bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoplastic cell enrichment of tumor tissues using coring and laser microdissection for proteomic and genomic analyses of pancreatic ductal adenocarcinoma
Authors: Li Qing Kay , Hu Yingwei , Chen Lijun , Schnaubelt Michael , Cui Zhou Daniel , Li Yize , Lu Rita Jui-Hsien , Thiagarajan Mathangi , Hostetter Galen , Newton Chelsea J. , Jewell Scott D. , Omenn Gil , Robles Ana I. , Mesri Mehdi , Bathe Oliver F. , Zhang Bing , Ding Li , Hruban Ralph H. , Chan Daniel W. , Zhang Hui 
Published: October 2022

Abstract
Background
The identification of differentially expressed tumor-associated proteins and genomic alterations driving neoplasia is critical in the development of clinical assays to detect cancers and forms the foundation for understanding cancer biology. One of the challenges in the analysis of pancreatic ductal adenocarcinoma (PDAC) is the low neoplastic cellularity and heterogeneous composition of bulk tumors. To enrich neoplastic cells from bulk tumor tissue, coring, and laser microdissection (LMD) sampling techniques have been employed. In this study, we assessed the protein and KRAS mutation changes associated with samples obtained by these enrichment techniques and evaluated the fraction of neoplastic cells in PDAC for proteomic and genomic analyses.

Methods
Three fresh frozen PDAC tumors and their tumor-matched normal adjacent tissues (NATs) were obtained from three sampling techniques using bulk, coring, and LMD; and analyzed by TMT-based quantitative proteomics. The protein profiles and characterizations of differentially expressed proteins in three sampling groups were determined. These three PDACs and samples of five additional PDACs obtained by the same three sampling techniques were also subjected to genomic analysis to characterize KRAS mutations.

Results
The neoplastic cellularity of eight PDACs ranged from less than 10% to over 80% based on morphological review. Distinctive proteomic patterns and abundances of certain tumor-associated proteins were revealed when comparing the tumors and NATs by different sampling techniques. Coring and bulk tissues had comparable proteome profiles, while LMD samples had the most distinct proteome composition compared to bulk tissues. Further genomic analysis of bulk, cored, or LMD samples demonstrated that KRAS mutations were significantly enriched in LMD samples while coring was less effective in enriching for KRAS mutations when bulk tissues contained a relatively low neoplastic cellularity.

Conclusions
In addition to bulk tissues, samples from LMD and coring techniques can be used for proteogenomic studies. The greatest enrichment of neoplastic cellularity is obtained with the LMD technique.
The resistomes of Mycobacteroides abscessus complex and their possible acquisition from horizontal gene transfer
Authors: Chong Shay Lee , Tan Joon Liang , Ngeow Yun Fong 
Published: October 2022

Abstract
Background
Mycobacteroides abscessus complex (MABC), an emerging pathogen, causes human infections resistant to multiple antibiotics. In this study, the genome data of 1,581 MABC strains were downloaded from NCBI database for phylogenetic relatedness inference, resistance profile identification and the estimation of evolutionary pressure on resistance genes in silico.

Results
From genes associated with resistance to 28 antibiotic classes, 395 putative proteins (ARPs) were identified, based on the information in two antibiotic resistance databases (CARD and ARG-ANNOT). The ARPs most frequently identified in MABC were those associated with resistance to multiple antibiotic classes, beta-lactams and aminoglycosides. After excluding ARPs that had undergone recombination, two ARPs were predicted to be under diversifying selection and 202 under purifying selection. This wide occurrence of purifying selection suggested that the diversity of commonly shared ARPs in MABC have been reduced to achieve stability. The unequal distribution of ARPs in members of the MABC could be due to horizontal gene transfer or ARPs pseudogenization events. Most (81.5%) of the ARPs were observed in the accessory genome and 72.2% ARPs were highly homologous to proteins associated with mobile genetic elements such as plasmids, prophages and viruses. On the other hand, with TBLASTN search, only 18 of the ARPs were identified as pseudogenes.

