bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexpected exacerbation of cryptococcal meningitis after unilateral adrenalectomy in a PMAH patient: a case report and literature review
Authors: Tan Lu , Zhao Lianling , Tang Guangmin , Ren Yan , Tian Haoming , Chen Tao 
Published: September 2023

Abstract
Background
Primary bilateral macronodular adrenal hyperplasia (PMAH) combined with infection by an opportunistic pathogen is complicated. Clinical evidence on managing PMAH patients with infections by opportunistic pathogens is insufficient.

Case presentation
A 66-year-old male was admitted with bilateral adrenal masses and was diagnosed with PMAH. Fever and disturbance of consciousness appeared after laparoscopic left adrenalectomy. Cryptococcal meningitis was confirmed by cerebrospinal fluid (CSF) culture. The exacerbation of his medical condition was suspected to result from immune reconstitution inflammatory syndrome (IRIS), and he had been treated with antifungal therapy and glucocorticoid replacement, but he responded poorly and eventually died of multiorgan failure. We summarized the clinical observations of 12 Cushing's syndrome (CS) patients infected by Cryptococcus. Seven out of nine patients who were treated for cryptococcus infection before receiving CS survived, while three patients treated for cryptococcus infection after CS treatment developed signs of IRIS and eventually died.

Conclusion
Cushing's syndrome, complicated with cryptococcal infection, has a high mortality rate, mainly when IRIS emerges. Carefully identifying the presence of the suspected infection, and controlling cryptococcal infection before removing the culprit adrenals could be the rational choice.
PR status is a more decisive factor in efficacy of adding pertuzumab into neoadjuvant therapy for HER2-positive and lymph node-positive breast cancer than ER status: a real-world retrospective study in China
Authors: Liu Xiaoyu , Liu Zhaoyun , Li Chao , Song Xiang , Wang Xinzhao , Li Sumei , Yu Zhiyong 
Published: September 2023

Abstract
Background
Although neoadjuvant trastuzumab and pertuzumab (HP)-based regimens are recommended for human epidermal receptor-positive (HER2 +)/lymph node-positive (N +) breast cancer (BC) patients according to NCCN guidelines, it is undeniable that many patients achieved pathological complete response (pCR) after trastuzumab (H)-based regimens without adding pertuzumab to treatment. Patients who specifically benefit from pertuzumab must be identified. The aim of this retrospective study was to evaluate progesterone receptor (PR) status as a predictor of response to the addition of pertuzumab in HER2 + /N + breast cancer.

Methods
One hundred forty-two patients who were diagnosed as HER2 + /N + BC without distant metastasis and followed by neoadjuvant HP-based or H-based therapy were retrospectively included. The endpoints were pCR and disease-free survival (DFS) times.

Results
In total, the pCR occurred in 25 of 87 patients (28.74%) in group H compared with 32 of 55 (58.18%) in group HP. The results revealed that hormone receptor (HR) status was significantly different on pCR in group HP. The odds of pCR for patients who have HR-positive tumors were 0.160 times (P = 0.011) that for patients with HR-negative tumors by multivariable analysis. Moreover, a similar probability of PR-positive (PR +) patients, whatever estrogen receptor (ER) status was, achieving pCR in group HP was observed. The ROC curves showed different anti-HER2 regimens provide worst predictive value in the PR + cohort (N = AUC = 0.521, 95% CI: 0.348–0.694, P = 0.813) compared with the overall cohort (AUC = 0.644, 95% CI: 0.550–0.738, P = 0.004) and ER + cohort (AUC: 0.559, 95% CI: 0.405–0.713, P = 0.451). And PR status (AUC = 0.760, 95% CI: 0.626–0.894, P = 0.001) had a greater predictive value than ER status (AUC = 0.658, 95% CI: 0.508–0.807, P = 0.048) in group HP. DFS analyses were done on 141 patients. Although ER and PR status did not show significant difference in group HP (P = 0.789 and 0.088, respectively), HP-based therapy contributed to better DFS in the ER − and PR − cohorts (P = 0.035 and 0.015, respectively).

