bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal effects of modifiable risk factors on kidney stones: a bidirectional mendelian randomization study
Authors: Liu Wen , Wang Miaomiao , Liu Jianyong , Yan Qiuxia , Liu Ming 
Published: April 2023

Abstract
Background
Increasing epidemiological studies demonstrated that modifiable risk factors affected the risk of kidney stones. We aimed to systemically assess these causal associations using a bidirectional Mendelian randomization study.

Methods
We obtained instrumental variables related to each exposure at the genome-wide significant threshold (P < 5 × 10–8). Summary level data for outcomes from the FinnGen consortium and UK Biobank were utilized in the discovery and replication stage. The Inverse-variance weighted (IVW) method was used as the primary analysis, with additional sensitivity analyses and fix-effect meta-analysis to verify the robustness of IVW results.

Results
Among 46 risk factors, five were significantly associated with nephrolithiasis risk in the FinnGen consortium, UK Biobank, and meta-analyses collectively. The odds ratios (ORs) (95% confidence intervals [95%CIs]) of kidney stones were 1.21 (1.13, 1.29) per standard deviation (SD) increase in serum calcium, 1.55 (1.01, 2.36) per SD increase in serum 25(OH)D, 1.14 (1.00, 1.29) per SD increase in total triglycerides, 2.38 (1.34, 4.22) per SD increase in fasting insulin, and 0.28 (0.23, 0.35) per unit increase in log OR of urine pH. In addition, genetically predicted serum phosphorus, urinary sodium, tea consumption, and income affected the risk of kidney stones (false discovery rate [FDR] P < 0.05) based on the outcome data from the FinnGen consortium, and the significant associations of education and waist-to-hip ratio with nephrolithiasis risks were found after FDR correction (FDR P < 0.05) based on the outcome data from UK Biobank.

Conclusions
Our findings comprehensively provide modifiable risk factors for the prevention of nephrolithiasis. Genome-wide association studies with larger sample sizes are needed to verify these causal associations in the future further.
Global longitudinal strain assessment in contrast-enhanced echocardiography in breast cancer patients: a feasibility study
Authors: Liang Shichu , Liu Mei , Liu Zhiyue , Zhong Xiaorong , Qin Yupei , Liang Ting , Wang Xi , Tang Zhuoqin , Li Qian , Huang He 
Published: April 2023

Abstract
Background
Left ventricular global longitudinal strain (GLS) obtained from two-dimensional speckle-tracking echocardiography (2D-STE) can reflect cancer therapy-related cardiac dysfunction in breast cancer (BC) patients, however, the accuracy and reproducibility of 2D-STE are restricted due to poor image quality.

Methods
Between January 2019 and October 2021, 160 consecutive BC patients aged ≥ 18 years were recruited. The 160 BC patients (mean age: 48.41 ± 9.93 years, 100% women) underwent both 2D-STE and Contrast-enhanced echocardiography (CEcho), 125 of whom were included in the measurement of GLS. The intraclass correlation coefficient (ICC) was used to determine the intra- and inter-observer reproducibility of 2D-STE and CEcho-STE. Correlation (r) was calculated using Pearson correlation. Statistical significance was set at P < 0.05.

Results
Among 160 BC patients, more segments were recognized by CEcho-STE than by 2D-STE (2,771, 99.53% vs. 2,440, 84.72%). The left ventricular ejection fraction (LVEF) obtained by 2D was lower than CEcho (61.75 ± 6.59% vs. 64.14 ± 5.97%, P < 0.0001). The GLS obtained by 2D-STE was lower than CEcho-STE (-21.74 ± 2.77% vs. -26.79 ± 4.30%, P = 0.001). The ICC of the intraobserver and interobserver agreements in the CEcho-STE group was lower than that in the 2D-STE group. GLS measurements were in good agreement between the 2D-STE and CEcho-STE groups (r = 0.773).

Conclusions
CEcho can overcome some imaging limitations and recognize more segments than 2D, which may provide an LVEF and GLS closer to the true value. Based on AutoStrain, CEcho-STE may serve as a complementary method for those with poor image quality.

