bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Cochlear Implant Fitting by Machine Learning Techniques
Authors: Koyama Hajime , Kashio Akinori , Yamasoba Tatsuya 
Published: May 2024

Objective
This study aimed to evaluate the differences in electrically evoked compound action potential (ECAP) thresholds and postoperative mapping current (T) levels between electrode types after cochlear implantation, the correlation between ECAP thresholds and T levels, and the performance of machine learning techniques in predicting postoperative T levels.

Study Design
Retrospective case review.

Setting
Tertiary hospital.

Patients
We reviewed the charts of 124 ears of children with severe-to-profound hearing loss who had undergone cochlear implantation.

Interventions
We compared ECAP thresholds and T levels from different electrodes, calculated correlations between ECAP thresholds and T levels, and created five prediction models of T levels at switch-on and 6 months after surgery.

Main Outcome Measures
The accuracy of prediction in postoperative mapping current (T) levels.

Results
The ECAP thresholds of the slim modiolar electrodes were significantly lower than those of the straight electrodes on the apical side. However, there was no significant difference in the neural response telemetry thresholds between the two electrodes on the basal side. Lasso regression achieved the most accurate prediction of T levels at switch-on, and the random forest algorithm achieved the most accurate prediction of T levels 6 months after surgery in this dataset.

Conclusion
Machine learning techniques could be useful for accurately predicting postoperative T levels after cochlear implantation in children.
Cochlear Implant Outcomes in Patients With TMTC2-Associated Sensorineural Hearing Loss and Auditory Neuropathy/Auditory Dys-Synchrony
Authors: North Lauren , Olivier Michael , Runge Christina L. 
Published: May 2024

Objective
To investigate the outcomes of cochlear implantation in patients with TMTC2-associated sensorineural hearing loss and auditory neuropathy/auditory dys-synchrony.

Patients
Adult and pediatric cochlear implant (CI) patients followed in an academic center who tested positive for TMTC2 genetic variant rs35725509.

Intervention
Cochlear implantation.

Main Outcome Measures
Speech perception scores in quiet.

Results
Ten CI patients were identified with TMTC2 variant rs35725509 out of 157 patients who underwent genetic testing (i.e., 6.3% of patients tested). All demonstrated progressive, bilateral hearing loss with severe-to-profound audiometric thresholds preoperatively. Pre-CI and 1-year post-CI speech recognition percent correct scores were compared. Post-CI speech perception (mean 61.0%, standard deviation 31.4%) was significantly higher than pre-CI speech perception (mean 21.0%, standard deviation 27.0%) (p = 0.002). Individually, 9 of the 10 subjects experienced significant improvements in speech perception pre- to post-CI (p < 0.05). Electrically evoked compound action potential measures were available for five patients, and all showed normal electrically evoked compound action potential thresholds.

Conclusion
Patients with TMTC2-associated sensorineural hearing loss and auditory neuropathy/auditory dys-synchrony have significantly improved speech perception outcomes with cochlear implantation and should be considered candidates for this intervention if there are no other contraindications.
Extracellular Vesicle - MDM2-DNA as a Potential Liquid Biopsy Biomarker for Disease Identification in Retroperitoneal Liposarcoma
Authors: Calore Federica , Casadei Lucia , Sarchet Patricia D. , Fadda Paolo , Nigita Giovanni , Coombes Kevin R. , Cascione Luciano , Costas C. de Faria Fernanda , Tahara Sayumi , Iwenofu O Hans , Pollock Raphael E. , Grignol Valerie P. 
Published: May 2024

Objective:
We aimed to assess the levels of MDM2-DNA within extracellular vesicles (EVs) isolated from the serum of retroperitoneal liposarcoma (RLS) patients versus healthy donors, as well as within the same patients at the time of surgery versus post-operative surveillance visits. To determine whether EV-MDM2 may serve as a possible first-ever biomarker of liposarcoma recurrence.

Background:
A hallmark of well-differentiated and de-differentiated (WD/DD) retroperitoneal liposarcoma is elevated MDM2 due to genome amplification, with recurrence rates of >50% even after complete resection. Imaging technologies frequently cannot resolve recurrent WD/DD-RLS versus postoperative scarring. Early detection of recurrent lesions, for which biomarkers are lacking, would guide surveillance and treatment decisions.

