bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial carrier homolog 2 is important for mitochondrial functionality and non-small cell lung cancer cell growth
Authors: Zhao Yong , Wu Siyang , Cao Guohong , Song Peidong , Lan Chang-gong , Zhang Lin , Sang Yong-hua
Published: February 2025

Discovering new molecular targets for non-small cell lung cancer (NSCLC) is critically important. Enhanced mitochondrial function can promote NSCLC progression by enabling metabolic reprogramming, resistance to apoptosis, and increased cell proliferation. Mitochondrial carrier homolog 2 (MTCH2), located in the outer mitochondrial membrane, is pivotal in regulating mitochondrial activities. This study examines MTCH2 expression and its functional role in NSCLC. Bioinformatic analysis showed that MTCH2 is overexpressed in NSCLC tissues, correlating with poor prognosis and other key clinical parameters of the patients. In addition, single-cell sequencing data revealed higher MTCH2 expression levels in cancer cells of NSCLC tumor mass. Moreover, MTCH2 is also upregulated in locally-treated NSCLC tissues and multiple primary/established human NSCLC cells. In various NSCLC cells, silencing MTCH2 via targeted shRNA or knockout (KO) using the CRISPR/Cas9 method significantly hindered cell proliferation, migration and invasion, while inducing apoptosis. MTCH2 knockdown or KO robustly impaired mitochondrial function, as indicated by reduced mitochondrial respiration, decreased complex I activity, lower ATP levels, lower mitochondrial membrane potential (mitochondrial depolarization), and increased reactive oxygen species (ROS) production. Conversely, ectopic overexpression of MTCH2 in primary NSCLC cells enhanced mitochondrial complex I activity and ATP production, promoting cell proliferation and migration. In vivo, the intratumoral injection of MTCH2 shRNA adeno-associated virus (aav) impeded the growth of subcutaneous xenografts of primary NSCLC cells in nude mice. In MTCH2 shRNA aav-injected NSCLC xenograft tissues, there was decreases in MTCH2 expression, mitochondrial complex I activity, ATP content, and the glutathione (GSH)/glutathione disulfide (GSSG) ratio, but increase in thiobarbituric acid reactive substances (TBAR) activity. Additionally, MTCH2 silencing led to reduced Ki-67 staining but increased apoptosis in NSCLC xenografts. Collectively, these findings demonstrate that overexpressed MTCH2 promotes NSCLC cell growth potentially through the maintenance of mitochondrial hyper-function, highlighting MTCH2 as a novel and promising therapeutic target for treating this disease.
The impact of e-cigarette use on periodontal health: a systematic review and meta-analysis
Authors: Tattar Rajpal , Jackson Joshua , Holliday Richard
Published: February 2025

Background

Electronic Nicotine Delivery Systems (ENDS, e-cigarettes) are a popular alternative to traditional tobacco smoking. Objective: To evaluate the effect of ENDS use on periodontal health.

Methods

A protocol was published in accordance with PRISMA standards. Subjects with periodontal health, gingivitis and periodontitis were included. Reviews, case reports, letters, abstracts, narratives and expert opinions were excluded. Databases searched included PubMed, Embase, Web of Science, CINAHL Plus, and Dentistry & Oral Sciences Source up until February 2024. Risk of bias was evaluated using the Newcastle-Ottawa Scale, ROBINS-I and the RoB 2 tools.

Results

40 eligible studies were included. Smokers had poorer clinical outcomes than ENDS users and non-smokers/former smokers, apart from bleeding on probing and gingival indices. There was no difference between ENDS users and non-smokers/former smokers in markers of periodontal destruction (pocket probing depths/marginal bone loss). ENDS users had higher plaque scores than non-smokers/former smokers. ENDS use leads to unique microbial changes compared to tobacco smokers and higher pro-inflammatory markers compared to non-smokers/former smokers.

Conclusion

Within the limitations of the included studies which are at high risk of bias, we found evidence that ENDS use had some impact on periodontal parameters compared to non-smokers/former smokers. Tobacco smokers had consistently worst outcomes.

Registration PROSPERO 2024

CRD42024496560.
IoT integrated and deep learning assisted electrochemical sensor for multiplexed heavy metal sensing in water samples
Authors: Lahari Sreerama Amrutha , Kumawat Nikhil , Amreen Khairunnisa , Ponnalagu R. N. , Goel Sanket
Published: February 2025

Heavy metal measurement is vital for ecological risk assessment and regulatory compliance. This study reports a sensor using gold nanoparticle-modified carbon thread electrodes for the simultaneous detection of Cd²⁺, Pb²⁺, Cu²⁺, and Hg²⁺ in water samples. Differential pulse voltammetry (DPV) was employed, achieving detection limits of 0.99 µM, 0.62 µM, 1.38 µM, and 0.72 µM, respectively, with a linear span of 1–100 µM. The sensor operated effectively in acidic conditions, with excellent selectivity, repeatability, and reproducibility. Real water samples from various lakes in Hyderabad, India, were analyzed to validate their practical application. To extract the sensing features a convolutional neural network (CNN) model was used to process DPV signals, enhancing heavy metal ion classification with high accuracy. Performance metrics such as precision, recall, and F1 score were evaluated. Integration with IoT technology has improved the user experience, advanced heavy metal quantification capabilities, and further enabled remote monitoring.
LMNA R482L mutation causes impairments in C2C12 myoblasts subpopulations, alterations in metabolic reprogramming during differentiation, and oxidative stress
Authors: Ivanova Oksana A. , Predeus Alexander V. , Sorokina Margarita Y. , Ignatieva Elena V. , Bobkov Danila E. , Sukhareva Kseniia S. , Kostareva Anna A. , Dmitrieva Renata I.
Published: February 2025

