bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoregulated splicing of
TRA2
β programs T cell fate in response to antigen-receptor stimulation
Authors: Karginov Timofey A. , Ménoret Antoine , Leclair Nathan K. , Harrison Andrew G. , Chandiran Karthik , Suarez-Ramirez Jenny E. , Yurieva Marina , Karlinsey Keaton , Wang Penghua , O’Neill Rachel J. , Murphy Patrick A. , Adler Adam J. , Cauley Linda S. , Anczuków Olga , Zhou Beiyan , Vella Anthony T.
Published: September 2024

T cell receptor (TCR) sensitivity to peptide–major histocompatibility complex (MHC) dictates T cell fate. Canonical models of TCR sensitivity cannot be fully explained by transcriptional regulation. In this work, we identify a posttranscriptional regulatory mechanism of TCR sensitivity that guides alternative splicing of TCR signaling transcripts through an evolutionarily ultraconserved poison exon (PE) in the RNA-binding protein (RBP) TRA2β in mouse and human.
TRA2
β
-
PE splicing, seen during cancer and infection, was required for TCR-induced effector T cell expansion and function.
Tra2
β-PE skipping enhanced T cell response to antigen by increasing TCR sensitivity. As antigen levels decreased,
Tra2
β-PE reinclusion allowed T cell survival. Finally, we found that
TRA2
β-PE was first included in the genome of jawed vertebrates that were capable of TCR gene rearrangements. We propose that
TRA2
β
-
PE splicing acts as a gatekeeper of TCR sensitivity to shape T cell fate.
Inhibition of diastatic yeasts by
Saccharomyces
killer toxins to prevent hyperattenuation during brewing
Authors: Zhong Victor , Ketchum Nicholas , Mackenzie James K. , Garcia Ximena , Rowley Paul A.
Published: September 2024

Secondary fermentation in beer can result in undesirable consequences, such as off-flavors, increased alcohol content, hyperattenuation, gushing, and the spontaneous explosion of packaging. Strains of
Saccharomyces cerevisiae var. diastaticus
are a major contributor to such spoilage due to their production of extracellular glucoamylase enzyme encoded by the
STA1
gene.
Saccharomyces
yeasts can naturally produce antifungal proteins named “killer” toxins that inhibit the growth of competing yeasts. Challenging diastatic yeasts with killer toxins revealed that 91% of strains are susceptible to the K1 killer toxin produced by
S. cerevisiae
. Screening of 192 killer yeasts identified novel K2 toxins that could inhibit all K1-resistant diastatic yeasts. Variant K2 killer toxins were more potent than the K1 and K2 toxins, inhibiting 95% of diastatic yeast strains tested. Brewing trials demonstrated that adding killer yeast during a simulated diastatic contamination event could prevent hyperattenuation. Currently, most craft breweries can only safeguard against diastatic yeast contamination by good hygiene and monitoring for the presence of diastatic yeasts. The detection of diastatic yeasts will often lead to the destruction of contaminated products and the aggressive decontamination of brewing facilities. Using killer yeasts in brewing offers an approach to safeguard against product loss and potentially remediate contaminated beer.

IMPORTANCE

The rise of craft brewing means that more domestic beer in the marketplace is being produced in facilities lacking the means for pasteurization, which increases the risk of microbial spoilage. The most damaging spoilage yeasts are “diastatic” strains of
Saccharomyces cerevisiae
that cause increased fermentation (hyperattenuation), resulting in unpalatable flavors such as phenolic off-flavor, as well as over-carbonation that can cause exploding packaging. In the absence of a pasteurizer, there are no methods available that would avert the loss of beer due to contamination by diastatic yeasts. This manuscript has found that diastatic yeasts are sensitive to antifungal proteins named “killer toxins” produced by
Saccharomyces
yeasts, and in industrial-scale fermentation trials, killer yeasts can remediate diastatic yeast contamination. Using killer toxins to prevent diastatic contamination is a unique and innovative approach that could prevent lost revenue to yeast spoilage and save many breweries the time and cost of purchasing and installing a pasteurizer.
PULSE Ambassadors program: empowering departments to transform STEM education for inclusion and student success
Authors: Fink Alix D. Dowling , Allen Taylor , Arriola Paul E. , Barea-Rodriguez Edwin J. , Jacob Nitya P. , Kelrick Michael Ira , Otto Joann , Reiness C. Gary , Washington Jacqueline
Published: September 2024

The Partnership for Undergraduate Life Sciences Education (PULSE) is a non-profit educational organization committed to promoting the transformation of undergraduate STEM education by supporting departments in removing barriers to access, equity, and inclusion and in adopting evidence-based teaching and learning practices. The PULSE Ambassadors Campus Workshop program enables faculty and staff members of host departments to 1) develop communication, shared leadership, and inclusion skills for effective team learning; 2) implement facilitative leadership skills (e.g., empathic listening and collaboration); 3) create a shared vision and departmental action plan; and 4) integrate diversity, equity, and inclusion practices in the department and curriculum. From the first workshop in 2014, teams of trained Ambassadors conducted workshops at 58 institutions, including associate, bachelor, master, and doctoral institutions. In their workshop requests, departments cited several motivations: desire to revise and align their curriculum with
Vision and Change
recommendations, need for assistance with ongoing curricular reform, and wish for external assistance with planning processes and communication. Formative assessments during and immediately following workshops indicated that key outcomes were met. Post-workshop interviews of four departments confirm progress achieved on action items and development of individual department members as agents of change. The PULSE Ambassadors program continues to engage departments to improve undergraduate STEM education and prepare departments for the challenges and uncertainties of the changing higher education landscape.
How to introduce a new bacteriophage on the block: a short guide to phage classification
Authors: Valencia-Toxqui Guadalupe , Ramsey Jolene
Published: September 2024

