bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted long-read sequencing enables higher diagnostic yield of ADPKD by accurate PKD1 genetic analysis in an assisted reproductive center
Authors: Gao Yuan , Sun Qian , Xu Peiwen , Mao Aiping , Huang Sexin , Li Jie , Chen Libao , Kan Haopeng , Li Jing , Huang Ju , Ji Wenkai , Si Dayong , Yan Junhao , Gao Xuan 
Published: November 2024

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by disease-causing variants in two large multi-exon genes of PKD1 and PKD2. Genetic diagnosis of ADPKD has been challenging due to the variant heterogeneity, presence of duplicated segments, and high GC content of exon 1 in PKD1. In our reproductive center, a total of 312 patients with ADPKD phenotype have been genetically tested using a next-generation sequencing (NGS) panel. Among all the cases, 40 patients were either genetically undiagnosed or diagnosed without single-nucleotide resolution. Therefore, a combination of long-rang PCR and long-read sequencing (LRS) approach for PKD1 and PKD2 was performed on these 40 ADPKD patients. LRS additionally identified 10 pathogenic or likely pathogenic PKD1 variants, including eight single-nucleotide variants (SNVs) and insertions/deletions (indels) and two large deletions. Among the eight SNV/indels, LRS identified four patients with microgene conversion (c.160_166dup, c.2180T>C, and c.8161+1G>A) between PKD1 and its pseudogenes, three patients with indels (c.-49_43del, c.2985+2_2985+4del, and c.10709_10760dup), and one patient with likely pathogenic deep intronic variant c.2908-107G>A. In addition, LRS identified nine PKD1 CNVs including eight large deletions and one duplication, and meanwhile LRS can precisely determine the breakpoints; while NGS had failed to identify two of these CNVs. In conclusion, target LRS enables higher diagnostic yield of ADPKD by accurate and precise PKD1 genetic analysis, which could provide significant benefits for genetic counseling and assisted reproductive treatments.
Prognostic difference between early breast cancer patients with HER2-low and HER2-zero status: A multicenter cohort study using propensity-score matched analysis
Authors: Chung Min Sung , CHA Chihwan , Kim Kyung Eun , Kim Jungbin , Um Eunhae , Choi Nayeon , Lee Jungsun , Gwak Geumhee , Kim Jae Il 
Published: November 2024

Abstract

Background
Since the approval of the trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)-low breast cancer, evidence suggests that low-HER2 expression may affect prognosis; however, it remains unclear how HER2-low subtype affects outcomes. Thus, this study aimed to investigate the differences in prognosis between patients with HER2-low and HER2-zero status.
Methods
This retrospective cohort study conducted at multi-institution included 1,627 patients diagnosed with HER2-low or HER2-zero breast cancer (stages I–III). For comparing outcomes between two groups, the survival analysis after propensity score matching was used. Survival outcomes including distant recurrence-free survival, and overall survival were evaluated using the Kaplan–Meier analyses.
Results
After propensity score matching, 445 patients with HER2-low and 707 patients with HER2-zero status were included. Among them, 914 (79.3%) and 238 (20.7%) patients had hormone receptor-positive and -negative disease. Median follow-up was 92.7 months. Locoregional recurrence-free survival and distant recurrence-free survival were comparable between patients with HER2-low and HER2-zero status (p = 0.872, p = 0.746, respectively). HER2-low status did not affect overall survival. However, in a subgroup with lymph node metastases, patients with HER2-low status showed better recurrence-free survival compared with that of patients with HER2-zero status (p = 0.033).
Conclusions
In this study, survival outcomes were comparable between patients with HER2-low and HER2-zero breast cancer. Additionally, patients with HER2-low status showed better survival outcomes compared with those with HER2-zero in the subgroup with lymph node metastasis. Further studies are needed to examine the biological mechanism underlying these prognostic differences.
Partial sternotomy as an alternative surgical approach for atrioventricular valves and interatrial septal diseases
Authors: Coutinho Henrique , Bittencourt Gabriel , Kikiuta Gustavo , Jazbik Pedro Ricardo , Sant'Anna Zely , Brasil Bernardo , Coutinho Joaquim Henrique Souza Aguiar , Saito Eduardo Haruo , Nunes Rodolfo Acatauassú 
Published: November 2024

