bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the relationship between spiritual well-being and death anxiety in patients with gynecological cancer: a cross-section study
Authors: Feng Yue , Liu Xingcan , Lin Tangwei , Luo Biru , Mou Qianqian , Ren Jianhua , Chen Jing 
Published: June 2021

Abstract
Background
In recent years, spiritual well-being has gradually gained the attention of health care providers in China, especially those in oncology departments, who have recognized the importance of improving spiritual well-being in cancer patients. Since most of the current research on spiritual well-being has been carried out in areas with religious beliefs, this study was conducted in the context of no development of formal religion. The purpose of this study was to explore the relationship between death anxiety and spiritual well-being and the related factors of spiritual well-being among gynecological cancer patients.

Methods
This cross-section study was conducted among 586 gynecological cancer patients. The European Organization for Research and Treatment for Cancer Quality of Life Questionnaire-spiritual well-being32 (EORTC QLQ-SWB32) and Templer's Death Anxiety Scale (T-DAS) were used to measure spiritual well-being and death anxiety. The Multiple Linear Regression Model was used to determine the relationship between spiritual well-being and death anxiety.

Results
For all participants, the highest QLQ-SWB32 centesimal score was 75.13 on the Relationship with Other scale, and the lowest was 60.33 on the Relationship with Someone or Something Greater Scale. The mean Death Anxiety score was 5.31 (SD 3.18). We found that Relationship with Someone or Something Greater was the only scale not associated with death anxiety. Overall, patients with lower death anxiety have a higher level of spiritual well-being. Besides, a high Relationship with Other score was associated with living with a partner (B = 2.471, P < 0.001) and married (B = -6.475, P = 0.001). Patients with higher Global-SWB were retired (B = 0.387, P = 0.019).

Conclusions
Our study found that the spiritual well-being of patients with gynecological cancer in China was no worse than in other countries with religious beliefs and patients with lower death anxiety have a higher level of spiritual well-being. Clinical staff should pay attention to the spiritual health of cancer patients, and spiritual care should be regarded as an essential element in cancer care.
Ethical factors determining ECMO allocation during the COVID-19 pandemic
Authors: Dao Bernadine , Savulescu Julian , Suen Jacky Y. , Fraser John F. , Wilkinson Dominic J. C. 
Published: June 2021

AbstractBackgroundECMO is a particularly scarce resource during the COVID-19 pandemic. Its allocation involves ethical considerations that may be different to usual times. There is limited pre-pandemic literature on the ethical factors that ECMO physicians consider during ECMO allocation. During the pandemic, there has been relatively little professional guidance specifically relating to ethics and ECMO allocation; although there has been active ethical debate about allocation of other critical care resources. We report the results of a small international exploratory survey of ECMO clinicians’ views on different patient factors in ECMO decision-making prior to and during the COVID-19 pandemic. We then outline current ethical decision procedures and recommendations for rationing life-sustaining treatment during the COVID-19 pandemic, and examine the extent to which current guidelines for ECMO allocation (and reported practice) adhere to these ethical guidelines and recommendations.MethodsAn online survey was performed with responses recorded between mid May and mid August 2020. Participants (n = 48) were sourced from the ECMOCard study group—an international group of experts (n = 120) taking part in a prospective international study of ECMO and intensive care for patients during the COVID-19 pandemic. The survey compared the extent to which certain ethical factors involved in ECMO resource allocation were considered prior to and during the pandemic.ResultsWhen initiating ECMO during the pandemic, compared to usual times, participants reported giving more ethical weight to the benefit of ECMO to other patients not yet admitted as opposed to those already receiving ECMO, (p < 0.001). If a full unit were referred a good candidate for ECMO, participants were more likely during the pandemic to consider discontinuing ECMO from a current patient with low chance of survival (53% during pandemic vs. 33% priorp = 0.002). If the clinical team recommends that ECMO should cease, but family do not agree, the majority of participants indicated that they would continue treatment, both in usual circumstances (67%) and during the pandemic (56%).ConclusionsWe found differences during the COVID-19 pandemic in prioritisation of several ethical factors in the context of ECMO allocation. The ethical principles prioritised by survey participants were largely consistent with ECMO allocation guidelines, current ethical decision procedures and recommendations for allocation of life-sustaining treatment during the COVID-19 pandemic.
Effect of probiotic supplementation along with calorie restriction on metabolic endotoxemia, and inflammation markers in coronary artery disease patients: a double blind placebo controlled randomized clinical trial
Authors: Moludi Jalal , Kafil Hossein Samadi , Qaisar Shaimaa A. , Gholizadeh Pourya , Alizadeh Mohammad , Vayghyan Hamed Jafari 
Published: June 2021

Abstract
Purpose
Alterations in the gut microbiome (dysbiosis) has been associated with increased microbial translocation, leading to chronic inflammation in coronary artery disease (CAD). It has been proposed that modulation of gut microbiota by probiotic might modify metabolic endotoxemia. Therefore, the purpose of this study was to examine the effects of Lactobacillus rhamnosus GG (LGG) on endotoxin level, and biomarkers of inflammation in CAD participants.

