bluuebunny/crossref_metadata_2025_split huggingface dataset:
Axillary ultrasound for predicting response to neoadjuvant treatment in breast cancer patients—a single institution experience
Authors: Pislar Nina , Gasljevic Gorana , Music Maja Marolt , Borstnar Simona , Zgajnar Janez , Perhavec Andraz 
Published: September 2023

Abstract
Background
In node-positive breast cancer patients at diagnosis (cN +) that render node-negative after neoadjuvant systemic treatment (NAST), axillary lymph node dissection (ALND) can be avoided in selected cases. Axillary ultrasound (AUS) is most often used for re-staging after NAST. We aimed to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AUS after NAST for predicting nodal response at the Institute of Oncology, Ljubljana.

Methods
Biopsy-confirmed cN + patients consecutively diagnosed at our institution between 2008 and 2021, who received NAST, followed by surgery were identified retrospectively. Only patients that underwent AUS after NAST were included. AUS results were compared to definite nodal histopathology results. We calculated sensitivity, specificity, PPV and NPV of AUS. We also calculated the proportion of patients with false-positive AUS that results in surgical overtreatment (unnecessary ALND).

Results
We identified 437 cN + patients. In 244 (55.8%) AUS after NAST was performed. Among those, 42/244 (17.2%) were triple negative (TN), 78/244 (32.0%) Her-2 positive (Her-2 +), and 124/244 (50,8%) luminal Her-2 negative cancers. AUS was negative in 179/244 (73.4%), suspicious/positive in 65/244 (26.6%) (11/42 (26.2%) TN, 19/78 (24.4%) Her-2 + , and 35/124 (28.2%) luminal Her-2 negative cancers). On definite histopathology, nodal complete response (pCR) was observed in 89/244 (36.5%) (19/42 (45.2%) TN, 55/78 (70.5%) Her-2 + , and 15/124 (12.1%) luminal Her-2 negative cancers). Among patients with suspicious/positive AUS, pCR was observed in 20/65 (30.8%) (6/11 (54.5%) TN, 13/19 (68.4%) Her-2 + and 1/35 (2.9%) luminal Her-2 negative cancers). Sensitivity was 29.0%, specificity 77,5%, PPV 69.2%, NPV 38.5%. Specificity and PPV in TN was 68.4% and 45.4%, in Her-2 + 76.4% and 31.6%, in luminal Her-2 negative 93,3% and 97,1%, respectively.

Conclusion
In approximately half of the patients, AUS falsely predicts nodal response after NAST and may lead to overtreatment in 30% of the cases (ALND). However, AUS has to be interpreted in context with tumor subtype. In luminal Her-2 negative cancers, it has a high PPV and is therefore useful.
Association of serum 25-hydroxyvitamin D levels with all-cause and cause-specific mortality among postmenopausal females: results from NHANES
Authors: Shi Jia-Wei , Wu Jiang-Nan , Zhu Xiao-Yong , Zhou Wen-Hui , Yang Jin-Ying , Li Ming-Qing 
Published: September 2023

Abstract
Background
Vitamin D deficiency is common among the population, but its relationship with mortality of postmenopausal females is unclear. The aim of this study is to explore the association between serum 25-Hydroxyvitamin D (25(OH)D) and all-cause and cause-specific mortality among postmenopausal women in the United States.

Methods
6812 participants of postmenopausal females from the National Health and Nutrition Examination Survey (2001–2018) were included in this study. The mortality status of the follow-up was ascertained by linkage to National Death Index (NDI) records through 31 December 2019. We used cox proportional hazards models to estimate the association of serum 25(OH)D concentrations and mortality of postmenopausal females.

Results
The mean level of serum 25(OH)D was 72.57 ± 29.93 nmol/L, and 65.34% had insufficient vitamin D. In postmenopausal females, low serum 25(OH)D concentrations were significantly associated with higher levels of glycohemoglobin, glucose, and lower levels of HDL. During follow-up, 1448 all-cause deaths occurred, including 393 cardiovascular disease (CVD)-related deaths and 263 cancer deaths. After multivariate adjustment, higher serum 25(OH)D levels were significantly related with lower all-cause and CVD mortality. In addition, serum 25(OH)D presented a L-shaped relationship with all-cause mortality, while appeared a U-shaped with CVD mortality, and the cut-off value is 73.89 nmol/L and 46.75 nmol/L respectively.

