bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Characteristics of Flocs Produced via Leachate Electrocoagulation using Stationary and Vibration Electrode Plates
Authors: Tarmizi Tasnim , Muhammad Niza Ir Dr Noorzalila
Published: December 2024

The microbubbles produced during electrocoagulation (EC) are important as they attract colloids, destabilise to flocculate, and carry them up to the surface, where they can be easily removed. The structure of the flocs continuously changes throughout the different stages of flocculation. Therefore, although the mechanisms of electrolytic microbubble adhesion and flotation warrant closer examination, not many studies have examined them. As such, the present study compared the structure and chemical composition of flocs formed via EC with stationary electrode plates (SEPs) and vibrating electrode plates (VEPs) under constant parameters of current intensity (CI)=4.5A, reaction time (t)=50 minutes, pH=5, VEPs=2.8V, and SEPs=0V. Scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, and fourier transform infrared (FTIR) spectroscopy were used to compare the characteristics of the flocs’ structure. The SEM images provided detailed visualisations of the flocs’ morphology, specifically, that the structure of the flocs produced via VEPs were denser and more intricate. This could be because the higher mechanical energy was more effective at particle destabilisation and aggregation. The EDX results were significant for EC using VEPs and SEPs for carbon (C), oxygen (O), sodium (Na), chlorine (Cl), and potassium (K). Higher concentrations of aluminium (Al) were detected post-VEP as agitation helps the aggregated flocs to float to the surface of the solution. Lastly, the results of the FTIR analysis indicate the presence of functional groups related to organic and inorganic constituents in the leachate. In overall, this study is reported that VEPs undergoes better results in comparison to SEPs due to pollutant particles are easily to be removed by achieving optimum parameters has been applied in this study.
Perception on integrated energy services’ design and management among residents in China
Authors: Xiangyu Xu , Syadia Zainordin Nazatul , Hamzah Sharaai Amir , Nor Rahimah Nik Ab Rahim Nik
Published: December 2024

Integrated energy services (IES) in China provide the residents with efficient multiple energy supply services through safe and reliable design. The aim of this study is to determine Chinese residents’ perception on IES energy planning and design, as well as the operation and maintenance. By distributing questionnaires to 450 Chinese residents, socio-demographic data, and information on IES design and management were collected. Descriptive analysis was used to summarize the data, while the Mann-Whitney U analysis and Kruskal-Wallis analysis were conducted to identify significant differences between different groups. The results of the descriptive analysis show that residents generally agree with the energy services that IES providers should provide. However, in Tianjin, young people and middle-income residents hold neutral perceptions. The Mann-Whitney U and the Kruskal-Wallis analysis results show that there are significant differences in the perception of IES in gender, marital status, ages, occupations, and income salaries. Gender differences are reflected in the emphasis on the importance of residents  opinions in energy design and attention to the diverse needs of energy forms; differences in marital status and residents  differences in family life planning; age differences are reflected in the concern for the innovation and stability of energy services; occupational differences are reflected in concerns about the rationality and practicality of energy services; while income differences are mainly reflected in the need for a balance between affordability and quality of energy services. However, educational background did not significantly influence respondents  perceptions. Analyzing the perception of different residents on IES and the reasons behind differences can help IES providers improve the quality of energy services and provide residents with more efficient and reliable energy services.
Catalytic Efficiency of Calcium Oxide Catalyst doped with Magnesium in Biodiesel Transesterification from Recycled Cooking Oil
Authors: Zulkurnain Nursyamimi , Fathiah Ahmad Aisyah , Jamal Mat Rosid Salmiah , Azid Azman , Toemen Susilawati , Nazwanie Wan Abdullah Wan , Mat Rosid Sarina
Published: December 2024

The rising demand for alternative fuels due to the depletion of diesel oil has accelerated biodiesel production, primarily synthesized through base-catalyzed transesterification. In this study, recycled cooking oil was used as the feedstock, with an alumina-supported calcium oxide catalyst doped with magnesium (Ca/Mg/Al2O3), synthesized via the wet impregnation method, serving as the heterogeneous base catalyst. The catalyst optimization involved adjusting calcination temperatures, the dopant-to-base ratio, and reaction times. The optimal conditions were attained with a 10% Mg loading, calcined at 800°C, and a reaction time of one hour. Under these parameters, biodiesel yield reached 48.30%. XRD analysis revealed CaCO3 and MgAl2O4 as the active species on the catalyst surface, while FESEM analysis showed the catalyst’s irregular shape and particle aggregation, contributing to the yield. These findings suggest that the Ca/Mg (90:10)/Al2O3 catalyst is a promising heterogeneous base catalyst with significant potential for biodiesel production.
Seismic assessment of buildings constructed under previous generations of codes
Authors: Boshnakov Krasimir , Kardjiev Vasil
Published: December 2024

The primary engineering problem of seismic assessment of existing buildings constructed under previous codes is evaluating their capacitive behavior under seismic actions defined by the codes at construction time to define the rehabilitation necessity. The paper is focused on the methodological aspects of this process. Examples from the practice present the proposed workflow.
Simulating the Non-linear Bond Behaviour of Plain Rebar-Recycled Aggregate Concrete
Authors: Abdulahad Emad , Danhash Ghoson
Published: December 2024