Methods:
WD/DD-RLS serum samples were collected both at the time of surgery and during follow-up visits from 42 patients, along with sera from healthy donors (n=14). EVs were isolated, DNA purified and MDM2-DNA levels determined through q-PCR analysis. Non-parametric tests were employed to compare EV-MDM2 DNA levels from patients versus control group, as well as the time of surgery versus post-surgery conditions.

Results:
EV-MDM2 levels were significantly higher in WD/DD-RLS than controls (P= 0.00085). Moreover, EV-MDM2 levels were remarkably decreased in WD/DD-RLS patients after resection (P=0.00036), reaching values comparable to control group (P=0.124). During post-operative surveillance, significant increases of EV-MDM2 was observed in some patients, correlating with CT scan evidence of recurrent or persistent post-resection disease.

Conclusions:
Serum EV-MDM2 may serve as a potential biomarker of early recurrent or post-operatively persistent WD/DD-RLS, a disease currently lacking such determinants.
Outcomes of Visceral Arterial Interposition Graft Reconstruction for Locally Advanced Pancreatic Cancer
Authors: Yonkus Jennifer A. , Alva-Ruiz Roberto , Colglazier Jill J. , Kendrick Michael L. , Kalra Manju , Rasmussen Todd E. , Demartino Randall D. , Bower Thomas C. , Truty Mark J. , Mendes Bernardo C. 
Published: May 2024

Objective:
The aim of this study is to determine perioperative outcomes and the patency of interposition conduits for visceral arterial reconstruction in this setting.

Summary Background Data:
Visceral arterial encasement in locally advanced pancreatic cancer was historically a contraindication for surgery. With modern effective neoadjuvant strategies, our recent experience has made advanced vascular resection and reconstruction feasible in selected patients.

Methods:
A retrospective review was performed of patients undergoing pancreatic tumor resection with en bloc arterial resection and interposition revascularization between 6/2002-10/2022. Endpoints included graft patency, vascular-related complications, reinterventions, morbidity, and mortality.

Results:
Visceral arterial reconstruction with interposition grafting was performed in 111 patients undergoing en bloc arterial resections for pancreatic cancer. Graft types included autologous arterial conduits (n=66, 58 superficial femoral artery (SFA) and 8 splenic artery), cryopreserved arterial allografts (n=24), autologous saphenous veins (n=12), synthetic conduits (n=8), and composite autologous artery and synthetic (n=1). Perioperative 90-day mortality decreased significantly over time to 5% in the last six years. Vascular complications related to arterial reconstruction occurred in 11% (n=12) and included pseudoaneurysm (n=6), graft thrombus (n=2), stenosis requiring reintervention (n=2), hepatic failure (n=1), and hepatic and intestinal ischemia (n=1). Nine (8%) patients underwent vascular-related reinterventions. After median follow-up of 17-months, primary patency was 81% for the entire cohort and was highest in the SFA group (95%). The donor limb/harvest site complication rate was 8% with 100% primary patency.

Conclusion:
Visceral arterial resection with interposition reconstruction for locally advanced pancreatic cancer can be performed with acceptable vascular morbidity and durable patency. Autologous SFA was the most suitable conduit for reconstructions in our experience, with highest primary patency.
Percent Thrombus Predicts Popliteal Artery Aneurysm Related Limb Threatening Events
Authors: Bellomo Tiffany R. , Goudot Guillaume , Lella Srihari K. , Gaston Brandon , Sumetsky Natalie , Patel Shiv , Zacharias Nikolaos , Dua Anahita 
Published: May 2024

Objective:
The objective of this study was to identify clinical and anatomic characteristics of Popliteal artery aneurysms (PAAs) associated with acutely limb threatening events.

Summary Background Data:
Popliteal artery aneurysms (PAAs) are associated with high morbidity and mortality. Current guidelines recommend operative repair for PAAs with a diameter greater than 20 mm based on very limited evidence.

Methods:
This retrospective cross-sectional cohort was derived from a multi-institutional database queried for all patients with a PAA from 2008 to 2022. Duplex ultrasound (DUS) characteristics of PAAs were abstracted by registered physicians in vascular interpretation. Symptom status at the time of DUS was divided into three categories: asymptomatic PAA, symptomatic PAA with claudication or chronic limb ischemia, and acutely limb threatening PAAs with a thromboembolic event, acute limb ischemia, or rupture.

