bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pregnancy outcomes of 4 endometrial preparation protocols in adenomyosis patients with thin endometrium during frozen embryo transfer: a retrospective cohort study
Authors: Yu Yi , Zhang Xi , Xu Xinxin , Yan Lei , Zhang Ya-nan 
Published: December 2023

Introduction:
This study aimed to compare the pregnancy outcomes of different endometrial preparation protocols in patients with adenomyosis and thin endometrium during frozen embryo transfer.

Methods:
The study, which was conducted at the Reproductive Hospital Affiliated to Shandong University, included 236 patients with adenomyosis and thin endometrium who underwent frozen embryo transfer between January 1, 2011, and December 12, 2022. The pregnancy outcomes and maternal and infant complications among the 4 groups were further compared.

Results:
These patients with adenomyosis and thin endometrium were divided into 4 groups based on the endometrial preparation protocols used: natural cycle treatment (n=53), hormone replacement therapy group (n=73), gonadotropin-releasing hormone agonists + hormone replacement therapy group (n=49), and ovarian induction group (n=61). The demographic, cycle, and embryologic characteristics were similar between groups. The livebirth rates (P=0.29), full-term pregnancy rates (P=0.55), preterm pregnancy rates (P=0.33), clinical pregnancy rates (P=0.77), biochemical pregnancy miscarriage rates (P=0.28), early miscarriage rates (P=0.16), and late miscarriage rates (P=0.69) were comparable among 4 groups. In addition, there were no significant differences in maternal and infant complications.

Conclusion:
The pregnancy outcomes of frozen-embryo transfer among 4 endometrial preparation protocols in patients with adenomyosis and thin endometrium were comparable, indicating no significant disparities. In addition, no noteworthy variations were observed in terms of maternal and infant complications in these patients.
The role of postoperative piriformis fossa and greater trochanter tubercle distance to predict cutout failure after cephalomedullary nail fixation
Authors: Tien Derming , Chang Wen-Chieh , Cheng Ming-Fai , Hsu Kuei-Hsiang , Su Yu-Ping 
Published: December 2023

Background:
This study investigated the association between postoperative piriformis fossa and greater trochanter tubercle distance (distance from the deepest point of piriformis fossa to the most lateral greater trochanter tubercle [PG]) and cutout failure after cephalomedullary nail (CMN) osteosynthesis for intertrochanter fracture (ITF). A rotating femur model was designed to analyze PG variation during femur rotation.

Methods:
From 2005 to 2010, 311 patients diagnosed of ITF (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association [AO/OTA] 31-A2 and A3) underwent CMN fixation at our institute were reviewed. Of these, 281 (90.3%) patients achieved union without complication, 21 (6.8%) had cutout failure, six (1.9%) had femoral head osteonecrosis, and three (1%) had nonunion during postoperative 2-year follow-up. The side difference of postoperative PG compared to contralateral uninjured hip (dPG) was analyzed between patients who had cutout failure and those who did not. In the rotating femur model, the PG was measured for every 2.5° increments of internal and external rotation from 0° to 50°.

Results:
The dPG was significantly higher in the failure group (10.2 ± 4.2 vs 6.6 ± 3.5 mm, p <0.001). The odds ratio for lag screw cutout was 6.35 (95% CI, 1.10-11.6, p =0.003) for every 1 mm dPG increment. dPG exhibited high diagnostic performance in predicting cutout failure according to receiver operating characteristic curve analysis. The area under the curve was 0.774 (95% CI, 0.711-0.837). dPG yielded the greatest sensitivity (78.4%) and specificity (78.4%) to predict lag screw cutout when cutoff value being 8.65 mm. In rotating femur model, PG change from baseline demonstrated significant (p <0.001) positive and negative correlation with increased external and internal rotation, respectively.

