bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Intraoperative Extracochlear Electrocochleography Correlate With Postoperative Audiometric Hearing Thresholds in Cochlear Implant Surgery? A Retrospective Analysis of Cochlear Monitoring
Authors: Haumann Sabine , Mynarek (née Bradler) Marlene , Maier Hannes , Helmstaedter Victor , Büchner Andreas , Lenarz Thomas , Teschner Magnus J. 
Published: May 2024

In recent years, tools for early detection of irreversible trauma to the basilar membrane during hearing preservation cochlear implant (CI) surgery were established in several clinics. A link with the degree of postoperative hearing preservation in patients was investigated, but patient populations were usually small. Therefore, this study's aim was to analyze data from intraoperative extracochlear electrocochleography (ECochG) recordings for a larger group. During hearing preservation CI surgery, extracochlear recordings were made before, during, and after CI electrode insertion using a cotton wick electrode placed at the promontory. Before and after insertion, amplitudes and stimulus response thresholds were recorded at 250, 500, and 1000 Hz. During insertion, response amplitudes were recorded at one frequency and one stimulus level. Data from 121 patient ears were analyzed. The key benefit of extracochlear recordings is that they can be performed before, during, and after CI electrode insertion. However, extracochlear ECochG threshold changes before and after CI insertion were relatively small and did not independently correlate well with hearing preservation, although at 250 Hz they added some significant information. Some tendencies—although no significant relationships—were detected between amplitude behavior and hearing preservation. Rising amplitudes seem favorable and falling amplitudes disadvantageous, but constant amplitudes do not appear to allow stringent predictions. Extracochlear ECochG measurements seem to only partially realize expected benefits. The questions now are: do gains justify the effort, and do other procedures or possible combinations lead to greater benefits for patients?
An LGR6 frameshift variant abrogates receptor expression on select leukocyte subsets and is associated with viral infections
Authors: Gomez Esteban A. , De Matteis Roberta , Udomjarumanee Palita , Munroe Patricia B. , Dalli Jesmond 
Published: May 2024

Abstract
The leucine-rich repeat-containing G-protein–coupled receptor 6 (LGR6) was recently identified as the cognate receptor for the proresolving mediator maresin 1 (MaR1). To address the biological role of LGR6 in humans, we investigated the functional impact of a genetic variant in the gene encoding for LGR6, which is predicted to lead to a frameshift mutation in one of the receptor isoforms, on both receptor expression and immune cell responses. In neutrophils, monocytes, and natural killer (NK) cells from volunteers homozygous for this variant, we found a significant downregulation in the expression of LGR6 when compared with controls without the variant; whereas the LGR6 expression was essentially similar in monocyte-derived macrophages and CD8+ T cells. Functionally, loss of LGR6 expression was linked with a decreased ability of neutrophils and monocytes to phagocytose bacteria. We observed an increase in neutrophil chemotaxis and leukotriene B4 production and increased expression of activation markers, including markers for platelet-leukocyte phagocyte heterotypic aggregates, such as CD41, in neutrophils and monocytes from the variant group. Using data from the UK Biobank, we found that at a population level the rs4266947 variant, which is in high linkage disequilibrium with rs74355478, was associated with a higher incidence of viral infections. Intriguingly, neutrophils, NK cells, and CD8+ T cells from volunteers with the LGR6 variant displayed altered viral responses when stimulated with Toll-like receptor 3 (TLR3), TLR7/TLR8, and TLR9 agonists. Together, these findings shed new light on the cell type–specific regulation of LGR6 expression and the role of this receptor in directing host immune responses.
Mediastinitis and septic shock complicating spontaneous esophageal rupture “Boerhaave’s syndrome”: a case report
Authors: Kortli Said , Andrianjafy Hery 
Published: May 2024

AbstractBoerhaave’s syndrome, also known as spontaneous esophageal rupture, is a rare but life-threatening condition characterized by a tear in the esophagus. It is most commonly caused by a sudden increase in intraesophageal pressure, often due to severe vomiting or retching.Early diagnosis of Boerhaave’s syndrome is crucial for improving patient outcomes. The classic triad of symptoms includes severe chest pain, vomiting, and subcutaneous emphysema (air under the skin). However, not all patients present with this triad, and the diagnosis can be challenging, especially in patients without the typical symptoms.In this case report, we present the clinical details of a 52-year-old male patient who presented to the emergency department (ED) with severe abdominal pain and vomiting for several days. The patient had a history of chronic alcohol abuse and a recent episode of vigorous vomiting.
Integrated approach to generate artificial samples with low tumor fraction for somatic variant calling benchmarking
Authors: Sergi Aldo , Beltrame Luca , Marchini Sergio , Masseroli Marco 
Published: May 2024

