bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sil1-deficient fibroblasts generate an aberrant extracellular matrix leading to tendon disorganisation in Marinesco-Sjögren syndrome
Authors: Amodei Laura , Ruggieri Anna Giulia , Potenza Francesca , Viele Marianna , Dufrusine Beatrice , Franciotti Raffaella , Pietrangelo Laura , Ardini Matteo , Stuppia Liborio , Federici Luca , De Laurenzi Vincenzo , Sallese Michele 
Published: August 2024

Abstract
Background
Marinesco-Sjögren syndrome (MSS) is an autosomal recessive neuromuscular disorder that arises in early childhood and is characterized by congenital cataracts, myopathy associated with muscle weakness, and degeneration of Purkinje neurons leading to ataxia. About 60% of MSS patients have loss-of-function mutations in the SIL1 gene. Sil1 is an endoplasmic reticulum (ER) protein required for the release of ADP from the master chaperone Bip, which in turn will release the folded proteins. The expression of non-functional Sil1 leads to the accumulation of unfolded proteins in the ER and this triggers the unfolded protein response (UPR). A dysfunctional UPR could be a key element in the pathogenesis of MSS, although our knowledge of the molecular pathology of MSS is still incomplete.

Methods
RNA-Seq transcriptomics was analysed using the String database and the Ingenuity Pathway Analysis platform. Fluorescence confocal microscopy was used to study the remodelling of the extracellular matrix (ECM). Transmission electron microscopy (TEM) was used to reveal the morphology of the ECM in vitro and in mouse tendon.

Results
Our transcriptomic analysis, performed on patient-derived fibroblasts, revealed 664 differentially expressed (DE) transcripts. Enrichment analysis of DE genes confirmed that the patient fibroblasts have a membrane trafficking issue. Furthermore, this analysis indicated that the extracellular space/ECM and the cell adhesion machinery, which together account for around 300 transcripts, could be affected in MSS. Functional assays showed that patient fibroblasts have a reduced capacity of ECM remodelling, reduced motility, and slower spreading during adhesion to Petri dishes. TEM micrographs of negative-stained ECM samples from these fibroblasts show differences of filaments in terms of morphology and size. Finally, structural analysis of the myotendinous junction of the soleus muscle and surrounding regions of the Achilles tendon revealed a disorganization of collagen fibres in the mouse model of MSS (woozy).

Conclusions
ECM alterations can affect the proper functioning of several organs, including those damaged in MSS such as the central nervous system, skeletal muscle, bone and lens. On this basis, we propose that aberrant ECM is a key pathological feature of MSS and may help explain most of its clinical manifestations.
Robotic assessment of bilateral and unilateral upper limb functions in adults with cerebral palsy
Authors: Poitras I. , Dukelow S. P. , Campeau-Lecours A. , Mercier C. 
Published: August 2024

Abstract
Background
Children with unilateral cerebral palsy (CP) exhibit motor impairments predominantly on one side of the body, while also having ipsilesional and bilateral impairments. These impairments are known to persist through adulthood, but their extent have not been described in adults with CP. This study’s aim is to characterize bilateral and unilateral upper limbs impairments in adults with CP.

Methods
Nineteen adults with CP (34.3 years old ± 11.5) performed three robotic assessments in the Kinarm Exoskeleton Lab, including two bilateral tasks (Object Hit [asymmetric independent goals task] and Ball on Bar [symmetric common goal task]) and one unilateral task (Visually Guided Reaching, performed with the more affected arm [MA] and less affected arm [LA]). Individual results were compared to sex, age and handedness matched normative data, describing the proportion of participants exhibiting impairments in each task-specific variable (e.g., Hand speed), each performance category (e.g., Feedforward control) and in global task performance. Associations were assessed using Spearman correlation coefficients between: 1: the results of the MA and LA of each limb in the unilateral task; and 2: the results of each limb in the unilateral vs. the bilateral tasks.