Conclusion:
Increased dPG is a risk factor of cutout failure for ITF osteosynthesis with CMN. In conjunction with tip-apex distance, fracture displacement, and reduction quality; dPG can help surgeons interpret postoperative radiograph and predict failure. However, it should be noticed that a proper and standard patient positioning is critical for accurate dPG measurement.
The percentage of unnecessary mastectomy due to false size prediction using preoperative ultrasonography and MRI in breast cancer patients who underwent neoadjuvant chemotherapy: a prospective cohort study
Authors: Han Yireh , Jung Ji Gwang , Kim Jang-il , Lim Changjin , Kim Hong-Kyu , Lee Han-Byoel , Moon Hyeong-Gon , Han Wonshik 
Published: December 2023

Background:
Imaging-estimated tumour extent after neoadjuvant chemotherapy tends to be discordant with the pathological extent. The authors aimed to prospectively determine the proportion of decisions regarding total mastectomy for potential breast-conserving surgery candidates owing to false size prediction with imaging in neoadjuvant chemotherapy and non-neoadjuvant chemotherapy patients.

Materials and methods:
The authors prospectively enroled clinical stage II or III breast cancer patients who are scheduled for total mastectomy between 2018 and 2021. This study was conducted at Seoul National University Hospital at South Korea. Before surgery, each surgeon recorded the hypothetical maximum tumour size at which the surgeon would have been able to attempt breast-conserving surgery if the patient had actually less than the size of the tumour at that location in the breast. After surgery, the hypothetical maximum tumour size was compared with the final pathologic total extent of the tumour, including invasive and in situ cancers.

Results:
Among the 360 enroled patients, 130 underwent neoadjuvant chemotherapy, and 230 did not undergo neoadjuvant chemotherapy. Of the total of each group, 47.7% in the neoadjuvant chemotherapy group and 21.3% in the non-neoadjuvant chemotherapy group had a smaller pathologic tumour extent than the pre-recorded hypothetical maximum tumour size (P<0.001). Further analyses were conducted for the neoadjuvant chemotherapy group. The proportions of total mastectomy with false size prediction were higher in HER2-positive (63.3%) and triple-negative (57.6%) patients compared with ER-positive/HER2-negative (25.0%) patients (P<0.001). Both magnetic resonance imaging-pathology and ultrasonography-pathology size discrepancies were significantly associated with false decisions for total mastectomy (both P<0.001). Without magnetic resonance imaging, the false decision may be reduced by 21.5%.

Conclusion:
A total of 47.7% of patients who received total mastectomy after neoadjuvant chemotherapy were breast-conserving surgery eligible, which was significantly higher than that of non-neoadjuvant chemotherapy patients. Magnetic resonance imaging contributed the most to false size predictions.
Bempedoic acid: a new player for statin-intolerant patients and beyond
Authors: Giordano Salvatore , Spaccarotella Carmen Anna Maria , Esposito Giovanni , Indolfi Ciro 
Published: December 2023

Purpose of review
Low-density lipoproteins (LDL) cause atherosclerotic cardiovascular disease, a condition associated with significant morbidity and mortality. Statins represent the cornerstone for preventing cardiovascular events in patients with elevated LDL-cholesterol (LDL-C) levels, however, they are associated with frequent musculoskeletal adverse effects, which lead to drug discontinuation or limit their use to low (and less effective) doses. Bempedoic acid (BA) is a newly approved, safe, cholesterol-lowering agent that inhibits ATP-citrate lyase, an enzyme upstream to 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the target of statins. Unlike statins, BA is not associated with musculoskeletal side effects, representing a promising drug for statin-intolerant patients. This review aims to summarize the current evidence on the efficacy, safety, and impact on clinical outcomes of BA, to review current indications for its use, and to highlight the ongoing clinical trials that will help deepen our knowledge of this promising compound.

Recent findings
BA improves clinical outcomes in statin-intolerant patients. Multiple ongoing studies are evaluating whether BA can be employed in other clinical settings.