Abstract

Introduction: Since its inception, cardiovascular surgery has posed numerous technical challenges for surgeons. In a continuous quest for enhancement, cardiovascular surgeons have sought to reduce surgical trauma through the refinement of minimally invasive techniques. Therefore, this study aims to introduce a novel approach among partial sternotomies, preserving both the manubrium and the xiphoid process. Our objective was to evaluate the feasibility of this surgical technique, the stability of the sternum bone in the postoperative period, the incidence of surgical wound infection, and the potential for patients to resume their regular activities within a 21-day timeframe.
Methods: This prospective, single-center, single-arm study was conducted to assess the safety of a surgical approach involving partial sternotomy for atrioventricular valve pathologies and septal defects. A total of 20 patients were evaluated and presented with the following: mitral insufficiency (n=8, 40%); mitral stenosis (n=5, 25%); ostium secundum-type interatrial communication (n=3, 15%); sinus venosus interatrial communication–superior vena cava (n=2, 10%); and myxoma (n=2, 10%). Patients underwent one of the following procedures: mitral valve replacement (n=13, 65%), atrial septal defect repair (n=5, 25%) or atrial myxoma resection (n=2, 10%).
Results: Three (15%) patients required conversion to full median sternotomy, and there were no cases of surgical wound infection. The mean length of stay was 5.4 days.
Conclusion: The results of this study revealed a technically feasible procedure, with no significant increase in surgical duration, and excellent outcomes regarding the absence of surgical site infection, sternal stability, and aesthetic considerations. Most patients resumed their usual activities within the proposed time. However, further extensive case studies and comparative analyses are needed to validate these outcomes in comparison with those of conventional sternotomy procedures.
DEPTH2 score was associated with cell proliferation and immune cell infiltrations but not with systemic treatment response in breast cancer
Authors: Chida Kohei , Wu Rongrong , Roy Arya Mariam , Ishikawa Takashi , Hakamada Kenichi , Takabe Kazuaki 
Published: November 2024

Abstract

Intratumoral genomic heterogeneity (ITGH), the existence of genotypic and phenotypic variation within an individual tumor, is known to be a key mechanism in treatment resistance. Deviating gene Expression Profiling Tumor Heterogeneity 2 (DEPTH2) algorithm was developed to estimate ITGH using solely RNA expression data unlike the others that require both DNA- and RNA-expression data. Total of 6,500 breast cancer patients from multiple independent cohorts were analyzed using DEPTH2. High DEPTH2 score patients were associated with worse overall survival consistently across all subtypes in METABRIC, but not in TCGA and SCAN-B cohort. Higher DEPTH2 score was linked to increased cell proliferation, as evidenced by elevated Nottingham histological grades and Ki67 gene expression, as well as enrichment of the cell proliferation-related gene sets, and immune cell infiltrations. DEPTH2 score was significantly higher in triple negative breast cancer among the subtypes but did not reflect with lymph node and distal metastasis. DEPTH2 scores decreased in two but showed no change in another two cohorts after neoadjuvant chemotherapy (NAC). DEPTH2 score was not associated with pathologic complete response after NAC in any subtypes across 3 cohorts. DEPTH2 score may not capture the entire biological aspects of ITGH in breast cancer patients.
The male sling implantation for urinary incontinence after prostate surgery: a real world multi-center study in China
Authors: Wang Lei , Chen Yin , Sun Weihao , Ren Guanyu , Piao Shuguang , Pan Tiejun , Liao Limin , Liu Zhiyong 
Published: November 2024

