bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of entrainment-mixing and turbulent fluctuations on droplet size distributions in a cumulus cloud: An investigation using Lagrangian microphysics with a sub-grid-scale model
Authors: Chandrakar Kamal Kant , Grabowski Wojciech W. , Morrison Hugh , Bryan George H.
Published: July 2021

Entrainment-mixing and turbulent fluctuations critically impact cloud droplet size distributions (DSDs) in cumulus clouds. This problem is investigated via a new sophisticated modeling framework using the CM1 LES model and a Lagrangian cloud microphysics scheme – the “super-droplet method” (SDM) – coupled with sub-grid-scale (SGS) schemes for particle transport and supersaturation fluctuations. This modeling framework is used to simulate a cumulus congestus cloud. Average DSDs in different cloud regions show broadening from entrainment and secondary cloud droplet activation (activation above the cloud base). DSD width increases with increasing entrainment-induced dilution as expected from past work, except in the most diluted cloud regions. The new modeling framework with SGS transport and supersaturation fluctuations allows a more sophisticated treatment of secondary activation compared to previous studies. In these simulations, it contributes about 25%of the cloud droplet population and impacts DSDs in two contrastingways: narrowing in extremely diluted regions and broadening in relatively less diluted. SGS supersaturation fluctuations contribute significantly to an increase in DSD width via condensation growth and evaporation. Mixing of super-droplets from SGS velocity fluctuations also broadens DSDs. The relative dispersion (ratio of DSD dispersion and mean radius) negatively correlates with grid-scale vertical velocity in updrafts, but is positively correlated in downdrafts. The latter is from droplet activation driven by positive SGS supersaturation fluctuations in grid-mean subsaturated conditions. Finally, the sensitivity to model grid length is evaluated. The SGS schemes have greater influence as the grid length is increased, and they partially compensate for the reduced model resolution.
Subseasonal-to-Seasonal Extreme Precipitation Events in the Contiguous United States: Generation of a Database and Climatology
Authors: Dickinson Ty A. , Richman Michael B. , Furtado Jason C.
Published: July 2021

Extreme precipitation across multiple time scales is a natural hazard that creates a significant risk to life, with a commensurately large cost through property loss. We devise a method to create 14-day extreme-event windows that characterize precipitation events in the contiguous United States (CONUS) for the years 1915–2018. Our algorithm imposes thresholds for both total precipitation and the duration of the precipitation to identify events with sufficient length to accentuate the synoptic and longer time scale contribution to the precipitation event. Kernel density estimation is employed to create extreme-event polygons that are formed into a database spanning from 1915 through 2018. Using the developed database, we clustered events into regions using a k-means algorithm. We define the “hybrid index,” a weighted composite of silhouette score and number of clustered events, to show that the optimal number of clusters is 15. We also show that 14-day extreme precipitation events are increasing in the CONUS, specifically in the Dakotas and much of New England. The algorithm presented in this work is designed to be sufficiently flexible to be extended to any desired number of days on the subseasonal-to-seasonal (S2S) time scale (e.g., 30 days). Additional databases generated using this framework are available for download from our GitHub. Consequently, these S2S databases can be analyzed in future works to determine the climatology of S2S extreme precipitation events and be used for predictability studies for identified events.
KOREA'S FIRST‐GENERATION DIVIDED FAMILIES: The End of the Line?
Authors: Foley James Alexander
Published: July 2021

This article describes and analyzes the desperate situation of Korean first‐generation divided family members who are still separated from their relatives nearly 70 years since the end of the Korean War (1950–1953). I aim to provide the reader with a reasonable quantification of the problem and make projections as to this first generation's likely future survival. The elements of the approach adopted to resolve the issue of family separation by the humanitarian bodies charged with addressing the problem, the Red Cross Societies of the two Koreas are described, and suggestions are made for improvement. The reunion program's successes and failures are critically assessed as is the key role played by the Red Cross Talks in the history of inter‐Korean relations. Finally, conclusions are drawn as to the practical measures which may contribute to a resolution to the problem before the final disappearance of Korea's first generation of aged, separated family members.
CRP and ferritin in addition to the EASIX score predict CAR-T–related toxicity
Authors: Greenbaum Uri , Strati Paolo , Saliba Rima M. , Torres Janet , Rondon Gabriela , Nieto Yago , Hosing Chitra , Srour Samer A. , Westin Jason , Fayad Luis E. , Lee Hun J. , Iyer Swaminathan P. , Nair Ranjit , Nastoupil Loretta J. , Parmar Simrit , Rodriguez Maria A. , Samaniego Felipe , Steiner Raphael E. , Wang Michael , Pinnix Chelsea C. , Flowers Christopher R. , Tummala Sudhakar , Ramdial Jeremy L. , Yalniz Fevzi F. , Hawkins Misha , Rezvani Katayoun , Champlin Richard E. , Shpall Elizabeth J. , Neelapu Sattva S. , Kebriaei Partow , Ahmed Sairah
Published: July 2021