Conclusion
Altogether, our results suggested an important role of horizontal gene transfer in shaping the resistome of MABC.
Genome-associations of extended-spectrum ß-lactamase producing (ESBL) or AmpC producing E. coli in small and medium pig farms from Khon Kaen province, Thailand
Authors: Pires João , Huber Laura , Hickman Rachel A. , Dellicour Simon , Lunha Kamonwan , Leangapichart Thongpan , Jiwakanon Jatesada , Magnusson Ulf , Sunde Marianne , Järhult Josef D. , Van Boeckel Thomas P. 
Published: October 2022

AbstractThailand is undergoing rapid intensification of livestock production where small subsistence farms and medium sized commercial farms coexist. In medium farms, antimicrobials are prescribed by a veterinarian, whereas in small farms antimicrobial use remains largely unsupervised. The impact of these differences as well as other farming practices on the emergence and composition of antimicrobial resistance genes (ARGs) remains largely unknown. We analyzed 363 genomes of extended-spectrum ß-lactamase producing (ESBL) and/or AmpC producing Escherichia coli recovered from humans and pigs at small and medium farms from the Khon Kaen province, Thailand. We tested for genome-wide associations to identify links between ARGs, host, and farm size. Pig isolates from small farms were associated with mcr and qnr genes conferring resistance to colistin and fluoroquinolones, respectively. In contrast, pig isolates from medium farms were associated with ARGs conferring resistance to drugs commonly used on medium farms (i.e., streptomycin). ESBL plasmids from small farms co-carried ARGs conferring resistance to critically important antimicrobials more frequently compared to plasmid from medium farms. Frequent ARG combinations included blaCTX-M-55 + qnrS1 (29.8% vs 17.5% in small and medium farms, respectively), blaCTX-M-55 + qnrS1 + mcr-3.19 (5% vs 0%), blaCTX-M-14 + qnrS1 (9.3% vs 6.2%), and blaCTX-M-14 + qnrS1 + mcr-1.1 (3.1% vs 0%). The co-location on plasmids of ARGs conferring resistance to critically important antimicrobials as defined by the World Health Organization is concerning, and actions to curb their spread are urgently needed. Legislation on limiting antimicrobial sales and initiatives to better inform farmers and veterinarians on appropriate antimicrobial usage and farm biosecurity could help reduce antimicrobial use on farms.
Detection of C8/T1 radiculopathy by measuring the root motor conduction time
Authors: Park Dougho , Lee Sang-Eok , Cho Jae Man , Yang Joong Won , Yang Donghoon , Kim Mansu , Kwon Heum Dai 
Published: October 2022

Abstract
Background
Root motor conduction time (RMCT) can noninvasively evaluate the status of the proximal root segment. However, its clinical application remains limited, and wider studies regarding its use are scarce. We aimed to investigate the association between C8/T1 level radiculopathy and RMCT.

Methods
This was a retrospective cross-sectional study. Subjects were extracted from a general hospital’s spine clinic database. A total of 48 C8/T1 root lesions from 37 patients were included, and 48 C8/T1 root levels from control subjects were matched for age, sex, and height. RMCT was measured in the abductor pollicis brevis muscle and the assessment of any delays owing to C8/T1 radiculopathy.

Results
The RMCT of the C8/T1 radiculopathy group was 1.7 ± 0.6 ms, which was significantly longer than that in the control group (1.2 ± 0.8 ms; p = 0.001). The delayed RMCT was independently associated with radiculopathy (adjusted odds ratio, 1.15; 95% confidence interval, 1.06–1.27; p = 0.011) after adjusting for the peripheral motor conduction time, amplitude of median compound motor nerve action potential, and shortest F-wave latency. The area under the Receiver Operating Characteristic curve for diagnosing C8/T1 radiculopathy using RMCT was 0.72 (0.61–0.82). The RMCT was significantly correlated with symptom duration (coefficient = 0.58; p < 0.001) but was not associated with the degree of arm pain.

Conclusion
Our findings illustrate the clinical applicability of the RMCT by demonstrating its utility in diagnosing radiculopathy at certain spinal levels.
Axillary vein thrombosis 30 h after caesarean section: a case report and literature review
Authors: Cai Benshuo , Li Gang 
Published: October 2022