Conclusions
Low serum 25(OH)D levels are associated with the higher risk of all-cause and CVD mortality in postmenopausal females. These findings provide new ideas and targets for the health management of postmenopausal women.
Deep dissection of stemness-related hierarchies in hepatocellular carcinoma
Authors: Liang Rui , Hong Weifeng , Zhang Yang , Ma Di , Li Jinwei , Shi Yisong , Luo Qing , Du Shisuo , Song Guanbin 
Published: September 2023

Abstract
Background
Increasing evidence suggests that hepatocellular carcinoma (HCC) stem cells (LCSCs) play an essential part in HCC recurrence, metastasis, and chemotherapy and radiotherapy resistance. Multiple studies have demonstrated that stemness-related genes facilitate the progression of tumors. However, the mechanism by which stemness-related genes contribute to HCC is not well understood. Here, we aim to construct a stemness-related score (SRscores) model for deeper analysis of stemness-related genes, assisting with the prognosis and individualized treatment of HCC patients.Further, we found that the gene LPCAT1 was highly expressed in tumor tissues by immunohistochemistry, and sphere-forming assay revealed that knockdown of LPCAT1 inhibited the sphere-forming ability of hepatocellular carcinoma cells.

Methods
We used the TCGA-LIHC dataset to screen stemness-related genes of HCC from the MSigDB database. Prognosis, tumor microenvironment, immunological checkpoints, tumor immune dysfunction, rejection, treatment sensitivity, and putative biological pathways were examined. Random forest created the SRscores model. The anti-PD-1/anti-CTLA4 immunotherapy, tumor mutational burden, medication sensitivity, and cancer stem cell index were compared between the high- and low-risk score groups. We also examined risk scores for different cell types using single-cell RNA sequencing data and correlated transcription factor activity in cancer stem cells with SRscores genes. Finally, we tested core marker expression and biological functions.

Results
Patients can be divided into two subtypes (Cluster1 and Cluster2) based on the TCGA-LIHC dataset's identification of 11 stemness-related genes. Additionally, a SRscores was developed based on subtypes. Cluster2 and the group with the lowest SRscores had superior survival and immunotherapy response than Cluster1 and the group with the highest SRscores. The group with a high SRscores was significantly more enriched in classical tumor pathways than the group with a low SRscores. Multiple transcription factors and SRscores genes are correlated. The core gene LPCAT1 is highly expressed in rat liver cancer tissues and promotes tumor cell sphere formation.

Conclusion
A SRscores model can be utilized to predict the prognosis of HCC patients as well as their response to immunotherapy.
A novel NET-related gene signature for predicting DLBCL prognosis
Authors: Shi Huizhong , Pan Yiming , Xiang Guifen , Wang Mingwei , Huang Yusong , He Liu , Wang Jue , Fang Qian , Li Ling , Liu Zhong 
Published: September 2023

Abstract
Background
Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy. Neutrophil extracellular traps (NETs) are pathogen-trapping structures in the tumor microenvironment that affect DLBCL progression. However, the predictive function of NET-related genes (NRGs) in DLBCL has received little attention. This study aimed to investigate the interaction between NRGs and the prognosis of DLBCL as well as their possible association with the immunological microenvironment.

Methods
The gene expression and clinical data of patients with DLBCL were downloaded from the Gene Expression Omnibus database. We identified 148 NRGs through the manual collection of literature. GSE10846 (n = 400, GPL570) was used as the training dataset and divided into training and testing sets in a 7:3 ratio. Univariate Cox regression analysis was used to identify overall survival (OS)-related NETs, and the least absolute shrinkage and selection operator was used to evaluate the predictive efficacy of the NRGs. Kaplan–Meier plots were used to visualize survival functions. Receiver operating characteristic (ROC) curves were used to assess the prognostic predictive ability of NRG-based features. A nomogram containing the clinical information and prognostic scores of the patients was constructed using multivariate logistic regression and Cox proportional risk regression models.