Results:
There were 470 PAAs identified in 331 patients. The mean age was 74 years at diagnosis, 94% of patients were white, and 97% of patients were male. In a univariate analysis, patient comorbidities and medications were not associated with symptom status. In a multivariate analysis including age, higher percent thrombus was significantly associated with symptomatic PAAs (RRR 15.2; CI 2.69-72.3; P<0.01) and PAAs with an acutely limb threatening event (RRR 17.9; CI 3.76-85.0; P<0.01). All other anatomic characteristics were not associated with symptom status.

Conclusion:
Percent thrombus was significantly associated with symptomatic PAAs and acutely limb threatening events, whereas diameter was not significantly associated with any symptom group. This analysis supports the use of percent thrombus in identifying high risk PAAs that warrant repair.
iSeq: An integrated tool to fetch public sequencing data
Authors: Chao Haoyu , Li Zhuojin , Chen Dijun , Chen Ming 
Published: May 2024

AbstractHigh-throughput sequencing technologies (Next Generation Sequencing; NGS) are increasingly utilized by researchers to tackle a diverse array of biological inquiries. Leveraging the remarkable scale and efficiency of modern sequencing, significant advancements are made across various fields, spanning from genome analysis to the intricate dynamics of protein-nucleic acid interactions. Recognizing that NGS data harbors rich biological information, the International Nucleotide Sequence Database Collaboration (INSDC) was established nearly 40 years ago to collect and disseminate public nucleotide sequence data and associated metadata. The National Genomics Data Center (NGDC) has also provided open access to vast amounts of raw sequence data. These databases have greatly enhanced the capacity for reanalyzing NGS data. In recent years, amid the rise of large language models, biological sequences and data have emerged as inputs for training models to address biological challenges. However, methods for programmatically accessing this public sequencing data remain limited. To address this gap, we have developed iSeq, an integrated tool that allows for quick and straightforward retrieval of metadata and NGS data via the command-line interface. iSeq is currently the only tool that supports simultaneous retrieval from multiple databases (GSA, SRA, ENA, DDBJ, and GEO). Additionally, iSeq supports a wide range of accession formats as input and features parallel downloads, multi-threaded processes, and FASTQ file merging. It is freely available on Bioconda (https://anaconda.org/bioconda/iseq) and GitHub (https://github.com/BioOmics/iSeq).HighlightsiSeq supports multiple databases for accessing a wide range of raw sequencing data and metadata.iSeq supports at least 25 different accession formats as input.iSeq supports parallel downloads, multi-threaded processes, FASTQ file merging, and integrity verification.
Targeting mitochondrial metabolism with CPI-613 in chemoresistant ovarian tumors
Authors: Udumula Mary P , Rashid Faraz , Singh Harshit , Pardee Tim , Luther Sanjeev , Bhardwaj Tanya , Anjaly Km , Piloni Sofia , Hijaz Miriana , Gogoi Radhika , Philip Philip A , Munkarah Adnan R , Giri Shailendra , Rattan Ramandeep 
Published: May 2024

AbstractBackgroundThere is evidence indicating that chemoresistance in tumor cells is mediated by the reconfiguration of the tricarboxylic acid cycle, leading to heightened mitochondrial activity and oxidative phosphorylation (OXPHOS). Previously, we have shown that ovarian cancer cells that are resistant to chemotherapy display increased OXPHOS, mitochondrial function, and metabolic flexibility. To exploit this weakness in chemoresistant ovarian cancer cells, we examined the effectiveness of the mitochondrial inhibitor CPI-613 in treating preclinical ovarian cancer.MethodsChemosensitive OVCAR3, and chemoresistant CAOV3 and F2 ovarian cancer cells lines and their xenografts in nude mice were used. Functional metabolic studies were performed using Seahorse instrument. Metabolite quantification was performed using LC/MS/MS.ResultsMice treated with CPI-613 exhibited a notable increase in overall survival and a reduction in tumor development and burden in OVCAR3, F2, and CAOV3 xenografts. CPI-613 suppressed the activity of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complex, which are two of its targets. This led to a reduction in OXPHOS and tricarboxylic acid cycle activity in all 3 xenografts. The addition of CPI-613 enhanced the responsiveness of chemotherapy in the chemoresistant F2 and CAOV3 tumors, resulting in a notable improvement in survival rates and a reduction in tumor size as compared to using chemotherapy alone. CPI-613 reduced the chemotherapy-induced OXPHOS in chemoresistant tumors. The study revealed that the mechanism by which CPI-613 inhibits tumor growth is through mitochondrial collapse. This is evidenced by an increase in superoxide production within the mitochondria, a decrease in ATP generation, and the release of cytochrome C, which triggers mitochondria-induced apoptosis. Our study demonstrates the translational potential of CPI-613 against chemoresistant ovarian tumors.
Spatial Transcriptomics Reveals Spatially Diverse Cancer-Associated Fibroblast in Lung Squamous Cell Carcinoma Linked to Tumor Progression
Authors: Choi Hongyoon , Na Kwon Joong , Jung Yeonjae , Lim Myunghyun , Lee Dongjoo , Lee Jae Eun , Im Hyung-Jun , Lee Daeseung , Koh Jaemoon , Kim Young Tae 
Published: May 2024