LMNA mutations causing classical familial partial lipodystrophy of Dunnigan type (FPLD2) usually affect residue R482. FPLD is a severe metabolic disorder that often leads to cardiovascular and skeletal muscle complications. How LMNA mutations affect the functional properties of skeletal muscles is still not well understood. In the present project, we investigated the LMNA-R482L mutation-specific alterations in a transgenic mouse C2C12 cell line of myoblasts. Using single-cell RNA sequencing we have studied transcriptional diversity of cultured in vitro C2C12 cells. The LMNA-R482L mutation induces changes in C2C12 cluster composition and increases the expression of genes related to connective tissue development, oxidative stress, stress defense, and autophagy in a population-specific manner. Bulk RNA-seq confirmed these results and revealed the dysregulation of carbohydrate metabolism in differentiated R482L myotubes that was supported by ATP production profile evaluation. The measurement of reactive oxygen species (ROS) levels and glutathione accumulation in myoblasts and myotubes indicates R482L mutation-related dysregulation in mechanisms that control ROS production and scavenging through antioxidant glutathione system. The increased accumulation of autophagy-related structures in R482L myoblasts was also shown. Overall, our experiments showed a connection between the redox status and metabolic alterations with skeletal muscle pathological phenotypes in cells bearing pathogenic LMNA mutation.
Polynomial modelling of high-quality yet incomplete rare earth element data sets and a holistic assessment of REE anomalies
Authors: Ernst David M. , Vogt Joachim , Bau Michael , Mues Malte
Published: February 2025

Rare earth elements (REEs) are powerful proxies used in many (bio-)geochemical studies. Interpretation of REE data relies on normalised REE patterns and anomaly quantification, and requires complete data. Therefore, older, high-quality REE data determined by neutron activation or isotope dilution methods are often ignored, as they did not provide complete data. Similarly, modern analytical data can lack certain REEs due to quantification limits, interferences or usage of REE spikes. However, such data may be the only information available since sample material was consumed, sample locations became inaccessible, or samples represent past states of a dynamic natural system. Therefore, the ability to impute such high-quality data is of value for many geoscientific sub-disciplines. We use a polynomial modelling approach to impute missing REE data, verify the method’s applicability with a large data set (>13,000 samples; PetDB), and complement three originally incomplete REE data sets. Good fitting results (SD <6%) are supported by Monte Carlo simulations for assessing the model uncertainties (± 12%). Additionally, we provide a procedure to quantify REE anomalies, including uncertainties, which were usually not determined in the past but are essential for scientific comparison of REE anomaly data between different data sets. All Python scripts are provided.
Numerical investigation of high-temperature proton exchange membrane fuel cell conductivity at different parameters
Authors: Samir A. , Maowwad M. S. , Farahat M. A. , Talaat M.
Published: February 2025

This study uses the finite element technique to analyse a multi-dimensional model for a polyelectrolyte membrane fuel cell at high working temperature. A computational fluid dynamics (CFD) technique implements and solves this model. In addition, the membrane’s thickness, and catalyst layer’s thickness parameters have been studied. Membrane thickness is varied from to and the length of the fuel cell from to. The performance of the fuel cell was studied, analysed, and discussed for each case using the polarization curves and output power. The results indicate that the performance of fuel cells is enhanced by a thinner membrane than a thicker one with an increase in loading. The performance is approximated at light loads. Furthermore, the concentration of water at the cathode side of the fuel cell is highly affected by the change in fuel cell length more than the thickness of the membrane. Comparative analysis with prior research demonstrates strong agreement with our consequences.
Hyperspectral imaging suggests potential for rapid quantification of fission products in spent nuclear fuel
Authors: Dunphy R. David , Parker Andrew J. , Bandala Manuel , Bennet Stuart , Boxall Colin , Chard Patrick , Cockbain Neil , Eaves David , Goddard Dave , Ma Xiandong , Taylor C. James , Wilbraham Richard , Zabalza Jaime , Murray Paul , Joyce Malcolm J.
Published: February 2025

An analysis of sintered uranium dioxide has been conducted using a hyperspectral camera sensitive to short-wave infrared wavelengths in the range 949–2472 nm. Three groups of sintered UO2 nuclear fuel pellets were prepared and analysed, with stable sub-group surrogates introduced at the preparation stage to emulate the presence of fission product elements. Results show a clear, consistent, and reproducible spectral response across the pellet groups for pure UO2. Furthermore, the addition of fission product elements is observed to affect the shortwave infrared response, causing an overall flattening of the spectra. We have shown that this spectral change is correlated significantly with the presence of lanthanides in the fuel matrix. This result could have important potential in post-irradiation examination for quantifying nuclear fuel burn-up and radiotoxicity at discharge, as the hyperspectral imaging setup allows multiple (> 20) samples to be analysed in a single image, captured in under 30 s.
A comprehensive and quantitative SEM–EDS analytical process applied to lithium-ion battery electrodes
Authors: Kato Teruki , Goto Kunihiro , Niwa Takahiro , Shimizu Tsukasa , Fujii Akinobu , Okumura Bunyo , Oka Hideaki , Kadoura Hiroaki
Published: February 2025