Results
We identified 36 NRGs that significantly affected patient overall survival (OS). Eight NRGs (PARVB, LYZ, PPARGC1A, HIF1A, SPP1, CDH1, S100A9, and CXCL2) were found to have excellent predictive potential for patient survival. For the 1-, 3-, and 5-year survival rates, the obtained areas under the receiver operating characteristic curve values were 0.8, 0.82, and 0.79, respectively. In the training set, patients in the high NRG risk group presented a poorer prognosis (p < 0.0001), which was validated using two external datasets (GSE11318 and GSE34171). The calibration curves of the nomogram showed that it had excellent predictive ability. Moreover, in vitro quantitative real-time PCR (qPCR) results showed that the mRNA expression levels of CXCL2, LYZ, and PARVB were significantly higher in the DLBCL group.

Conclusions
We developed a genetic risk model based on NRGs to predict the prognosis of patients with DLBCL, which may assist in the selection of treatment drugs for these patients.
Constructing phylogenetic networks via cherry picking and machine learning
Authors: Bernardini Giulia , van Iersel Leo , Julien Esther , Stougie Leen 
Published: September 2023

AbstractBackgroundCombining a set of phylogenetic trees into a single phylogenetic network that explains all of them is a fundamental challenge in evolutionary studies. Existing methods are computationally expensive and can either handle only small numbers of phylogenetic trees or are limited to severely restricted classes of networks.ResultsIn this paper, we apply the recently-introduced theoretical framework of cherry picking to design a class of efficient heuristics that are guaranteed to produce a network containing each of the input trees, for practical-size datasets consisting of binary trees. Some of the heuristics in this framework are based on the design and training of a machine learning model that captures essential information on the structure of the input trees and guides the algorithms towards better solutions. We also propose simple and fast randomised heuristics that prove to be very effective when run multiple times.ConclusionsUnlike the existing exact methods, our heuristics are applicable to datasets of practical size, and the experimental study we conducted on both simulated and real data shows that these solutions are qualitatively good, always within some small constant factor from the optimum. Moreover, our machine-learned heuristics are one of the first applications of machine learning to phylogenetics and show its promise.
Prospective randomized study on the efficacy of three-dimensional reconstructions of bronchovascular structures on preoperative chest CT scan in patients who are candidates for pulmonary segmentectomy surgery: the PATCHES (Prospective rAndomized sTudy efficaCy of tHree-dimensional rEconstructions Segmentecomy) study protocol
Authors: Zaraca Francesco , Kirschbaum Andreas , Pipitone Marco Damiano , Bertolaccini Luca ,   The PATCHES study group, Akar Firas Abu , Cannone Giorgio , Ismail Mahmoud , Jiménez Marcelo , Kostic Marko , Ng Calvin S.H. , Perkmann Reinhold , Priscindaro Elena , Spaggiari Lorenzo , Ugalde Paula 
Published: September 2023

Abstract
Introduction
Pulmonary segmentectomy, when combined with hilar and mediastinal lymphadenectomy, is currently considered the gold standard treatment for early-stage lung tumors (NSCLC) smaller than 2 cm in diameter. The preoperative planning for segmentectomies usually includes a contrast-enhanced CT with 2D reconstructions (axial, coronary, and sagittal). Recent technological advances allow 3D (volume rendering) reconstructions of preoperative CT scans, intended to improve the surgeon’s understanding of the segmental anatomy.
The study aims to investigate the added value of 3D reconstruction in enhancing the surgeon’s understanding of anatomical structures, thus facilitating surgical planning and improving oncological outcomes.

Methods and analysis
This is a prospective, randomized, controlled study.
Patients will be randomized into two groups:
1. Group 2D: the preoperative workup for these patients will consist of a contrast-enhanced chest CT with two-dimensional (2D) reconstructions (axial, coronary, and sagittal);
2. Group 3D: the preoperative workup for these patients will consist of a contrast-enhanced chest CT with two-dimensional (2D) reconstructions (axial, coronary, and sagittal) and a 3D reconstruction (volume rendering) of the same chest CT employing dedicated software.
The primary endpoints will be negative margin (R0) resection rate, resection margin (staple line-to-tumor distance), and thoracotomy conversions.
We will use Fisher’s exact test for binary outcomes and Mann–Whitney U test for continuous outcomes. For subgroup analyses, we will use regression. Multivariable analyses will be based on logistic regression for binary outcomes and linear regression for continuous outcomes.

