bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifunctional interaction of CihC/FbpC orthologs of relapsing fever spirochetes with host-derived proteins involved in adhesion, fibrinolysis, and complement evasion
Authors: Damm Ann-Sophie , Reyer Flavia , Langhoff Luisa , Lin Yi-Pin , Falcone Franco Harald , Kraiczy Peter 
Published: April 2024

IntroductionRelapsing fever (RF) remains a neglected human disease that is caused by a number of diverse pathogenic Borrelia (B.) species. Characterized by high cell densities in human blood, relapsing fever spirochetes have developed plentiful strategies to avoid recognition by the host defense mechanisms. In this scenario, spirochetal lipoproteins exhibiting multifunctional binding properties in the interaction with host-derived molecules are known to play a key role in adhesion, fibrinolysis and complement activation.MethodsBinding of CihC/FbpC orthologs to different human proteins and conversion of protein-bound plasminogen to proteolytic active plasmin were examined by ELISA. To analyze the inhibitory capacity of CihC/FbpC orthologs on complement activation, a microtiter-based approach was performed. Finally, AlphaFold predictions were utilized to identified the complement-interacting residues.Results and discussionHere, we elucidate the binding properties of CihC/FbpC-orthologs from distinct RF spirochetes including B. parkeri, B. hermsii, B. turicatae, and B. recurrentis to human fibronectin, plasminogen, and complement component C1r. All CihC/FbpC-orthologs displayed similar binding properties to fibronectin, plasminogen, and C1r, respectively. Functional studies revealed a dose dependent binding of plasminogen to all borrelial proteins and conversion to active plasmin. The proteolytic activity of plasmin was almost completely abrogated by tranexamic acid, indicating that lysine residues are involved in the interaction with this serine protease. In addition, a strong inactivation capacity toward the classical pathway could be demonstrated for the wild-type CihC/FbpC-orthologs as well as for the C-terminal CihC fragment of B. recurrentis. Pre-incubation of human serum with borrelial molecules except CihC/FbpC variants lacking the C-terminal region protected serum-susceptible Borrelia cells from complement-mediated lysis. Utilizing AlphaFold2 predictions and existing crystal structures, we mapped the putative key residues involved in C1r binding on the CihC/FbpC orthologs attempting to explain the relatively small differences in C1r binding affinity despite the substitutions of key residues. Collectively, our data advance the understanding of the multiple binding properties of structural and functional highly similar molecules of relapsing fever spirochetes proposed to be involved in pathogenesis and virulence.
Pain control and neonatal outcomes in 211 women under epidural anesthesia during childbirth at high altitude in Qinghai, China
Authors: Wang Pengxia , Li Kaihui , Wu Dongliang , Cheng Sen , Zeng Yinying , Gao Peng , Wang Zhibing , Liu Shanshan 
Published: April 2024

BackgroundHigh altitudes are characterized by low-pressure oxygen deprivation. This is further exacerbated with increasing altitude. High altitudes can be associated with reduced oxygenation, which in turn, can affect labor, as well as maternal and fetal outcomes. Epidural anesthesia can significantly relieve labor pain. This study aimed to assess the effects of elevation gradient changes at high altitude on the analgesic effect of epidural anesthesia, labor duration, and neonatal outcomes.MethodsWe divided 211 women who received epidural anesthesia into groups according to varying elevation of their residence (76 in Xining City, mean altitude 2,200 m; 63 in Haibei Prefecture, mean altitude 3,655 m; and 72 in Yushu Prefecture, mean altitude 4,493 m). The analgesic effect was assessed using a visual analog scale (VAS). Labor duration was objectively recorded. The neonatal outcome was assessed using Apgar scores and fetal umbilical artery blood pH.ResultsVAS scores among the three groups did not differ significantly (p &gt; 0.05). The neonatal Apgar scores in descending order were: Xining group &gt; Haibei group &gt; Yushu group (p &lt; 0.05). The stage of labor was similar among the three groups (p &gt; 0.05). Fetal umbilical artery blood pH in descending order were: Xining group &gt; Haibei group &gt; Yushu group (p &lt; 0.05).ConclusionElevation gradient changes in highland areas did not affect the efficacy of epidural anesthesia or labor duration. However, neonatal outcomes were affected.
Correlation analysis between HLA-DQA1*0102/DQB1*0602 genotypes and narcolepsy patients in China
Authors: Zhao Wanyu , Zhang Baokun , Yan Zian , Zhao Mengke , Zhang Xiao , Zhang Xiaoyu , Liu Xiaomin , Tang Jiyou 
Published: April 2024

