individuals could benefit from extra support in treatment settings.
Sex Differences in Clinical Presentation of Women and Men Evaluated at a Comprehensive Stroke Center for Suspected Stroke
Authors: Kühne Escolà Jordi , Bozkurt Bessime , Brune Bastian , Milles Lennart Steffen , Pommeranz Doreen , Dammann Philipp , Li Yan , Deuschl Cornelius , Forsting Michael , Kill Clemens , Kleinschnitz Christoph , Köhrmann Martin , Frank Benedikt
Published: February 2025

Introduction: Understanding sex differences in the clinical presentation of patients with suspected stroke is important to reduce sex-related disparities and improve care. We aimed to characterize presenting symptoms in women and men with suspected stroke evaluated at our comprehensive stroke center. Methods: This was a retrospective analysis of consecutive patients with suspected stroke treated at the University Hospital Essen between January 2017 and December 2021. Patient characteristics, signs and symptoms as well as final diagnoses in women and men were compared. Logistic regression analysis was performed to assess the association of individual symptoms with a diagnosis of cerebrovascular disease. Results: We included 6069 patients in our analysis. Cerebrovascular disease was diagnosed in 85.2% (2576/3022) of women and 88.0% (2681/3047) of men (p = 0.002). Aphasia (31.4% vs. 27.7%, p = 0.002), neglect (15.5% vs. 12.8%, p = 0.003), gaze deviation (21.0% vs. 18.8%, p = 0.034), as well as nonfocal symptoms including impairments in consciousness (17.0% vs 14.6%, p = 0.012), orientation (42.5 vs. 36.4%, p < 0.001) and completion of tasks (31.2% vs. 26.0%, p < 0.001) were more common among women. Limb ataxia (8.1% vs. 11.2%, p < 0.001) and dysarthria (44.0% vs. 46.8%, p = 0.030) were less frequent in women. Neglect and gaze deviation were independent positive predictors of cerebrovascular disease in women but not in men. Conclusion: Although clinical presentation was similar in both sexes, cortical and nonfocal symptoms were more common among women with suspected stroke. Awareness of sex differences and acknowledgement of the full clinical picture are important to ensure optimal management for women and men with suspected stroke. Our findings might serve as a target for educational programs in order to improve preclinical stroke detection in patients with predominantly nonfocal or subtle symptoms.
Decoding the Gut-Brain Axis: A Journey Towards Targeted Interventions for Disorders-of-Gut-Brain Interaction
Authors: Holtmann Gerald , Moniruzzaman MD , Shah Ayesha
Published: February 2025

Background: The gut-brain axis is a bidirectional communication pathway connecting the gastrointestinal tract and the brain. Disorders of Gut-Brain Interaction (DGBI) manifest as highly prevalent gastrointestinal disorders such as irritable bowel syndrome (IBS) or Functional Dyspepsia (FD).
Summary: The initial focus of DGBI research was on the effects of psychological stress on digestive functions like gastrointestinal motility, or secretion of gastric acid and pancreatic enzymes. Concepts related to DGBI have expanded in recent decades. Activation of mucosal or systemic immune functions has been observed in DGBI, and it is established that the gastrointestinal microbiome can alter mucosal integrity and permeability, leading to proinflammatory cytokine release that affects brain function. Pharmacologic treatments (e.g., tricyclic antidepressants), and non-pharmacologic interventions (e.g., cognitive behavioral therapy), are now standard for DGBI patients. Advances in culture-independent methods to study gastrointestinal microbes reveal new insights into DGBI and gut microbiota appear to play a crucial role in modulating the gut-brain axis and regulating various bodily functions.
Tumor Infiltrating Lymphocytes, CAR-, and T Cell Receptor- Modified T Cells in Solid Cancer Oncology
Authors: Echchannaoui Hakim , Legscha Kevin Jan , Theobald Matthias
Published: February 2025