Abstract
Background
High-throughput sequencing (HTS) has become the gold standard approach for variant analysis in cancer research. However, somatic variants may occur at low fractions due to contamination from normal cells or tumor heterogeneity; this poses a significant challenge for standard HTS analysis pipelines. The problem is exacerbated in scenarios with minimal tumor DNA, such as circulating tumor DNA in plasma. Assessing sensitivity and detection of HTS approaches in such cases is paramount, but time-consuming and expensive: specialized experimental protocols and a sufficient quantity of samples are required for processing and analysis. To overcome these limitations, we propose a new computational approach specifically designed for the generation of artificial datasets suitable for this task, simulating ultra-deep targeted sequencing data with low-fraction variants and demonstrating their effectiveness in benchmarking low-fraction variant calling.

Results
Our approach enables the generation of artificial raw reads that mimic real data without relying on pre-existing data by using NEAT, a fine-grained read simulator that generates artificial datasets using models learned from multiple different datasets. Then, it incorporates low-fraction variants to simulate somatic mutations in samples with minimal tumor DNA content. To prove the suitability of the created artificial datasets for low-fraction variant calling benchmarking, we used them as ground truth to evaluate the performance of widely-used variant calling algorithms: they allowed us to define tuned parameter values of major variant callers, considerably improving their detection of very low-fraction variants.

Conclusions
Our findings highlight both the pivotal role of our approach in creating adequate artificial datasets with low tumor fraction, facilitating rapid prototyping and benchmarking of algorithms for such dataset type, as well as the important need of advancing low-fraction variant calling techniques.
Response mechanisms of different Saccharomyces cerevisiae strains to succinic acid
Authors: Xie Cai-Yun , Su Ran-Ran , Wu Bo , Sun Zhao-Yong , Tang Yue-Qin 
Published: May 2024

Abstract
Background
The production of succinic acid (SA) from biomass has attracted worldwide interest. Saccharomyces cerevisiae is preferred for SA production due to its strong tolerance to low pH conditions, ease of genetic manipulation, and extensive application in industrial processes. However, when compared with bacterial producers, the SA titers and productivities achieved by engineered S. cerevisiae strains were relatively low. To develop efficient SA-producing strains, it’s necessary to clearly understand how S. cerevisiae cells respond to SA.

Results
In this study, we cultivated five S. cerevisiae strains with different genetic backgrounds under different concentrations of SA. Among them, KF7 and NBRC1958 demonstrated high tolerance to SA, whereas NBRC2018 displayed the least tolerance. Therefore, these three strains were chosen to study how S. cerevisiae responds to SA. Under a concentration of 20 g/L SA, only a few differentially expressed genes were observed in three strains. At the higher concentration of 60 g/L SA, the response mechanisms of the three strains diverged notably. For KF7, genes involved in the glyoxylate cycle were significantly downregulated, whereas genes involved in gluconeogenesis, the pentose phosphate pathway, protein folding, and meiosis were significantly upregulated. For NBRC1958, genes related to the biosynthesis of vitamin B6, thiamin, and purine were significantly downregulated, whereas genes related to protein folding, toxin efflux, and cell wall remodeling were significantly upregulated. For NBRC2018, there was a significant upregulation of genes connected to the pentose phosphate pathway, gluconeogenesis, fatty acid utilization, and protein folding, except for the small heat shock protein gene HSP26. Overexpression of HSP26 and HSP42 notably enhanced the cell growth of NBRC1958 both in the presence and absence of SA.

Conclusions
The inherent activities of small heat shock proteins, the levels of acetyl-CoA and the strains’ potential capacity to consume SA all seem to affect the responses and tolerances of S. cerevisiae strains to SA. These factors should be taken into consideration when choosing host strains for SA production. This study provides a theoretical basis and identifies potential host strains for the development of robust and efficient SA-producing strains.
Clinico-pathological study of esophageal mucoepidermoid carcinoma: a 10-year survival from a single center
Authors: Wang Yi , Wu Yajing , Zheng Chen , Li Qihui , Jiao Wenpeng , Wang Jianing , Xiao Linlin , Pang Qingsong , Zhang Wencheng , Wang Jun 
Published: May 2024

Abstract
Background
Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC.

Methods
Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC.

Results
The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC.

