bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic regulation of carnitine metabolism controls lipid damage repair and aging RBC hemolysis in vivo and in vitro
Authors: Nemkov Travis , Key Alicia , Stephenson Daniel , Earley Eric J. , Keele Gregory R. , Hay Ariel , Amireault Pascal , Casimir Madeleine , Dussiot Michaël , Dzieciatkowska Monika , Reisz Julie A. , Deng Xutao , Stone Mars , Kleinman Steve , Spitalnik Steven L. , Hansen Kirk C. , Norris Philip J. , Churchill Gary A. , Busch Michael P. , Roubinian Nareg , Page Grier P. , Zimring James C. , Arduini Arduino , D’Alessandro Angelo
Published: March 2024

Recent large-scale multiomics studies suggest that genetic factors influence the chemical individuality of donated blood. To examine this concept, we performed metabolomics analyses of 643 blood units from volunteers who donated units of packed red blood cells (RBCs) on 2 separate occasions. These analyses identified carnitine metabolism as the most reproducible pathway across multiple donations from the same donor. We also measured l-carnitine and acyl-carnitines in 13 091 packed RBC units from donors in the Recipient Epidemiology and Donor Evaluation study. Genome-wide association studies against 879 000 polymorphisms identified critical genetic factors contributing to interdonor heterogeneity in end-of-storage carnitine levels, including common nonsynonymous polymorphisms in genes encoding carnitine transporters (SLC22A16, SLC22A5, and SLC16A9); carnitine synthesis (FLVCR1 and MTDH) and metabolism (CPT1A, CPT2, CRAT, and ACSS2), and carnitine-dependent repair of lipids oxidized by ALOX5. Significant associations between genetic polymorphisms on SLC22 transporters and carnitine pools in stored RBCs were validated in 525 Diversity Outbred mice. Donors carrying 2 alleles of the rs12210538 SLC22A16 single-nucleotide polymorphism exhibited the lowest l-carnitine levels, significant elevations of in vitro hemolysis, and the highest degree of vesiculation, accompanied by increases in lipid peroxidation markers. Separation of RBCs by age, via in vivo biotinylation in mice, and Percoll density gradients of human RBCs, showed age-dependent depletions of l-carnitine and acyl-carnitine pools, accompanied by progressive failure of the reacylation process after chemically induced membrane lipid damage. Supplementation of stored murine RBCs with l-carnitine boosted posttransfusion recovery, suggesting this could represent a viable strategy to improve RBC storage quality.
RUNX1 C-terminal mutations impair blood cell differentiation by perturbing specific enhancer-promoter networks
Authors: Jayne Nathan D. , Liang Zhengyu , Lim Do-Hwan , Chen Poshen B. , Diaz Cristina , Arimoto Kei-Ichiro , Xia Lingbo , Liu Mengdan , Ren Bing , Fu Xiang-Dong , Zhang Dong-Er
Published: March 2024

The transcription factor RUNX1 is a master regulator of hematopoiesis and is frequently mutated in myeloid malignancies. Mutations in its runt homology domain (RHD) frequently disrupt DNA binding and result in loss of RUNX1 function. However, it is not clearly understood how other RUNX1 mutations contribute to disease development. Here, we characterized RUNX1 mutations outside of the RHD. Our analysis of the patient data sets revealed that mutations within the C-terminus frequently occur in hematopoietic disorders. Remarkably, most of these mutations were nonsense or frameshift mutations and were predicted to be exempt from nonsense-mediated messenger RNA decay. Therefore, this class of mutation is projected to produce DNA-binding proteins that contribute to the pathogenesis in a distinct manner. To model this, we introduced the RUNX1R320∗ mutation into the endogenous gene locus and demonstrated the production of RUNX1R320∗ protein. Expression of RUNX1R320∗ resulted in the disruption of RUNX1 regulated processes such as megakaryocytic differentiation, through a transcriptional signature different from RUNX1 depletion. To understand the underlying mechanisms, we used Global RNA Interactions with DNA by deep sequencing (GRID-seq) to examine enhancer-promoter connections. We identified widespread alterations in the enhancer-promoter networks within RUNX1 mutant cells. Additionally, we uncovered enrichment of RUNX1R320∗ and FOXK2 binding at the MYC super enhancer locus, significantly upregulating MYC transcription and signaling pathways. Together, our study demonstrated that most RUNX1 mutations outside the DNA-binding domain are not subject to nonsense-mediated decay, producing protein products that act in concert with additional cofactors to dysregulate hematopoiesis through mechanisms distinct from those induced by RUNX1 depletion.
PD1 inhibits PKCθ-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation
Authors: Chmiest Daniela , Podavini Silvia , Ioannidou Kalliopi , Vallois David , Décaillet Chantal , Gonzalez Montserrat , Quadroni Manfredo , Blackney Kevin , Schairer Rebekka , de Leval Laurence , Thome Margot
Published: March 2024

