bluuebunny/crossref_metadata_2025 huggingface dataset:
A Mendelian randomization study on causal effects of 25(OH) vitamin D levels on diabetic nephropathy
Authors: He Mingjie , Yang Ting , Zhou Ping , Bu Peiyan , Yang Xionghui , Zou Yan , Zhong Aimin
Published: June 2023

Background

Vitamin D supplementation is associated with a lower incidence of diabetic nephropathy (DN); however, whether this association is causative is uncertain.

Methods

We used two-sample Mendelian randomization to examine the causal influence of vitamin D on diabetic nephropathy in 7,751 individuals with type I diabetes-related nephropathy (T1DN) and 9,933 individuals with type II diabetes-related nephropathy (T2DN). Meanwhile, we repeated some previous studies on the influence of KIM-1 (kidney injury molecule 1) and body mass index (BMI) on DN. Additionally, to test the validity of the instruments variable for vitamin D, we conducted two negative controls Mendelian randomization (MR) on breast and prostate cancer, and a positive control MR on multiple sclerosis.

Results

Results of the MR analysis showed that there was no causal association between 25(OH)D with the early/later stage of T1DN (early: OR = 0.903, 95%CI: 0.229 to 3.555; later: OR = 1.213, 95%CI: 0.367 to 4.010) and T2DN (early: OR = 0.588, 95%CI: 0.182 to 1.904; later: OR = 0.904, 95%CI: 0.376 to 2.173), nor with the kidney function of patients with diabetes mellitus: eGFRcyea (creatinine-based estimated GFR) (Beta = 0.007, 95%CI: -0.355 to 0.369)) or UACR (urinary albumin creatinine ratio) (Beta = 0.186, 95%CI: -0.961 to 1.333)).

Conclusions

We found no evidence that Vitamin D was causally associated with DN or kidney function in diabetic patients.
Mallory-Weiss syndrome in four hemodialysis patients: a case study
Authors: Shi Shuai-Shuai , Yang Xian-Zhu , Zhang Xiao-ye , Huang Lei , Guo Hui-Dan , Li Shuang-fang , Zhang Wei , Zhang Yi-Qiang
Published: June 2023

Background

Hemodialysis patients are prone to gastrointestinal bleeding, and Mallory-Weiss syndrome (MWS) is one of the causes. Mallory-Weiss syndrome is often induced by severe vomiting, manifests as upper gastrointestinal bleeding, and is self-limited with a good prognosis. However, mild vomiting in hemodialysis patients can lead to the occurrence of MWS, and the mild early symptoms are easy to misdiagnose, leading to the aggravation of the disease.

Case presentation

In this paper, we report four hemodialysis patients with MWS. All patients displayed symptoms of upper gastrointestinal bleeding. The diagnosis of MWS was confirmed by gastroscopy. One patient had a history of severe vomiting; however, the other three reported histories of mild vomiting. Three patients received the conservative hemostasis treatment, and the gastrointestinal bleeding stopped. One patient underwent the gastroscopic and interventional hemostasis treatments. The conditions of three of the patients improved. Unfortunately, one of the patients died due to the cardia insufficiency.

Conclusions

We think that the mild symptoms of MWS are easily covered up by other symptoms. This may lead to delays in diagnosis and treatment. For patients with severe symptoms, gastroscopic hemostasis is still the first choice, and interventional hemostasis can also be considered. For patients with mild symptoms, drug hemostasis is the first consideration.
Neuroinflammation-associated miR-106a-5p serves as a biomarker for the diagnosis and prognosis of acute cerebral infarction
Authors: Du Wei , Fan Lingyan , Du Juan
Published: June 2023

Background

Acute cerebral infarction (ACI) is a common cerebrovascular disease. Previous studies have shown that some abnormally expressed microRNAs (miRNAs) play important roles in ACI. This study aimed to investigate the role of miR-106a-5p in the diagnosis and prognosis of ACI patients, and analyze the regulatory potential of miR-106a-5p on the inflammation of BV-2 microglial cells.

Method

Serum and cerebrospinal fluid (CSF) samples were collected from 98 ACI patients, and the expression of serum miR-106a-5p was analyzed using qRT-PCR. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of miR-106a-5p. The association of miR-106a-5p with ACI prognosis was evaluated using the logistic analysis. In vitro experiments were performed in BV-2 cells by oxygen glucose deprivation (OGD) treatment, and the effects of miR-106a-5p on BV-2 inflammation were assessed using an enzyme linked immunosorbent assay (ELISA).

Result

It was observed that miR-106a-5p was significantly upregulated in the serum and CSF of ACI patients (all P < 0.001), and had considerable diagnostic accuracy. The highest serum miR-106a-5p was observed in severe ACI cases, and miR-106a-5p expression was significantly increased in unfavorable prognosis patients. Serum and CSF expression of miR-106a-5p was positively correlated with proinflammatory cytokines in ACI patients, and the inflammation of OGD-induced BV-2 cells was suppressed by miR-106a-5p reduction.

Conclusion

MiR-106a-5p is overexpressed in ACI patients and may serve as a diagnostic and prognostic biomarker for ACI. Furthermore, miR-106a-5p may be involved in ACI progression by regulating neuroinflammation.
Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels
Authors: He Jingqi , Wei Yisen , Li Jinguang , Tang Ying , Liu Junyu , He Zhangyin , Zhou Risheng , He Xingtao , Ren Honghong , Liao Yanhui , Gu Lin , Yuan Ning , Chen Xiaogang , Tang Jinsong
Published: June 2023

Background

Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the pro-inflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL-6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels.

