bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of serious and life-threatening COVID-19 pneumonia as the SARS-CoV-2 pandemic progressed: an observational study of mortality to 60 days after admission to a 15-hospital US health system
Authors: Murthy Sudish C , Gordon Steven M , Lowry Ashley M , Blackstone Eugene H 
Published: July 2024

ObjectiveIn order to predict at hospital admission the prognosis of patients with serious and life-threatening COVID-19 pneumonia, we sought to understand the clinical characteristics of hospitalised patients at admission as the SARS-CoV-2 pandemic progressed, document their changing response to the virus and its variants over time, and identify factors most importantly associated with mortality after hospital admission.DesignObservational study using a prospective hospital systemwide COVID-19 database.Setting15-hospital US health system.Participants26 872 patients admitted with COVID-19 to our Northeast Ohio and Florida hospitals from 1 March 2020 to 1 June 2022.Main outcome measures60-day mortality (highest risk period) after hospital admission analysed by random survival forests machine learning using demographics, medical history, and COVID-19 vaccination status, and viral variant, symptoms, and routine laboratory test results obtained at hospital admission.ResultsHospital mortality fell from 11% in March 2020 to 3.7% in March 2022, a 66% decrease (p<0.0001); 60-day mortality fell from 17% in May 2020 to 4.7% in May 2022, a 72% decrease (p<0.0001). Advanced age was the strongest predictor of 60-day mortality, followed by admission laboratory test results. Risk-adjusted 60-day mortality had all patients been admitted in March 2020 was 15% (CI 3.0% to 28%), and had they all been admitted in May 2022, 12% (CI 2.2% to 23%), a 20% decrease (p<0.0001). Dissociation between observed and predicted decrease in mortality was related to temporal change in admission patient profile, particularly in laboratory test results, but not vaccination status or viral variant.ConclusionsHospital mortality from COVID-19 decreased substantially as the pandemic evolved but persisted after hospital discharge, eclipsing hospital mortality by 50% or more. However, after accounting for the many, even subtle, changes across the pandemic in patients’ demographics, medical history and particularly admission laboratory results, a patient admitted early in the pandemic and predicted to be at high risk would remain at high risk of mortality if admitted tomorrow.
Exploring fidelity of enactment in a cluster randomised controlled trial testing the effectiveness of ‘gatekeeper’ training for pesticide vendors in reducing self-poisoning in rural Sri Lanka: protocol for a multimethod qualitative study
Authors: Kanapathy Rajaratnam , Agampodi Thilini , Eddleston Michael , Konradsen Flemming , Pearson Melissa , Sanjula Bimali , Malalasekara Charuni , Naseer Nasman , Agampodi Suneth , Weerasinghe Manjula 
Published: July 2024

IntroductionPesticide self-poisoning causes severe health and socioeconomic hardship in low- and middle-income countries, including Sri Lanka. A stepped-wedge cluster randomised controlled trial (cRCT) has been designed to test whether ‘gatekeeper’ training for pesticide vendors reduces pesticide self-poisoning in rural Sri Lanka (Vendor cRCT). Ensuring intervention fidelity in RCTs is essential for consistently replicating interventions, accurately assessing their impact and improving outcomes. Thus, the overarching goal of this proposed study is to explore to what extent the pesticide vendors use the ‘gatekeeper’ strategies.Methods and analysisA multimethod qualitative research design is being used to explore the pesticide-selling behaviours of vendors after the ‘gatekeeper’ training. A subsample of the Vendor cRCT Study population is being recruited using a stratified purposive sampling method in all six intervention districts in Sri Lanka to ensure that the sample is representative of the pesticide vendors in the study area. Participant diaries, observations and focus group discussions are being adopted to collect data. Data triangulation will be performed and data will be analysed thematically.Ethics and disseminationThe study was approved by the Ethics and Research Committee, Faculty of Medicine and Allied Sciences, at the Rajarata University of Sri Lanka (ERC/2023/09). All participants will provide informed consent. Findings will be disseminated in scientific peer-reviewed journals and conference presentations.
EASIER trial (Erector-spinAe analgeSia for hepatopancreaticobiliary pain In the Emergency Room): a single-centre open-label cohort-based randomised controlled trial analysing the efficacy of the ultrasound-guided erector-spinae plane block compared with intravenous morphine in the treatment of acute hepatopancreaticobiliary pain in the emergency department
Authors: David Sandeep Nathanael , Murali Vignesh , Kattumala Pradeep Daniel , Abhilash Kundavaram Paul Prabhakar , Thomas Ajith , Chowdury Sudipta Dhar , Karuppusami Reka 
Published: July 2024

