bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis to identify a target site in Shiga-toxin for the inhibitor discovery against growth of Shiga toxin-producing E. coli
Authors: Prabhudesai anuja , Shaikh Samir , Ashwinbhai Kayasth Zarna , Gupta Reeshu 
Published: November 2023

Abstract
Background: Certain peptides that can bind to Shiga toxin 2 (Stx2) have been reported to treat Shiga toxin-producing E. coli (STEC) infections. However, their mechanisms of action remain unknown. We used the PEP-FOLD server to predict the 3-D structure of the five peptides that have been used against STEC growth. The modelled structures were docked with Stx2 using ClusPro server. The physiochemical properties of therapeutic peptides were computed using the ‘peptides’ package of the RStudio and ProtParam tool.
Results:Of these five therapeutic peptides, one tetravalent peptide (TVP) was shortlisted based on its interaction with the active sites of Stx2. The structure of stx2-TVP complex was evaluated using the ERRAT, iMODS, and Procheck servers. The 3D refined model of TVP was generated using Galaxyserver and evaluated using ERRAT, ANOLEA, and QMEAN. PyMOL was used to visualize the docking complexes. The current study demonstrated that blocking Y77-E259 and Y114-E167 interactions is required to inhibit STEC growth. Of the five therapeutic peptides used in this study, only MAPPPRRRRA (TVP) blocked the interaction between Y77 and E259 residues of the A1 subunit of Stx2, making it active and ultimately leading to STEC cell death. However, all therapeutic peptides showed strong polar interactions with Y77 and E259, but they did not block the Y77-E259 or Y114-E167 interactions. We also demonstrated that helix-loop-helix formation near the ribosome-binding site of Stx2 might lead to the differential gene expression regulated by Stx2. The 3D refined model of TVP showed a positive G-factor, high QMEAN score, low MolProbity score, and low energy zones in the ANOLEA profile compared to original TVP. Moreover, the low radius of gyration in the refined TVP during the molecular simulation suggests that it is more compact than the original TVP. However, the low antigenicity of TVP makes it an unsuitable drug candidate. We also evaluated three antibiotics that have been used as active ingredients in FDA-approved peptides. Only Oritavancin diphosphate showed strong polar interactions with Y77-E259 and also had the highest binding affinity.
Conclusions: This study identified a new target (Y77-E259) for inhibitor discovery against STEC growth.
Symmetries of algebras captured by actions of weak Hopf algebras
Authors: Calderon Fabio , Huang Hongdi , Wicks Elizabeth , Won Robert 
Published: November 2023

Abstract

In this paper, we present a generalization of well-established results regarding symmetries of 𝕜-algebras, where 𝕜 is a field. Traditionally, for a 𝕜-algebra A, the group 𝕜-algebra automorphisms of A captures the symmetries of A via group actions. Similarly, the Lie algebra of derivations of A captures the symmetries of A via Lie algebra actions. In this paper, given a category C whose objects possess 𝕜-linear monoidal categories of modules, we introduce an object SymC (A) that captures the symmetries of A via actions of objects in C. Our study encompasses various categories whose objects include groupoids, Lie algebroids, and more generally, cocommutative weak Hopf algebras. Notably, we demonstrate that for a positively graded non-connected 𝕜-algebra A, some of its symmetries are naturally captured within the weak Hopf framework.
2020 Mathematics Subject Classification. 18B40, 16T05, 18M05.
Impact of COVID-19 Pandemic on Physician-Scientist Trainees to Faculty One Year into the Pandemic
Authors: Obradovic Aleksandar , Toubat Omar , Chen Nathan W. , Siebert Aisha , Jansen Carey , Christophers Briana , Leveille Etienne , Noch Evan , Kwan Jennifer M. 
Published: November 2023