Background and objectiveAt present, the etiology of narcolepsy is not fully understood, and it is generally believed to be an autoimmune reaction caused by interactions between environmental and genetic factors. Human leukocyte antigen (HLA) class II genes are strongly associated with this gene, especially HLA-DQB1*0602/DQA1*0102. In this study, we mainly analyzed the correlation between different genotypes of HLA-DQB1*0602/DQA1*0102 and clinical manifestations in Chinese patients with narcolepsy.Experimental methodNarcolepsy patients who were treated at the Department of Neurology, The First Affiliated Hospital of Shandong First Medical University from January 2021 to September 2023 were selected. General information, sleep monitoring data, cerebrospinal fluid (CSF) orexin levels, and human leukocyte antigen gene typing data were collected. The statistical analysis was performed using SPSS 26.0, and the graphs were drawn using GraphPad Prism 9.5.Main resultsA total of 78 patients were included in this study. The DQA1 and DQB1 gene loci were detected in 54 patients, and only the DQB1 gene locus was detected in 24 narcoleptic patients. The most common allele at the HLA-DQB1 locus was *0602 (89.7%), and the most common genotype at this locus was *0602*0301 (19.2%), followed by *0602*0602 (17.9%). The most common phenotype of the HLA-DQA1 locus is *0102 (92.6%), and the most common genotype of this locus is *0102*0102 (27.8%), followed by *0102*0505 (14.8%). There were significant differences (p &lt; 0.05) between HLA-DQB1*0602-positive and HLA-DQB1*0602-negative patients in terms of orexin-A levels, presence or absence of cataplexy, UNS, PSG sleep latency, REM sleep latency, N1 sleep percentage, oxygen depletion index, and average REM latency on the MSLT. The HLA-DQA1*0102-positive and HLA-DQA1*0102-negative patients showed significant differences (p &lt; 0.05) in disease course, presence or absence of sudden onset, PSG REM sleep latency, N1 sleep percentage, and average REM latency on the MSLT. There were significant differences in the average REM latency of the MSLT between HLA-DQB1*0602/DQA1*0102 homozygous and heterozygous patients p &lt; 0.05, and no differences were found in the baseline data, orexin-A levels, scale scores, or other sleep parameters.ConclusionDifferent genotypes of HLA-DQA1*0102/DQB1*0602 are associated with symptoms of cataplexy in Chinese narcoleptic patients. Homozygous individuals have a shorter mean REM latency in the MSLT, greater genetic susceptibility, and relatively more severe sleepiness.
Novel insights into tumorigenesis revealed by molecular analysis of Lynch syndrome cases with multiple colorectal tumors
Authors: Olkinuora Alisa , Mäki-Nevala Satu , Ukwattage Sanjeevi , Ristimäki Ari , Ahtiainen Maarit , Mecklin Jukka-Pekka , Peltomäki Päivi 
Published: April 2024

BackgroundLynch syndrome (LS) is an autosomal dominant multi-organ cancer syndrome with a high lifetime risk of cancer. The number of cumulative colorectal adenomas in LS does not generally exceed ten, and removal of adenomas via routine screening minimizes the cancer burden. However, abnormal phenotypes may mislead initial diagnosis and subsequently cause suboptimal treatment.AimCurrently, there is no standard guide for the care of multiple colorectal adenomas in LS individuals. We aimed to shed insight into the molecular features and reasons for multiplicity of adenomas in LS patients.MethodsWe applied whole exome sequencing on nine adenomas (ten samples) and three assumed primary carcinomas (five samples) of an LS patient developing the tumors during a 21-year follow-up period. We compared the findings to the tumor profiles of two additional LS cases ascertained through colorectal tumor multiplicity, as well as to ten adenomas and 15 carcinomas from 23 unrelated LS patients with no elevated adenoma burden from the same population. As LS associated cancers can arise via several molecular pathways, we also profiled the tumors for CpG Island Methylator Phenotype (CIMP), and LINE-1 methylation.ResultsAll tumors were microsatellite unstable (MSI), and MSI was present in several samples derived from normal mucosa as well. Interestingly, frequent frameshift variants in RNF43 were shared among substantial number of the tumors of our primary case and the tumors of LS cases with multiple tumors but almost absent in our control LS cases. The RNF43 variants were completely absent in the normal tissue, indicating tumor-associated mutational hotspots. The RNF43 status correlated with the mutational signature SBS96. Contrary to LS tumors from the reference set with no elevated colorectal tumor burden, the somatic variants occurred significantly more frequently at C&gt;T in the CpG context, irrespective of CIMP or LINE-1 status, potentially indicating other, yet unknown methylation-related mechanisms. There were no signs of somatic mosaicism affecting the MMR genes. Somatic variants in APC and CTNNB1 were unique to each tumor.ConclusionFrequent somatic RNF43 hot spot variants combined with SBS96 signature and increased tendency to DNA methylation may contribute to tumor multiplicity in LS.
Case report: A rare case of very well-differentiated gastric adenocarcinoma of gastric type with a lymphovascular invasion
Authors: Chen Jiaqi , Cui Xiujie , Wu Honglei , Zhou Chengjun 
Published: April 2024