Background: Adoptive cellular therapy (ACT) is a promising treatment approach aiming at enhancing T cell antitumor immune response. ACT includes tumor-infiltrating lymphocytes (TILs), chimeric antigen receptor (CAR) and T-cell receptor (TCR) gene-modified T cells. Despite a milestone achievement with CAR-T cells in hematopoietic malignancies, ACT has shown modest clinical responses in refractory solid cancers and durable responses remain limited to a minor fraction of patients. Summary: In this review, we highlight major advances, limitations and current developments of T cell therapies for solid cancers. We discuss emerging promising strategies as next-generation ACT, exploring local delivery routes to maximise efficacy and improve safety, integrating predictive biomarkers to optimize selection of patients who most likely would benefit from ACT, using combination therapy to overcome the immunosuppressive tumor microenvironment, targeting multiple tumor antigen to avoid tumor antigen escape, selection of the most potent T cell product to overcome T cell dysfunction and incorporating cutting edge new technologies, such as gene-editing to further improve anti-tumor T cell functions and reduce therapy-related toxicity. Key Messages: Advances made in ACT trials have move the field of immunotherapy for refractory solid cancers to a new stage, by constantly incorporating new strategies to develop next-generation therapies designed to enhance efficacy and improve safety and to allow a broaden access to a large numbers of patients.
Vitamin D supplementation mediates a shift towards anti-inflammatory cytokine response in Multiple Sclerosis.
Authors: Al-Shammri Suhail , Chattopadhyay Arpita , Raghupathy Raj
Published: February 2025

Objective: In this study, we assessed the regulatory effect of Vitamin-D supplementation on cytokine profile in newly diagnosed drug-naïve Multiple Sclerosis (MS) patients.
Methods: We recruited 16 patients with incident MS, and they were followed up for 12 months. Serum levels of 25-hydroxy-vitamin-D were measured at recruitment and follow-up. Peripheral blood mononuclear cells were isolated from blood samples and stimulated with a mitogen in tissue culture to elicit cytokine production. Culture supernatants were tested after 4 days of culture for levels of pro-inflammatory (TNFα, IFN γ, IL-6, IL-12) and anti-inflammatory cytokines (IL-4, IL-5, IL-10).
Results: Baseline blood samples analysis revealed that patients(n=16) had low Vitamin-D levels [16.77(12.41-31.38)nmol/L]. Thirteen Patients expressed a normal iPTH [5.53(4.2-6.9)] and were given Caltrate D twice a day; 3 patients having elevated iPTH (mean± sd:12.83±1.47) were prescribed 50,000IU vitamin-D once weekly and Caltrate D twice daily. Interferon-β1α was prescribed after a confirmed diagnosis of relapsing-remitting MS in 13 patients, 3 patients declined immunotherapy. Irrespective of immunotherapy, we observed a gradual and significant decrease in pro-inflammatory cytokine levels and a steady significant decline in ratios of several pro-inflammatory to anti-inflammatory cytokines. The patients with a higher pro: anti-inflammatory cytokine ratios were more prone to have relapses.
Conclusions: High pro-inflammatory cytokine and low vitamin D levels in drug-naïve patients support the contention that hypovitaminosis D may play an immune-pathogenetic role in the development of MS. Moreover, Vitamin D supplementation possibly plays a protective role in the prognosis of MS through an immune-pathologic pathway and is of therapeutic importance.
CLIC1 supports mechanisms related to platelet activation and thrombosis
Authors: Knowles Lynn M. , Ampofo Emmanuel , Menger Michael D. , Drawz Anna , Eichler Hermann , Pilch Jan
Published: February 2025

Background: Chloride intracellular channel 1 (CLIC1) is expressed in platelets, but CLIC1 action in these cells has not been clarified. Methods: CLIC1 function was probed in platelets in vitro as well as in a mouse dorsal skin fold chamber model in vivo to assess thrombus formation. Results: Co-localization of CLIC1 with F-actin was detected in lamellipodia of platelets, which relocate CLIC1 to their cell surface in an integrin-dependent manner. Treatment with the CLIC1 inhibitor IAA94 hindered CLIC1 relocation to the platelet membrane, diminished platelet aggregation and reduced integrin αIIbβ3 activation. Injecting mice with IAA94 delayed vaso-occlusion in a mouse model of photo-chemical thrombus formation in vivo. The role of CLIC1 for platelet activation could be reproduced in platelet concentrates, which even after prolonged storage expressed minimal CLIC1 on the platelet surface unless platelets were exposed to an activating stimulus. Conclusion: These data show that CLIC1 is regulated by adhesive interactions with integrin ligands that cause CLIC1 to relocate to the platelet cell surface. This process in turn appears to be relevant for integrin-mediated functions involved in platelet thrombus formation in vitro and in vivo. Moreover, CLIC1 has the potential to be a useful marker for monitoring the activation state of platelet concentrates during prolonged storage.
A case of a SMARCB1 (INI1)-deficient intrathoracic neoplasm that did not respond to chemotherapy for non-small cell lung cancer and rapidly progressed
Authors: Moriyasu Yutaro , Tsuda Takeshi , Matsuyama Kei , Mizushima Isami , Azechi Kenji , Masaki Yasuaki , Abo Hitoshi , Aikawa Akane , Ishizawa Shin , Taniguchi Hirokazu
Published: February 2025

