bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering newly identified aldehyde dehydrogenase 2 genetic variants that lead to acetaldehyde accumulation after an alcohol challenge
Authors: Rwere Freeborn , White Joseph R. , Hell Rafaela C. R. , Yu Xuan , Zeng Xiaocong , McNeil Leslie , Zhou Kevin N. , Angst Martin S. , Chen Che-Hong , Mochly-Rosen Daria , Gross Eric R. 
Published: July 2024

Abstract
Background
Aldehyde dehydrogenase 2 (ALDH2) is critical for alcohol metabolism by converting acetaldehyde to acetic acid. In East Asian descendants, an inactive genetic variant in ALDH2, rs671, triggers an alcohol flushing response due to acetaldehyde accumulation. As alcohol flushing is not exclusive to those of East Asian descent, we questioned whether additional ALDH2 genetic variants can drive facial flushing and inefficient acetaldehyde metabolism using human testing and biochemical assays.

Methods
After IRB approval, human subjects were given an alcohol challenge (0.25 g/kg) while quantifying acetaldehyde levels and the physiological response (heart rate and skin temperature) to alcohol. Further, by employing biochemical techniques including human purified ALDH2 proteins and transiently transfected NIH 3T3 cells, we characterized two newly identified ALDH2 variants for ALDH2 enzymatic activity, ALDH2 dimer/tetramer formation, and reactive oxygen species production after alcohol treatment.

Results
Humans heterozygous for rs747096195 (R101G) or rs190764869 (R114W) had facial flushing and a 2-fold increase in acetaldehyde levels, while rs671 (E504K) had facial flushing and a 6-fold increase in acetaldehyde levels relative to wild type ALDH2 carriers. In vitro studies with recombinant R101G and R114W ALDH2 enzyme showed a reduced efficiency in acetaldehyde metabolism that is unique when compared to E504K or wild-type ALDH2. The effect is caused by a lack of functional dimer/tetramer formation for R101G and decreased Vmax for both R101G and R114W. Transiently transfected NIH-3T3 cells with R101G and R114W also had a reduced enzymatic activity by ~ 50% relative to transfected wild-type ALDH2 and when subjected to alcohol, the R101G and R114W variants had a 2-3-fold increase in reactive oxygen species formation with respect to wild type ALDH2.

Conclusions
We identified two additional ALDH2 variants in humans causing facial flushing and acetaldehyde accumulation after alcohol consumption. As alcohol use is associated with a several-fold higher risk for esophageal cancer for the E504K variant, the methodology developed here to characterize ALDH2 genetic variant response to alcohol can lead the way precision medicine strategies to further understand the interplay of alcohol consumption, ALDH2 genetics, and cancer.
Exploring work ability, psychosocial job demands and resources of employees in low-skilled jobs: a German cross-sectional study
Authors: Kaboth Arthur , Hünefeld Lena , Lück Marcel 
Published: July 2024

Abstract
Background
Extending working lives due to labour market and pension regulations makes maintaining and promoting work ability necessary. The coronavirus pandemic has shown that employees in low-skilled jobs (no qualification required) contribute significantly to society and the economy. Research on these employees has been neglected in Germany for many decades despite demanding working conditions. Therefore, we investigate the relationship between low-skilled jobs and work ability. Moreover, we explore this relationship’s variation by psychosocial work demands and resources.

Methods
We use two waves of the German Study on Mental Health at Work (S-MGA). We calculate Ordinary-Least-Squares (OLS) regression models with pooled data (n = 6,050) to analyse the relationship between job requirement level and work ability. We also explore the contribution of job demands and resources on this relationship with interaction models. We use the Copenhagen Psychosocial Questionnaire (COPSOQ), to assess psychosocial work demands and resources.

Results
Employees performing low-skilled jobs report significantly less work ability than those in medium- or high-skilled jobs. Interaction models show significantly greater work ability for employees in medium- and high-skilled jobs with high influence on their work (amount or tasks). Unexpectedly, employees in low-skilled jobs have lower work ability with more influence on their work. Furthermore, high role clarity, describing responsibility, authority and work goals, is associated with lower levels of work ability among employees in low-skilled jobs.

