bluuebunny/crossref_metadata_2025 huggingface dataset:
An iterative approach to promoting departmental wellbeing during COVID‐19
Authors: Acai Anita , Gonzalez Andrea , Saperson Karen ,   on behalf of the Department of Psychiatry and Behavioural Neurosciences COVID‐19 Wellness Working Group
Published: August 2021

Rationale, Aims, and Objectives

Addressing wellbeing among learners, faculty, and staff during the COVID‐19 pandemic is a challenge for many clinical departments. Continued and systemic supports are needed to combat the pandemic's impact on mental health and wellbeing. This article describes an iterative approach to conducting a needs assessment and implementing a COVID‐19‐related wellness initiative in a psychiatry department.

Methods

Development of the initiative followed the Plan‐Do‐Study‐Act (PDSA) quality improvement cycle and was informed by Shanafelt and colleagues' framework for supporting healthcare workers during the COVID‐19 pandemic. Key features included the establishment of a Wellness Working Group, the curation of relevant resources on the Department's website, and the deployment of regular, monthly surveys that informed the creation of further supports, such as a weekly online drop‐in support group.

Results

Survey response rates ranged from 22% to 32% (n = 90‐127) throughout our initiative. Across multiple surveys, approximately 80% of respondents reported feeling supported or very supported by the Department, and 90% were satisfied or very satisfied with the quantity and quality of information provided. Our support group and resources page were accessed by nearly one‐quarter and one‐third of respondents, respectively, with satisfaction rates of 81% or higher. Consistent with the Department's mandate, ensuring equity was a key focus of the Working Group throughout its operations.

Conclusions

There is potential for this model to be scaled to create a faculty‐wide, institution‐wide, or regional approach to addressing wellbeing. Other departments may also wish to adopt similar approaches to supporting their members during this challenging time.
The effects of computer‐assisted cognitive rehabilitation on cognitive impairment after stroke: A systematic review and meta‐analysis
Authors: Nie Pingying , Liu Fang , Lin Shaohong , Guo Jiaying , Chen Xinming , Chen Sulian , Yu Liqiang , Lin Ruhui
Published: August 2021

Objectives

To determine the effectiveness of computer‐assisted cognitive rehabilitation in improving cognitive function in patients with post‐stroke cognitive impairment.

Background

In recent years, computer‐assisted cognitive rehabilitation has been accepted as a good substitute or supplement for traditional cognitive rehabilitation. Some clinical randomised controlled trials have been carried out, but no relevant systematic evaluations have been performed. Therefore, we conducted a systematic review of studies involving computer‐assisted cognitive rehabilitation to provide evidence‐based data for its promotion and application.

Methods

Nine databases (Cochrane Library, PubMed, Web of Science, Embase, OVID, Wanfang Data, CNKI, VIP and SinoMed databases) were systematically searched. Randomised controlled trials that assessed computer‐assisted cognitive rehabilitation for patients with post‐stroke cognitive impairment were included. Two reviewers appraised the risks of bias through the Cochrane Collaboration's tool and performed the meta‐analysis, including the assessment of heterogeneity. We follow the PRISMA 2020 guidelines.

Results

Thirty‐two studies comprising 1837 participants were included. Compared with conventional therapy alone, the addition of computer‐assisted cognitive rehabilitation significantly improved the global cognition of patients, evaluated using the Montreal cognitive assessment, mini‐mental state examination and Loewenstein occupational therapy cognitive assessment (p < .01 for all tests). The therapy also significantly improved activities of daily living, assessed using the Barthel index, modified Barthel index and functional independence measure (p < .05 for all tests).

Conclusion

Computer‐assisted cognitive rehabilitation significantly improved the cognitive function and activities of daily living of patients with post‐stroke cognitive impairment.

Relevance to clinical practice

Computer‐assisted cognitive rehabilitation can be a valuable technique for cognitive rehabilitation after stroke. It is advantageous for improving patient cognition and restoring the overall functional state of patients. Moreover, the research findings can provide suggestions and inspiration for researchers to implement the proposal, which is conducive to the design of more rigorous and high‐quality randomised controlled trials.
Rice ubiquitin‐conjugating enzyme OsUBC26 is essential for immunity to the blast fungus Magnaporthe oryzae
Authors: Liu Xin , Song Linlin , Zhang Heng , Lin Yijuan , Shen Xiaolei , Guo Jiayuan , Su Meiling , Shi Gaosheng , Wang Zonghua , Lu Guo‐Dong
Published: August 2021

The functions of ubiquitin‐conjugating enzymes (E2) in plant immunity are not well understood. In this study, OsUBC26, a rice ubiquitin‐conjugating enzyme, was characterized in the defence against Magnaporthe oryzae. The expression of OsUBC26 was induced by M. oryzae inoculation and methyl jasmonate treatment. Both RNA interference lines and CRISPR/Cas9 null mutants of OsUBC26 reduced rice resistance to M. oryzae. WRKY45 was down‐regulated in OsUBC26 null mutants. In vitro E2 activity assay indicated that OsUBC26 is an active ubiquitin‐conjugating enzyme. Yeast two‐hybrid assays using OsUBC26 as bait identified the RING‐type E3 ligase UCIP2 as an interacting protein. Coimmunoprecipitation assays confirmed the interaction between OsUBC26 and UCIP2. The CRISPR/Cas9 mutants of UCIP2 also showed compromised resistance to M. oryzae. Yeast two‐hybrid screening using UCIP2 as bait revealed that APIP6 is a binding partner of UCIP2. Moreover, OsUBC26 working with APIP6 ubiquitinateds AvrPiz‐t, an avirulence effector of M. oryzae, and OsUBC26 null mutation impaired the proteasome degradation of AvrPiz‐t in rice cells. In summary, OsUBC26 plays important roles in rice disease resistance by regulating WRKY45 expression and working with E3 ligases such as APIP6 to counteract the effector protein AvrPiz‐t from M. oryzae.
The puzzle of learning by doing and the gradability of knowledge‐how
Authors: Piñeros Glasscock Juan S.
Published: August 2021