Bacteriophage (phage) studies established the field of molecular biology and continue to propel life science research forward due to their diversity, abundance, and potential applications. In this Gem article, we orient newcomers to four common ways phages are currently classified: infection cycle, morphology, taxonomy, and supergroup. By using these classifications, researchers can determine where any novel phage fits into the scheme of the known “phage-verse”.
Sequencing of historic samples provides complete coding sequences of chicken calicivirus from the United States
Authors: Goraichuk Iryna V. , Davis James F. , Afonso Claudio L. , Suarez David L.
Published: September 2024

Here, we report the coding-complete genomic sequences of two chicken caliciviruses from US poultry flocks in 2003 and 2004. They show the same genomic organization as that of other members of the
Bavovirus
genus and have the highest nucleotide identity (~88%) with strains from clinically normal chickens from Germany in 2004 and Netherlands in 2019.
Severe postural hypotension and sinus bradycardia with thalidomide in patients with erythema nodosum leprosum
Authors: Kaur Maninder , Budania Anil , Agrawal Akriti , Lahoria Utkrisht
Published: September 2024

Two men in their 60s and 40s were diagnosed with erythema nodosum leprosum based on the development of recurrent painful ulcers and nodules, respectively, for the previous 6 months. Thalidomide 100 mg four times a day, along with MB-MDT, was started in both patients. Both patients experienced severe dizziness on rising from a seated posture soon after initiation of thalidomide and a decrease in blood pressure and heart rate. Cardiovascular/neurology examination and routine blood investigations were normal. An autonomic nervous system assessment indicated bradycardia, postural hypotension and decreased cardiac autonomic function. The dosage of thalidomide was then gradually reduced over 4–5 days to 100 mg/day following a suspicion that thalidomide was the cause of postural hypotension. The dizziness subsided, and blood pressure and heart rate returned to normal.We concluded that thalidomide was the culprit behind bradycardia and dose- dependent postural hypotension.
Recognising angiosarcoma presenting as an enlarging ecchymotic plaque
Authors: Wu Michelle , Papps Theone , Blaya-Alvarez Bruno
Published: September 2024

Cutaneous angiosarcoma (cAS) is a rare malignant neoplasm of vascular endothelial origin with an unfavourable prognosis. Its diagnosis often faces delays due to its manifestation as an inconspicuous ‘bruise-like’ lesion in an otherwise asymptomatic individual, leading to a generally low index of suspicion for angiosarcoma. Here, we present a case of a man who presented to his general practitioner with an ecchymotic plaque on his forehead, initially thought to be benign. Over the subsequent 6 weeks, the lesion progressively enlarged and became ulcerated, prompting the patient to represent to his general practitioner. He was urgently referred to a dermatologist and a subsequent biopsy confirmed the diagnosis of cAS. Our presentation of this case serves as a reminder for physicians to maintain a high index of suspicion and low threshold for biopsy for patients with atraumatic ecchymotic lesions.
Accidental scalding burn injury in a 2-day-old neonate
Authors: Sosale Shivaprakash , Chandrashekar Aditya , Kariyappa Mallesh , Shah Pritik
Published: September 2024

Neonatal burns are a rare and challenging issue that is often overlooked during caregiver counselling. While iatrogenic burns account for the majority of reported cases, domestic burns are more prevalent in developing countries. Here, we report a case of a neonate with accidental scald burns due to spillage of a hot beverage on the body by the mother. Prevention is essential, and counselling and raising awareness about the cautious handling of hot beverages are of paramount importance in reducing the occurrence of accidental scald burns.To improve community acceptance of safe practices, it is crucial to include senior family members and ASHA workers in counselling sessions. Regular supervision, effective hospital policies, and training of caregivers and healthcare professionals are the key measures to be implemented to prevent accidental burns.
Case of B-acute lymphoblastic leukaemia with t(1;19)(q23;p13.3)TCF3::PBX1and co-occurringCBLmutation in an elderly patient
Authors: Zabel Kenneth Matthew , Rebbe Ryan , Vasef Mohammad , Foucar Charles
Published: September 2024

The t(1;19) (q23;p13)TCF3::PBX1is a well-described, recurring chromosomal abnormality in B-acute lymphoblastic leukaemia (B-ALL) that has historically been associated with a worse prognosis in paediatric patients. Gene expression profiling has demonstrated thatTCF3::PBX1results in a distinct subtype of B-ALL, leading to its recognition in the most recent WHO and ICC classifications. Though initially believed to be a poor prognostic sign in the adult population, emerging evidence suggests its presence may instead be intermediate or even favourable in B-ALL. However, adults withTCF3::PBX1are typically younger and often qualify for treatment with paediatric-inspired regimens. Thus, the prognostic significance in this population remains unclear. This translocation appears to be very rare in older adults with B-ALL and its predictive and prognostic nature in this population is unknown. Herein, we explore a case of this translocation occurring in a patient in her 70s. She initially presented to the emergency department with abdominal pain and thrombocytopenia and was subsequently diagnosed with B-ALL. In addition to t(1;19) (q23;p13), a pathologic mutation in theCBLgene was identified.CBLmutations have been implicated in cancer progression and are mostly described in paediatric B-ALL. She was treated with modified Ph-negative EWALL induction (Vincristine, Idarubicin, dexamethasone) and achieved a complete remission. However, she subsequently experienced an early relapse and was refractory to targeted therapy with blinatumomab. After treatment with inotuzumab ozogamicin, she achieved a second complete remission. Unfortunately, she then suffered a central nervous system (CNS) relapse and passed away from complications of her disease. This case serves as an example of the heterogeneous nature of B-ALL. It demonstrates that patients with ostensibly favourable prognostic factors may experience poor response rates to traditional chemotherapy as well as targeted salvage agents. It also illustrates the challenges of treating B-ALL in the elderly population.
Acute mesenteric ischaemia: a rare complication mimicking necrotising enterocolitis in a premature infant
Authors: Chan Siew-Boon , Ng Benjamin Wei-Liang , Chieng Chae-Hee
Published: September 2024