Methods

The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by gender, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously.

Result

The results showed that patients with TRS had higher serum IL-6 levels than patients with PRS (p = 0.002). In females, IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005). And a positive correlation tendency was observed between IL-6 levels and PANSS general sub-scores (r = 0.31, p = 0.039), although this correlation was not significant after correcting for multiple comparisons. Whereas, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124) in males.

Conclusion

Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.
Traffic noise in the bedroom in association with markers of obesity: a cross-sectional study and mediation analysis of the respiratory health in Northern Europe cohort
Authors: Veber Triin , Pyko Andrei , Carlsen Hanne Krage , Holm Mathias , Gislason Thorarinn , Janson Christer , Johannessen Ane , Sommar Johan Nilsson , Modig Lars , Lindberg Eva , Schlünssen Vivi , Toompere Karolin , Orru Hans
Published: June 2023

Background

Previous research suggests an association between road traffic noise and obesity, but current evidence is inconclusive. The aim of this study was to assess the association between nocturnal noise exposure and markers of obesity and to assess whether sleep disturbance might be a mediator in this association.

Methods

We applied data from the Respiratory Health in Northern Europe (RHINE) cohort. We used self-measured waist circumference (WC) and body mass index (BMI) as outcome values. Noise exposure was assessed as perceived traffic noise in the bedroom and/or the bedroom window’s location towards the street. We applied adjusted linear, and logistic regression models, evaluated effect modifications and conducted mediation analysis.

Results

Based on fully adjusted models we found that women, who reported very high traffic noise levels in bedroom, had 1.30 (95% CI 0.24–2.37) kg/m2 higher BMI and 3.30 (95% CI 0.39–6.20) cm higher WC compared to women, who reported no traffic noise in the bedroom. Women who reported higher exposure to road traffic noise had statistically significant higher odds of being overweight and have abdominal obesity with OR varying from 1.15 to 1.26 compared to women, who reported no traffic noise in the bedroom. For men, the associations were rather opposite, although mostly statistically insignificant. Furthermore, men, who reported much or very much traffic noise in the bedroom, had a statistically significantly lower risk of abdominal obesity. Sleep disturbance fully or partially mediated the association between noise in bedroom and obesity markers among women.

Conclusion

Our results suggest that self-reported traffic noise in the bedroom may be associated to being overweight or obese trough sleep disturbance among women, but associations were inconclusive among men.
Socio-psychological factors associated with anticipated stigma toward COVID-19: a cross-sectional study in Japan
Authors: Fujii Kana , Hashimoto Hideki
Published: June 2023

Background

The stigmatization against COVID-19 has become a public issue. However, it remains unknown which individual factor contributes to anticipated stigma formation. This study explored socio-psychological factors associated with anticipated stigma toward coronavirus disease 2019 (COVID-19).

Methods

We obtained cross-sectional data regarding 1,638 middle-aged community residents (mean age, 48.5 years) from a population-based survey in metropolitan Tokyo, Japan during the third wave of the COVID-19 pandemic, when a regional public health emergency had been declared in December 2020 and January 2021. We hypothesized that perceived risk of infection, normative beliefs about preventive behaviors, and past experiences of stigmatization unrelated to COVID-19 would be associated with anticipated stigma. Modified Poisson regression was conducted to examine associations after adjustments for demographic and socioeconomic statuses.

Results

Higher perceived risk (adjusted prevalence ratio [APR] = 1.17; 95% confidence interval [CI, 1.08–1.27]), past experiences of stigmatization (APR = 1.09; 95% CI [1.00–1.19]), and higher normative beliefs about preventive behaviors (APR = 1.18; 95% CI [1.11–1.26]) were independently associated with anticipated stigma.

Conclusions

These results suggest that intervention messages to increase risk perception and normative beliefs to enhance protective behaviors may have the unintended effect of increasing anticipated stigma in the context of the COVID-19 pandemic.
Preserving or peeling the inferior mesenteric arterial sheath during laparoscopic rectal cancer surgery: a prospective study of surgical outcomes
Authors: Li Qian , Wang Ye , Wang Jia-wei , Qian Long , Wang Song , Cao Ting-ting , Xia Ya-bin , Huang Xiao-xu , Xu Li
Published: June 2023

Background

We mainly evaluated whether preserving the inferior mesenteric artery (IMA) sheath to dissecting IMA root lymph nodes (also called No.253 lymph nodes) would benefit patients in terms of comparable lymph-node yield removed during operation and postoperative complications in laparoscopic radical resection of rectal cancer.

Methods

This is a prospective study included 141 rectal cancer patients who received laparoscopic radical resection during September 2018 to December 2020. All patients were randomly assigned to the preserved group (n = 71) and the peeled group (n = 70). The baseline characteristics, pathological features, intraoperative and postoperative data outcomes and complications were analyzed by independent samples t test, chi-square test or Fisher’s exact test between the 2 groups.

Results

The baseline characteristic and pathological features had no statistical difference between the 2 groups. The preserved group had a shorter operative time (P = 0.002), a shorter lymph node dissection time (P < 0.001), less intraoperative bleeding (P = 0.004), an earlier time to first flatus (P = 0.013), an earlier time to fluid intake (P = 0.033) and a shorter length of hospitalization (P = 0.012) than the peeled group. The differences between the 2 groups were not statistically significant (P > 0.05) in regard to the total number of lymph nodes cleared, positive lymph nodes, bleeding, anastomotic leakage, pneumonia, wound infection, abscess, ileus, urinary retention, urinary tract infection and chyle leakage.