Abstract

Purpose
Urinary incontinence after prostate treatment (IPT) is a distressing phenomenon. The aim of this real-world study was to evaluate the efficacy of the male sling in treating IPT in China.
Methods
A total of 66 patients (83.8% with moderate and severe urinary incontinence) with IPT underwent male sling implantation in four medical centers. Incontinence was assessed using pad weight, pad usage per day (PPD), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Surgical efficacy, surgical modalities, BMI and complications were evaluated.
Results
Median follow-up was 23 months. Of 66 patients with transobturator (2-arm) and transobturator and anterior pubic (4-arm), 16 (24.2%) were cured, 40 (60.6%) improved and 10 (15.1%) failed according to PPD. In terms of 24-h pad weights, 16 (24.2%) and 24 (36.3%) achieved continence (dry pad) or mild incontinence (< 100 mL/day); 22 (33.3%) and 4 (6%) were still with moderate (100–400 mL/day) or severe (> 400 mL/day) incontinence. 4 (100.0%) patients preoperatively with mild incontinence were not cured ,but all improved in terms of PPD; Of 39 patients preoperatively with moderate incontinence, 9 (23.1%) were cured, 24 (61.5%) improved and 6 (35.8%) failed; Of 23 patients preoperatively with severe incontinence, 7 (30.4%) were cured, 12 (52.1%) improved and 4 (17.4%) failed. The improvement rate for patients with three different level incontinence were 100%, 84.6% and 82.6% respectively. There was no significant correlation between the degree of recovery and BMI. Common postoperative complications include pain, incision infection, foreign body sensation and urinary retention or dysuria.
Conclusion
The majority of patients receiving male urethral sling implantation are moderate and severe patients .Real-world studies show that male urethral suspension is more often used to treat male urinary incontinence than AUS in China, medical insurance policies and economic costs are important influencing factors. The utilization of this intervention has yielded a considerable rate of amelioration for IPT. It must also be admitted comparative analysis indicates that male slings confer a superior overall prognostic improvement for patients presenting with mild urinary incontinence relative to those with moderate and severe manifestations of the condition, especially for severe urinary incontinence has improved, but a large proportion of patients still have symptoms.
Anterior-plane Retroperitoneoscopic Resection of Adrenal Tumor: a Clinical Study Based on Propensity Score with Inverse Probability of Treatment Weighting
Authors: Hu Deng , Li Xiang , Wang Yaodong , He Kai , Jiang Shichun , Wang Decai 
Published: November 2024

Abstract

To investigate the clinical efficacy, safety and economy of anterior-plane retroperitoneoscopic c adrenalectomy in treating ≤ 5cm benign adrenal tumors.From January 2019 to August 2023,276 patients undergoing anterior-plane or three-plane retroperitoneoscopic resection of adrenal tumors were retrospectively analyzed. Propensity score with inverse probability of treatment weighting (PS-IPTW) was used to adjust the balance of baseline characteristics and linear regression was conducted to compare the weighted outcomes between the two groups.After PS-IPTW, standardized mean difference (SMD) of the baseline data less than 0.1. In anterior-plane group, operation time decreased by 39.16 minutes (P < 0.05), intraoperative blood loss decreased by 12.18 ml (P < 0.05), postoperative gastrointestinal function recovery time accelerated by 6.24 hours (P < 0.05), postoperative 24-hour blood drainage decreased by 18.06 ml (P < 0.05), postoperative extubation time shortened by 15.99 hours (P < 0.05), postoperative length of hospital stay shortened by 0.77 days (P < 0.05), and total hospitalization costs reduced by 2,379.30 Chines yuan (P < 0.05).Anterior-plane retroperitoneoscopic adrenalectomy is effective, safe, and economy in treating ≤ 5cm benign adrenal tumors.Therefore, this method is expected to promote enhanced recovery after surgery (ERAS) program for urological tumors. Specifically, obese people may benefit more from this surgical approach.
Nutrient Profiles of Enteral Feeds in Two Selected Hospitals in Accra, Ghana.
Authors: Adom Rosa , Mensah Daniel , Nortey Eunice , Asante Matilda , Boateng Laurene 
Published: November 2024