AbstractWhile cancer-associated fibroblasts (CAFs) are crucial in influencing tumor growth and immune responses in lung cancer, we still lack a comprehensive understanding of their spatial organization associated with tumor progression and clinical outcomes. This gap highlights the need to elucidate how the intricate spatial arrangement of CAFs affects their interactions within the tumor microenvironment, ultimately shaping cancer progression and patient prognosis. Here, we unveil the spatial diversity of CAFs in lung squamous cell carcinoma (LUSC), a prevalent and aggressive lung cancer type, elucidating their impact on tumor progression and patient outcomes using spatial transcriptomics (ST). Image-based ST data from 33 LUSC patients demonstrated a significant association of spatial interactions of tumor epithelium and CAFs with tumor size and metabolic activity measured by [18F]fluorodeoxyglucose PET. Furthermore, the proximity of fibroblasts to tumor epithelial cells was linked to recurrence-free survival in LUSC patients. By characterizing CAFs based on their spatial relationship, we identified distinct molecular signatures related to spatially distinct fibroblast subpopulations. In addition, barcode-based ST data from 8 LUSC patients revealed spatially overlapping fibroblast regions characterized by upregulated glycolysis pathways. Our study underscores the importance of the complex spatial dynamics of the tumor microenvironment revealed by ST and its implications for patient outcomes in LUSC.
FoodAtlas: Automated Knowledge Extraction of Food and Chemicals from Literature
Authors: Youn Jason , Li Fangzhou , Simmons Gabriel , Kim Shanghyeon , Tagkopoulos Ilias 
Published: May 2024

AbstractAutomated generation of knowledge graphs that accurately capture published information can help with knowledge organization and access, which have the potential to accelerate discovery and innovation. Here, we present an integrated pipeline to construct a large-scale knowledge graph using large language models in an active learning setting. We apply our pipeline to the association of raw food, ingredients, and chemicals, a domain that lacks such knowledge resources. By using an iterative active learning approach of 4,120 manually curated premise-hypothesis pairs as training data for ten consecutive cycles, the entailment model extracted 230,848 food-chemical composition relationships from 155,260 scientific papers, with 106,082 (46.0%) of them never been reported in any published database. To augment the knowledge incorporated in the knowledge graph, we further incorporated information from 5 external databases and ontology sources. We then applied a link prediction model to identify putative food-chemical relationships that were not part of the constructed knowledge graph. Validation of the 443 hypotheses generated by the link prediction model resulted in 355 new food-chemical relationships, while results show that the model score correlates well (R2= 0.70) with the probability of a novel finding. This work demonstrates how automated learning from literature at scale can accelerate discovery and support practical applications through reproducible, evidence-based capture of latent interactions of diverse entities, such as food and chemicals.
iLipidome: enhancing statistical power and interpretability using hidden biosynthetic interdependencies in the lipidome
Authors: Lin Wen-Jen , Chiang Austin W.T. , Zhou Evanston H. , Liang Chenguang , Liu Chia-Hsin , Ma Wen-Lung , Cheng Wei-Chung , Lewis Nathan E. 
Published: May 2024