The inhibitory surface receptor programmed cell death protein 1 (PD1) is a major target for antibody–based cancer immunotherapies. Nevertheless, a substantial number of patients fail to respond to the treatment or experience adverse effects. An improved understanding of intracellular pathways targeted by PD1 is thus needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering inhibited the phosphorylation and physical association with protein kinase Cθ (PKCθ) of a variety of cytoskeleton-related proteins. PD1 blocked activation and recruitment of PKCθ to the forming immune synapse (IS) in a Src homology-2 domain–containing phosphatase-1/2 (SHP1/SHP2)-dependent manner. Consequently, PD1 engagement led to impaired synaptic phosphorylation of cytoskeleton-related proteins and formation of smaller IS. T-cell receptor induced phosphorylation of the PKCθ substrate and binding partner vimentin was long-lasting and it could be durably inhibited by PD1 triggering. Vimentin phosphorylation in intratumoral T cells also inversely correlated with the levels of the PD1 ligand, PDL1, in human lung carcinoma. Thus, PKCθ and its substrate vimentin represent important targets of PD1-mediated T-cell inhibition, and low levels of vimentin phosphorylation may serve as a biomarker for the activation of the PD1 pathway.
Mechanisms of resistance to bispecific T-cell engagers in multiple myeloma and their clinical implications
Authors: Letouzé Eric , Moreau Philippe , Munshi Nikhil , Samur Mehmet , Minvielle Stéphane , Touzeau Cyrille
Published: March 2024

Bispecific T-cell engagers (TCEs) are revolutionizing patient care in multiple myeloma (MM). These monoclonal antibodies, that redirect T cells against cancer cells, are now approved for the treatment of triple-class exposed relapsed/refractory MM (RRMM). They are currently tested in earlier lines of the disease, including in first line. Yet, primary resistance occurs in about one-third of patients with RRMM, and most responders eventually develop acquired resistance. Understanding the mechanisms of resistance to bispecific TCE is thus essential to improve immunotherapies in MM. Here, we review recent studies investigating the clinical and molecular determinants of resistance to bispecific TCE. Resistance can arise from tumor-intrinsic or tumor-extrinsic mechanisms. Tumor-intrinsic resistance involves various alterations leading to the loss of the target antigen, such as chromosome deletions, point mutations, or epigenetic silencing. Loss of major histocompatibility complex (MHC) class I, preventing MHC class I: T-cell receptor (TCR) costimulatory signaling, was also reported. Tumor-extrinsic resistance involves abundant exhausted T-cell clones and several factors generating an immunosuppressive microenvironment. Importantly, some resistance mechanisms impair response to 1 TCE while preserving the efficacy of others. We next discuss the clinical implications of these findings. Monitoring the status of target antigens in tumor cells and their immune environment will be key to select the most appropriate TCE for each patient and to design combination and sequencing strategies for immunotherapy in MM.
Gasdermin B, an asthma-susceptibility gene, promotes MAVS-TBK1 signalling and airway inflammation
Authors: Liu Tao , Liu Siqi , Rui Xianliang , Cao Ye , Hecker Julian , Guo Feng , Zhang Yihan , Gong Lu , Zhou Yihan , Yu Yuzhen , Krishnamoorthyni Nandini , Bates Samuel , Chun Sung , Boyer Nathan , Xu Shuang , Park Jin-Ah , Perrella Mark A. , Levy Bruce D. , Weiss Scott T. , Mou Hongmei , Raby Benjamin A. , Zhou Xiaobo
Published: March 2024

Rationale

Respiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction of interferon-stimulated genes (ISGs). How asthma-susceptibility genes modulate cellular response upon viral infection by fine-tuningISGinduction and subsequent airway inflammation in genetically susceptible asthma patients remains largely unknown.

Objectives

To decipher the functions of gasdermin B (encoded byGSDMB) in respiratory virus-induced lung inflammation.

Methods

In two independent cohorts, we analysed expression correlation betweenGSDMBandISGs. In human bronchial epithelial cell line or primary bronchial epithelial cells, we generatedGSDMB-overexpressing andGSDMB-deficient cells. A series of quantitative PCR, ELISA and co-immunoprecipitation assays were performed to determine the function and mechanism ofGSDMBforISGinduction. We also generated a novel transgenic mouse line with inducible expression of human uniqueGSDMBgene in airway epithelial cells and infected the mice with respiratory syncytial virus to determine the role ofGSDMBin respiratory syncytial virus-induced lung inflammationin vivo.

Results

GSDMBis one of the most significant asthma-susceptibility genes at 17q21 and acts as a novel RNA sensor, promoting mitochondrial antiviral-signalling protein (MAVS)-TANK binding kinase 1 (TBK1) signalling and subsequent inflammation. In airway epithelium,GSDMBis induced by respiratory viral infections. Expression ofGSDMBandISGssignificantly correlated in respiratory epithelium from two independent asthma cohorts. Notably, inducible expression of humanGSDMBin mouse airway epithelium led to enhancedISGsinduction and increased airway inflammation with mucus hypersecretion upon respiratory syncytial virus infection.

Conclusions

GSDMBpromotesISGsexpression and airway inflammation upon respiratory virus infection, thereby conferring asthma risk in risk allele carriers.
Ensemble learning for integrative prediction of genetic values with genomic variants
Authors: Gu Lin-Lin , Yang Run-Qing , Wang Zhi-Yong , Jiang Dan , Fang Ming
Published: March 2024

Background

Whole genome variants offer sufficient information for genetic prediction of human disease risk, and prediction of animal and plant breeding values. Many sophisticated statistical methods have been developed for enhancing the predictive ability. However, each method has its own advantages and disadvantages, so far, no one method can beat others.