Methods
This study was a 12-weeks randomized, double-blind, and intervention on 44 patients with CAD. Patients were randomly allocated to receive either one LGG capsule 1.6 × 109 colony-forming unit (CFU) or the placebo capsules for 12 weeks. In addition, all the participants were also prescribed a calorie-restricted diet. Serum levels of interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), interleukin-10 (IL-10), and lipopolysaccharide (LPS), were assessed before and after the intervention.

Results
A significant decrease in IL1-Beta concentration (− 1.88 ± 2.25, vs. 0.50 ± 1.58 mmol/L, P = 0.027), and LPS levels (− 5.88 ± 2.70 vs. 2.96+ 5.27 mg/L, P = 0.016), was observed after the probiotic supplementation compared with the placebo. Participants who had ≥2.5 kg weight loss showed significantly improved cardiovascular-related factors, compared to patients with < 2.5 kg weight reduction, regardless of the supplement they took.

Conclusion
These data provide preliminary evidence that probiotic supplementation has beneficial effects on metabolic endotoxemia, and mega inflammation in participants with CAD.
Development of a non-invasive method for skin cholesterol detection: pre-clinical assessment in atherosclerosis screening
Authors: Ni Jingshu , Hong Haiou , Zhang Yang , Tang Shiqi , Han Yongsheng , Fang Zhaohui , Zhang Yuanzhi , Zhou Nan , Wang Quanfu , Liu Yong , Li Zhongsheng , Wang YiKun , Dong Meili 
Published: June 2021

Abstract
Background
Establishing a high-accuracy and non-invasive method is essential for evaluating cardiovascular disease. Skin cholesterol is a novel marker for assessing the risk of atherosclerosis and can be used as an independent risk factor of early assessment of atherosclerotic risk.

Methods
We propose a non-invasive skin cholesterol detection method based on absorption spectroscopy. Detection reagents specifically bind to skin cholesterol and react with indicator to produce colored products, the skin cholesterol content can be obtained through absorption spectrum information on colored products detected by non-invasive technology. Gas chromatography is used to measure cholesterol extracted from the skin to verify the accuracy and reliability of the non-invasive test method. A total of 342 subjects were divided into normal group (n = 115), disease group (n = 110) and risk group (n = 117). All subjects underwent non-invasive skin cholesterol test. The diagnostic accuracy of the measured value was analyzed by receiver-operating characteristic (ROC) curve.

Results
The proposed method is able to identify porcine skin containing gradient concentration of cholesterol. The values measured by non-invasive detection method were significantly correlated with gas chromatography measured results (r = 0.9074, n = 73, p < 0.001). Bland–Altman bias was − 72.78 ± 20.03 with 95% limits of agreement − 112.05 to − 33.51, falling within the prespecified clinically non-significant range. We further evaluated the method of patients with atherosclerosis and risk population as well as normal group, patients and risk atherosclerosis group exhibited higher skin cholesterol content than normal group (all P < 0.001). The area under the ROC curve for distinguishing Normal/Disease group was 0.8642 (95% confidence interval, 0.8138 to 0.9146), meanwhile, the area under the ROC curve for distinguishing Normal/Risk group was 0.8534 (95% confidence interval, 0.8034 to 0.9034).

Conclusions
The method demonstrated its capability of detecting different concentration of skin cholesterol. This non-invasive skin cholesterol detection system may potentially be used as a risk assessment tool for atherosclerosis screening, especially for a large population.
COVID-19 ARDS is characterized by higher extravascular lung water than non-COVID-19 ARDS: the PiCCOVID study
Authors: Shi Rui , Lai Christopher , Teboul Jean-Louis , Dres Martin , Moretto Francesca , De Vita Nello , Pham Tài , Bonny Vincent , Mayaux Julien , Vaschetto Rosanna , Beurton Alexandra , Monnet Xavier 
Published: June 2021

Abstract
Background
In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin.

Methods
Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020.

Results
Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14–21) vs. 15 (11–19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18–27) vs. 21 (15–24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70–109) vs. 100 (80–124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort.

Conclusion
Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups.