AbstractNumerous biological processes and diseases are influenced by lipid composition. Advances in lipidomics are elucidating their roles, but analyzing and interpreting lipidomics data at the systems level remain challenging. To address this, we present iLipidome, a method for analyzing lipidomics data in the context of the lipid biosynthetic network, thus accounting for the interdependence of measured lipids. iLipidome enhances statistical power, enables reliable clustering and lipid enrichment analysis, and links lipidomic changes to their genetic origins. We applied iLipidome to investigate mechanisms driving changes in cellular lipidomes following supplementation of docosahexaenoic acid (DHA) and successfully identified the genetic causes of alterations. We further demonstrated how iLipidome can disclose enzyme-substrate specificity and pinpoint prospective glioblastoma therapeutic targets. Finally, iLipidome enabled us to explore underlying mechanisms of cardiovascular disease and could guide the discovery of early lipid biomarkers. Thus, iLipidome can assist researchers studying the essence of lipidomic data and advance the field of lipid biology.
Zinc finger transcription factorsBnaSTOP2sregulate sulfur metabolism and confer resistance toSclerotinia sclerotioruminBrassica napus
Authors: Dai Lihong , Xie Zhaoqi , Ai Tianxu , Jiao Yushun , Lian Xiaoyi , Long Angchen , Zhang Jinyun , Yang Guangsheng , Hong Dengfeng 
Published: May 2024

ABSTRACTRapeseed (Brassica napusL.) has a high sulfur requirement for optimal growth, development, and pathogen resistance. In this study, we identified zinc finger transcription factors,BnaSTOP2s, that play key roles in sulfur metabolism andSclerotinia sclerotiorumresistance. First, our results suggested thatBnaSTOP2sare involved in sulfur as evidenced from extensive protein interaction screening. Knockout ofBnaSTOP2sreduced the response sensitivity in both sulfur-deficient and sulfur-excessive conditions by promoting the elongation of primary roots of seedlings. Furthermore, the content of essential sulfur-containing metabolites, including glucosinolate and glutathione, were substantially down-regulated in roots and leaves ofBnastop2mutants, which is consistent with the significantly lowered transcriptional levels of key players of GSL synthesis and transportation,BnaMYB28sandBnaGTR2s, respectively. Through comprehensive RNA-seq analysis, we revealed the substantial effect ofBnaSTOP2son sulfur metabolism from source to sink. Additionally, we observed a significant decrease while increase in leaf lesion sizes of theBnaSTOP2-OE andBnastop2mutants, respectively, when compared to the wild type duringSclerotinia sclerotioruminfection, suggesting the vital role ofBnaSTOP2in plant defense response. Overall, our findings highlight thatBnaSTOP2sseems to be global regulators of sulfur metabolism and confer resistance toSclerotinia sclerotioruminfection inB. napus.
Small but mitey: long-read assembly of a streamlined mite genome from contaminated host plant sequencing data
Authors: Chen Stephanie H , Jones Ashley , Lu-Irving Patricia , Yap Jia-Yee S , van der Merwe Marlien , Bragg Jason G , Edwards Richard J 
Published: May 2024

AbstractTechnological advances have propelled DNA sequencing of non-model organisms, making sequencing more accessible and cost effective, which has also increased the availability of raw data in public repositories. However, contamination is a significant concern, and the use and reuse of sequencing data requires quality control and curation. A reference genome for the Australian native rainforest treeRhodamnia argenteaBenth. (malletwood) was assembled from Oxford Nanopore Technologies (ONT) long-reads, 10x Genomics Chromium linked-reads, and Hi-C data (N50 = 32.3 Mbp and BUSCO completeness 98.0%) with 99.0% of the 347 Mbp assembly anchored to 11 chromosomes (2n= 22). TheR.argenteagenome will inform conservation efforts for Myrtaceae species threatened by the global spread of the fungal disease myrtle rust. We observed contamination in the sequencing data and further investigation revealed an arthropod source. Here, we demonstrate the feasibility of assembling a high-quality gapless telomere-to-telomere mite genome using contaminated host plant sequencing data. The mite exhibits genome streamlining and has a 35 Mbp genome (68.6% BUSCO completeness) on two chromosomes, capped with a novel TTTGG telomere sequence. Phylogenomic analysis suggests that it is a previously unsequenced eriophyoid mite. Despite its unknown identity, this complete nuclear genome provides a valuable resource to investigate invertebrate genome reduction. This study emphasises the importance of checking sequencing data for contamination, especially when working with non-model organisms. It also enhances our understanding of two species, including a tree that faces substantial conservation challenges, contributing to broader biodiversity initiatives.SignificanceThe genomes ofRhodamnia argenteaand an associated eriophyoid mite, which contaminated the tree raw sequencing data, were assembled for the first time. We generated valuable chromosome-level genomic resources for the conservation of myrtle rust impacted tree species, pest genomics, and understanding genome streamlining. The research underscores the growing prevalence of sequencing experiments in non-model organisms while emphasising the importance of quality control and curation of sequencing data.