bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol consumption and hepatocellular carcinoma: novel insights from a prospective cohort study and nonlinear Mendelian randomization analysis
Authors: Liu Zhenqiu , Song Ci , Suo Chen , Fan Hong , Zhang Tiejun , Jin Li , Chen Xingdong 
Published: October 2022

Abstract
Background
Heavy drinking was well associated with an increased risk of hepatocellular carcinoma (HCC), whereas the effect of low-to-moderate drinking on HCC remains under debate.

Methods
Participants from the UK Biobank with detailed information on alcohol use and free of common diseases were included. Daily pure alcohol intake (g/day) was calculated, and the predominant alcoholic beverage type was assigned for each participant. Additive Cox regression model and nonlinear Mendelian randomization (NLMR) analyses were performed to evaluate the association of alcohol intake with HCC.

Results
Of 329,164 participants (52.3% females, mean [SD] age = 56.7 [8.0] years), 201 incident HCC cases were recorded during the median follow-up of 12.6 years. The best-fitted Cox regression model suggested a J-shaped relationship between daily alcohol intake level and HCC risk. However, NLMR analysis did not detect a nonlinear correlation between alcohol use and HCC (nonlinearity P-value: 0.386). The J-shaped correlation pattern was detected only in subjects who mainly drank wine but not in those who mainly drank beer, spirits, or fortified wine. Moderate wine drinking showed a significant alanine transaminase (ALT)- and aspartate aminotransferase-lowering effect compared to that of the nondrinkers. In low-risk populations of HCC including women, people aged < 60 years, subjects with normal ALT levels, and those carrying non-risk genotypes of PNPLA3 rs738409 and TM6SF2 rs58542926, we observed a J-shaped correlation between alcohol use and HCC; however, a positive dose–response correlation was found in their respective counterparts, even in those predominantly drinking wine.

Conclusions
Low-to-moderate drinking may be inversely associated with the risk of HCC in low-risk populations, which may be largely driven by wine drinking. However, those in high-risk populations of HCC, such as men and older people, and those with abnormal ALT levels and carry genetic risk variants, should abstain from drinking alcohol. Given the small HCC case number, further validations with larger case numbers are warranted in future works.
A facile process for adipic acid production in high yield by oxidation of 1,6-hexanediol using the resting cells of Gluconobacter oxydans
Authors: Pyo Sang-Hyun , Sayed Mahmoud , Örn Oliver Englund , Amorrortu Gallo Jorge , Fernandez Ros Nídia , Hatti-Kaul Rajni 
Published: October 2022

Abstract
Background
Adipic acid (AA) is one of the most important industrial chemicals used mainly for the production of Nylon 6,6 but also for making polyurethanes, plasticizers, and unsaturated polyester resins, and more recently as a component in the biodegradable polyester poly(butylene adipate terephthalate) (PBAT). The main route for AA production utilizes benzene as feedstock and generates copious amounts of the greenhouse gas NO2. Hence, alternative clean production routes for AA from renewable bio-based feedstock are drawing increasing attention. We have earlier reported the potential of Gluconobacter oxydans cells to oxidize 1,6-hexanediol, a potentially biobased diol to AA.

Results
The present report involves a study on the effect of different parameters on the microbial transformation of 1,6-hexanediol to adipic acid, and subsequently testing the process on a larger lab scale for achieving maximal conversion and yield. Comparison of three wild-type strains of G. oxydans DSM50049, DSM2003, and DSM2343 for the whole-cell biotransformation of 10 g/L 1,6-hexanediol to adipic acid in batch mode at pH 7 and 30 °C led to the selection of G. oxydans DSM50049, which showed 100% conversion of the substrate with over 99% yield of adipic acid in 30 h. An increase in the concentrations of the substrate decreased the degree of conversion, while the product up to 25 g/L in batch and 40 g/L in fed-batch showed no inhibition on the conversion. Moreover, controlling the pH of the reaction at 5–5.5 was required for the cascade oxidation reactions to work. Cell recycling for the biotransformation resulted in a significant decrease in activity during the third cycle. Meanwhile, the fed-batch mode of transformation by intermittent addition of 1,6-hexanediol (30 g in total) in 1 L scale resulted in complete conversion with over 99% yield of adipic acid (approximately 37 g/L). The product was recovered in a pure form using downstream steps without the use of any solvent.