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study’s objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T–related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.
Risk of pulmonary emboli after removal of an upper extremity central catheter associated with a deep vein thrombosis
Authors: Houghton Damon E. , Billett Henny Heisler , Gaddh Manila , Onadeko Oluwatomiloba , George Gemlyn , Wang Tzu-Fei , Oo Thein H. , Feng Mingen , Dasgupta Mahua , Jaglal Michael , Streiff Michael B. , Simpson Pippa , Gali Radhika , Baumann Kreuziger Lisa
Published: July 2021

Standard treatment of catheter-associated upper extremity deep vein thrombosis (UE-DVT) is anticoagulation, although catheters are often removed for this indication. The optimal time for catheter removal and whether the act and/or timing of catheter removal is associated with pulmonary embolism (PE) remain unknown. A retrospective cohort study was performed at 8 participating institutions through the Venous thromboEmbolism Network US. Patients with hematologic malignancies and central venous catheter (CVC)–associated UE-DVT were included from 1 January 2010 through 31 December 2016. The primary outcome was objectively confirmed PE within 7 days of UE-DVT diagnosis in anticoagulated patients comparing early (≤48 hours) vs delayed (>48 hours) catheter removal. A total of 626 patients were included, among whom 480 were treated with anticoagulation. Among anticoagulated patients, 255 underwent early CVC removal, while 225 had delayed or no CVC removal; 146 patients received no anticoagulation, among whom 116 underwent CVC removal alone. PE within 7 days occurred in 2 patients (0.78%) with early removal compared with 1 patient (0.44%) with delayed or no CVC removal (P > .9). PE or any cause of death within 7 days occurred in 3 patients in both the early removal (1.18%) and delayed/no removal (1.33%) groups (P > .9). In patients treated with CVC removal only (no anticoagulation), there were no PEs but 3 deaths within 7 days. In patients with hematological malignancy and CVC-associated UE-DVT, early removal of CVCs was not associated with an increased risk of PE compared with delayed or no removal.
Awake prone positioning and oxygen therapy in patients with COVID-19: the APRONOX study
Authors: Perez-Nieto Orlando R. , Escarraman-Martinez Diego , Guerrero-Gutierrez Manuel A. , Zamarron-Lopez Eder I. , Mancilla-Galindo Javier , Kammar-García Ashuin , Martinez-Camacho Miguel A. , Deloya-Tomás Ernesto , Sanchez-Díaz Jesús S. , Macías-García Luis A. , Soriano-Orozco Raúl , Cruz-Sánchez Gabriel , Salmeron-Gonzalez José D. , Toledo-Rivera Marco A. , Mata-Maqueda Ivette , Morgado-Villaseñor Luis A. , Martinez-Mazariegos Jenner J. , Flores Ramirez Raymundo , Medina-Estrada Josue L. , Ñamendys-Silva Silvio A.
Published: July 2021

Background

The awake prone positioning strategy for patients with acute respiratory distress syndrome is a safe, simple and cost-effective technique used to improve hypoxaemia. We aimed to evaluate intubation and mortality risk in patients with coronavirus disease 2019 (COVID-19) who underwent awake prone positioning during hospitalisation.

Methods

In this retrospective, multicentre observational study conducted between 1 May 2020 and 12 June 2020 in 27 hospitals in Mexico and Ecuador, nonintubated patients with COVID-19 managed with awake prone or awake supine positioning were included to evaluate intubation and mortality risk through logistic regression models; multivariable and centre adjustment, propensity score analyses, and E-values were calculated to limit confounding.