Summary
BA safely and effectively reduces the levels of multiple atherogenic markers and can be employed to reach LDL-C targets independently from statin tolerance.
Pancreatic cystic neoplasms: a comprehensive approach to diagnosis and management
Authors: Parray Amir M. , Singh Anoop , Chaudhari Vikram , Supe Avinash 
Published: December 2023

Abstract
Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low- and high-grade malignancies. Their prevalence varies widely, notably increasing with age, reaching 75% in individuals older than 80 years. Accurate diagnosis is crucial, as errors occur in approximately one-third of resected cysts discovered incidentally. Various imaging modalities such as computed tomography, magnetic resonance imaging, and endoscopic techniques are available to address this challenge. However, risk stratification remains problematic, with guideline inconsistencies and diagnostic accuracy varying according to cyst type. This review proposed a stepwise management approach, considering patient factors, imaging results, and specific features. This patient-centered model offers a structured framework for optimizing the care of individuals with pancreatic cystic neoplasms.
Immunotherapy for mucosal melanoma
Authors: Du Yu , Bai Xue , Si Lu 
Published: December 2023

Abstract
Mucosal melanoma (MM) is extremely rare in Caucasians, whereas it is the second predominant melanoma subtype in Asian and other non-Caucasian populations. Distinct from cutaneous melanoma in terms of epidemiology, biology, and molecular characteristics, MM is characterized by more aggressive biological behavior, lower mutational burden, more chromosomal structure variants, and poorer prognosis. Because of the rarity of MM, its biological features are not fully understood, and potential novel therapies are less well depicted. Whereas immunotherapy has shown encouraging efficacy for cutaneous melanoma, its efficacy in MM is unclear due to limited sample sizes in clinical trials. Thus, in this review, we describe the epidemiological, clinical, and molecular features of MM and summarize the efficacies of different immunotherapies for MM, including immune checkpoint inhibitors, vaccines, oncolytic virus therapy, adoptive T-cell therapy, and various combination therapies.
Utilizing bioinformatics for integrated analysis of multiple genes in the diagnosis and pathogenesis of metastatic pheochromocytoma and paraganglioma
Authors: Zhang Chun-Lei , Wang Rui , Li Fo-Rong , Chang De-Hui 
Published: December 2023

Abstract

Objective
The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas (PPGLs).

Methods
Data were collected from GEO datasets GSE67066 and GSE60458. The R software and various packages were utilized for the analysis of differentially expressed genes, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, receiver operating characteristic curve assessment, logistic model construction, and correlation analysis. The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks. In addition, the TIMER database was used to estimate the immune scores.

Results
A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458, respectively. These genes are implicated in cytokine and cytokine receptor interactions, extracellular matrix–receptor interactions, and platelet activation signaling pathways. Notably, MAMLD1, UST, MATN2, LPL, TWIST1, SFRP4, FRMD6, RBM24, PRIMA1, LYPD1, KCND2, CAMK2N1, SPOCK3, and ALPK3 were identified as the key genes. Among them, MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers, whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration. Eight miRNAs were identified as potential regulators of key gene expression, and it was noted that TWIST1 might be regulated by SUZ12. Notably, the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.

Conclusions
The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential. These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.
A Teenage Boy With a Radiation-Induced High-Grade Astrocytoma
Authors: Louis-Gray Kathleen , Khanna Sangeeta , Camelo-Piragua Sandra , Capizzano Aristides A. , Trobe Jonathan D. , Robertson Patricia L. , Foroozan Rod , Mohila Carrie A. 
Published: December 2023

Abstract:
A 12-year-old boy developed acute headache and vomiting. MRI brain showed a partially cystic suprasellar mass. He underwent cyst fenestration, but the cyst regrew, so he underwent transcranial subtotal resection of the mass. The pathologic diagnosis was adamantinomatous craniopharyngioma. Residual tumor was treated with proton beam radiation therapy, and panhypopituitarism was treated with hormone replacement therapy, including growth hormone. Serial brain MRI scans over several years showed no evidence of tumor recurrence. But at four years after radiation, surveillance MRI showed a new focus of nonenhancing FLAIR hyperintensity in the left basal ganglia attributed to gliosis caused by radiotherapy. Seven months later, he developed progressive right hemiparesis, expressive aphasia, and blurred vision, prompting reevaluation. MRI brain showed new enhancing and T2/FLAIR hyperintense lesions in the midbrain, basal ganglia, thalamus, anterior temporal lobe, and optic tract. The abnormal regions showed low diffusivity and relatively high regional blood flow. Stereotactic biopsy disclosed a WHO Grade 4 astrocytoma, likely radiation-induced. A germline ataxia telangiectasia mutation was found in the tumor tissue. The risk of radiation-induced pediatric brain malignancies is low but may have been increased by the mutation.
Tissue-Specific Dose Equivalents of Secondary Mesons and Leptons during Galactic Cosmic Ray Exposures for Mars Exploration
Authors: Pak Sungmin , Cucinotta Francis A. 
Published: December 2023