Much of our know‐how is acquired through practice: we learn how to cook by cooking, how to write by writing, and how to dance by dancing. As Aristotle argues, however, this kind of learning is puzzling, since engaging in it seems to require possession of the very knowledge one seeks to obtain. After showing how a version of the puzzle arises from a set of attractive principles, I argue that the best solution is to hold that knowledge‐how comes in degrees, and through practice a person gradually learns how to do something. However, the two standard accounts of know‐how in the literature, intellectualism and anti‐intellectualism, cannot properly account for the distinctive way in which know‐how is gradually acquired by practice, a process in which conceptual representations and practical abilities are intimately interwoven. Drawing on Gareth Evans's work, I outline an account that may do so, and use this account to distinguish between two forms of learning to explain why skill generally cannot be learnt through testimony, and requires practice.
Leading by example: The women of respiratory health in Australia
Authors: Leong Tracy L. , Smallwood Natasha
Published: August 2021

See related Editorial
Air pollution and the pandemic: Long‐term PM2.5 exposure and disease severity in COVID‐19 patients
Authors: Mendy Angelico , Wu Xiao , Keller Jason L. , Fassler Cecily S. , Apewokin Senu , Mersha Tesfaye B. , Xie Changchun , Pinney Susan M.
Published: August 2021

Background and objective

Ecological studies have suggested an association between exposure to particulate matter ≤2.5 μm (PM2.5) and coronavirus disease 2019 (COVID‐19) severity. However, these findings are yet to be validated in individual‐level studies. We aimed to determine the association of long‐term PM2.5 exposure with hospitalization among individual patients infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).

Methods

We estimated the 10‐year (2009–2018) PM2.5 exposure at the residential zip code of COVID‐19 patients diagnosed at the University of Cincinnati healthcare system between 13 March 2020 and 30 September 2020. Logistic regression was used to determine the odds ratio (OR) and 95% CI for COVID‐19 hospitalizations associated with PM2.5, adjusting for socioeconomic characteristics and comorbidities.

Results

Among the 14,783 COVID‐19 patients included in our study, 13.6% were hospitalized; the geometric mean (SD) PM2.5 was 10.48 (1.12) μg/m3. In adjusted analysis, 1 μg/m3 increase in 10‐year annual average PM2.5 was associated with 18% higher hospitalization (OR: 1.18, 95% CI: 1.11–1.26). Likewise, 1 μg/m3 increase in PM2.5 estimated for the year 2018 was associated with 14% higher hospitalization (OR: 1.14, 95% CI: 1.08–1.21).

Conclusion

Long‐term PM2.5 exposure is associated with increased hospitalization in COVID‐19. Therefore, more stringent COVID‐19 prevention measures may be needed in areas with higher PM2.5 exposure to reduce the disease morbidity and healthcare burden.
The effect of oil export on direct external democratizing pressures
Authors: Woo Jungmoo
Published: August 2021

Objective

I argue that an autocracy’s oil export discourages democracies from employing foreign policies fostering democracy in the autocracy because three characteristics of oil trade—the importance of oil as a primary energy source, the international oil market’s exporter‐favored structure, and the price inelasticity of supply of and demand for petroleum—increase costs of such policies. Thus, an autocracy’s oil export hinders democratization by reducing both domestic and external democratizing pressures.

Methods

To measure the effect of oil export on direct external democratizing pressures, I gather the dyad‐level oil trade ties using numerous oil trade datasets, and calculate each state’s oil export leverage using closeness centrality in weighted networks. Using this measure, I test the effect of oil export on the likelihood of democratization.

Results

Empirical results support that as an autocracy’s oil export leverage increases, the autocracy’s
likelihood of democratization should decrease.
Laser-based comparison calibration of laboratory standard microphones
Authors: Wagner Randall P. , Allen Richard A. , Dong Qian
Published: August 2021

A precision laser-based comparison calibration method for laboratory standard microphones is described that uses reference microphones calibrated by the pressure reciprocity method. Electrical drive current and diaphragm velocity are measured while the microphones are driven as transmitters/sources of sound; the diaphragm velocity is measured using scanning laser Doppler vibrometry. Sensitivities determined using this method display very good agreement with those determined directly by reciprocity for seven such test microphones at 250 and 1000 Hz. At these frequencies, the expanded (coverage factor k = 2) uncertainties of this comparison calibration method for these microphones are ±0.05 dB.
Modal analysis of free archtop guitar top plates
Authors: Salvi Davide , Gonzalez Sebastian , Antonacci Fabio , Sarti Augusto
Published: August 2021