The combination of scanning electron microscopy (SEM) images and energy-dispersive X-ray spectroscopy (EDS) maps (SEM–EDS analysis) enables the analysis of the relationship between the microstructures and elemental compositions of the surfaces of materials. However, conventional SEM–EDS analyses lack comprehensiveness and quantitativeness, resulting in potential inaccuracies in reflecting the properties of the entire sample and variations in the results depending on the analyst. Therefore, herein, we propose an objective SEM–EDS analytical process that addresses the aforementioned issues. Comprehensiveness was addressed by acquiring large volumes of SEM images through automated capturing, whereas quantitativeness was addressed through microstructural analysis of the SEM images based on image features, model-based dimension reduction and clustering methods, and similarity analysis of the elemental distribution in EDS maps based on statistical distances. The proposed method was used to analyze the degradation of lithium-ion battery electrodes, affording objective results that align with subjective insights into the changes in the morphology and composition of solid electrolyte interphase (SEI) films accompanying degradation.
Coordinating multiple mental faculties during learning
Authors: Luo Xiaoliang , Mok Robert M. , Roads Brett D. , Love Bradley C.
Published: February 2025

Complex behavior is supported by the coordination of multiple brain regions. How do brain regions coordinate absent a homunculus? We propose coordination is achieved by a controller-peripheral architecture in which peripherals (e.g., the ventral visual stream) aim to supply needed inputs to their controllers (e.g., the hippocampus and prefrontal cortex) while expending minimal resources. We developed a formal model within this framework to address how multiple brain regions coordinate to support rapid learning from a few example images. The model captured how higher-level activity in the controller shaped lower-level visual representations, affecting their precision and sparsity in a manner that paralleled brain measures. In particular, the peripheral encoded visual information to the extent needed to support the smooth operation of the controller. Alternative models optimized by gradient descent irrespective of architectural constraints could not account for human behavior or brain responses, and, typical of standard deep learning approaches, were unstable trial-by-trial learners. While previous work offered accounts of specific faculties, such as perception, attention, and learning, the controller-peripheral approach is a step toward addressing next generation questions concerning how multiple faculties coordinate.
SNORD80-guided 2’-O-methylation stabilizes the lncRNA GAS5 to regulate cellular stress responses
Authors: Xu Liang , Zhao Xiao Hong , Zhang Yuan Yuan , Zhang Meng Yao , Zhang Long Yue , Ye Kai Hong , Teng Liu , Han Man Man , Yue Yi Meng , Yang Jiezhen , Ogle Rachel , Netherton Jacob , Tang Deng , Lan Siqi , Baker Mark , Ye Yan , Liu Tao , Wang Yu Fang , Zhang Xu Dong , Fan Tianli , Jin Lei
Published: February 2025

The introns of the gene encoding the long noncoding RNA (lncRNA) GAS5 host up to 10 C/D box small nucleolar RNAs (snoRNAs). However, whether there is a regulatory and functional relationship between these snoRNAs and GAS5 is unknown. Here, we show that the expression of SNORD80, but not the other snoRNAs, parallels GAS5 expression and is regulated alongside GAS5 in response to cellular stress. The 2′-O-methylation at the A496 site, located within a segment of GAS5 complementing the conserved RNA-binding region on SNORD80, promotes GAS5 stability and consequent upregulation. This methylation requires SNORD80, as it is diminished by knockdown of SNORD80 and increased by SNORD80 overexpression, similar to the effects of manipulating the expression of fibrillarin, the methyltransferase of the box C/D small nucleolar ribonucleoprotein particle (snoRNP). The upregulation of SNORD80 in response to cellular stress is due to an enhancement in its stability, which is associated with an increase in its interaction with fibrillarin. Collectively, these results identify a role for SNORD80 in guiding 2′-O-methylation to stabilize GAS5. This uncovers a feedforward regulatory loop at the
GAS5
gene locus in response to cellular stress and sheds light on posttranscriptional mechanisms governing lncRNA expression.
Single-cell copy number calling and event history reconstruction
Authors: Kuipers Jack , Anıl Tuncel Mustafa , Ferreira Pedro F , Jahn Katharina , Beerenwinkel Niko
Published: February 2025

Motivation

Copy number alterations are driving forces of tumour development and the emergence of intra-tumour heterogeneity. A comprehensive picture of these genomic aberrations is therefore essential for the development of personalised and precise cancer diagnostics and therapies. Single-cell sequencing offers the highest resolution for copy number profiling down to the level of individual cells. Recent high-throughput protocols allow for the processing of hundreds of cells through shallow whole-genome DNA sequencing. The resulting low read-depth data poses substantial statistical and computational challenges to the identification of copy number alterations.

Results

We developed SCICoNE, a statistical model and MCMC algorithm tailored to single-cell copy number profiling from shallow whole-genome DNA sequencing data. SCICoNE reconstructs the history of copy number events in the tumour and uses these evolutionary relationships to identify the copy number profiles of the individual cells. We show the accuracy of this approach in evaluations on simulated data and demonstrate its practicability in applications to two breast cancer samples from different sequencing protocols.

Availability

SCICoNE is available at https://github.com/cbg-ethz/SCICoNE.