Graphical Abstract
The association between multi-disciplinary staffing levels and mortality in acute hospitals: a systematic review
Authors: Dall’Ora Chiara , Rubbo Bruna , Saville Christina , Turner Lesley , Ball Jane , Ball Cheska , Griffiths Peter 
Published: April 2023

Abstract
Objectives
Health systems worldwide are faced with the challenge of adequately staffing their hospital services. Much of the current research and subsequent policy has been focusing on nurse staffing and minimum ratios to ensure quality and safety of patient care. Nonetheless, nurses are not the only profession who interact with patients, and, therefore, not the only professional group who has the potential to influence the outcomes of patients while in hospital. We aimed to synthesise the evidence on the relationship between multi-disciplinary staffing levels in hospital including nursing, medical and allied health professionals and the risk of death.

Methods
Systematic review. We searched Embase, Medline, CINAHL, and the Cochrane Library for quantitative or mixed methods studies with a quantitative component exploring the association between multi-disciplinary hospital staffing levels and mortality.

Results
We included 12 studies. Hospitals with more physicians and registered nurses had lower mortality rates. Higher levels of nursing assistants were associated with higher patient mortality. Only two studies included other health professionals, providing scant evidence about their effect.

Conclusions
Pathways for allied health professionals such as physiotherapists, occupational therapists, dietitians, pharmacists, to impact safety and other patient outcomes are plausible and should be explored in future studies.
The interplay between IGF-1R signaling and Hippo-YAP in breast cancer stem cells
Authors: Chan Yu-Tzu , Lin Ruey-Jen , Wang Ya-Hui , Hung Tsai-Hsien , Huang Yenlin , Yu John , Yu Jyh-Cherng , Yu Alice L. 
Published: April 2023

Abstract
Background
Both IGF-1R/PI3K/AKT/mTOR and Hippo pathways are crucial for breast cancer stem cells (BCSCs). However, their interplay remains unclear.

Methods
Four triple negative breast cancer cell lines derived from CSC of two patient-derived xenografts (PDXs), AS-B145, AS-B145-1R, AS-B244, and AS-B244-1R, were used to elucidate the role of YAP in BCSCs. YAP silenced BCSCs were analyzed by cell proliferation, aldehyde dehydrogenase (ALDH) activity, mammosphere formation, and tumorigenesis. The effects of modulating IGF-1R and IGF-1 on YAP expression and localization were evaluated. The clinical correlation of YAP and IGF-1R signaling with the overall survival (OS) of 7830 breast cancer patients was analyzed by KM plotter.

Results
Knockdown of YAP abates the viability and stemness of BCSCs in vitro and tumorigenicity in vivo. Depletion of IGF-1R by shRNA or specific inhibitor decreases YAP expression. In contrast, IGF-1 addition upregulates YAP and enhances its nuclear localization. YAP overexpression increased the mRNA level of IGF-1, but not IGF-1R. Data mining of clinical breast cancer specimens revealed that basal-like breast cancer patients with higher level of IGF-1 and YAP exhibit significantly shorter OS.

Conclusions
YAP contributes to stemness features of breast cancer in vitro and in vivo. The expression and localization of YAP was regulated by IGF-1R and YAP expression in turns upregulates IGF-1, but not IGF-1R. Clinically, higher level of YAP and IGF-1 significantly correlated with shorter OS in basal-like breast cancer. Taken together, these findings suggest the clinical relevance of interplay between YAP and IGF-1/IGF-1R pathway in sustaining the properties of BCSCs.
Decidual derived exosomal miR-99a-5p targets Ppp2r5a to inhibit trophoblast invasion in response to CeO2NPs exposure
Authors: Zhong Hangtian , Geng Yanqing , Gao Rufei , Chen Jun , Chen Zhuxiu , Mu Xinyi , Zhang Yan , Chen Xuemei , He Junlin 
Published: April 2023

Abstract
Background
The biological effects of cerium dioxide nanoparticles (CeO2NPs), a novel material in the biomedical field, have attracted widespread attention. Our previous study confirmed that exposure to CeO2NPs during pregnancy led to abnormal trophoblast invasion during early placental development, thereby impairing placental development. The potential mechanisms may be related to low-quality decidualization triggered by CeO2NPs exposure, such as an imbalance in trophoblast invasion regulators secreted by decidual cells. However, the intermediate link mediating the “dialogue” between decidual cells and trophoblasts during this process remains unclear. As an important connection between cells, exosomes participate in the “dialogue” between endometrial cells and trophoblasts. Exosomes transfer bioactive microRNA into target cells, which can target and regulate the level of mRNA in target cells.