Acute mesenteric ischaemia (AMI) is a life-threatening gastrointestinal complication uncommonly described in premature infants. The diagnosis of AMI is challenging and may be delayed due to the limitation of accurate diagnostic imaging and non-specific clinical signs. Furthermore, AMI can be misdiagnosed as necrotising enterocolitis (NEC) due to the overlapping clinical and radiological features. Though known to be associated with high mortality rates, early recognition and intervention can improve the survival rates in infants with AMI. We describe a case of a premature infant who presented with an acute abdomen and haemodynamic collapse, initially treated for NEC but later diagnosed with AMI intraoperatively. Due to the extensive bowel necrosis, surgical intervention was rendered futile and the infant finally succumbed to the disease.
Jejunogastric intussusception after pancreaticoduodenectomy in a patient with HIV
Authors: Marable Julian K , Tumminello Mariana E , Ihemelandu Chukwuemeka U
Published: September 2024

The incidence of jejunogastric intussusception (JGI) after gastric surgery is 0.1%. We report a case of JGI after pancreaticoduodenectomy in a patient with HIV. After presenting to the hospital with abdominal pain and emesis, a CT abdomen/pelvis showed evidence of gastrojejunal anastomosis intussusception into the stomach. Oesophagogastroduodenoscopy was performed, but endoscopic reduction was unsuccessful. Exploratory laparotomy was subsequently performed with a successful reduction of the intussusception and resection of a portion of the small bowel. With only five previously reported cases of JGI after pancreaticoduodenectomy, our case is novel in that it describes JGI in a patient with HIV on highly active antiretroviral therapy, which has been associated with an increased risk of intussusception. While rare, we highlight the importance of having high clinical suspicion for intussusception in patients with risk factors who present with abdominal pain after pancreaticoduodenectomy. Timely diagnosis is critical to optimise patient outcomes.
Effectiveness of modified vaccinia Ankara-Bavarian Nordic vaccine against mpox infection: emulation of a target trial
Authors: Navarro Christine , Lau Cindy , Buchan Sarah A , Burchell Ann N , Nasreen Sharifa , Friedman Lindsay , Okpokoro Evaezi , Austin Peter C , Tan Darrell H S , Gubbay Jonathan B , Kwong Jeffrey C , Mishra Sharmistha
Published: September 2024

Objective

To estimate the real world effectiveness of modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine against mpox infection.

Design

Emulation of a target trial.

Setting

Linked databases in Ontario, Canada.

Participants

9803 men aged ≥18 years with a history of being tested for syphilis and a laboratory confirmed bacterial sexually transmitted infection (STI) in the previous year, or who filled a prescription for HIV pre-exposure prophylaxis in the previous year. On each day between 12 June 2022 and 27 October 2022, those who had been vaccinated 15 days previously were matched 1:1 with unvaccinated men by age, geographical region, past HIV diagnosis, number of bacterial STI diagnoses in the previous three years, and receipt of any non-MVA-BN vaccine in the previous year.

Main outcome measure

The main outcome measure was vaccine effectiveness ((1–hazard ratio)×100) of one dose of subcutaneously administered MVA-BN against laboratory confirmed mpox infection. A Cox proportional hazards model was used to estimate hazard ratios to compare the rate of laboratory confirmed mpox between the two groups.

Results

3204 men who received the vaccine were matched to 3204 unvaccinated controls. A total of 71 mpox infections were diagnosed, with 0.09 per 1000 person days (95% confidence interval (CI) 0.05 to 0.13) in the vaccinated group and 0.20 per 1000 person days (0.15 to 0.27) in the unvaccinated group over the study period of 153 days. Estimated vaccine effectiveness of one dose of MVA-BN against mpox infection was 58% (95% CI 31% to 75%).

Conclusion

The findings of this study, conducted in the context of a targeted vaccination programme and evolving outbreak of mpox, suggest that one dose of MVA-BN is moderately effective in preventing mpox infection.
Effect of laughter exercise versus 0.1% sodium hyaluronic acid on ocular surface discomfort in dry eye disease: non-inferiority randomised controlled trial
Authors: Li Jing , Liao Yinglin , Zhang Shi-Yao , Jin Ling , Congdon Nathan , Fan Zixin , Zeng Yangfa , Zheng Yingfeng , Liu Zuguo , Liu Yizhi , Liang Lingyi
Published: September 2024

Objective

To assess efficacy and safety of laughter exercise in patients with symptomatic dry eye disease.

