bluuebunny/crossref_metadata_2025_split huggingface dataset:
The enrichment of Fanconi anemia/homologous recombination pathway aberrations in ATM/ATR-mutated NSCLC was accompanied by unique molecular features and poor prognosis
Authors: Wei Wei , Shi Fangfang , Xu Yang , Jiao Yang , Zhang Ying , Ou Qiuxiang , Wu Xue , Yang Lingyi , Lai Jinhuo 
Published: December 2023

Abstract
Background
ATM and ATR are two critical factors to regulate DNA damage response (DDR), and their mutations were frequently observed in different types of cancer, including non-small cell lung cancer (NSCLC). Given that the majority of identified ATM/ATR mutations were variants of uncertain significance, the clinical/molecular features of pathogenic ATM/ATR aberrations have not been comprehensively investigated in NSCLC.

Methods
Next-generation sequencing (NGS) analyses were conducted to investigate the molecular features in 191 NSCLC patients who harbored pathogenic/likely pathogenic ATM/ATR mutations and 308 NSCLC patients who did not have any types of ATM/ATR variants. The results were validated using an external cohort of 2727 NSCLC patients (including 48 with ATM/ATR pathogenic mutations).

Results
Most pathogenic ATM/ATR genetic alterations were frameshift and nonsense mutations that disrupt critical domains of the two proteins. ATM/ATR-mutated patients had significantly higher tumor mutational burdens (TMB; P < 0.001) and microsatellite instabilities (MSI; P = 0.023), but not chromosomal instabilities, than those without any ATM/ATR variations. In particular, KRAS mutations were significantly enriched in ATM-mutated patients (P = 0.014), whereas BRCA2 mutations (P = 0.014), TP53 mutations (P = 0.014), and ZNF703 amplification (P = 0.008) were enriched in ATR-mutated patients. Notably, patients with ATM/ATR pathogenic genetic alterations were likely to be accompanied by mutations in Fanconi anemia (FA) and homologous recombination (HR) pathways, which were confirmed using both the study (P < 0.001) and validation (P < 0.001) cohorts. Furthermore, the co-occurrence of FA/HR aberrations could contribute to increased TMB and MSI, and patients with both ATM/ATR and FA/HR mutations tended to have worse overall survival.

Conclusions
Our results demonstrated the unique clinical and molecular features of pathogenic ATM/ATR mutations in NSCLC, which helps better understand the cancerous involvement of these DDR regulators, as well as directing targeted therapies and/or immunotherapies to treat ATM/ATR-mutated NSCLC, especially those with co-existing FA/HR aberrations.
A comparative study on ctDNA and tumor DNA mutations in lung cancer and benign cases with a high number of CTCs and CTECs
Authors: Xie Jianzhu , Hu Binjie , Gong Yanping , He Sijia , Lin Jun , Huang Qian , Cheng Jin 
Published: December 2023

Abstract
Background
Liquid biopsy provides a non-invasive approach that enables detecting circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) using blood specimens and theoretically benefits early finding primary tumor or monitoring treatment response as well as tumor recurrence. Despite many studies on these novel biomarkers, their clinical relevance remains controversial. This study aims to investigate the correlation between ctDNA, CTCs, and circulating tumor-derived endothelial cells (CTECs) while also evaluating whether mutation profiling in ctDNA is consistent with that in tumor tissue from lung cancer patients. These findings will help the evaluation and utilization of these approaches in clinical practice.

Methods
104 participants (49 with lung cancer and 31 with benign lesions) underwent CTCs and CTECs detection using integrating subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy. The circulating cell-free DNA (cfDNA) concentration was measured and the mutational profiles of ctDNA were examined by Roche AVENIO ctDNA Expanded Kit (targeted total of 77 genes) by next generation sequencing (NGS) in 28 patients (20 with lung cancer and 8 with benign lesions) with highest numbers of CTCs and CTECs. Mutation validation in matched tumor tissue DNA was then performed in 9 patients with ctDNA mutations using a customized xGen pan-solid tumor kit (targeted total of 474 genes) by NGS.