Supplementary information

Supplementary data are available at Bioinformatics online.
Beyond methane consumption: “Exploring the potential of methanotrophic bacteria to produce secondary metabolites
Authors: Krause Sascha M B , van den Berg Naomi Iris , Brenzinger Kristof , Zweers Hans , Bodelier Paul L E
Published: February 2025

Microbial methane-consuming communities significantly impact biogeochemical processes and greenhouse gas emissions. In this study we explored secondary metabolites produced by methane-oxidizing bacteria (MOB) and their ecological roles. We analyzed volatile profiles of four MOB strains under controlled conditions and conducted a meta-analysis using high-quality genomes from 62 cultured MOB strains and 289 metagenome-assembled genomes to investigate their potential for producing secondary metabolites. Results show species-specific volatile production, such as germacrene by Methylobacter luteus, which may play a role in the regulation of environmental methane consumption. The meta-analysis revealed that biosynthetic gene clusters (BGCs) for terpenes and betalactones were more prevalent in the Methylocystaceae and/or Beijerinckiaceae families, while aryl polyene BGCs were dominant in the Methylococcaceae family, reflecting habitat-specific adaptations. These findings advance our understanding of the metabolic capabilities of MOB and underscore the importance of integrating experimental data with genomic and metabolomic analyses to elucidate their ecology, environmental interactions, and contributions to methane cycling.
Electrical stimulation attenuates muscle atrophy induced by brachial plexus injury via upregulating HO-1 expression in rats
Authors: Qin Hongjiu , Du Xing , Hu Bin , Ma Tao
Published: February 2025

Background:

In cases of global brachial plexus injury, long-term denervation results in severe muscle atrophy in the hand. This study was conducted to investigate the protective effect of electrical stimulation (ES) on denervated intrinsic forepaw muscle (IFM) induced by global brachial plexus avulsion (GBPA) in rats, and whether heme oxygenase-1 (HO-1) is involved in the effect of ES on denervated IFM atrophy.

Methods:

We established a GBPA rat model and denervated IFM was electrically stimulated at different frequencies (2, 10 and 20 Hz). Muscle fiber cross-sectional area, capillary supply and muscular HO-1 protein level were measured. Additionally, the expression of HO-1 was locally blocked by injecting the siRNA into IFM to determine the possible role of HO-1 in ES antiatrophic effect. Several key regulators of muscle protein synthesis and degradation were determined.

Results:

All the stimulation protocols were able to ameliorate muscle capillary loss after denervation. ES at 20 Hz significantly attenuated denervated IFM atrophy. The protective effects of ES were markedly weakened by local injection of the HO-1 siRNA. Meanwhile, the expressions of MuRF-1, MAFbx, BNIP3 and LC3B-II/I ratio were upregulated by denervation, whereas ES treatment attenuated the increment. Low muscular HO-1 level almost completely suppressed the ability of ES to inhibit the hydrolysis activity of autophagy-lysosomal pathway.

Conclusion:

ES at 20 Hz, using a clinically translatable protocol, is recommended to delay denervated IFM atrophy. Activation of HO-1 is an important mechanism involved in the protective effects of ES against denervation-related muscle atrophy.

Clinical relevance statement:

Muscular HO-1 may be a potential molecular marker for the instruction and optimization of stimulus settings. Muscle-targeted upregulation of HO-1 may be a promising strategy for retarding denervation-related muscle atrophy.
The Effects of Orbicularis Muscle and Suborbicularis Fat Fixation in Subbrow Blepharoplasty
Authors: Hu Xiaogen , Wang Chengyuan
Published: February 2025

Background:

Subbrow blepharoplasty has become popular in Asian populations for redundant skin and lateral hooding in the upper lid. How to imrpove the effects of the procedure becomes urgent.

Objective:

To investigate the effects of orbicularis muscle and suborbicularis fat fixation in subbrow blepharoplasty.

Methods:

This was a retrospective study. Thirty-eight patients were subjected to the operation from January 2018 to June 2024. All patients had dermatochalasis and lateral hooding of the upper eyelid. In the procedure of subbrow blepharoplasty, the orbicularis muscle flap in combination of the suborbicularis fat was pulled up and fixed to the periosteum over the suraorbital rim. The follow-up period ranged from 6 months to 2 years. The results were evaluated. The complications were reviewed.

Results:

The resection of skin was 12.2±1.9 mm in width. The length of subbrow skin excised was 39.4±4.4 mm. The height correction of the brow descending was 2.8±1.0 mm at the midpupil line and 3.8±1.0 mm at the lateral canthus line. The operative time of both sides was about 50 minutes. Thirty-seven patients (97.4%) were satisfied with the surgical results, 1 patient (2.6%) complained about slight asymmetry. There was no serious complications related to surgery.