Results

We herein propose an Ensemble Learning method for Prediction of Genetic Values (ELPGV), which assembles predictions from several basic methods such as GBLUP, BayesA, BayesB and BayesCπ, to produce more accurate predictions. We validated ELPGV with a variety of well-known datasets and a serious of simulated datasets. All revealed that ELPGV was able to significantly enhance the predictive ability than any basic methods, for instance, the comparisonp-value of ELPGV over basic methods were varied from 4.853E−118 to 9.640E−20 for WTCCC dataset.

Conclusions

ELPGV is able to integrate the merit of each method together to produce significantly higher predictive ability than any basic methods and it is simple to implement, fast to run, without using genotype data. is promising for wide application in genetic predictions.
Evaluating emergency response at a hospital near the Gaza border within 24 h of increased conflict
Authors: Levi Hezi , Givaty Gili , Ovadia Yaniv S. , Alon Yaniv , Saban Mor
Published: March 2024

Background

Frontline hospitals near active hostilities face unique challenges in delivering emergency care amid threats to infrastructure and personnel safety. Existing literature focuses on individual aspects like mass casualty protocols or medical neutrality, with limited analysis of operating acute services directly under fire.

Objectives

To describe the experience of a hospital situated meters from hostilities and analyze strategies implemented for triage, expanding surge capacity, and maintaining continuity of care during attacks with limited medical staff availability due to hazardous conditions. A focus will be placed on assessing how the hospital functioned and adapted care delivery models in the event of staffing limitations preventing all teams from arriving on site.

Methods

A retrospective case study was conducted of patient records from Barzilai University Medical Center at Ashkelon (BUMCA) Medical Center in Israel within the first 24 h after escalated conflict began on October 7, 2023. Data on 232 admissions were analyzed regarding demographics, treatment protocols, time to disposition, and mortality. Missile alert data correlated patient surges to attacks. Statistical and geospatial analyses were performed.

Results

Patients predominantly male soldiers exhibited blast/multisystem trauma. Patient surges at the hospital were found to be correlated with the detection of incoming missile attacks from Gaza within 60 min of launch. While 131 (56%) patients were discharged and 55 (24%) transferred within 24 h, probabilities of survival declined over time reflecting injury severity limitations. 31 deaths occurred from severe presentation.

Conclusion

Insights gleaned provide a compelling case study on managing mass casualties at the true frontlines. By disseminating BUMCA's trauma response experience, strategies can strengthen frontline hospital protocols optimizing emergency care delivery during hazardous armed conflicts through dynamic surge capacity expansion, early intervention prioritization, and infrastructure/personnel protection measures informed by risks.
Development and validation of cognitive ageing risk score (CARS) for early detection of subtle cognitive deficits in older people
Authors: Fung Ada Wai Tung , Lee Allen Ting Chun , Ma Suk Ling , Lam Linda Chiu Wa
Published: March 2024

Background

Early cognitive deficits commonly seen in older people have not been well defined and managed in primary care. The objectives are (1) to develop and validate a new risk score to estimate the risk of dementia in Chinese older population; and (2) to evaluate the use of risk score in conjunction with cognitive screening in detecting early cognitive deficits in community older people.

Methods

A development cohort of 306 cognitive healthy older adults aged 60 or above were followed for 6 years. A CARS was constructed using the estimated coefficients of risk factors associated with dementia at follow up. Validation was carried out in another five-year cohort of 383 older adults. The usefulness of CARS in detecting early cognitive deficits was evaluated.

Results

Risk factors include older age, male gender, low level of education, poorly controlled diabetes, prolonged sleep latency, fewer mind body or light exercise, loneliness, and being apolipoprotein e4 carriers. A cutoff of CARS at -1.3 had a sensitivity of 83.9% and a specificity of 75.4% to predict dementia. The area under curve was 82.5% in the development cohort. Early cognitive deficits were characterized by impaired retention (p <.001, 95% CI 0.2–0.9) and attention (p =.012, 95% CI 0.1–0.8).

Conclusion

The CARS can be used as a standard risk assessment of dementia or in conjunction with a computerized cognitive screening to evaluate a full cognitive profile for detecting early cognitive deficits. The result put forward the integration of risk algorithm into smart healthcare system to provide personalized lifestyle interventions.
A systemic infection involved in lung, brain and spine caused by Scedosporium apiospermum species complex after near-drowning: a case report and literature review
Authors: Yan Peng , Chen Junfeng , Wang Haodi , Jia Qi , Xie Jungang , Mo Guoxin
Published: March 2024