We analyze the modal response of the top plates of archtop guitars using free boundary conditions. Starting from the three-dimensional scan of a real archtop guitar, we build a mesh of its top plate using a non-invasive process. Once the mesh of the plate is built, we compute its vibrational response by finite element method simulations and perform many different analyses. The outer surface of the mesh matches the scan, while we retain the freedom to control the shape of the inner surface. This way we can change some of its aspects (e.g., thickness distribution) depending on what we intend to study. We investigate the similarities of its mode shapes with those of similar instruments (e.g., violin and classical guitar), analyze the carving process of the plate's inner surface and study the influence of resonant holes on its final vibratory response.
Rifampicin-Monoresistant Tuberculosis Is Not the Same as Multidrug-Resistant Tuberculosis: a Descriptive Study from Khayelitsha, South Africa
Authors: Salaam-Dreyer Zubeida , Streicher Elizabeth M. , Sirgel Frederick A. , Menardo Fabrizio , Borrell Sonia , Reinhard Miriam , Doetsch Anna , Cudahy Patrick G. T. , Mohr-Holland Erika , Daniels Johnny , Dippenaar Anzaan , Nicol Mark P. , Gagneux Sebastien , Warren Robin M. , Cox Helen
Published: August 2021

Rifampin monoresistance (RMR; rifampin resistance and isoniazid susceptibility) accounts for 38% of all rifampin-resistant tuberculosis (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) in a setting with high TB, RR-TB, and HIV burdens.
Anti-LPS IgA and IgG Can Inhibit Serum Killing of Pseudomonas aeruginosa in Patients with Cystic Fibrosis
Authors: Pham Amy , Ledger Emma L. , Coggon Carrie F. , Henderson Ian R. , Reid David W. , Bell Scott C. , Smith Daniel J. , Wells Timothy J.
Published: August 2021

Pseudomonas aeruginosais one of the principal pathogens implicated in respiratory infections of patients with cystic fibrosis (CF) and non-CF bronchiectasis. Previously, we demonstrated that impaired serum-mediated killing ofP. aeruginosawas associated with increased severity of respiratory infections in patients with non-CF bronchiectasis.
Fjord network in Namibia: A snapshot into the dynamics of the late Paleozoic glaciation
Authors: Dietrich Pierre , Griffis Neil P. , Le Heron Daniel P. , Montañez Isabel P. , Kettler Christoph , Robin Cécile , Guillocheau François
Published: August 2021

Fjords are glacially carved estuaries that profoundly influence ice-sheet stability by draining and ablating ice. Although abundant on modern high-latitude continental shelves, fjord-network morphologies have never been identified in Earth's pre-Cenozoic glacial epochs, hindering our ability to constrain ancient ice-sheet dynamics. We show that U-shaped valleys in northwestern Namibia cut during the late Paleozoic ice age (LPIA, ca. 300 Ma), Earth's penultimate icehouse, represent intact fjord-network morphologies. This preserved glacial morphology and its sedimentary fill permit a reconstruction of paleo-ice thicknesses, glacial dynamics, and resulting glacio-isostatic adjustment. Glaciation in this region was initially characterized by an acme phase, which saw an extensive ice sheet (1.7 km thick) covering the region, followed by a waning phase characterized by 100-m-thick, topographically constrained outlet glaciers that shrank, leading to glacial demise. Our findings demonstrate that both a large ice sheet and highland glaciers existed over northwestern Namibia at different times during the LPIA. The fjords likely played a pivotal role in glacier dynamics and climate regulation, serving as hotspots for organic carbon sequestration. Aside from the present-day arid climate, northwestern Namibia exhibits a geomorphology virtually unchanged since the LPIA, permitting unique insight into this icehouse.
Early Pleistocene climate-induced erosion of the Alaska Range formed the Nenana Gravel
Authors: Sortor Rachel N. , Goehring Brent M. , Bemis Sean P. , Ruleman Chester A. , Caffee Marc W. , Ward Dylan J.
Published: August 2021

The Pliocene-Pleistocene transition resulted in extensive global cooling and glaciation, but isolating this climate signal within erosion and exhumation responses in tectonically active regimes can be difficult. The Nenana Gravel is a foreland basin deposit in the northern foothills of the Alaska Range (USA) that has long been linked to unroofing of the Alaska Range starting ca. 6 Ma. Using 26Al/10Be cosmogenic nuclide burial dating, we determined the timing of deposition of the Nenana Gravel and an overlying remnant of the first glacial advance into the northern foothills. Our results indicate that initial deposition of the Nenana Gravel occurred at the onset of the Pleistocene ca. 2.34 Ma and continued until at least ca. 1.7 Ma. The timing of initial deposition is correlative with expansion of the Cordilleran ice sheet, suggesting that the deposit formed due to increased glacial erosion in the Alaska Range. Abandonment of Nenana Gravel deposition occurred prior to the first glaciation extending into the northern foothills. This glaciation was hypothesized to have occurred ca. 1.5 Ma, but we found that it occurred ca. 0.39 Ma. A Pleistocene age for the Nenana Gravel and marine oxygen isotope stage 10 age for the oldest glaciation of the foothills necessitate reanalysis of incision and tectonic rates in the northern foothills of the Alaska Range, in addition to a shift in perspective on how these deposits fit into the climatic and tectonic history of the region.
A molecular biomarker for end-Permian plant extinction in South China
Authors: Wang Chunjiang , Visscher Henk
Published: August 2021