Abstract

Purpose
Physician-scientists play a crucial role in advancing biomedical sciences. Proportionally fewer physicians are actively engaged in scientific pursuits, attributed to attrition in the training and retention pipeline. This national study evaluated the ongoing and longer-term impact of the COVID-19 pandemic on research productivity for physician-scientists at all levels of training.
Methods
A survey of medical students, graduate students, and residents/fellows/junior faculty (RFJF) was conducted from April to August 2021 to assess the impact of COVID-19 on individual stress, productivity, and optimism. Multivariate regression analyses were performed to identify associated variables and unsupervised variable clustering techniques were employed to identify highly correlated responses.
Results
A total 677 respondents completed the survey, representing different stages of physician-scientist training. Respondents report high levels of stress (medical students: 85%, graduate students: 63%, RFJF: 85%) attributed to impaired productivity concerns, concern about health of family and friends, impact on personal health and impairment in training or career development. Many cited impaired productivity (medical students: 65% graduate students: 79%, RFJF: 78%) associated with pandemic impacts on training, labs closures and loss of facility/resource access, and social isolation. Optimism levels were low (medical students: 37%, graduate students: 38% and RFJF: 39%) with females less likely to be optimistic and more likely to report concerns of long-term effects of COVID-19. Optimism about the future was correlated with not worrying about the long-term effects of COVID-19. Since the COVID-19 pandemic, all respondents reported increased prioritization of time with family/friends (67%) and personal health (62%) over career (25%) and research (24%).
Conclusions
This national survey highlights the significant and protracted impact of the COVID-19 pandemic on stress levels, productivity, and optimism among physician-scientists and trainees. These findings underscore the urgent need for tailored support, including mental health, academic, and career development assistance for this biomedical workforce.
MRI-Visualized T2 Hyperintense Breast Lesions: Identifying Clinical and Imaging Factors Linked to Malignant Biopsy Outcomes
Authors: Bissell Mary Beth , Keshavarzi Sareh , Fleming Rachel , Au Frederick , Kulkarni Supriya , Ghai Sandeep , Freitas Vivianne 
Published: November 2023

Abstract
Purpose
To determine the malignancy rate for MRI-guided breast biopsies performed for T2 hyperintense breast lesions and to assess additional clinical and MRI characteristics that can predict benign and malignant outcomes.
Methods
A retrospective chart review of consecutive MRI-guided breast biopsies performed in two tertiary hospitals was conducted over two years. Biopsies performed for T2 hyperintense lesions were selected, and further lesion imaging characteristics and patient risk factors were collected. Univariate and multivariate modeling regression was used to determine additional imaging and patient factors associated with malignant outcomes for biopsies of T2 hyperintense lesions.
Results
Out of 369 MRI-guided breast biopsies, 100 (27%) were performed for T2 hyperintense lesions. Two biopsy-proven benign lesions were excluded as the patient was lost on follow-up. With a study cohort of 98 lesions, the final pathology results were benign for 80 (80%) of these lesions, while 18 (18%) were malignant. Using multivariate logistic modeling, patient age > 50 (OR 5.99 (1.49,24.08 95%CI), p < 0.05) and lesion size > 3cm (OR 5.54 (1.54–18.7), p < 0.01) were found to be important predictors of malignant outcomes for MRI biopsies performed for T2 hyperintense lesions.
Conclusion
Our study observed a high malignancy rate, challenging the assumption that T2 hyperintensity can be considered a benign imaging characteristic for otherwise suspicious MRI-detected lesions. Decision-making regarding tissue sampling should be made based on a thorough evaluation of more reliable additional demographic and imaging factors, including patient age and lesion size.
Selective agents, microbial ecology, and horizontal gene transfer underly the fate of resistance genes during biological wastewater treatment
Authors: Pruden Amy , Brown Connor , Maile-Moskowitz Ayella , Lopatkin Allison , Xia Kang , Logan Latania , Davis Benjamin , Zhang Liqing , Vikesland Peter 
Published: November 2023