BackgroundVery well-differentiated gastric adenocarcinoma (VWDA) is a rare variant of gastric cancer, for which the diagnostic criteria and clinical behavior are not fully established. We reported a case of an intramucosal VWDA of gastric type with a lymphovascular invasion (LVI).Case presentationA 67-year-old female was diagnosed as intramucosal gastric adenocarcinoma after a biopsy at the local hospital 3 weeks ago and then visited our hospital for further treatment. The endoscopic examination in our hospital showed a rough, slightly faded, 30-mm, flat, and elevated lesion on the lesser curvature of the middle gastric body. Histopathologically, the lesion consisted of superficial foveolar-type papillary adenocarcinoma and deep pyloric gland-type tubular adenocarcinoma. The immunostaining results showed that the foveolar-type papillary adenocarcinoma was positive for MUC5AC and had a high index of Ki-67, but the pyloric gland-type tubular adenocarcinoma was positive for MUC6 and had a low index of Ki-67. Both components were negative for MSH2 and MSH6, which suggested the high microsatellite instability phenotype. Moreover, a LVI was detected in the lesion. The pathological diagnosis was VWDA of gastric type.ConclusionThe case has unique histological and immunophenotypic characteristics, which not only indicates the importance of architectural features in the diagnosis of VWDA but also further proves that the aggressive behavior of VWDA is correlated with tumor histological type and immunophenotype.
Neonatal outcomes in preterm infants with severe congenital heart disease: a national cohort analysis
Authors: Aly Safwat , Qattea Ibrahim , Kattea Mohammad O. , Aly Hany Z. 
Published: April 2024

BackgroundPrematurity and congenital heart disease (CHD) are the leading causes of neonatal mortality and morbidity. Limited data are available about the outcomes of premature infants with severe CHD.MethodsWe queried The National Inpatient Database using ICD-10 codes for premature patients (&lt;37 weeks) with severe CHD from 2016 to 2020. Severe CHDs were grouped into three categories: A. left-sided lesions with impaired systemic output, B. Cyanotic CHD, and C. Shunt lesions with pulmonary overcirculation. Patients with isolated atrial or ventricular septal defects and patent ductus arteriosus were excluded. We also excluded patients with chromosomal abnormalities and major congenital anomalies. Patients' demographics, clinical characteristics, and outcomes were evaluated by comparing premature infants with vs. without CHD adjusting for gestational age (GA), birth weight, and gender.ResultsA total of 27710 (1.5%) out of 1,798,245 premature infants had severe CHD. This included 27%, 58%, and 15% in groups A, B, and C respectively. The incidence of severe CHD was highest between 25 and 28 weeks of gestation and decreased significantly with increasing GA up to 36 weeks (p &lt; 0.001). Premature infants with severe CHD had a significantly higher incidence of neonatal morbidities including necrotizing enterocolitis (NEC) [OR = 4.88 (4.51–5.27)], interventricular hemorrhage [OR = 6.22 (5.57–6.95)], periventricular leukomalacia [OR = 3.21 (2.84–3.64)] and bronchopulmonary dysplasia [OR = 8.26 (7.50–10.06) compared to preterm infants of similar GA without CHD. Shunt lesions had the highest incidence of NEC (8.5%) compared to 5.3% in cyanotic CHD and 3.7% in left-sided lesions (p &lt; 0.001). Mortality was significantly higher in premature infants with CHD compared to control [11.6% vs. 2.5%, p &lt; 0.001]. Shunt lesions had significantly higher mortality (11.0%) compared to those with left-sided lesions (8.3%) and cyanotic CHD (6.4%), p &lt; 0.001.ConclusionPremature infants with severe CHD are at high risk of neonatal morbidity and mortality. Morbidity remains increased across all GA groups and in all CHD categories. This significant risk of adverse outcomes is important to acknowledge when managing this patient population and when counseling their families. Future research is needed to examine the impact of specific rather than categorized congenital heart defects on neonatal outcomes.
In the fed state, autophagy plays a crucial role in assisting the insect vector Rhodnius prolixus mobilize TAG reserves under forced flight activity
Authors: Santos-Araujo Samara , Gomes Fabio , Carvalho-Kelly Luiz Fernando , Meyer-Fernandes José Roberto , Gondim Katia C. , Ramos Isabela 
Published: April 2024