Scedosporium apiospermum species complex are widely distributed fungi that can be found in a variety of polluted environments, including soil, sewage, and decaying vegetation. Those opportunistic pathogens with strong potential of invasion commonly affect immunosuppressed populations However, few cases of scedosporiosis are reported in immunocompetent individuals, who might be misdiagnosed, leading to a high mortality rate. Here, we reported an immunocompetent case of systemtic infection involved in lung, brain and spine, caused by S. apiospermum species complex (S. apiospermum and S. boydii). The patient was an elderly male with persistent fever and systemtic infection after near-drowning. In the two tertiary hospitals he visited, definite diagnosis was extremely difficult. After being admitted to our hospital, he was misdiagnosed as tuberculosis infection, before diagnosis of S. apiospermum species complex infection by the metagenomic next-generation sequencing. His symptoms were alleviated after voriconazole treatment. In the present case, the details associated with its course were reported and published studies on Scedosporium spp. infection were also reviewed, for a better understanding of this disease and reducing the misdiagnosis rate.
Genome-wide analyses in Lyme borreliosis: identification of a genetic variant associated with disease susceptibility and its immunological implications
Authors: Vrijmoeth Hedwig D. , Ursinus Jeanine , Botey-Bataller Javier , Kuijpers Yunus , Chu Xiaojing , van de Schoor Freek R. , Scicluna Brendon P. , Xu Cheng-Jian , Netea Mihai G. , Kullberg Bart Jan , van den Wijngaard Cees C. , Li Yang , Hovius Joppe W. , Joosten Leo A. B.
Published: March 2024

Background

Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms.

Methods

We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients—divided into a discovery and validation cohort—were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments.

Results

We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses.

Conclusions

Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures.

Trial registration

The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015–02-13).
Association between short-term blood pressure variability and target organ damage in non-dialysis patients with chronic kidney disease
Authors: Chen Zhaoting , Jiang Xinying , Wu Jingcan , Lin Lin , Zhou Zhengping , Li Man , Wang Cheng
Published: March 2024

Background

It is unclear whether short-term blood pressure variability (BPV) is associated with target organ damage in patients with non-dialysis chronic kidney disease (CKD).

Methods

A cross-sectional, single-center study was conducted among 3442 non-dialysis CKD patients hospitalized in the department of Nephrology of the Fifth Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2022 and collected the demographic, laboratory, clinic blood pressure, ambulatory blood pressure data, and short-term BPV assessed by the weighted standard deviation (wSD) derived from ambulatory blood pressure monitoring (ABPM). Multivariate logistic analyses were used to evaluate the independent effects between short-term BPV and subclinical target organ damage, including left ventricular hypertrophy (LVH), abnormal carotid intima-media thickness (CIMT), low estimated glomerular filtration rate (eGFR), and albuminuria.

Results

The average age of the participants was 47.53 ± 14.06 years and 56% of participants were male. The baseline eGFR was 69 mL/min/1.73 m2. Based on the tertile distribution of wSD according to equal numbers, patients were divided into three categories with T1(< 9.66 mmHg), T2(9.66–12.23 mmHg), and T3(> 12.23 mmHg) of SBPV; T1(< 8.17 mmHg), T2(8.17–9.93 mmHg), and T3(> 9.93 mmHg) of DBPV. The participants with the higher wSD group had a higher prevalence of target organ damage than their counterparts (P-trend < 0.05). An increasing trend in short-term variability was present with advancing CKD stages (P-trend < 0.001). Multivariate logistic analyses results showed that the odds ratio (OR) of SBP wSD was (1.07 [1.03,1.11], P < 0.001) for LVH, (1.04 [1.01,1.07, P = 0.029) for abnormal CIMT, (1.05 [1.02,1.08], P = 0.002) for low eGFR, and (1.06 [1.02,1.09], P = 0.002) for albuminuria; The OR of DBP wSD was (1.07 [1.02,1.12], P = 0.005) for LVH, (1.05 [1.01,1.09], P = 0.028) for abnormal CIMT, (1.05 [1.01,1.09], P = 0.022) for low eGFR, and (1.05 [1.01,1.10], P = 0.025) for albuminuria when adjusted for confounding factors and mean BP.

Conclusions

In conclusion, short-term BPV is associated with target organ damage, and irresponsible of average blood pressure levels, in Chinese non-dialysis CKD participants.
Clinical significance of low expression of CADM3 in breast cancer and preliminary exploration of related mechanisms
Authors: Ren Huiyang , Wang Zhen , Zhang Lei , Zhu Guolian , Li Feng , Chen Bo
Published: March 2024

Background

Cell adhesion molecule 3 (CADM3), a transmembrane glycoprotein on cell membranes, plays a role in the way of ligand and receptor interaction. However, there are few studies on CADM3 in tumors, and how it works in breast cancer (BC) remains unclear.

Methods

The Cancer Genome Atlas (TCGA) database and clinical samples were used to analyze CADM3 expression and its correlation with clinicopathological factors and prognosis. Its correlation with immune infiltration was analyzed by TCGA. The effects of CADM3 on proliferation and migration were investigated by cell clonal formation, CCK-8, cell scratch and transwell assay. Protein interaction network was prepared and the function prediction of related genes was conducted. The correlation between CADM3 and MAPK pathway was further explored by western blot experiment.

Results

The expression of CADM3 in BC tissues were significantly lower than that in adjacent normal tissues. High level of CADM3 was related to better prognosis of BC patients. CADM3 was an independent prognostic factor for BC. Expression of CADM3 was significantly associated with the status of ER and PR, age and PAM50 subtypes. CADM3 positively related to many immune infiltrating cells. Overexpression of CADM3 can notably reduce cell proliferation and migration. CADM3 was related to MAPK pathway and the phosphorylation of ERK1/2 and JNK1 was inhibited in BC cells with high CADM3.

