bluuebunny/crossref_metadata_2025_split huggingface dataset:
Removal of the vicinal disulfide enhances the platelet-capturing function of von Willebrand factor
Authors: Tischer Alexander , Moon-Tasson Laurie , Auton Matthew 
Published: January 2023

Abstract
A redox autoinhibitory mechanism has previously been proposed, in which the reduced state of the vicinal disulfide bond in the von Willebrand factor (VWF) A2 domain allows A2 to bind to A1 and inhibit platelet adhesion to the A1 domain. The VWF A1A2A3 tridomain was expressed with and without the vicinal disulfide in A2 (C1669S/C1670S) via the atomic replacement of sulfur for oxygen to test the relevance of the vicinal disulfide to the physiological platelet function of VWF under shear flow. A comparative study of the shear-dependent platelet translocation dynamics on these tridomain variants reveals that the reduction of the vicinal disulfide moderately increases the platelet-capturing function of A1, an observation counter to the proposed hypothesis. Surface plasmon resonance spectroscopy confirms that C1669S/C1670S slightly increases the affinity of A1A2A3 binding to glycoprotein Ibα (GPIbα). Differential scanning calorimetry and hydrogen-deuterium exchange mass spectrometry demonstrate that reduction of the vicinal disulfide destabilizes the A2 domain, which consequently disrupts interactions between the A1, A2, and A3 domains and enhances the conformational dynamics of A1-domain secondary structures known to regulate the strength of platelet adhesion to VWF. This study clarifies that the reduced state of the A2 vicinal disulfide is not inhibitory but rather slightly activating.
Cytokine expression profiles in white blood cells of patients with small fiber neuropathy
Authors: Kreß Luisa , Egenolf Nadine , Sommer Claudia , Üçeyler Nurcan 
Published: January 2023

Abstract
Background
The role of cytokines in the pathophysiology, diagnosis, and prognosis of small fiber neuropathy (SFN) is incompletely understood. We studied expression profiles of selected pro- and anti-inflammatory cytokines in RNA from white blood cells (WBC) of patients with a medical history and a clinical phenotype suggestive for SFN and compared data with healthy controls.

Methods
We prospectively recruited 52 patients and 21 age- and sex-matched healthy controls. Study participants were characterized in detail and underwent complete neurological examination. Venous blood was drawn for routine and extended laboratory tests, and for WBC isolation. Systemic RNA expression profiles of the pro-inflammatory cytokines interleukin (IL)-1ß, IL-2, IL-8, tumor necrosis factor-alpha (TNF) and the anti-inflammatory cytokines IL-4, IL-10, transforming growth factor beta-1 (TGF) were analyzed. Protein levels of IL-2, IL-8, and TNF were measured in serum of patients and controls. Receiver operating characteristic (ROC)-curve analysis was used to determine the accuracy of IL-2, IL-8, and TNF in differentiating patients and controls. To compare the potential discriminatory efficacy of single versus combined cytokines, equality of different AUCs was tested.

Results
WBC gene expression of IL-2, IL-8, and TNF was higher in patients compared to healthy controls (IL-2: p = 0.02; IL-8: p = 0.009; TNF: p = 0.03) and discriminated between the groups (area under the curve (AUC) ≥ 0.68 for each cytokine) with highest diagnostic accuracy reached by combining the three cytokines (AUC = 0.81, sensitivity = 70%, specificity = 86%). Subgroup analysis revealed the following differences: IL-8 and TNF gene expression levels were higher in female patients compared to female controls (IL-8: p = 0.01; TNF: p = 0.03). The combination of TNF with IL-2 and TNF with IL-2 and IL-8 discriminated best between the study groups. IL-2 was higher expressed in patients with moderate pain compared to those with severe pain (p = 0.02). Patients with acral pain showed higher IL-10 gene expression compared to patients with generalized pain (p = 0.004). We further found a negative correlation between the relative gene expression of IL-2 and current pain intensity (p = 0.02). Serum protein levels of IL-2, IL-8, and TNF did not differ between patients and controls.