Design

Non-inferiority randomised controlled trial.

Setting

Recruitment was from clinics and community and the trial took place at Zhongshan Ophthalmic Center, Sun Yat-sen University, the largest ophthalmic centre in China, between 18 June 2020 to 8 January 2021.

Participants

People with symptomatic dry eye disease aged 18-45 years with ocular surface disease index scores ranging from 18 to 80 and tear film break-up time of eight seconds or less.

Interventions

Participants were randomised 1:1 to receive laughter exercise or artificial tears (0.1% sodium hyaluronic acid eyedrop, control group) four times daily for eight weeks. The laughter exercise group viewed an instructional video and participants were requested to vocalise the phrases “Hee hee hee, hah hah hah, cheese cheese cheese, cheek cheek cheek, hah hah hah hah hah hah” 30 times per five minute session. Investigators assessing study outcomes were masked to group assignment but participants were unmasked for practical reasons.

Main outcome measures

The primary outcome was the mean change in the ocular surface disease index (0-100, higher scores indicating worse ocular surface discomfort) from baseline to eight weeks in the per protocol population. The non-inferiority margin was 6 points of this index score. Main secondary outcomes included the proportion of patients with a decrease from baseline in ocular surface disease index score of at least 10 points and changes in dry eye disease signs, for example, non-invasive tear break up time at eight weeks.

Results

299 participants (mean age 28.9 years; 74% female) were randomly assigned to receive laughter exercise (n=149) or 0.1% sodium hyaluronic acid (n=150). 283 (95%) completed the trial. The mean change in ocular surface disease index score at eight weeks was −10.5 points (95% confidence interval (CI) −13.1 to −7.82) in the laughter exercise group and −8.83 (−11.7 to −6.02) in the control group. The upper boundary of the CI for difference in change between groups was lower than the non-inferiority margin (mean difference −1.45 points (95% CI −5.08 to 2.19); P=0.43), supporting non-inferiority. Among secondary outcomes, the laughter exercise was better in improving non-invasive tear break up time (mean difference 2.30 seconds (95% CI 1.30 to 3.30), P<0.001); other secondary outcomes showed no significant difference. No adverse events were noted in either study group.

Conclusions

The laughter exercise was non-inferior to 0.1% sodium hyaluronic acid in relieving subjective symptoms in patients with dry eye disease with limited corneal staining over eight weeks intervention.

Trial registration

ClinicalTrials.gov
NCT04421300
.
Online yoga programme for resident physicians in Québec: an evaluation of feasibility and impact on mental health
Authors: Bélisle Marie-Pier , Dupuis Gilles , Fleet Richard
Published: September 2024

Objectives

To evaluate the feasibility of the Bali Yoga Programme for Residents (PYB-R), an 8-week virtual yoga-based intervention and determine its impact on the mental health of resident physicians.

Design

Single-group repeated measures study.

Setting

Associations from the four postgraduate medical education programmes in Québec, Canada.

Participants

Overall, 55 resident physicians were recruited to participate of which 53 (96.4%) completed the assessment pre-PYB-R. The postintervention assessment was completed by 43 residents (78.2%) and 39 (70.9%) completed all phases (including 3-month follow-up). Most were in their first year (43.4%) or second year (32.1%) of residency. The majority were female (81.1%) with a mean age of 28±3.6 years.

Primary and secondary outcome measures

The primary outcome measure was feasibility as measured by participation in the PYB-R. Secondary outcome measures were psychological variables (anxiety, depression, burn-out, emotional exhaustion, compassion fatigue and compassion satisfaction) and satisfaction with the PYB-R. Residents were further subgrouped based on the quality of work life and a number of PYB-R sessions attended.

Results

The attrition rate for programme completion was 19%. Of the 43 residents who completed the PYB-R, 90.6% attended between 6 and 8 sessions. Repeated-measures analysis of variances (ANOVAs) at three time points (baseline, PYB-R completion and 3-month follow-up) confirmed a decrease in scores for depression and anxiety, and an increase in scores for compassion satisfaction. No changes were observed in the other psychological variables evaluated. ANOVAs also confirmed that a better quality of life at work helps develop compassion satisfaction, a protective factor to compassion fatigue. Most participants (92.9%) indicated they were satisfied or very satisfied with the quality of the programme.

Conclusions

A virtual yoga-based programme is feasible and has lasting positive effects for up to 3 months on the mental health of resident physicians. Further research is warranted to validate these findings using a larger sample of residents with a control group.
Evaluation of hospital quality of care outcomes in a teaching hospital in Ethiopia: a retrospective database study
Authors: Arega Balew , Mengistu Mekoya , Mersha Amdemeskel , Agunie Asnake
Published: September 2024

Objectives

We aimed to evaluate hospital mortality rates, readmission rates and length of hospital stay (LOS) among adult medical patients admitted to a teaching hospital in Ethiopia.

Design

We performed a retrospective study using routinely collected electronic data.

Setting

Data were collected from Yekatit 12 Hospital Medical College between January 2021 and July 2023.

Participants

The analysis included 3499 (4111 admissions) adult medical patients with complete data.

Outcome measures

We used mortality rates, readmission rates and LOS to measure the quality of the outcomes for the top 15 admission diagnoses. A multivariable Cox proportional hazard model was used to identify the statistically significant predictors of mortality with p values<0.05 and a 95% CI. The Kaplan-Meier curve was used to estimate the failure rate (mortality) of the admitted patients.