Conclusion

Preserving of the IMA sheath in laparoscopic radical surgery for rectal cancer will reduce the total operation time and the length of hospitalization. This surgical method could lead to lower complication rate and faster recovery.

Trial registration

The study was approved by the Ethics Committee of The First Affiliated Hospital of Wannan Medical College and registered by the China Clinical Trials Registry (ChiCTR2200060830, Date of Registration:2022-06-12 -retrospective registration) http://www.chictr.org.cn/index.aspx.
A comparison of palliative care and rapid emergency screening (P-CaRES) tool, broad and narrow criteria, and surprise questions to predict survival of older emergency department patients
Authors: Koyavatin Siripan , Liu Shan Woo , Sri-on Jiraporn
Published: June 2023

Background

Palliative care is a form of medical care designed to enhance the quality of life of patients with life-threatening conditions. This study was conducted to compare the accuracy of predicted survival the 1 and 3-month survival rate of Broad and narrow criteria, Surprise questions (SQ), and Palliative Care and Rapid Emergency Screening (P-CaRES) after admission to the emergency department (ED).

Methods

This prospective cohort study was conducted at an urban teaching hospital in Thailand. Patients aged ≥ 65 years admitted to the ED were classified according to their emergency severity index (ESI) (Level: 1–3). We collected data on SQ, P-CaRES, and broad and narrow criteria. A survival data of participants were collected at 1 and 3 months after admission to the ED. The survival rate was calculated using the Kaplan–Meier and log-rank tests.

Results

A total of 269 patients completed the study. P-CaRES positive and P-CaRES negative patients had 1-month survival rates of 81% and 94.8%, respectively (P = 0.37), and at 3-month survival rates of 70.7% and 90.1%, respectively (P < 0.001). SQ (not surprised) had a 1-month survival rate of 79.3%, while SQ (surprised) had a 97% survival rate (P = 0.01), and SQ (not surprised) had a 75.4% survival rate at 3-months, while SQ (surprised) had a 96.3% survival rate (P = 0.01). Broad and narrow criteria that were positive and negative had 1-month survival rates of 88.1% and 92.5%, respectively (P = 0.71), while those that were positive and negative had 3-month survival rates of 78.6% and 87.2%, respectively (P = 0.19). The hazard ratio (HR) of SQ (not surprised) at 1 month was 3.22( 95%CI:1.16–8.89). The HR at 3 months of P-CaRES (positive) was 3.31 with a 95% confidence interval (CI): 1.74 − 6.27, while the HR for SQ (not surprise) was 7.33, 95% CI: 3.03–19.79; however, broad and narrow criteria had an HR of 1.78, 95% CI:0.84–3.77.

Conclusions

Among older adults who visited the ED, the SQ were good prognosis tools for predicting 1 and 3-month survival, and P-CaRES were good prognostic tools for predicting 3-month survival.
The mediating effect of job satisfaction and emotional exhaustion on the relationship between psychological empowerment and turnover intention among Chinese nurses during the COVID-19 pandemic: a cross-sectional study
Authors: Ding Jinliang , Wu Yufang
Published: June 2023

Background

Turnover intention occurs frequently in nurses and psychological empowerment has been shown to be major factors that influence turnover intention. However, little is known about the driving force behind turnover intention among nurses in China during the COVID-19 pandemic.

Objectives

To investigate the mediating role of job satisfaction and emotional exhaustion on the association between psychological empowerment and turnover intention among Chinese nurses during the COVID-19 pandemic.

Methods

A cross-sectional design was conducted in China. A total of 507 nurses completed scales of psychological empowerment, job satisfaction, emotional exhaustion and turnover intention anonymously. Descriptive analysis, Pearson’s correlation analysis in SPSS 23.0 and structural equation modeling (SEM) by Mplus 7.4

Results

Psychological empowerment had a significantly effect on turnover intention through three significantly indirect pathways: (1) through job satisfaction (B = -0.14, SE = .03, 95% CI = [-.19, -.09]). (2) through emotional exhaustion (B = -0.07, SE = .02, 95% CI = [-.11, -.03]). (3) through the chain mediating effect of “job satisfaction → emotional exhaustion” (B = -0.12, SE = .02, 95% CI = [-.16, -.09]).

Conclusions

Intervention measures to reduce the incidence of turnover intention of nurses should include the evaluations of work demands and emotional exhaustion of nurses and organization’s management strategies to promote their psychological empowerment and job satisfaction.
Perceptions of nurses regarding quality of adult cardiopulmonary resuscitation in Ghana: a qualitative study
Authors: Amoako-Mensah Esther , Achempim-Ansong Gloria , Gbordzoe Newton Isaac , Adofo Cornelia Esson , Sarfo Jacob Owusu
Published: June 2023

Objectives

Cardiopulmonary resuscitation (CPR) is a necessary life-saving emergency intervention for patients with cardiac arrest and other medical conditions. The study’s primary objective was to qualitatively explore nurses’ perceptions of the quality of adult cardiopulmonary resuscitation in Ghana.

Methods

An exploratory descriptive qualitative study was conducted among 13 purposively sampled nurses in Ghana. We collected thirteen face-to-face and telephone interviews using a semi-structured interview guide. Data were transcribed verbatim and analysed using the thematic analysis approach recommended by Braun and Clarke.

