bluuebunny/crossref_metadata_2025_split huggingface dataset:
A four‐step biosynthetic pathway involving C‐3 oxidation–reduction reactions from cycloastragenol to astragaloside IV in Astragalus membranaceus
Authors: Zhang Meng , Bao Yang‐Oujie , Zhao Chun‐Xue , Tian Yun‐Gang , Wang Zi‐Long , Qiao Xue , Ye Min 
Published: August 2024

SUMMARYAstragaloside IV is a significant chemical component derived from the medicinal plant Astragalus membranaceus. Despite the characterization of several glycosyltransferases from A. membranaceus, the complete biosynthetic pathway of astragaloside IV has not been fully elucidated. In this study, we propose a biosynthetic pathway for astragaloside IV that involves a sequence of oxidation–reduction reactions. The biosynthesis pathway from cycloastragenol to astragaloside IV encompasses four key steps: C‐3 oxidation, 6‐O‐glucosylation, C‐3 reduction, and 3‐O‐xylosylation. We identified a hydroxysteroid dehydrogenase AmHSD1 from A. membranaceus. AmHSD1 catalyzes the C‐3 oxidation of cycloastragenol, yielding cycloastragenol‐3‐one, and the C‐3 reduction of cycloastragenol‐3‐one‐6‐O‐glucoside, resulting in cycloastragenol‐6‐O‐glucoside. Additionally, the glycosyltransferases AmGT8 and AmGT1, previously reported by our groups, were identified as catalyzing the 6‐O‐glucosylation and 3‐O‐xylosylation steps, respectively. Astragaloside IV was successfully synthesized in transient expression in Nicotiana benthamiana using the combination of AmHSD1, AmGT8 and AmGT1. These results support the proposed four‐step biosynthetic pathway and suggest that AmHSD1 probably plays a crucial role in the biosynthesis of astragaloside IV within A. membranaceus.
Comprehensive Analysis of the Tumour Immune Microenvironment in Canine Urothelial Carcinoma Reveals Immunosuppressive Mechanisms Induced by the COX–Prostanoid Cascade
Authors: Eto Shotaro , Kato Daiki , Saeki Kohei , Iguchi Takaaki , Shiyu Qin , Kamoto Satoshi , Yoshitake Ryohei , Shinada Masahiro , Ikeda Namiko , Tsuboi Masaya , Chambers James , Uchida Kazuyuki , Nishimura Ryohei , Nakagawa Takayuki 
Published: August 2024

ABSTRACTA comprehensive understanding of the tumour immune microenvironment (TIME) is essential for advancing precision medicine and identifying potential therapeutic targets. This study focused on canine urothelial carcinoma (cUC) recognised for its high sensitivity to cyclooxygenase (COX) inhibitors. Using immunohistochemical techniques, we quantified the infiltration of seven immune cell populations within cUC tumour tissue to identify clinicopathological features that characterise the TIME in cUC. Our results revealed several notable factors, including the significantly higher levels of CD3+ T cells and CD8+ T cells within tumour cell nests in cases treated with preoperative COX inhibitors compared to untreated cases. Based on the immunohistochemistry data, we further performed a comparative analysis using publicly available RNA‐seq data from untreated cUC tissues (n = 29) and normal bladder tissues (n = 4) to explore the link between COX–prostanoid pathways and the immune response to tumours. We observed increased expression of COX‐2, microsomal prostaglandin E2 synthase‐1 (mPGES‐1) and mPGES‐2 in cUC tissues. However, only mPGES‐2 showed a negative correlation with the cytotoxic T‐cell (CTL)–related genes CD8A and granzyme B (GZMB). In addition, a broader analysis of solid tumours using The Cancer Genome Atlas (TCGA) database revealed similar patterns in several human tumours, suggesting a common mechanism in dogs and humans. Our results suggest that the COX‐2/mPGES‐2 pathway may act as a cross‐species tumour‐intrinsic factor that weakens anti‐tumour immunity, and that COX inhibitors may convert TIME from a ‘cold tumour’ to a ‘hot tumour’ state by counteracting COX/mPGES‐2–mediated immunosuppression.
The inclusion of cereal crops with maize and soyabean rotations impacts the morphology and phenology of Amaranthus tuberculatus
Authors: Hamberg Ryan C. , Yadav Ramawatar , Owen Micheal D. K. 
Published: August 2024