Results
The sensitivity and specificity of total number of CTCs and CTECs for the diagnosis of NSCLC were 67.3% and 77.6% [AUC (95%CI): 0.815 (0.722–0.907)], 83.9% and 77.4% [AUC (95%CI): 0.739 (0.618–0.860)]. The concentration of cfDNA in plasma was statistically correlated with the size of the primary tumor (r = 0.430, P = 0.022) and CYFRA 21–1 (r = 0.411, P = 0.041), but not with the numbers of CTCs and CTECs. In this study, mutations were found to be poorly consistent between ctDNA and tumor DNA (tDNA) in patients, even when numerous CTCs and CTECs were present.

Conclusion
Detection of CTCs and CTECs could be the potential adjunct tool for the early finding of lung cancer. The cfDNA levels are associated with the tumor burden, rather than the CTCs or CTECs counts. Moreover, the poorly consistent mutations between ctDNA and tDNA require further exploration.
Family planning integration in Ethiopia’s primary health care system: a qualitative study on opportunities, challenges and best practices
Authors: Titiyos Addisalem , Mehretie Yohannes , Alemayehu Yibeltal Kiflie , Ejigu Yohannes , Yitbarek Kiddus , Abraham Zelalem , O’Connell Kathryn A. , Kassaw Jemal 
Published: December 2023

Abstract
Background
Family planning (FP) service integration into primary health care (PHC) is an effective approach to realize reproductive autonomy, increase the use of contraceptives, and improve maternal and child health outcomes. The Ethiopian government promotes integration of FP services into primary health care (PHC). However, there is paucity of evidence on the status of FP service integration. The aim of this study is to explore the state of FP integration into PHC services and identify facilitators and barriers to integration.

Methods
A qualitative study nested with a larger national study was conducted from July to October 2022. A total of 60 interviews were conducted with FP stakeholders including, government organizations, non-governmental organizations, donors, service providers, and clients. Interviews were audio recorded, transcribed, and coded using OpenCode 4.03. The coded data were analyzed using framework analysis approach, using the Primary Health Care Performance Initiative (PHCPI) framework. Direct quotes and results from the coding and categorization were used to develop the report.

Results
Family planning is largely provided in designated units by dedicated staff within PHC facilities. The provision of integrated FP service within each service unit is in its early stage. Successful examples of integration include integration of FP with postnatal care, abortion care, and youth-friendly service centers. Facilitators of integration include commitment of the government and partners, the presence of policies and guidelines, and positive attitude of service providers and clients. However, integration of FP also faces challenges that are largely related to challenges of the FP program even before integration. These include resource shortage, health workers shortage, health workers’ capacity/skill gaps, misconceptions about FP, religious and socio-cultural norms, and lack of awareness.

Conclusions
Integration of FP with PHC services in the Ethiopian public health facilities is viable. Pre-existing challenges of the FP program continued to be barriers to integration. Expanding the experiences of good practices in the integration of FP with post abortion care, post-natal care, and youth-friendly service centers to other components of PHC warrants attention. Addressing both supply- and demand-side challenges of the FP program is needed to facilitate the integration of FP with other PHC services.
Mixed methods usability evaluation of an assistive wearable robotic hand orthosis for people with spinal cord injury
Authors: Dittli Jan , Meyer Jan T. , Gantenbein Jessica , Bützer Tobias , Ranzani Raffaele , Linke Anita , Curt Armin , Gassert Roger , Lambercy Olivier 
Published: December 2023

Abstract
Background
Robotic hand orthoses (RHO) aim to provide grasp assistance for people with sensorimotor hand impairment during daily tasks. Many of such devices have been shown to bring a functional benefit to the user. However, assessing functional benefit is not sufficient to evaluate the usability of such technologies for daily life application. A comprehensive and structured evaluation of device usability not only focusing on effectiveness but also efficiency and satisfaction is required, yet often falls short in existing literature. Mixed methods evaluations, i.e., assessing a combination of quantitative and qualitative measures, allow to obtain a more holistic picture of all relevant aspects of device usability. Considering these aspects already in early development stages allows to identify design issues and generate generalizable benchmarks for future developments.

Methods
We evaluated the short-term usability of the RELab tenoexo, a RHO for hand function assistance, in 15 users with tetraplegia after a spinal cord injury through a comprehensive mixed methods approach. We collected quantitative data using the Action Research Arm Test (ARAT), the System Usability Scale (SUS), and timed tasks such as the donning process. In addition, qualitative data were collected through semi-structured interviews and user observations, and analyzed with a thematic analysis to enhance the usability evaluation. All insights were attributed and discussed in relation to specifically defined usability attributes such as comfort, ease of use, functional benefit, and safety.

