bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung ultrasound of the dependent lung detects real-time changes in lung volume in the preterm lamb
Authors: Sett Arun , Kenna Kelly R , Sutton Rebecca J , Perkins Elizabeth J , Sourial Magdy , Chapman Jack D , Donath Susan M , Sasi Arun , Rogerson Sheryle R , Manley Brett J , Davis Peter G , Pereira-Fantini Prue M , Tingay David G 
Published: June 2022

BackgroundEffective lung protective ventilation requires reliable, real-time estimation of lung volume at the bedside. Neonatal clinicians lack a readily available imaging tool for this purpose.ObjectiveTo determine the ability of lung ultrasound (LUS) of the dependent region to detect real-time changes in lung volume, identify opening and closing pressures of the lung, and detect pulmonary hysteresis.MethodsLUS was performed on preterm lambs (n=20) during in vivo mapping of the pressure-volume relationship of the respiratory system using the super-syringe method. Electrical impedance tomography was used to derive regional lung volumes. Images were blindly graded using an expanded scoring system. The scores were compared with total and regional lung volumes, and differences in LUS scores between pressure increments were calculated.ResultsChanges in LUS scores correlated moderately with changes in total lung volume (r=0.56, 95% CI 0.47-0.64, p<0.0001) and fairly with right whole (r=0.41, CI 0.30-0.51, p<0.0001), ventral (r=0.39, CI 0.28-0.49, p<0.0001), central (r=0.41, CI 0.31-0.52, p<0.0001) and dorsal (r=0.38, CI 0.27-0.49, p<0.0001) regional lung volumes. The pressure-volume relationship of the lung exhibited hysteresis in all lambs. LUS was able to detect hysteresis in 17 (85%) lambs. The greatest changes in LUS scores occurred at the opening and closing pressures.ConclusionLUS was able to detect large changes in total and regional lung volume in real time and correctly identified opening and closing pressures but lacked the precision to detect small changes in lung volume. Further work is needed to improve precision prior to translation to clinical practice.
WHO’s support for COVID-19 research and knowledge management in the Eastern Mediterranean Region
Authors: Rashidian Arash , Wu Kaiyue , Al Ariqi Lubna , Aly Eman , Mandil Ahmed , Barakat Amal , Kodama Chiori , Kheirandish Mehrnaz , Nour Eldin Hassan Hatem , Doctor Henry Victor , Hemachandra Nilmini , Fahmy Kamal , Dingwall Phillip , Nour Mohamed , Krishnamurthy Reddiar Sumithra 
Published: June 2022

Health research, innovation and knowledge management remain major priorities of the WHO’s response to the COVID-19 pandemic. WHO’s Eastern Mediterranean Regional Office (EMRO) supports priority research initiatives that address gaps in current knowledge regarding the COVID-19 pandemic. Through a specific call for proposals, 122 research proposals were received and reviewed in 2020, of which 17 were recommended for funding from eight countries. Ten countries in the region participated in the global solidarity trial to assess potential therapies for COVID-19. In addition, WHO advocated for early serological and epidemiological investigations (‘COVID-19 Unity Studies’) on the general population, healthcare workers, pregnant women and neonates, and extending technical, financial and material support for them.Starting in early 2020, scholarly articles on COVID-19 have been published in every issue of theEastern Mediterranean Health Journal. More than 6300 publications on COVID-19 were made available on the WHO knowledge management portal in the last year alone. WHO is also supporting countries in conducting studies to assess the field effectiveness of vaccines deployed nationally. To build and strengthen country capacities, regional webinars and intercountry meetings were conducted on research ethics, national health information systems and evidence-based health policy making. With support from WHO EMRO’s new research and knowledge management pillar, countries in the region were well equipped to contribute to a global understanding of the novel virus’s characteristics, as well as employ a national response based on informed evidence.
Thrombolysis, time-to-treatment and in-hospital outcomes among young adults with ischaemic stroke in China: findings from a nationwide registry study in China
Authors: Wang Hai-Yan , Gu Hong-Qiu , Zhou Qi , Jiang Ying-Yu , Yang Xin , Wang Chun-Juan , Zhao Xing-Quan , Wang Yi-Long , Liu Li-Ping , Meng Xia , Li Hao , Liu Chelsea , Li Zi-Xiao , Wang Yong-Jun , Jiang Yong 
Published: June 2022