The present research is interested in studying the plain rebar–recycled aggregate concrete bond behaviour, where the force-slip curve is obtained using the pull-out test. Five mixes were prepared, varying the replacement ratios of the natural aggregates with recycled ones: 0, 25, 50, 75, and 100%. The bond length of the rebar in the concrete was five times the rebar diameter. Fifteen pull-out specimens were cast with 14 [mm] steel plain rebar in the centre of the cubic specimen (150×150×150 mm), three specimens for each mix. The experimental procedure results showed the bond strength decreased, starting from 6% for 25% replacement ratio up to 23% for 100% replacement ratio. A numerical simulation of the pull-out test was performed using finite element method program (ABAQUS), and for describing the concrete behaviour, concrete damage plasticity was adopted in parallel with damage behaviour and cohesive behaviour for describing the interaction between rebar and recycled aggregate concrete. The cohesive behaviour of the rebar-recycled aggregate concrete interaction area was modelled using cohesive behaviour, where the parameters of the cohesive behaviour and the traction-separation behaviour were discussed for verifying the applicability of this property in predicting the rebar-recycled aggregate concrete bond behaviour. The force-slip curve obtained from the numerical simulation model exhibited good agreement with the experimental results.
Predicting the parameters of reinforced concrete elements by neural network
Authors: Yakov Vladimir , Hristov Petar
Published: December 2024

Obtaining predictive results at planning and conceptual design phase often represents a serious problem on which the choice of design options depends to a significant extent This paper seeks solutions to the problem using neural networks and artificial intelligence and illustrates the idea by simple examples of pre-trained neural network models.
Changes in daily stress reactivity and changes in physical health across 18 years of adulthood
Authors: Rush Jonathan , Charles Susan T , Willroth Emily C , Cerino Eric S , Piazza Jennifer R , Almeida David M
Published: December 2024

Background

Stress plays a pivotal role in physical health. Although many studies have linked stress reactivity (daily within-person associations between stress exposure and negative affect) to physical health outcomes, we know surprisingly little about how changes in stress reactivity are related to changes in physical health.

Purpose

The current study examines how change in stress reactivity over 18 years is related to changes in functional health and chronic health conditions.

Methods

Three measurement bursts from the National Study of Daily Experiences (N = 2880; 55% female) each included daily measures of stressor exposure and negative affect across 8 consecutive days, yielding 33 944 days of data across 18 years of adulthood. At each wave, participants reported their functional health limitations (ie, basic activities of daily living [ADL] and instrumental activities of daily living [IADL]) and chronic health conditions. Multilevel structural equation models simultaneously modeled stress reactivity at Level 1, longitudinal changes in stress reactivity at Level 2, and the association between changes in stress reactivity and changes in functional limitations and chronic conditions at Level 3.

Results

Higher levels of stress reactivity at baseline were associated with more functional health limitations 18 years later (ADLs: Est. = 0.90, P = .001; IADLs: Est. = 1.78, P < .001). Furthermore, individuals who increased more in their stress reactivity across the 18-year period also showed greater increases in their functional health limitations (ADLs: Est. = 4.02, P = .017; IADLs: Est. = 5.74, P < .001) and chronic conditions (Est. = 11.17, P = .008).

Conclusions

These findings highlight the strong connection between health and stress in daily life, and how they travel together across adulthood.
Coenzyme Q improves mitochondrial and muscle dysfunction caused by CUG expanded repeats in Caenorhabditis elegans
Authors: Teixeira Joana , Harju Anu-Mari , Othman Alaa , Eriksson Ove , Battersby Brendan J , Garcia Susana M D A
Published: December 2024

Expansion of nucleotide repeat sequences is associated with more than 40 human neuromuscular disorders. The different pathogenic mechanisms associated with the expression of nucleotide repeats are not well understood. We use a Caenorhabditis elegans model that expresses expanded CUG repeats only in cells of the body wall muscle and recapitulate muscle dysfunction and impaired organismal motility to identify the basis by which expression of RNA repeats is toxic to muscle function. Here, we performed 2 consecutive RNA interference screens and uncovered coenzyme Q metabolism and mitochondrial dysfunction as critical genetic modifiers of the motility phenotype. Furthermore, coenzyme Q supplementation reduced the toxic phenotypes, ameliorating the motility impairment and mitochondrial phenotypes. Together our data show how the expression of expanded RNA repeats can be toxic to mitochondrial homeostasis.
Employment responses to a partner’s disability onset (care shocks’): Do working conditions matter?
Authors: Beaufils Constance , Geiger Ben Baumberg , Glaser Karen
Published: December 2024

Objectives

This study examines employment responses to a partner’s disability onset and how this is moderated by working conditions: job satisfaction and psychosocial job demands.