Conclusions
The moderating effect of role clarity on the work ability of employees in low-skilled jobs can possibly be attributed to skills mismatch and limited responsibility, as well as a lack of self-perceived collective purpose of the job. The moderation of the influence on work dimension supports results of previous studies. Too much job autonomy can have negative effects under certain circumstances and is therefore perceived as a job demand in some studies. Consequently, mechanisms concerning psychosocial work demands and resources must be investigated in further studies with different theoretical approaches. The imbalance of job demands and resources shows that employers should invest in preserving the work ability to prevent early exit from the labour market in an aging society.
Using a thermal gradient table to study plant temperature signalling and response across a temperature spectrum
Authors: Praat Myrthe , Jiang Zhang , Earle Joe , Smeekens Sjef , van Zanten Martijn 
Published: July 2024

AbstractPlants must cope with ever-changing temperature conditions in their environment. In many plant species, suboptimal high and low temperatures can induce adaptive mechanisms that allow optimal performance. Thermomorphogenesis is the acclimation to high ambient temperature, whereas cold acclimation refers to the acquisition of cold tolerance following a period of low temperatures. The molecular mechanisms underlying thermomorphogenesis and cold acclimation are increasingly well understood but neither signalling components that have an apparent role in acclimation to both cold and warmth, nor factors determining dose-responsiveness, are currently well defined. This can be explained in part by practical limitations, as applying temperature gradients requires the use of multiple growth conditions simultaneously, usually unavailable in research laboratories. Here we demonstrate that commercially available thermal gradient tables can be used to grow and assess plants over a defined and adjustable steep temperature gradient within one experiment. We describe technical and thermodynamic aspects and provide considerations for plant growth and treatment. We show that plants display the expected morphological, physiological, developmental and molecular responses that are typically associated with high temperature and cold acclimation. This includes temperature dose-response effects on seed germination, hypocotyl elongation, leaf development, hyponasty, rosette growth, temperature marker gene expression, stomatal conductance, chlorophyll content, ion leakage and hydrogen peroxide levels. In conclusion, thermal gradient table systems enable standardized and predictable environments to study plant responses to varying temperature regimes and can be swiftly implemented in research on temperature signalling and response.
Clinical cases series and pathogenesis of Lamb-Shaffer syndrome in China
Authors: Lian Ruofei , Wu Gongao , Xu Falin , Zhao Shichao , Li Mengchun , Wang Haiyan , Jia Tianming , Dong Yan 
Published: July 2024

Abstract
Background
Lamb-Shaffer syndrome (LAMSHF, OMIM: 616803) is a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, which is attributed to haploinsufficiency by heterozygous variants of SOX5 gene (SRY-Box Transcription Factor 5, HGNC: 11201) on chromosome 12p12. A total of 113 cases have been reported in the world, however, only 3 cases have been reported.in China. Here, we aimed to report novel variants of SOX5 gene and provide examples for clinical diagnosis by reporting the clinical phenotype of a series of Chinese patients with LAMSHF.

Methods
This study retrospectively collected the information of families of LAMSHF patients in China. Whole Exome Sequencing (WES) were performed to confirm the diagnosis of 4 children with unexplained developmental delay or epilepsy. A minigene splicing assay was used to verify whether the splice variant affected splicing. Meanwhile, a literature review was conducted to analyze the clinical and genetic characteristics of patients with LAMSHF.

Results
Three of the LAMSHF patients had a de novo heterozygous mutation in the SOX5 gene respectively, c.290delC (p.Pro97fs*30), chr12:23686019_24048958del, c.1772-1C > A, and the remaining one had a mutation inherited from his father, c.1411C > T (p.Arg471*). The main clinical manifestations of these children were presented with global developmental delays, and one of them also had seizures. And the results of the minigene experiment indicated that the splice variant, c.1772-1C > A, transcribed a novel mRNA product which leaded to the formation of a truncated protein.