Background and purposeWe aimed to determine whether young adults (<50 years) with acute ischaemic stroke (AIS) are more likely to receive intravenous tissue plasminogen activator (IV tPA) and have shorter time to treatment than older patients with stroke.MethodsWe analysed data from the Chinese Stroke Center Alliance registry for patients with AIS hospitalised between August 2015 and July 2019. Patients were classified into two groups according to age: young adults (<50 years of age) and older adults (≥50 years of age).ResultsOf 793 175 patients with AIS admitted to 1471 hospitals, 9.1% (71 860) were young adults. Compared with older adults, a higher proportion of young adults received IV tPA among patients without contraindicaitons (7.2% vs 6.1%, adjusted OR (aOR) 1.13, 95% CI 1.10 to 1.17) and among patients without contraindications and with onset-to-door time ≤3.5 hours (23.6% vs 19.3%, aOR 1.20, 95% CI 1.15 to 1.24). We did not observe differences in onset-to-needle time (median hours 2.7 hours) or door-to-needle time (DNT) (median minutes 60 min) between young and older adults. The proportion of DNT ≤30 min, DNT ≤45 min and DNT ≤60 min in young and older IV tPA-treated patients were 16.9% vs 18.8%, 30.2% vs 32.8% and 50.2% vs 54.2%, respectively. Compared with older adults, young adults treated with IV tPA had lower odds of in-hospital mortality (0.5% vs 1.3%, aOR 0.54, 95% CI 0.35 to 0.82) and higher odds of independent ambulation at discharge (61.0% vs 53.6%, aOR 1.15, 95% CI 1.08 to 1.22), and the associations may be partly explained by stroke severity measured by the National Institutes of Health Stroke Scale score.ConclusionYoung adults with AIS were more likely to receive IV tPA than older adults, although there was no difference between the two groups in time to treatment. Compared with older adults, young adults may had better in-hospital outcomes.
Shorter versus longer durations of antibiotic treatment for patients with community-acquired pneumonia: a protocol for a systematic review and meta-analysis
Authors: Agarwal Arnav , Gao Ya , Colunga Lozano Luis Enrique , Asif Saad , Bakaa Layla , Ghadimi Maryam , Basmaji John , Das Aninditee , Loeb Mark , Guyatt Gordon 
Published: June 2022

IntroductionCommunity-acquired pneumonia (CAP), frequently encountered in both outpatient and inpatient settings, is the leading cause of infectious disease-related mortality. While equipoise regarding the optimal duration of antimicrobial therapy to treat CAP remains, recent studies suggest shorter durations of therapy may achieve optimal outcomes. We have therefore planned a systematic review and meta-analysis evaluating the impact of shorter versus longer durations of antibiotic therapy for patients with CAP.Methods and analysisWe searched Ovid MEDLINE, Embase, CINAHL and Cochrane Central Register of Controlled Trials from inception to September 2021 for randomised controlled trials evaluating shorter versus longer duration of antibiotics. Eligible studies will compare durations with a minimum difference of two days of antibiotic therapy, irrespective of antibiotic agent, class, route, frequency or dosage, and will report on any patient-important outcome of benefit or harm. Paired reviewers working independently will conduct title and abstract screening, full-text screening, data extraction and risk of bias (RoB) evaluation using a modified Cochrane RoB 2.0 tool. We will perform random-effects modelling for meta-analyses, with study weights generated using the inverse variance method, and will assess certainty in effect estimates using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN) tool will inform assessments of credibility of subgroup effects based on severity of illness, drug class, duration of therapy, setting of CAP acquisition and RoB.Ethics and disseminationThe results will be of importance to general practitioners and internists managing CAP, and may directly inform international clinical guidance. Where concerns regarding antimicrobial resistance continue to grow internationally, this evidence summary may motivate new recommendations regarding shorter durations of therapy. We intend to disseminate our findings via national and international conferences, and publication in a peer-reviewed journal.PROSPERO registration numberCRD42021283990.
Association between personality traits and experience of adverse periocular reactions to topical prostaglandin analogues
Authors: Kishimoto Nanami , Noro Takahiko , Kodaka Fumitoshi , Kurosawa Mei , Itoh Yoshinori , Ogawa Shumpei , Watanabe Tomoyuki , Kubota Masaomi , Hori Kiyotaka , Shigeta Masahiro , Nakano Tadashi 
Published: June 2022