Results
The RELab tenoexo provided an immediate functional benefit to the users, resulting in a mean improvement of the ARAT score by 5.8 points and peaking at 15 points improvement for one user (clinically important difference: 5.7 points). The mean SUS rating of 60.6 represents an adequate usability, however, indicating that especially the RHO donning (average task time = 295 s) was perceived as too long and cumbersome. The participants were generally very satisfied with the ergonomics (size, dimensions, fit) of the RHO. Enhancing the ease of use, specifically in donning, increasing the provided grasping force, as well as the availability of tailoring options and customization were identified as main improvement areas to promote RHO usability.

Conclusion
The short-term usability of the RELab tenoexo was thoroughly evaluated with a mixed methods approach, which generated valuable data to improve the RHO in future iterations. In addition, learnings that might be transferable to the evaluation and design of other RHO were generated, which have the potential to increase the daily life applicability and acceptance of similar technologies.
An observational study of an adjusted patient blood management protocol intended to lower rates of transfusion following total knee arthroplasty in patients with preoperative anemia
Authors: Hourlier Hervé , Fennema Peter 
Published: December 2023

Abstract
Background
Patients with preoperative anemia have a higher risk of requiring blood transfusion after major orthopedic surgery due to increased blood loss and closer transfusion thresholds. Various patient blood management (PBM) policies aim to reduce transfusion rates. This observational study aimed to investigate blood loss and evaluate the effectiveness of an adjusted surgical PBM protocol in patients with anemic chronic disease (ACD) undergoing elective total knee arthroplasty (TKA).

Methods
A consecutive cohort of patients underwent elective unilateral TKA with an adjusted PBM protocol. The protocol consisted of epoetin (EPO) alfa therapy prescribed by the surgeon, routine administration of tranexamic acid (TXA), and standardized postoperative pharmacologic prophylaxis for thromboembolism. The performance of this PBM protocol was analyzed in patients with a baseline hemoglobin level of less than 12 g/dl. Hemoglobin levels were controlled at admission, on postoperative day (POD) 1, and on POD 7 ± 1. A bleeding index (BI-7) was used as an estimate of blood loss up until POD 7. Multiple linear regression was used to assess whether there were any differences in BI-7 between ACD– and ACD + patients.

Results
A total of 751 patients with complete hemoglobin monitoring were included in the study. Of these patients, 68 (9.1%) had a baseline hemoglobin concentration of less than 12 g/dl (ACD group). In this group, 28 patients (41.2%) received preoperative EPO therapy. The mean adjusted BI-7 for the study population was 3.0 (95% CI, 2.9 to 3.0) g/dl in the ACD– group and 2.3 (95% CI, 2.0–2.6) g/dl in the ACD + group. The difference in BI-7 was statistically significant (difference, 0.6 [95% CI: 0.3 to 0.9] g/dl, p < 0.001). No major complications occurred in the ACD + group, whereas there were three complications in the ACD– group (p = 1.00).

Conclusions
ACD patients undergoing TKA did not have an increased risk of bleeding or bleeding complications with the use of the adjusted PBM protocol. None of ACD patients required transfusion. ACD patients undergoing TKA experienced significantly less blood loss than patients with no preoperative anemia with the use of the adjusted PBM. We now consider the use of EPO in ACD patients with no nutritional deficiencies undergoing TKA at a baseline hemoglobin level of 11 g/dl. However, this should be validated in larger cohorts with a higher prevalence of ACD patients.
Augmented reality-assisted versus conventional total hip arthroplasty: a systematic review and meta-analysis
Authors: Su Shilong , Wang Ruideng , Chen Zhengyang , Zhou Fang , Zhang Yunqing 
Published: December 2023

Abstract
Background
Extended reality (XR), including virtual reality, augmented reality (AR), and mixed reality, has been used to help achieve accurate acetabular cup placement in total hip arthroplasty (THA). This study aimed to compare the differences between XR-assisted and conventional THA.

Methods
In this systematic review and meta-analysis, electronic databases including PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov were searched for studies from inception to September 10, 2023. The outcomes were accuracy of inclination and anteversion, duration of surgery, and intraoperative blood loss. Meta-analysis was performed using Review Manager 5.4 software.