Abstract

Activated sludge is the centerpiece of biological wastewater treatment, as it facilitates removal of sewage-associated pollutants, fecal bacteria, and pathogens from wastewater through semi-controlled microbial ecology. Horizontal gene transfer (HGT) is believed to facilitate the spread of antibiotic resistance genes (ARGs) within sewage-associated microbiota, in part because of the presence of selective agents such as residual antibiotics in sewage. However, convincing evidence that selective agents promote resistance within activated sludge via HGT, or otherwise, has remained elusive. Here we used lab-scale sequencing batch reactors (SBRs) to simulate activated sludge treatment under controlled conditions. Replicate SBRs were fed field-collected municipal sewage augmented with either 0% or 10% hospital sewage to compare hypothetical low and high propensity conditions for ARG proliferation, respectively. Shotgun metagenomics, culture, pharmaceutical and personal care product screening, and bioinformatics were used to examine the impact of hospital sewage on SBR performance and the proliferation of ARGs. Hospital sewage had a modest impact on SBR performance and taxonomic composition determined via short read mapping. However, analysis of hospital- and municipal-sewage resistomes by the bioinformatic tool Kairos revealed microdiversity-level differences in ARG fate, including the disproportionate persistence of hospital-associated sulfonamide ARGs and municipal sewage derived macrolide ARGs. Correspondingly, it was found that levels of erythromycin and sulfamethoxazole sharply increased over the course of the experiment independent of hospital sewage. The relative abundances of metagenome assembled genomes bearing sulfonamide and macrolide ARGs showed drastically different trajectories in the presence of shifting antibiotic levels. In addition, in situ HGT events of the ARGs mphA and sul2 were detected in deeply sequenced samples. These included the potential transduction of mphA, which encodes an erythromycin phosphotransferase, between Dokdonella sp., Myxococcia, and Polyangia. Multiple potential pathways of transfer were noted for putative in situ HGT of sul2 between Bacteroidia, Gammaproteobacteria, and Alphaproteobacteria. These findings highlight complex ecological interactions enveloping the dissemination of ARGs in activated sludge and implicate roles for selective agents, microbial ecology, and HGT.
Oxaliplatin lipidated prodrug synergistically enhances the anti-colorectal cancer effect of IL12 mRNA
Authors: Liu Hui , Du Yating , Zhan Desheng , Yu Wenjun , Li Yan , Wang Aiping , Yin Jianpeng , Cao Haiqiang , Fu Yuanlei 
Published: November 2023

Abstract
Chemotherapy drugs are the main way to treat cancer, but there are strong toxic side effects in anti-tumor, of which oxaliplatin (OXA) is a commonly used platinum anti-tumor chemotherapy drug, colorectal cancer (CRC), non-small cell lung cancer and gastric cancer and other malignant tumors have a good therapeutic effect, but OXA also has strong side effects such as peripheral neurotoxicity, bone marrow suppression, etc. Therefore, by modifying the structure of OXA and introducing long alkyl chains in the platinum coordination of OXA, we greatly improve the fat solubility of the drug, which is more conducive to the drug crossing the biofilm and improving the anti-tumor efficacy. In addition to chemotherapy, cytokines are one of the earliest immunotherapies used in the treatment of human cancer, based on this, we prepared a new type of lipid nanoparticles (LNPs), wrapped with cytokines encoding interleukin-12 (IL12), which can directly deliver immune stimulation to tumors, and accumulate in tumors, improve the local immune environment of tumors, and directly or indirectly kill tumors. In this study, we combined the administration of modified prodrug OXA-LIP and mRNA-LNP, through in vivo pharmacodynamics and cytotoxicity experiments proving that combined administration can play a long-term anti-tumor effect, chemotherapy, and immunotherapy combination therapy is a very potential anti-tumor method, the combination of the two can play a synergistic effect, reduce the toxic side effects in tumor treatment, and the advantages in biological safety and anti-tumor activity provide broad application prospects for anti-cancer.
TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population
Authors: Chi Xiaodong , Wu Yingying , Zhang Chao , Duan Shaofei , Li Yushan , Bajpai Akhilesh Kumar , Lu Lu , Yang Chunhua , Mi Jia , Tian Geng , Xu Fuyi , Qi Donglai , Xu Zhaowei 
Published: November 2023

Abstract
The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause Non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidemia, etc. Systematic investigation of the key factors related to hepatic glucose metabolism may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. Here, we quantified oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes in BXD mice under chow and high-fat diet conditions. Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background. To further identify the candidate genes associated with hepatic glucose metabolism, and the results revealed 9 genetic regulating loci on chromosomes 1, 4, 7 and 11, respectively by QTL mapping. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate functional genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 significantly decreased the glucose uptake. RT-PCR assays confirmed that the down-regulation of those three candidates inhibited the transcription of genes related to insulin and glucose metabolism pathways. Consequently, our study uncovered the role of TEAD1, MYO7A and NDUFC2 that influenced the mitochondrial function in to regulate glucose homeostasis and provided novel targets for the diagnosis, treatment, and prognosis of glucose metabolism-related diseases.
Detection of rare malignant cells in gastric lavage using Hexokinase 2 and single-cell sequencing for early-stage gastric cancer diagnosis
Authors: QIAN PEIYU , Sun Jie , Tao Yining , Mu Haoran , Yang Liu , Lu Peihua 
Published: November 2023