To help resolve current controversies surrounding the fundamental question of synchrony between end-Permian mass extinction on land and in the sea, we examined the marine Permian–Triassic reference section at Meishan (southeastern China) for land-derived molecular degradation products of pentacyclic triterpenoids with oleanane carbon skeletons, diagnostic for the Permian plant genus Gigantopteris. We identified a continuous quantitative record of mono-aromatic des-A-oleanane, which abruptly ends in the main marine extinction interval just below the Permian-Triassic boundary. This taxon-specific molecular biomarker, therefore, reveals in unmatched detail the timing and tempo of the demise of one of the most distinctive Permian plants and provides evidence of synchronous extinction among continental and marine organisms. Parallel reduction in the relative abundance of lignin phenols confirms that aridity-driven extinction was not restricted to Gigantopteris but likely affected the entire wetland flora of the equatorial South China microcontinent.
Comparison of intraosseous and intravenous epinephrine administration during resuscitation of asphyxiated newborn lambs
Authors: Roberts Calum T , Klink Sarah , Schmölzer Georg M , Blank Douglas A , Badurdeen Shiraz , Crossley Kelly J , Rodgers Karyn , Zahra Valerie , Moxham Alison , Roehr Charles Christoph , Kluckow Martin , Gill Andrew William , Hooper Stuart B , Polglase Graeme R
Published: August 2021

Objective

Intraosseous access is recommended as a reasonable alternative for vascular access during newborn resuscitation if umbilical access is unavailable, but there are minimal reported data in newborns. We compared intraosseous with intravenous epinephrine administration during resuscitation of severely asphyxiated lambs at birth.

Methods

Near-term lambs (139 days’ gestation) were instrumented antenatally for measurement of carotid and pulmonary blood flow and systemic blood pressure. Intrapartum asphyxia was induced by umbilical cord clamping until asystole. Resuscitation commenced with positive pressure ventilation followed by chest compressions and the lambs received either intraosseous or central intravenous epinephrine (10 μg/kg); epinephrine administration was repeated every 3 min until return of spontaneous circulation (ROSC). The lambs were maintained for 30 min after ROSC. Plasma epinephrine levels were measured before cord clamping, at end asphyxia, and at 3 and 15 min post-ROSC.

Results

ROSC was successful in 7 of 9 intraosseous epinephrine lambs and in 10 of 12 intravenous epinephrine lambs. The time and number of epinephrine doses required to achieve ROSC were similar between the groups, as were the achieved plasma epinephrine levels. Lambs in both groups displayed a similar marked overshoot in systemic blood pressure and carotid blood flow after ROSC. Blood gas parameters improved more quickly in the intraosseous lambs in the first 3 min, but were otherwise similar over the 30 min after ROSC.

Conclusions

Intraosseous epinephrine administration results in similar outcomes to intravenous epinephrine during resuscitation of asphyxiated newborn lambs. These findings support the inclusion of intraosseous access as a route for epinephrine administration in current guidelines.
Low-dose transscleral cyclophotocoagulation with subsequent phacoemulsification in the treatment of prolonged acute primary angle closure
Authors: Shi Yan , Oatts Julius , Tian Jiaxin , Qiao Chunyan , Zhang Qing , Han Ying , Wang Ningli
Published: August 2021

Background

To explore the outcomes and mechanisms of intraocular pressure (IOP) control using low-dose transscleral cyclophotocoagulation (LDTSCP) followed by phacoemulsification in patients with prolonged acute primary angle closure (APAC).

Methods

Patients with prolonged APAC refractory to all other treatment modalities were prospectively recruited, and underwent LDTSCP (10 shots, 2 s duration, 120° treatment with the energy starting at 1500 mW and titrated to the level with audible burst but not exceeding 2000 mW) and anterior chamber paracentesis 1 week prior to phacoemulsification with intraocular lens implantation and viscogoniosynechiolysis. Postoperative IOP, vision, anatomic changes on anterior segment optical coherence tomography and complications were recorded.

Results

Twenty eyes with prolonged APAC were recruited. Median follow-up was 12 months (range 9–18), at which point the vision in all eyes had improved and IOP was ≤17 mm Hg on no antiglaucoma medications. Following LDTSCP at postoperative day (POD) 1, IOP decreased in all eyes to a median 15 mm Hg (range: 6–28 mm Hg). Post-LDTSCP supraciliary effusion (SCE) occurred in 90% of eyes on POD1 or POD7 and ciliary body defect (CBD) was detected in 30% of eyes and resolved in all cases by postoperative month 1. Lower post-LDTSCP IOP was associated with more number of bursts (r=−0.558, p=0.011) and higher grade of SCE (r=−0.877, p<0.001), but not with total energy (p=0.240). Eyes with CBD (p=0.018) and a higher number of bursts (r=0.657, p=0.002) had higher grade SCE.

Conclusions

LDTSCP-induced SCE may explain the post-LDTSCP IOP reduction seen in eyes with prolonged APAC. LDTSCP instead of traditional more extensive treatment, was sufficient to provide a relatively safe and effective bridge therapy prior to phacoemulsification.

Trial registration number

Chinese Clinical Trials Registry (ChiCTR1900023567).
Study protocol: long-term effect of the New Nordic Renal Diet on phosphorus and lipid homeostasis in patients with chronic kidney disease, stages 3 and 4: a randomised controlled trial
Authors: Hansen Nikita Misella , Rix Marianne , Kamper Anne-Lise , Feldt-Rasmussen Bo , Christoffersen Christina , Astrup Arne , Salomo Louise
Published: August 2021

Introduction

Chronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. New Nordic Renal Diet (NNRD) is a new dietary concept designed by the present research group that aims to offer patients with moderate CKD a whole food approach with a markedly reduction in dietary phosphorus intake, corresponding to 850 mg/day. The present protocol describes a randomised controlled trial aiming to test the long-term effects of dietary intervention with NNRD versus a non-restricted habitual diet on important parameters of phosphorus and lipid homeostasis.