AbstractDuring a human mission to Mars, astronauts would be continuously exposed to galactic cosmic rays (GCRs) consisting of high energy protons and heavier ions coming from outside our solar system. Due to their high energy, GCR ions can penetrate spacecraft and space habitat structures, directly reaching human organs. Additionally, they generate secondary particles when interacting with shielding materials and human tissues. Baryon secondaries have been the focus of many previous studies, while meson and lepton secondaries have been considered to a much lesser extent. In this work, we focus on assessing the tissue-specific dose equivalents and the effective dose of secondary mesons and leptons for the interplanetary cruise phase and the surface phase on Mars. We also provide the energy distribution of the secondary pions in each human organ since they are dominant compared to other mesons and leptons. For this calculation, the PHITS3.27 Monte Carlo simulation toolkit is used to compute the energy spectra of particles in organs in a realistic human phantom. Based on the simulation data, the dose equivalent has been estimated with radiation quality factors in ICRP Publication 60 and in the latest NASA Space Cancer Risk model (NSCR-2022). The effective dose is then assessed with the tissue weighting factors in ICRP Publication 103 and in the NSCR model, separately. The results indicate that the contribution of secondary mesons and leptons to the total effective dose is 6.173%, 9.239%, and 11.553% with the NSCR model in interplanetary space behind 5, 20, and 50 g/cm2aluminum shielding, respectively with similar values using the ICRP model. The outcomes of this work lead to an improved understanding of the potential health risks induced by secondary particles for exploration missions to Mars and other destinations.
ProtPipe: A Multifunctional Data Analysis Pipeline for Proteomics and Peptidomics
Authors: Li Ziyi , Weller Cory A. , Shah Syed , Johnson Nicholas , Hao Ying , Roberts Jessica , Bereda Colleen , Klaisner Sydney , Machado Pedro , Fratta Pietro , Petrucelli Leonard , Prudencio Mercedes , Oskarsson Björn , Staff Nathan P. , Dickson Dennis W. , Cookson Mark R. , Ward Michael E. , Singleton Andrew B. , Nalls Mike A. , Qi Yue A. 
Published: December 2023

AbstractMass spectrometry (MS) is a technique widely employed for the identification and characterization of proteins, personalized medicine, systems biology and biomedical applications. By combining MS with different proteomics approaches such as immunopurification MS, immunopeptidomics, and total protein proteomics, researchers can gain insights into protein-protein interactions, immune responses, cellular processes, and disease mechanisms. The application of MS-based proteomics in these areas continues to advance our understanding of protein function, cellular signaling, and complex biological systems. Data analysis for mass spectrometry is a critical process that includes identifying and quantifying proteins and peptides and exploring biological functions for these proteins in downstream analysis. To address the complexities associated with MS data analysis, we developed ProtPipe to streamline and automate the processing and analysis of high-throughput proteomics and peptidomics datasets. The pipeline facilitates data quality control, sample filtering, and normalization, ensuring robust and reliable downstream analysis. ProtPipe provides downstream analysis including identifying differential abundance proteins and peptides, pathway enrichment analysis, protein-protein interaction analysis, and MHC1-peptide binding affinity. ProtPipe generates annotated tables and diagnostic visualizations from statistical postprocessing and computation of fold-changes across pairwise conditions, predefined in an experimental design. ProtPipe is well-documented open-source software and is available athttps://github.com/NIH-CARD/ProtPipe, accompanied by a web interface.
Protein language model-guided engineering of an anti-CRISPR protein for precise genome editing in human cells
Authors: Marsiglia Julia , Vaalavirta Kia , Knight Estefany , Nakamura Muneaki , Cong Le , Hughes Nicholas W. 
Published: December 2023