Conclusions:

Subbrow blepharoplasty incorporated with orbicularis muscle and suborbicularis fat fixation is reliable with high patient satisfaction in the patients with dermatochalasis and lateral hooding of the upper eyelid.
Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture
Authors: Nadour Malika , Valette Reveno Leatis Robert I. , Biard Marie , Frébault Noémie , Rivollet Lise , St-Louis Philippe , Blanchette Cassandra R. , Thackeray Andrea , Perrat Paola , Bevilacqua Carlo , Prevedel Robert , Cappadocia Laurent , Rapti Georgia , Doitsidou Maria , Bénard Claire Y.
Published: February 2025

Neuronal architecture established embryonically must persist lifelong to ensure normal brain function. However, little is understood about the mechanisms behind the long-term maintenance of neuronal organization. To uncover maintenance mechanisms, we performed a suppressor screen insax-7/L1CAMmutants, which exhibit progressive disorganization with age. We identified the conserved extracellular matrix protein MIG-6/papilin as a key regulator of neuronal maintenance. Combining incisive molecular genetics, structural predictions,in vivoquantitative imaging, and cutting-edge Brillouin microscopy, we show that MIG-6/papilin remodels extracellular matrix collagen IV, working in concert with the secreted enzymes MIG-17/ADAMTS and PXN-2/peroxidasin. This remodeling impacts tissue biomechanics and ensures neuronal stability, even under increased mechanical stress. Our findings highlight an extracellular mechanism by which MIG-6/papilin supports the integrity of neuronal architecture throughout life. This work provides critical insights into the molecular basis of sustaining neuronal architecture and offers a foundation for understanding age-related and neurodegenerative disorders.
Electric dipole polarizability of
Ni58
Authors: Brandherm I. , Bonaiti F. , von Neumann-Cosel P. , Bacca S. , Colò G. , Jansen G. R. , Li Z. Z. , Matsubara H. , Niu Y. F. , Reinhard P.-G. , Richter A. , Roca-Maza X. , Tamii A.
Published: February 2025

The electric dipole strength distribution in Ni58 between 6 and 20 MeV has been determined from proton inelastic scattering experiments at very forward angles at RCNP, Osaka. The experimental data are rather well reproduced by quasiparticle random-phase approximation calculations including vibration coupling, despite a mild dependence on the adopted Skyrme interaction. They allow an estimate of the experimentally inaccessible high-energy contribution above 20 MeV, leading to an electric dipole polarizability αD(Ni58)=3.48(31)fm3. This serves as a test case for recent extensions of coupled-cluster calculations with chiral effective field theory interactions to nuclei with two nucleons on top of a closed-shell system.

Published by the American Physical Society
2025
Philosophical and practical dimensions of Gramsci’s conjunctural analysis: a contribution to case study research
Authors: Gürcan Efe Can , Otero Gerardo
Published: February 2025

Purpose

This article employs interpretive conceptual analysis to provide a coherent research philosophy and practical insights for conjunctural analysis as a Marxist alternative to traditional case study methods. How can Gramsci’s writings inform our understanding of research philosophy? How does this philosophy shape his own method as applied to the case of the French Revolution?

Design/methodology/approach

Gramsci’s methodology is based on a dynamic and agentive understanding of what he calls “organized matter,” which is supplemented with a historicist epistemology. His philosophy brings to the fore the notion of “reciprocity” rather than mere causation and prioritizes the study of “regularities,” as opposed to fixed and universal laws. It incorporates both structural forces and human agency as valid sources of knowledge.

Findings

Using the French Revolution as a case study, Gramsci applies these principles to conjunctural analysis by examining socioeconomic convulsions as pivotal moments that elucidate the interaction between organic movements – indicative of profound, long-term structural changes such as the ascent of the bourgeoisie, the consolidation of their political power, industrialization, capitalist development and the emergence of the modern nation-state – and conjunctural periods, which are triggered by immediate, specific events precipitating these extensive structural transformations.

Originality/value

This article fills an important gap in the literature, considering that previous research has not systematically addressed Gramsci’s contributions to research philosophy and his study of the French Revolution using conjunctural analysis.
Robustness Optimization of the Tip Seat of an Indexable Cutting Tool
Authors: Camuz Soner , Liljerehn Anders , Lindkvist Lars , Wärmefjord Kristina , Söderberg Rikard
Published: February 2025

In the machining industry, fixturing of indexable inserts in the tool holders play a critical role in ensuring high-quality outcomes by minimizing insert movement during operations. Ensuring consistent pressure distribution in an indexable cutting tool interface is essential for extending the lifespan of a carbide insert. However, existing methods either lack the necessary complexity to accommodate varying loads or are overly intricate for implementation in the early stages of product development. To address this gap, a novel approach was developed that integrates the contact index algorithm into a robust locating scheme optimization. The results show that it is possible to design an indexable cutting tool where clearly defined contacting points (half-spheres) can support and maintain minimal movement in an indexable insert during its expected lifetime.
Generalization of q‐Integral Inequalities for (α, ℏ − m)‐Convex Functions and Their Refinements
Authors: Egami Ria H. , Bibi Waseela , Younis B. A. , Farid Ghulam , Ali Mohammed
Published: February 2025

This article finds q‐ and h‐integral inequalities in implicit form for generalized convex functions. We apply the definition of q − h‐integrals to establish some new unified inequalities for a class of (α, ℏ − m)‐convex functions. Refinements of these inequalities are given by applying a class of strongly (α, ℏ − m)‐convex functions. Several q‐integral inequalities for various kinds of convex and strongly convex functions are deduced under specific conditions.
Critical appraisal tool for homeopathic intervention studies – CATHIS
Authors: Gaertner Katharina , Hahn Robert G. , Razlog Radmila , Musial Frauke , Baumgartner Stephan , Loef Martin , Walach Harald
Published: February 2025