Results
A total of five studies with 396 patients were included in our study. The pooled results indicated AR-assisted THA had better accuracy of inclination and anteversion than conventional THA (SMD = − 0.51, 95% CI [− 0.96 to − 0.07], P = 0.02; SMD = − 0.96, 95% CI [− 1.19 to − 0.72], P < 0.00001), but duration of surgery and intraoperative blood loss were similar in the two groups.

Conclusion
This systematic review and meta-analysis found that AR-assisted THA had better accuracy of inclination and anteversion than conventional THA, but the duration of surgery and intraoperative blood loss were similar in the two groups. Based on the pooled results, we suggested that AR can provide more precise acetabular cup placement than conventional methods in THA.
Hedgehog-Gli1-derived exosomal circ-0011536 mediates peripheral neural remodeling in pancreatic cancer by modulating the miR-451a/VGF axis
Authors: Dai Weiqi , Wu Xiaoli , Li Jingjing , Tang Wenxi , Wang Ying , Xu Wenqiang , Han Dengyu , Xu Xiaorong , Xu Xuanfu 
Published: December 2023

Abstract
Background
Hedgehog-Gli1 signaling induces development of two common neurological features seen in pancreatic ductal adenocarcinoma (PDAC): peripheral neural invasion (PNI) and peripheral neural remodeling (PNR). However, the underlying molecular mechanisms in cancer cells and nerves within Gli1-derived PNR have not previously been comprehensively analyzed.

Methods
In this study, RNA sequencing was used to screen meaningful circRNAs in PNR. An in vitro model of PNR was subsequently constructed through a co-culture system comprising PDAC cells and murine dorsal root ganglia (DRG) (as the neuronal element), and the relevant mechanisms were explored using a series of molecular biology experiments. A subcutaneous nude mouse tumorigenesis model was established to further verify the occurrence of PNR that was detected in human PDAC samples.

Results
We first confirmed the molecular mechanisms of PNR development through crosstalk between exosomal circ-0011536 and DRG. In Gli1-overpressed PDAC, circ-0011536 is mainly secreted by exosomes. After being ingested by DRG, it can promote the activity of DRG by degrading miR-451a and upregulating the expression of VGF. Overexpression of Gli1 can accelerate the proliferation of subcutaneous tumors in mice and is closely related to the density of nerve plexuses, while downregulating circ-RNA inhibits tumor proliferation and reduces the density of nerve plexuses. In addition, TMA results confirmed that Gli1 overexpression significantly increased the expression of VGF and was closely associated with increased nerve plexus density.

Conclusion
Hedgehog-Gli1-induced exosomal circ-0011536 promoted PNR via the miR-451a/VGF axis, thereby establishing that it may contribute to PDAC-associated nerve changes with activated Hedgehog signaling.
Hybrid-hybrid correction of errors in long reads with HERO
Authors: Kang Xiongbin , Xu Jialu , Luo Xiao , Schönhuth Alexander 
Published: December 2023

AbstractAlthough generally superior, hybrid approaches for correcting errors in third-generation sequencing (TGS) reads, using next-generation sequencing (NGS) reads, mistake haplotype-specific variants for errors in polyploid and mixed samples. We suggest HERO, as the first “hybrid-hybrid” approach, to make use of both de Bruijn graphs and overlap graphs for optimal catering to the particular strengths of NGS and TGS reads. Extensive benchmarking experiments demonstrate that HERO improves indel and mismatch error rates by on average 65% (27$$\sim$$
∼
95%) and 20% (4$$\sim$$
∼
61%). Using HERO prior to genome assembly significantly improves the assemblies in the majority of the relevant categories.
The association between the metabolic score for insulin resistance (METS-IR) index and urinary incontinence in the United States: results from the National Health and Nutrition Examination Survey (NHANES) 2001–2018
Authors: Cao Shangqi , Meng Linghao , Lin Lede , Hu Xu , Li Xiang 
Published: December 2023

Abstract
Background
The association between insulin resistance and urinary incontinence (UI) has not been investigated widely. The purpose of this study is to assess the relationship between a novel indicator for assessing insulin resistance the metabolic score for insulin resistance (METS-IR) index and urinary incontinence (UI).