Conclusion
A facile, efficient microbial process for oxidation of 1,6-hexanediol to adipic acid, having potential for scale up was demonstrated. The entire process is performed in aqueous medium at ambient temperatures with minimal greenhouse gas emissions. The enzymes involved in catalyzing the oxidation steps are currently being identified.
Social acceptance of livestock-administered endectocides for malaria control in Vhembe District, Limpopo Province, South Africa
Authors: Makhanthisa Takalani I. , Braack Leo , Bornman Maria S. , Lutermann Heike 
Published: October 2022

Abstract
Background
Malaria continues to be a leading cause of morbidity and mortality in Africa and conventional malaria control strategies, such as indoor residual spraying and insecticide-treated bed nets, have limited effectiveness for some malarial vectors. Consequently, the development of alternative or supplementary strategies is required. One potential strategy is the use of livestock-administered endectocides to control vector mosquitoes that feed outdoors on livestock. However, since this strategy requires support from local communities and livestock owners consenting for their animals to be treated, it can only be implemented if agreed to by affected communities. The aim of this study was to assess the social acceptance of the use of livestock-administered endectocides in the malaria endemic villages of Vhembe District, Limpopo Province, South Africa, where malaria incidence is high.

Methods
Questionnaires were administered to 103 livestock-owning households from four villages, namely, Gumbu, Malale, Manenzhe and Bale. The assessment included questions on the acceptability of the strategy, the type and number of livestock owned, distances between houses and kraals (overnight pens) as well as previous use and awareness of endectocides. The results were analysed using descriptive statistics and multinomial logistic regression.

Results
The types of livestock owned by the participants comprised, cattle, goats, sheep and donkeys, with the most dominant being goats (n = 1040) and cattle (n = 964). The majority of kraals were less than 10 m from homesteads. Most participants (72.5%) were already using chemicals to treat their livestock for parasites. All participants were amenable to the implementation of the strategy, and would give consent for their animals to be treated by endectocides.

Conclusions
The use of livestock-administered endectocides appears to be a feasible and acceptable approach for control of animal-feeding malaria vector species in the malaria endemic villages of Vhembe District. This is based on a high percentage of rural residents keeping suitable livestock close to their homes and expressing willingness to use endectocides for mosquito control.
Distribution of lipid levels and prevalence of hyperlipidemia: data from the NHANES 2007–2018
Authors: Li Zhenhan , Zhu Guoqi , Chen Guo , Luo Mei , Liu Xuebo , Chen Zhongpei , Qian Jun 
Published: October 2022

Abstract
Background
Lipid-lowering therapy is important, and the distribution of lipid levels and the incidence of hyperlipidemia may vary in different subgroups of the population. We aimed to explore the distribution of lipid levels and the prevalence of hyperlipidemia in subpopulations with subgroup factors, including age, sex, race, and smoking status.

Methods
Our study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, ultimately enrolling and analyzing 15,499 participants. A cross-sectional analysis was performed to assess the distribution of lipids and prevalence of hyperlipidemia in subpopulations, and multifactorial logistic regression analyses were performed for the prevalence of hyperlipidemia, adjusted for age, sex, race and smoking status.