Background: The quality of homeopathic research studies is controversially discussed. In order to improve the overall assessment of homeopathic studies and subsequently facilitate evidence-based clinical decision-making, we aimed to combine methodological tools for scientific rigor with tools for external and model validity into one global tool.
Method: Against the background of previous literature and the results of a preparatory survey, a first draft of a potential overarching tool was presented to an expert panel. Then, Delphi feedback rounds were conducted to elicit responses on the feasibility. The resulting preliminary tool was pilot-tested by five research experts on five randomly selected studies. After further optimization another five studies were assessed by the same experts and another three experts tested the second version. The ratings were tested for interrater-reliability using Gwet’s AC2.
Results: The appraisal tool comprises four domains. These are the assessment of risk-of-bias (1) using the Cochrane Tool, the studies’ credibility (2) including the CONSORT statement and its extension on homeopathy, the study interventions’ coherence (3) with homeopathic textbooks and previous research, and of the studies’ clinical relevance (4). Each domain is assessed using a point system, which is then added up to an overall score. The instrument was evaluated as useful and “easy to apply” by the raters. The interrater reliability was 0.81 (95% CI 0.75 to 0.88) for five raters, and 0.64 (95% CI 0.49 to 0.79) for additional three raters in round 2, signifying good to moderate interrater reliability.
Conclusion: We have developed an applicable and reliable assessment tool for homeopathic intervention studies. Using it in systematic reviews and meta-analyses will increase their scientific value.
Characterization of ferroptosis-related genes in aplastic anaemia: an integrated analysis of bulk and single-cell RNA sequencing data
Authors: Shen Chuyun , Wang Fengming
Published: February 2025

Introduction: Ferroptosis offers novel perspectives for treating multiple blood-related diseases, yet its role in aplastic anaemia (AA) is rare. This study aimed to explore key ferroptosis-related genes (FRGs) in AA using bulk and single-cell RNA sequencing (scRNA-seq) data.
Methods: scRNA-seq and bulk RNA-seq data, along with FRG lists, were obtained from public databases. Differentially expressed FRGs (DEFRGs) between AA and control samples were identified, followed by functional enrichment and protein–protein interaction analyses. Single-cell analyses were conducted to reveal cell types in samples and DEFRGs activity in each cell was assessed. Moreover, DEGs between AA and control samples at the cellular level were explored, followed by integration with DEFRGs to determine common key genes. The KEGG pathway analysis of these genes was performed at the cellular level. Immune infiltration analysis evaluated the relationship between key genes and immune cells.
Results: A total of 38 DEFRGs were identified, enriched in pathways such as the intrinsic apoptotic signalling pathway. scRNA-seq analysis identified seven cell types, with elevated DEFRGs activity in platelets and stromal cells. Key genes DDIT4 and NCF2, identified through integrated analysis, were involved in autophagy, mTOR signalling, and osteoclast differentiation pathways, with their expression positively correlated with activated dendritic cells, in AA samples.
Conclusion: Our findings highlight the roles of DDIT4 and NCF2, in AA progression, providing potential insights for further mechanistic exploration of AA.
WHEN AND HOW IS SURGERY REQUIRED FOR LARGE ENDOMETRIOMA PRIOR TO IN VITRO FERTILIZATION (IVF): A SURVEY OF PRACTICES
Authors: Vibert Jonas Jean Mathieu , Alec Milena , Laganà Antonio Simone , Benagiano Giuseppe , Pluchino Nicola
Published: February 2025

Introduction: Proper management of large endometriomas in patients scheduled for IVF continues to be a matter of debate. While small endometriomas are no longer an absolute indication for surgery, the large ones present unique challenges, potentially impacting ovarian response and follicle accessibility. This study aims to evaluate current practices among gynecologists in managing large endometriomas before IVF.
Methodology: An online survey with 18 questions was distributed to gynecologists through various professional societies. The survey addressed their clinical experience, type of practice, threshold size for surgery, surgical techniques used, hormonal treatment protocols, and the timing of ovarian stimulation post-surgery. Data were collected anonymously and analyzed using SPSS 29.0.2.0.
Results: Of the 111 respondents, 73% practiced in academic settings, and 61% had over 15 years of experience. Laparoscopic cystectomy was the most common procedure (48.2%). The median threshold size for surgery was 50 mm (IQR 40–60). Despite the same median threshold, surgeons performing laparoscopic surgery as their main clinical activity had a significantly different distribution of thresholds (IQR 40–60 vs. 47–89, p = 0.006), with a tendency to recommend surgery for smaller endometriomas. Techniques like CO2 laser ablation and plasma energy were less commonly used. Notably, 40.5% of participants indicated they would change their practice if a CO2 laser or plasma energy device were available in their surgical armamentarium. Most participants (67.9%) adjusted their strategy based on pre-operative AMH levels. The average timing for IVF stimulation post-surgery was 6 weeks(IQR 4-8) with no difference across different experiences.
Conclusion: Managing large endometriomas before IVF involves balancing surgical benefits with risks to ovarian reserve. The survey highlights significant variability in practices, with a median surgical threshold size of 50 mm. Laparoscopic cystectomy, while common, is associated with ovarian tissue loss, whereas emerging techniques like CO2 laser ablation show promise in preserving ovarian reserve. The need for up-to-date evidence-based guidelines is essential to standardize practices and optimize outcomes for IVF patients.
The Efficacy of Ultrasound-Guided Selective Nerve Block in the Endovascular Treatment of Arteriovenous Fistulas
Authors: Wen Jing , Zhan Shen , Wang Yu-zhu , Zhang Li-hong , Li Han
Published: February 2025