Conclusions
MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.
Genetically predicted gut microbiota mediate the association between plasma lipidomics and primary sclerosing cholangitis
Authors: Zhou Jie , Zhu Dagang , Xu Yixin , Chen Chao , Wang Kun 
Published: May 2024

Abstract
Background
Primary sclerosing cholangitis (PSC) is a complex disease with pathogenic mechanisms that remain to be elucidated. Previous observational studies with small sample sizes have reported associations between PSC, dyslipidemia, and gut microbiota dysbiosis. However, the causality of these associations is uncertain, and there has been no systematic analysis to date.

Methods
The datasets comprise data on PSC, 179 lipid species, and 412 gut microbiota species. PSC data (n = 14,890) were sourced from the International PSC Study Group, while the dataset pertaining to plasma lipidomics originated from a study involving 7174 Finnish individuals. Data on gut microbiota species were derived from the Dutch Microbiome Project study, which conducted a genome-wide association study involving 7738 participants. Furthermore, we employed a two-step Mendelian randomization (MR) analysis to quantify the proportion of the effect of gut microbiota-mediated lipidomics on PSC.

Results
Following a rigorous screening process, our MR analysis revealed a causal relationship between higher levels of gene-predicted Phosphatidylcholine (O-16:1_18:1) (PC O-16:1_18:1) and an increased risk of developing PSC (inverse variance-weighted method, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.03–1.63). There is insufficient evidence to suggest that gene-predicted PSC impacts the levels of PC O-16:1_18:1 (OR 1.01, 95% CI 0.98–1.05). When incorporating gut microbiota data into the analysis, we found that Eubacterium rectale-mediated genetic prediction explains 17.59% of the variance in PC O-16:1_18:1 levels.

Conclusion
Our study revealed a causal association between PC O-16:1_18:1 levels and PSC, with a minor portion of the effect mediated by Eubacterium rectale. This study aims to further explore the pathogenesis of PSC and identify promising therapeutic targets. For patients with PSC who lack effective treatment options, the results are encouraging.
Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer
Authors: Shen Lang , Zeng Hong , Fu Yu , Ma Wenmin , Guo Xiaoling , Luo Guoqun , Hua Rui , Wang Xiaocong , Shi Xiao , Wu Biao , Luo Chen , Quan Song 
Published: May 2024

Abstract
Background
Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL.

Methods
In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR.

Results
BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes.

Conclusion
Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.
Navigating geographical disparities: access to obstetric hospitals in maternity care deserts and across the United States
Authors: Fontenot Jazmin , Brigance Christina , Lucas Ripley , Stoneburner Ashley 
Published: May 2024

Abstract
Background
Access to maternity care in the U.S. remains inequitable, impacting over two million women in maternity care “deserts." Living in these areas, exacerbated by hospital closures and workforce shortages, heightens the risks of pregnancy-related complications, particularly in rural regions. This study investigates travel distances and time to obstetric hospitals, emphasizing disparities faced by those in maternity care deserts and rural areas, while also exploring variances across races and ethnicities.

Methods
The research adopted a retrospective secondary data analysis, utilizing the American Hospital Association and Centers for Medicaid and Medicare Provider of Services Files to classify obstetric hospitals. The study population included census tract estimates of birthing individuals sourced from the U.S. Census Bureau's 2017-2021 American Community Survey. Using ArcGIS Pro Network Analyst, drive time and distance calculations to the nearest obstetric hospital were conducted. Furthermore, Hot Spot Analysis was employed to identify areas displaying significant spatial clusters of high and low travel distances.

Results
The mean travel distance and time to the nearest obstetric facility was 8.3 miles and 14.1 minutes. The mean travel distance for maternity care deserts and rural counties was 28.1 and 17.3 miles, respectively. While birthing people living in rural maternity care deserts had the highest average travel distance overall (33.4 miles), those living in urban maternity care deserts also experienced inequities in travel distance (25.0 miles). States with hotspots indicating significantly higher travel distances included: Montana, North Dakota, South Dakota, and Nebraska. Census tracts where the predominant race is American Indian/Alaska Native (AIAN) had the highest travel distance and time compared to those of all other predominant races/ethnicities.