Conclusions

Our research reveals the clinical significance of CADM3 in BC and indicates the critical roles of CADM3 in immune infiltration and MAPK pathway.
Academic performance and musculoskeletal pain in adolescents with uncorrected vision problems
Authors: Thorud Hanne-Mari Schiøtz , Mudvari Prabeen Raj , Falkenberg Helle K.
Published: March 2024

Background

Undetected vision problems are common in school children, and a prevalence of up to 40% has previously been reported. Uncorrected vision and lack of optimal eye wear can have a significant impact on almost all aspects of everyday life, such as development and learning, academic performance, pain and discomfort, and quality of life. This study aimed to analyze the relationship between uncorrected vision problems, educational outcomes, and musculoskeletal pain symptoms.

Methods

A total of 152 school children (15.1 ± 0.8 years, mean ± SD; 40% males) were included in the study. All participants were recruited from a free-of-charge school vision testing program in Kathmandu, Nepal. Academic grades were collected from the school records of the participants’ nationwide final grade examinations. A questionnaire was used to record the use of digital devices, screen time, and associated symptoms, including musculoskeletal pain (Wong-Baker FACES Pain Rating Scales).

Results

A total of 61 children (40%) had uncorrected vision, with a cycloplegic refraction of SER − 0.53 ± 0.52 (mean ± SD). Children with uncorrected vision had significantly more third division grades (26 vs. 9%, p = 0.004) and shoulder pain in general/during screen use (66 vs. 43/40%, p = 0.008/0.003; 2.1/1.9 vs. 1.1/1.0 mean pain score, p = 0.002/0.001) compared with children with normal vision. Sex based subanalyses showed that only girls with uncorrected vision had more third division grades (25 vs. 4%, p = 0.006), and only boys with uncorrected vision had more shoulder pain in general/during screen use (76 vs. 28/31%, p < 0.001; 2.2/2.4 vs. 0.7 mean pain score, p < 0.001), compared with children with normal vision.

Conclusions

The results of this study showed that even small refractive errors may impact educational outcomes and musculoskeletal pain in adolescents. Most of the participating children had low myopia, easily corrected with glasses. This suggests that regular eye examinations are important in school children, and there is a need for raised awareness among parents, and school- and healthcare personnel.
The assessment of microbial infection in children with autism spectrum disorders and genetic folate cycle deficiency
Authors: Maltsev Dmitry , Solonko Iryna , Sydorenko Olena
Published: March 2024

Background

The results of disparate clinical studies indicate abnormally frequent cases of certain microorganisms in children with autism spectrum disorders (ASD). However, these data require clarification and systematization. The study aims to study the structure of the microbial profile in children with ASD and genetic folate cycle deficiency (GFCD) and consider differences in diagnostic approaches for identifying microorganisms of different types.

Methods

The study analyzed medical data from 240 children (187 boys and 63 girls) with GFCD aged 2 to 9 years. The children had clinical manifestations of ASD (the study group, SG). The control group (CG) included 53 clinically healthy children (37 boys and 16 girls) of the same age but without GFCD. Both groups of children were tested on active herpetic infections (HSV-1/2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8), ТТV, Streptococcus pyogenes, Candida albicans, Borrelia burgdorferi, Mycoplasma pneumoniae, Chlamydia pneumoniae, Yersinia enterocolitica, Toxoplasma gondii, congenital CMV neuroinfection and postnatal HSV-1/2 encephalitis. The testing used diagnostic methods specified in PubMed-indexed studies.

Results

In the SG, TTV was found in 196 children (82%), HHV-7 – in 172 (72%), HHV-6 – in 162 (68%), EBV – in 153 (64%), Streptococcus pyogenes – in 127 (53%), Candida albicans – in 116 (48%), Borrelia – in 107 (45%), Mycoplasma pneumoniae – in 94 (39%), Chlamydia pneumoniae – in 85 (35%), Yersinia entеrocolitica – in 71 (30%), Toxoplasma gondii – in 54 (23%), congenital CMV neuroinfection – in 26 (11%), and postnatal HSV-1/2 encephalitis – in 11 children (5% of cases) (p < p0.05; Z < Z0.05). In the SG, there was a higher microbial load in older children (p < p0.05; Z < Z0.05). No gender differences were found.

Conclusions

The study described and characterized a specific abnormal microbial spectrum with a predominance of viral opportunistic agents in children with ASD associated with GFCD.
Content and face validity of Workplace COVID-19 Knowledge & Stigma Scale (WoCKSS)
Authors: Baharuddin Izyan Hazwani , Ismail Nurhuda , Naing Nyi Nyi , Ibrahim Khalid , Yasin Siti Munira , Patterson Megan S.
Published: March 2024

Background

The COVID-19 pandemic has led to fear, rumours, and stigma, particularly against those infected with the virus. In Malaysia, the manufacturing industry is particularly vulnerable to COVID-19 clusters, making it critical to assess stigma attitudes among workers. To address this issue, The Workplace COVID-19 Knowledge & Stigma Scale (WoCKSS) was developed specifically for use in the manufacturing industry which served as the sample population for testing this scale. It was developed in the Malay language to ensure alignment with the local context. This study examines the content and face validity of WoCKSS, which can help assess the level of knowledge and stigma associated with COVID-19 among workers.