Results
The majority of participants exhibited impairments in bilateral tasks (84%). The bilateral performance categories (i.e., Bimanual) identifying bilateral coordination impairments were impaired in the majority of participants (Object Hit: 57.8%; Ball on Bar: 31.6%). Most of the participants were impaired when performing a unilateral task with their MA arm (63%) and a smaller proportion with their LA arm (31%). The Feedforward control was the unilateral performance category showing the highest proportion of impaired participants while displaying the strongest relationship between the MA and LA arms impairments (rs = 0.93). Feedback control was the unilateral performance category most often associated with impairments in bilateral tasks (6 out of 8 performance categories).

Conclusions
Adults with CP experienced more impairment in bilateral tasks while still having substantial impairments in unilateral tasks. They frequently display Feedforward control impairments combined with a higher reliance on Feedback control during both bilateral and unilateral tasks, leading to poorer motor performance.
Characterization of pathogenic genetic variants in Russian patients with primary ciliary dyskinesia using gene panel sequencing and transcript analysis
Authors: Zlotina Anna , Barashkova Svetlana , Zhuk Sergey , Skitchenko Rostislav , Usoltsev Dmitrii , Sokolnikova Polina , Artomov Mykyta , Alekseenko Svetlana , Simanova Tatiana , Goloborodko Maria , Berleva Olga , Kostareva Anna 
Published: August 2024

Abstract
Background
Primary ciliary dyskinesia (PCD) is a group of rare genetically heterogeneous disorders caused by defective cilia and flagella motility. The clinical phenotype of PCD patients commonly includes chronic oto-sino-pulmonary disease, infertility, and, in about half of cases, laterality defects due to randomization of left–right body asymmetry. To date, pathogenic variants in more than 50 genes responsible for motile cilia structure and assembly have been reported in such patients. While multiple population-specific mutations have been described in PCD cohorts from different countries, the data on genetic spectrum of PCD in Russian population are still extremely limited.

Results
The present study provides a comprehensive clinical and genetic characterization of 21 Russian families with PCD living in various country regions. Anomalies of ciliary beating in patients` respiratory epithelial cells were confirmed by high-speed video microscopy. In the most cases, custom-designed panel sequencing allowed to uncover causative variants in well-known or rarely mentioned PCD-related genes, including DNAH5, DNAH11, CFAP300, LRRC6, ZMYND10, CCDC103, HYDIN, ODAD4, DNAL1, and OFD1. The variations comprised common mutations, as well as novel genetic variants, some of which probably specific for Russian patients. Additional targeted analysis of mRNA transcripts from ciliated cells enabled us to specify functional effects of newly identified genetic variants in DNAH5 (c.2052+3G>T, c.3599-2A>G), HYDIN (c.10949-2A>G, c.1797C>G), and ZMYND10 (c.510+1G>C) on splicing process. In particular, the splice site variant c.2052+3G>T, detected in four unrelated families, resulted in skipping of exon 14 in DNAH5 transcripts and, according to haplotype analysis of affected probands, was proposed as an ancestral founder mutation in Udmurt population.

Conclusions
The reported data provide a vital insight into genetic background of primary ciliary dyskinesia in the Russian population. The findings clearly illustrate the utility of gene panel sequencing coupled with transcriptional analysis in identification and clinical interpretation of novel genetic variants.
Changes in urinary renal injury markers in children with Mycoplasma pneumoniae pneumonia and a prediction model for related early renal injury
Authors: Zhang Ju , Ma He-kai , Li Bao-wen , Ma Ke-Ke , Zhang Yu-Ling , Li Shu-jun 
Published: August 2024

Abstract
Background
This study aims to analyse changes in urinary kidney injury markers in children with Mycoplasma pneumoniae pneumonia (MPP), investigate the risk factors for MPP-related acute kidney injury (AKI) and establish a model to predict MPP-related AKI.

Methods
Ninety-five children were enrolled based on the study’s inclusion and exclusion criteria. They were divided into a severe MPP (SMPP) group and a non-SMPP group and then into an AKI group and a non-AKI group according to the presence of AKI. A univariate logistic regression analysis was performed to explore the early risk factors for AKI. Based on a multivariate logistic regression analysis and a least absolute shrinkage and selection operator regression analysis, appropriate variables were selected to establish a prediction model, and R 4.2.2 software was used to draw nomograms and generate a dynamic nomogram website.