Results
Blacks had significantly lower mean serum total cholesterol and triglycerides and higher serum high-density lipoprotein cholesterol (HDL-C) than whites (P < 0.001). In contrast, Mexican Americans had markedly higher mean serum triglycerides and lower serum HDL-C than whites (P < 0.001). Furthermore, the prevalence of hypercholesterolemia and hypertriglyceridemia was lower in blacks than in whites (P = 0.003 and P < 0.001, respectively), while the prevalence of hypertriglyceridemia was significantly higher in Mexican Americans than in whites (P = 0.002). In addition, total cholesterol and triglyceride levels were significantly higher in women aged 65 years or older and markedly higher than in men in the same age group (P < 0.001). In addition, overall mean total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels were higher in smokers than in nonsmokers (P = 0.01, P < 0.001, and P = 0.005, respectively).

Conclusion
Based on NHANES data, the mean lipid levels and prevalence of hyperlipidemia differed by sex, age, race, and smoking status.
Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury
Authors: Manto Kristen M. , Govindappa Prem Kumar , Martinazzi Brandon , Han Aijie , Hegarty John P. , Koroneos Zachary , Talukder M. A. Hassan , Elfar John C. 
Published: October 2022

Abstract
Background
Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury.

Methods
In this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice.

Results
EPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury.

Conclusion
This study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI.
Were US Asian Indian decedents with atherosclerosis more likely to have concurrent diabetes mellitus? Analysis of national multiple cause of mortality data (2012–2019)
Authors: Nair Deepak R. , Chauhan Abhyuday , Vaidya Dhananjay 
Published: October 2022

Abstract
Background
Asian Indians (AI) are at high risk for both atherosclerotic diseases (ATH) and diabetes mellitus (DM). We analyze the clustering of these two comorbidities as contributing causes of death in AI versus Non-AI populations in the US.

Methods
Using Mortality Multiple Cause-of-Death Files (2012–2019) from the National Center for Health Statistics, we included deaths at age ≥ 45 years among US residents where AI versus Non-AI status could be ascertained (n = 55,461 AI; n = 20,090,038 Non-AI) and identsified ATH (ICD10: I20-I25, I63, I70) and DM (ICD10: E10-E14) as contributing causes of death. We calculated the tetrachoric correlation (Rho) between these contributing causes and the difference in the fraction of deaths involving DM in those with versus without ATH.

Results
Among AI decedents, 29.9% of deaths included ATH as a contributing cause, 16.4% included DM as a contributing cause with 8.3% deaths being included in the overlap (Rho = 0.36, SE = 0.007) whereas, among Non-AI, 22.4% of deaths included ATH as a contributing cause, 10.0% included DM as a contributing cause with 4.1% deaths being included in the overlap (Rho = 0.31, SE = 0.001). Thus, DM and ATH as co-occurring causes correlated more strongly in AI versus Non-AI (p < 0.001). Further, this difference in clustering of DM with ATH was highest for younger AI women (age < 60 years) compared to comparable Non-AI women.

Conclusions
The more frequent co-occurrence of DM and ATH as causes of death among AI compared to Non-AI suggest that the increased burden of these diseases among AI during life has vicious synergistic consequences in terms of mortality. Public health strategies targeted to AI should focus on prevention and clinical treatment of both conditions jointly, in all adults, and especially in women < 60 years.
Isolation, in vitro evaluation of Bacillus spp. against Fusarium oxysporum f.sp. ciceris and their growth promotion activity
Authors: Venkataramanamma K. , Reddy B. V. Bhaskara , Jayalakshmi R. Sarada , Jayalakshmi V. , Rajendran L. 
Published: October 2022

Abstract
Background
Fusarium oxysporum f.sp. ciceris is one of the potential threats to chickpea cultivation as it causes greater a yield loss under favorable conditions. Management of this disease is difficult because of its soil-borne nature and also existence of races. Fungicide application is not economical and not practical. Application of antagonistic bacteria like Bacillus species is one of the best approaches for its management.