BackgroundAesthetically unappealing adverse periocular reactions to prostaglandin (PG) eye-drops are a major challenge in glaucoma treatment. This study analysed the personality traits of patients with glaucoma based on a five-factor model and examined the associations between these factors and adverse periocular reactions.MethodsOne hundred and forty-seven patients with glaucoma were surveyed anonymously regarding their personality traits and how often adverse periocular reactions were experienced.ResultsThe analysis included 117 valid responses (71 men and 46 women, age: 61.9±11.5 years). Patients who experienced hypertrichosis of the eyelashes scored significantly higher on extraversion (p<0.05), with no significant differences in the other four personality traits. Patients who experienced eyelid hyperpigmentation and deepening of the upper eyelid sulcus showed no significant differences in any of the personality traits. Younger patients scored significantly higher on hypertrichosis (p<0.05).ConclusionThe experience of adverse reactions differed according to patient age and personality traits. Therefore, eye-drops should be chosen based on these factors.Trial registration numberUMIN000035155.
Predictive validity of the Infant Toddler Checklist in primary care at the 18-month visit and developmental diagnosis at 3–5 years: a prospective cohort study
Authors: Borkhoff Cornelia M , Atalla Marina , Bayoumi Imaan , Birken Catherine S , Maguire Jonathon L , Parkin Patricia C 
Published: June 2022

ObjectiveThere is international variation in recommendations regarding developmental screening and growing recognition of the low sensitivity of commonly used developmental screening tools. Our objective was to examine the predictive validity of the Infant Toddler Checklist (ITC) at 18 months to predict a developmental diagnosis at 3–5 years, in a primary care setting.MethodsWe designed a prospective cohort study, recruiting in primary care in Toronto, Canada. Parents completed the ITC at the 18-month visit and reported developmental diagnosis at 3–5 years (developmental delay, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), learning problem). We calculated screening test properties with 95% CIs. We used multivariable logistic regression analyses adjusted for important covariates.ResultsIn the final sample (n=488), mean age at screening was 18.5 (SD 1.1) months, and at follow-up was 46.6 (SD 10.0) months. At screening, 46 (9.4%) had a positive ITC. At follow-up, 26 (5.3%) had a developmental diagnosis, including: developmental delay (n=22), ASD (n=4), ADHD (n=1), learning problem (n=1); parents of two children each reported two diagnoses (total of 28 diagnoses). Of four children with a diagnosis of ASD at follow-up, three had a positive ITC at 18 months. The ITC specificity (92%, 95% CI: 89% to 94%) and negative predictive value (96%, 95% CI: 95% to 97%) were high; false positive rate was low (8%, 95% CI: 6% to 11%); sensitivity was low (31%, 95% CI: 14% to 52%). There was a strong association between a positive ITC at 18 months and later developmental diagnosis (adjusted OR 4.48, 95% CI: 1.72 to 11.64; p=0.002).ConclusionThe ITC had high specificity, high negative predictive value, low false positive rate, and identified children with later developmental delay and ASD. The ITC had low sensitivity, similar to other screening tools underscoring the importance of continuous developmental surveillance at all health supervision visits.
Projections of smoking-related cancer mortality in Australia to 2044
Authors: Luo Qingwei , Steinberg Julia , Yu Xue Qin , Weber Marianne , Caruana Michael , Yap Sarsha , Grogan Paul B , Banks Emily , O’Connell Dianne L , Canfell Karen 
Published: June 2022