Ethics and dissemination
The protocol and the model informed consent forms have been reviewed and approved by the ethics committee (N.: 1–2023) concerning scientific content and compliance with applicable research and human subject regulations.
A Subcommittee on Publications was established to review all publications and report its recommendations to the steering committee. The anonymized participant-level dataset and statistical code for generating the results will not be publicly available.

Trial registration
The protocol was registered at ClinicalTrials.gov (ID: NCT05716815; Prospective rAndomized sTudy efficaCy tHree-dimensional rEconstructions Segmentectomy - Full-Text View - ClinicalTrials.gov). Jan 19, 2023.
Chalcone/1,3,4-Oxadiazole/Benzimidazole hybrids as novel anti-proliferative agents inducing apoptosis and inhibiting EGFR & BRAFV600E
Authors: Hagar Fatma Fouad , Abbas Samar H. , Gomaa Hesham A. M. , Youssif Bahaa G. M. , Sayed Ahmed M. , Abdelhamid Dalia , Abdel-Aziz Mohamed 
Published: September 2023

Abstract
Introduction
One of the most robust global challenges and difficulties in the 21st century is cancer. Treating cancer is a goal which continues to motivate researchers to innovate in design and development of new treatments to help battle the disease.

Objectives
Our objective was developing new antiapoptotic hybrids based on biologically active heterocyclic motifs "benzimidazole?oxadiazole-chalcone hybrids'' that had shown promising ability to inhibit EGFR and induce apoptosis. We expected these scaffolds to display anticancer activity via inhibition of BRAF, EGFR, and Bcl-2 and induction of apoptosis through activation of caspases.

Methods
The new hybrids 7a-x were evaluated for their anti-proliferative, EGFR & BRAFV600E inhibitory, and apoptosis induction activities were detected. Docking study & dynamic stimulation into EGFR and BRAFV600E were studied.

Results
All hybrids exhibited remarkable cell growth inhibition on the four tested cell lines with IC50 ranging from 0.95 μM to 12.50 μM. which was comparable to Doxorubicin. Compounds 7k-m had the most potent EGFR inhibitory activity. While, compounds 7e, 7g, 7k and 7l showed good inhibitory activities against BRAFV600E. Furthermore, Compounds 7k, 7l, and 7m increased Caspases 3,8 & 9, Cytochrome C and Bax levels and decreased Bcl-2 protein levels. Compounds 7k-m received the best binding scores and showed binding modes that were almost identical to each other and comparable with that of the co-crystalized Erlotinib in EGFR and BRAF active sites.

Conclusion
Compounds 7k-m could be used as potential apoptotic anti-proliferative agents upon further optimization.
Drivers of longevity of wild-caught Aedes albopictus populations
Authors: Blanco-Sierra Laura , Mariani Simone , Escartin Santi , Eritja Roger , Palmer John R. B. , Bartumeus Frederic 
Published: September 2023

Abstract
Background
Age structure and longevity constitute fundamental determinants of mosquito populations’ capacity to transmit pathogens. However, investigations on mosquito-borne diseases primarily focus on aspects such as abundance or dispersal rather than survival and demography. Here, we examine the post-capture longevity of wild-caught populations of the Asian tiger mosquito Aedes albopictus to investigate the influence of environmental factors and individual frailty on longevity.

Methods
We captured females of Ae. albopictus from June to November 2021 in a vegetated and an urban area by two methods of capture (BG traps and Human Landing catch). They were kept in semi-controlled conditions in the field, and survival was monitored daily across the 859 individuals captured. We studied the differences in longevity per capture method and location and the influence on longevity of seasonal, climatic and individual factors.

Results
Photoperiod, GDD, minimum and maximum temperature and relative humidity showed an effect on the risk of death of females in the field. Females captured in urban area with Human Landing catch methods had greater longevity than females captured in non-urban areas with BG traps. Individual variance, reflecting individual frailties, had an important effect on the risk of death: the greater the frailty, the shorter the post-capture longevity. Overall, longevity is affected not only by climate and seasonal drivers like temperature and photoperiod but also by the individual frailty of mosquitoes.