Results

Data analysis revealed that nurses were filled with positive emotions when patients regained consciousness following resuscitation. When the otherwise happens, they tend to become tortured psychologically and filled with negative emotions. Besides, environmental factors such as the time of initiating CPR following a cardiac arrest, the availability and appropriateness of equipment and medications, workplace ergonomics, and institutional regulations affected the quality of resuscitation practices of nurses. Participants perceived that attitudes of condemnation, prejudice, apathy and skills deficiency also impacted the quality of resuscitation practices. Significant aspects of self-reported behavioural competence that affected resuscitation were knowledge and skills of CPR, confidence in initiating CPR, and the need for effort maximisation.

Conclusion

This study revealed several non-medical factors that influenced the resuscitation practices of nurses from their perspective. Nurses need to maximise their effort toward seeking further education in speciality areas such as emergency nursing and critical care nursing to guide their CPR practices and other newly emerging evidence-based protocols.
Patient and clinician perspectives of a remote monitoring program for COVID-19 and lessons for future programs
Authors: Chaiyachati Krisda H. , Shea Judy A. , Ward Michaela , Nelson Maria N. , Ghosh Medha , Reilly Julianne , Kelly Sheila , Chisholm Deena L. , Barbati Zoe , Hemmons Jessica E. , Abdel-Rahman Dina , Ebert Jeffrey P. , Xiong Ruiying A. , Snider Christopher K. , Lee Kathleen C. , Friedman Ari B. , Meisel Zachary F. , Kilaru Austin S. , Asch David A. , Delgado M. Kit , Morgan Anna U.
Published: June 2023

COVID Watch is a remote patient monitoring program implemented during the pandemic to support home dwelling patients with COVID-19. The program conferred a large survival advantage. We conducted semi-structured interviews of 85 patients and clinicians using COVID Watch to understand how to design such programs even better. Patients and clinicians found COVID Watch to be comforting and beneficial, but both groups desired more clarity about the purpose and timing of enrollment and alternatives to text-messages to adapt to patients’ preferences as these may have limited engagement and enrollment among marginalized patient populations. Because inclusiveness and equity are important elements of programmatic success, future programs will need flexible and multi-channel human-to-human communication pathways for complex clinical interactions or for patients who do not desire tech-first approaches.
Circular RNA FEACR inhibits ferroptosis and alleviates myocardial ischemia/reperfusion injury by interacting with NAMPT
Authors: Ju Jie , Li Xin-Min , Zhao Xue-Mei , Li Fu-Hai , Wang Shao-Cong , Wang Kai , Li Rui-Feng , Zhou Lu-Yu , Liang Lin , Wang Yin , Zhang Yu-Hui , Wang Kun
Published: June 2023

Background

Emerging research has reported that circular RNAs (circRNAs) play important roles in cardiac cell death after myocardial ischemia and reperfusion (I/R). Ferroptosis, a new form of cell death discovered in recent years, has been proven to participate in the regulation of myocardial I/R. This study used circRNA sequencing to explore the key circRNA in the regulation of cardiac ferroptosis after I/R and study the mechanisms of potential circRNA function.

Methods

We performed circRNA sequencing to explore circRNAs differentially expressed after myocardial I/R. We used quantitative polymerase chain reactions to determine the circRNA expression in different tissues and detect the circRNA subcellular localization in the cardiomyocyte. Gain- and loss-of-function experiments were aimed to examine the function of circRNAs in cardiomyocyte ferroptosis and cardiac tissue damage after myocardial I/R. RNA pull-down was applied to explore proteins interacting with circRNA.

Results

Here, we identified a ferroptosis-associated circRNA (FEACR) that has an underlying regulatory role in cardiomyocyte ferroptosis. FEACR overexpression suppressed I/R-induced myocardial infarction and ameliorated cardiac function. FEACR inhibition induces ferroptosis in cardiomyocytes and FEACR overexpression inhibits hypoxia and reoxygenation-induced ferroptosis. Mechanistically, FEACR directly bound to nicotinamide phosphoribosyltransferase (NAMPT) and enhanced the protein stability of NAMPT, which increased NAMPT-dependent Sirtuin1 (Sirt1) expression, which promoted the transcriptional activity of forkhead box protein O1 (FOXO1) by reducing FOXO1 acetylation levels. FOXO1 further upregulated the transcription of ferritin heavy chain 1 (Fth1), a ferroptosis suppressor, which resulted in the inhibition of cardiomyocyte ferroptosis.

Conclusions

Our finding reveals that the circRNA FEACR-mediated NAMPT-Sirt1-FOXO1-FTH1 signaling axis participates in the regulation of cardiomyocyte ferroptosis and protects the heart function against I/R injury. Thus, FEACR and its downstream factors could be novel targets for alleviating ferroptosis-related myocardial injury in ischemic heart diseases.
Treatment of obstructive sleep apnea in high risk pregnancy: a multicenter randomized controlled trial
Authors: Tantrakul Visasiri , Ingsathit Atiporn , Liamsombut Somprasong , Rattanasiri Sasivimol , Kittivoravitkul Prapun , Imsom-Somboon Nutthaphon , Lertpongpiroon Siwaporn , Jantarasaengaram Surasak , Somchit Werapath , Suwansathit Worakot , Pengjam Janejira , Siriyotha Sukanya , Panburana Panyu , Guilleminault Christian , Preutthipan Aroonwan , Attia John , Thakkinstian Ammarin
Published: June 2023

Background

Obstructive sleep apnea (OSA) during pregnancy is a risk factor for preeclampsia possibly through a link to placental physiology. This study evaluates the efficacy of continuous positive airway pressure (CPAP) on the modulation of blood pressure and the reduction in preeclampsia in women with high-risk pregnancy and OSA.