Methods

The WoCKSS was developed with 20 and 31 items for knowledge and stigma domains, respectively, based on an extensive review of COVID-19 literature. Content validation was conducted by four experts using a content validation form to assess the relevancy of each item to the intended construct. Content Validity Index (CVI) was calculated to measure the agreement between the experts on the relevance of each item to the intended construct. Face validation was then conducted by randomly selecting 10 respondents from the manufacturing industry, who rated the clarity and comprehension of each item using a face validation form. The Item Face Validity Index (I-FVI) was calculated to determine the clarity and comprehension of each question, and only items with an I-FVI ≥ 0.83 were retained.

Results

The WoCKSS achieved excellent content validity in both knowledge and stigma domains. Only 19 items from the knowledge domain and 24 items from the stigma domain were retained after CVI analysis. All retained items received a CVI score of 1.00, indicating perfect agreement among the experts. FVI analysis resulted in 17 items for the knowledge domain and 22 items for the stigma domain. The knowledge domain achieved a high level of agreement among respondents, with a mean I-FVI of 0.91 and a S-FVI/UA of 0.89. The stigma domain also showed high agreement, with a mean I-FVI of 0.99 and a S-FVI/UA of 0.86.

Conclusion

In conclusion, the WoCKSS demonstrated high content and face validity. However, further testing on a larger sample size is required to establish its construct validity and reliability.
Influence of academic involution atmosphere on college students’ stress response: the chain mediating effect of relative deprivation and academic involution
Authors: Liu Aichun , Shi Yanjin , Zhao Yibo , Ni Jianchao
Published: March 2024

Background

In recent years, the phenomenon of academic involution atmosphere among college students has gradually attracted the focus of education and social circles. Thus, this study targets college students as the research object and constructs a hypothetical model to explore the relationship between academic involution atmosphere and college students’ stress response, as well as the mediating role of relative deprivation and academic involution.

Methods

A survey was conducted on 1090 college students using the Academic Involution Atmosphere Scale, Relative Deprivation Scale, Personal Academic Involution Scale, and Stress Response Scale.

Results

The results show that: (1) Academic involution atmosphere, relative deprivation, and academic involution are significantly and positively correlated with stress response; (2) Academic involution atmosphere not only directly predicts college students’ stress response, but also indirectly predicts them through relative deprivation and academic involution, respectively; (3) Relative deprivation and academic involution have a chain mediating effect between academic involution atmosphere and stress response.

Conclusions

The findings of this study reveal the influence of academic involution atmosphere on college students’ stress response and the mechanism, providing beneficial insights for reducing college students’ stress response and maintaining their psychological well-being.
Optimizing targeting strategies for lithotripsy through in-vitro and in vivo studies with consideration of respiratory regularity
Authors: Cho Sung Yong , Park Hyeji , Park Jae Suk , Kim Seong Chan , Kwon Oh bin , Song Hyun jae , Choi Min Joo
Published: March 2024

Background

This work aimed to identify a method to achieve improved stone targeting and safety in shockwave lithotripsy by accounting for respiration.

Methods

We set up an electromotive device simulating renal movement during respiration to place artificial stones within the phantom gel, measuring stone weight changes before and after shockwave exposure and the cavitation damage. We conducted clinical trials using respiratory masks and sensors to monitor and analyze patient respiration during shockwave lithotripsy.

Results

The in vitro efficiency of lithotripsy was higher when adjusted for respiration than when respiration was not adjusted for. Slow respiration showed the best efficiency with higher hit rates when not adjusted for respiration. Cavitation damage was also lowest during slow respiration. The clinical study included 52 patients. Respiratory regularity was maintained above 90% in regular respiration. When respiration was regular, the lithotripsy rate was about 65.6%, which stayed at about 40% when respiration was irregular. During the lithotripsy, the participants experienced various events, such as sleep, taking off their masks, talking, movement, coughing, pain, nervousness, and hyperventilation. The generation of shockwaves based on respiratory regularity could reduce pain in patients.

Conclusion

These results suggest a more accurate lithotripsy should be performed according to respiratory regularity.
Quantitative and qualitative condylar changes following stabilization splint therapy in patients with temporomandibular joint disorders with and without skeletal lateral mandibular asymmetry: a cone beam computed tomographic study
Authors: Musa Mazen , Awad Riham , Izeldin Salma , Zhao Yunshan , Wu Hao , Wang Lu , Al-hadad Saba Ahmed , Saif Bdr Sultan , Ahmed Madiha Mohammed Saleh , Chen Xi
Published: March 2024

Background

Temporomandibular disorders (TMDs) encompass pain and dysfunction in the jaw, muscles, and adjacent structures. This study aimed to explore the quantitative (condylar position, morphology) and qualitative (bone mineral density (BMD)) therapeutic outcomes following a stabilization splint (S.S.) therapy in adult patients diagnosed with TMD (Arthralgia) with/without lateral mandibular asymmetry (MA) using cone beam computed tomography (CBCT).

Methods

In this retrospective clinical study, 60 adult TMD patients who received S.S. therapy were enrolled and allocated into the TMD group (TMDG) and TMD with MA group (TMD + MAG). The diagnosis was made according to the Diagnostic Criteria for TMD (DC/TMD) AXIS I. MA was measured from the mid-sagittal plane to the Menton point. CBCT was used to scan the temporomandibular joints pre- (T0) and post- (T1)-treatment for three-dimensional analysis. Intra- and intergroup statistical comparisons were performed using the Wilcoxon signed ranks and the Kruskal‒Wallis test.