Abstract
Objective:Gastric cancer is a highly prevalent cancer. Endoscopy is the best way to diagnose gastric cancer at an early stage, but it relies on patient compliance and endoscopy physicians’ experience, which makes it difficult to be used as a screening method for a large population. The aim of this study is to develop a novel method for early gastric cancer diagnosis by detecting exfoliated tumor cells in gastric lavage.
Methods: In our experiment, Hexokinase 2 (HK2) was firstly used as a metabolic function-associated marker to detect gastric exfoliated tumor cells engaging increased glycolysis in gastric lavage. And further the malignancy of HK2-derived high glycolytic tumor cells (hgTCs) was examinedby single-cell sequencing (SCS) by surveying genome-wide copy number variation (CNV).
Results: In a study of 60 individuals including 10 gastric cancer patients (9 IA and 1 IIA), 26 precancerous lesions patients, 15 patients with benign gastric diseases, and 9 healthy controls, the HK2 test showed diagnostic sensitivity and diagnostic specificity were 80% (8/10 patients with gastric cancer IA and IIA) and 96% (23/24 patients with benign gastric diseases and healthy controls), respectively. One point that is worth paying attention to is that the diagnostic sensitivity in patients with severe dysplasia was 57% (4/7), which showed promising application prospects in gastric cancer early diagnosis and prevention.
Conclusions: Thus, our results demonstrated a new approach using a gastric lavage-based HK2 assay combined with SCS validation. It has the great potential to be used for early gastric cancer detection with high accuracy, especially to improve the quality of gastroscopy at the early stage.
Azzola as a novel bio-fertilizer and inorganic nitrogen on Marketable yield and quality response of tomato fruits
Authors: Zeleke Yenetiru Getaw , Haile Ashenafi , Kiflu Alemayehu , Alemayehu Habtamu 
Published: November 2023

Abstract

Many people are concerned about the environment and believe that organic products are healthier than conventional ones, so there is a growing demand for organic vegetable products. According to studies, organically grown tomato fruits contain higher levels of carotenoids, polyphenols, and antioxidants than conventionally grown tomatoes. Enhancing tomato marketable yield and quality through the application of optimal organic and inorganic fertilizers is a crucial agronomic practice. The purpose of this study was to compare the effects of organic and inorganic fertilization on the marketable yield and quality characteristics of tomato fruits. A pot experiment with three replications and two fertilization treatments with four levels each (nitrogen as an inorganic fertilizer and Azzola as an organic fertilizer) was set up in a completely randomized design. The findings revealed that nitrogen and Azzola biofertilizer had a significant effect on fruit diameter and all quality parameters. The interaction effects of Azzola and nitrogen on cluster number per plant, flower number per cluster, fruit set percentage, and fruit number per cluster, and marketability were significant. Consequently, tomato growers are advised to apply 1.5 g of nitrogen and 75 g of Azzola.
Design, development and evaluation of a biomass fueled cabinet dryer for high quality cassava flour production
Authors: Asiru Wahabi Bolanle , Adegbite Suraju Adeyemi , Okewole Oyewole , Awoyale Wasiu , Kolawole Peter , Diallo Thierno A , Abass Adebayo 
Published: November 2023

Abstract
Cassava, a vital staple crop in developing countries, plays a significant role in ensuring food security and income generation for smallholder farmers. However, the lack of modern drying technology in rural area necessitate the need for a more efficient and controllable drying process which reduces post-harvest losses and ensure better product quality while taking sustainability into account by utilizing biomass as the energy source. Therefore, drying cassava roots to produce high-quality cassava flour was the goal of the biomass heat-generated cabinet dryer, which was designed and built for drying in rural locations. The main components of the dryer include heat exchanger, blower, and drying chamber unit which was designed based on engineering standards utilizing locally available materials. The drying chamber consists of two racks of 10 trays each for drying. The dryer was found to be capable of drying 40, 60, and 80 kg of wet cassava mash each batch, when the loading capacity was 2, 3, or 4 kg/tray. At temperatures ranging from 50 to 115°C, with drying duration of 10 to 120 minutes, thermal efficiency, drying time, and heating energy were investigated. Moisture levels reduced to 10.6%, 11.0% and 11.2% from initial moisture content of 38.21%. At 40 kg, 60 kg, and 80 kg material capacities, drying efficiencies averaged 74.77%, 59.22%, and 88.24%, respectively, with biomass efficiencies 3.0%, 3.5%, and 4.0%. Despite a low biomass efficiency, drying efficiency shows that the dryer is relatively efficient in drying. Hence, biomass fueled dryer should be employed for drying.
Association of systemic immune-inflammatory index with cancer prevalence and mortality: Results from NHANES 1999-2010
Authors: Zhang Yuzhuo , Jia Wenyu , Lan Tian , Zhang Xinru , Li Bangjie , Chen Ju , Li Yin , Tian Huaqin 
Published: November 2023