SMARCB1 (INI1)-deficient intrathoracic neoplasms are rare and highly malignant. We report a case of a patient with this tumor who was initially diagnosed with non-small cell lung cancer and whose disease rapidly progressed to death despite chemotherapy. A man in his 60s was diagnosed with a mass exceeding 10 cm in the lower lobe of the right lung and a right pleural effusion on the first examination. Transbronchial biopsy of the primary lesion revealed a tumor with rhabdoid features, which was diagnosed as an undifferentiated malignant neoplasm. Clinically, the patient was diagnosed with non-small cell lung cancer and was treated with carboplatin, nab-paclitaxel, durvalumab, and tremelimumab. However, at the end of the second course, there was rapid disease progression. Based on a pathological review, the tumor was considered a SMARCB1-deficient intrathoracic neoplasm. Although we considered further treatment, his general condition deteriorated, and he died about two months after his first visit. This disease is rare, and we believe that it is necessary to disseminate the concept of this disease and accumulate knowledge to establish a treatment.
Efficiency enhanced adaptive quasi-sliding mode controller for variable-speed induction motor drive
Authors: Jacob Shaija Palackappillil , Daniel Asha Elizabeth
Published: February 2025

Recent advancements in automated manufacturing and processing industries necessitate fast-responding, efficient, and robust methods for controlling induction motor (IM) drives. Classical proportional-integral (PI) controllers provide optimal performance only at specific operating points and are sensitive to parameter variations. This work proposes an adaptive quasi-sliding mode controller (AQSMC), which utilizes a tangent (tanh) function as the switching function and demonstrates enhanced robustness and adaptability across a wider range of operating conditions. The AQSMC employs an adaptation law to estimate the dynamic disturbances, offering insensitivity to structured and unstructured uncertainties. Numerical simulations are carried out with the AQSMC that analytically deduces the optimum field flux ensuring efficient performance. A lookup table derived from the efficiency optimization algorithm (EOA) is incorporated to further streamline the computational requirements. To validate simulation results, a prototype was developed using a 1 HP induction motor, a DSP controller board with a TI C2000 Delfino MCU F28379D microcontroller, and an IGBT-based Inverter module. Simulations show a 6.3% efficiency improvement at half load and 300 rpm, while experimental analysis records a 3.9% improvement with the EOA, highlighting the potential for enhancing energy efficiency in various industrial applications.
Optimal placement of energy storage system in hybrid AC/DC microgrid to enhance stability
Authors: Yamuna Pagidela , Visali N.
Published: February 2025

Nowadays, growing interest in sustainable energy solutions, hybrid AC/DC microgrids are becoming more and more recognized as a reliable and efficient option. In order to improve the stability of such microgrids advanced solutions for ESS placement are required due to the unpredictable nature of renewable energy sources and the complexity of load needs. The precision needed to maximize microgrid stability in the face of these obstacles is lacking. In this paper, an artificial neural networks (ANN)-based framework for the strategic allocation and sizing of ESS is proposed. This study uses ANN and the process is to determine the best locations and capacities for energy storage systems (ESS) to minimize system losses while accounting for variations in renewable generating and demand profiles. Simulation is carried on IEEE 12 bus system for studying the usefulness of the proposed method and stability is determined. The power flow datasets generated through simulation are utilized to train the ANN in order to determine the most appropriate placements for ESS. Furthermore, a series of simulations were performed to examine the impact of ESS characteristics on the performance of system loss under various circumstances.
Enhancing efficiency and stability in CPT systems: a state feedback controller approach
Authors: Al-Hattami Ahmed , Saat Shakir , Yusop Yusmarnita , Awal Md Rabiul , Shapri A. H. M. , Husin Huzaimah
Published: February 2025

This work aims to present an innovative design and simulation of an auto-tuning capacitive power transfer (CPT) system. The system utilizes a Class-E converter, renowned for its exceptional efficiency. Challenges arise when trying to regulate the output voltage of a Class-E converter in the presence of load fluctuations, leading to an escalation in switching losses. By employing first harmonic approximation (FHA) and generalized state space averaging (GSSA), a state-space model of the system is constructed to effectively address this problem. The output voltage is regulated by a state feedback controller developed using the Lyapunov approach. This paper presents a comparative analysis of a traditional PID controller and a recently suggested state feedback controller, with a primary emphasis on system stabilization. The study examines the similarities and differences between the two controllers. The efficacy of the proposed controller design is demonstrated through the utilization of simulation data. Furthermore, these results confirm the validity of the comparative study, making it a substantial contribution to the field of CPT systems.
Teaching learning optimization technique FOPID controlled Cuk and SEPIC converter-based PF rectification
Authors: Mishra Alok Kumar , Das Soumya Ranjan , Giri Nimay Chandra , Routray Sangram Kishore , Syam Fathy Abdelaziz , Elwakil Ehab S.
Published: February 2025