Methods

We use longitudinal nationally representative data from the English Longitudinal Study of Aging. Following the health shock literature, we identify individuals whose partners report the onset of difficulties in activities of daily living (ADL) or instrumental activities of daily living (IADL) between two waves (n=1,020) as experiencing a ‘care shock’. We combine coarsened exact matching and entropy balancing, and logistic modelling to estimate the impact of such a ‘care shock’ on the probability of leaving paid work, working part-time, changing jobs, or looking for a new job. We also explore the moderating effect of gender and working conditions (i.e., job demands and job satisfaction) on the impact of a ‘care shock’ on work transitions

Results

Our findings show that ‘care shocks’ significantly increase individuals’ likelihood of leaving paid work. This effect is moderated by job demands and job satisfaction. Individuals who report high job demands and job dissatisfaction before the care shock are significantly more likely to leave paid work. In contrast, those with low job demands or job satisfaction show no significant difference in their likelihood of leaving paid work.

Discussion

Our study highlights the role of working conditions in moderating the impact of care shocks on paid work. It informs workplace policies, as our results suggest that adapting working conditions may facilitate participation in the labour market in late career stages.
A TAF11 variant contributes to non-syndromic cleft lip only through modulating neural crest cell migration
Authors: Li Dandan , Tian Yu , Vona Barbara , Yu Xin , Lin Junyan , Ma Lan , Lou Shu , Li Xiaofeng , Zhu Guirong , Wang Yuting , Du Mulong , Wang Lin , Pan Yongchu
Published: December 2024

The NC_000006.12: g.34887814C>G variant in TAF11 was identified as a potential functional variant in a Chinese pedigree including two non-syndromic cleft lip only (NSCLO) cases. Applying Chromatin Immunoprecipitation (ChIP), Electrophoretic mobility shift and super-shift assays, we found that the mutant G allele recruited more STAT1 and STAT3, and increased the expression of TAF11. RNA sequencing, GO and KEGG pathway enrichment, ChIP and dual-luciferase reporter assays revealed that TAF11 downregulated CDH1 and CTNND1 in the cell adhesion pathway by binding to their promoter regions and inhibiting transcriptional activities. Alcian blue staining, time-lapse photography, whole-mount in situ hybridization, phospho-Histone H3 immunofluorescence and TUNEL assays indicated that TAF11 and taf11 overexpression (TAF11OE and taf11OE, respectively) contributed to disturbed migration of cranial neural crest cells and abnormal craniofacial development, as well as increased death and deformity rates in zebrafish. In conclusion, a functionally relevant TAF11 variant, affecting cell migration via modulating CDH1 and CTNND1, was associated with etiology of NSCLO.
Combined Sequential Antiretroviral Therapy–Induced Immune Reconstitution Bone Loss and Estrogen Deficiency Bone Loss Are Cumulative in Mice Models
Authors: Dabeer Sadaf , Tripathi Ashish Kumar , Weiss Daiana , Vikulina Tatyana , Ofotokun Ighovwerha , Weitzmann M Neale
Published: December 2024

Background

Antiretroviral therapy causes osteoporosis and bone fractures, increasing morbidity and mortality in people with HIV (PWH). Antiretroviral therapy induces immune reconstitution bone loss (IRBL), an inflammatory reaction associated with immune system reactivation. Women represent >50% of PWH, and many are now undergoing menopause, a major cause of postmenopausal osteoporosis that also increases fracture risk. However, the interactions between IRBL and postmenopausal bone loss are poorly understood and were investigated in this study.

Methods

We used a mouse model of IRBL, which was applied simultaneously or sequentially with surgical ovariectomy (Ovx) as a mouse model of postmenopausal osteoporosis. Cortical and trabecular bone in vertebrae and femurs was assessed with micro–computed tomography, and bone turnover was quantified by serum markers of bone resorption and formation via enzyme-linked immunosorbent assay. T-cell production of osteoclastogenic cytokines was analyzed by flow cytometry.

Results

Although simultaneous Ovx and IRBL did not have additive effects, sequential Ovx and IRBL caused cumulative bone loss. Vertebral bone loss from combined Ovx and IRBL (Δ = −42.6 vs control, P < .01) was blunted by the anti-inflammatory agent abatacept (Δ = −13.9 vs control, not significant) and the probiotic Lactobacillus rhamnosus GG (Δ = −8.6 vs control, not significant). Both treatments reduced bone resorption, stimulated formation, and suppressed CD4+ T-cell production of the osteoclastogenic cytokines TNF-α and IL-17A.

Conclusions

Sequential IRBL and postmenopausal bone loss appear to be cumulative. If validated in humans, early screening and prophylaxis could reduce fracture risk in postmenopausal women with HIV. Probiotic therapy may provide a beneficial alternative to pharmacotherapy.
The Persian Translation of Śivapurāṇa and Eighteenth-Century North Indian Śaivism
Authors: Kotler Ayelet
Published: December 2024

This article examines the Persian translation of the Śivapurāṇa composed in 1730 by Kishan Singh ‘Nashat’. By historically contextualising Nashat’s life and work and closely reading the preface attached to the translation, this study sheds light on hitherto unexplored aspects of eighteenth-century Persianised Hindu scribal communities and their textual production on Hinduism. Against the backdrop of the emerging Persian Vaiṣṇava literature in the eighteenth century, Nashat’s Shiv Puran stands out in its Śaiva devotional sentiment. Through a careful examination of the translation against a range of Sanskrit sources and catalogues of Sanskrit manuscripts, this article further illuminates the muddled history of the textual transmission of the Śivapurāṇa in Sanskrit. Ultimately, this study shows that Persian translations produced by Hindus, outside of the Mughal courtly context, are a rich source for the study of popular Hinduism in the early modern period.
The nuclear sulfenome of Arabidopsis: spotlight on histone acetyltransferase GCN5 regulation through functional thiols
Authors: De Smet Barbara , Yang Xi , Plskova Zuzana , Castell Carmen , Fernández-Fernández Alvaro , Dard Avilien , Masood Jan , Mhamdi Amna , Huang Jingjing , Vertommen Didier , Chan Kai Xun , Pyr dit Ruys Sébastien , Messens Joris , Kerchev Pavel I , Van Breusegem Frank
Published: December 2024