AbstractSimple crop rotations like maize and soyabean grown in succession often coincide with simple weed management tactics, resulting in weed infestations that are highly adapted to the conditions maintained for the selected crops. Amaranthus tuberculatus is a prominent weed species which possesses biological characteristics that allow it to persist in maize–soyabean rotations. Spring wheat and oats emerge earlier than A. tuberculatus and are grown in narrower rows than maize and soyabean, which may increase their competitive capability. A field study which measured morphological and phenological characteristics of three A. tuberculatus cohorts that emerged under fallow, maize, soyabean, spring wheat and oats was conducted to compare their competitive ability. Early emerged A. tuberculatus grew similarly in fallow, maize and soyabeans and grew to heights of >150 cm but was significantly reduced in spring wheat and oats, never exceeding 40 cm. Heights of the last emerged cohorts were more influenced by crop canopies never reaching 15 cm in spring wheat and oats compared to >70 cm in fallow. Early emerged A. tuberculatus canopy diameter and branches plant−1 were reduced by >80% in spring wheat and oats compared to fallow. Flowering was delayed in spring wheat and oats compared to fallow and seed production and biomass were reduced by 99% across cohorts. Growth suppression of A. tuberculatus, based on the findings, can be achieved under dense, competitive crop canopies such as in spring wheat and oats and these crops should be considered as additional crops in maize–soyabean rotations.
Skeletal muscle myosin heavy chain fragmentation as a potential marker of protein degradation in response to resistance training and disuse atrophy
Authors: Plotkin Daniel L. , Mattingly Madison L. , Anglin Derick A. , Michel J. Max , Godwin Joshua S. , McIntosh Mason C. , Kontos Nicholas J. , Bergamasco João G. A. , Scarpelli Maíra C. , Angleri Vitor , Taylor Lemuel W. , Willoughby Darryn S. , Mobley C. Brooks , Kavazis Andreas N. , Ugrinowitsch Carlos , Libardi Cleiton A. , Roberts Michael D. 
Published: August 2024

AbstractWe examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men (n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study (n = 7) and a study involving 2 weeks of leg immobilization (n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHCTotal) increased 3 h post‐RE (∼200%, P = 0.018) and returned to pre‐exercise levels by 6 h post‐RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post‐RE (8.6 ± 6.3‐fold vs. 2.1 ± 0.7‐fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24 h post‐RE (+65% and +36%, P < 0.001); however, the last RE bout response was attenuated compared to the first bout (P = 0.045). Although cycling exercise did not alter MyHCTotal fragmentation, ∼8% VL atrophy with 2 weeks of leg immobilization increased MyHCTotal fragmentation (∼108%, P < 0.001). Mechanistic C2C12 myotube experiments indicated that MyHCTotal fragmentation is likely due to calpain proteases. In summary, RE and disuse atrophy increase MyHC protein fragmentation. Research into how ageing and disease‐associated muscle atrophy affect these outcomes is needed.Highlights
What is the central question of this study?How different exercise stressors and disuse affect skeletal muscle myosin heavy chain fragmentation.
What is the main finding and its importance?This investigation is the first to demonstrate that resistance exercise and disuse atrophy lead to skeletal muscle myosin heavy chain protein fragmentation in humans. Mechanistic in vitro experiments provide additional evidence that MyHC fragmentation occurs through calpain proteases.
Randomised controlled decentralised feasibility trial of a fixed low-dose combination antihypertensive drug strategy to attenuate cognitive decline in high-risk adults
Authors: Carcel Cheryl , Clancy Lauren , Harris Katie , Peters Ruth , Byrne Aisling , Bassett Kimberley , Freed Ruth , Hoyos Camilla M , Rodgers Anthony , Lindley Richard , Chalmers John , Xu Ying , Woodward Mark , Ouyang Menglu , Naismith Sharon L , Anderson Craig 
Published: August 2024