Results
Here, we constructed a mice primary uterine stromal cell-induced decidualization model in vitro, and detected the effect of CeO2NPs exposure on the expression of decidual-derived exosomal miRNAs by high-throughput sequencing. Bioinformatics analysis and dual-luciferase reporter assays were performed to identify target genes of the screened key miRNAs in regulating trophoblast invasion. Finally, the role of the screened miRNAs and their target genes in regulating trophoblast (HTR-8/SVneo cells) invasion was confirmed. The results showed that CeO2NPs exposure inhibited trophoblast invasion by promoting miR-99a-5p expression in decidual-derived exosomes, and Ppp2r5a is a potential target gene for miR-99a-5p to inhibit trophoblast invasion.

Conclusions
This study revealed the molecular mechanism by which CeO2NPs exposure inhibits trophoblast invasion from the perspective of decidual derived exosomal miRNAs. These results will provide an experimental basis for screening potential therapeutic targets for the negative biological effects of CeO2NPs exposure and new ideas for studying the mechanism of damage to trophoblast cells at the decidual-foetal interface by harmful environmental or occupational factors.
Role and research progress of hematological markers in laryngeal squamous cell carcinoma
Authors: Qi Hui 
Published: April 2023

AbstractLaryngeal cancer is one of the most common malignant tumors of the head and neck, accounting for about 20%. Due to its high disability rate, the diagnosis and treatment of laryngeal cancer have always been the focus and difficulty of head and neck surgery. The outcome of cancer is affected not only by tumor-related factors but also by host-related factors, especially systemic inflammation, this is usually reflected by a variety of hematological markers. Studies have confirmed that there is a significant correlation between hematological markers and the occurrence, development, and prognosis of laryngeal squamous cell carcinoma (LSCC), and has a certain value in auxiliary diagnosis and prognosis prediction of LSCC. We reviewed various hematological markers related to LSCC aim to summarize the role and research progress of hematological markers in LSCC.
Huge left atrial myxoma: about 2 cases resected in the Democratic Republic of Congo
Authors: Nzomvuama Alphonse Ndonga N’sungu , Mutuale Cédric Nyombo , Kongo Roger Minga , Mbanzulu Irène Nsolani , Nsiala Joseph Makunza 
Published: April 2023

Abstract
Background
Myxoma is the most common cardiac tumor, found in 75–80% of cases in the left atrium. It can grow quietly and therefore reach a large size before being symptomatic. Poor availability of echocardiography also contributes to delayed diagnosis. In Sub-Saharan African countries, myxoma diagnosis can be missed for many patients. Myxoma resection surgery, although technically simple, is not always possible, because of the lack of cardiac surgery development. The aim of this report is to describe the first two consecutive resection cases of huge left-atrial myxoma performed in Kinshasa, Democratic Republic of Congo (DRC) and to discuss the specificities of this surgery in this low-resource context.

Case presentation
Two patients, 54 and 48 years old, were diagnosed with giant myxoma of the left atrium in the management of progressive dyspnea The first patient's transthoracic echocardiography revealed a pedunculated atrial mass (37 × 48 mm) on the interatrial septum, passing through the mitral valve. For the second patient, the mass (64 × 26 mm) was attached to the roof of the left atrium and protruded into the mitral valve, with significant mitro-tricuspid regurgitation The first patient underwent a simple resection of the myxoma. For the second patient, it was associated to a mitro-tricuspid annuloplasty. The postoperative course was simple for the first patient, but the second patient developed a biventricular failure requiring vasoactive drugs. Both patients were discharged alive from the hospital on postoperative days 10 and 12, respectively. They are regularly followed up and are doing well 2 years after surgery.

Discussion and conclusion
Surgical resection is the only effective treatment of myxoma. Our first results are encouraging The poor availability of the echocardiography is a challenge in the diagnosis of myxoma. The development of cardiac surgery in DRC and ongoing country-level efforts to address diagnostic challenges for these often silent tumors will allow us to expect more resections to be performed locally and larger series published.
Leveraging the glymphatic and meningeal lymphatic systems as therapeutic strategies in Alzheimer’s disease: an updated overview of nonpharmacological therapies
Authors: Formolo Douglas A. , Yu Jiasui , Lin Kangguang , Tsang Hector W. H. , Ou Haining , Kranz Georg S. , Yau Suk-Yu 
Published: April 2023