Results

827 nonintubated patients with COVID-19 in the awake prone (n=505) and awake supine (n=322) groups were included for analysis. Fewer patients in the awake prone group required endotracheal intubation (23.6%versus40.4%) or died (19.8%versus37.3%). Awake prone positioning was a protective factor for intubation even after multivariable adjustment (OR 0.35, 95% CI 0.24–0.52; p<0.0001, E=2.12), which prevailed after propensity score analysis (OR 0.41, 95% CI 0.27–0.62; p<0.0001, E=1.86) and mortality (adjusted OR 0.38, 95% CI 0.26–0.55; p<0.0001, E=2.03). The main variables associated with intubation among awake prone patients were increasing age, lower baseline peripheral arterial oxygen saturation/inspiratory oxygen fraction ratio (PaO2/FIO2) and management with a nonrebreather mask.

Conclusions

Awake prone positioning in hospitalised nonintubated patients with COVID-19 is associated with a lower risk of intubation and mortality.
A variance component estimation approach to infer associations between Mendelian polledness and quantitative production and female fertility traits in German Simmental cattle
Authors: Scheper Carsten , Emmerling Reiner , Götz Kay-Uwe , König Sven
Published: July 2021

Background

Managing beneficial Mendelian characteristics in dairy cattle breeding programs implies that the correlated genetic effects are considered to avoid possible adverse effects in selection processes. The Mendelian trait polledness in cattle is traditionally associated with the belief that the polled locus has unfavorable effects on breeding goal traits. This may be due to the inferior breeding values of former polled bulls and cows in cattle breeds, such as German Simmental, or to pleiotropic or linkage effects of the polled locus.

Methods

We focused on a variance component estimation approach that uses a marker-based numerator relationship matrix reflecting gametic relationships at the polled locus to test for direct pleiotropic or linked quantitative trait loci (QTL) effects of the polled locus on relevant traits. We applied the approach to performance, health, and female fertility traits in German Simmental cattle.

Results

Our results showed no evidence for any pleiotropic QTL effects of the polled locus on test-day production traits milk yield and fat percentage, on the mastitis indicator ‘somatic cell score’, and on several female fertility traits, i.e. 56 days non return rate, days open and days to first service. We detected a significant and unfavorable QTL effect accounting for 6.6% of the genetic variance for protein percentage only.

Conclusions

Pleiotropy does not explain the lower breeding values and phenotypic inferiority of polled German Simmental sires and cows relative to the horned population in the breed. Thus, intensified selection in the polled population will contribute to increased selection response in breeding goal traits and genetic merit and will narrow the deficit in breeding values for production traits.
Patients and general practitioners assessment of the main outcomes employed in the acute and preventive treatment of migraine: a cross sectional study
Authors: Trigo-López Javier , Guerrero-Peral Ángel Luis , Sierra Álvaro , Martínez-Pías Enrique , Gutiérrez-Sánchez María , Huzzey Elizabeth , García-Azorín David
Published: July 2021

Background

We aim to describe and compare patients and general practitioners’ opinions about the different variables related to acute and preventive treatment for migraine.

Patients and methods

An observational descriptive study was performed. Patients with episodic migraine and general practitioners, from our healthcare area, were invited to answer a survey about the different variables related to migraine treatment. They were asked for their opinions on the different variables, and to consider the desired efficacy in percentage terms and the desired action times of treatment.

Results

Fifty-five patients and fifty-five general practitioners were selected. Effectiveness was considered the most important variable for symptomatic and preventive treatment. Cost was considered the least important variable. Patients desired percentage of efficacy was 84.0% (±16.7%) for symptomatic treatment and 79.9% (±17.1%) for preventive treatment. General practitioners desired percentage of efficacy was 75.0% (±14.0) for symptomatic treatment and 70.4% (±14.3) for preventive treatment. For symptomatic treatment the desired action time for pain cessation was selected as 27.5 min (±13.8) for patients and 24.0 min (±18.3) for GPs. For preventive treatment the desired action time for effect was 7.1 days (±4.5) for patients and 13.9 days (±8.9) for general practitioners.