Results

The median age of patients was 50 years and men accounted for 1827 (52.3%) of all admitted cases. Non-communicable diseases accounted for 2537 (72.5%) admissions. In descending order, stroke, 644 (18.29%); heart failure, 640 (18.41%); and severe pneumonia, 422 (12.06%) were the three most common causes of admission. The readmission rate was 25.67% (1056/411), and 61.9% of them were readmitted within 30 days of index discharge. The overall median LOS was 8 days. The median LOSs in the index admission (11 vs 8 days, p value=0.001) of readmitted patients was significantly higher than not readmitted. The in-hospital mortality rate was 438 (12.5%), with the highest number of deaths occurred between days 30 and 50 of admission. The mortality rate is significantly higher among patients with communicable diseases (adjusted HR, 1.64, 95% CI: 1.34, 2.10) and elderly patients (≥65 years) (adjusted HR, 1.79, 95% CI: 1.44, 2.22). Septicemia, chronic liver diseases with complications and HIV with complications were the three common causes of death with a proportional mortality rate of 55.2%, 27.93% and 22.46%, respectively.

Conclusions

Mortality, median LOSs and readmission rate were comparable to other national and international studies. Multicentre compressive research using these three quality patient outcomes is required to establish national standards and evaluate institutional performance.
Ten-year postintervention follow-up of adolescents participating in the management of overweight and social inequalities (PRALIMAP-INÈS intervention): the PRALIMAP-CINeCO survey protocol
Authors: Legrand Karine , Manneville Florian , Langlois Johanne , Böhme Philip , Dosda Arnaud , Beguinet Mélanie , Briançon Serge , Spitz Elisabeth , Lecomte Edith , Omorou Abdou Y
Published: September 2024

Introduction

The short-term effectiveness of the PRomotion de l’ALIMentation et de l’Activité Physique–INÈgalités de Santé’ (PRALIMAP-INÈS) intervention to reduce social inequalities in overweight and obesity management among adolescents between 2012 and 2015 was demonstrated. This longitudinal mixed-methods study is a 10-year postintervention follow-up of the PRALIMAP-INÈS intervention with the aim of investigating social, economic, educational and health (especially weight) trajectories from adolescence to young adulthood.

Methods and analysis

Among adolescents enrolled in PRALIMAP-INÈS (n=1419), we estimate the number of participants to be 852. Adolescents who were included in the PRALIMAP-INÈS intervention will be contacted 10 years later and invited to participate in a follow-up visit. Participants will self-report their sociodemographic characteristics, body image perceptions, overweight/obesity care pathway, lifestyle and dietary behaviours and attitudes, psychological health and experience of the PRALIMAP-INÈS intervention. A check-up visit will be scheduled by a clinical research nurse to record waist circumference and weight and height for body mass index calculation and to construct the healthcare pathway from adolescence to young adulthood. 40 participants will be invited to participate in a semistructured interview conducted by a sociologist to deepen the understanding of trajectories regarding social aspects that are likely to influence health behaviours in participants.

Ethics and dissemination

The PRALIMAP-CINeCO trial was approved by French Persons Protection Committee (no. 2021-A00949-32) and a conformity declaration was made with French National Commission for Data Protection and Liberties. Results will be presented at conferences and published in international peer-reviewed journals.

Trial registration number

NCT05386017; Pre-results
Anti-inflammatory effect of colchicine on organ damage during the perioperative period of cardiac surgery: a study protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial
Authors: Li Xin , Luo Yuanxi , Cai Xiujuan , Lv Zhikang , Kong Youru , Guo Qiuyong , Zhu Jiawei , Pan Tuo , Wang Dongjin
Published: September 2024

Introduction

The systemic inflammatory response syndrome during the perioperative period of cardiac surgery can lead to serious postoperative complications and significantly increase the hospital mortality rate. Colchicine, a widely used traditional anti-inflammatory drug, has good clinical value in cardiovascular anti-inflammatory therapy. Our preliminary single-centre study had confirmed the protective value of colchicine in patients undergoing cardiac surgery with cardiopulmonary bypass. For this multicentre investigation, we aim to further validate the anti-inflammatory and organ-protective effects of low-dose colchicine during the perioperative period in a low-risk population.

Methods and analysis

This study is a multicentre, randomised, double-blind, placebo-controlled clinical trial. A total of 768 patients undergoing elective cardiac surgery will be enrolled from eight heart centres in China. The participants will be randomly assigned to two groups: the colchicine group will receive low-dose colchicine (0.5 mg once-a-day dosing regimen (QD) orally for 3 days before the surgery and 0.5 mg dosing frequency of every other day (QOD) continuously for 10 days after the surgery), whereas the placebo group will be given starch tablets for the same time and dosage. Primary endpoints are the occurrence of postoperative inflammatory diseases, including postoperative atrial fibrillation, acute respiratory distress syndrome, preoperative myocardial injury and post-pericardiotomy syndrome. Secondary endpoints included laboratory tests on postoperative days 1, 3, 5, 7 and 10, intensive care unit data, APACHE II score, Murray lung injury score, medication-related gastrointestinal reactions, 30-day and 90-day all-cause mortality, surgical data, chest radiograph on postoperative days 1, 2 and 3, and chest CT within 14 days after surgery.

Ethics and dissemination

This research has received approval from the Medical Ethics Committee of Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical College (approval number 2023-366-01). The study findings will be made available by publishing them in an open access journal.