Conclusions
Through a comprehensive review and analysis of existing literature and this study showed intellectual disability, speech delay and facial dysmorphisms were common clinical manifestation, while the seizures and EEG abnormalities were rare (21/95, 22.16%). Notably, we represent the largest sample size of LAMSHF in Asia that encompasses previously unreported SOX5 gene mutation, and a minigene testing have been conducted to validate the pathogenicity of the c.1772-1C > A splice variant. The research further expands the phenotype and genotype of LAMSHF while offers novel insights for potential pathogenicity of genes locus.
Natural history in Malan syndrome: survey of 28 adults and literature review
Authors: Huynh T. N. , Delagrammatikas C. G. , Chiriatti L. , Panfili A. , Ventarola K. , Menke L. A. , Tartaglia M. , Huisman S. A. , Priolo M. 
Published: July 2024

Abstract
Background
Malan syndrome (MALNS), previously referred to as “Sotos syndrome 2” due to its resemblance to Sotos syndrome (SS), is an ultra-rare neurodevelopmental disorder characterized by overgrowth, typical craniofacial features, intellectual disability (ID), and a range of psychobehavioral, musculoskeletal, vision and neurological signs. As MALNS and SS partly overlap, it is essential to more accurately profile their clinical presentations and highlight their differences in order to improve syndrome specific management. An increasing number of individuals with MALNS reach adult-age though the natural history of the disorder is poorly characterized due to the small number of adult individuals described so far. As a consequence, current guidelines are limited to the pediatric population. Further delineation of MALNS is essential to optimize care in adulthood.

Results
A mixed approach based on cross-sectional data collection with a survey disseminated to caregivers of adults with molecularly confirmed MALNS and literature review was conducted. Twenty-eight caregivers completed the survey. Clinical presentation in adulthood is multisystemic and defined by psychobehavioral comorbidities (96%), musculoskeletal involvement (96%), vision impairment (96%) and neurological complications (86%). The most common signs were anxiety (79%), hypotonia (75%), movement difficulty (75%), scoliosis (64%), problems with coordination (61%), strabismus (57%), constipation (54%), breastbone abnormalities (54%) and advanced bone age during childhood (54%). Impaired vision was complicated by vision decline (36%) and optic atrophy (32%). We report some previously unidentified features, including high pain threshold (46%), incontinence (25%), tremors (21%), muscle hypoplasia (18%) and tics (18%).

Conclusions
This survey in the adult population has allowed a more complete description of the natural history of MALNS. Our findings will contribute to the development and improvement of standards of care for adults with MALNS to assure optimal health monitoring and treatment of evolutive complications. We propose additional recommendations to the previous dataset of clinical evaluations specifically applied to adults. The comparison of MALNS and SS adult presentation highlights significant differences in terms of prevalence and severity of ID, behavioral issues, and vision problems, confirming that a proper differential diagnosis between the two conditions is indispensable to guide physicians and mental health professionals to syndrome specific management.
Upadacitinib monotherapy versus methotrexate monotherapy in patients with rheumatoid arthritis: efficacy and safety through 5 years in the SELECT-EARLY randomized controlled trial
Authors: van Vollenhoven Ronald , Strand Vibeke , Takeuchi Tsutomu , Chávez Nilmo , Walter Pablo Mannucci , Singhal Atul , Swierkot Jerzy , Khan Nasser , Bu Xianwei , Li Yihan , Penn Sara K. , Camp Heidi S. , Aelion Jacob 
Published: July 2024

Abstract
Background
To evaluate the efficacy and safety of upadacitinib monotherapy versus methotrexate (MTX) monotherapy over 5 years among MTX-naïve patients with moderately to severely active rheumatoid arthritis (RA) in the long-term extension (LTE) of the phase 3 SELECT-EARLY trial.

Methods
Patients were randomized to receive upadacitinib 15 mg or 30 mg or MTX. Patients who did not achieve CDAI remission and had < 20% improvement in tender and swollen joint counts at week 26 received rescue therapy (addition of MTX in the upadacitinib group and addition of upadacitinib in the MTX group). Efficacy assessments were evaluated over 5 years and are reported as observed (AO) for patients who received continuous monotherapy with upadacitinib 15/30 mg or MTX and by randomized group applying non-responder imputation (NRI). Treatment-emergent adverse events (TEAEs) per 100 patient-years were summarized over 5 years.