Results

For quantitative comparisons, there was a statistically significant difference between T0 and T1 in the joint spaces of TMD + MAG (anterior, superior, posterior, and coronal lateral on the deviated side as well as in the superior, coronal medial joint space of the contralateral side). Morphologically, the deviated side had a narrower condylar width, reduced condylar height, and a steeper eminence angle. In contrast, the contralateral side tended to have a greater condylar length. For qualitative measurements, BMD also showed statistical significance between T0 and T1 in the majority of the condyle slopes (AS, SS, PS, and LS on the deviated side and in AS and MS on the contralateral side) of TMD + MAG. Additionally, only the AS and PS showed significance in TMDG.

Conclusion

Multiple joint space widening (AJS and CMS) and narrowing (SJS, PJS, and CLS) could characterize the deviated side in TMD + MA. Factors like narrower condylar width, reduced condylar height, and steeper eminence angle on the deviated side can worsen TMD + MA. Proper alignment of the condyle-disc position is essential for optimal function and load distribution, potentially affecting bone mineral density (BMD). MA plays a prominent role in disturbing bone densities. S.S. therapy shows more evident outcomes in TMD + MAG (on the deviated side compared to the contralateral side) than the TMDG.
The oral phenotype and dental management in patients with maple syrup urine disease; case report and scoping review
Authors: Hassona Yazan , Alqaisi Dua’a , Flaifl Yara , Alkilani Asma
Published: March 2024

Background and objectives

The literature about oral manifestations and dental management in maple syrup urine disease (MSUD) is sparse. The aim of this report is to present a new case of MSUD with special emphasis on oral findings and to review the relevant literature.

Method

A case report of a 4-year-old boy with MSUD was described according to the CARE guidelines for describing case reports. Scoping review of relevant literature was performed, according to the PRISMA-ScR guidelines, by searching PubMed, Medline, Embase, and the grey literature for articles describing dental management and/or oral manifestations in MSUD.

Results

The initial search identified 219 articles, but only 4 met the inclusion criteria. Rampant caries and plaque induced gingivitis were the main oro-dental findings in MSUD. Other oral findings included enamel hypoplasia, skeletal abnormalities, and abnormal oral behaviors. Disease-related factors appeared to play a major role in the development of the observed oral phenotype.

Conclusion

Oral health in MSUD seems to be influenced by the reliance on semi-synthetic diet and associated neurocognitive complications. Tailored oral health promotional interventions should be included in the multidisciplinary management of patients with MSUD.
Epidemiology and risk factors of oral frailty among older people: an observational study from China
Authors: Yin Yueheng , Zhao Yue , Fei Yang , Liu Ying , Ji Yun , Shan Enfang , Niu Shuzhen , Xing Ying , Ding Jingjing , Li XianWen
Published: March 2024

Objectives

This study aimed to compare the prevalence of oral frailty among community-dwelling older people in Nanjing, China with the usage of different measurements, and to investigate the potential risk factors of oral frailty.

Design

Cross-sectional study.

Setting and participants

A total of 338 community-dwelling older people in Nanjing, China were recruited.

Methods

Oral frailty was measured based on the Oral Frailty Index-8 (OFI-8) scale and other measurement methods including the number of natural teeth (TN), repetitive saliva-swallowing test (RSST), and oral diadochokinesis (ODK). The chi-square test and the binary logistic regression analysis were performed to identify potential risk factors for oral frailty.

Results

There were 310 participants included in the analysis. Prevalence of oral frailty by using the OFI-8, OFI-8 + TN, OFI-8 + ODK, OFI-8 + TN + ODK and RSST measurement methods were 69.0%, 27.4%, 51.9%, 21.0% and 2.9%, respectively. Passive smoking (OR = 2.04; 95%CI 1.03–4.03), being widowed/unmarried (OR1 = 2.53; 95%CI 1.25–5.10; OR2 = 2.94; 95%CI 1.12–7.77), pre-frailty (OR = 1.76; 95%CI 1.03–3.01), frailty (OR = 3.01; 95%CI 1.39–6.54), and aged 80 years and above (OR = 3.99; 95%CI 1.35–11.81) were found to be risk factors of oral frailty by the usage of the four kinds of measurement methods.

Conclusions and implications

The definition and diagnostic criteria of oral frailty are strongly needed to be unified in future research. Only subjective assessment is not enough for assessing oral frailty. Among objective indicators, RSST is not suitable as a screening method for oral frailty. In addition, objective indicators including TN and ODK should be valued for early screening and preventive interventions. The risk factors of oral frailty include physical frailty, passive smoking, and being widowed.
Measuring patients’ medical treatment preferences in advance care planning: development and validation of the Treat-Me-ACP instrument – a secondary analysis of a cluster-randomized controlled trial
Authors: Jaschke Julia , Schnakenberg Rieke , Silies Katharina , Berg Almuth , Kirchner Änne , Hoffmann Falk , Meyer Gabriele , Köpke Sascha , Köberlein-Neu Juliane
Published: March 2024

Background

Advance Care Planning interventions should be evaluated as broadly as possible to gain a holistic understanding of the Advance Care Planning process. However, validated early stage outcome instruments are lacking. Therefore, the Treatment-Preference-Measure-Advance Care Planning (Treat-Me-ACP) instrument was developed and validated as part of the cluster-randomized controlled trial STADPLAN (Study on Advance Care Planning in care-dependent community-dwelling older persons) to assess the effects of Advance Care Planning interventions on patients’ medical treatment preferences.