BackgroundUltrasound-guided (USG) erector-spinae plane block (ESPB) may be better than intravenous opioids in treating acute hepatopancreaticobiliary (HPB) pain in the ED.MethodsThis open-label randomised controlled trial was conducted in the ED of a tertiary-care hospital between March and August 2023. All adult patients with severe HPB pain were recruited during times that a primary investigator was present. Unconsenting patients, numeric rating scale (NRS) ≤6, age ≤18 and ≥80 years, pregnant, unstable or with allergies to local anaesthetics or opioids were excluded. Patients in the intervention arm received bilateral USG ESPB with 0.2% ropivacaine at T7 level, by a trained ED consultant, and those in the control arm received 0.1 mg/kg intravenous morphine. Pain on a 10-point NRS was assessed by the investigators at presentation and at 1, 3, 5 and 10 hours after intervention by the treatment team, along with rescue analgesia requirements and patient satisfaction. Difference in NRS was analysed using analysis of co-variance (ANCOVA) and t-tests.Results70 participants were enrolled, 35 in each arm. Mean age was 40.4±13.2 years, mean NRS at presentation in the intervention arm was 8.0±0.9 and 7.6±0.6 in the control arm. NRS at 1 hour was significantly lower in the ESPB group (ANCOVA p<0.001). At 1, 3, 5 and 10 hours, reduction of NRS in the intervention arm (7±1.6, 6.7±1.9, 6.6±1.8, 6.1±1.9) was significantly greater than the control arm (4.4±2, 4.6±1.8, 3.7±2.2, 3.8±1.8) (t-test, p<0.001). Fewer patients receiving ESPB required rescue analgesia at 5 (t-test, p=0.031) and 10 hours (t-test, p=0.04). More patients were ‘very satisfied’ with ESPB compared with receiving only morphine at each time period (p<0.001).ConclusionESPB is a promising alternative to morphine in those with HPB pain.Trial registration numberCTRI/2023/03/050595.
Complete replacement of soybean meal with black soldier fly larvae meal in feeding program for broiler chickens from placement through to 49 days of age: impact on gastrointestinal, breast, skeletal, plasma, and litter attributes
Authors: Facey Hannah , Kithama Munene , Mohammadigheisar Mohsen , Barbut Shai , Huber Lee-Anne , Shoveller Anna K. , Kiarie Elijah G. 
Published: July 2024

We previously reported that high levels (≥50%) of black soldier fly larvae meal (BSFLM) reduced growth and altered organs morphology in broiler chickens. Herein we further examined gastrointestinal, breast, bone, plasma, and litter attributes in broiler chickens fed partial to complete replacement of soybean meal (SBM) with BSFLM. A total of 1152 day-old Ross × Ross 708 male chicks ( n = 8) were allocated to 48 pens and assigned one of six diets: a basal corn-SBM diet (0BSFLM), four diets in which SBM in 0BSFLM was replaced with BSFLM at 12.5%, 25%, 50%, and 100% (12.5BSFLM, 25BSFLM, 50BSFLM, and 100BSFLM) and a final diet (0 + AGP) in which 0BSFLM was fed with coccidiostat and antibiotic. Birds were bled for plasma and necropsied for samples. Litter samples were collected on days 45 to 47. Breast weight, woody breast, and hardness scores and tibia morphometry reduced linearly in response to BSFLM inclusion ( P < 0.001). BSFLM linearly increased plasma Lys, Met, Thr, uric acid, creatine kinase and decreased Arg and potassium ( P < 0.05). Litter ammonium nitrogen and potassium decreased linearly in response to BSFLM ( P < 0.001). In conclusion, the data suggested physiological and metabolic inefficiencies in broiler chickens fed isocaloric and isonitrogenous diets with ≥50% BSFLM replacement of SBM.
Novel Therapies in Cancer: Trials and Tribulations
Authors: Waqar Saiama N. , Govindan Ramaswamy 
Published: July 2024