In aerobic life forms, reactive oxygen species (ROS) are produced by the partial reduction of oxygen during energy-generating metabolic processes. In plants, ROS production increases during periods of both abiotic and biotic stress, severely overloading the antioxidant systems. Hydrogen peroxide (H2O2) plays a central role in cellular redox homeostasis and signaling by oxidising crucial cysteines to sulfenic acid, which is considered a biologically relevant post-translational modification (PTM). Until now, the impact of the nucleus on cellular redox homeostasis has been relatively unexplored. The regulation of histone-modifying enzymes by oxidative PTMs at redox-sensitive cysteine or tyrosine residues is particularly intriguing because it allows the integration of redox signaling mechanisms with chromatin control of transcriptional activity. One of the most extensively studied histone acetyltransferases is the conserved GENERAL CONTROL NONDEPRESSIBLE 5 (GCN5) complex. This study investigated the nuclear sulfenome in Arabidopsis thaliana by expressing a nuclear variant of the Yeast Activation Protein-1 (YAP1) probe and identified 225 potential redox-active proteins undergoing S-sulfenylation. Mass spectrometry analysis further confirmed the S-sulfenylation of GCN5 at cysteines 293, 368, and 400, and their functional significance and impact on the GCN5 protein-protein interaction network were assessed using cysteine-to-serine mutagenesis.
Machine learning-optimized targeted detection of alternative splicing
Authors: Yang Kevin , Islas Nathaniel , Jewell San , Wu Di , Jha Anupama , Radens Caleb M , Pleiss Jeffrey A , Lynch Kristen W , Barash Yoseph , Choi Peter S
Published: December 2024

RNA sequencing (RNA-seq) is widely adopted for transcriptome analysis but has inherent biases that hinder the comprehensive detection and quantification of alternative splicing. To address this, we present an efficient targeted RNA-seq method that greatly enriches for splicing-informative junction-spanning reads. Local splicing variation sequencing (LSV-seq) utilizes multiplexed reverse transcription from highly scalable pools of primers anchored near splicing events of interest. Primers are designed using Optimal Prime, a novel machine learning algorithm trained on the performance of thousands of primer sequences. In experimental benchmarks, LSV-seq achieves high on-target capture rates and concordance with RNA-seq, while requiring significantly lower sequencing depth. Leveraging deep learning splicing code predictions, we used LSV-seq to target events with low coverage in GTEx RNA-seq data and newly discover hundreds of tissue-specific splicing events. Our results demonstrate the ability of LSV-seq to quantify splicing of events of interest at high-throughput and with exceptional sensitivity.
The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the MT-ND3 mRNA
Authors: Yang Xuan , Stentenbach Maike , Hughes Laetitia A , Siira Stefan J , Lau Kelvin , Hothorn Michael , Martinou Jean-Claude , Rackham Oliver , Filipovska Aleksandra
Published: December 2024

Expression of the compact mitochondrial genome is regulated by nuclear encoded, mitochondrially localized RNA-binding proteins (RBPs). RBPs regulate the lifecycles of mitochondrial RNAs from transcription to degradation by mediating RNA processing, maturation, stability and translation. The Fas-activated serine/threonine kinase (FASTK) family of RBPs has been shown to regulate and fine-tune discrete aspects of mitochondrial gene expression. Although the roles of specific targets of FASTK proteins have been elucidated, the molecular mechanisms of FASTK proteins in mitochondrial RNA metabolism remain unclear. Therefore, we resolved the structure of FASTKD4 at atomic level that includes the RAP domain and the two FAST motifs, creating a positively charged cavity resembling that of the very short patch repair endonuclease. Our biochemical studies show that FASTKD4 binds the canonical poly(A) tail of MT-ND3 enabling its maturation and translation. The in vitro role of FASTKD4 is consistent with its loss in cells that results in decreased MT-ND3 polyadenylation, which destabilizes this messenger RNA in mitochondria.
A multi-institutional retrospective cohort of adult-onset medulloblastoma in the modern era
Authors: Bonm Alipi V , Rutenberg Michael S , Therkelsen Kate E , Herbst John , Sanaf Anurag , Sherwood Marissa A , Rhee John Y , McGranahan Tresa M , Cimino Patrick J , Gonzalez Castro L Nicolas , Tsang Derek S , Karajannis Matthias A , Nagpal Seema , Amdur Robert J , Shih Helen , Barber Jason , Taylor Lynne P
Published: December 2024

Background

Adult onset medulloblastoma (aMB) is a rare tumor with limited available evidence. We present a large multi-institutional retrospective cohort of aMB patients treated in the modern era, with an emphasis on understanding the role of chemotherapy at initial diagnosis.