Trial registration number and date of registration
ClinicalTrials.gov (NCT04337983). Registered 30 March 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983.
Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation
Authors: Padmanabhan Nisha , Kyon Huang Kie , Boot Arnoud , Lim Kevin , Srivastava Supriya , Chen Shuwen , Wu Zhiyuan , Lee Hyung-Ok , Mukundan Vineeth T. , Chan Charlene , Chan Yarn Kit , Xuewen Ong , Pitt Jason J. , Isa Zul Fazreen Adam , Xing Manjie , Lee Ming Hui , Tan Angie Lay Keng , Ting Shamaine Ho Wei , Luftig Micah A. , Kappei Dennis , Kruger Warren D. , Bian Jinsong , Ho Ying Swan , Teh Ming , Rozen Steve George , Tan Patrick 
Published: June 2021

Abstract
Background
CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumor suppressors. Currently, for most cancers including gastric cancer (GC), mechanisms underlying CIMP remain poorly understood. We sought to discover molecular contributors to CIMP in GC, by performing global DNA methylation, gene expression, and proteomics profiling across 14 gastric cell lines, followed by similar integrative analysis in 50 GC cell lines and 467 primary GCs.

Results
We identify the cystathionine beta-synthase enzyme (CBS) as a highly recurrent target of epigenetic silencing in CIMP GC. Likewise, we show that CBS epimutations are significantly associated with CIMP in various other cancers, occurring even in premalignant gastroesophageal conditions and longitudinally linked to clinical persistence. Of note, CRISPR deletion of CBS in normal gastric epithelial cells induces widespread DNA methylation changes that overlap with primary GC CIMP patterns. Reflecting its metabolic role as a gatekeeper interlinking the methionine and homocysteine cycles, CBS loss in vitro also causes reductions in the anti-inflammatory gasotransmitter hydrogen sulfide (H2S), with concomitant increase in NF-κB activity. In a murine genetic model of CBS deficiency, preliminary data indicate upregulated immune-mediated transcriptional signatures in the stomach.

Conclusions
Our results implicate CBS as a bi-faceted modifier of aberrant DNA methylation and inflammation in GC and highlights H2S donors as a potential new therapy for CBS-silenced lesions.
An update on targeted therapies in systemic sclerosis based on a systematic review from the last 3 years
Authors: Campochiaro Corrado , Allanore Yannick 
Published: June 2021

AbstractNew molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study and the results obtained were reviewed. Of the 973 references identified, 21 (4 conference abstracts and 17 articles) were included in the systematic review. A total of 15 phase 1/phase 2 clinical trials, 2 phase 3 clinical trials and 2 observation studies were analysed. The drugs studied in phase 1/phase 2 studies included the following: inebilizumab, dabigatran, C-82, pomalidomide, rilonacept, romilkimab, tocilizumab, tofacitinib, pirfenidone, lenabasum, abatacept, belimumab, riociguat, SAR100842 and lanifibranor. All but 3 studies were performed in early diffuse SSc patients with different inclusion criteria, while 3 studies were performed in SSc patients with interstitial lung disease (ILD). Phase 3 clinical trials investigated nintedanib and tocilizumab. Nintedanib was investigated in SSc-ILD patients whereas tocilizumab focused on early diffuse SSc patients with inflammatory features. Two observational studies including > 50 patients with rituximab as the targeted drug were also evaluated. All these studies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc.
Subcellular localization of the mouse PRAMEL1 and PRAMEX1 reveals multifaceted roles in the nucleus and cytoplasm of germ cells during spermatogenesis
Authors: Liu Wan-Sheng , Lu Chen , Mistry Bhavesh V. 
Published: June 2021

Abstract
Background
Preferentially expressed antigen in melanoma (PRAME) is a cancer/testis antigen (CTA) that is predominantly expressed in normal gametogenic tissues and a variety of tumors. Members of the PRAME gene family encode leucine-rich repeat (LRR) proteins that provide a versatile structural framework for the formation of protein–protein interactions. As a nuclear receptor transcriptional regulator, PRAME has been extensively studied in cancer biology and is believed to play a role in cancer cell proliferation by suppressing retinoic acid (RA) signaling. The role of the PRAME gene family in germline development and spermatogenesis has been recently confirmed by a gene knockout approach. To further understand how PRAME proteins are involved in germ cell development at a subcellular level, we have conducted a systematic immunogold electron microscopy (IEM) analysis on testis sections of adult mice with gene-specific antibodies from two members of the mouse Prame gene family: Pramel1 and Pramex1. Pramel1 is autosomal, while Pramex1 is X-linked, both genes are exclusively expressed in the testis.