AbstractBackgroundAxillary vein thrombosis is a very rare disorder. However, a case of axillary vein thrombosis shortly after caesarean section has not been reported previously. We report a case of axillary vein thrombosis 30 h after caesarean section due to an unidentified aetiology.CaseA 37-year-old multiparous woman developed swelling and pain of the forearm and hand 30 h after undergoing a caesarean section. Doppler ultrasonography revealed a 14.9 mm × 5.3 mm thrombosis in the left axillary vein although a prophylaxis of anticoagulation was administrated. After an adjusted-dose of low-molecular-weight heparin (LMWH) was administered, the patient recovered and was discharged.ConclusionObstetricians should be fully aware of the possibility of upper extremity deep vein thrombosis (DVT) despite its rarity, especially after the surgery. Lying in the lateral decubitus position for long periods postoperatively should be avoided as much as possible.
HELENA: HER2-Low as a prEdictive factor of response to Neoadjuvant chemotherapy in eArly breast cancer
Authors: Cherifi François , Da Silva Angélique , Johnson Alison , Blanc-Fournier Cécile , Abramovici Olivia , Broyelle Antonin , Levy Christelle , Allouache Djelila , Hrab Ioana , Segura Carine , Morel Adeline , Villemin Maud , Boscher Clémence , Dubot-Poitelon Coraline , Rottier Pauline , Lequesne Justine , Emile George 
Published: October 2022

Abstract
Background
HER2 expression has a prognostic and predictive impact in early-stage breast cancer (BC). HER2 positive BC (immunohistochemistry (IHC) score 3 + or 2 + with in situ hybridization (ISH) amplification) are treated with HER2 targeted therapies. The concept of HER2-low BC (IHC score 1 + or 2 + without ISH amplification) is drawing attention as anti-HER2 treatment has recently shown efficacy in this subgroup. We aimed to explore the response to neoadjuvant chemotherapy (NAC) in HER2-low early BC according to the HER2 score (1 + or 2 + without amplification).

Methods
We conducted a retrospective study in two French comprehensive cancer centers. All patients with HER2-low BC treated with NAC from January 2014 to December 2020 were included. The primary objective was to analyze the pathological complete response (pCR) rate to NAC using the Sataloff or RCB system, according to the HER2 score. Secondary objectives were to assess disease free survival (DFS), overall survival (OS) and to explore the immune environment through the Neutrophil-to-Lymphocyte Ratio (NLR), according to HER2 expression. Univariate and multivariate analyses were performed.

Results
We included 237 tumors for 229 patients. Of these, 160 (67.5%) tumors were HER2 1 + , 77 (32.5%) were HER2 2 + , and 152 (64.1%) were hormone receptor (HR) positive. The median age was 53.9 years. No differences in tumor characteristics were observed between HER2 1 + and HER2 2 + subgroups. pCR was achieved in 38 tumors (17%), without any difference between HER2 1 + and HER2 2 + subgroups (p = 0.77). DFS and OS were significantly different between HER2 1 + and HER2 2 + patients (HR = 0.41,CI95%[0.17;0.97] p = 0.037 and HR = 0.31,CI95%[0.09;1.02] p = 0.042, respectively). HER2 status was still associated with DFS and OS after adjustment for age, HR status and NLR, with better outcomes in favor of HER2 score 2 + (HR = 0.35 [0.15–0.84] and HR = 0.24 [0.07–0.81], respectively). NLR was not associated with worse DFS or OS.

Conclusion
In HER2-low early BC, no differences in pCR were observed between HER2 1 + and HER2 2 + tumors, however patients with HER2 2 + tumors had a better DFS and OS than those with HER2 1 + . Further investigations are needed to describe the intrinsic differences in the spectrum of HER2-low BC.
Explainable machine learning methods and respiratory oscillometry for the diagnosis of respiratory abnormalities in sarcoidosis
Authors: de Lima Allan Danilo , Lopes Agnaldo J. , do Amaral Jorge Luis Machado , de Melo Pedro Lopes 
Published: October 2022