Methods
This study utilized data from National Health and Nutrition Examination Survey (NHANES) 2001–2018. Weighted multivariable logistic regression models were conducted to explore the association of METS-IR index with three types of UI [stress UI (SUI), urgency UI (UUI), and mixed UI (MUI)]. Smooth curve fitting was utilized to investigate the linear relationship. Subgroup analysis was used to examine the stability of the connection between METS-IR index and UI in different stratifications.

Results
A total of 17,474 participants were included in this study, of whom 23.76% had SUI, 20.05% had UUI, and 9.59% had MUI. METS-IR index was positively associated with three types of UI with full adjustment [SUI: odds ratio (OR) = 1.023, 95% confidence interval (CI) 1.019–1.027; UUI: OR = 1.015, 95% CI 1.011–1.019; MUI: OR = 1.020, 95% CI 1.016–1.025, all p < 0.001]. After transferring METS-IR index into a categorical variable by quartiles, the positive connection between METS-IR index and UI was still observed in the highest METS-IR group compared to the lowest METS-IR interval (SUI: OR = 2.266, 95% CI 1.947–2.637, p < 0.001; UUI: OR = 1.534, 95% CI 1.344–1.750, p < 0.001; MUI: OR = 2.044, 95% CI 1.707–2.448, p < 0.001). The analysis of smooth curves fitting showed that METS-IR index was positively linearly related to three types of UI. Moreover, the association between METS-IR index and SUI was more significant in females compared to males (p for interaction < 0.05).

Conclusion
An elevated METS-IR index was related to increased risks of three types of UI (SUI, UUI, and MUI) in the United States population. METS-IR index was more significantly connected to SUI in females than males. The association between insulin resistance and UI needs to be explored with more studies.
Adipose tissue specific insulin resistance and prognosis of nondiabetic patients with ischemic stroke
Authors: Zhou Qi , Yan Hongyi , Jin Aoming , Meng Xia , Lin Jinxi , Li Hao , Wang Yongjun , Pan Yuesong 
Published: December 2023

Abstract
Background
Insulin resistance is linked to atherosclerotic cardiovascular diseases and stroke, whereas less is known about adipose tissue specific insulin resistance and outcomes after ischemic stroke. This study aimed to estimate the association between adipose tissue specific insulin resistance and prognosis of nondiabetic patients with ischemic stroke.

Methods
Patients with ischemic stroke without a history of diabetes mellitus in the Third China National Stroke Registry were included. Adipose tissue specific insulin resistance index (Adipo-IR) was calculated by fasting serum insulin and free fatty acids and categorized into 5 groups according to the quintiles. Outcomes included stroke recurrence (ischemic or hemorrhagic), combined vascular events, all-cause death, and poor outcome (modified Rankin Scale, 3–6) at 12 months after stroke onset. We assessed the association between Adipo-IR and risk of prognosis by multivariable Cox/logistic regression models adjusted for potential covariates.

Results
Among 2,222 patients, 69.0% were men with a mean age of 62.5 years. At 12 months, 185 (8.3%) patients had recurrent stroke, 193 (8.7%) had combined vascular events, 58 (2.6%) died, and 250 (11.5%) had a poor outcome. Compared with patients with the lowest quintile, patients with the second, third, fourth, fifth quintiles of the Adipo-IR were associated with an increased risk of stroke recurrence (hazard ratio [HR], 1.77; 95% CI, 1.04–3.03; P = 0.04; HR, 2.19; 95% CI, 1.30–3.68; P = 0.003; HR, 1.84; 95% CI, 1.06–3.21; P = 0.03; HR, 2.11; 95% CI, 1.20–3.71; P = 0.01, respectively) and marginally associated with an increased risk of combined vascular events ( HR, 1.60; 95%CI, 0.97–2.64; P = 0.07; HR, 1.91; 95% CI, 1.17–3.13; P = 0.01; HR, 1.62; 95% CI, 0.96–2.75; P = 0.07; HR, 1.80; 95% CI, 1.05–3.09; P = 0.03, respectively) at 12 months after adjustment for potential covariates. Adipo-IR was not associated with mortality and poor outcome at 12 months.

Conclusions
These findings suggest that adipose tissue specific insulin resistance is independently associated with recurrent stroke and combined vascular events after acute ischemic stroke in nondiabetic patients.