Summary
Clinical trials are the backbone for advancing therapeutic options for patients diagnosed with cancer. Yet only 7.1% of patients with cancer participate in clinical trials in the United States. In this article, we review some of the reasons for poor accrual and discuss potential solutions.
See related article by van Berge Henegouwen et al., p. 3937
ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma
Authors: Benitz Simone , Steep Alec , Nasser Malak M. , Preall Jonathan , Mahajan Ujjwal Mukund , McQuithey Holly , Loveless Ian , Davis Erick T. , Wen Hui-Ju , Long Daniel W. , Metzler Thomas , Zwernik Samuel , Louw Michaela , Rempinski Donald , Salas-Escabillas Daniel J. , Brender Sydney M. , Song Linghao , Huang Ling , Theisen Brian K. , Zhang Zhenyu , Steele Nina G. , Regel Ivonne , Bednar Filip , Crawford Howard C. 
Published: July 2024

Abstract
Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor PDX1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in a mouse and human. We identified the receptor tyrosine kinase ROR2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition.
Significance: We discovered the receptor tyrosine kinase ROR2 as an important regulator of cellular identity in pancreatic precancerous lesions and pancreatic cancer. ROR2 drives an aggressive PDAC phenotype and confers resistance to KRAS inhibitors, suggesting that targeting ROR2 will enhance sensitivity to this new generation of targeted therapies.
See related commentary by Marasco and Misale, p. 2018
A Classical Epithelial State Drives Acute Resistance to KRAS Inhibition in Pancreatic Cancer
Authors: Singhal Anupriya , Styers Hannah C. , Rub Jonathan , Li Zhuxuan , Torborg Stefan R. , Kim Jung Yun , Grbovic-Huezo Olivera , Feng Huijin , Tarcan Zeynep Cagla , Sahin Ozkan Hulya , Hallin Jill , Basturk Olca , Yaeger Rona , Christensen James G. , Betel Doron , Yan Yan , Chio Iok In Christine , de Stanchina Elisa , Tammela Tuomas 
Published: July 2024

Abstract
Intratumoral heterogeneity in pancreatic ductal adenocarcinoma (PDAC) is characterized by a balance between basal and classical epithelial cancer cell states, with basal dominance associating with chemoresistance and a dismal prognosis. Targeting oncogenic KRAS, the primary driver of pancreatic cancer, shows early promise in clinical trials, but efficacy is limited by acquired resistance. Using genetically engineered mouse models and patient-derived xenografts, we find that basal PDAC cells are highly sensitive to KRAS inhibitors. Employing fluorescent and bioluminescent reporter systems, we longitudinally track cell-state dynamics in vivo and reveal a rapid, KRAS inhibitor–induced enrichment of the classical state. Lineage tracing uncovers that these enriched classical PDAC cells are a reservoir for disease relapse. Genetic or chemotherapy-mediated ablation of the classical cell state is synergistic with KRAS inhibition, providing a preclinical proof of concept for this therapeutic strategy. Our findings motivate combining classical state–directed therapies with KRAS inhibitors to deepen responses and counteract resistance in pancreatic cancer.
Significance: KRAS inhibitors hold promise in pancreatic cancer, but responses are limited by acquired resistance. We find that a classical epithelial cancer cell state is acutely resistant to KRAS inhibition and serves as a reservoir for disease relapse. Targeting the classical state alongside KRAS inhibition deepens responses, revealing a potent therapeutic strategy.
See related commentary by Marasco and Misale, p. 2018
Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses
Authors: Liu Lu , Cai Peng , Gu Weifang , Duan Xingxun , Gao Shiwen , Ma Xuelian , Ma Yuhui , Ma Siyuan , Li Guoqing , Wang Xiangyu , Cai Kuojun , Wang Yanfeng , Cai Tao , Zhao Hongqiong 
Published: July 2024

AbstractRhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines.
Highly active repeat-mediated recombination in the mitogenome of the aquatic grass Hygroryza aristata
Authors: Wang Huijun , Wu Zhigang , Li Tao , Zhao Jindong 
Published: July 2024

Abstract
Background
Floating bamboo (Hygroryza aristata) is an endangered species with a narrow native distribution and is renowned for its unique aesthetic qualities, which holds significant ecological and ornamental value. However, the lack of genetic information research, with only one complete plastome available, significantly hampers conservation efforts and further research for this species.

Results
In this research, we sequenced and assembled the organelle genomes of floating bamboo, including the mitogenome (587,847 bp) and plastome (135,675 bp). The mitogenome can recombine into various configurations, which are mediated by 25 repeat pairs (13 SRs, 6 MRs, 1 LR, and 5 CRs). LR1 and SR5 are particularly notable as they have the ability to combine with other contigs, forming complex repeat units that facilitate further homologous recombination. The rate of homologous recombination varies significantly among species, yet there is still a pronounced positive correlation observed between the length of these repeat pairs and the rate of recombination they mediate. The mitogenome integrates seven intact protein-coding genes from the chloroplast. The codon usage patterns in both organelles are similar, with a noticeable bias towards C and T on the third codon. The gene map of Poales shows the entire loss of rpl6, succinate dehydrogenase subunits (sdh3 and sdh4). Additionally, the BOP clade retained more variable genes compared to the PACMAD clade.

Conclusions
We provided a high-quality and well-annotated mitogenome for floating bamboo and demonstrated the presence of diverse configurations. Our study has revealed the correlation between repeat length and their corresponding recombination rate despite variations among species. Although the mitogenome can potentially exist in the form of a unicircular in vivo, this occurrence is rare and may not be stable.
Effects of a co-bacterial agent on the growth, disease control, and quality of ginseng based on rhizosphere microbial diversity
Authors: Li Xinyue , Liu Qun , Gao Yugang , Zang Pu , Zheng Tong 
Published: July 2024

Abstract
Background
The ginseng endophyte Paenibacillus polymyxa Pp-7250 (Pp-7250) has multifaceted roles such as preventing ginseng diseases, promoting growth, increasing ginsenoside accumulation, and degrading pesticide residues, however, these effects still have room for improvements. Composite fungicides are an effective means to improve the biocontrol effect of fungicides, but the effect of Pp-7250 in combination with its symbiotic bacteria on ginseng needs to be further investigated, and its mechanism of action has not been elucidated. In this study, a series of experiments was conducted to elucidate the effect of Paenibacillus polymyxa and Bacillus cereus co-bacterial agent on the yield and quality of understory ginseng, and to investigate their mechanism of action.

Results
The results indicated that P. polymyxa and B. cereus co-bacterial agent (PB) treatment improved ginseng yield, ginsenoside accumulation, disease prevention, and pesticide degradation. The mechanism is that PB treatment increased the abundance of beneficial microorganisms, including Rhodanobacter, Pseudolabrys, Gemmatimonas, Bacillus, Paenibacillus, Cortinarius, Russula, Paecilomyces, and Trechispora, and decreased the abundance of pathogenic microorganisms, including Ellin6067, Acidibacter, Fusarium, Tetracladium, Alternaria, and Ilyonectria in ginseng rhizosphere soil. PB co-bacterial agents enhanced the function of microbial metabolic pathways, biosynthesis of secondary metabolites, biosynthesis of antibiotics, biosynthesis of amino acids, carbon fixation pathways in prokaryotes, DNA replication, and terpenoid backbone biosynthesis, and decreased the function of microbial plant pathogens and animal pathogens.