Methods

A multicenter open-label, randomized controlled trial comparing CPAP treatment versus usual antenatal care was conducted in three academic hospitals in Bangkok, Thailand. Participants included singleton pregnant women aged older than 18 years with any high-risk condition (i.e., chronic hypertension, obesity, history of preeclampsia or gestational diabetes in the previous pregnancy, or diabetes), and OSA (respiratory disturbance index 5–29.99 events/hour by polysomnography), who presented either in the first trimester (gestational age, GA 0–16 weeks) or subsequently developed OSA during the 2nd trimester (GA 24–28 weeks). The primary endpoint was blood pressure during antenatal care. Secondary endpoints included the incidence of preeclampsia. An intention-to-treat analysis was performed with additional per-protocol and counterfactual analyses for handling of nonadherence.

Results

Of 340 participants, 96.5% were recruited during the first trimester. Thirty participants were later excluded leaving 153 and 157 participants in the CPAP and usual-care groups for the modified-intention-to-treat analysis. CPAP adherence rate was 32.7% with average use of 2.5 h/night. Overall, CPAP treatment significantly lowered diastolic blood pressure (DBP) by − 2.2 mmHg [95% CI (− 3.9, − 0.4), p = 0.014], representing approximately − 0.5 mmHg per hour of CPAP use [95%CI (− 0.89, − 0.10), p = 0.013]. CPAP treatment also altered the blood pressure trajectory by continuously lowering DBP throughout pregnancy with mean differences (95% CI) of − 3.09 (− 5.34, − 0.93), − 3.49 (− 5.67, − 1.31) and − 3.03 (− 5.20, − 0.85) mmHg at GA 18–20, 24–28, and 32–34 weeks, respectively compared to 0–16 weeks. Preeclampsia rate was 13.1% (20/153 participants) in the CPAP and 22.3% (35/157 participants) in the usual-care group with a risk difference (95% CI) of − 9% (− 18%, − 1%, p-value = 0.032) and a number-needed-to-treat (95% CI) of 11 (1, 21).

Conclusions

CPAP treatment in women with even mild-to-moderate OSA and high-risk pregnancy demonstrated reductions in both DBP and the incidence of preeclampsia. CPAP treatment also demonstrated a sustained reduction in DBP throughout gestation.

Trial registration ClinicalTrial.GovNCT03356106, retrospectively registered November 29, 2017.
Implementation of PM-JAY in India: a qualitative study exploring the role of competency, organizational and leadership drivers shaping early roll-out of publicly funded health insurance in three Indian states
Authors: Srivastava Swati , Bertone Maria Paola , Basu Sharmishtha , De Allegri Manuela , Brenner Stephan
Published: June 2023

Background

The Pradhan Mantri Jan Arogya Yojana (PM-JAY), a publicly funded health insurance scheme, was launched in India in September 2018 to provide financial access to health services for poor Indians. PM-JAY design enables state-level program adaptations to facilitate implementation in a decentralized health implementation space. This study examines the competency, organizational, and leadership approaches affecting PM-JAY implementation in three contextually different Indian states.

Methods

We used a framework on implementation drivers (competency, organizational, and leadership) to understand factors facilitating or hampering implementation experiences in three PM-JAY models: third-party administrator in Uttar Pradesh, insurance in Chhattisgarh, and hybrid in Tamil Nadu. We adopted a qualitative exploratory approach and conducted 92 interviews with national, state, district, and hospital stakeholders involved in program design and implementation in Delhi, three state capitals, and two anonymized districts in each state, between February and April 2019. We used a deductive approach to content analysis and interpreted coded material to identify linkages between organizational features, drivers, and contextual elements affecting implementation.

Results and conclusion

PM-JAY guideline flexibilities enabled implementation in very different states through state-adapted implementation models. These models utilized contextually relevant adaptations for staff and facility competencies and organizational and facilitative administration, which had considerable scope for improvement in terms of recruitment, competency development, programmatic implementation support, and rationalizing the joint needs of the program and implementers. Adaptations also created structural barriers in staff interactions and challenged implicit power asymmetries and organizational culture, indicating a need for aligning staff hierarchies and incentive structures. At the same time, specific adaptations such as decentralizing staff selection and task shifting (all models); sharing of claims processing between the insurer and state agency (insurance and hybrid model); and using stringent empanelment, accreditation, monitoring, and benchmarking criteria for performance assessment, and reserving secondary care benefit packages for public hospitals (both in the hybrid model) contributed to successful implementation. Contextual elements such as institutional memory of previous schemes and underlying state capacities influenced all aspects of implementation, including leadership styles and autonomy. These variations make comparisons across models difficult, yet highlight constraints and opportunities for cross-learning and optimizing implementation to achieve universal health coverage in decentralized contexts.
Retraction Note: Down-regulation of kappa opioid receptor promotes ESCC proliferation, invasion and metastasis via the PDK1-AKT signaling pathway
Authors: Huang Han-Ming , He Xin-Hua , Huang Xiao-Yu , Wang Guo-Yun , Xia Qiao-Xi , Du Ze-Peng , Zhang Yong-Fa
Published: June 2023