Trial registration number

ClinicalTrials.gov (NCT06118034).
Combining predictive soil mapping and process models to estimate future carbon sequestration potential under no-till
Authors: Sorenson P.T. , Bedard-Haughn A.K. , St. Luce M.
Published: September 2024

There is increasing interest in soil organic carbon (SOC) sequestration as a climate change mitigation strategy. There is a need to estimate the quantity of SOC sequestered historically due to no-till, and the remaining sequestration potential in Saskatchewan. To answer this question, predictive soil mapping results were linked with the Century model to predict SOC stock change over time to a depth of 20 cm considering three different future climate change scenarios. Climate scenarios included low, moderate, and high amounts of climate change and included estimated changes to monthly minimum, average, and maximum temperature, total monthly precipitation, and average monthly relative humidity at an 800 m × 800 m resolution. Historically, the modelled average SOC gain for Saskatchewan was 2.8 Mg ha−1. Future potential simulated SOC was lower over the next 30 years, with average SOC gains estimated to range from 1.4 to 1.7 Mg ha−1 by 2054 and 2.3 to 3.1 Mg ha−1 by 2100. There is also unequal spatial distribution of SOC stock gain potential, with the northern grain growing regions showing lower future potential. The predicted future gains will be at a lower rate than in the past with carbon sequestration rates dropping from 0.06 to less than 0.02 Mg ha−1 year−1. Additional management practices such as improved residue management and the introduction of crop varieties with increased below ground carbon inputs and more stable residues should be explored to offset the diminishing SOC returns from no-till.
Mechanochemical Ball Mill Goethite to Activate Sodium Persulfate for the Treatment of Organic Wastewater Containing Tetracycline Hydrochloride
Authors: Guo Yifan , Wang Shenyang , Xu Lijun , Zhang Li , Zhu Jianming , Huang Qing , Song Qingbin , Yuan Wenyi
Published: September 2024

The contamination of aquatic systems by tetracycline hydrochloride (TC) has emerged as an urgent environmental concern necessitating immediate intervention. Herein, a mechanochemical approach was utilized to synthesize a FeOOH@AC nanocomposite through the co-grinding of goethite (FeOOH), hydroxylamine hydrochloride (NH2OH⋅HCl), and activated carbon (AC). The FeOOH@AC nanocomposite acted as a catalyst for the activation of sodium persulfate (PS), producing strong oxidizing radicals for the removal of TC from water. The results demonstrated that the physicochemical properties and crystal structure of FeOOH were altered via ball-milling treatment. The activation of PS-generated sulfate radicals (SO[Formula: see text] and hydroxyl radicals ([Formula: see text]OH) synergistically degraded TC. Additionally, the degradation rate of TC in a 50[Formula: see text]mg/L solution reached 91.26% after the addition of FeOOH@AC and PS. This work offers a theoretical and technical foundation for the mechanochemical ball milling preparation of FeOOH@AC, facilitating PS activation for the degradation of TC in water.
Hydrothermal synthesis and optical luminescence center attribution in samarium-doped zirconia nanocrystals
Authors: Ouyang Jing , Zhou Wentao , Peng Yonghui , Kou Baohong , Liang Xianfeng , Wang Gang , Zhang Qi , Yuan Bo
Published: September 2024

Sm[Formula: see text] -doped ZrO2 (SDZ) nanocrystals were prepared via a hydrothermal route without subsequent calcination. These samples underwent a series of characterizations, including X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet–visible (UV–Vis) spectroscopy, and photoluminescence (PL) spectral. The results showed pure cubic ZrO2 nanocrystals, with a crystallite size of 8.4 nm, were achieved by doping 8 mol% Sm[Formula: see text]. It was observed that the concentration of Sm[Formula: see text] had a significant impact on the crystallite structure of the samples, which exhibited an array of spherical shape and irregular aggregates. The inclusion of PL emission bands, spanning from the ultraviolet to blue-green range, highlighted three distinct bands. These were analyzed using Gaussian fittings and were attributed to three different types of defects, referred to as the F, F1, and F2 centers, respectively.
Robot path planning based on IAPF-A-Star algorithm
Authors: Wang Yixuan , Wang Lei , Li Dongdong , Cai Jingcao , Wang Tiancheng , Xia Qiangqiang
Published: September 2024

The traditional A-Star algorithm has the problem of performing much invalid traversal work of nodes near concave obstacles when dealing with path planning tasks in the presence of concave obstacles. To solve this problem, a fusion algorithm (called IAPF-A-Star here) based on improved artificial potential field (IAPF) and A-Star is proposed. In IAPF-A-Star, to better measure the distances between the nodes and the target node, the potential energy of the artificial potential field is used to represent the node’s proximity to the target node, and an iterative correction method is used to improve the potential field in order to eliminate the local low-potential energy that may exist in the artificial potential field. The improved potential field effectively avoids the occurrence of local low-potential fields and makes it possible to measure the position of nodes in relation to their target node by means of the potential field. Finally, the obtained path is converted to a curve path by using a cubic spline curve. In addition, to solve the problem that the curve path generated by the cubic spline curve may collide with obstacles, a path optimization strategy based on an adaptive cubic spline curve is proposed to make the final path smooth and collision avoidance, shorter and closer to the actual situation. Simulation experiments show that the proposed IAPF-A-Star algorithm in this paper can effectively avoid the problem of additional local energy consumption caused by concave obstacles when processing path planning tasks, and the traversal of invalid nodes facing different complex concave obstacles is effectively avoided.
Artificial gravity: an effective countermeasure for microgravity-induced headward fluid shift?
Authors: Kramer Larry A. , Hasan Khader M. , Zhang Xu , Mulder Edwin , Gerlach Darius A. , Marshall-Goebel Karina , Macias Brandon R. , Laurie Steven S. , Strangman Gary , Iyer Raj , Bershad Eric M.
Published: September 2024