Results
Seven urinary kidney injury markers were abnormally elevated in the SMPP group and the non-SMPP group: urinary N-acetyl-β-D-glucosaminidase (NAG), β2-microglobulin, α1-microglobulin, retinol-binding protein, urinary immunoglobulin G, urinary transferrin and urinary microalbumin. Sixteen children were identified with AKI during hospitalisation. The AKI group had higher levels of urinary NAG, α1-microglobulin, β2-microglobulin, urinary microalbumin, urinary transferrin and retinol-binding protein than the non-AKI group (P < 0.05). The MPP-related AKI prediction model consists of four indicators (serum immunoglobulin M [IgM], C-reactive protein [CRP], urine NAG and sputum plug presence) and a dynamic nomogram.

Conclusion
Urinary kidney injury markers are often elevated in children with MPP; urinary NAG is the marker most likely to be elevated, and it is especially evident in severe cases. The nomogram of the prediction model, comprising serum IgM, CRP, urinary NAG and sputum plug presence, can predict the probability of AKI in children with MPP.
Integrated prenatal and postnatal management for neonates with transposition of the great arteries: thirteen-year experience at a single center
Authors: Lin Xieyi , Huang Ying , Xie Wen , Chen Lu , Huang Yuping , Huang Yu , Ma Bingyu , Wen Shusheng , Pan Wei 
Published: August 2024

Abstract
Background
Transposition of the great arteries (TGA) is the most common cyanotic congenital heart defect in neonates but with low prenatal detection rate. This study sought to review the prenatal diagnosis, associated abnormalities, and mid-term postnatal outcomes of fetuses with TGA and investigate the integrated prenatal and postnatal management for TGA neonates.

Methods
A total of 134 infants prenatally diagnosed with TGA in Guangdong Provincial People’s Hospital, China, from January 2009 to December 2022 were included in the study. The prenatal ultrasound data and neonatal records were reviewed to assess the accuracy of prenatal diagnosis. Univariate and multivariate logistic and Cox analyses were used to identify risk factors associated with prognosis in such individuals.

Results
The population originated from 40 cities in 10 provinces in China, with integrated antenatal and postnatal management rate reaching 94.0% (126/134) and a high accuracy rate (99.3%) of prenatal primary diagnosis. The median period of follow-up was 1.6 [interquartile range (IQR) 0.1–4.3] years. There were 3 (2.2%) postnatal deaths, 118 (88.1%) patients undergoing arterial switch operation (ASO), 3 (2.2%) undergoing Rastelli operations and 5 (3.7%) doing stage operations. Of 118 patients receiving ASO, the major morbidity occurred in 64 patients (54.2%), and right ventricular outflow tract obstruction (RVOTO) in 31 (26.3%). In the multivariate logistic analysis, gestational ages at birth (OR = 0.953, 95% CI 0.910–0.991; p = 0.025) and cardiopulmonary bypass (CPB) time (OR = 1.010, 95% CI 1.000–1.030; p = 0.038) were identified as independent risk factors associated with major morbidity. In the Cox multivariate analysis, aortic cross-clamping time (HR = 1.030, 95% CI 1.000–1.050; p = 0.017) was identified as independent risk factor associated with RVOTO.

Conclusion
Earlier gestational ages at birth and longer CPB time are significantly associated with increased morbidity. Integrated prenatal and postnatal management is recommended for patients with prenatal diagnosis of TGA.
Real-time identification of epistatic interactions in SARS-CoV-2 from large genome collections
Authors: Innocenti Gabriel , Obara Maureen , Costa Bibiana , Jacobsen Henning , Katzmarzyk Maeva , Cicin-Sain Luka , Kalinke Ulrich , Galardini Marco 
Published: August 2024