Conclusions
We identified higher systemic gene expression of IL-2, IL-8, and TNF in SFN patients than in controls, which may be of potential relevance for diagnostics and patient stratification.
Physiological and transcriptomic analyses provide insight into thermotolerance in desert plant Zygophyllum xanthoxylum
Authors: Bai Wan-Peng , Li Hu-Jun , Hepworth Shelley R. , Liu Hai-Shuang , Liu Lin-Bo , Wang Gai-Ni , Ma Qing , Bao Ai-Ke , Wang Suo-Min 
Published: January 2023

Abstract
Background
Heat stress has adverse effects on the growth and reproduction of plants. Zygophyllum xanthoxylum, a typical xerophyte, is a dominant species in the desert where summer temperatures are around 40 °C. However, the mechanism underlying the thermotolerance of Z. xanthoxylum remained unclear.

Results
Here, we characterized the acclimation of Z. xanthoxylum to heat using a combination of physiological measurements and transcriptional profiles under treatments at 40 °C and 45 °C, respectively. Strikingly, moderate high temperature (40 °C) led to an increase in photosynthetic capacity and superior plant performance, whereas severe high temperature (45 °C) was accompanied by reduced photosynthetic capacity and inhibited growth. Transcriptome profiling indicated that the differentially expressed genes (DEGs) were related to transcription factor activity, protein folding and photosynthesis under heat conditions. Furthermore, numerous genes encoding heat transcription shock factors (HSFs) and heat shock proteins (HSPs) were significantly up-regulated under heat treatments, which were correlated with thermotolerance of Z. xanthoxylum. Interestingly, the up-regulation of PSI and PSII genes and the down-regulation of chlorophyll catabolism genes likely contribute to improving plant performance of Z. xanthoxylum under moderate high temperature.

Conclusions
We identified key genes associated with of thermotolerance and growth in Z. xanthoxylum, which provide significant insights into the regulatory mechanisms of thermotolerance and growth regulation in Z. xanthoxylum under high temperature conditions.
Mesenchymal circulating tumor cells and Ki67: their mutual correlation and prognostic implications in hepatocellular carcinoma
Authors: Yang Xihua , Ni Hanghang , Lu Zhan , Zhang Jie , Zhang Qian , Ning Shangwu , Qi Lunan , Xiang Bangde 
Published: January 2023

Abstract
Background
Mesenchymal circulating tumor cells (M-CTCs) may be related to tumor progression, and Ki67 expression is known to be involved in tumor proliferation. The aim of the present study was to explore the relationship between M-CTCs and Ki67 in hepatocellular carcinoma (HCC) and their ability to predict prognosis.

Methods
Peripheral blood samples were obtained from 105 HCC patients before radical surgery. CTCs were isolated using CanPatrol enrichment and classified via in situ hybridization. Ki67 expression in HCC tissue was assessed through immunohistochemistry. Potential relationships of M-CTC, Ki67 with clinicopathological factors and prognosis were evaluated. Overall survival (OS) was analyzed using the Kaplan–Meier method and Cox regression. The prognostic efficacy of M-CTC, Ki67 and both together (M-CTC + Ki67) was assessed in terms of time-dependent receiver operating characteristic (ROC) curves and Harrell's concordance index.

Results
Of the 105 patients, 50 were positive for M-CTCs (count ≥ 1 per 5 mL) and 39 showed high Ki67 expression (≥ 50% tumor cells were Ki67-positive). The presence of M-CTC was significantly associated with alpha-fetoprotein (AFP) ≥ 400 ng/mL (P = 0.007), tumor size ≥ 5 cm (P = 0.023), multiple tumors (P < 0.001), poorly differentiated tumors (P = 0.003), incomplete tumor capsule (P < 0.001), Barcelona Clinic liver cancer (BCLC) stage B or C (P < 0.001), microvascular invasion (MVI) (P = 0.05) and portal vein tumor thrombosis (PVTT) (P = 0.006). High Ki67 expression correlated with AFP ≥ 400 ng/mL (P = 0.015), tumor size ≥ 5 cm (P = 0.012), incomplete tumor capsule (P < 0.001), MVI (P = 0.001), PVTT (P = 0.003), advanced BCLC stage (P = 0.01), and vessel carcinoma embolus (VCE) (P = 0.001). M-CTC positively correlated with Ki67. Patients positive for M-CTCs had a significantly shorter OS than patients negative for them. Similarly, high Ki67 expression was associated with a significantly lower OS. The high-risk group (positive for M-CTCs and high Ki67 expression) had worse OS than the other groups (P < 0.0001). Uni- and multivariate analyses showed that OS was independently predicted by M-CTC [hazard ratio (HR) 1.115; P < 0.001], Ki67 (HR 1.666; P = 0.046) and the combination of both (HR 2.885; P = 0.008). Based on ROC curves and the concordance index, the combination of M-CTC and Ki67 was superior to either parameter alone for predicting the OS of HCC patients.