ObjectivesThe Action To promote brain HEalth iN Adults study aimed to determine the feasibility and applicability of recruitment using home blood pressure (BP) monitoring, routine blood biochemistry and videoconference measures of cognition, in adults at high risk of dementia.DesignA decentralised double-blind, placebo-controlled, randomised feasibility trial with a four-stage screening process.SettingConducted with participants online in the state of New South Wales, Australia.ParticipantsParticipants were aged 50–70 years with moderately elevated BP (systolic >120 and <160 mm Hg or diastolic >80 and <95 mm Hg) and ≥1 additional enrichment risk factor of monotherapy treatment of hypertension, diabetes mellitus, elevated low-density lipoprotein cholesterol, obesity, current smoking or a first degree relative with dementia, which indicated an elevated risk for future cognitive decline.InterventionTriple Pill (active antihypertensive treatment of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg) or placebo Triple Pill (blinded study capsules).Primary and secondary outcome measuresPrimary outcome was feasibility of the study expressed as the percentage of participants randomised from those who were screened. Secondary outcomes were the applicability of videoconference measures of cognition and the overall trial, tolerability of the Triple Pill, safety outcomes and medication adherence.ResultsThe proportion (95% CI) of patients randomised to those screened was 5% (2%–10%). The applicability of the trial expressed as percentage of those who completed all remote assessments over the number of randomised participants was 67% (95% CI 05 to 22%). There were no serious adverse events or withdrawals from treatment. All participants adhered to study medication, except for one person who had two capsules left at the end of the study period.ConclusionsThe feasibility of this decentralised trial on BP lowering in patients at high risk for dementia is low. However, the applicability of remote assessments of cognitive function is acceptable.Trial registration numberAustralian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000121864.
Cohort profile: study design and baseline characteristics of an observational longitudinal weight loss cohort and biorepository of patients undergoing sleeve gastrectomy in the USA
Authors: Vanegas Sally M , Curado Silvia , Gujral Akash , Valverde Gabriela , Parraga Susan , Aleman Jose O , Reid Migdalia , Elbel Brian , Schmidt Ann Marie , Heffron Sean P , Segal Eran , Li Huilin , Abrams Courtney , Sevick Mary A , Popp Collin , Armijos Evelyn , Merriwether Ericka N , Ivezaj Valentina , Ren-Fielding Christine , Parikh Manish , Jay Melanie 
Published: August 2024

PurposeWe developed a comprehensive sleeve gastrectomy (SG) weight loss study cohort and biorepository to uncover mechanisms, biomarkers and predictive factors of weight loss, weight maintenance and amelioration of obesity-related comorbidities. For this purpose, we collected psychosocial, anthropometric, clinical data and a variety of samples pre-surgery, intraoperatively and 1.5, 3, 12 and 24 months post-surgery. For longer-term assessment, the collection of psychosocial and anthropometric data was extended to 10 years. Here, we present in-depth characterisation of the cohort and detailed overview of study procedures as a foundation for future analyses.ParticipantsWe consented 647 participants between June 2017 and March 2020 from two bariatric surgery clinics in New York City—one major urban hospital and one private hospital. Of 355 participants who provided baseline data, 300 underwent SG. Of these, 79% are females with an average age of 38 years, 68% are Hispanic, 20% are non-Hispanic Black and 11% are non-Hispanic White.Findings to dateWe collected intraoperative adipose and stomach tissues from 282 patients and biosamples (blood, urine, saliva, stool) from 245 patients at 1.5 months, 238 at 3 month, 218 at 12 months and 180 at 24 months post-surgery. We are currently collecting anthropometric and psychosocial data annually until 10 years post-surgery. Data analysis is currently underway.Future plansOur future research will explore the variability in weight loss outcomes observed in our cohort, particularly among Black and Hispanic patients in comparison to their White counterparts. We will identify social determinants of health, metabolic factors and other variables that may predict weight loss success, weight maintenance and remission of obesity-related comorbidities. Additionally, we plan to leverage our biorepository for collaborative research studies. We will complete long-term follow-up data by December 2031. We plan to apply for funding to expand biosample collection through year 10 to provide insights into the mechanisms of long-term weight maintenance.
Trends in the burden of hospitalised patients with cirrhosis in Switzerland: a cross-sectional study of cirrhosis-related hospitalisations between 1998 and 2020
Authors: Favre-Bulle Timothee , Moradpour Darius , Marques-Vidal Pedro , Vaucher Julien 
Published: August 2024