Conclusion
The combination of P. polymyxa and B. cereus may be a potential biocontrol agent to promote the resistance of ginseng to disease and improve the yield, quality, and pesticide degradation.
The application of varying amount of green manure combined with nitrogen fertilizer altered the soil bacterial community and rice yield in karst paddy areas
Authors: Zhong Juxin , Li Zhongyi , Tang Hongqin , Dong Wenbin , Wei Caihui , He Tieguang 
Published: July 2024

AbstractLong-term application of green manure (GM) and nitrogen (N) fertilizers markedly improved soil fertility and boosted rice yield in ecologically fragile karst paddy fields. However, the precise response mechanisms of the soil bacterial community to varying amounts of green manure alone and in combination with N fertilizer in such environments remain poorly elucidated. In this study, we investigated the soil bacterial communities, keystone taxa, and their relationship with soil environmental variables across eight fertilization treatments. These treatments included group without N addition (N0M0, no N fertilizer and no GM; N0M22.5, 22.5 t/ha GM; N0M45, 45 t/ha GM, N0M67.5, 67.5 t/ha GM) and group with N addition (NM0, N fertilizer and no GM; NM22.5, N fertilizer and 22.5 t/ha GM; NM45, N fertilizer and 45 t/ha GM; NM67.5, N fertilizer and 67.5 t/ha GM). The results revealed that increasing green manure input significantly boosted rice yield by 15.51–22.08% and 21.84–35% in both the group without and with N addition, respectively, compared to N0M0 treatment. Moreover, with escalating green manure input, soil TN, AN, AK, and AP showed an increasing trend in the group without N addition. However, following the addition of N fertilizer, TN and AN content initially rose, followed by a decline due to the enhanced nutrient availability for rice. Furthermore, the application of a large amount of N fertilizer decreased the C: N ratio in the soil, resulting in significant changes in both the soil microbial community and its function. Particularly noteworthy was the transition of keystone taxa from their original roles as N-fixing and carbon-degrading groups (oligotrophs) to roles in carbon degradation (copiotrophs), nitrification, and denitrification. This shift in soil community and function might serve as a primary factor contributing to enhanced nutrient utilization efficiency in rice, thus significantly promoting rice yield.
Construction and validation of a nomogram for predicting survival in elderly patients with severe acute pancreatitis: a retrospective study from a tertiary center
Authors: Zhu Qingcheng , Lu Mingfeng , Ling Bingyu , Tan Dingyu , Wang Huihui 
Published: July 2024

Abstract
Purpose
There is a lack of adequate models specifically designed for elderly patients with severe acute pancreatitis (SAP) to predict the risk of death. This study aimed to develop a nomogram for predicting the overall survival of SAP in elderly patients.

Methods
Elderly patients diagnosed with SAP between January 1, 2017 and December 31, 2022 were included in the study. Risk factors were identified through least absolute shrinkage and selection operator regression analysis. Subsequently, a novel nomogram model was developed using multivariable logistic regression analysis. The predictive performance of the nomogram was evaluated using metrics such as the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA).

Results
A total of 326 patients were included in the analysis, with 260 in the survival group and 66 in the deceased group. Multivariate logistic regression indicated that age, respiratory rate, arterial pH, total bilirubin, and calcium were independent prognostic factors for the survival of SAP patients. The nomogram demonstrated a performance comparable to sequential organ failure assessment (P = 0.065). Additionally, the calibration curve showed satisfactory predictive accuracy, and the DCA highlighted the clinical application value of the nomogram.

Conclusion
We have identified key demographic and laboratory parameters that are associated with the survival of elderly patients with SAP. These parameters have been utilized to create a precise and user-friendly nomogram, which could be an effective and valuable clinical tool for clinicians.