Abstract

Background
Hospital-prepared enteral feeds have demonstrated significant benefits for critically ill patients, primarily by maintaining gut integrity, reducing stress, and supporting immunity. These feeds are often preferred over commercial formulas due to their cost-effectiveness and patient tolerability. However, despite these advantages, hospital-prepared enteral feeds can exhibit inconsistent energy and nutrient values, which may impact their effectiveness. In Africa, and specifically in Ghana, there is a notable gap in documented research regarding the nutrient profiles of these feeds. This lack of data makes it challenging to standardize and optimize enteral nutrition practices across hospitals. Recognizing this gap, our study aims to assess the nutrient profiles of hospital-prepared enteral feeds in two selected hospitals in Accra
Methods
Twenty-one (21) dietitians and six (6) diet cooks were interviewed. Three (3) hospital-prepared enteral feed samples were collected from the two hospitals on three different days and their energy and nutrient values were analysed. The recipes used in the preparation of the feeds were collected through interviews with diet cooks. Energy and nutrient values obtained from chemical analyses of hospital-prepared enteral feeds, were compared to a commercial formula using one sample t-test.
Results
Most dietitians in both hospitals (90% in Hospital A and 73% in Hospital B) utilized hospital-prepared enteral feeds, such as fortified porridges and soups. However, the energy and nutrient values of these feeds were significantly lower compared to a commercial formula (Ensure original). When enteral feeds from the 2 hospitals were compared, statistically significant differences were found for all nutrients except energy, carbohydrate, vitamin C, and sodium.
Conclusions
The study highlighted differences in the nutritional profiles of hospital-prepared enteral feeds between the 2 hospitals, and significantly lower energy and nutrient content compared to a commercial formula, Ensure Original. Low energy and nutrient content in hospital-prepared feeds could lead to suboptimal patient outcomes, including slower recovery times and increased susceptibility to infections. Further research is needed to explore ways to improve the nutrient profiles of hospital-prepared feeds and develop enteral feeding protocols in hospitals in Ghana.
BMI, Waist Circumference, and Waist-to-hip Trajectories and All-cause, CVD, and Cancer Mortality by Sex in Nondiabetic People
Authors: Alman Amy , Xing Zailing , Schocken Douglas , Zgibor Janice 
Published: November 2024

Abstract

Objective: We examined the associations of BMI, waist circumference, and waist-to-hip ratio trajectories with mortality in non-diabetic people.
Methods:We analyzed 7 601 nondiabetic people from the Atherosclerosis Risk in Communities Study. We used latent class analysis to identify trajectory patterns for BMI, waist circumference, and waist-to-hip. We employed propensity score matching to enhance the balance of covariates and used Cox proportional hazards regression models to examine the associations.
Results: In females, the high trajectory of BMI was associated with higher cancer mortality risks than the low group, with HRs and 95% CIs of 1.76(1.14-2.73). The high waist circumference trajectory was related to increased all-cause, CVD, and cancer mortality risks in males. The moderate and high waist-to-hip ratio trajectories were associated with elevated all-cause and CVD mortality risks in females, and the high trajectory was associated with high all-cause mortality risks in males. The mean lifespan of deceased females did not significantly differ across the trajectories. However, the mean lifespan of males in the waist circumference high group (73.0 years) was shorter than the low group (75.3 years).
Conclusion: Sex differences were observed in the long-term impact of high BMI, waist circumference, and waist-to-hip ratio on mortality risks and lifespan in non-diabetic people.
Comparison of the sustainability of the impact of team-based versus individual clinician-focused training of primary care professionals in serious illness conversations on caregiver burden of care: a secondary analysis of a cluster randomized trial
Authors: Lokossou Kouessiba Lorielle , Assan Odilon Quentin , Gadio Souleymane , Uwizeye Claude-Bernard , Dofara Georgina Suelene , Bouba Dalil Asmaou , Guay-Bélanger Sabrina , Michaels LeAnn , Archambault Patrick , Paquette Jean-Sébastien , Izumi Seiko , Totten Annette , Rivest Louis-Paul , Légaré France 
Published: November 2024