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12964-022-00833-3.
Unique features of the arterial blood–brain barrier
Authors: Bell Batia , Anzi Shira , Sasson Esther , Ben-Zvi Ayal
Published: June 2023

CNS vasculature differs from vascular networks of peripheral organs by its ability to tightly control selective material exchange across capillary barriers. Capillary permeability is mostly defined by unique cellular components of the endothelium. While capillaries are extensively investigated, the barrier properties of larger vessels are understudied. Here, we investigate barrier properties of CNS arterial walls. Using tracer challenges and various imaging modalities, we discovered that at the mouse cortex, the arterial barrier does not reside at the classical level of the endothelium. The arterial wall’s unique permeability acts bi-directionally; CSF substances travel along the glymphatic path and can penetrate from the peri-vascular space through arteriolar walls towards the lumen. We found that caveolae vesicles in arteriole endothelial are functional transcytosis machinery components, and that a similar mechanism is evident in the human brain. Our discoveries highlight vascular heterogeneity investigations as a potent approach to uncover new barrier mechanisms.
Gegen Qinlian Decoction treatment of asymptomatic hyperuricemia by targeting circadian immune function
Authors: Wang Xiaojun , Liu Xuanqi , Gao Qiushuang , Gu Xuchao , Zhang Guannan , Sheng Zhiyuan , Wu Tao , Su Zheling , Wang Wenhao , Ye Maoqing
Published: June 2023

Background

The Gegen Qinlian Decoction (GGQLD) is a renowned traditional Chinese medicinal formula that has been used for centuries to effectively treat asymptomatic Hyperuricemia (HUA). This study aims to investigate the underlying mechanism of GGQLD's therapeutic effects on HUA.

Methods

The study enrolled a total of 25 healthy participants and 32 middle-aged and elderly individuals with asymptomatic HUA. All asymptomatic HUA participants were treated with GGQLD. Venous blood samples were collected from all participants to isolate peripheral blood mononuclear cells (PBMCs), which were then analyzed for biological profiles using flow cytometry. Network pharmacology analysis was utilized to identify the potential pathways involved in the therapeutic effects of GGQLD. Transcriptomic patterns of cultured proximal tubule epithelial cells (PTECs) were evaluated via bulk RNA-seq, and critical differentially expressed genes (DEGs) were identified and verified through ELISA. Molecular docking and molecular dynamics (MD) simulation were employed to investigate the potential compounds in GGQLD that may be involved in treating HUA.

Results

Network pharmacology analysis revealed that immune-related pathways might be involved in the therapeutic mechanism of GGQLD. RNA-seq analysis confirmed the involvement of innate lymphoid cell (ILC) development-related genes and clock genes. Polychromatic flow cytometric analysis demonstrated that GGQLD treatment reduced the proportion of ILC3s in total ILCs in asymptomatic HUA patients. ELISA results showed that GGQLD treatment reduced the levels of activating factors, such as ILC3-IL-18 and IL-1β, in the plasma of HUA patients. GGQLD was also found to regulate circadian clock gene expression in PBMCs to treat asymptomatic HUA. Furthermore, the interaction between 40 compounds in GGQLD and HDAC3 (Histone Deacetylase 3), NLRP3 (NOD-like receptor protein 3), RORA (RAR-related orphan receptor A), and REV-ERBα (nuclear receptor subfamily 1) revealed that GGQLD may regulate ILCs and clock genes to treat asymptomatic HUA.

Conclusions

The regulation of circadian clock gene expression and the proportion of ILC cells may be involved in the therapeutic effects of GGQLD on asymptomatic HUA patients.
LCK facilitates DNA damage repair by stabilizing RAD51 and BRCA1 in the nucleus of chemoresistant ovarian cancer
Authors: Dey Goutam , Bharti Rashmi , Braley Chad , Alluri Ravi , Esakov Emily , Crean-Tate Katie , McCrae Keith , Joehlin-Price Amy , Rose Peter G. , Lathia Justin , Gong Zihua , Reizes Ofer
Published: June 2023

Poly-ADP Ribose Polymerase (PARP) targeted therapy is clinically approved for the treatment of homologous recombination (HR) repair deficient tumors. The remarkable success of this therapy in the treatment of HR repair deficient cancers has not translated to HR-proficient cancers. Our studies identify the novel role of non-receptor lymphocyte-specific protein tyrosine kinase (LCK) in the regulation of HR repair in endometrioid epithelial ovarian cancer (eEOC) model. We show that DNA damage leads to direct interaction of LCK with the HR repair proteins RAD51 and BRCA1 in a kinase dependent manner RAD51 and BRCA1 stabilization. LCK expression is induced and activated in the nucleus in response to DNA damage insult. Disruption of LCK expression attenuates RAD51, BRCA1, and BRCA2 protein expression by hampering there stability and results in inhibition of HR-mediated DNA repair including suppression of RAD51 foci formation, and augmentation of γH2AX foci formation. In contrast LCK overexpression leads to increased RAD51 and BRCA1 expression with a concomitant increase in HR DNA damage repair. Importantly, attenuation of LCK sensitizes HR-proficient eEOC cells to PARP inhibitor in cells and pre-clinical mouse studies. Collectively, our findings identify a novel therapeutic strategy to expand the utility of PARP targeted therapy in HR proficient ovarian cancer.