Autophagy is a cellular degradation pathway mediated by highly conserved autophagy-related genes (Atgs). In our previous work, we showed that inhibiting autophagy under starvation conditions leads to significant physiological changes in the insect vector of Chagas disease Rhodnius prolixus; these changes include triacylglycerol (TAG) retention in the fat body, reduced survival and impaired locomotion and flight capabilities. Herein, because it is known that autophagy can be modulated in response to various stimuli, we further investigated the role of autophagy in the fed state, following blood feeding. Interestingly, the primary indicator for the presence of autophagosomes, the lipidated form of Atg8 (Atg8-II), displayed 20%–50% higher autophagic activation in the first 2 weeks after feeding compared to the third week when digestion was complete. Despite the elevated detection of autophagosomes, RNAi-mediated suppression of RpAtg6 and RpAtg8 did not cause substantial changes in TAG or protein levels in the fat body or the flight muscle during blood digestion. We also found that knockdown of RpAtg6 and RpAtg8 led to modest modulations in the gene expression of essential enzymes involved in lipid metabolism and did not significantly stimulate the expression of the chaperones BiP and PDI, which are the main effectors of the unfolded protein response. These findings indicate that impaired autophagy leads to slight disturbances in lipid metabolism and general cell proteostasis. However, the ability of insects to fly during forced flight until exhaustion was reduced by 60% after knockdown of RpAtg6 and RpAtg8. This change was accompanied by TAG and protein increases as well as decreased ATP levels in the fat body and flight muscle, indicating that autophagy during digestion, i.e., under fed conditions, is necessary to sustain high-performance activity.
The COVID-19 pandemic, psychologists’ professional quality of life and mental health
Authors: Kercher Amy , Rahman Jodie , Pedersen Mangor 
Published: April 2024

BackgroundPsychologists are at known risk of work-related stress, secondary trauma, and burnout. The COVID-19 pandemic increased stress and anxiety for communities worldwide and corresponded with an increased demand for mental health services. Our study investigated the impact of COVID-19 on psychologists’ professional quality of life, psychological symptoms, and work-related stress in Aotearoa, New Zealand (NZ).MethodNinety-nine registered psychologists were recruited via NZ professional psychology organizations, representing 3% of the total workforce. Survey data collected included symptoms of compassion fatigue and satisfaction, psychological symptoms, COVID-19-related stress and resilience, and professional and personal circumstances during the third year of the pandemic, 2022.ResultsSeventy percent reported that their work stress had increased, and 60% reported that their caseload intensity had increased during the COVID-19 pandemic. Psychologists reported receiving little to no additional personal or professional support, while 55% reported increased personal responsibilities during the pandemic (for example, closed childcare and schools during lockdowns). High rates of compassion fatigue (burnout and secondary traumatic stress) and low resilience were reported. We observed that psychological distress was higher than the community averages before the pandemic and comparable with frontline healthcare professionals. Compassion fatigue was associated with COVID-related stress, psychological distress, years in practice, and more frequent supervision, but not with working with at-risk clients, levels of personal support, or having children at home. Despite these difficulties, high Compassion Satisfaction scores were also reported, with over 90% indicating they had no intention of leaving the profession in the foreseeable future.ConclusionPsychologists’ compassion fatigue appears to have worsened during the COVID-19 pandemic, as have their symptoms of psychological distress. Increased workplace and clinical demands, telehealth difficulties, stress relating to the pandemic, inadequate support, and increased personal responsibilities were reported by psychologists. Mental health workforces are not immune to the personal and professional impacts of crises and are at risk of burnout and secondary traumatic stress. We hope that increased awareness and understanding of psychologists’ own difficulties during COVID-19 can be used to better tackle future crises and support mental health professionals.
Association between sugar-sweetened beverages and duration of physical exercise with psychological symptoms among Tibetan university students at high altitude
Authors: Song Wei , Su Fan , Li Shengpeng , Song Yongjing , Chai Guangxin 
Published: April 2024