Methods

We included 267 consecutive patients with aMB treated at 7 different institutions from 2000-present, controlling for chemotherapy regimen and cycles received.

Results

Treatment factors were highly intercorrelated with one another and with treating institution. Concurrent chemotherapy was not associated with overall survival (OS). Adjuvant chemotherapy was associated with OS on univariable analyses (HR = 0.55, P = .029) and on multivariable analysis when adjusting for risk status (HR 0.55, P = .026) but not when also adjusting for treating institution. Proton craniospinal irradiation was associated with improved survival on univariable (HR = 0.50, P = .019) and multivariable analysis adjusting for risk status (HR = 0.51, P = .024) but not when treating institution was also considered. On subgroup analysis, adjuvant chemotherapy was associated with improved survival in M0 (HR = 0.55, P = .043) but not M1 disease, in patients with subtotal resection (HR = 0.43, P = .048) but not those with GTR. Similarly, progression-free survival was improved with chemotherapy in patients with M0 (HR = 0.57, P = .032) but not M1 disease, and in patients with subtotal (HR = 0.50, P = .054) but not gross total resection.

Conclusions

There was no benefit of concurrent chemotherapy. Adjuvant chemotherapy was associated with improved overall survival and this effect was driven by select subgroups, specifically those with M0 disease and those with residual tumor. We could not confirm that these associations are independent of the treating institution.
Navigating UK internal medicine training applications: 10 essential tips
Authors: Khalid Sara , Heather Thomas , Palin Victoria , Brown Oliver I , Drozd Michael
Published: December 2024

Internal medicine training applications in the UK have become increasingly competitive. This article provides ten tips for optimizing internal medicine training applications covering portfolio development, teaching experience, project selection, and interview preparation. We outline strategies for maximizing application scores through efficient resource allocation, effective project selection, and structured interview preparation. These tips are designed to help candidates navigate the competitive selection process while developing skills valuable for their future medical careers.
Exploring the Italian Population’s attitudes toward health data sharing for healthcare purpose and scientific research: a cross-sectional study
Authors: Scaioli G , Lo Moro G , Martella M , Mara A , Varì M G , Previti C , Rolfini E , Scacchi A , Bert F , Siliquini R
Published: December 2024

Background

This study aimed to explore the Italian population’s knowledge and perceptions regarding health data storage and sharing for treatment and research and to identify factors associated with citizens’ attitudes toward data storage and sharing.

Methods

A cross-sectional questionnaire, distributed to 1389 participants, collected sociodemographic information, assessed knowledge and gauged attitudes toward sharing data for treatment and research. Descriptive analyses and logistic regressions were performed to examine the associations between sociodemographic factors and knowledge/attitudes about data storage and sharing.

Results

Most respondents wrongly believed that healthcare providers could access personal health–related data across the entire national territory, while 94% expressed willingness to share personal health data nationwide. A substantial percentage of respondents (73%) fully agreed that storing and sharing personal health–related data could improve research and quality of care.

Males and younger individuals (<41 years) were likelier to have higher data-sharing knowledge. Lower educational-level respondents exhibited lower positive attitudes towards sharing health data for treatment and research purposes.

Conclusions

The results provide valuable insights for policymakers, healthcare professionals and researchers seeking to improve data management, promote collaboration and leverage the full potential of health data for personalized care and scientific advancements.
iPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases
Authors: Li Huirong , Sharma Ruchi , Bharti Kapil
Published: December 2024

Retinal pigment epithelium (RPE) atrophy is a significant cause of human blindness worldwide, occurring in polygenic diseases such as age-related macular degeneration (AMD) and monogenic diseases such as Stargardt diseases (STGD1) and late-onset retinal degeneration (L-ORD). The patient-induced pluripotent stem cells (iPSCs)-derived RPE (iRPE) model exhibits many advantages in understanding the cellular basis of pathological mechanisms of RPE atrophy. The iRPE model is based on iPSC-derived functionally mature and polarized RPE cells that reproduce several features of native RPE cells, such as phagocytosis of photoreceptor outer segments (POS) and replenishment of visual pigment. When derived from patients, iRPE are able to recapitulate critical cellular phenotypes of retinal degenerative diseases, such as the drusen-like sub-RPE deposits in the L-ORD and AMD models; lipid droplets and cholesterol accumulation in the STGD1 and AMD models. The iRPE model has helped discover the unexpected role of RPE in understanding retinal degenerative diseases, such as a cell-autonomous function of ABCA4 in STGD1. The iRPE model has helped uncover the pathological mechanism of retinal degenerative diseases, including the roles of alternate complement cascades and oxidative stress in AMD pathophysiology, abnormal POS processing in STGD1 and L-ORD, and its association with lipid accumulation. These studies have helped better understand—the role of RPE in retinal degenerative diseases, and molecular mechanisms underlying RPE atrophy, and have provided a basis to discover therapeutics to target RPE-associated diseases.
Race structure of Pyrenophora tritici-repentis in the Kansas wheat pathogen population
Authors: Mangel Dylan , Bruce Myron , Rupp Noller Jessica
Published: December 2024