Results
Of 945 patients randomized and treated, 775 (82%) completed week 48 and entered the LTE on study drug. Higher proportions of patients consistently achieved disease activity targets over 5 years with upadacitinib than MTX. In AO analyses, 53%/59% of patients attained CDAI remission with upadacitinib 15/30 mg versus 43% with MTX at week 260. NRI analyses showed better CDAI, DAS28(CRP), and ACR responses with upadacitinib relative to MTX at week 260 (all comparisons, nominal P < .001). Upadacitinib treatment also resulted in numerically greater inhibition of structural joint progression through week 260 compared to MTX. Most TEAEs, serious AEs, and AEs leading to discontinuation were numerically higher in patients receiving upadacitinib 30 mg. Rates of serious infections, herpes zoster, creatine phosphokinase elevation, nonmelanoma skin cancer, and neutropenia were numerically higher with upadacitinib than MTX. The observed safety profile of upadacitinib over 5 years was consistent with earlier trial results and integrated phase 3 safety analyses.

Conclusions
Upadacitinib showed better clinical responses versus MTX in patients with RA throughout the 5-year trial. Higher rates of several AEs were observed with upadacitinib, especially in the 30 mg group, compared to MTX. When used as monotherapy in MTX-naïve patients, the approved upadacitinib 15 mg dose showed better long-term efficacy versus MTX and an overall favorable benefit-risk profile.

Trial registration
NCT02706873.
HbpA from Glaesserella parasuis induces an inflammatory response in 3D4/21 cells by activating the MAPK and NF-κB signalling pathways and protects mice against G. parasuis when used as an immunogen
Authors: Yang Zhen , Zhang Yiwen , Zhao Qin , Du Senyan , Huang Xiaobo , Wu Rui , Yan Qigui , Han Xinfeng , Wen Yiping , Cao San-Jie 
Published: July 2024

AbstractGlaesserella parasuis is usually a benign swine commensal in the upper respiratory tract, but virulent strains can cause systemic infection characterized by pneumonia, meningitis, and fibrinous polyserositis. The intensive pulmonary inflammatory response following G. parasuis infection is the main cause of lung injury and death in pigs. Vaccination has failed to control the disease due to the lack of extended cross-protection. Accumulating evidence indicates that the heme-binding protein A (HbpA) is a potential virulence determinant and a promising antigen candidate for the development of a broader range of vaccines. However, it is not yet known whether HbpA contributes to G. parasuis virulence or has any potential immune protective effects against G. parasuis. Here, we show that HbpA can induce the transcription and secretion of proinflammatory cytokines (IL-6, TNF-α, and MCP-1) in porcine alveolar macrophages (PAM, 3D4/31). The HbpA protein is recognized by Toll-like receptors 2 and 4 on 3D4/21 macrophages, resulting in the activation of MAP kinase and NF-κB signalling cascades and the transcription and secretion of proinflammatory cytokines. HbpA contributes to virulence and bacterial pulmonary colonization in C57BL/6 mice and plays a role in adhesion to host cells and evasion of the bactericidal effect of pulmonary macrophages. In addition, mice immunized with HbpA were partially protected against challenge by G. parasuis SC1401. The results suggest that HbpA plays an important role in the pathogenesis of disease caused by G. parasuis and lay a foundation for the development of a subunit or chimeric anti-G. parasuis vaccine.
Effect of Air Pollutants Particulate Matter PM2.5, PM10, Carbon Monoxide (CO), Nitrogen Dioxide (NO2), Sulfur Dioxide (SO2), and Ozone (O3) on Fractional Exhaled Nitric Oxide (FeNO)
Authors: Meo Sultan Ayoub , Salih Mustafa , Alkhalifah Joud Mohammed , Alsomali Abdulaziz Hassan , Almushawah Abdullah Abdulrahman 
Published: July 2024