Conclusions
Our study revealed significant disparities in obstetric hospital access, especially affecting birthing individuals in maternity care deserts, rural counties, and communities predominantly composed of AIAN individuals, resulting in extended travel distances and times. To rectify these inequities, sustained investment in the obstetric workforce and implementation of innovative programs are imperative, specifically targeting improved access in maternity care deserts as a priority area within healthcare policy and practice.
Factors influencing presentation delay among cancer patients: a cross-sectional study in Malaysia
Authors: Gyeltshen Tshewang , Teh Hoon Shien , Loo Ching Ee , Hing Nicholas Yee Liang , Lim Wei Yin , Subramaniam Shridevi , Wong Wen Jun , Wong Zoie Shui-Yee , Hwong Wen Yea 
Published: May 2024

Abstract
Background
Cancer represents a significant global public health challenge, with escalating incidence rates straining healthcare systems. Malaysia, like many nations, has witnessed a rise in cancer cases, particularly among the younger population. This study aligns with Malaysia’s National Strategic Plan for Cancer Control Programme 2021–2025, emphasizing primary prevention and early detection to address cancer’s impact. Therefore, we aim to describe the timeliness of cancer care for symptom presentation, socio-demographic, patient, as well as organizational-related factors among patients in Malaysia diagnosed with breast, colorectal, nasopharyngeal, and cervical cancer.

Methods
This cross-sectional study enrolled adult cancer patients diagnosed with breast, cervical, colorectal, or nasopharyngeal cancer from 2015 to 2020 in seven public hospitals/oncology centres across Malaysia. Data were collected through patient-administered surveys and medical records. Presentation delay, defined as the duration between symptom onset and the patient's first visit to a healthcare professional exceeding 30 days, was the primary outcome. Statistical analysis included descriptive statistics and chi-square tests.

Results
The study included 476 cancer patients, with breast cancer (41.6%), colorectal cancer (26.9%), nasopharyngeal cancer (22.1%), and cervical cancer (9.5%). Over half (54.2%) experienced presentation delays with a median interval of 60 days. Higher proportions of presentation delay were observed among nasopharyngeal cancer patients, employed patients with lower socioeconomic statuses, and those without family history of cancer. Most patients self-discovered their first cancer symptoms (80%), while only one-third took immediate action for medical check-ups. Emotional and organizational factors, such as long waiting times during doctor's visits (47%), were potential barriers to seeking cancer care.

Conclusion
This study highlights the significant problem of presentation delay among cancer patients in Malaysia. The delay is influenced by various factors encompassing sociodemographic characteristics, health-seeking behaviours, and healthcare system-related issues. A comprehensive approach addressing both individual barriers and institutional obstacles is imperative to mitigate this presentation delay and improve cancer outcomes.
Long-term exposure to PM2.5 and mortality in a national cohort in South Korea: effect modification by community deprivation, medical infrastructure, and greenness
Authors: Byun Garam , Kim Sera , Choi Yongsoo , Kim Ayoung , Team AiMS-CREATE , Lee Jong-Tae , Bell Michelle L. 
Published: May 2024

Abstract
Background
Long-term exposure to PM2.5 has been linked to increased mortality risk. However, limited studies have examined the potential modifying effect of community-level characteristics on this association, particularly in Asian contexts. This study aimed to estimate the effects of long-term exposure to PM2.5 on mortality in South Korea and to examine whether community-level deprivation, medical infrastructure, and greenness modify these associations.

Methods
We conducted a nationwide cohort study using the National Health Insurance Service-National Sample Cohort. A total of 394,701 participants aged 30 years or older in 2006 were followed until 2019. Based on modelled PM2.5 concentrations, 1 to 3-year and 5-year moving averages of PM2.5 concentrations were assigned to each participant at the district level. Time-varying Cox proportional-hazards models were used to estimate the association between PM2.5 and non-accidental, circulatory, and respiratory mortality. We further conducted stratified analysis by community-level deprivation index, medical index, and normalized difference vegetation index to represent greenness.

Results
PM2.5 exposure, based on 5-year moving averages, was positively associated with non-accidental (Hazard ratio, HR: 1.10, 95% Confidence Interval, CI: 1.01, 1.20, per 10 µg/m3 increase) and circulatory mortality (HR: 1.22, 95% CI: 1.01, 1.47). The 1-year moving average of PM2.5 was associated with respiratory mortality (HR: 1.33, 95% CI: 1.05, 1.67). We observed higher associations between PM2.5 and mortality in communities with higher deprivation and limited medical infrastructure. Communities with higher greenness showed lower risk for circulatory mortality but higher risk for respiratory mortality in association with PM2.5.

Conclusions
Our study found mortality effects of long-term PM2.5 exposure and underlined the role of community-level factors in modifying these association. These findings highlight the importance of considering socio-environmental contexts in the design of air quality policies to reduce health disparities and enhance overall public health outcomes.