Conclusion

The most important endpoints were, for acute: effectiveness, a short action time and a persistent effect. For prophylactic: effectiveness, sustained effect and tolerability. Both patients and general practitioners agreed on the most and least preferred endpoints. Desired percentage of efficacy was above 75% for both symptomatic and preventive treatment; and the desired action time was below 30 min for acute treatment and 2 weeks for preventive treatment.
Changes in vitamin D and calcium metabolism markers in patients undergoing adjuvant chemotherapy for breast cancer
Authors: Viala Marie , Firmin Nelly , Touraine Célia , Pouderoux Stéphane , Metge Manon , Rifai Lobna , Romieu Gilles , de Forges Hélène , Roca Lise , Guiu Séverine , D’Hondt Véronique , Jacot William
Published: July 2021

Background

Changes in calcium metabolism and calcium urinary excretion during chemotherapy have not been thoroughly assessed in patients with early breast cancer (EBC), a population who frequently present vitamin D insufficiency. As hypercalciuria is a classical contra-indication to vitamin D (VD) supplementation, this study evaluated changes in VD and calcium metabolism parameters in patients with EBC undergoing adjuvant chemotherapy (CT).

Methods

In patients with EBC who received six cycles of adjuvant CT, VD and calcium parameters were monitored at inclusion, and then every 3 weeks, at each CT cycle initiation. The primary endpoint was the percentage of patients showing hypercalciuria during adjuvant CT (between Day 1, Cycle 1 [D1C1] and Day 1, Cycle 6 [D1C6]).

Results

The primary endpoint could be evaluated in 82 patients. Most patients (n = 66, 80.5%) had VD insufficiency (< 30 ng/mL) at baseline. Hypercalciuria was detected in 29 patients (35.4%; 95% CI: 25.6–46.5) between D1C1 and D1C6, but was not clinically significant in any of the affected patients. The percentage of hypercalciuria events was not different between patients with sufficient and insufficient baseline VD levels (34.8% vs. 37.5%), and between patients who received or not VD supplementation (37.5% vs. 34.5%,).

Conclusions

This comprehensive study on VD and calcium parameter changes in patients with EBC during adjuvant chemotherapy shows that hypercalciuria is a frequent abnormality in this setting, although asymptomatic. Therefore, it should not be considered as a limitation for high dose VD supplementation in this population.

Trial registration

EudraCT:2014-A01454-43. Registered 29 august 2016.
Atomic force microscopy comparative analysis of the surface roughness of two posterior chamber phakic intraocular lens models: ICL versus IPCL
Authors: Gros-Otero Juan , Ketabi Samira , Cañones-Zafra Rafael , Garcia-Gonzalez Montserrat , Villa-Collar Cesar , Casado Santiago , Teus Miguel A.
Published: July 2021

Background

To compare the anterior surface roughness of two commercially available posterior chamber phakic intraocular lenses (IOLs) using atomic force microscopy (AFM).

Methods

Four phakic IOLs were used for this prospective, experimental study: two Visian ICL EVO+ V5 lenses and two iPCL 2.0 lenses. All of them were brand new, were not previously implanted in humans, were monofocal and had a dioptric power of − 12 diopters (D). The anterior surface roughness was assessed using a JPK NanoWizard II® atomic force microscope in contact mode immersed in liquid. Olympus OMCL-RC800PSA commercial silicon nitride cantilever tips were used. Anterior surface roughness measurements were made in 7 areas of 10 × 10 μm at 512 × 512 point resolution. The roughness was measured using the root-mean-square (RMS) value within the given regions.

Results

The mean of all anterior surface roughness measurements was 6.09 ± 1.33 nm (nm) in the Visian ICL EVO+ V5 and 3.49 ± 0.41 nm in the iPCL 2.0 (p = 0.001).

Conclusion

In the current study, we found a statistically significant smoother anterior surface in the iPCL 2.0 phakic intraocular lenses compared with the VISIAN ICL EVO+ V5 lenses when studied with atomic force microscopy.
Developmental delay and its predictors among children under five years of age with uncomplicated severe acute malnutrition: a cross-sectional study in rural Pakistan
Authors: Saleem Javeria , Zakar Rubeena , Bukhari Gul Mehar Javaid , Fatima Aneela , Fischer Florian
Published: July 2021

Background

In developing countries, malnutrition in children and developmental delays are two major challenges for public health. To achieve the vision of the Sustainable Development Goals from the broader perspective of child health, early identification of developmental delays and timely intervention are crucial. The aim of this study is to assess the prevalence of suspected developmental delay and their predictors in children under the age of 5 years with uncomplicated severe acute malnutrition in rural areas of Pakistan.