AbstractBackgroundIn this work, we developed many machine learning classifiers to assist in diagnosing respiratory changes associated with sarcoidosis, based on results from the Forced Oscillation Technique (FOT), a non-invasive method used to assess pulmonary mechanics. In addition to accurate results, there is a particular interest in their interpretability and explainability, so we used Genetic Programming since the classification is made with intelligible expressions and we also evaluate the feature importance in different experiments to find the more discriminative features.Methodology/principal findingsWe used genetic programming in its traditional tree form and a grammar-based form. To check if interpretable results are competitive, we compared their performance to K-Nearest Neighbors, Support Vector Machine, AdaBoost, Random Forest, LightGBM, XGBoost, Decision Trees and Logistic Regressor. We also performed experiments with fuzzy features and tested a feature selection technique to bring even more interpretability. The data used to feed the classifiers come from the FOT exams in 72 individuals, of which 25 were healthy, and 47 were diagnosed with sarcoidosis. Among the latter, 24 showed normal conditions by spirometry, and 23 showed respiratory changes. The results achieved high accuracy (AUC > 0.90) in two analyses performed (controls vs. individuals with sarcoidosis and normal spirometry and controls vs. individuals with sarcoidosis and altered spirometry). Genetic Programming and Grammatical Evolution were particularly beneficial because they provide intelligible expressions to make the classification. The observation of which features were selected most frequently also brought explainability to the study of sarcoidosis.ConclusionsThe proposed system may provide decision support for clinicians when they are struggling to give a confirmed clinical diagnosis. Clinicians may reference the prediction results and make better decisions, improving the productivity of pulmonary function services by AI-assisted workflow.
Influence of baseline arterial stiffness on effects of intensive compared with standard blood pressure control: a post hoc analysis of the STEP trial
Authors: Song Qirui , Ling Qianhui , Bai Jingjing , Zhang Hongwei , Bu Peili , Chen Fang , Wu Shouling , Zhang Weili , Chen Mulei , Cai Jun 
Published: October 2022

Abstract
Background
The benefits and risks of intensive versus standard systolic blood pressure (SBP) treatment in older patients with arterial stiffness (AS) remains unclear. This study aims to investigate the interaction between the baseline AS and SBP treatments on cardiovascular outcomes.

Methods
In this post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial, we involved 6865 participants with complete data regarding baseline brachial-ankle pulse wave velocity (baPWV). Patients were categorized by baseline AS status (AS, baPWV ≥ 1800 cm/s; non-AS, baPWV < 1800 cm/s). The primary outcome was a composite of cardiovascular events. The secondary outcomes were stroke, acute coronary syndrome (ACS), major cardiovascular events (MACE), and all-cause death. Cox regression was used to calculate hazard ratios for the outcomes.

Results
During a mean follow-up of 2.69 years, a total of 248 primary outcome events and 81 all-cause deaths occurred. The hazard ratios for the primary outcome were 0.76 (95% confidence interval (CI), 0.54–1.09) and 0.63 (95% CI, 0.43–0.92) in the AS and non-AS groups, respectively (P for interaction = 0.43), and that for stroke was 0.58 (95% CI, 0.33–1.02) and 0.48 (95% CI, 0.23–0.99) in the AS and non-AS groups, respectively (P for interaction = 0.68). Effects of intensive SBP treatment on safety outcomes and all-cause death were also similar in the two groups (P for interaction > 0.05 for all).

Conclusions
In the STEP trial, the beneficial effects of intensive SBP treatment were similar among those in the AS group and the non-AS group at baseline.

Trial registration
STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.
The effects of visual context on visual-vestibular mismatch revealed by electrodermal and postural response measures
Authors: Al-Sharif Doaa S. , Tucker Carole A. , Coffman Donna L. , Keshner Emily A. 
Published: October 2022

AbstractBackgroundNo objective criteria exist for diagnosis and treatment of visual-vestibular mismatch (VVM).ObjectiveTo determine whether measures of electrodermal activity (EDA) and trunk acceleration will identify VVM when exposed to visual-vestibular conflict.MethodsA modified VVM questionnaire identified the presence of VVM (+ VVM) in 13 of 23 young adults (34 ± 8 years) diagnosed with vestibular migraine. Rod and frame tests and outcome measures for dizziness and mobility were administered. Participants stood on foam while viewing two immersive virtual environments. Trunk acceleration in three planes and electrodermal activity (EDA) were assessed with wearable sensors. Linear mixed effect (LME) models were used to examine magnitude and smoothness of trunk acceleration and tonic and phasic EDA. Welch’s t-test and associations between measures were assessed with a Pearson Correlation Coefficient. Effect sizes of group mean differences were calculated.ResultsGreater than 80% of all participants were visually dependent. Outcome measures were significantly poorer in the + VVM group: tonic EDA was lower (p < 0.001) and phasic EDA higher (p < 0.001). Postural accelerations varied across groups; LME models indicated a relationship between visual context, postural, and ANS responses in the + VVM group.ConclusionsLower tonic EDA with + VVM suggests canal-otolith dysfunction. The positive association between vertical acceleration, tonic EDA, and visual dependence suggests that increased vertical segmental adjustments are used to compensate. Visual context of the spatial environment emerged as an important control variable when testing or treating VVM.
Functional results of modified Mason–Allen suture versus horizontal mattress suture in the arthroscopic Broström–Gould procedure for chronic ankle instability
Authors: Liu Jinlang , Chen Mingliang , Xu Tao , Tian Zhipeng , Xu Liuhai , Zhou You 
Published: October 2022

Abstract
Background
The arthroscopic Broström–Gould procedure (ABG) gained particular attention among clinicians and researchers due to its high rate of satisfactory results. There is a lack of evidence regarding the differences in clinical outcomes for the various suture techniques. The purpose of this study was to compare the differences in clinical effect in patients treated with one-anchor modified Mason–Allen suture or two-anchor horizontal mattress suture for chronic ankle instability (CAI).