Objectives: This study aimed to investigate the effect of Environmental Pollutants Particulate Matter PM2.5, PM10, Carbon Monoxide (CO), Nitrogen Dioxide (NO2), Sulfur Dioxide (SO2), and Ozone (O3) on lung airway inflammation by assessing the Fractional Exhaled Nitric Oxide (FeNO) in students studying in schools located in or away from air-polluted areas.
Methods: This matched case-control cross-sectional study was conducted in the Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia from August 2022 to July 2023. In this study, two schools were selected, one was located near a traffic-polluted area (School #1), and the second was located away from the traffic-polluted area (School #2). A total of 300 students were recruited, 150 (75 male and 75 female) students from the school located in a traffic-polluted area, and 150 students (75 male and 75 female) from the school located away from a traffic-polluted area. Environmental pollutants PM2.5, PM10, CO, NO2, O3, and SO2, were recorded. The Fractional Exhaled Nitric Oxide (FeNO) was measured using a Niox Mino.
Results: The mean concentration of PM2.5, PM10, CO, NO2, O3, and SO2 were 35.00±0.65 significantly higher in a school located in motor vehicle polluted area compared to a school located away from a motor vehicle-polluted area (29.95±0.32) (p=0.001). The mean values for FeNO were significantly higher (18.75±0.90) among students studying in a school located in the motor vehicle-polluted area compared to students studying in a school located away from the motor vehicle-polluted area (11.26±0.56) (p=0.001).
Conclusions: Environmental pollution can cause lung inflammation among students in schools located in traffic-polluted areas.
doi: https://doi.org/10.12669/pjms.40.8.9630
How to cite this: Meo SA, Salih MA, Alkhalifah JM, Alsomali AH, Almushawah AA. Effect of Air Pollutants Particulate Matter PM2.5, PM10, Carbon Monoxide (CO), Nitrogen Dioxide (NO2), Sulfur Dioxide (SO2), and Ozone (O3) on Fractional Exhaled Nitric Oxide (FeNO). Pak J Med Sci. 2024;40(8):---------. doi: https://doi.org/10.12669/pjms.40.8.9630
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Clinical efficacy of Apatinib combined with Epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) in nonsmall cell lung cancer after EGFR-TKI resistance
Authors: Tian Ruifen , Guo Yi , Zhang Xing , Zhang Xia , Song Xia 
Published: July 2024

Objective: To evaluate the efficacy and safety of Apatinib combined with epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) in the treatment of patients with non-small cell lung cancer (NSCLC) and acquired EGFR-TKI resistance.
Methods: Clinical records of 106 patients with NSCLC at Shanxi Tumor Hospital of the Chinese Academy of Medical Sciences Cancer Hospital from January 2017 to October 2020, with acquired drug resistance after EGFR-TKI treatment were retrospectively analyzed. Among them, 52 patients received Apatinib combined with EGFR-TKI (Apatinib group), and 54 patients received a standard chemotherapy (pemetrexed combined with platinum) (chemotherapy group). Clinical efficacy indicators, follow-up results, and adverse reactions in both groups were compared.
Results: There was no significant difference in the objective response rate and disease control rate between the two groups (P>0.05). The progression free survival (PFS) of the Apatinib group was significantly longer than that of the chemotherapy group (10.5 months vs. 5.7 months; P<0.05). There was no significant difference in adverse reactions between the two groups (P>0.05).
Conclusions: Compared with standard chemotherapy, Apatinib combined with EGFR-TKI has the same efficacy in treating NSCLC patients with EGFR-TKI resistance, and was associated with longer PFS with no significant increase in adverse reactions.
doi: https://doi.org/10.12669/pjms.40.8.9682
How to cite this: Tian R, Guo Y, Zhang X, Zhang X, Song X. Clinical efficacy of Apatinib combined with Epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) in nonsmall cell lung cancer after EGFR-TKI resistance. Pak J Med Sci. 2024;40(8):---------. doi: https://doi.org/10.12669/pjms.40.8.9682
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Technologia w służbie komunizmu
Authors: Lekki Wiktor Jan 
Published: July 2024

Celem niniejszego artykułu recenzyjnego jest przybliżenie książki W Pełni Zautomatyzowany Luksusowy Komunizm. Manifest autorstwa Aarona Bastaniego. W tym celu przeprowadzone jest krótkie omówienie struktury tej książki i zawartych w niej tez przy równoczesnej próbie umiejscowienia jej treści w szerszym kontekście filozoficznym. Tematem ostatniej części pracy jest bliższe porównanie metodologii oraz pojęciowości wykorzystywanej przez Aarona Bastaniego i Karola Marksa oraz wskazanie różnic, które są przyczyną istotnych różnic w postrzeganiu politycznego wymiaru przemian społecznych przez obu autorów.