Conclusion
This work unravels environmental drivers of key demographic parameters such as longevity, as modulated by individual frailty, in disease vectors with strong seasonal dynamics. Further demographic understanding of disease vectors in the wild is needed to adopt new surveillance and control strategies and improve our understanding of disease risk and spread.
Exploratory study of volatile fatty acids and the rumen-and-gut microbiota of dairy cows in a single farm, with respect to subclinical infection with bovine leukemia virus
Authors: Suzuki Takehito , Murakami Hironobu , Uchiyama Jumpei , Sato Reiichiro , Takemura-Uchiyama Iyo , Ogata Masaya , Sogawa Kazuyuki , Ishida Hiroho , Atipairin Apichart , Matsushita Osamu , Nagai Makoto 
Published: September 2023

Abstract
Background
Subclinical infection with bovine leukemia virus (BLV) in cows can cause economic losses in milk and meat production in many countries, as BLV-related negative effects. The volatile fatty acids (VFAs) and microbiota present in the digestive tracts of cows can contribute to cow health. Here, we exploratorily investigated the VFAs and microbiota in the rumen and gut with respect to subclinical BLV infection using cows housed at a single farm.

Results
We analyzed a herd of 38 cows kept at one farm, which included 15 uninfected and 23 BLV-infected cows. First, the analysis of the VFAs in the rumen, gut, and blood revealed an absence of statistically significant differences between the uninfected and BLV-infected groups. Thus, BLV infection did not cause major changes in VFA levels in all tested specimens. Next, we analyzed the rumen and gut microbiota. The analysis of the microbial diversity revealed a modest difference between the uninfected and BLV-infected groups in the gut; by contrast, no differences were observed in the rumen. In addition, the investigation of the bacteria that were predominant in the uninfected and BLV-infected groups via a differential abundance analysis showed that no significant bacteria were present in either of the microbiota. Thus, BLV infection possibly affected the gut microbiota to a small extent. Moreover, bacterial associations were compared between the uninfected and BLV-infected groups. The results of this analysis suggested that BLV infection affected the equilibrium of the bacterial associations in both microbiota, which might be related to the BLV-related negative effects. Thus, BLV infection may negatively affect the equilibrium of bacterial associations in both microbiota.

Conclusions
Subclinical BLV infection is likely to affect the rumen and gut microbiota, which may partly explain the BLV-related negative effects.
Daily dose of metformin caused acute kidney injury with lactic acidosis: a case report
Authors: Ariga Maho , Hagita Junichiro , Soda Midori , Oida Yasuhisa , Teramachi Hitomi , Kitaichi Kiyoyuki 
Published: September 2023

Abstract
Background
Metformin-induced lactic acidosis with acute kidney injury is rare but well known. Here we report a case of a Japanese patient taking metformin who experienced severe acute renal failure accompanied with significantly elevated metformin plasma concentrations and signs of lactic acidosis.

Case presentation
A 60-year-old Japanese man with type II diabetes, who was taking metformin (500 mg three times a day) along with several other medications, visited the emergency department with dizziness, malaise, and oliguria. The initial laboratory test results showed elevated levels of serum creatinine and blood urea nitrogen, although his renal function was normal approximately 2 weeks earlier. His lactate level was raised (4.27 mmol/L), and he was diagnosed with lactic acidosis. Considering the low creatinine clearance and elevated urinary albumin/serum creatinine ratio, urinary N-acetyl-β-d-glucosaminidase level, and β2-microglobulin level, the patient was further diagnosed with AKI (in other words, acute tubular necrosis). A renal biopsy performed on day 3 after admission revealed renal tubular epithelium necrosis, supporting this diagnosis. The patient underwent intermittent hemodialysis until he was discharged on day 13. The metformin concentrations on days 3, 5, and 7 were 8.95, 2.58, and 0.16 μg/mL, respectively, which is significantly higher than the maximal steady-state concentration of metformin at the recommended dosage (approximately 1 μg/mL). The calculated pharmacokinetic parameters of metformin suggested poor renal excretion and a low distribution volume at higher metformin levels. Other possible acute kidney injury-causing factors included dehydration, alcohol consumption, and the use of an angiotensin receptor blocker or SGLT2 inhibitor.

Conclusions
This is the first reported case of acute kidney injury possibly caused by high levels of metformin with lactic acidosis in a patient treated with the recommended metformin dose. Thus, the development of metformin-induced acute kidney injury should be considered for patients with several acute kidney injury risk factors who are taking metformin.