Abstract

Background: Training health professionals in serious illness conversations is important for patients with serious illnesses and for their caregivers. However, most training focuses on individual clinicians rather than on healthcare teams. We aimed to compare the sustainability of the impact of a team-based training program in serious illness conversations with that of an individual clinician-focused training program on the burden of care of caregivers of patients with serious illnesses.
Methods:We performed a secondary analysis of caregivers’ data from a preliminary cluster randomized trial in the USA and Canada in which 42 primary care clinics were randomized to an interprofessional team-based training arm (intervention) or an individual clinician-focused training arm (control). Seriously ill patients who had had a serious illness conversation with the trained clinicians were asked to refer a caregiver. We used the Zarit Burden Interview (range: 0-48) to assess caregiver burden immediately after the serious illness conversation (T1), six months later (T2) and 12 months later (T3). Statistical analysis using a linear mixed model were performed to compare caregiver burden between the two arms at the three times.
Results: We included 192 caregivers from 42 primary care clinics. Most were female (67.8%); aged 65-74 (28.6%). The mean caregiver burden scores were low, and similar in both the arms at the three times. The difference in mean burden between the two study arms was 1.05 (95% CI -1.47 to 3.59; p=0.40), -0.24 (95% CI -2.57 to 2.08; p=0.82), and 0.09 (95% CI -2.61 to 2.81; p=0.94) at T1, T2 and T3 respectively. The p-value of the interaction term between study arm and time was p=0.47. Mean difference between arms after performing a model with time effect and after adjusting was 0.90 (95% CI -0.76 to 2.57; p=0.28). Various other factors such as caregivers feeling anxious or depressedwere associated with caregiver burden.
Conclusion:Analysis showed that there was no difference between perceived caregiver burden after the interprofessional team-based training approach and after the individual clinician-focused training approach. Our study did however underline the importance of recognizing other factors influencing caregiver well-being.
Trial registration: ClinicalTrials.gov (ID: NCT03577002).
Circulating Tumor DNA Determinants of Response and Outcome in Relapsed/Refractory Mantle Cell Lymphoma
Authors: Meriranta Leo , Jørgensen Rasmus , Pasanen Annika , Kolstad Arne , Hutchings Martin , Niemann Carsten , El_Galaly Tarec , Riise Jon , Haaber Jacob , Sonnevi Kristina , Pedersen Lone Bredo , Wader Karin , Glimelius Ingrid , Leppä Sirpa , Jerkeman Mats 
Published: November 2024

Abstract

Clinical tools to guide treatment decisions in relapsed and refractory mantle cell lymphoma (R/R MCL) are limited, and the translational potential of circulating tumor DNA (ctDNA) has remained largely undemonstrated. We designed and applied panel-based duplex sequencing to uncover molecular determinants of response and outcome in the ctDNA of R/R MCL patients treated with venetoclax, lenalidomide, and rituximab (Ven-R2). Genetic analysis revealed molecular predictors of response and outcome that were independent of clinical prognostic factors with SMARCA4-mutated R/R MCLs responding to therapy whereas TP53 mutations conferred resistance. Pretreatment ctDNA captured spatial heterogeneity and its concentration associated with clinicopathological disease features and survival independently of molecular predictors. Dynamic ctDNA assessment for minimal residual disease complemented clinical response evaluation and uncovered refractoriness in select patients with molecular remission according to contemporary real-time quantitative PCR assay. Features of clonal hematopoiesis (CH) at baseline were associated with hematological toxicity during treatment and poor outcome. Positive selection of TP53-related CH during treatment did not compromise specificity of ctDNA response analysis, and fragmentation signatures allowed discrimination of MCL ctDNA and CH. Taken together, we report novel features in the MCL ctDNA that unlock new minimally invasive tools to potentially transform clinical decision-making in R/R MCL.
Multi-component and multi-phase field modelling of solidification microstructural evolution in Inconel 625 alloy during laser powder bed fusion additive manufacturing
Authors: Maji Soma , Amirthalingam Murugaiyan 
Published: November 2024

Abstract

Inconel 625 alloy, known for exceptional mechanical properties and corrosion resistance, is widely used in aerospace, power generation, and marine applications. Laser powder bed fusion (LPBF) excels in manufacturing complex geometries with good surface finish. However, LPBF printed microstructure is highly heterogeneous due to the rapid and complex thermal cycles, necessitating careful parameter selection to prevent the stabilisation of detrimental phases. Experimental parametric optimization of LPBF is challenging due to the cost, and complex inter-playing process variables. Therefore, mathematical modelling is advantageous for optimizing LPBF parameters. \\A 3D-heat source model was developed using finite-element-method (FEM) to analyse thermal cycles with bed-preheating and varying laser parameters in LPBF of IN625. The model focused on a simplified thermal cycle method, where all elements in a layer were set to melt at once to reduce the computational time. A multi-phase-field method (MPFM) was developed to simulate the microstructural evolution as a function of FEM-generated thermal boundary conditions. The morphological and elemental segregation behaviour of evolving microstructure was simulated. Numerical and experimental analyses of primary dendritic arm spacing (PDAS) and elemental segregation agreed well with the experiments. Optimal LPBF conditions were identified for defect-free printing of IN625 parts from this work.