Conclusions
The presence of M-CTC correlates with high Ki67 expression in HCC patients, and both factors are associated with poor prognosis. Furthermore, the combination of M-CTC and Ki67 is a useful prognostic indicator for predicting OS in patients with HCC after hepatectomy, performing better than either parameter on its own.
Determinants of depression and anxiety among type 2 diabetes patients in governments’ hospitals at Harari regional state, Eastern Ethiopia: A multi-center cross-sectional study
Authors: Nigussie Kabtamu , Sertsu Addisu , Ayana Galana Mamo , Dessie Yadeta , Bete Tilahun , Abdisa Lemesa , Debele Gebiso Roba , Wadaje Dawud , Negash Abraham 
Published: January 2023

AbstractBackgroundType 2 diabetes mellitus is the most common health problem globally. Depression and anxiety can exacerbate disease complications, make patients suffer more, and increase healthcare costs. Even though, depression and anxiety are common among type 2 diabetes mellitus patients, there have been limited studies conducted about the determinants of depression and anxiety in Ethiopia. Therefore, the purpose of this study was to assess the magnitude and determinants of depression and anxiety symptoms among Type 2 diabetes mellitus patients, attending out-patient treatment at Harari regional state government hospitals, Eastern Ethiopia.MethodAn institutional based cross-sectional study was conducted from March to April at Harari regional state government hospitals in eastern Ethiopia. A total of 421 participants were recruited using the systematic sampling technique. Data was collected by using Afan Oromo version of interviewer-administered structured and semi-structured questionnaires. Depression and Anxiety symptoms were assessed by the Hospital Anxiety and Depression Scale. Bivariate and multivariate logistic regression analysis was done to identify variables related to both depression and anxiety symptoms. The association was described using an adjusted odds ratio and a 95% confidence interval (CI), with P-values of 0.05 used as a cutoff for a significant association in the adjusted analysis.ResultOut of the 416 participants included in this study, 42.3%, 40.4% had depression and anxiety symptoms, respectively. Being female (Adjusted Odds Ratio = 1.85(1.09–3.15)), no formal education (Adjusted Odds Ratio = 2.65, (1.04–6.73)), age ≥ 70 (Adjusted Odds Ratio = 2.88 (1.28–6.48)), family history of mental illness (Adjusted Odds Ratio = 1.71 (1.35–3.82)) and poor social support (Adjusted Odds Ratio = 2.35(1.12–6.03)) were statistically associated with depression. While having a family history of mental illness (AOR 1.74(1.03–2.95)), being widowed (AOR = 3.45(1.49–8.01)), and having poor social support (AOR = 2.15(1.12, 4.89)) were statistically significant associated with anxiety at ap-value < 0.05.ConclusionCurrent study results showed that the magnitude of depression and anxiety were relatively high among type 2 diabetes mellitus patients.Having a family history of mental illness and poor social support were statistically associated with both depression and anxiety symptoms. Screening, early detection, and appropriate treatment of depression and anxiety symptoms in type 2 diabetes mellitus patients should be prioritized by health care providers.
Prevalence of suicide attempts and correlates among first-episode and untreated major depressive disorder patients with comorbid dyslipidemia of different ages of onset in a Chinese Han population: a large cross-sectional study
Authors: Jiang Yang , Lu Yaoyao , Cai Yi , Liu Chengjiang , Zhang Xiang-Yang 
Published: January 2023

Abstract
Background
Patients with dyslipidemia are at increased risk for suicide, especially those with major depressive disorder (MDD). Few studies have investigated the independent effects of suicide attempts on comorbid dyslipidemia in patients with MDD. Moreover, there are no comparisons of differences in factors associated with suicide attempts among patients with MDD with dyslipidemia at different ages of onset. The aim of this study was to investigate the prevalence of suicide attempts and associated variables in first episode and untreated patients with MDD with comorbid dyslipidemia at different ages of onset.

Methods
We recruited 1718 patients with first-episode untreated MDD in this study. Demographical and clinical data were collected, and lipid profiles, thyroid function, and blood glucose levels were measured. The Hamilton Depression Scale 17 (HAMD-17), Hamilton Anxiety Scale (HAMA), Clinical Global Impression Severity Scale (CGI), and Positive and Negative Syndrome Scale (PANSS) positive subscale were assessed for depression, anxiety and illness severity, as well as psychotic symptoms, respectively.