ObjectiveLiver cirrhosis is an increasing cause of morbidity and mortality worldwide with a heavy load on healthcare systems. We analysed the trends in hospitalisations for cirrhosis in Switzerland.DesignCross-sectional study.SettingLarge nationwide inpatient database, years between 1998 and 2020.ParticipantsHospitalisations for cirrhosis of adult patients were selected.Main outcomes and measuresHospitalisations with either a primary diagnosis of cirrhosis or a cirrhosis-related primary diagnosis with a mandatory presence of cirrhosis as a secondary diagnosis were considered following the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes. Trends in demographic and clinical characteristics, in-hospital mortality and length of stay were analysed. Causes and costs of cirrhosis-related hospitalisations were available from 2012 onwards.ResultsCirrhosis-related hospitalisations increased from 1631 in 1998 to 4052 in 2020. Of the patients, 68.7% were men. Alcohol-related liver disease was the leading cause, increasing from 44.1% (95% CI, 42.4% to 45.9%) in 2012 to 47.9% (95% CI, 46.4% to 49.5%) in 2020. Assessed by exclusion of other coded causes, non-alcoholic fatty liver disease was the second cause at 42.7% (95% CI, 41.2% to 44.3%) in 2020. Hepatitis C virus-related cirrhosis decreased from 12.3% (95% CI, 11.2% to 13.5%) in 2012 to 3.2% (95% CI, 2.7% to 3.8%) in 2020. Median length of stay decreased from 11 to 8 days. Hospitalisations with an intensive care unit stay increased from 9.8% (95% CI, 8.4% to 11.4%) to 15.6% (95% CI, 14.5% to 16.8%). In-hospital mortality decreased from 12.1% (95% CI, 10.5% to 13.8%) to 9.7% (95% CI, 8.8% to 10.7%). Total costs increased from 54.4 million US$ (51.4 million €) in 2012 to 92.6 million US$ (87.5 million €) in 2020.ConclusionsCirrhosis-related hospitalisations and related costs increased in Switzerland from 1998 to 2020 but in-hospital mortality decreased. Alcohol-related liver disease and non-alcoholic fatty liver disease were the most prevalent and preventable aetiologies of cirrhosis-related hospitalisations.
Effect of health extension workers-led home-based multicomponent intervention on blood pressure reduction among hypertensive patients in rural districts of northwest Ethiopia: a cluster-randomised controlled trial
Authors: Teshome Destaw Fetene , Alemu Shitaye , Ayele Tadesse Awoke , Atnafu Asmamaw , Gelaye Kassahun Alemu 
Published: August 2024

ObjectivesTo evaluate effects of health extension workers-led home-based multicomponent intervention on blood pressure change in hypertensive patients in rural districts of northwest Ethiopia.DesignTwo-arm cluster randomised controlled trial was conducted.ParticipantsHypertensive patients’ age ≥25 years were included. 20 clusters or kebeles with 456 participants were randomly assigned to the intervention group (10 clusters with 228 participants) and the control group (10 clusters with 228 participants).InterventionsParticipants in the intervention kebeles received health extension workers-led home-based multicomponent interventions every other month for 40–60 min for 9 months.Main outcome measuresThe primary outcomes were the differences in mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) changes from baseline between patients in the intervention and control groups. Intention-to-treat analysis was used for the primary analyses. Linear mixed effect model was used to evaluate the intervention’s effect on change in mean SBP and DBP. Effect sizes of mean difference and relative benefit increase were used.ResultsAt 9 months, the mean SBP decreased by 15.8 mm Hg (95% CI: 13.5, 18.1) in the intervention and 10.8 mm Hg (95% CI: 8.7, 12.9) in the control groups; with a 5.0 mm Hg (95% CI: 1.9, 8.1) greater reduction in the intervention group. The mean DBP decreased by 12.1 mm Hg (95% CI: 10.6, 13.5) in the intervention and 8.4 mm Hg (95% CI: 7.0, 9.8) in the control group. The proportion of optimal blood pressure control was higher in the intervention group (45.8%) than the control group (28.2%) with percentage difference of 17.6% (95% CI: 8.5, 26.7).ConclusionsHealth extension workers-led home-based multicomponent intervention has resulted significant reduction of blood pressure and achieved a higher proportion of optimal blood pressure control. This strategy is effective, but further research is needed to determine its cost effectiveness for scaling up and integrating in primary care settings.Trial registrationThe trial is registered with Pan African clinical trial registry (PACTR202102729454417).
Building expert consensus regarding sharing of individual research results in Alzheimer’s disease research: a Delphi study protocol
Authors: Sankary Lauren R , Rico Valerie , Zelinsky Megan , Webster Helen S , Lerner Alan J , Martinez Kathryn , Ford Paul J , Tousi Babak , Leverenz James 
Published: August 2024