Methods and analysis

This trial will be executed at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Sixty patients aged>18 years with CKD stages 3 and 4 (estimated glomerular filtration rate between 15 and 45 mL/min) will be recruited and randomly assigned to the intervention or control group. The other inclusion criterion includes a medically stable condition for at least 2 months prior to the start of the study. Exclusion criteria are treatment with phosphate binders, metabolic disorders that require specific dietary regulation, pregnancy and breast feeding, any types of food allergies or those who are vegans. The observation period is 26 weeks including seven study visits at the outpatient clinic combined with a weekly telephone consultation in both groups. A follow-up visit 3 months after study completion finalises the intervention. The primary outcome is the difference in the change in 24-hour urine phosphorus excretion from baseline to week 26 between the two study groups. Secondary outcomes include changes in phosphate-related and lipid metabolism-related blood and urine biochemistry, blood pressure and body composition. Moreover, we wish to explore adherence to the diet as well as quality of life.

Ethics and dissemination

The study has been approved by the Scientific Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. The results of the studies will be presented at national and international scientific meetings, and publications will be submitted to peer-reviewed journals.

Trial registration number

ClinicalTrials.gov (wwwclinicaltrialsgov) Registry (NCT04579315).

Protocol version

The protocol, version 2, has been approved by the Ethical Committee Denmark on 18 September 2020. The protocol has also been approved by Data Protection Regulation and Data Protection Law on 15 September 2020. This study protocol is in accordance with the Standard Protocol Items: Recommendations for International Trials.
Remote-Management of COPD: Evaluating the Implementation of Digital Innovation to Enable Routine Care (RECEIVER): the protocol for a feasibility and service adoption observational cohort study
Authors: Taylor Anna , Lowe David J , McDowell Grace , Lua Stephanie , Burns Shane , McGinness Paul , Carlin Christopher M
Published: August 2021

Introduction

Reductions in exacerbation and hospitalisations are the outcomes rated as most important by people with chronic obstructive pulmonary disease (COPD). Most COPD management is currently based on a reactive approach, and delays in recognising treatable opportunities underpin COPD care quality gaps. Innovations that empower COPD self-management, facilitate integrated clinical care and support delivery of evidence-based treatment interventions are urgently required.

Methods and analysis

The Remote-Management of COPD: Evaluating the Implementation of Digital Innovation to Enable Routine Care trial is a prospective observational cohort hybrid implementation and effectiveness study that will explore the adoption of a digital service model for people with ‘high-risk’ COPD and evaluate the feasibility of this approach versus current standards of care. People with COPD, who have had recent severe exacerbation and/or COPD–obstructive sleep apnoea overlap or chronic hypercapnic respiratory failure requiring home non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP), with internet access will be recruited into the study and enrolled into the digital service.

Study endpoints will examine participant utilisation, clinical service impact and clinical outcomes compared with historical and contemporary control patient data. The digital infrastructure will also provide a foundation to explore the feasibility of approaches to predict outcomes and exacerbation in people with COPD through machine learning analysis.

Ethics and dissemination

Ethical approval for this clinical trial has been obtained from the West of Scotland Research Ethics Service. The trial will commence in September 2019 for a duration of 2 years. Results will be presented at local, national and international meetings, as well as submission for publication to peer-reviewed journals.

Trial registration number

NCT04240353.
Integrated analysis of the faecal metagenome and serum metabolome reveals the role of gut microbiome-associated metabolites in the detection of colorectal cancer and adenoma
Authors: Chen Feng , Dai Xudong , Zhou Chang-Chun , Li Ke-xin , Zhang Yu-juan , Lou Xiao-Ying , Zhu Yuan-Min , Sun Yan-Lai , Peng Bao-Xiang , Cui Wei
Published: August 2021

Objective

To profile gut microbiome-associated metabolites in serum and investigate whether these metabolites could distinguish individuals with colorectal cancer (CRC) or adenoma from normal healthy individuals.

Design

Integrated analysis of untargeted serum metabolomics by liquid chromatography-mass spectrometry and metagenome sequencing of paired faecal samples was applied to identify gut microbiome-associated metabolites with significantly altered abundance in patients with CRC and adenoma. The ability of these metabolites to discriminate between CRC and colorectal adenoma was tested by targeted metabolomic analysis. A model based on gut microbiome-associated metabolites was established and evaluated in an independent validation cohort.

Results

In total, 885 serum metabolites were significantly altered in both CRC and adenoma, including eight gut microbiome-associated serum metabolites (GMSM panel) that were reproducibly detected by both targeted and untargeted metabolomics analysis and accurately discriminated CRC and adenoma from normal samples. A GMSM panel-based model to predict CRC and colorectal adenoma yielded an area under the curve (AUC) of 0.98 (95% CI 0.94 to 1.00) in the modelling cohort and an AUC of 0.92 (83.5% sensitivity, 84.9% specificity) in the validation cohort. The GMSM model was significantly superior to the clinical marker carcinoembryonic antigen among samples within the validation cohort (AUC 0.92 vs 0.72) and also showed promising diagnostic accuracy for adenomas (AUC=0.84) and early-stage CRC (AUC=0.93).