Conclusions
Compared with ER status, PR status might be a more valuable factor predicting the efficacy of adding pertuzumab into neoadjuvant therapy for HER2 + /N + BC. PR + patients benefit little from the addition of pertuzumab.
GDF15 affects venous thrombosis by promoting EndMT through smad2/p-smad2 pathway
Authors: Li Yeping , Zhu Huiqi , Xin Wanghao , Wang Jiaoyan , Yan Chao , Ying Kejing 
Published: September 2023

AbstractBackgroundEndothelial-to-mesenchymal transition (EndMT) is a pathophysiological change in the vascular endothelium commonly seen in the cardiovascular system. Elevated serum Growth differiention factor 15 (GDF15) has been reported in VTE patients, but the relationship and mechanism between GDF15, EndMT and VTE are still unclear.MethodsWe performed a retrospective clinical study, and human serum GDF15 expression levels were detected. The mouse DVT model was established through subtotal ligation of the mouse inferior vena cava, and then we detected intimal changes and thrombi in the stenotic inferior vena cava by haematoxylin-eosin (HE) staining, Masson staining, and Sirius Red staining. The expression levels of GDF15 and SM22 were detected by immunohistochemistry and RT‒qPCR. Serum samples of mice were collected, and the expression level of GDF15 in serum was detected. Human umbilical vein endothelial cells (HUVECs) were stimulated with a cytokine mixture (TGF-β1 + TNF-α + IL-1β). The role and mechanism of GDF15 in EndMT and VTE were detected in HUVECs and in a DVT mice model.ResultsWe found that serum GDF15 levels in both VTE patients and mouse DVT models were higher than those in the control group. EndMT was increased in the stenotic vascular tissue of mice. Further experiments showed that GDF15 could promote the EndMT of HUVECs and reduce their anticoagulation and antifibrinolytic ability through the smad2/p-smad2/snail pathway. Inhibition of mature GDF15 release can significantly reduce venous thrombotic fibre deposition in mice.ConclusionsGDF15 positively promotes EndMT through activation of the Smad2/psmad2/snail pathway, and inhibition of GDF15 expression can alleviate the EndMT process, further improving the coagulation and fibrinolytic function of endothelial cells and thus reducing the local fibre deposition of venous thrombi.
Psychosocial status and risk perception among Iranian healthcare workers during the fifth wave of the COVID-19 pandemic
Authors: Khazaee-Pool Maryam , Moradi Masoud , Pashaei Tahereh , Ponnet Koen 
Published: September 2023

Abstract
Background
Healthcare workers (HCWs) are essential resources, and their health and wellbeing are key not only for offering constant and useful care facilities to clients, but also for maintaining the safety of the workforce and patients. The risk of severe mental health problems among HCWs may have increased during large outbreaks of COVID-19. To evaluate the psychosocial status and risk perception of HCWs who participated in treating COVID-19 patients in Northern Iran, we performed a web-based cross-sectional study.

Methods
The web-based cross-sectional design was applied between June 27 and September 2, 2021. Using convenience sampling, 637 HCWs were recruited from hospitals in Northern Iran (Mazandaran). The HCWs completed self-report questionnaires that included a sociodemographic information form, the 12-item General Health Questionnaire, Impact of the Event Scale-Revised, Risk Perception Questionnaire, and Anxiety Stress Scale‐21. The data were analyzed via descriptive and inferential statistics and univariate/multivariate logistic regression to assess the risk factors linked to each psychosocial consequence.

Results
The results reveal that the COVID-19 pandemic had an adverse psychosocial influence on HCWs, which was already apparent 1.5 years after the crisis began. Based on the results, 71.6%, 55.6%, and 32.3% of HCWs reported having anxiety, depression, and stress symptoms, respectively, since the outbreak of this disease. The logistic regression models displayed that marital status, having children, and working hours with patients were all risk factors of psychosocial impairment.

Conclusions
The outbreak of COVID-19 can be considered an important experience of a bio-disaster resulting in a significant rate of psychiatric problems in HCWs. There is a need for designing and promoting supportive programs to help HCWs cope and to improve their psychosocial state, and the present study has detected for whom psychosocial support may be effective and practical 1.5 years after the primary outbreak. Moreover, detecting and managing concerns and reducing infection-related embarrassment/stigma are essential for improving HCWs’ mental health.
Resilience of primary healthcare system across low- and middle-income countries during COVID-19 pandemic: a scoping review
Authors: Pradhan Nousheen Akber , Samnani Amir Ali Barket Ali , Abbas Kiran , Rizvi Narjis 
Published: September 2023

Abstract
Introduction
Globally, the coronavirus disease 2019 (COVID-19) pandemic tested the resilience of the health system and its shock-absorbing capacity to continue offering healthcare services. The available evidences does not provide comprehensive insight into primary health care (PHC) system functioning across low- and middle- income countries (LMICs) during the pandemic. Therefore, the objective of this scoping review was to generate evidence on the resilience of PHC systems in LMICs during the COVID-19 pandemic.