The foremost cause of harmonic contamination is the ample utilization of loads of non-linear type such as static power converters. Because of this load, the input power factor (PF) decreases heavily as they draw a current of non-sinusoidal in nature. This article gives a general presentation investigation of two PF rectification (PFR) converter (PFRC) geographies: Cuk type and single-ended primary-inductance converter or SEPIC type converter. The average current control (ACC) technique is utilized here. Notwithstanding, for control of output voltage, techniques like conventional proportional integral derivative controller (PIDC) or fractional order proportional integral derivative controller (FOPIDC) are used, and the gains of the controller are calculated using a novel teaching learning optimization technique (TLOT), considering integral time absolute error (ITAE). The analysis of both PFRC acted in Simulink/MATLAB and the estimated converters are studied under consistent and dynamic state conditions. The FOPIDC Cuk PFRC is providing 2.97% of THD compared to other converters.
Design and implementation of 4-quadrant chopper for speed control of EVs and regenerative braking analysis
Authors: Abdelfatah Magdy Saoudi , Solanki Parmal Singh , Sreedharan Sasidharan
Published: February 2025

This paper presents a novel 4-quadrant chopper design for controlling the speed of electric vehicles, featuring a regenerative braking mechanism to improve energy efficiency. Regenerative braking recovers energy during deceleration by converting kinetic energy into electrical energy stored in the battery. This process activates automatically when the accelerator pedal is released, slowing the vehicle while reducing reliance on mechanical brakes, which remain available for emergency situations. The system’s voltage control is achieved using a pulse-width modulation (PWM) technique that adjusts the duty cycle of switching devices. A microcontroller serves as the system’s core, generating PWM signals and coordinating its operation. The performance of the chopper was evaluated through simulations and experiments, demonstrating that optimal energy recovery occurs at duty cycles of 55-65%. The results revealed that up to 400 joules of energy can be regenerated per braking cycle, particularly in stop-start driving conditions. This innovative design contributes to a 5-10% extension in battery life per charge cycle, enhancing the overall efficiency and sustainability of electric vehicles. The proposed system demonstrates significant potential for energy recovery and reduced wear on mechanical braking systems, paving the way for more efficient electric vehicle technologies.
Efficient SOC estimation for electric vehicles: Extended Kalman filter approach for lithium-ion battery systems
Authors: Mossaddek Meriem , Laadissi El Mehdi , Bouzaid Sohaib , Hajjaji Abdelowahed
Published: February 2025

This study investigates the estimation of the state of charge (SOC) in lithium-ion batteries by utilizing the extended Kalman filter (EKF) algorithm. A simulation model was developed in MATLAB, integrating the Thevenin model with the EKF algorithm to assess SOC levels. The results from the simulations confirm the accuracy and reliability of the proposed approach in estimating SOC. Moreover, a Simulink-based model of the Thevenin equivalent circuit and the EKF algorithm was implemented to further verify the effectiveness of the EKF in SOC estimation. This research underscores the potential of the EKF algorithm to deliver precise SOC estimates, which is crucial for optimizing battery management systems, particularly in electric vehicles.
Global solar energy estimation using improved greedy based genetic algorithm with deep convolutional neural network
Authors: Devaraj Tintu Beena , Kottoor Charu Navaneeth Raveendran
Published: February 2025

Demand for solar energy increases and it is required to manage the supply of energy effectively. Accurate detection on patterns of energy consumed assist in taking appropriate decisions on generating energy. Even though many traditional techniques have predicted the consumption rate, still improvement is needed in prediction accuracy. The pre-processing is performed initially for handling missing values. The feature selection is accomplished using improved greedy based genetic algorithm (GGA) to extract best features to enhance the performance of the model. Output from feature-selection is passed as input to the classification phase using proposed deep convolutional neural network (CNN) in which future solar energy patterns are classified and predicted timely basis power consumption and it optimize the model by minimize the error. The prediction accuracy is estimated through evaluation metrics such as mean square error (MSE), mean absolute percentage error (MAPE) and root mean square error (RMSE) 0.423, 0.652, and 0.215, respectively. The outcomes achieved in terms of accuracy at 99.75, precision at 99.28, sensitivity, and recall at 100 revealed the efficiency of the proposed classification model. As a result, the proposed future prediction of solar energy was considered efficient since it achieved reduced error values than other prediction algorithms. It assists in maintaining stability in solar-energy based systems.