Methods
This retrospective cohort study examined CAI patients who underwent either one-anchor modified Mason–Allen suture or two-anchor horizontal mattress suture ABG between January 2018 and January 2020. Patients were divided into two groups based on the suture knot type used and the associated number of anchors. The operative time, surgical cost, Visual Analog Scale (VAS), American Orthopedic Foot & Ankle Society (AOFAS) Score, Karlsson Ankle Functional Score (KAFS), the rate of return to sports, complications, and measured biomechanical strength using standardized equipment were compared between groups.

Results
Sixty-four CAI patients were included (one-anchor modified Mason–Allen suture group n = 30, two-anchor horizontal mattress suture group n = 34). Compared to the two-anchor horizontal mattress suture group, the one-anchor modified Mason–Allen suture group had significantly shorter operative time (p < .001) and lower surgical cost (p < .001). There were no postoperative complications in the two groups, and no significant differences in the VAS, AOFAS, KAFS, and rate of return to sports in postoperative follow-up between the two groups at 1 and 2 years after surgery. There was no statistically significant difference in biomechanical strength anterior drawer test displacement (p > .05) between the one-anchor modified Mason–Allen suture and two-anchor horizontal mattress suture at 2 years after surgery.

Conclusion
ABG using a one-anchor modified Mason–Allen suture showed comparable clinical results to a two-anchor horizontal mattress suture in the treatment of CAI at intermediate-term follow-up time. However, one-anchor modified Mason–Allen suture may be a faster, simpler, cost-effective substitute technology.

Level of evidence
Level III, comparative study.
CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis
Authors: Jiang Yang , Zhao Junshuang , Li Rongqing , Liu Yingliang , Zhou Lin , Wang Chengbin , Lv Caihong , Gao Liang , Cui Daming 
Published: October 2022

Abstract
Background
Ferroptosis is a novel form of iron-dependent cell death and participates in the malignant progression of glioblastoma (GBM). Although circular RNAs (circRNAs) are found to play key roles in ferroptosis via several mechanisms, including regulating iron metabolism, glutathione metabolism, lipid peroxidation and mitochondrial-related proteins, there are many novel circRNAs regulating ferroptosis need to be found, and they may become a new molecular treatment target in GBM.

Methods
The expression levels of circLRFN5, PRRX2 and GCH1 were detected by qPCR, western blotting, and immunohistochemistry. Lentiviral-based infections were used to overexpress or knockdown these molecules in glioma stem cells (GSCs). The biological functions of these molecules on GSCs were detected by MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium), the 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, transwell, neurosphere formation assays, Extreme Limiting Dilution Analysis (ELDA) and xenograft experiments. The content of ferroptosis levels in GSCs was detected by BODIPY 581/591 C11 assay, glutathione (GSH) assay and malondialdehyde (MDA) assay. The regulating mechanisms among these molecules were studied by RNA immunoprecipitation assay, RNA pull-down assay, ubiquitination assay, dual-luciferase reporter assay and chromatin immunoprecipitation assay.

Results
We found a novel circRNA circLRFN5 is downregulated in GBM and associated with GBM patients’ poor prognosis. CircLRFN5 overexpression inhibits the cell viabilities, proliferation, neurospheres formation, stemness and tumorigenesis of GSCs via inducing ferroptosis. Mechanistically, circLRFN5 binds to PRRX2 protein and promotes its degradation via a ubiquitin-mediated proteasomal pathway. PRRX2 can transcriptionally upregulate GCH1 expression in GSCs, which is a ferroptosis suppressor via generating the antioxidant tetrahydrobiopterin (BH4).

Conclusions
Our study found circLRFN5 as a tumor-suppressive circRNA and identified its role in the progression of ferroptosis and GBM. CircLRFN5 can be used as a potential GBM biomarker and become a target for molecular therapies or ferroptosis-dependent therapy in GBM.