AbstractPromiscuous editing by CRISPR/Cas systems within the human genome is a major challenge that must be addressed prior to applying these systems therapeutically. In bacteria, CRISPR/Cas systems have evolved in a co-evolutionary arms race with infectious phage viruses that contain inhibitory anti-CRISPR proteins within their genomes. Here, we harness the outcome of this co-evolutionary arms race to engineer an AcrIIA4 anti-CRISPR protein to increase the precision of CRISPR/Cas-based genome targeting. We developed an approach that specifically leveraged (1) protein language models, (2) deep mutational scanning, and (3) highly parallel DNA repair measurements within human cells. In a single experiment, ∼10,000 AcrIIA4 variants were tested to identify lead AcrIIA4 variants that eliminated detectable off-target editing events while retaining on-target activity. The candidates were further tested in a focused round of screening that included a high-fidelity version of Cas9 as a benchmark. Finally, arrayed experiments using Cas9 delivered as ribonucleoprotein were conducted that demonstrated an increase in gene editing precision across two independent genomic loci and a reduction in the frequency of translocation events between an on-target and off-target site. Thus, language-model-guided high-throughput screening is an effective way to efficiently engineer AcrIIA4 to increase gene editing precision, which could be used to improve the fidelity of gene editing-based therapeutics and to reduce genotoxicity.
Design of a Computational Intelligence System for Detection of Multiple Sclerosis with Visual Evoked Potentials
Authors: Mohsenpourian Moussa , Suratgar Amir Abolfazl , Talebi Heidar Ali , Arzani Mahsa , Moghadasi Abdorreza Naser , Moghaddam Fariba , Malakouti Seyed Matin , Menhaj Mohammad Bagher 
Published: December 2023

AbstractIn this study, a new approach for modification of membership functions of a fuzzy inference system (FIS) is demonstrated, in order to serve as a pattern recognition tool for classification of patients diagnosed with multiple sclerosis (MS) from healthy controls (HC) using their visually evoked potential (VEP) recordings. The new approach utilizes Krill Herd (KH) optimization algorithm to modify parameters associated with membership functions of both inputs and outputs of an initial Sugeno-type FIS, while making sure that the error corresponding to training of the network is minimized.This novel pattern recognition system is applied for classification of VEP signals in 11 MS patients and 11 HC’s. A feature extraction routine was performed on the VEP signals, and later substantial features were selected in an optimized feature subset selection scheme employing Ant Colony Optimization (ACO) and Simulated Annealing (SA) algorithms. This alone provided further information regarding clinical value of many previously unused VEP features as an aide for making the diagnosis. The newly designed computational intelligence system is shown to outperform popular classifiers (e.g., multilayer perceptron, support-vector machine, etc.) and was able to distinguish MS patients from HC’s with an overall accuracy of 90%.
Neurexins control the strength and precise timing of glycinergic inhibition in the auditory brainstem
Authors: Jiang He-Hai , Xu Ruoxuan , Nie Xiupeng , Su Zhenghui , Xu Xiaoshan , Pang Ruiqi , Zhou Yi , Luo Fujun 
Published: December 2023

AbstractNeurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are involved in shaping functional properties of the glycinergic synapses, which mediate prominent inhibition in the brainstem and spinal cord. To address these issues, we examined the role of neurexins in a model glycinergic synapse between the principal neuron in the medial nucleus of the trapezoid body (MNTB) and the principal neuron in the lateral superior olive (LSO) in the auditory brainstem. Combining RNAscope with stereotactic injection of AAV-Cre in the MNTB of neurexin1/2/3 conditional triple knockout mice, we showed that MNTB neurons highly express all isoforms of neurexins although their expression levels vary remarkably. Selective ablation of all neurexins in MNTB neurons not only reduced the amplitude but also altered the kinetics of the glycinergic synaptic transmission at LSO neurons. The synaptic dysfunctions primarily resulted from an impaired Ca2+sensitivity of release and a loosened coupling between voltage-gated Ca2+channels and synaptic vesicles. Together, our current findings demonstrate that neurexins are essential in controlling the strength and temporal precision of the glycinergic synapse, which therefore corroborates the role of neurexins as key presynaptic organizers in all major types of fast chemical synapses.