BackgroundWhile many high-income countries including Australia have successfully implemented a range of tobacco control policies, smoking remains the leading preventable cause of cancer death in Australia. We have projected Australian mortality rates for cancer types, which have been shown to have an established relationship with cigarette smoking and estimated numbers of cancer deaths attributable to smoking to 2044.MethodsCancer types were grouped according to the proportion of cases currently caused by smoking: 8%–30% and >30%. For each group, an age–period– cohort model or generalised linear model with cigarette smoking exposure as a covariate was selected based on the model fit statistics and validation using observed data. The smoking-attributable fraction (SAF) was calculated for each smoking-related cancer using Australian smoking prevalence data and published relative risks.ResultsDespite the decreasing mortality rates projected for the period 2015–2019 to 2040–2044 for both men and women, the overall number of smoking-related cancer deaths is estimated to increase by 28.7% for men and 35.8% for women: from 138 707 (77 839 men and 60 868 women) in 2015–2019 to 182 819 (100 153 men and 82 666 women) in 2040–2044. Over the period 2020–2044, there will be 254 583 cancer deaths (173 943 men and 80 640 women) directly attributable to smoking, with lung, larynx, oesophagus and oral (comprising lip, oral cavity and pharynx) cancers having the largest SAFs.InterpretationCigarette smoking will cause over 250 000 cancer deaths in Australia from 2020 to 2044. Continued efforts in tobacco control remain a public health priority, even in countries where smoking prevalence has substantially declined.
Associations between short-term exposure to PM2.5and cardiomyocyte injury in myocardial infarction survivors in North Carolina
Authors: Wyatt Lauren , Kamat Gauri , Moyer Joshua , Weaver Anne M , Diaz-Sanchez David , Devlin Robert B , Di Qian , Schwartz Joel D , Cascio Wayne E , Ward-Caviness Cavin K 
Published: June 2022

ObjectiveShort-term ambient fine particulate matter (PM2.5) is associated with adverse cardiovascular events including myocardial infarction (MI). However, few studies have examined associations between PM2.5and subclinical cardiomyocyte damage outside of overt cardiovascular events. Here we evaluate the impact of daily PM2.5on cardiac troponin I, a cardiomyocyte specific biomarker of cellular damage.MethodsWe conducted a retrospective cohort study of 2924 patients identified using electronic health records from the University of North Carolina Healthcare System who had a recorded MI between 2004 and 2016. Troponin I measurements were available from 2014 to 2016, and were required to be at least 1 week away from a clinically diagnosed MI. Daily ambient PM2.5concentrations were estimated at 1 km resolution and assigned to patient residence. Associations between log-transformed troponin I and daily PM2.5were evaluated using distributed lag linear mixed effects models adjusted for patient demographics, socioeconomic status and meteorology.ResultsA 10 µg/m3elevation in PM2.53 days before troponin I measurement was associated with 0.06 ng/mL higher troponin I (95% CI=0.004 to 0.12). In stratified models, this association was strongest in patients that were men, white and living in less urban areas. Similar associations were observed when using 2-day rolling averages and were consistently strongest when using the average exposure over the 5 days prior to troponin I measurement.ConclusionsDaily elevations in PM2.5were associated with damage to cardiomyocytes, outside of the occurrence of an MI. Poor air quality may cause persistent damage to the cardiovascular system leading to increased risk of cardiovascular disease and adverse cardiovascular events.
When can we compute analytically lookback time, age of the universe, and luminosity distance?
Authors: Jose Sonia , Leblanc Alexandre , Faraoni Valerio 
Published: June 2022

AbstractIn Friedmann–Lemaître–Robertson–Walker cosmology, it is sometimes possible to compute analytically lookback time, age of the universe, and luminosity distance versus redshift, expressing them in terms of a finite number of elementary functions. We classify these situations using the Chebyshev theorem of integration and providing examples.
Cooper pairs localization in tree-like networks of superconducting islands
Authors: Romeo Francesco , De Luca Roberto 
Published: June 2022