Tan spot, caused by Pyrenophora tritici-repentis (Ptr) carries any of at least three identified necrotrophic effectors (NE) as part of its host invasion repertoire (Ptr ToxA, Ptr ToxB, and Ptr ToxC). The 8 possible combinations of these genes, or their absence, are described using a race system. These races characterize the disease phenotype observed on a wheat differential set. The primary NE, Ptr ToxA, enables pathogenesis through an interaction with the wheat susceptibility gene, Tsn1. This study aimed to determine the race structure of the Ptr population in Kansas. To complete this objective, a survey was conducted to collect isolates of the pathogen from the Kansas wheat production region. In addition, 16 historic isolates were also included. The isolates were screened against the wheat differential set, and molecularly characterized for presence of the genes ToxA, and ToxB, and a non-functioning ToxB haplotype called toxb. The survey identified 63 Ptr isolates. Our results revealed the predominance of race 1, which contains ToxA and ToxC. However, we also identified isolates of race 2, 3, and 4. The results of molecular assays matched the screening results for Ptr ToxA and Ptr ToxB in most cases. Some isolates caused atypical symptoms which did not match the current race structure. The prevalence of race 1 Ptr in the Kansas population suggests that breeding for resistance in Kansas should focus on selecting against Tsn1 which encodes susceptibility to Ptr ToxA. This research provides critical insights that will inform breeders and pathologists for improved control of Ptr.
tPA‐GFP is a reliable probe for detecting compound exocytosis in human pancreatic β‐cells
Authors: Makam Aishwarya A. , Sharma Shruti , Nagle Prajwal , Sundaram Nandhini M. , Prasad Vidya Mangala , Gandasi Nikhil R.
Published: December 2024

Pancreatic β‐cells secrete insulin stored in large dense core vesicles (LDCV) by fusion of vesicle and plasma membrane during a process called insulin exocytosis. Insulin secretion is biphasic with a fast first phase and a sustained second phase. Previous studies have pointed out that exocytosis of insulin can occur via (1) single LDCVs fusing with the plasma membrane to release their content or (2) multiple vesicles are involved during a process called compound exocytosis. Compound exocytosis represents a specialized form of secretion in which vesicles undergo homotypic fusion either before (multi‐vesicular exocytosis) or continuous fusion in a sequential manner from (sequential exocytosis) within the same site at the plasma membrane. We see that the number of multi‐vesicles is few and not localized in the vicinity of the plasma membrane. Studying the kinetics of this process and correlating it with biphasic insulin secretion is not possible since there are no specific probes to detect them. It is challenging to identify compound exocytosis with probes that exist for simple exocytosis. To advance our understanding, we need a fluorescent probe that could detect secretory vesicles undergoing compound exocytosis and allow us to distinguish it from other modes of exocytosis. Here, we used two cargo proteins (NPY and tPA) labeled with different fluorescent proteins (mCherry GFP and eGFP) and employed total internal reflection fluorescence microscopy (TIRF‐M) to capture distinct single‐granule and multi‐granular fusion events. We identified tPA‐GFP as a better probe for studying compound exocytosis, as it can detect both simple and sequential exocytosis reliably. Using these probes, we have studied the kinetics of compound exocytosis in human β‐cells. These observations, with additional experiments, may open a whole new field to study the impact of compound exocytosis on biphasic secretion of insulin. Identifying targets to increase the compound exocytosis process can help potentiate insulin secretion in diabetics.
Targeting GSK‐3β for adipose dysfunction and cardiovascular complications of metabolic disease: An entangled WNT/β‐catenin question
Authors: Alotaiq Nasser , Khalifa Ahmed S. , Youssef Amr , El‐Nagar Esraa G. , Elwali Nasr Eldin , Habib Hosam M. , AlZaim Ibrahim , Eid Ali H. , Bakkar Nour‐Mounira Z. , El‐Yazbi Ahmed F.
Published: December 2024

Individuals with metabolic syndrome have a high risk of developing cardiovascular disorders that is closely tied to visceral adipose tissue dysfunction, as well as an altered interaction between adipose tissue and the cardiovascular system. In metabolic syndrome, adipose tissue dysfunction is associated with increased hypertrophy, reduced vascularization, and hypoxia of adipocytes, leading to a pro‐oxidative and pro‐inflammatory environment. Among the pathways regulating adipose tissue homeostasis is the wingless‐type mammary tumor virus integration site family (Wnt) signaling pathway, with both its canonical and non‐canonical arms. Various modulators of the Wnt signaling have been identified to contribute to the development of metabolic diseases and their cardiovascular complications, with a particularly significant role played by Glycogen Synthase Kinase‐3β (GSK‐3β). GSK‐3β levels and activities have various and often contrasting roles in obesity and related metabolic disorders, as well as their cardiovascular sequelae. Here, we explore the possibility that altered Wnt signaling and GSK‐3β activities could serve as a connection between adipose tissue dysfunction and the development of cardiovascular disease in individuals with metabolic syndrome. We attempt to define a context‐specific approach for intervention, which could possibly serve as a novel disease modifying therapy for the mitigation of such complications.
Outcomes of Growth-Friendly Surgical Treatment of Early Onset Scoliosis in Children With Prune Belly Syndrome: A Preliminary Report
Authors: Ashebo Leta , Sponseller Paul , Hedequist Daniel , Ramirez Norman , Oetgen Matthew , Li Ying ,   Pediatric Spine Study Group
Published: December 2024

Background:

Prune belly syndrome (PBS) is a rare condition characterized by absence of abdominal musculature, cryptorchidism, and obstructive uropathy. The most common orthopaedic problem is scoliosis, yet no reports on growth-friendly surgical treatment of early-onset scoliosis (EOS) exist. Our purpose was to evaluate outcomes of distraction-based implants in children with PBS.