Brief exposure to continuous or intermittent artificial gravity via short-arm centrifugation was insufficient in mitigating the intracranial pathophysiological effects of the headward fluid shift simulated during head-down tilt bed rest (HDTBR). Our results suggest that greater centrifugation session duration, gravitational force, or both may be required to prevent the development of spaceflight-associated neuro-ocular syndrome and should be considered in future ground-based countermeasure studies.
Biological Applications of Nanoparticles Synthesized via Olea europaea Plant: A Comprehensive Review
Authors: Khanahmad Alireza , Ebrahimi Zohre , Abreshteh Azadeh , Pajavand Hamid , Satarzadeh Naghmeh , Dousari Amin Sadeghi
Published: September 2024

Today, the emergence of nanotechnology and its various and unique medical applications has facilitated the diagnosis and treatment of diseases. In medicine, nanoparticles have extraordinary antibacterial, antifungal, antiviral, antioxidant, and antitumor properties. The nanoparticles’ unique properties depend greatly on the synthesis method because it determines the shape, size, and properties of the nanoparticle. In recent years, the green nanoparticle synthesis method has been considered a substitute for chemical and physical methods; the green synthesis of nanoparticles using plants has attracted the attention of many researchers worldwide because these methods are environmentally friendly, easy to perform, safe, energy‐efficient, and affordable. One of the plants known for a long time, whose many healing properties have been widely mentioned, is the Olea europaea plant. This review is aimed at examining the studies that have used the Olea europaea plant in the green synthesis of nanoparticles and investigating the biological applications of these nanoparticles.
Neuroendocrine Differentiation in Prostate Cancer Requires ASCL1
Authors: Rodarte Kathia E. , Nir Heyman Shaked , Guo Lei , Flores Lydia , Savage Trisha K. , Villarreal Juan , Deng Su , Xu Lin , Shah Rajal B. , Oliver Trudy G. , Johnson Jane E.
Published: September 2024

Most patients with prostate adenocarcinoma develop resistance to therapies targeting the androgen receptor (AR). Consequently, a portion of these patients develop AR-independent neuroendocrine (NE) prostate cancer (NEPC), a rapidly progressing cancer with limited therapies and poor survival outcomes. Current research to understand the progression to NEPC suggests a model of lineage plasticity whereby AR-dependent luminal-like tumors progress toward an AR-independent NEPC state. Genetic analysis of human NEPC identified frequent loss of RB1 and TP53, and the loss of both genes in experimental models mediates the transition to a NE lineage. Transcriptomics studies have shown that lineage transcription factors ASCL1 and NEUROD1 are present in NEPC. In this study, we modeled the progression of prostate adenocarcinoma to NEPC by establishing prostate organoids and subsequently generating subcutaneous allograft tumors from genetically engineered mouse models harboring Cre-induced loss of Rb1 and Trp53 with Myc overexpression (RPM). These tumors were heterogeneous and displayed adenocarcinoma, squamous, and NE features. ASCL1 and NEUROD1 were expressed within NE-defined regions, with ASCL1 being predominant. Genetic loss of Ascl1 in this model did not decrease tumor incidence, growth, or metastasis; however, there was a notable decrease in NE identity and an increase in basal-like identity. This study provides an in vivo model to study progression to NEPC and establishes the requirement for ASCL1 in driving NE differentiation in prostate cancer.

Significance: Modeling lineage transitions in prostate cancer and testing dependencies of lineage transcription factors have therapeutic implications, given the emergence of treatment-resistant, aggressive forms of neuroendocrine prostate cancer.

See related commentary by McQuillen and Brady, p. 3499
Table S2 from Targeting TREX1 Induces Innate Immune Response in Drug-Resistant Small-Cell Lung Cancer
Authors: Murayama Takahiko , Mahadevan Navin R. , Meador Catherine B. , Ivanova Elena V. , Pan Yuqiao , Knelson Erik H. , Tani Tetsuo , Nakayama Jun , Ma Xueying , Thai Tran C. , Hung Yin P. , Kim William , Watanabe Hideo , Cai Kathy Q. , Hata Aaron N. , Paweletz Cloud P. , Barbie David A. , Cañadas Israel
Published: September 2024

Treatment history of PDX tumors
Figure S5 from Targeting TREX1 Induces Innate Immune Response in Drug-Resistant Small-Cell Lung Cancer
Authors: Murayama Takahiko , Mahadevan Navin R. , Meador Catherine B. , Ivanova Elena V. , Pan Yuqiao , Knelson Erik H. , Tani Tetsuo , Nakayama Jun , Ma Xueying , Thai Tran C. , Hung Yin P. , Kim William , Watanabe Hideo , Cai Kathy Q. , Hata Aaron N. , Paweletz Cloud P. , Barbie David A. , Cañadas Israel
Published: September 2024