Results
Ten Bacillus isolates were collected from healthy chickpea rhizosphere soil, identified and confirmed them as Bacillus based on the results obtained in Gram staining and biochemical characterization (up to species level). They were evaluated against Fusarium oxysporum f.sp. ciceris under in vitro conditions and selected two potential isolates (Bacillus-5 and Bacillus-7), screened for plant growth promotion properties and found thatBacillus-5 was able to solubilize phosphates, Bacillus-7 produced cellulases, both produced HCN and both were unable to produce IAA and chitinases. Identification of these two isolates was done by means of 16Sr DNA sequence analysis. Two universal primers such as 63F and 1387R were used which resulted in 1300 bp product. Blast analysis results indicated that they have more similarities with Bacillus cereus.

Conclusions
Two potential Bacillus isolates out of 10 were selected based on in vitro assay and subjected to study for plant growth promotion characters and found thatBacillus-5 solubilizes phosphates, Bacillus-7 produced cellulases and both produced HCN. Based on 16S rDNA analysis, these potential antagonists have more similar sequences of Bacillus cereus. Further, field efficacy studies need to do in future.
Genome-wide identification and characterization of thaumatin-like protein family genes in wheat and analysis of their responses to Fusarium head blight infection
Authors: Ren Runsheng , Zhou Xinli , Zhang Xu , Li Xin , Zhang Pingping , He Yi 
Published: October 2022

AbstractThaumatin-like proteins (TLPs) play potential roles in plant resistance to various diseases. Identifying TLPs is necessary to determine their function and apply them to plant disease resistance. However, limited information is available about TLP-family genes in wheat, especially regarding their responses to Fusarium species, which cause Fusarium head blight in wheat. In this study, we conducted a comprehensive genome-wide survey of TLP genes in wheat and identified 129 TLP genes in the wheat genome, which were unevenly distributed on 21 wheat chromosomes, with 5A containing the highest number. Phylogenetic analysis showed that these 129 wheat TLP genes together with 24 Arabidopsis TLPs were classified into 7 groups based on the protein sequences. We systematically analyzed the genes in terms of their sequence characterization, chromosomal locations, exon–intron distribution, duplication (tandem and segmental) events and expression profiles in response to Fusarium infection. Furthermore, we analyzed differentially expressed TLP genes based on publicly available RNA-seq data obtained from a resistant near isogenic wheat line at different time points after Fusarium graminearum inoculation. Then, the expression of 9 differentially expressed TLP genes was confirmed by real-time PCR, and these 9 genes were all upregulated in the resistant Sumai 3 variety, which was generally consistent with the RNA-seq data. Our results provide a basis for selecting candidate wheat TLP genes for further studies to determine the biological functions of the TLP genes in wheat.
Graphical Abstract
Evaluation of the Clinical Utility of the Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP): A Case-Based Pilot Assessment
Authors: Alcorn Sara R. , LaVigne Anna W. , Elledge Christen R. , Fiksel Jacob , Hu Chen , Kleinberg Lawrence , Levin Adam , Smith Thomas , Cheng Zhi , Kim Kibem , Rao Avani D. , Sloan Lindsey , Page Brandi , Stinson Susan F. , Voong K. Ranh , McNutt Todd R. , Bowers Michael R. , DeWeese Theodore L. , Zeger Scott , Wright Jean L. 
Published: October 2022