Methods:

This was a multicenter retrospective review. Children with PBS treated with TGR, MCGR, or VEPTR with a minimum 2-year follow-up were identified. Demographics, radiographic/surgical data, complications, and unplanned returns to the operating room (UPROR) were collected. Quality of life was measured using EOSQ-24.

Results:

Seven patients (100% male) were identified. The mean age at index surgery was 5.6 years. The mean length of follow-up was 4 years (range: 2 to 11 y). Implant types included MCGR (4 patients), TGR (2 patients), and VEPTR (1 patient). Two patients had pelvic fixation. The mean major curve magnitude was 87 degrees preindex, 47 degrees postindex, and 53 degrees at the last follow-up. Mean kyphosis was 55 degrees preindex, 25 degrees postindex, and 42 degrees at the most recent follow-up. Mean T1-T12 and T1-S1 lengths increased 4.4 and 4.8 cm, respectively, between preindex and last follow-up.

Complications occurred in 3 patients. One patient had 3 TGR breakages resulting in 3 UPRORs to revise the rods and 1 superficial wound infection treated with antibiotics. Another patient was readmitted for respiratory failure after TGR lengthening and a third patient had a superficial infection manifested by incisional swelling after MCGR insertion that resolved with antibiotics. Two patients have undergone definitive fusion and 1 patient has retained his TGR definitively. The other patients are still undergoing rod lengthening.

Conclusions:

Children with PBS can develop severe scoliosis at a young age. Distraction-based implants can successfully control scoliosis while allowing spinal growth. The complication rate is comparable to patients with idiopathic EOS treated with growth-friendly implants.

Level of Evidence:

Therapeutic level IV.
Developmental Coaching for Clinician Educators: Just What the Doctor Ordered
Authors: Branzetti Jeremy
Published: December 2024

Despite intensive attempts to create scholarship equity at academic medical centers, clinician educators continue to face a challenging professional promotion environment that puts them at risk for burnout, stalled career advancement, and abandonment of academic medicine altogether. Coaching, which has a wealth of supportive evidence from outside of medicine, is distinguished by (1) being driven by the agentic coachee that is inherently capable, creative, and resourceful, (2) not requiring the coach and coachee to have shared content expertise, and (3) not being centered around transfer of expertise from the more knowledgeable or experienced party to the recipient. Initial evidence from within medicine indicates that coaching reduces burnout and improves learner self-reflection, teaching effectiveness, goal setting, reflective capacity, professional identity formation, career planning, and development of adaptive expertise. In this article, faculty coaching is presented as a powerful means to help clinician educators overcome the myriad challenges to professional advancement and career fulfillment. The current evidence in support of coaching—both within and outside of medicine—is reviewed. Finally, a conceptual model is provided, as are guidelines demonstrating specific roles, behaviors, and responsibilities for faculty coaches and coachees.
Secondary Hemophagocytic Lymphohistiocytosis Syndrome Developing in a Patient With Chronic Lymphocytic Leukemia Under a Long-term Ibrutinib Therapy: A Case Report and Literature Review
Authors: Gao Liang , Wang Lihong , Wang Bingjie , Wang Qian , Cen Xinan , Dong Yujun
Published: December 2024

Secondary hemophagocytic lymphohistiocytosis (HLH) syndrome, a fatal disorder characterized by NK/T-cell deficiency, cytokine storm, and organ damage, is rare in chronic lymphocytic leukemia (CLL). Ibrutinib, the first generation of irreversible Bruton’s tyrosine kinase inhibitor, has been the first-line therapy for CLL. As an off-target effect, it can also block IL-2 inducible T-cell kinase (ITK), which is essential in maintaining normal NK and T-cell functions. Up to now, 4 cases reported secondary HLH developed in CLL patients shortly after ibrutinib therapy, which indicated ibrutinib might be associated with HLH via NK/T cell damage as a result of ITK inhibition. We herein report the first case describing EBV-driven HLH developed in a CLL patient under long-term ibrutinib monotherapy (4 year﻿), also showing concurrent NK and T cell deficiency. Therefore, the relationship between the long-term use of ibrutinib and the pathophysiology of HLH, as well as the mediating role of NK/T cell disorder caused by ITK blockade therein, deserves attention and further studies.
Impact of eicosapentaenoic acid on cardiovascular outcomes after acute coronary syndrome: a systematic review and meta-analysis of randomized clinical trials
Authors: Fallahtafti Parisa , Nayebirad Sepehr , Karimi Elaheh , Hassanzadeh Ali , Habibzadeh Amirhossein , Safaee Ehsan , Ebrahimi Rasoul , Tajdini Masih , Najafi Kimia , Askari Mani K. , Harrison Anil , Nelson John R. , Hosseini Kaveh
Published: December 2024

Background and purpose:

Studies show that individuals recovering from acute coronary syndrome (ACS) benefit from intensive lipid-lowering treatment, which offers better protection against cardiovascular events than standard regimens. While the benefits of polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA), in coronary artery disease are well-established, their use in ACS patients remains debated. This systematic review and meta-analysis aimed to evaluate the effects of EPA supplementation on cardiovascular outcomes in ACS patients.