Methods

The design of Treat-Me-ACP is based on the Emanuel Medical Directive and the Life Support Preferences Questionnaires. Using a multi-stage team approach a preliminary version of the Treat-Me-ACP was developed and pre-tested. The pre-tested instrument consists of one global medical care goal-item, five hypothetical scenarios with five hypothetical treatments, and one how would you feel-item within each scenario. A total of five scenario preference scores and five treatment preference scores can be formed. This version was subsequently applied to a subsample of the STADPLAN project (n = 80) to assess patient’s preferences at baseline (T0) and at 12-month follow-up (T2). The further validation steps were based on this subsample and included: (1) acceptance by using completion rate and frequencies of missing data, (2) internal consistency by using Cronbach’s α to test whether it was possible to create preference scores by scenario and treatment, (3) concurrent validation examining the association between the global medical care goal-item and the preference scores and the association between the how would you feel-items and the scenario preference scores, and (4) responsiveness of the instrument to changes in preferences for life-sustaining treatments by comparing preference scores from T0 to T2 between study groups.

Results

Acceptance of the instrument was high. Results of concurrent validation indicate that the five scenarios represent the global medical care goal well. The preference scores showed an average tendency for decreasing preferences for life-sustaining treatments across all scales for the intervention group during study follow-up.

Conclusions

The Treat-Me-ACP can be used to evaluate the dynamics of patients’ medical treatment preferences in Advance Care Planning. It has been validated for care-dependent community-dwelling older persons and can be used as an additional outcome measure in evaluating the effectiveness of ACP interventions.

Trial registration

German Clinical Trials Register: DRKS00016886 on 04/06/2019.
Evaluation of patient health outcomes of a student-run free clinic in East Harlem
Authors: Jiang Joy J. , Link Katie , Mellgard George , Silvestri Francesca , Qian Daniel , Chennareddy Susmita , Tran Michelle , Goldstein Yoni , Frid Gabriela , Band Isabelle , Saali Alexandra , Thomas David C. , Jasti Harish , Meah Yasmin S.
Published: March 2024

Background

Most United States medical schools have affiliated student-run free clinics, but the quality of services provided in such contexts compared to national metrics is unknown. This study determines whether a student-run, attending-supervised free clinic servicing a low-income and minority race patient population in New York City can meet national metrics of care.

Methods

Through chart review from January 1, 2020 to December 31, 2020, patient outcomes and service utilization in the Healthcare Effectiveness Data and Information Set were examined and compared to national rates of patients using Medicaid HMO or Medicare. Patients are ≥ 21 years of age, residents of East Harlem, and ineligible for health insurance because of legal residency requirements. The majority identify as Hispanic and speak Spanish as their primary language. All patients who were seen in the clinic during the 2020 calendar year were included. The primary study outcome is the number of Healthcare Effectiveness Data and Information Set measures in which patients, seen in a student-run free clinic, meet or exceed national comparisons.

Results

The healthcare outcomes of 238 patients, mean age 47.8 years and 54.6% female, were examined in 18 Healthcare Effectiveness Data and Information Set measures. The student-run free clinic met or exceeded national metrics in 16 out of 18 categories.

Conclusions

The student-run free clinic met or exceeded the national standard of care according to national metrics. Evidence-based priorities have been clarified for future improvement. Other student-run free clinics should similarly evaluate the quality of their services.
The effect of spaced learning on the learning outcome and retention of nurse anesthesia students: a randomized-controlled study
Authors: Khalafi Ali , Fallah Zahra , Sharif-Nia Hamid
Published: March 2024

Background

Poor learning and retention are common problems of students, which may be alleviated by optimization of widely used educational methods such as lectures. This study aimed to investigate the effect of spaced learning on the learning outcome and retention of nurse anesthesia students.

Methods

This was a randomized controlled study with a pre-and post-test design on 64 nurse anesthesia students who were divided into two groups of spaced lecture (n = 32) and conventional lecture (n = 32). The spaced lectures included three 30-minute training sessions with 10-minute intervals while the conventional sessions including 90 min of continuous training. Students’ knowledge was measured using one valid and reliable questionnaire developed by the research team. All students in both groups took a pre-test, and their level of knowledge acquisition was evaluated immediately after the training. Their level of knowledge retention was tested two and four weeks after the lecture.

Results

There was no significant difference between the two groups regarding demographic characteristics (p > 0.05). In the pre-test, the mean score of knowledge in the intervention group was lower than that in the control group, there was no significant difference (p = 0.177). But after the intervention, the mean scores of learning outcome and retention in the intervention group were significantly higher than those in the control group (p < 0.001, eta = 0.576). Also, the results showed that learning outcome and retention across the three academic semesters in the two groups are significantly different, and students with a higher academic semester obtained a significantly higher mean score of knowledge and retention (p < 0.001, eta = 0.604).

Conclusion

Spaced learning improves nurse anesthesia students’ knowledge and retention more than conventional method. Future studies focusing on spaced learning should specifically examine the impact of duration and number of intervals, as well as the time gap between training and measurement of learning retention.