Results
The percentage of patients with MDD with comorbid dyslipidemia was 61% (1048/1718). Among patients with MDD with comorbid dyslipidemia, the incidence of suicide attempts was 22.2% (170/765) for early adulthood onset and 26.5% (75/283) for mid-adulthood onset. Independent factors associated with suicide attempts in early adulthood onset patients with MDD with dyslipidemia were as follows: HAMA score (B = 0.328, P < 0.0001, OR = 1.388), Suspicion /persecution (B = -0.554, P = 0.006, OR = 0.575), CGI (B = 0.878, P < 0.0001, OR = 2.406), systolic blood pressure (B = 0.048, P = 0.004, OR = 1.049), hallucinatory behavior (B = 0.334, P = 0.025, OR = 1.397), and TPOAb (B = 0.003, p < 0.0001, OR = 1.003). Independent factors associated with suicide attempts in mid-adulthood onset patients with MDD with comorbid dyslipidemia were as follows: HAMA score (B = 0.182, P < 0.0001, OR = 1.200), CGI (B = 1.022, P < 0.0001, OR = 2.778), and TPOAb (B = 0.002, P = 0.009, OR = 1.002).

Conclusion
Our findings suggest an elevated risk of suicide attempts in patients with MDD with comorbid dyslipidemia. The incidence of suicide attempts was similar in the early- and mid-adulthood onset subgroups among patients with MDD with dyslipidemia, but the factors associated with suicide attempts were different in these two subgroups.
Evaluation of a technology-enhanced, integrated community health and wellness program for seniors (HWePS): protocol of a non-randomized comparison trial
Authors: Kim Hongsoo , Choi Hyoungshim , Jung Young-il , Kim Eunji , Lee Woojoo , Yi Jae Yoon 
Published: January 2023

Abstract
Background
Healthy aging for all in the community is a shared public health agenda for countries with aging populations, but there is a lack of empirical evidence on community-wide preventive models that promote the health of older people residing in socially-disadvantaged communities. The Health and Wellness Program for Seniors (HWePS) is a technology-enhanced, multi-level, integrated health equity intervention model. This study evaluates the effect of the HWePS on the health and well-being of older adults residing in urban, low-income communities.

Methods/design
HWePS is a prospective, non-randomized comparison trial conducted in an intervention and a control neighborhood (dong) in Seoul, South Korea, over 12 months. Older people who reside in the small areas and meet the inclusion/exclusion criteria are eligible to participate. The multi-level, multi-faceted HWePS intervention is a preventive community care model for older residents guided by the expanded chronic care model, the comprehensive health literacy intervention model, and the Systems for Person-centered Elder Care model along with health equity frameworks. HWePS consists of four components: a health literacy intervention based on individual and community needs assessments, personalized (self-)care management featuring nurse coaching and peer support, a healthy-living and healthy-aging community initiative, and information and communication technology (ICT) systems. The primary outcomes are self-reported health and health-related quality of life. Outcome assessors and data analysts are blinded to group assignment. Process evaluation will be also conducted.

Discussion
As a multi-level health equity project, HWePS has adopted a novel study design that simultaneously targets individual- and community-level factors known to contribute to health inequality in later life in the community. The study will provide insights into the effectiveness and implementation process of an integrated, multi-level, preventive community care model, which in turn can help improve the health outcomes of older residents and reduce disparities in underserved urban communities.

Trial registration
ISRCTN29103760. Registered 2 September 2021, https://www.isrctn.com/ISRCTN29103760
Central hepatectomy versus major hepatectomy for patients with centrally located hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Gadallah Edward Atef , Elkomos Beshoy Effat , Khalil Ahmed , fawzy Fawzy Salah , Abdelaal Amr 
Published: January 2023

Abstract
Background and aim
For those with a centrally located HCC, the two types of liver sectionectomy that can be performed are extended hepatectomy (EH) and central hepatectomy (CH). This meta-analysis aimed to compare the short- and long-term outcomes between patients treated with CH and patients treated with EH for those with centrally located HCC.

Method
We searched PubMed, Scopus, Web of Science, and Cochrane library for eligible studies from inception to 1 April 2022 and a systematic review and meta-analysis were done to compare the outcomes between the two groups.