Figure S5 shows TREX1 expression is induced in post-treated SCLC PDX
Figure S4 from Targeting TREX1 Induces Innate Immune Response in Drug-Resistant Small-Cell Lung Cancer
Authors: Murayama Takahiko , Mahadevan Navin R. , Meador Catherine B. , Ivanova Elena V. , Pan Yuqiao , Knelson Erik H. , Tani Tetsuo , Nakayama Jun , Ma Xueying , Thai Tran C. , Hung Yin P. , Kim William , Watanabe Hideo , Cai Kathy Q. , Hata Aaron N. , Paweletz Cloud P. , Barbie David A. , Cañadas Israel
Published: September 2024

Figure S4 shows TREX1 depletion increases sensitivity of resistant SCLC cells to chemotherapy
Social Characteristics of Culturally and Linguistically Diverse Cancer Patients Enrolled in Early Phase Clinical Trials in South Western Sydney
Authors: Childs Sarah , Nindra Udit , Shivasabesan Gowri , Yoon Robert , Haider Sana , Hong Martin , Cooper Adam , Roohullah Aflah , Wilkinson Kate , Chua Wei , Pal Abhijit
Published: September 2024

Introduction: Early phase clinical trials (EPCTs) enable access to novel therapies for patients who have exhausted standard of care treatment and contribute a crucial role in drug development and research. Culturally and linguistically diverse (CALD) or socially disadvantaged patients have notably lower rates of participation in these trials. We aimed to characterise the social and cultural demographics of patients enrolled on an EPCT in South Western Sydney. Methods: We conducted a 10-year retrospective review of patients enrolled on a EPCT at Liverpool Hospital. CALD patients were defined as those born overseas or whose preferred language was other than English. The patient residential address was used to calculate distance travelled, and the Index of Relative Socioeconomic Disadvantage (IRSD) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) scores were calculated and used as a surrogate for socioeconomic status (SES). Results: Our study included 233 patients across 39 EPCTs. Ninety-one patients (39%) were identified as CALD. The median IRSD and IRSAD scores were 941 and 944, respectively, with 62.7–67.4% of patients residing in an area with greater disadvantage compared to the median of Australia. The median distance travelled was 17 kilometres with only 12% of participants travelling more than 50 km. CALD patients were more likely to reside in an area of low SES (OR 3.4, 95% CI: 1.8–6.5, p < 0.01) and travelled shorter median distances (10 vs. 23 km) when compared to non-CALD patients. Conclusion: Our study cohort contained a lower proportion of CALD patients and a higher SES than what we might have expected from our local population. Furthermore, there was a trend toward greater SES disadvantage (lower IRSD/IRSAD scores) for the CALD population. This study provides novel Australian data to support the underrepresentation of culturally diverse or disadvantaged patients on EPCTs. Future efforts should be made to reduce barriers to participation and improve equity in clinical trial participation.
Retinal Pigment Epithelial Proliferation Secondary to Retinal Ischemia: A Case Report and Literature Review
Authors: Alnaim Abdullah F. , Alsakran Wael A. , Alotaibi Hammam A.
Published: September 2024

Introduction: Antiphospholipid syndrome is one of the most common causes of acquired hypercoagulable conditions which is correlated with ocular conditions not least of which is retinal ischemia due to arterial or venous occlusive insults. Case Presentation: We describe a case of unilateral retinal ischemia in the setting of combined central retinal artery and vein occlusion with associated proliferation of retinal pigment epithelium. The patient was worked-up for the etiology of her presentation which was found to be antiphospholipid syndrome. Conclusion: Although pigment epithelial proliferation occurs commonly after retinal ischemia, no study has reported complete multimodal imaging of such a pathology or proposed the possible mechanisms explaining such an association.
Virulence-Related Genes Expression in Planktonic Mixed Cultures of Candida albicans and Non-Albicans Candida Species
Authors: Soriano-Abarca Melanie , Tapia Juan Carlos , Cáceres-Valdiviezo María José , Morey-León Gabriel , Fernández-Cadena Juan , Díaz-Cevallos Linda , Andrade-Molina Derly
Published: September 2024

Introduction: Candida albicans is the most common opportunistic pathogen causing fungal infections worldwide, especially in high-risk patients. Its pathogenicity is related to virulence factors gene expression, such as hyphal growth (HWP1), cell adhesion (ALS3), and protease secretion (SAP1) during infection spreading mechanisms. In recent years, an increase in non-albicans Candida infections has been reported, which may present coinfection or competitive interactions with C. albicans, potentially aggravating the patient’s condition. This study aims to evaluate the expression of genes related to virulence factors of C. albicans and non-albicans Candida during planktonic stage. Methods: C. albicans (ATCC MYA-3573) as well as with three clinical strains (C. albicans DCA53, C. tropicalis DCT6, and C. parapsilosis DCP1) isolated from blood samples, were grown in 24-well plates at 37°C for 20 h, either in monocultures or mixed cultures. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of the genes HWP1, ALS3, and SAP1 in cells collected during the planktonic stage. In addition, hyphal filamentation was observed using a Scanning Electron Microscope. Results: The overexpression of HWP1 and ASL3 genes in mixed growth conditions between C. albicans and non-albicans Candida species suggests a synergistic relationship as well as an increased capacity for hyphal growth and adhesion. In contrast, C. parapsilosis versus C. tropicalis interaction shows an antagonistic relationship during mixed culture, suggesting a decreased virulence profile of C. parapsilosis during initial coinfection with C. tropicalis. Conclusion: The expression of HWP1, ALS3, and SAP1 genes associated with virulence factors varies under competitive conditions among species of the genus Candida during planktonic stage.