PURPOSE The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clinical environment. METHODS Ten Radiation Oncology physicians reviewed 55 patient cases at two time points: without and then with the use of BMETS-DSP. Assessment included 12-month survival estimate, confidence in and likelihood of sharing estimates with patients, and recommendations for open surgery, systemic therapy, hospice referral, and radiotherapy (RT) regimen. Paired statistics compared pre- versus post-DSP outcomes. Reported statistical significance is P < .05. RESULTS Pre- versus post-DSP, overestimation of true minus estimated survival time was significantly reduced (mean difference –2.1 [standard deviation 4.1] v –1 month [standard deviation 3.5]). Prediction accuracy was significantly improved at cut points of < 3 (72 v 79%), ≤ 6 (64 v 71%), and ≥ 12 months (70 v 81%). Median ratings of confidence in and likelihood of sharing prognosis significantly increased. Significantly greater concordance was seen in matching use of 1-fraction RT with the true survival < 3 months (70 v 76%) and < 10-fraction RT with the true survival < 12 months (55 v 62%) and appropriate use of open surgery (47% v 53%), without significant changes in selection of hospice referral or systemic therapy. CONCLUSION This pilot study demonstrates that BMETS-DSP significantly improved physician survival estimation accuracy, prognostic confidence, likelihood of sharing prognosis, and use of prognosis-appropriate RT regimens in the care of symptomatic bone metastases, supporting future multi-institutional validation of the platform.
Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non–Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study
Authors: de Castro Gilberto , Kudaba Iveta , Wu Yi-Long , Lopes Gilberto , Kowalski Dariusz M. , Turna Hande Z. , Caglevic Christian , Zhang Li , Karaszewska Boguslawa , Laktionov Konstantin K. , Srimuninnimit Vichien , Bondarenko Igor , Kubota Kaoru , Mukherjee Rinee , Lin Jianxin , Souza Fabricio , Mok Tony S.K. , Cho Byoung Chul 
Published: October 2022

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co‐primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report 5-year results from the phase III KEYNOTE-042 study (ClinicalTrials.gov identifier: NCT02220894 ). Eligible patients with locally advanced/metastatic non–small-cell lung cancer (NSCLC) without EGFR/ALK alterations and with programmed death ligand-1 (PD-L1) tumor proportion score (TPS) ≥ 1% received pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin + paclitaxel or pemetrexed) for 4-6 cycles with optional maintenance pemetrexed. Primary end points were overall survival (OS) in PD-L1 TPS ≥ 50%, ≥ 20%, and ≥ 1% groups. Patients who completed 35 cycles of pembrolizumab with ≥ stable disease could begin second-course pembrolizumab upon progression. One thousand two hundred seventy‐four patients were randomly assigned (pembrolizumab, n = 637; chemotherapy, n = 637). Median follow-up time was 61.1 (range, 50.0-76.3) months. OS outcomes favored pembrolizumab ( v chemotherapy) regardless of PD-L1 TPS (hazard ratio [95% CI] for TPS ≥ 50%, 0.68 [0.57 to 0.81]; TPS ≥ 20%, 0.75 [0.64 to 0.87]; TPS ≥ 1%, 0.79 [0.70 to 0.89]), with estimated 5-year OS rates with pembrolizumab of 21.9%, 19.4%, and 16.6%, respectively. No new toxicities were identified. Objective response rate was 84.3% among 102 patients who completed 35 cycles of pembrolizumab and 15.2% among 33 patients who received second-course pembrolizumab. First-line pembrolizumab monotherapy continued to show durable clinical benefit versus chemotherapy after 5 years of follow-up in PD-L1–positive, locally advanced/metastatic NSCLC without EGFR/ALK alterations and remains a standard of care.
Single-cell transcriptional and functional analysis of dopaminergic neurons in organoid-like cultures derived from human fetal midbrain
Authors: Birtele Marcella , Storm Petter , Sharma Yogita , Kajtez Janko , Wahlestedt Jenny Nelander , Sozzi Edoardo , Nilsson Fredrik , Stott Simon , He Xiaoling L. , Mattsson Bengt , Ottosson Daniella Rylander , Barker Roger A. , Fiorenzano Alessandro , Parmar Malin 
Published: October 2022

ABSTRACT
Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells for application in disease modeling, diagnostics, drug screening and cell-based therapies for Parkinson's disease. An increased understanding of the timing and molecular mechanisms that promote the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from pluripotent stem cells. Here, we use droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11 weeks post-conception) and their subsequent differentiation into functional mature DA neurons in primary fetal 3D organoid-like cultures. This approach reveals that 3D cultures are superior to monolayer conditions for their ability to generate and maintain mature DA neurons; hence, they have the potential to be used for studying human VM development. These results provide a unique transcriptional profile of the developing human fetal VM and functionally mature human DA neurons that can be used to guide stem cell-based therapies and disease modeling approaches in Parkinson's disease.