AbstractBackgroundThe emergence of the SARS-CoV-2 virus has highlighted the importance of genomic epidemiology in understanding the evolution of pathogens and guiding public health interventions. The Omicron variant in particular has underscored the role of epistasis in the evolution of lineages with both higher infectivity and immune escape, and therefore the necessity to update surveillance pipelines to detect them early on.ResultsIn this study, we apply a method based on mutual information between positions in a multiple sequence alignment, which is capable of scaling up to millions of samples. We show how it can reliably predict known experimentally validated epistatic interactions, even when using as little as 10,000 sequences, which opens the possibility of making it a near real-time prediction system. We test this possibility by modifying the method to account for the sample collection date and apply it retrospectively to multiple sequence alignments for each month between March 2020 and March 2023. We detected a cornerstone epistatic interaction in the Spike protein between codons 498 and 501 as soon as seven samples with a double mutation were present in the dataset, thus demonstrating the method’s sensitivity. We test the ability of the method to make inferences about emerging interactions by testing candidates predicted after March 2023, which we validate experimentally.ConclusionsWe show how known epistatic interaction in SARS-CoV-2 can be detected with high sensitivity, and how emerging ones can be quickly prioritized for experimental validation, an approach that could be implemented downstream of pandemic genome sequencing efforts.
Enhanced extracellular production of maltotetraose amylase from Pseudomonas saccharophila in Bacillus subtilis through regulatory element optimization
Authors: Cong Guilong , Li Mingyu , Dong Sitong , Ai Teng , Ren Xiaopeng , Li Xianzhen , Wang Conggang , Yang Fan 
Published: August 2024

AbstractMaltotetraose amylase (Mta) catalyzes the hydrolysis of amylaceous polysaccharides into maltotetraose, which is an important functional sugar used in the food industry. However, the lack of efficient expression systems for recombinant Mta has hindered its scale-up production and application. In this study, a codon-optimized mta gene from Pseudomonas saccharophila was efficiently produced in Bacillus subtilis by optimizing the regulatory elements. First, a plasmid library containing 173 different signal peptide sequences placed upstream of mta gene was constructed, and transformed into B. subtilis strain WB800N(amyEΔ1) for high-throughput screening. The signal peptide yhcR was found to significantly enhance the secretion of Mta, reaching an activity of 75.4 U/mL in the culture medium. After optimization of the promoters, the Mta activity was further increased to 100.3 U/mL using a dual-promoter PHpaIIPamyE. Finally, the carbon sources and nitrogen sources for recombinant Mta production were optimized, yielding a highest Mta activity of 288.9 U/mL under the optimal culture conditions. The crude enzyme solution containing recombinant Mta produced a highest maltotetraose yield of 70.3% with 200 g/L of maltodextrin as the substrate. Therefore, the present study have demonstrated a high yield of Mta produced in B. subtilis, laying the foundation for large-scale Mta production and application.
Problematic anger among military personnel after combat deployment: prevalence and risk factors
Authors: Nordstrand Andreas Espetvedt , Anyan Frederick , Bøe Hans Jakob , Hjemdal Odin , Noll Laura Katherine , Reichelt Jon Gerhard , Forbes David , Adler Amy B. 
Published: August 2024

Abstract
Background
Problematic anger, characterized by excessive frequency, intensity, and duration of anger which causes substantial emotional distress and functional interference, poses a marked challenge in military populations. Despite its importance, research on this topic is limited. This study contributes to the literature by exploring problematic anger in a large sample of Norwegian military personnel who served in NATO missions in Afghanistan.

Methods
All Norwegian military personnel who deployed to Afghanistan between 2001 and 2020 were sent a link to a cross-sectional web-based survey by the Joint Medical Services of the Norwegian Armed Forces in 2020. A total of 6205 individuals (response rate: 67.7%) participated. The cross-sectional survey assessed problematic anger, mental and physical health, war zone stressor exposure, and quality of life.

Results
Overall, 8.4% of participants reported problematic anger. Mental health disorders, deployment-related shame and guilt, chronic pain, and challenges with the military-to-civilian transition were independently associated with problematic anger. Both staying in service and maintaining a part-time connection with the military as a reservist mitigated the risk of problematic anger after deployment, compared to complete separation from military service.