Introduction Delivering requisite anesthesia for endovascular treatment of dysfunctional arteriovenous fistulas (AVFs) under a targeted nerve block can achieve reasonable analgesia. We evaluated the efficacy and safety of ultrasound-guided selective nerve block during percutaneous transluminal angioplasty (PTA) of dysfunctional arteriovenous access.
Methods 246 patients with dysfunctional radiocephalic arteriovenous fistula undergoing PTA were enrolled in this prospective, randomized controlled trial at the Department of Nephrology, Haidian Hospital, Peking University Third Hospital from June 1, 2022 to August 31, 2023. The patients were randomized into either the selective nerve block group (SNB group, n=123) or the local anesthesia group (LA group, n=123) . A visual analogue scale(VAS) from no pain (= 0) to worst pain possible (= 10) was used to assess the pain intensity. Patient and operator satisfaction were graded from 0 to 2: 0, not satisfied at all; 1, partially satisfied; 2, satisfied. The arteriovenous fistula patency at 1 and 3 months after PTA was also evaluated.
Results Compared with the local anesthesia group, the selective nerve block group had significantly lower VAS scores (Z = -7.193, p < 0.001) and required fewer additional anesthetics during the operation (² = -4.847, p = 0.028). Patient and operator satisfaction were significantly higher in the selective nerve block group (p < 0.05). Eight patients in the selective nerve block group encountered grade 3 motor paralysis after the operation and they all recovered within 60 minutes. There was no significant difference in primary patency rates of the fistula between the two groups either at 1 month or 3 months after the operation (p > 0.05).
Conclusion Compared with local anesthesia, ultrasound-guided selective nerve block has advantages over the local anesthesia during endovascular treatment of dysfunctional hemodialysis fistulas. It can provide safe and efficient analgesia with excellent procedural satisfaction in hemodialysis patients.
Management of Neonatal Severe Hyperparathyroidism Due to Homozygous CASR Mutation: Challenges and Literature Insights
Authors: Karakaş Hasan , Aksakal Nihat , Tarçın Gürkan , Çolakoğlu Ahsen , Bayram Mehmet Emre , Velioğlu Haşlak Gökçe , Uçar Mert , Altun İlayda , Bingöl Aydın Dilek , Turan Hande , Bayramoğlu Elvan , Evliyaoğlu Olcay
Published: February 2025

Introduction: Neonatal severe hyperparathyroidism (NSHPT) is a rare but life-threatening disorder caused by inactivating variants in the calcium-sensing receptor (CaSR), resulting in severe hypercalcemia during the neonatal period. Infants with NSHPT may present with severe hypercalcemia, hyperparathyroidism, growth retardation, and respiratory distress. If untreated, NSHPT can lead to life-threatening complications. Due to its rarity, few cases have been reported in the literature.
Case presentation: A 4-day-old girl presented with jaundice, weight loss, and hypercalcemia (16 mg/dL). On physical examination, she appeared dehydrated, hypotonic, and had facial dysmorphisms. Laboratory results revealed markedly elevated parathyroid hormone (PTH) levels (1769 pg/mL) and low urinary calcium excretion. Despite initial treatment with hydration and furosemide, her hypercalcemia persisted. Cinacalcet was started but failed to control calcium levels, leading to the need for a subtotal parathyroidectomy at 2.5 months of age. Genetic testing identified a homozygous mutation in the CASR gene (p.Met741LeufsTer24). Postoperatively, the patient developed hypocalcemia due to hungry bone syndrome and later experienced recurrent hypercalcemia, which was managed with pamidronate followed by calcitriol. At 21 months of age, she remains normocalcemic on daily calcitriol.
Conclusion: This case highlights the challenges in managing NSHPT, especially in cases resistant to medical treatment. Subtotal parathyroidectomy proved essential for controlling hypercalcemia. Continued documentation of NSHPT cases will help improve treatment strategies and outcomes for this rare condition.
Electrocardiographic markers in Motoric Cognitive Risk syndrome
Authors: Verghese Joe , Sreeram Sharika , Joseph Vijin , Adhikari Dristi , Sigamani Alben , Blumen Helena M. , Kumar V. G. Pradeep , Ayers Emmeline
Published: February 2025

Introduction: Presence of cardiovascular disease is linked to the prevalence and incidence of Motoric Cognitive Risk syndrome (MCR), a pre-dementia syndrome characterized by cognitive complaints and slow gait. Electrocardiograms (ECGs) may offer a cost-effective, non-invasive, and reliable method for detecting cardiovascular abnormalities in individuals with MCR. This approach can not only diagnose cardiovascular disease but also facilitate timely interventions to prevent further cognitive decline in MCR cases.
Methods: We examined the association of ECG abnormalities with prevalent MCR in 451 older adults with ECGs participating in the Kerala Einstein Study (KES), based in Indian state of Kerala. Logistic regression analysis adjusted for age and sex were used to examine associations, and reported as odds ratios (OR) with 95% confidence intervals (CI).
Results: ECG abnormalities were present in 191 (42.4%) participants. Of the 43 participants diagnosed with MCR, 23 (53.5%) had ECG abnormalities. Abnormal Q waves (OR 5.1, 95% CI 1.7-14.9) and heart block (OR 6.0, 95% CI 2.1-17.4) were more common in individuals with MCR compared to controls. There were no statistically significant group differences in the prevalence of other ECG abnormalities.
Conclusion: ECG abnormalities are common in MCR patients, and can be considered for cardiovascular disease risk-stratification in MCR cases.
Impact of an App-Based Resilience Training on Enhancing Stress Regulation and Mental Health
Authors: Lenger Melanie , Schönthaler Elena M.D. , Hantke Alina , Dalkner Nina , Guggemos Suher , Pszeida Martin , Mosbacher Jochen A. , Draxler Sandra , Lutz Thomas , Russegger Silvia , Nateqi Jama , Albert Dietrich , Paletta Lucas , Reininghaus Eva Z.
Published: February 2025