Methods

A multicentre cross-sectional study was conducted among 185 children with uncomplicated severe acute malnutrition. We screened children aged 6–59 months for their nutritional status and clinical complications. Children fulfilling the inclusion criteria underwent the Denver Development Screening Tool II (DDST-II). The children’s global developmental profile was calculated according to the established protocols of DDST-II, which are based on four important domains of development: personal and social behaviour, language, gross motor adaptive skills and fine motor adaptive skills. A pretested questionnaire was used to collect data on socio-demographic and nutritional factors for assessing predictors of developmental delay, which were analysed using a multivariate logistic regression model.

Results

Out of 177 children with severe acute malnutrition, 69 (38.9%) had normal global development and 108 (61.1%) had delayed global development. Significant associations were found between global developmental delay and younger children (6–24 months vs. 25–59 months; AOR = 4.53, 95% CI: 1.56–13.10,p < 0.01), children who were not exclusively breastfed (AOR = 3.07, 95% CI: 1.24–7.56,p = 0.01), and a history of contact with a tuberculosis smear-positive adult (AOR = 2.67, 95% CI: 1.30–5.49,p < 0.01).

Conclusion

About two thirds of the study participants showed delayed or unstable global development. Thus, according to DDST-II-established protocols, there is a high prevalence of suspected developmental delay among children under the age of five years with uncomplicated severe acute malnutrition in rural areas of Pakistan. Children in their first 2 years of life were at particularly high risk due to insufficient breastfeeding. This emphasizes the need to provide adequate infrastructure and information to parents for the prevention of developmental delay in remote areas.
Pain in Veterans with COPD: relationship with physical activity and exercise capacity
Authors: Raphaely Rebecca A. , Mongiardo Maria A. , Goldstein Rebekah L. , Robinson Stephanie A. , Wan Emily S. , Moy Marilyn L.
Published: July 2021

Background

Pain is a common but underappreciated symptom experienced by people with Chronic Obstructive Pulmonary Disease (COPD). The relationships between pain and physical activity (PA) and exercise capacity are poorly understood.

Methods

This retrospective secondary analysis includes three cohorts of Veterans with COPD who participated in longitudinal studies evaluating PA and exercise capacity with objective measures of daily step counts and 6-min walk test (6MWT) distance, respectively. Pain was assessed using the bodily pain domain of the Veterans RAND-36. In two cohorts, participants were randomly assigned to a web-based, pedometer-mediated PA intervention which has previously been demonstrated to improve PA.

Results

Three-hundred and seventy-three (373) unique study participants were included in this analysis. Eighty-three percent (n = 311) of the population reported at least mild pain and/or at least a little bit of interference due to pain at baseline. Cross-sectionally, greater bodily pain was associated with lower 6MWT distance (β = 0.51; 95% CI 0.20, 0.82; p = 0.0013). Longitudinally, worsening bodily pain was associated with a decline in 6MWT distance (β = 0.30; 95% CI 0.03, 0.58; p = 0.0312). There was no association between baseline bodily pain and baseline daily step counts, baseline bodily pain and change in PA, or change in bodily pain and change in PA. Compared to usual care, our PA intervention improved bodily pain scores (β = 6.17; 95% CI 1.84, 10.45; p = 0.0054). Bodily pain scores did not affect the impact of the intervention on daily step counts.

Conclusion

Pain is highly prevalent and significantly associated with lower exercise capacity among Veterans with COPD. Worsening pain co-occurred with decline in exercise capacity but not PA. Our intervention reduced pain, although pain did not affect the impact of the intervention on PA.
Association between working in awkward postures, in particular overhead work, and pain in the shoulder region in the context of the 2018 BIBB/BAuA Employment Survey
Authors: Barthelme Julia , Sauter Martha , Mueller Charlotte , Liebers Falk
Published: July 2021

Background

Musculoskeletal disorders are the leading cause of work-related sick leave and incur substantial socioeconomic costs. With the aging of our society and employees, the problem is exacerbating, and prevention is becoming increasingly important. According to previous studies, exposure to awkward postures, such as overhead work, is associated with musculoskeletal problems.