AbstractUnderstanding and treating Alzheimer’s disease (AD) has been a remarkable challenge for both scientists and physicians. Although the amyloid-beta and tau protein hypothesis have largely explained the key pathological features of the disease, the mechanisms by which such proteins accumulate and lead to disease progression are still unknown. Such lack of understanding disrupts the development of disease-modifying interventions, leaving a therapeutic gap that remains unsolved. Nonetheless, the recent discoveries of the glymphatic pathway and the meningeal lymphatic system as key components driving central solute clearance revealed another mechanism underlying AD pathogenesis. In this regard, this narrative review integrates the glymphatic and meningeal lymphatic systems as essential components involved in AD pathogenesis. Moreover, it discusses the emerging evidence suggesting that nutritional supplementation, non-invasive brain stimulation, and traditional Chinese medicine can improve the pathophysiology of the disease by increasing glymphatic and/or meningeal lymphatic function. Given that physical exercise is a well-regarded preventive and pro-cognitive intervention for dementia, we summarize the evidence suggesting the glymphatic system as a mediating mechanism of the physical exercise therapeutic effects in AD. Targeting these central solute clearance systems holds the promise of more effective treatment strategies.
Practical assessment of risk of VILI from ventilating power: a conceptual model
Authors: Marini John J. , Thornton Lauren T. , Rocco Patricia R. M. , Gattinoni Luciano , Crooke Philip S. 
Published: April 2023

AbstractAt the bedside, assessing the risk of ventilator-induced lung injury (VILI) requires parameters readily measured by the clinician. For this purpose, driving pressure (DP) and end-inspiratory static ‘plateau’ pressure ($$P_{s}$$

P
s

) of the tidal cycle are unquestionably useful but lack key information relating to associated volume changes and cumulative strain. ‘Mechanical power’, a clinical term which incorporates all dissipated (‘non-elastic’) and conserved (‘elastic’) energy components of inflation, has drawn considerable interest as a comprehensive ‘umbrella’ variable that accounts for the influence of ventilating frequency per minute as well as the energy cost per tidal cycle. Yet, like the raw values of DP and $$P_{s}$$

P
s

, the absolute levels of energy and power by themselves may not carry sufficiently precise information to guide safe ventilatory practice. In previous work we introduced the concept of ‘damaging energy per cycle’. Here we describe how—if only in concept—the bedside clinician might gauge the theoretical hazard of delivered energy using easily observed static circuit pressures ($$P_{s}$$

P
s

and positive end expiratory pressure) and an estimate of the maximally tolerated (threshold) non-dissipated (‘elastic’) airway pressure that reflects the pressure component applied to the alveolar tissues. Because its core inputs are already in use and familiar in daily practice, the simplified mathematical model we propose here for damaging energy and power may promote deeper comprehension of the key factors in play to improve lung protective ventilation.
pycoMeth: a toolbox for differential methylation testing from Nanopore methylation calls
Authors: Snajder Rene , Leger Adrien , Stegle Oliver , Bonder Marc Jan 
Published: April 2023

AbstractWe presentpycoMeth, a toolbox to store, manage and analyze DNA methylation calls from long-read sequencing data obtained using the Oxford Nanopore Technologies sequencing platform. Building on a novel, rapid-access, read-level and reference-anchored methylation storage formatMetH5, we propose efficient algorithms for haplotype aware, multi-sample consensus segmentation and differential methylation testing. We show thatMetH5is more efficient than existing solutions for storing Oxford Nanopore Technologies methylation calls, and carry out benchmarking forpycoMethsegmentation and differential methylation testing, demonstrating increased performance and sensitivity compared to existing solutions designed for short-read methylation data.
Glucagon-like peptide-1 analogues: a new way to quit smoking? (SKIP)—a structured summary of a study protocol for a randomized controlled study
Authors: Lengsfeld Sophia , Burkard Thilo , Meienberg Andrea , Jeanloz Nica , Coynel David , Vogt Deborah R. , Hemkens Lars G. , Speich Benjamin , Zanchi Davide , Erlanger Tobias E. , Christ-Crain Mirjam , Winzeler Bettina 
Published: April 2023

Abstract
Background
Cigarette smoking is the leading preventable cause of premature death. Despite dedicated programmes, quit rates remain low due to barriers such as nicotine withdrawal syndrome or post-cessation weight gain. Glucagon-like peptide-1 (GLP-1) analogues reduce energy intake and body weight and seem to modulate addictive behaviour. These GLP-1 properties are of major interest in the context of smoking cessation. The aim of this study is to evaluate the GLP-1 analogue dulaglutide as a new therapy for smoking cessation.