Introduction. Recent research suggests various app-based-programs to promote mental health, resilience and stress management. Insights gained from studies with healthy participants could potentially offer training strategies that could also prove beneficial for people with mental disorders. The effectiveness of an app-based resilience-training was evaluated. Methods. In the present study, 68 mentally healthy participants were included. They all received both the intervention as two-month resilience training via an app and the control condition (waiting group) as part of a cross-over design. In addition, the participants were interviewed before, and after each condition with the Stress and Coping Inventory (SCI), the Brief Symptom Inventory (BSI) and the Resilience Scale (RS13), measuring psychological stress and symptoms. Results. The results of the ANCOVA indicate that the app-training does not significantly improve resilience in healthy people (p = .278). However, it significantly enhances stress regulation in the intervention group and the control group (p = .030), independent of the initial stress level. Furthermore, a significant positive correlation was found between effective stress regulation and improved mental health (measured by the BSI). Conclusion. Emphasizing mindfulness and reflection through resilience training and the enhanced perception of mental health, can improve stress regulation, thereby underscoring its crucial role. To maximize the benefits of resilience training, it is imperative to further develop training apps, enhancing their attractiveness and suitability for long-term use, and extend its use. Future work should focus on refining these interventions to ensure sustained engagement and effectiveness.
Choroidal Thickening and Outer Retinal Alterations in Vitamin A Deficiency – A Case Report
Authors: Jaggi Damian , Lincke Joel-Benjamin , Heussen Florian M. , Unterlauft Jan D. , Zinkernagel Martin S. , Berger Lieselotte E.
Published: February 2025

Purpose:
The purpose of this study was to report a case of retinal alterations due to proven Vitamin A deficiency.
Methods:
We report a case of a 39-year-old woman who presented with progressing nyctalopia and mildly reduced visual acuity over a period of 1-2 years, despite being on oral Vitamin A supplementation, following a history of gastric bypass and biliopancreatic diversion surgeries many years ago.
Results:
Vitamin A levels were severely reduced (<0.1 µmol/L, reference range: 1.05–2.08 µmol/L). The outer retinal layers exhibited structural alterations and a reduction in thickness, while choroidal thickness was increased. The electroretinogram showed complete depletion of scotopic responses and a mild reduction in photopic responses. After intravenous Vitamin A supplementation, complete resolution of both functional and structural changes was achieved.
Conclusion:
This case highlights the importance of considering Vitamin A deficiency even in patients receiving ongoing oral Vitamin A supplementation, particularly if symptoms and clinical findings suggest its presence. Choroidal thickening and outer retinal thinning may provide further insights into the pathophysiology of this condition in future analyses.
Membranoproliferative glomerulonephritis with striated ultrastructural deposits with significantly elevated fibrinogen and fibronectin on mass spectrometry analysis: A case report and literature review
Authors: Ishida Manna , Yamamoto Shinya , Iwashige Yohei , Miyazawa Shuma , Nakata Hirosuke , Koichi Seta , Yahata Kensei , Minamiguchi Sachiko , Endo Yoko , Mii Akiko , Shimizu Akira , Yanagita Motoko
Published: February 2025

Glomerular diseases with organized deposits can be classified into various etiologies. A diagnostic algorithm based on clinical and pathological findings has been proposed. However, some cases cannot be diagnosed using existing algorithms. Here, we report the case of a 77-year-old man diagnosed with membranoproliferative glomerulonephritis (MPGN) with striated ultrastructural deposits, microfilament-like substructures with straight bands arranged in parallel in the subendothelial space by two sequential renal biopsies. His examinations and clinical findings were incompatible with known glomerular diseases with organized deposits. Dialysis was initiated 10 months after the second biopsy procedure. Furthermore, we report the first mass spectrometry analysis of laser micro-dissected glomeruli with striated ultrastructural deposits, which revealed significant levels of fibrinogen and fibronectin. Immunostaining was positive for fibrinogen, fibrin, and fibronectin in the subendothelial space. These findings suggest that the deposits were composed of a fibrin-fibronectin complex, and that accumulation of these fibrin-fibronectin complexes possibly induced endothelial injury, leading to MPGN. We also reviewed the literature on the clinical and pathological characteristics of the four cases with striated ultrastructural deposits. Our investigation showed that all patients had the MPGN pattern and striated ultrastructural deposits in the subendothelial space, and all underwent hemodialysis within 3 years after renal biopsy. Clinicians should be aware of the findings of glomerulonephritis with striated ultrastructural deposits since this disease may be a new entity and has a poor prognosis.