BackgroundSugar-sweetened beverages (SSBs) and duration of physical exercise are strongly associated with physical health. Unfortunately, there are few studies focused on the association with psychological symptoms, let alone Tibetan university students at high altitudes in China.MethodsA stratified cluster sampling method was used to include 8,268 Tibetan university students aged 19–22 years in Qinghai and Tibet, both of which are high-altitude regions of China. Self-assessment questionnaires on SSBs, duration of physical exercise, and psychological symptoms were administered. The chi-square test and logistic regression analysis were used to analyze the associations among them.ResultsThe detection rate of psychological symptoms among Tibetan university students in high-altitude areas of China was 16.7%, with in girls (18.2%) higher than that in boys (14.8%), and the difference was statistically significant (χ2 = 11.73, p &lt; 0.01). The proportion of SSBs for university students ≤1 time/week, 2–5 times/week, and ≥ 6 times/week were 54.2, 24.3, and 21.5%, respectively. The proportion of duration of physical exercise for &gt;60 min/d was only 5.4%. Logistic regression analysis showed that compared with the SSBs ≤1 time/week group of university students, SSBs 2–5 times/week (OR = 1.45, 95% CI: 1.24–1.70) and ≥ 6 times/week (OR = 3.06, 95% CI: 2.62–3.57) had an increased risk of psychological symptoms (p &lt; 0.001). In the reference group, the risk of psychological symptoms was also significantly increased in the group of university students with duration of physical exercise &gt;60 min/d (OR = 2.08, 95% CI: 1.48–2.93), and the risk of psychological symptoms was also significantly increased in the group with duration of physical exercise &lt;30 min/d (OR = 2.08, 95% CI: 1.48–2.93). The risk of psychological symptoms was also significantly increased in the university students with the duration of physical exercise &lt;30 min/d (OR = 2.08, 95% CI: 1.48 ~ 2.93) group.ConclusionSSBs and exercise time may be important influences on the psychological symptoms of Tibetan university students at high altitudes in China. This study has important implications for mental health planning in universities in highland areas and may also provide guidance for mental health interventions for Tibetan university students.
Factors influencing self-regulatory fatigue in patients undergoing chemotherapy for gynecologic cancer: a cross-sectional study
Authors: Lin Chunhui , Zhang Fengzhi , Yang Fangfang , Lin Yuanting , Tian Tian , Shi Kaige , Li Manman , Li Xiaoxue 
Published: April 2024

ObjectiveTo understand the current status of self-regulatory fatigue among gynecologic cancer chemotherapy patients and explore influencing factorsMethodsUsing convenient sampling, a total of 232 gynecological cancer chemotherapy patients from two tertiary hospitals in Zhengzhou, Henan, China, were selected as study subjects from February 2023 to April 2023. General information questionnaire, Self-Regulatory Fatigue Scale (SRF-S), Strategies Used by People to Promote Health (SUPPH) Scale, Connor-Davidson resilience scale (CD-RISC) and Perceived Social Support Scale (PSSS) were employed for data collection. The data were analyzed using SPSS 26.0 software. Chi-square test and binary logistic regression were executed to explore the correlates of self-regulatory fatigue, the significance level (α) was set at 0.05.ResultsThe self-regulatory fatigue score of the 232 patients was 44 (36, 56). Binary logistic regression analyses revealed significant associations, demonstrating that residing in urban areas (OR=0.241, P=0.015), having no comorbidities (OR=0.158, P=0.015), increased perceived social support (OR=0.937, P=0.001), strong self-efficacy (OR=0.959, P=0.021), and heightened psychological resilience (OR=0.895, P&lt;0.001) acted as protective factors against self-regulatory fatigue (P &lt; 0.05).ConclusionPatients residing in rural areas, having more than two comorbidities, lower self-efficacy and psychological resilience levels, and lower perceived social support are indicative of higher levels of self-regulatory fatigue. Identifying these influencing factors can provide references and support for developing individualized support and intervention measures to improve patients’ physical and mental well-being.