IntroductionInformed decisions to enrol in the clinical investigations of Alzheimer’s disease and related dementias (ADRD) require careful consideration of complex risks and uncertain benefits. Decisions regarding whether to receive information about biomarker status are complicated by lack of scientific consensus regarding biomarkers as surrogate endpoints for Alzheimer’s disease and how information about individual risk should be evaluated and shared with research participants. This study aims to establish stakeholder consensus regarding ethically optimal approaches to sharing individual results with ADRD research participants.Methods and analysisThis Delphi consensus-building study consists of multiple online surveys conducted with Alzheimer’s disease research experts, including neurologists, neuropsychologists, ethicists, research oversight specialists and clinical trialists. Panellists will be administered questionnaires developed from a synthesis of researcher- and participant-endorsed considerations and decisional needs identified in published literature and a decisional needs assessment conducted with support from an Alzheimer’s Association Research Grant. Panellists will also be asked their views on the content and implementation of processes for sharing individual research results. ≥75% agreement will be required to achieve consensus. Response rates, level of agreement, medians, interquartile ranges and group rankings will be analysed. Following each round of data collection, our research team will undertake qualitative content analysis of open-ended responses.Ethics and disseminationEthical approval will be obtained from the Cleveland Clinic Institutional Review Board (Study Number 22–766). Delphi panellists will receive participant information sheets describing the study before agreeing to participate in the Delphi process. Results from the data we anticipate will be generated through this research and will be submitted for peer-reviewed journal publication and presentation at international conferences.
Aflibercept for central retinal vein occlusions: long-term outcomes of a ‘Treat-and-Extend’ regimen
Authors: Jaggi Damian , Nagamany Thanoosha , Wolf Sebastian , Zinkernagel Martin S. , Heussen Florian M. 
Published: August 2024

Background/aimsThis study reports on the long-term functional and anatomical outcomes of patients with central retinal vein occlusion (CRVO) treated under the Bern treat-and-extend (T&E) protocol.MethodsObservational study. Treatment-naive patients with CRVO and consecutive macular oedema treated with aflibercept were included. The T&E protocol involved 2 monthly injections followed by an extension based on individual assessments. At each visit, best-corrected visual acuity (BCVA), optical coherence tomography imaging and a 2 mg aflibercept injection were administered. Changes in BCVA, proportion of patients gaining ≥15 letters, central subfield thickness (CST) and treatment intervals were analysed.ResultsOut of 173 patients, 64 had a follow-up of at least 2 years. BCVA improved from 46.7±25.3 at baseline to 78.3±0.5 at year 9. The proportion of patients with ≥15 letters gained was 56%, 53%, 56%, 62%, 52%, 52%, 43%, 50% and 33% at years 1–9, respectively. CST decreased significantly from 660±242 µm at baseline to 359±63 µm at year 9. Treatment intervals extended from 4 weeks initially to an average of 13.0±4.1 weeks by year 8.ConclusionsThe T&E regimen for CRVO shows sustained visual improvements and reduced CST over time. Patients maintained stable visual gains for many years, demonstrating the effectiveness of this treatment approach. However, no control group was available to compare our T&E regimen with other strategies.