Graphical Abstract
Comparison of anti-Müllerian hormone and antral follicle count in the prediction of ovarian response: a systematic review and meta-analysis
Authors: Liu Yang , Pan Zhengmei , Wu Yanzhi , Song Jiamei , Chen Jingsi
Published: June 2023

Background

Increasingly studies reported that the Anti-Müllerian hormone (AMH) seems to be a promising and reliable marker of functional ovarian follicle reserve, even better than the AFC test. Our study aimed to conduct a meta-analysis to assess the predictive value of AMH and AFC for predicting poor or high response in IVF treatment. An electronic search was conducted, and the following databases were used: PubMed, EMBASE, and the Cochrane Library (up to 7 May 2022). The bivariate regression model was used to calculate the pooled sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve. Subgroup analyses and meta-regression also were used in the presented study. Overall performance was assessed by estimating pooled ROC curves between AMH and AFC.

Results

Forty-two studies were eligible for this meta-analysis. Comparison of the summary estimates for the prediction of poor or high response showed significant difference in performance for AMH compared with AFC [poor (sensitivity: 0.80 vs 0.74, P < 0.050; specificity: 0.81 vs 0.85, P < 0.001); high (sensitivity: 0.81 vs 0.87, P < 0.001)]. However, there were no significant differences between the ROC curves of AMH and AFC for predicting high (P = 0.835) or poor response (P = 0.567). The cut-off value was a significant source of heterogeneity in the present study.

Conclusions

The present meta-analysis demonstrated that both AMH and AFC have a good predictive ability to the prediction of poor or high responses in IVF treatment.
ExplaiNN: interpretable and transparent neural networks for genomics
Authors: Novakovsky Gherman , Fornes Oriol , Saraswat Manu , Mostafavi Sara , Wasserman Wyeth W.
Published: June 2023

Deep learning models such as convolutional neural networks (CNNs) excel in genomic tasks but lack interpretability. We introduce ExplaiNN, which combines the expressiveness of CNNs with the interpretability of linear models. ExplaiNN can predict TF binding, chromatin accessibility, and de novo motifs, achieving performance comparable to state-of-the-art methods. Its predictions are transparent, providing global (cell state level) as well as local (individual sequence level) biological insights into the data. ExplaiNN can serve as a plug-and-play platform for pretrained models and annotated position weight matrices. ExplaiNN aims to accelerate the adoption of deep learning in genomic sequence analysis by domain experts.
CrebH protects against liver injury associated with colonic inflammation via modulation of exosomal miRNA
Authors: Lee Sang-Hee , Moon Sung-Je , Woo Seung Hee , Ahn Gwangsook , Kim Won Kon , Lee Chul-Ho , Hwang Jung Hwan
Published: June 2023

Background

Hepatic liver disease, including primary sclerosing cholangitis (PSC), is a serious extraintestinal manifestations of colonic inflammation. Cyclic adenosine monophosphate (cAMP)-responsive element-binding protein H (CrebH) is a transcription factor expressed mostly in the liver and small intestine. However, CrebH’s roles in the gut–liver axis remain unknown.

Methods

Inflammatory bowel disease (IBD) and PSC disease models were established in wild-type and CrebH−/− mice treated with dextran sulfate sodium, dinitrobenzene sulfonic acid, and diethoxycarbonyl dihydrocollidine diet, respectively. RNA sequencing were conducted to investigate differential gene expression. Exosomes were isolated from plasma and culture media. miRNA expression profiling was performed using the NanoString nCounter Mouse miRNA Panel. Effects of miR-29a-3p on adhesion molecule expression were investigated in bEnd.3 brain endothelial cells.

Results

CrebH−/− mice exhibited accelerated liver injury without substantial differences in the gut after administration of dextran sulfate sodium (DSS), and had similar features to PSC, including enlarged bile ducts, enhanced inflammation, and aberrant MAdCAM-1 expression. Furthermore, RNA-sequencing analysis showed that differentially expressed genes in the liver of CrebH−/− mice after DSS overlapped significantly with genes changed in PSC-liver. Analysis of plasma exosome miRNA isolated from WT and CrebH−/− mice indicates that CrebH can contribute to the exosomal miRNA profile. We also identified miR-29a-3p as an effective mediator for MAdCAM-1 expression. Administration of plasma exosome from CrebH−/− mice led to prominent inflammatory signals in the liver of WT mice with inflammatory bowel disease (IBD).

Conclusions

CrebH deficiency led to increased susceptibility to IBD-induced liver diseases via enhanced expression of adhesion molecules and concomitant infiltration of T lymphocytes. Exosomes can contribute to the progression of IBD-induced liver injury in CrebH−/− mice. These study provide novel insights into the role of CrebH in IBD-induced liver injury.
Gender and racial differences in first and senior authorship of high-impact critical care randomized controlled trial studies from 2000 to 2022
Authors: Chander Subhash , Luhana Sindhu , Sadarat Fnu , Leys Lorenzo , Parkash Om , Kumari Roopa
Published: June 2023

Background

Females and ethnic minorities are underrepresented in the first and senior authorships positions of academic publications. This stems from various structural and systemic inequalities and discrimination in the journal peer-review process, as well as educational, institutional, and organizational cultures.

Methods

A retrospective bibliometric study design was used to investigate the representation of gender and racial/ethnic groups in the authorship of critical care randomized controlled trials in 12 high-impact journals from 2000 to 2022.