Objective

This study aimed to determine the current prevalence of employees who work in awkward postures, specifically overhead, stratified by age, gender and occupation in the context of the 2018 BIBB/BAuA Employment Survey and to analyze associations between awkward working postures, in particular overhead work, and pain in the shoulder region.

Method

The study is based on secondary data from the German 2018 BIBB/BAuA Employment Survey. We have included 14,327 of the 20,012 employees aged < 67 years who work at least 35 h per week who took part in the survey. The classification of participants in occupational groups is based on the Blossfeld classification. The multivariate analysis was conducted by applying robust Poisson regression models adjusted block by block to obtain the relation between the self-reported frequency of working in awkward postures, in particular overhead work, and the occurrence of arm pain and neck and shoulder pain. Prevalence ratios (PR) are reported as effect estimates.

Results

12.7% of participants indicated that they are often exposed to awkward postures at work; 5.0% stated they often performed overhead work. The majority of these employees worked in agricultural, unskilled and skilled manual occupations. The crude prevalence is 17.4% for arm pain and 48.4% for neck and shoulder pain. If subjects reported that they often performed overhead work, the risk of arm pain increased by 18% (PR 1.18, CI 1.04–1.34, final model).

Conclusion

Working in awkward postures, especially overhead work, is a risk factor for upper extremity musculoskeletal disorders. The development of prevention strategies should focus on the workforce in agricultural, unskilled and skilled manual occupations.
Addressing barriers to the conduct and application of research in complementary and alternative medicine: a scoping review
Authors: Veziari Yasamin , Kumar Saravana , Leach Matthew
Published: July 2021

Background

Over the past few decades, the popularity of complementary and alternative medicine (CAM) has grown considerably and along with it, scrutiny regarding its evidence base. While this is to be expected, and is in line with other health disciplines, research in CAM is confronted by numerous obstacles. This scoping review aims to identify and report the strategies implemented to address barriers to the conduct and application of research in CAM.

Methods

The scoping review was undertaken using the Arksey and O’Malley framework. The search was conducted using MEDLINE, EMBASE, EMCARE, ERIC, Scopus, Web of Science, The Cochrane Library, JBI and the grey literature. Two reviewers independently screened the records, following which data extraction was completed for the included studies. Descriptive synthesis was used to summarise the data.

Results

Of the 7945 records identified, 15 studies met the inclusion criteria. Using the oBSTACLES instrument as a framework, the included studies reported diverse strategies to address barriers to the conduct and application of research in CAM. All included studies reported the use of educational strategies and collaborative initiatives with CAM stakeholders, including targeted funding, to address a range of barriers.

Conclusions

While the importance of addressing barriers to the conduct and application of research in CAM has been recognised, to date, much of the focus has been limited to initiatives originating from a handful of jurisdictions, for a small group of CAM disciplines, and addressing few barriers. Myriad barriers continue to persist, which will require concerted effort and collaboration across a range of CAM stakeholders and across multiple sectors. Further research can contribute to the evidence base on how best to address these barriers to promote the conduct and application of research in CAM.
Dynamic changes of functional fitness, antibodies to SARS-CoV-2 and immunological indicators within 1 year after discharge in Chinese health care workers with severe COVID-19: a cohort study
Authors: Xiong Lijuan , Li Qian , Cao Xiongjing , Xiong Huangguo , Huang Ming , Yang Fengwen , Liu Qingquan , Meng Daquan , Zhou Mei , Wang Gang , Tong Jun , Chen Tengfei , Zhang Yanzhao , He Xinliang , Fan Yunzhou , Zhang Yupeng , Tang Liang , Jin Yang , Xia Jiahong , Hu Yu
Published: July 2021

Background

Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China.

Methods

We conducted an ambidirectional cohort study in “Rehabilitation Care Project for Medical Staff Infected with COVID-19” in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ2, and Fisher’s exact test were used to assess the variance between two or more groups where appropriate.

Results

Of 333 HCWs with severe COVID-19, the HCWs’ median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3+ T cells and CD4+ T cells.