Methods
This is a placebo-controlled, double-blind, parallel group, superiority, single-centre randomized study including 255 patients. The intervention consists of a 12-week dulaglutide treatment phase with 1.5 mg once weekly or placebo subcutaneously, in addition to standard of care (behavioural counselling and pharmacotherapy with varenicline). A 40-week non-treatment phase follows. The primary outcome is the point prevalence abstinence rate at week 12. Smoking status is self-reported and biochemically confirmed by end-expiratory exhaled carbon monoxide measurement. Further endpoints include post-cessational weight gain, nicotine craving analysis, glucose homeostasis and long-term nicotine abstinence.
Two separate substudies assess behavioural, functional and structural changes by functional magnetic resonance imaging and measures of energy metabolism (i.e. resting energy expenditure, body composition).

Discussion
Combining behavioural counselling and medical therapy, e.g. with varenicline, improves abstinence rates and is considered the standard of care. We expect a further increase in quit rates by adding a second component of medical therapy and assume a dual effect of dulaglutide treatment (blunting nicotine withdrawal symptoms and reducing post-cessational weight gain). This project is of high relevance as it explores novel treatment options aimed at preventing the disastrous consequences of nicotine consumption and obesity.

Trial registration
ClinicalTrials.gov NCT03204396. Registered on June 26, 2017.
CD33 as a leukocyte-associated marker expressed on human spermatozoa
Authors: Sereshki Nasrin , Rafiee Mitra , Alipour Razieh , Rahimyan Kourosh , Wilkinson David 
Published: April 2023

Abstract
Objective
Sialic acid-binding immunoglobulin-type lectins (Siglecs) are commonly present on immune cells and often mediate cell-to-cell interactions and signaling. Studies have shown the presence of Siglecs 1, 2, 5, 6, 10 and 14 on human spermatozoa. To the best of our knowledge, the expression of CD33 on spermatozoa has not yet been studied. Semen samples were collected from 25 healthy men with normal semen status. CD33 expression on purified spermatozoa was evaluated by flow cytometry methods.

Results
The results demonstrate the expression of CD33 on the surface of purified spermatozoa. The mean (± SD) of MFI (mean fluorescence intensity) was 12.85 (± 1.33) and the mean percentage of spermatozoa that express CD33 was 73.75 (± 3.75). Results were obtained showing that spermatozoa express CD33 (or Siglec-3) on their surface. The physiological role of these molecules on spermatozoa remains to be determined. It is recommended that further research be undertaken regarding the role of Siglecs (such as CD33) on spermatozoa apoptosis.
Higher performance for women than men in MRI-based Alzheimer’s disease detection
Authors: Klingenberg Malte , Stark Didem , Eitel Fabian , Budding Céline , Habes Mohamad , Ritter Kerstin ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2023

AbstractIntroductionAlthough machine learning classifiers have been frequently used to detect Alzheimer’s disease (AD) based on structural brain MRI data, potential bias with respect to sex and age has not yet been addressed. Here, we examine a state-of-the-art AD classifier for potential sex and age bias even in the case of balanced training data.MethodsBased on an age- and sex-balanced cohort of 432 subjects (306 healthy controls, 126 subjects with AD) extracted from the ADNI data base, we trained a convolutional neural network to detect AD in MRI brain scans and performed ten different random training-validation-test splits to increase robustness of the results. Classifier decisions for single subjects were explained using layer-wise relevance propagation.ResultsThe classifier performed significantly better for women (balanced accuracy$$87.58\pm 1.14\%$$87.58±1.14%) than for men ($$79.05\pm 1.27\%$$79.05±1.27%). No significant differences were found in clinical AD scores, ruling out a disparity in disease severity as a cause for the performance difference. Analysis of the explanations revealed a larger variance in regional brain areas for male subjects compared to female subjects.DiscussionThe identified sex differences cannot be attributed to an imbalanced training dataset and therefore point to the importance of examining and reporting classifier performance across population subgroups to increase transparency and algorithmic fairness. Collecting more data especially among underrepresented subgroups and balancing the dataset are important but do not always guarantee a fair outcome.