Conclusion

Gut microbiome reprogramming in patients with CRC is associated with alterations of the serum metabolome, and GMSMs have potential applications for CRC and adenoma detection.
Residual homing of α4β7-expressing β1+PI16+regulatory T cells with potent suppressive activity correlates with exposure-efficacy of vedolizumab
Authors: Becker Emily , Dedden Mark , Gall Christine , Wiendl Maximilian , Ekici Arif Bülent , Schulz-Kuhnt Anja , Schweda Anna , Voskens Caroline , Hegazy Ahmed , Vitali Francesco , Atreya Raja , Müller Tanja Martina , Atreya Imke , Neurath Markus F , Zundler Sebastian
Published: August 2021

Objective

The anti-α4β7 integrin antibody vedolizumab is administered at a fixed dose for the treatment of IBDs. This leads to a wide range of serum concentrations in patients and previous studies had suggested that highest exposure levels are associated with suboptimal clinical response. We aimed to determine the mechanisms underlying these non-linear exposure-efficacy characteristics of vedolizumab.

Design

We characterised over 500 samples from more than 300 subjects. We studied the binding of vedolizumab to T cells and investigated the functional consequences for dynamic adhesion, transmigration, gut homing and free binding sites in vivo. Employing single-cell RNA sequencing, we characterised α4β7 integrin-expressing T cell populations ‘resistant’ to vedolizumab and validated our findings in vitro and in samples from vedolizumab-treated patients with IBD. We also correlated our findings with a post-hoc analysis of the Gemini II and III studies.

Results

Regulatory T (TReg) cells exhibited a right-shifted vedolizumab binding profile compared with effector T (TEff) cells. Consistently, in a certain concentration range, the residual adhesion, transmigration, homing of and availability of functional α4β7 on TRegcells in vivo was higher than that of/on TEffcells. We identified a vedolizumab-‘resistant’ α4β7-expressing β1+PI16+TRegcell subset with pronounced regulatory properties as the substrate for this effect. Our observations correlated with exposure-efficacy data from Gemini II and III trials.

Conclusion

Completely blocking TEffcell trafficking with vedolizumab, while simultaneously permitting residual homing of powerful TRegcells in an optimal ‘therapeutic window’ based on target exposure levels might be a strategy to optimise treatment outcomes in patients with IBD.
Epidemiology of paediatric drowning hospitalisations in the USA: a population-based study
Authors: Theodorou Christina M. , Rajasekar Ganesh , McFadden Nikia R. , Brown Erin G. , Nuño Miriam
Published: August 2021

Background

Drowning is a leading cause of death in children ≤5 years old. Detailed data on the epidemiology of drowning in this high-risk population can inform preventative efforts. We aimed to study trends in incidence and case fatality rates (CFR) in the USA among young children hospitalised after drowning.

Methods

Children ≤5 years old hospitalised in the USA after drowning were identified from the Kids Inpatient Database 2000–2016. Incidence and CFRs by calendar year, age, sex, race/ethnicity and hospital region were calculated. Trends over time were evaluated. Factors associated with fatal drowning were assessed.

Results

Among 30 560 804 hospitalised children ≤5 years old, 9261 drowning cases were included. Patients were more commonly male (62.3%) and white (47.4%). Two years old had the highest incidence of hospitalisation after drowning, regardless of race/ethnicity, sex and region. Overall drowning hospitalisations decreased by 49% from 2000 to 2016 (8.38–4.25 cases per 100 000 children). The mortality rate was 11.4% (n=1060), and most occurred in children ≤3 years old (83.0%). Overall case fatality decreased between 2000 and 2016 (risk ratio (RR) 0.44, 95% CI 0.25 to 0.56). The lowest reduction in incidence and case fatality was observed among Black children (Incidence RR 0.92, 95% CI 0.75 to 1.13; case fatality RR 0.80, 95% CI 0.41 to 1.58).

Conclusions

Hospitalisations and CFRs for drowning among children ≤5 years old have decreased from 2000 to 2016. Two years old are at the highest risk of both fatal and non-fatal drowning. Disparities exist for Black children in both the relative reduction in drowning hospitalisation incidence and case fatality. Interventions should focus on providing equitable preventative care measures to this population.
Pilot study to evaluate school safety zone built environment interventions
Authors: Rothman Linda , Ling Rebecca , Hagel Brent E , Macarthur Colin , Macpherson Alison K , Buliung Ron , Fuselli Pamela , Howard Andrew William
Published: August 2021

Background

School safety zones were created in 2017 under the City of Toronto’s Vision Zero Road Safety Plan. This pilot study examined the effect of built environment interventions on driver speeds, active school transportation (AST) and dangerous driving.

Methods

Interventions were implemented at 34 schools and 45 matched controls (2017–2019). Drivers travelling over the speed limit of >30 km/hour and 85th percentile speeds were measured using pneumatic speed tubes at school frontages. Observers examined AST and dangerous driving at school arrival times. Repeated measures beta and multiple regression analyses were used to study the intervention effects.

Results

Most schools had posted speed limits of 40 km/hour (58%) or ≥50 km/hour (23%). A decrease in drivers travelling over the speed limit was observed at intervention schools post-intervention (from 44% to 40%; OR 0.79, 95% CI 0.66 to 0.96). Seventy-one per cent of drivers travelled >30 km/hour and the 85th percentile speed was 47 km/hour at intervention schools, with no change in either postintervention. There were no changes in speed metrics in the controls. AST increased by 5% (OR 1.22, 95% CI 0.97 to 1.54) at intervention schools. Reductions in dangerous driving were observed at all schools.

Conclusions

Posted speed limits were >30 km/hour at most schools and high proportions of drivers were travelling above the speed limits. There were reductions in drivers exceeding the speed limit and in dangerous driving, and modest increased AST post intervention. Bolder interventions to slow traffic are required to effectively reduce speeding around schools, which may increase safe AST.
Risk of major chronic diseases in transport, rescue and security industries: a longitudinal register-based study
Authors: Herttua Kimmo , Ahrenfeldt Linda Juel , Paljarvi Tapio
Published: August 2021

Objective

To investigate the risk of hospitalisation for major chronic diseases across representative transport, rescue and security industries.