Conclusion
Findings demonstrate a sizeable prevalence of problematic anger among veterans of combat deployments. Given the associations between problematic anger and mental health disorders, chronic pain, and transition challenges, interventions designed to mitigate problematic anger need to be multi-faceted, including the possibility of maintaining an ongoing connection to military service. By reducing the risk of problematic anger, occupational, interpersonal and health outcomes may be improved for service members. Future research should examine the impact of problematic anger on adjustment over time, prevention strategies, and problematic anger in other high-risk occupations.
CAR Macrophages: a promising novel immunotherapy for solid tumors and beyond
Authors: Lu Jialin , Ma Yuqing , Li Qiuxin , Xu Yihuan , Xue Yiquan , Xu Sheng 
Published: August 2024

AbstractWith the advent of adoptive cellular therapy, chimeric antigen receptor (CAR)-T cell therapy has gained widespread application in cancer treatment and has demonstrated significant efficacy against certain hematologic malignancies. However, due to the limitations of CAR-T cell therapy in treating solid tumors, other immune cells are being modified with CAR to address this issue. Macrophages have emerged as a promising option, owing to their extensive immune functions, which include antigen presentation, powerful tumor phagocytosis, and particularly active trafficking to the tumor microenvironment. Leveraging their unique advantages, CAR-macrophages (CAR-M) are expected to enhance the effectiveness of solid tumor treatments as a novel form of immunotherapy, potentially overcoming major challenges associated with CAR-T/NK therapy. This review outlines the primary mechanism underlying CAR-M and recent progressions in CAR-M therapy, while also discussing their further applications.
Oral nicotinamide provides robust, dose-dependent structural and metabolic neuroprotection of retinal ganglion cells in experimental glaucoma
Authors: Cimaglia Gloria , Tribble James R. , Votruba Marcela , Williams Pete A. , Morgan James E. 
Published: August 2024

AbstractA compromised capacity to maintain NAD pools is recognized as a key underlying pathophysiological feature of neurodegenerative diseases. NAD acts as a substrate in major cell functions including mitochondrial homeostasis, cell signalling, axonal transport, axon/Wallerian degeneration, and neuronal energy supply. Dendritic degeneration is an early marker of neuronal stress and precedes cell loss. However, little is known about dendritic structural preservation in pathologic environments and remodelling in mature neurons. Retinal ganglion cell dendritic atrophy is an early pathological feature in animal models of the disease and has been demonstrated in port-mortem human glaucoma samples. Here we report that a nicotinamide (a precursor to NAD through the NAD salvage pathway) enriched diet provides robust retinal ganglion cell dendritic protection and preserves dendritic structure in a rat model of experimental glaucoma. Metabolomic analysis of optic nerve samples from the same animals demonstrates that nicotinamide provides robust metabolic neuroprotection in glaucoma. Advances in our understanding of retinal ganglion cell metabolic profiles shed light on the energetic shift that triggers early neuronal changes in neurodegenerative diseases. As nicotinamide can improve visual function short term in existing glaucoma patients, we hypothesize that a portion of this visual recovery may be due to dendritic preservation in stressed, but not yet fully degenerated, retinal ganglion cells.
Multi-objective optimization and long-time simulation of a multi-borehole ground heat exchanger system
Authors: Sarshar Saghar , Gharali Kobra , Saffaripour Meghdad , Nathwani Jatin , Dusseault Maurice B. 
Published: August 2024

AbstractMulti-objective optimization and CFD simulation are conducted to optimize the design of a multi-borehole ground heat exchanger (GHE) system and assess its long-time performance. The multi-objective optimization is performed to minimize the entropy generation number (EGN) and total cost rate by using various evolutionary algorithms, including NSGA-II, GDE-3, MOEA/D, PESA-II, SPEA-II, and SMPSO. NSGA-II and GDE-3 algorithms perform best in obtaining Pareto optimal solutions. Three prominent points on the NSGA-II Pareto frontier, representing the results of single-objective thermodynamic, single-objective economic, and multi-objective optimizations, are simulated in three dimensions over three months. The trends of EGN variations extracted from the transient CFD simulation agree well with those from the steady analytical model. The EGN obtained from multi-objective optimization is 58.8% lower than the EGN obtained using single-objective economic optimization and 1.9 times higher than that calculated from single-objective thermodynamic optimization. Likewise, the total cost rate obtained from multi-objective optimization is 64.4% lower than the value obtained from single-objective thermodynamic optimization and four times higher than that calculated using single-objective economic optimization. The proposed optimization approach can be reliably applied to improve the design of multi-borehole GHE systems.