Methods:

A systematic search was conducted in PubMed, Embase, Scopus, Cochrane Library, and ClinicalTrials.gov from inception to March 22, 2024, focusing on randomized clinical trials (RCTs) and post hoc analyses of adults with ACS examining the effects of adding EPA to statin therapy. The risk of bias was assessed using the Cochrane risk of bias-2 tool. Data synthesis included calculating relative risks (RR) and assessing heterogeneity with I² and Cochran’s Q test, using fixed or random-effects models as appropriate. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, and stroke.

Results:

A total of 1,333 subjects with recent ACS were included across five RCTs, with 653 receiving standard statin therapy and 680 receiving statins plus EPA. EPA supplementation trended toward reduced all-cause and cardiac death. Meta-analysis revealed a significant reduction in composite outcomes for the EPA group compared to controls (RR: 0.67, 95% confidential interval: 0.45–1.00, P = 0.04). No significant differences were found in re-infarction, coronary revascularization, or atherosclerotic plaque characteristics between the groups.

Conclusions:

Our study shows that adding EPA to statins after recent ACS reduces cardiovascular events. Despite limitations, our findings support early EPA use in ACS patients.
Recent Advances in the Diagnosis and Management of Limbal Stem Cell Deficiency
Authors: Kittipibul Thanachaporn , Dalin Chea Piseth , Masoudi Ali , Zheng Jie , Deng Sophie X.
Published: December 2024

This concise review focuses on the latest advancements in the diagnosis and management of limbal stem cell deficiency (LSCD). Ensuring the standard of care for individuals affected by LSCD involves the crucial task for physicians to meticulously and accurately diagnose the condition and determine its specific stage. A standardized diagnostic approach forms the foundation for formulating and delivering customized therapeutic interventions to maximize treatment outcomes for each patient. In this review, we introduce a systematic diagnostic algorithm to guide the assessment of LSCD. In addition, the current management algorithm and emerging therapies for LSCD are summarized.
Digital Interventions for Promoting Skin Self-Examination Behaviors of Melanoma Survivors
Authors: Li Leilei , Qu Hui , Fu Chaohong , Niu Jianpei , Yang Changyong
Published: December 2024

Background

Regular and thorough skin self-examination (SSE) is an important strategy to reduce mortality among melanoma survivors. However, less than a quarter of melanoma survivors participate in skin self-examination.

Objective

The aim of this study was to systematically review the effectiveness of digital interventions on SSE-related practices in melanoma survivors.

Methods

Cochrane Library, Web of Science, PubMed, and EBSCO were used to identify literature with a search period from January 1, 2000, to June 11, 2024. Two researchers conducted the quality evaluation and summarized and analyzed the included literature.

Results

Twelve articles were included, with a quality score of 5-9 and an average score of 7.67 for the included studies. The digital intervention methods are web based (n = 5), mobile applications (n = 5), videos (n = 1), and interactive multimedia (n = 1). Eleven studies used at least 1 theoretical framework to guide their intervention design. Ten studies reported SSE rates, 2 studies reported SSE areas, and 2 studies reported SSE frequencies and other practical effects. Compared with the control group, the increase in SSE rate ranged from 26.2% to 78.9%; 90% of participants had a frequency of SSE ≥ 2 times per month, with an average of 5.14 areas of SSE; the usage rate of mirrors ranged from 67% to 88%.

Conclusions

Digital intervention can effectively improve the rates, frequency, and number of areas of SSE for melanoma survivors.

Implications for Practice

Digital intervention can be used in clinical practice to provide efficient and effective SSE for melanoma survivors in the short to medium term.
A Scoping Review of Chemotherapy-induced Peripheral Neuropathy-Related Gait Abnormalities in Children With Cancer
Authors: Washist Regan , Steventon Dan , Samuelson Paige , Anderson Brittany , Berg-Poppe Patti , Milanovich Samuel
Published: December 2024

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) with associated weakness, areflexia, neuropathic pain, and sensory loss, is a common occurrence in children treated for cancer. However, accurate, quantifiable descriptions of gait deviations due to CIPN are lacking. This scoping review explores common gait abnormalities in children with CIPN.

Methods:

Using extensive database and manual literature reviews, 3 relevant studies were identified that assessed CIPN-related gait changes in children.

Results:

Though each study used different methods to analyze gait patterns, decreased ankle dorsiflexion with slower and shorter gait were common findings across the studies. Changes to ankle dorsiflexion range of motion can lead to slower walking speeds and compensatory changes that can cause developmental effects on a child’s gait.

Conclusions:

Relevant research on the topic of CIPN-related gait abnormalities in children with cancer identifies knowledge gaps and the need for more studies on the effects of CIPN on children.