Results
we included 9 studies with a total of 1674 patients in this study. The pooled results in this meta-analysis showed equal long-term overall survival, Disease-free survival, recurrence and mortality between the two groups (5-year OS, RR = 1.14, 95% CI = 0.96–1.35, P = 0.12; I2 = 56%), (5-year DFS, RR = 0.81, 95% CI = 0.61–1.08, P = 0.15; I2 = 60%), (Recurrence, RR = 1.04, 95% CI = 0.94–1.15, P = 0.45; I2 = 27%), and (Mortality, RR = 0.55, 95% CI = 0.26–1.15, P = 0.11; I2 = 0%). In addition to that, no significant difference could be detected in the overall incidence of complications between the two groups (Complications, RR = 0.94, 95% CI = 0.76–1.16, P = 0.57; I2 = 0%). However, CH is associated with a remarkable increase in the rate of biliary fistula (Biliary fistula, RR = 1.90, 95% CI = 1.07–3.40, P = 0.03; I2 = 0%). And Liver cell failure was higher in the case of EH (LCF, RR = 0.47, 95% CI = 0.30–0.76, P = 0.002; I2 = 0%). Regarding the operative details, CH is associated with longer operative time (Time of the operation, Mean difference = 0.82, 95% CI = 0.36, 1.27, P = 0.0004; I2 = 57%).

Conclusion
No significant difference in the short and long-term survival and recurrence between CH and MH for CL-HCC. However, CH is associated with greater future remnant liver volume that decreases the incidence of LCF and provides more opportunities for a repeat hepatectomy after tumour recurrence.
Exploring the impacts of a coffin-lying experience on life and death attitudes of medical and nursing students: preliminary findings
Authors: Chiou Ruei-Jen , Tsai Po-Fang , Han Der-Yan 
Published: January 2023

Abstract
Background
Physicians and nurses often exhibit strong negative emotional and behavioral reactions when patients they care for die, and death education helps them cope with these difficulties. When implementing death education, the literature shows that experiential activities are more effective than lecturing, and progressive exposure is the best way to reduce death anxieties. This study examined the effects of coffin-lying, an activity sometimes seen in Asian cultures, on life and death attitudes of medical and nursing students.

Methods
During a period from 2020 to 2021, 134 medical and nursing students from a medical university in northern Taiwan voluntarily participated in this study. Among them, 53 were in the experimental group, who participated in a coffin-lying activity for nearly 3 hours, and the other 81 were in the control group. All participants filled out questionnaires 1 week before the activity (T1), 1 week after the activity (T2), and 6 ~ 11 weeks after the activity (T3). Three waves of data were analyzed by a repeated-measure multivariate analysis of variance (MANOVA).

Results
The effects of “love and care” and “feeling of existence” were only manifested at T2, however, the scores of “fear of death” and “death avoidance” between the experimental and control groups significantly differed at T2 and T3. In addition, there were no significant differences between the experimental and control groups in “neutral acceptance”, “approach acceptance”, or “escape acceptance”.

Conclusions
The coffin-lying activity based on desensitization was effective in improving “fear of death” and “death avoidance”, and the effects were sustained to 6 ~ 11 weeks. Coffin-lying is not only a well-designed activity that quickly reduces negative tendencies toward death, but it is also worth adopting by medical and nursing schools to make death education more comprehensive.
The relationship between toxic leadership and organizational performance: the mediating effect of nurses’ silence
Authors: Farghaly Abdelaliem Sally Mohammed , Abou Zeid Mennat Allah G. 
Published: January 2023

Abstract
Aims
To assess toxic leadership and organizational performance among nurses of a University Hospital, and explore the mediating effect of nurses ‘silence.

Background
Toxic Leadership behaviours are hurtful to feelings, leading to emotive fatigue and nurses silence within the legislative framework. In fact, it is very harmful to all organizations. However, little emphasis has been paid to research on the mediating mechanism and border factors of their connection.

Methods
A cross-sectional design was applied. Data was collected from 750 nurses over the course of three months. The researchers employed structured equation modeling [SEM] to investigate the role of nurses’ silence in mediating the association between toxic leadership and organizational performance.

Results
The toxic leadership level and Organisational performance level were both high. In addition to, the nurses’ silence level was moderate. The SEM revealed that toxic Leadership accounted for the prediction of 65% of the variance of nurses’ silence and 87% of the variance of organizational performance. Also, nurses silence as a mediating factor accounted for 73% of the variance of organizational performance.

Conclusions
This study emphasized on the importance of creating a work environment that encourages and promotes open communication, as well as eliminating toxic leadership behaviours from the organizational culture among nurses as it effects on the organizational performance.