Methods
A scoping review was carried out utilizing an iterative search strategy using the National Library of Medicine (NLM) and the WHO COVID-19 electronic databases. Data from the identified studies in LMICs were charted in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist in the first step. The analysis framework was adapted and modified using COVID-19 and health systems resilience framework developed by Sagan et al., Blanchet et al., and the WHO position paper on ‘Building health systems resilience for universal health coverage and health security during the COVID-19 pandemic and beyond’. A total of 26 documents were included on the basis of predefined eligibility criteria for our analysis.

Results
Our review explored data from 44 LMICs that implemented strategies at the PHC level during the COVID-19 pandemic. Most of the LMICs developed national guidelines on sexual, reproductive, maternal, newborn, child, and adolescent health (SRMNCAH). Most of the countries also transformed and reoriented PHC service delivery by introducing digital healthcare services to continue essential services. Task shifting, task sharing, and redeployment of retired staff were some frequently adopted health workforce strategies adopted by most of the countries. Only a few of the countries demonstrated the availability of necessary monetary resources to respond to the pandemic.

Conclusions
The functionality of the PHC system during the COVID-19 pandemic was demonstrated by a variety of resilience strategies across the six building blocks of the health system. To strengthen PHC resilience, we recommend strengthening community-based PHC, cross-sectoral collaboration, establishing surveillance systems, capacity building in financial risk planning, and investing in strengthening the digital healthcare system.
The discovery, structure, and function of 5-HTR1E serotonin receptor
Authors: Sharma Vinay Kumar , Loh Y. Peng 
Published: September 2023

AbstractSerotonin (5-hydroxytryptamine, 5-HT) is a unique neurotransmitter which can regulate various biological processes by activating thirteen different receptors. These serotonin receptors are divided into seven different classes based on their structure and functions. Since these receptors co-express in various tissue and cell types and share the same ligand (5-HT), it has been a challenge for the researchers to define specific pathway and separate physiological role for each of these serotonin receptors. Though the evidence of operational diversity of these receptors is continuously emerging, much work remains to be done. 5-HTR1E is a member of 5-HT1 receptor family which belongs to G-protein coupled receptors (GPCRs). Even after three decades since its discovery, 5-HTR1E remains the least explored serotonin receptor. Very high similarity with another family member (5-HTR1F) and its non-existence in mice or rats makes 5-HTR1E a difficult target to study. Despite these challenges, recent findings on the role of 5-HTR1E in neuroprotection and diseases such as cancer, have excited many researchers to explore this receptor in detail. Here, we provide the first review of 5-HTR1E, since its discovery in 1989 to 2023. We highlight the structural and functional characteristics of this important serotonin receptor in detail and propose future directions in developing 5-HTR1E as a drug target.
Arginase-1 promotes lens epithelial-to-mesenchymal transition in different models of anterior subcapsular cataract
Authors: Li Qingyu , Wang Yuchuan , Shi Luoluo , Wang Qing , Yang Guang , Deng Lin , Tian Ye , Hua Xia , Yuan Xiaoyong 
Published: September 2023

Abstract
Background
Arginase-1 (ARG1) promotes collagen synthesis and cell proliferation. ARG1 is highly expressed in various tumour cells. The mechanisms of ARG1 in epithelial-to-mesenchymal transition (EMT)-associated cataracts were studied herein.