Conclusion

The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19.
Somatic mutations in benign breast disease tissues and association with breast cancer risk
Authors: Winham Stacey J. , Wang Chen , Heinzen Ethan P. , Bhagwate Aditya , Liu Yuanhang , McDonough Samantha J. , Stallings-Mann Melody L. , Frost Marlene H. , Vierkant Robert A. , Denison Lori A. , Carter Jodi M. , Sherman Mark E. , Radisky Derek C. , Degnim Amy C. , Cunningham Julie M.
Published: July 2021

Background

Benign breast disease (BBD) is a risk factor for breast cancer (BC); however, little is known about the genetic alterations present at the time of BBD diagnosis and how these relate to risk of incident BC.

Methods

A subset of a long-term BBD cohort was selected to examine DNA variation across three BBD groups (42 future estrogen receptor-positive (ER+) BC, 36 future estrogen receptor-negative (ER−) BC, and 42 controls cancer-free for at least 16 years post-BBD). DNA extracted from archival formalin fixed, paraffin-embedded (FFPE) tissue blocks was analyzed for presence of DNA alterations using a targeted panel of 93 BC-associated genes. To address artifacts frequently observed in FFPE tissues (e.g., C>T changes), we applied three filtering strategies based on alternative allele frequencies and nucleotide substitution context. Gene-level associations were performed using two types of burden tests and adjusted for clinical and technical covariates.

Results

After filtering, the variant frequency of SNPs in our sample was highly consistent with population allele frequencies reported in 1 KG/ExAC (0.986, p < 1e−16). The top ten genes found to be nominally associated with later cancer status by four of 12 association methods(p < 0.05) were MED12, MSH2, BRIP1, PMS1, GATA3, MUC16, FAM175A, EXT2, MLH1 and TGFB1, although these were not statistically significant in permutation testing. However, all 10 gene-level associations had OR < 1 with lower mutation burden in controls compared to cases, which was marginally statistically significant in permutation testing (p = 0.04). Comparing between the three case groups, BBD ER+ cases were closer to controls in mutation profile, while BBD ER− cases were distinct. Notably, the variant burden was significantly higher in controls than in either ER+ or ER− cases. CD45 expression was associated with mutational burden (p < 0.001).

Conclusions

Somatic mutations were more frequent in benign breast tissue from women who did not develop cancer, opening questions of clonal diversity or immune-mediated restraint on future cancer development. CD45 expression was positively associated with mutational burden, most strongly in controls. Further studies in both normal and premalignant tissues are needed to better understand the role of somatic gene mutations and their contribution to future cancer development.
Variation in brief treatment for substance use disorder: a qualitative investigation of four federally qualified health centers with SBIRT services
Authors: Watson Dennis P. , Staton Monte D. , Dennis Michael L. , Grella Christine E. , Scott Christy K.
Published: July 2021

Background

Brief treatment (BT) can be an effective, short-term, and low-cost treatment option for many people who misuse alcohol and drugs. However, inconsistent implementation is suggested to result in BT that often looks and potentially costs similar to regular outpatient care. Prior research is also rife with inconsistent operationalizations regarding the measurement of BT received by patients. As such, there is a need to more explicitly identify and document variations in BT practice.

Methods

A qualitative investigation of BT in four Federally Qualified Health Centers (FQHC) was undertaken as a sub study of a larger clinical trial. Researchers interviewed 12 staff (administrators and clinicians) involved in BT oversight, referral, or delivery within the four FQHCs. Data were analyzed following an inductive approach guided by the primary research questions.

Results

Findings demonstrate considerable differences in how BT was conceptualized and implemented within the FQHCs. This included a variety of ways in which BT was presented and described to patients that likely impacts how they perceive the BT they receive, including potentially not understanding they received substance use disorder treatment at all.