Abstract
Objective: To study the predictive effect of systemic immune-inflammatory index (SII) on cancer prevalence and mortality.
Methods: Participants with SII and cancer status were screened from the National Health and Nutrition Examination Survey database from 1999 to 2010, and their baseline characteristics were analyzed according to the SII tertile. Multivariable logistical or Cox proportional hazards models were used to analyze the associations between SII with cancer prevalence or mortality. The mortality was followed through December 31 2018. For further evaluation on associations of SII with specified outcomes, restricted cubic spline and two piecewise regression models were adopted.
Results: This study eventually included 26,049 individuals, of whom 2,432 were cancer patients. According to the SII tertile group, cancer prevalence increased significantly with the rise of SII. In the highest tertile of SII, SII was significantly related to cancer prevalence (OR=1.45, 95%CI= 1.31 - 1.61, p<0.05). Moreover, during a median follow-up of 12.75 year, 329, 351, and 1,202 cardiovascular, cancer and all-cause deaths occurred among cancer patients, respectively. The results indicated that highest level of SII was significantly associated with increased cardiovascular mortality (HR=1.80, 95%CI= 1.28 - 2.52), cancer mortality (HR=1.64, 95%CI= 1.28 - 2.09) and all-cause mortality (HR=1.56, 95%CI= 1.31- 1.85). The model adjusted for multiple covariates still showed the same trend. U-shaped dose-response associations between log-transformed SII (ln-SII) with prevalence and mortality of cancer were detected. The threshold values of ln-SII for the lowest risk associated with cancer prevalence, cardiovascular mortality cancer mortality and all-cause mortality were 5.44, 6.21, 6.27 and 6.21, respectively. Above thresholds, SII was positively associated with increased risk of above outcomes.
Conclusion: SII may be a potential earlier warning marker for the prevalence and mortality of total cancers.
Safety and effectiveness of a drug-loaded haemostatic sponge in chronic rhinosinusitis:A randomized, controlled, double-blind study
Authors: Jia Xujin , Meng Jia , Wang Jiayan , Wang Wei , Wu Di , Xu Ming 
Published: November 2023

Abstract
The aim of this study was to investigate the safety and efficacy of a novel drug-loaded haemostatic sponge (DLHS) in the sinus. In this clinical trial, 49 patients were randomly divided into 2 groups: group A (n = 25) had the DLHS placed into the sinus, and group B (n = 24) had the Nasopore placed after Endoscopic sinus surgery (ESS). Endoscopic follow-up was performed for 12 weeks, and the findings were classified using the discharge, inflammation, polyps/oedema (DIP) endoscopic appearance scores. All patients completed questionnaires to evaluate their sinonasal symptoms by using the sinonasal outcome test-22 (SNOT-22) and visual analogue scale (VAS). Serum cortisol concentration in group A was measured prior to surgery and at days 1, 3, 7, and 14 after nasal surgery. Comparing group A and group B, at 2 weeks, no significant differences were observed in either objective or subjective parameters. The mean value of VAS for rhinorrhoea and DIP for oedema and the mean value of nasal adhesion appeared to be significantly lower in Group A than in Group B at 6 and 12 weeks, but a significant difference did not occur in SNOT-22 and VAS for dysosmia between the two groups at 6 and 12 weeks. The mean serum cortisol concentrations in group A at the follow-up were within normal limits without remarkable fluctuations. This study demonstrates the safety and efficacy of the DLHS with the possibility of being used in CRS patients.