Methods

We performed a register-based study of 624 571 workers from six industries in Denmark between 2000 and 2005, followed up hospitalisation for chronic diseases up to 17 years, and compared with a 20% random sample of the economically active population.

Results

HR from the Cox regression models showed that seafarers had higher risk of lung cancer (men: 1.54, 95% CI 1.31 to 1.81; women: 1.63, 95% CI 1.13 to 2.36), and male seafarers had higher risk of diabetes (1.32, 95% CI 1.21 to 1.43) and oral cancer (1.51, 95% CI 1.21 to 1.88). Men and women in land transport had increased risk of diabetes (men: 1.68, 95% CI 1.63 to 1.73; women 1.55, 95% CI 1.40 to 1.71) and chronic respiratory disease (men: 1.21, 95% CI 1.16 to 1.25; women 1.42, 95% CI 1.32 to 1.53). Among women, a higher risk of gastrointestinal cancer was observed in aviation (1.53, 95% CI 1.23 to 1.89) and police force (1.29, 95% CI 1.01 to 1.65), oral cancer in defence forces (1.83, 95% CI 1.20 to 2.79), and chronic respiratory disease in rescue service (1.47, 95% CI 1.21 to 1.77), while men in defence forces, police force and rescue service had mainly lower risk of these chronic diseases.

Conclusions

We observed considerable health disparities from chronic diseases across transport, rescue and security industries, with workers in seafaring and land transport generally bearing the greatest relative burden.
Provision of instructions to drink ad libitum or according to thirst sensation: impact during 120 km of cycling in the heat in men
Authors: Claveau Pascale , Deshayes Thomas A. , Jeker David , Pancrate Timothée , Goulet Eric D.B.
Published: August 2021

The terms drinking to thirst and ad libitum drinking are used interchangeably, but should they? We investigated the differences in how athletes consumed fluids during exercise when instructed to drink according to thirst or ad libitum. Using a randomized, crossover, and counterbalanced design, 10 males (27 ± 4 y) cycled 120 km (48 ± 4% of peak power, 33 °C, 40% relative humidity) on 2 occasions, while drinking water according to thirst or ad libitum. Participants covered the cycling trials in 222 ± 11 min (p = 0.29). Although the body mass loss at the end of exercise and total volume of water consumed were similar between trials, thirst perception before each sip and the volume consumed per sip were significantly higher with thirst than ad libitum drinking, whereas the total number of sips was significantly lower with thirst than ad libitum drinking. Perceived exertion, rectal temperature, and heart rate were all significantly higher with thirst than ad libitum drinking, but the difference was trivial. In conclusion, thirst and ad libitum drinking are associated with different drinking patterns, but equally maintain fluid balance during prolonged exercise. The terms drinking to thirst and ad libitum drinking can be used interchangeably to guide fluid intake during prolonged exercise.

Novelty: Both strategies are associated with different patterns of fluid ingestion during prolonged exercise, but are equally effective in maintaining fluid balance. Perceived exertion, rectal temperature, and heart rate are regulated dissimilarly by thirst and ad libitum drinking, but the difference is trivial.
RNF38 inhibits osteosarcoma cell proliferation by binding to CRY1
Authors: Zhou Jian , Tang Zhen-yu , Sun Xiao-liang
Published: August 2021

The PI3K/AKT pathway plays an important role in the development of osteosarcoma. RNF38 interferes with activation of the AKT pathway. Cryptochrome1 (CRY1) inhibits osteosarcoma proliferation through the AKT pathway. We aimed to clarify whether RNF38 affects the proliferation of osteosarcoma cells by regulating the PI3K/AKT pathway through its interaction with CRY1. The mRNA levels of RNF38 were determined using qRT-PCR. Protein levels of RNF38, p-p70S6, p70S6, +p-AKT, AKT, p-mTOR, mTOR, and CRY1 were detected by western blotting. The proliferation of osteosarcoma cells was detected using CCK-8 and colony formation assays. The interaction between CRY1 and RNF38 was detected by co-immunoprecipitation and GST pull-down assays. RNF38 expression was higher in Saos-2 and U20S cells than in hFOB cells. Overexpression of RNF38 promoted the proliferation of osteosarcoma cells, the number of colonies, and p-AKT and p-mTOR levels, suggesting that overexpression of RNF38 activated the PI3K/AKT pathway. In addition, RNF38 directly binds to the N-terminal of CRY1. The simultaneous knockdown of RNF38 and CRY1 restored the level of p-AKT, which was reduced by RNF38 knockdown alone. RNF38 affects the proliferation of osteosarcoma cells by regulating the PI3K/AKT pathway through its interaction with CRY1.
Azimuthal dependence of two-particle transverse momentum current correlations
Authors: Magdy Niseem , Basu Sumit , Gonzalez Victor , Marin Ana , Evdokimov Olga , Lacey Roy A. , Pruneau Claude
Published: August 2021

Two-particle transverse momentum correlation functions are a powerful technique for understanding the dynamics of relativistic heavy-ion collisions. Among these, the transverse momentum correlator $$G_{2}\left( \varDelta \eta ,\varDelta \varphi \right) $$

G
2

Δ
η
,
Δ
φ

is of particular interest for its potential sensitivity to the shear viscosity per unit of entropy density $$\eta /s$$