Methods
C57BL/6 mice, a human lens epithelial cell line (HLEC-SRA01/04), and human lens capsule samples were used in this study. The right lens anterior capsule of the mouse eye was punctured through the central cornea with a 26-gauge hypodermic needle. Human lens epithelial cells (HLECs) were transfected with ARG1-targeted (siARG1) or negative control siRNA (siNC). For gene overexpression, HLECs were transfected with a plasmid bearing the ARG1 coding sequence or an empty vector. Medium containing 0.2% serum with or without transforming growth factor beta-2 (TGF-β2) was added for 6 or 24 h to detect mRNA or protein, respectively. The expression of related genes was measured by quantitative real-time polymerase chain reaction (RT–qPCR), western blotting, and immunohistochemical staining. Transwell assays and wound healing assays were used to determine cell migration. Cell proliferation, superoxide levels, nitric oxide (NO) levels, and arginase activity were estimated using Cell Counting Kit-8 assays, a superoxide assay kit, an NO assay kit, and an arginase activity kit.

Results
ARG1, alpha-smooth muscle actin (α-SMA), fibronectin, and Ki67 expression increased after lens capsular injury, while zonula occludens-1 (ZO-1) expression decreased.
Fibronectin and collagen type I alpha1 chain (collagen 1A1) expression increased, and cell migration increased significantly in ARG1-overexpressing HLECs compared with those transfected with an empty vector after TGF-β2 treatment. These effects were reversed by ARG1 knockdown.
The arginase-related pathway plays an important role in EMT. mRNAs of enzymes of the arginase-related pathway were highly expressed after ARG1 overexpression. ARG1 knockdown suppressed these expression changes.
Numidargistat (CB-1158) dihydrochloride (CB-1158), an ARG1 inhibitor, suppressed TGF-β2-induced anterior subcapsular cataract (ASC) by reducing the proliferation of lens epithelial cells (LECs) and decreasing fibronectin, α-SMA, collagen 1A1, and vimentin expression.
Compared with that in nonanterior subcapsular cataract (non-ASC) patients, the expression of ARG1, collagen 1A1, vimentin, fibronectin, and Ki67 was markedly increased in ASC patients.

Conclusions
ARG1 can regulate EMT in EMT-associated cataracts. Based on the pathogenesis of ASC, these findings are expected to provide new therapeutic strategies for patients.

Graphical abstract
A glycosylated Phr1 protein is induced by calcium stress and its expression is positively controlled by the calcium/calcineurin signaling transcription factor Crz1 in Candida albicans
Authors: Jiang Linghuo , Xu Huihui , Gu Yiying , Wei Liudan 
Published: September 2023

AbstractAs one of the most important human fungal pathogens, Candida albicans senses and adapts to host niches with different pH values through the pH-responsive Rim101 pathway. Its transcription factor Rim101 activates the expression of alkaline pH-induced genes including PHR1 that encodes a glycosylphosphatidylinsitol-anchored β(1,3)-glucanosyltransferase critical for hyphal wall formation. The calcium/calcineurin signaling pathway is mediated by the transcription factor Crz1 in yeasts and other lower eukaryotes. Here we report that deletion of PHR1 leads to calcium sensitivity of C. albicans cells. In addition, expression of Phr1 is induced by calcium stress and under the control of Crz1 in C. albicans. EMSA assay demonstrates that Crz1 binds to one CDRE element in the PHR1 promoter. Alkaline treatment induces two species of glycosylated Phr1 proteins with different degrees of glycosylation, which is independent of Crz1. In contrast, only one species of Phr1 protein with a low degree of glycosylation is induced by calcium stress in a Crz1-dependent fashion. Therefore, we have provided an evidence that regulation of cell wall remodeling is integrated through differential degrees of Phr1 glycosylation by both the pH-regulated Rim101 pathway and the calcium/calcineurin signaling pathway in C. albicans.
LFA-1 knockout inhibited the tumor growth and is correlated with treg cells
Authors: Niu Ting , Li Zhengyang , Huang Yiting , Ye Yuxiang , Liu Yilong , Ye Zhijin , Jiang Lingbi , He Xiaodong , Wang Lijing , Li Jiangchao 
Published: September 2023