AbstractWe study inhomogeneous Cooper pairs distribution and localization effects in tree-like networks of superconducting islands coupled via Josephson weak links. Using a generalized Feynman’s approach, reminiscent of the Bose–Hubbard model, we demonstrate that the Cooper pairs fraction which localizes on a specific network’s island is limited by the network topology and, if present, by the repulsive interaction. These findings contribute to clarify the interplay between confinement effects induced by the network’s topology and interaction and shed some light on recent experiments dealing with networks of Josephson junctions.
The Interaction of SWI/SNF with the Ribosome Regulates Translation and Confers Sensitivity to Translation Pathway Inhibitors in Cancers with Complex Perturbations
Authors: Ulicna Livia , Kimmey Samuel C. , Weber Christopher M. , Allard Grace M. , Wang Aihui , Bui Nam Q. , Bendall Sean C. , Crabtree Gerald R. , Bean Gregory R. , Van Rechem Capucine 
Published: June 2022

AbstractSubunits from the chromatin remodelers mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) are mutated, deleted, or amplified in more than 40% of cancers. Understanding their functions in normal cells and the consequences of cancerous alterations will provide insight into developing new targeted therapies. Here we examined whether mSWI/SNF mutations increase cellular sensitivity to specific drugs. Taking advantage of the DepMap studies, we demonstrate that cancer cells harboring mutations of specific mSWI/SNF subunits exhibit a genetic dependency on translation factors and are sensitive to translation pathway inhibitors. Furthermore, mSWI/SNF subunits were present in the cytoplasm and interacted with the translation initiation machinery, and short-term inhibition and depletion of specific subunits decreased global translation, implicating a direct role for these factors in translation. Depletion of specific mSWI/SNF subunits also increased sensitivity to mTOR-PI3K inhibitors. In patient-derived breast cancer samples, mSWI/SNF subunits expression in both the nucleus and the cytoplasm was substantially altered. In conclusion, an unexpected cytoplasmic role for mSWI/SNF complexes in translation suggests potential new therapeutic opportunities for patients afflicted by cancers demonstrating alterations in their subunits.Significance:This work establishes direct functions for mSWI/SNF in translation and demonstrates that alterations in mSWI/SNF confer a therapeutic vulnerability to translation pathway inhibitors in cancer cells.
Cancer-Associated Fibroblasts Suppress CD8+ T-cell Infiltration and Confer Resistance to Immune-Checkpoint Blockade
Authors: Jenkins Liam , Jungwirth Ute , Avgustinova Alexandra , Iravani Marjan , Mills Adam , Haider Syed , Harper James , Isacke Clare M. 
Published: June 2022

AbstractImmune-checkpoint blockade (ICB) promotes antitumor immune responses and can result in durable patient benefit. However, response rates in breast cancer patients remain modest, stimulating efforts to discover novel treatment options. Cancer-associated fibroblasts (CAF) represent a major component of the breast tumor microenvironment and have known immunosuppressive functions in addition to their well-established roles in directly promoting tumor growth and metastasis. Here we utilized paired syngeneic mouse mammary carcinoma models to show that CAF abundance is associated with insensitivity to combination αCTLA4 and αPD-L1 ICB. CAF-rich tumors exhibited an immunologically cold tumor microenvironment, with transcriptomic, flow cytometric, and quantitative histopathologic analyses demonstrating a relationship between CAF density and a CD8+ T-cell–excluded tumor phenotype. The CAF receptor Endo180 (Mrc2) is predominantly expressed on myofibroblastic CAFs, and its genetic deletion depleted a subset of αSMA-expressing CAFs and impaired tumor progression in vivo. The addition of wild-type, but not Endo180-deficient, CAFs in coimplantation studies restricted CD8+ T-cell intratumoral infiltration, and tumors in Endo180 knockout mice exhibited increased CD8+ T-cell infiltration and enhanced sensitivity to ICB compared with tumors in wild-type mice. Clinically, in a trial of melanoma patients, high MRC2 mRNA levels in tumors were associated with a poor response to αPD-1 therapy, highlighting the potential benefits of therapeutically targeting a specific CAF subpopulation in breast and other CAF-rich cancers to improve clinical responses to immunotherapy.Significance:Paired syngeneic models help unravel the interplay between CAF and tumor immune evasion, highlighting the benefits of targeting fibroblast subpopulations to improve clinical responses to immunotherapy.