η
/
s

of the quark-gluon plasma formed in heavy-ion collisions. We use the UrQMD, AMPT, and EPOS models for Au–Au at $$\sqrt{s_\mathrm{NN}}$$

s
NN

= 200 GeV and Pb–Pb at $$\sqrt{s_\mathrm{NN}}$$

s
NN

= 2760 GeV to investigate the long range azimuthal dependence of $$G_{2}\left( \varDelta \eta ,\varDelta \varphi \right) $$

G
2

Δ
η
,
Δ
φ

, and explore its utility to constrain $$\eta /s$$

η
/
s

based on charged particle correlations. We find that the three models yield quantitatively distinct transverse momentum Fourier harmonics coefficients $$a^{p_\mathrm{T}}_{n}$$

a
n

p
T

. We also observe these coefficients exhibit a significant dependence on $$\eta /s$$

η
/
s

in the context of the AMPT model. These observations suggest that exhaustive measurements of the dependence of $$G_{2}\left( \varDelta \varphi \right) $$

G
2

Δ
φ

with collision energy, system size, collision centrality, in particular, offer the potential to distinguish between different theoretical models and their underlying assumptions. Exhaustive analyses of $$G_{2}\left( \varDelta \varphi \right) $$

G
2

Δ
φ

obtained in large and small systems should also be instrumental in establishing new constraints for precise extraction of $$\eta /s$$

η
/
s

.
Equiprobable and attacked-square chess entropies by phases, levels of play and game outcomes
Authors: Islas-García J. D. A. , del Castillo-Escribano M. , del Castillo-Mussot M.
Published: August 2021

In any legal chess position, we define an attacked-square entropy [Formula: see text] for either Black or White pieces in terms of the square occupation probability [Formula: see text], where [Formula: see text] is the number of all possible movements to square [Formula: see text] (free or occupied by an opponent’s piece) and [Formula: see text] is the total mobility defined as the sum of all possible movements. Thus, each attacked square contributes to the entropy according to its received “firepower” concentration. A simpler nonsquare-dependant equiprobable entropy [Formula: see text] in terms of equal probabilities [Formula: see text] always yields [Formula: see text]. On average, the difference [Formula: see text] is very large in the Opening phase and [Formula: see text] decreases faster for lower ranked players after move 25. A major cause of the reduction of [Formula: see text] during a game is material loss, which is an irreversible process. By game outcome, gaps in average [Formula: see text] among winners, draws and losers are larger for Amateur players than for Elite players, both in the Middlegame and Endgame. Statistically, Elite players exhibit narrower dispersions in [Formula: see text]. Also, the entropy rates of the Elite level fluctuate much less than the entropies of other levels. Density of attacks in the four-square central zone is very high in the Opening, specially for Elite players.
Business Creation Among Participants in Entrepreneurship Education Programs: A Case Study Among University-Level Participants in a Context of Adverse Business Environment
Authors: Paul Bénédique , Hyppolite Andie , Mombeuil Claudel , Cadet Raulin L.
Published: August 2021

There is a scarcity of studies that investigate the underlying factors that boost aspiring entrepreneurs to effectively start a business after attending entrepreneurship education (EE) programs, particularly in an adverse business environment. To fill out this gap, this exploratory research answers the following question: What differentiates business creators from non-creators among participants after entrepreneurship education? To answer this question, we compare a group of 64 business creators to a group of 50 non-business creators, both groups selected randomly among 912 participants to an EE program in Haiti three years after the end of the program. Based on an institutional perspective, our results show that, in the context of an adverse business environment, participants who came from a family with an entrepreneurial background, have a useful network of contacts, and showed adaptive institutional reaction were more likely to create their business, in comparison to the others. Based on these results suggestions for EE training and future studies are provided.
OPTIMAL DYNAMIC FUTURES PORTFOLIO UNDER A MULTIFACTOR GAUSSIAN FRAMEWORK
Authors: LEUNG TIM , YAN RAPHAEL , ZHOU YANG
Published: August 2021

We study the problem of dynamically trading futures in continuous time under a multifactor Gaussian framework. We present a utility maximization approach to determine the optimal futures trading strategy. This leads to the explicit solution to the Hamilton–Jacobi–Bellman (HJB) equations. We apply our stochastic framework to two-factor models, namely, the Schwartz model and Central Tendency Ornstein–Uhlenbeck (CTOU) model. We also develop a multiscale CTOU model, which has a fast mean-reverting and a slow mean-reverting factor in the spot asset price dynamics. Numerical examples are provided to illustrate the investor’s optimal positions for different futures portfolios.
The non-Lipschitz stochastic Cahn–Hilliard–Navier–Stokes equations in two space dimensions
Authors: Sun Chengfeng , Huang Qianqian , Liu Hui
Published: August 2021

The stochastic two-dimensional Cahn–Hilliard–Navier–Stokes equations under non-Lipschitz conditions are considered. This model consists of the Navier–Stokes equations controlling the velocity and the Cahn–Hilliard model controlling the phase parameters. By iterative techniques, a priori estimates and weak convergence method, the existence and uniqueness of an energy weak solution to the equations under non-Lipschitz conditions have been obtained.
Graded torsion-free 𝔰𝔩2(ℂ)-modules of rank 2
Authors: Bahturin Yuri , Shihadeh Abdallah
Published: August 2021

In this paper, we explore the possibility of endowing simple infinite-dimensional [Formula: see text]-modules by the structure of graded modules. The gradings on the finite-dimensional simple modules over simple Lie algebras have been studied in [7,8].