AbstractCancer immunotherapy has been proven to be clinically effective in multiple types of cancers. Lymphocyte function-associated antigen 1 (LFA-1), a member of the integrin family of adhesion molecules, is expressed mainly on αβ T cells. LFA-1 is associated with tumor immune responses, but its exact mechanism remains unknown. Here, two kinds of mice tumor model of LFA-1 knockout (LFA-1−/−) mice bearing subcutaneous tumor and ApcMin/+;LFA-1−/− mice were used to confirm that LFA-1 knockout resulted in inhibition of tumor growth. Furthermore, it also demonstrated that the numbers of regulatory T cells (Treg cells) in the spleen, blood, mesenteric lymph nodes were decreased in LFA-1−/− mice, and the numbers of Treg cells in mesenteric lymph nodes were also decreased in ApcMin/+;LFA-1−/− mice compared with ApcMin/+ mice. LFA-1 inhibitor (BIRT377) was administered to subcutaneous tumor-bearing LFA-1+/+ mice, and the results showed that the tumor growth was inhibited and the number of Treg cells was reduced. The analysis of TIMER tumor database indicated that LFA-1 expression is positively associated with Treg cells and TNM stage. Conclusively, this suggests that LFA-1 knockout would inhibit tumor growth and is correlated with Treg cells. LFA-1 may be one potential target for cancer immunotherapy.
GPR65 inhibits human trophoblast cell adhesion through upregulation of MYLK and downregulation of fibronectin via cAMP-ERK signaling in a low pH environment
Authors: Mao Jia , Feng Ying , Zheng Yayun , Gao Yaqiu , Zhang Linyu , Sun Xinrui , Wu Yilun , Zhu Xiaofeng , Ma Fang 
Published: September 2023

Abstract
Background
Extravillous trophoblasts (EVTs) are essential cells during the formation of the placenta, with the major function of invading the maternal decidua, anchoring the developing placenta to the uterus, remodeling uterine arteries, and regulating immune responses to prevent rejection. During early pregnancy, the decidua undergoes a hypoxic and acidic microenvironment, which has been shown to participate in tumor cell migration, invasion, growth, and angiogenesis. Nevertheless, the mechanisms by which EVTs sense and respond to the acidic microenvironment, thereby executing their functions, remain poorly understood.

Methods
The effects of G protein-coupled receptor 65 (GPR65) on cell adhesion and other cellular functions were tested using JAR spheroids, mouse blastocysts, and HTR-8/SVneo cells. Specifically, we employed HTR-8/SVneo cells for gene overexpression and silencing to investigate the underlying mechanism of GPR65's impact on trophoblast cell function under acidic conditions. Additionally, villus tissue samples obtained from early pregnancy loss patients were utilized to explore the potential association between GPR65 and its related signaling pathway molecules with the disease.

Results
This study identified GPR65 expression widely in trophoblasts, with the highest level in EVTs. Importantly, optimal GPR65 levels are required for maintaining normal adhesion, migration, and invasion, whereas overexpression of GPR65 inhibits these functions by activating the cAMP-ERK signaling pathway, upregulating myosin light chain kinase (MYLK) and MYLK3 expression, and subsequently downregulating fibronectin. Consistently, elevated expression of GPR65, MYLK, and MYLK3 is observed in patients suffering from early pregnancy loss.

Conclusions
This work offers insights into the suppressive effects of GPR65 on EVT function under acidic conditions and highlights a putative target for therapeutic intervention in early pregnancy complications.
Regulation of phosphoglycerate kinase 1 and its critical role in cancer
Authors: Zhang Kexin , Sun Lixue , Kang Yuanyuan 
Published: September 2023

AbstractCells that undergo normal differentiation mainly rely on mitochondrial oxidative phosphorylation to provide energy, but most tumour cells rely on aerobic glycolysis. This phenomenon is called the "Warburg effect". Phosphoglycerate kinase 1 (PGK1) is a key enzyme in aerobic glycolysis. PGK1 is involved in glucose metabolism as well as a variety of biological activities, including angiogenesis, EMT, mediated autophagy initiation, mitochondrial metabolism, DNA replication and repair, and other processes related to tumorigenesis and development. Recently, an increasing number of studies have proven that PGK1 plays an important role in cancer. In this manuscript, we discussed the effects of the structure, function, molecular mechanisms underlying PGK1 regulation on the initiation and progression of cancer. Additionally, PGK1 is associated with chemotherapy resistance and prognosis in tumour patients. This review presents an overview of the different roles played by PGK1 during tumorigenesis, which will help in the design of experimental studies involving PGK1 and enhance the potential for the use of PGK1 as a therapeutic target in cancer.