Results

In the 1398 randomized controlled trials included in this study, only 24.61% of the first authors and 16.6% of the senior authors were female. Although female authorship increased during the study period, authorship was significantly higher for males throughout (Chi-square for trend, p < 0.0001). The educational attainment [χ2(4) = 99.2, p < 0.0001] and the country of the author's affiliated institution [χ2(42) = 70.3, p = 0.0029] were significantly associated with gender. Male authorship was significantly more prevalent in 10 out of 12 journals analyzed in this study [χ2(11) = 110.1, p < 0.0001]. The most common race/ethnic group in our study population was White (85.1% women, 85.4% males), followed by Asians (14.3% females, 14.3% males). Although there was a significant increase in the number of non-White authors between 2000 and 2022 [χ2(22) = 77.3, p < 0.0001], the trend was driven by an increase in non-White male and not non-White female authors. Race/ethnicity was significantly associated with the country of the author’s affiliated institution [χ2(41) = 1107, p < 0.0001] but not with gender or educational attainment.

Conclusions

Persistent gender and racial disparities in high-impact medical and critical care journals underscore the need to revise policies and strategies to encourage greater diversity in critical care research.
A kind of bivariate Bernoulli-type multiquadric quasi-interpolation operator with higher approximation order
Authors: Wu Ruifeng
Published: June 2023

In this paper, a kind of bivariate Bernoulli-type multiquadric quasi-interpolation operator is studied by combining the known multiquadric quasi-interpolation operator with the generalized Taylor polynomial as the expansion in the bivariate Bernoulli polynomials. Some error bounds and convergence rates of the combined operators are studied. A selection of numerical examples is presented to compare the performances of the obtained scheme. Furthermore, our method can be applied to time-dependent differential equations. Its advantage is that the algorithm is very simple and easy to implement.
Sand dune movement and flooding risk analysis for the pyramids of Meroe, Al Bagrawiya archaeological site, Sudan
Authors: Fahmy Abdelrhman , Domínguez-Bella Salvador , Martínez-López Javier , Molina-Piernas Eduardo
Published: June 2023

The pyramids of Meroe are a significant archaeological place at the Al Bagrawiya archaeological site (Sudan) with hundreds of pyramids dating back to the kingdom of Kush (1070 BC–550 AD). In this area, winds, heavy rains, and flooding events are the main geohazards that need assessments and solutions because pyramids are subjected to an accumulation of sand dunes around them and the risk of flooding, affecting their durability. This research aims to assess the impacts of sand dunes on the stability of pyramid structures in addition to assessing the risk of flooding using satellite image observations, and damage and decay assessments of pyramid building materials were carried out through digital mapping. The results from satellite image analysis and monitoring showed that sand dunes along with heavy rains and flooding are the main decay factors, causing the collapse, disintegration, crumbling, alveolarization, loss of materials, and cracking of the sandstone ashlars, detecting an increase in deterioration, even considering only the last three decades.
Dog breeds and conformations predisposed to osteosarcoma in the UK: a VetCompass study
Authors: O’Neill Dan G. , Edmunds Grace L. , Urquhart-Gilmore Jade , Church David B. , Rutherford Lynda , Smalley Matthew J. , Brodbelt Dave C.
Published: June 2023

Background

Osteosarcoma is a malignant bone neoplasia that has high welfare consequences for affected dogs. Awareness of breed and canine conformational risk factors for osteosarcoma can assist with earlier diagnosis and improved clinical management. Study of osteosarcoma in dogs also offers translational value for humans. Anonymised clinical data within VetCompass on dogs under primary veterinary care in the UK were searched for osteosarcoma cases. Descriptive statistics reported overall and breed-specific prevalence. Risk factor analysis used multivariable logistic regression modelling.

Results

From 905,552 study dogs, 331 osteosarcoma cases were confirmed yielding a one-year period prevalence of 0.037% (95% CI: 0.033–0.041). Breeds with the highest annual prevalence were the Scottish Deerhound (3.28%, 95% CI 0.90–8.18), Leonberger (1.48%, 95% CI 0.41- 3.75), Great Dane (0.87%, 95% CI 0.43- 1.55) and Rottweiler (0.84%, 95% CI 0.64–1.07). The median age at diagnosis was 9.64 years (IQR: 7.97–11.41).

Following multivariable modelling, 11 breeds showed increased odds of osteosarcoma compared with crossbred dogs. Breeds with the highest odds included Scottish Deerhound (OR 118.40, 95% CI 41.12–340.95), Leonberger (OR 55.79, 95% CI 19.68–158.15), Great Dane (OR 34.24, 95% CI 17.81–65.83) and Rottweiler (OR 26.67, 95% CI 18.57–38.29). Compared with breeds with mesocephalic skull conformation, breeds with dolichocephalic skull conformation (OR 2.72, 95% CI 2.06–3.58) had increased odds while breeds with brachycephalic skull conformation showed reduced odds (OR 0.50, 95% CI 0.32–0.80). Chondrodystrophic breeds had 0.10 times the odds (95% CI 0.06–0.15) compared with non-chondrodystrophic breeds. Increasing adult bodyweight was associated with increasing odds of osteosarcoma.

Conclusions

The current study cements the concept that breed, bodyweight and longer leg or longer skull length are all strong risk factors for osteosarcoma in dogs. With this awareness, veterinarians can update their clinical suspicion and judgement, breeders can select towards lower-risk animals, and researchers can robustly define more useful study populations for fundamental and translational bioscience.