Results
Our IEM data revealed that both PRAMEL1 and PRAMEX1 proteins were localized in various cell organelles in different development stages of spermatogenic cells, including the nucleus, rER, Golgi, mitochondria, germ granules [intermitochondrial cement (IMC) and chromatoid body (CB)], centrioles, manchette, and flagellum. Unlike other germ cell-specific makers, such as DDX4, whose proteins are evenly distributed in the expressed-organelle(s), both PRAMEL1 and PRAMEX1 proteins tend to aggregate together to form clusters of protein complexes. These complexes were highly enriched in the nucleus and cytoplasm (especially in germ granules) of spermatocytes and spermatids. Furthermore, dynamic distribution of the PRAMEL1 protein complexes were observed in the microtubule-based organelles, such as acroplaxome, manchette, and flagellum, as well as in the nuclear envelope and nuclear pore. Dual staining with PRAMEL1 and KIF17B antibodies further revealed that the PRAMEL1 and KIF17B proteins were co-localized in germ granules.

Conclusion
Our IEM data suggest that the PRAMEL1 and PRAMEX1 proteins are not only involved in transcriptional regulation in the nucleus, but may also participate in nucleocytoplasmic transport, and in the formation and function of germ cell-specific organelles during spermatogenesis.
Joint contributions of the gut microbiota and host genetics to feed efficiency in chickens
Authors: Wen Chaoliang , Yan Wei , Mai Chunning , Duan Zhongyi , Zheng Jiangxia , Sun Congjiao , Yang Ning 
Published: June 2021

Abstract
Background
Feed contributes most to livestock production costs. Improving feed efficiency is crucial to increase profitability and sustainability for animal production. Host genetics and the gut microbiota can both influence the host phenotype. However, the association between the gut microbiota and host genetics and their joint contribution to feed efficiency in chickens is largely unclear.

Results
Here, we examined microbial data from the duodenum, jejunum, ileum, cecum, and feces in 206 chickens and their host genotypes and confirmed that the microbial phenotypes and co-occurrence networks exhibited dramatic spatial heterogeneity along the digestive tract. The correlations between host genetic kinship and gut microbial similarities within different sampling sites were weak, with coefficients ranging from − 0.07 to 0.08. However, microbial genome-wide analysis revealed that genetic markers near or inside the genes MTHFD1L and LARGE1 were associated with the abundances of cecal Megasphaera and Parabacteroides, respectively. The effect of host genetics on residual feed intake (RFI) was 39%. We further identified three independent genetic variations that were related to feed efficiency and had a modest effect on the gut microbiota. The contributions of the gut microbiota from the different parts of the intestinal tract on RFI were distinct. The cecal microbiota accounted for 28% of the RFI variance, a value higher than that explained by the duodenal, jejunal, ileal, and fecal microbiota. Additionally, six bacteria exhibited significant associations with RFI. Specifically, lower abundances of duodenal Akkermansia muciniphila and cecal Parabacteroides and higher abundances of cecal Lactobacillus, Corynebacterium, Coprobacillus, and Slackia were related to better feed efficiency.

Conclusions
Our findings solidified the notion that both host genetics and the gut microbiota, especially the cecal microbiota, can drive the variation in feed efficiency. Although host genetics has a limited effect on the entire microbial community, a small fraction of gut microorganisms tends to interact with host genes, jointly contributing to feed efficiency. Therefore, the gut microbiota and host genetic variations can be simultaneously targeted by favoring more-efficient taxa and selective breeding to improve feed efficiency in chickens.
Regional lithium prescription rates and recurrence in bipolar disorder
Authors: Sköld Martin , Rolstad Sindre , Joas Erik , Kardell Mathias , Pålsson Erik , Goodwin Guy M. , Landén Mikael 
Published: June 2021

AbstractBackgroundLithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes.AimsTo estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden.MethodData from 14,616 patients with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified were extracted from the Swedish national quality assurance register for bipolar disorders (BipoläR). Lithium prescription frequencies were calculated for 21 counties. Logistic regression analyses were run adjusted for confounders, with any type of recurrence as primary outcome, and incident elated and depressive episodes as secondary outcomes. Subsets of patients with bipolar I, II and not otherwise specified disorder were also analysed separately.ResultsLithium prescription rates for populations with all bipolar subtypes ranged across counties from 37.7 to 84.9% (mean 52.4%). Higher regional prescription rates were significantly associated with lower rate of any type of recurrence. The association was stronger when bipolar I disorder was analysed separately.ConclusionsThe advantages for lithium use long acknowledged for bipolar I disorder are also seen for the rest of the bipolar spectrum. Results suggest that population level outcomes of bipolar disorder could be improved by increasing the number of patients using lithium.