Conclusions

The findings raise questions regarding the validity of prior research, demonstrating more objective definitions of BT and fidelity checklists are needed to ensure integrity of results. Future work in this area should seek to understand BT as practiced among a larger sample of providers and the direct experiences and perspectives of patients. There is also a need for more consistent implementation, quality assurance guidelines, and standardized stage of change assessments to aid practitioners.
Neutrophil extracellular traps in cancer: not only catching microbes
Authors: Ronchetti Livia , Boubaker Nouha Setti , Barba Maddalena , Vici Patrizia , Gurtner Aymone , Piaggio Giulia
Published: July 2021

Neutrophils are the most abundant type of white blood cells circulating throughout the bloodstream and are often considered the frontline defenders in innate immunity. However, neutrophils are increasingly being recognized as having an important role in tumorigenesis and carcinogenesis due to their aberrant activation by molecules released into the tumor microenvironment. One defensive response of neutrophils that is aberrantly triggered during the neoplastic process is called NETosis, where activated neutrophils expel their DNA and intracellular contents in a web-like structure known as a neutrophil extracellular trap (NET). In cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism. NET structures released by neutrophils can also serve as a scaffold for clot formation, shining new light on the role of neutrophils and NETosis in coagulation-mediated diseases.

Here, we review current available knowledge regarding NET and the related NETosis process in cancer patients, with an emphasis on pre-clinical and clinical data fostering the identification and validation of biomarkers of NET with a predictive/prognostic role in cancer patients treated with immunotherapy agents. NETosis biomarkers, e.g., citH3, may integrate correlates of immunogenicity currently available (e.g., PD-L1 expression, TMB, TILs) and help select the subsets of patients who may most benefit from the use of the therapeutic weapons under discussion.
Transcatheter arterial embolization for severe blunt liver injury in hemodynamically unstable patients: a 15-year retrospective study
Authors: Tamura Satoshi , Maruhashi Takaaki , Kashimi Fumie , Kurihara Yutaro , Masuda Tomonari , Hanajima Tasuku , Kataoka Yuichi , Asari Yasushi
Published: July 2021

Background

Transcatheter arterial embolization (TAE) is the first-line nonsurgical treatment for severe blunt liver injury in patients, whereas operative management (OM) is recommended for hemodynamically unstable patients. This study investigated the comparative efficacy of TAE in hemodynamically unstable patients who responded to initial infusion therapy.

Methods

This retrospective study enrolled patients with severe blunt liver injuries, which were of grades III–V according to the American Association for the Surgery of Trauma Organ Injury Scale (OIS). Patients who responded to initial infusion therapy underwent computed tomography to determine the treatment plan. A shock index > 1, despite undergoing initial infusion therapy, was defined as hemodynamic instability. We compared the clinical outcomes and mortality rates between patients who received OM and those who underwent TAE.

Results

Sixty-two patients were included (eight and 54 who underwent OM and TAE, respectively; mean injury severity score, 26.6). The overall in-hospital mortality rate was 6% (13% OM vs. 6% TAE, p = 0.50), and the hemodynamic instability was 35% (88% OM vs. 28% TAE, p < 0.01). Hemodynamically unstable patients who underwent TAE had 7% in-hospital mortality and 7% clinical failure. Logistic regression analysis showed that the treatment choice was not a predictor of outcome, whereas hemodynamic instability was an independent predictor of intensive care unit stay ≥7 days (odds ratio [OR], 3.80; p = 0.05) and massive blood transfusion (OR, 7.25; p = 0.01); OIS grades IV–V were predictors of complications (OR, 6.61; p < 0.01).

Conclusions

TAE in hemodynamically unstable patients who responded to initial infusion therapy to some extent has acceptable in-hospital mortality and clinical failure rates. Hemodynamic instability and OIS, but not treatment choice, affected the clinical outcomes.
Health service experiences and preferences of frail home care clients and their family and friend caregivers during the COVID-19 pandemic
Authors: Weeks Lori E. , Nesto Sue , Hiebert Bradley , Warner Grace , Luciano Wendy , Ledoux Kathleen , Donelle Lorie
Published: July 2021

Objective

The COVID-19 pandemic has brought about a major upheaval in the lives of older adults and their family/friend caregivers, including those utilizing home care services. In this article, we focus on results from a qualitative component added to a pragmatic randomized controlled trial that focuses on the experiences of our study participants during COVID-19. A total of 29 participants responded to the COVID-19 related questions focused on their health services experiences and preferences from March-June 2020 including 10 home care clients and 19 family/friend caregivers in the provinces of Ontario and Nova Scotia, Canada.

Results

Many participants were affected drastically by the elimination or reduction of access to services, highlighting the vulnerability of home care clients and their caregivers during COVID-19. This took an emotional toll on home care clients and increased the need for family/friend caregiver support. While many participants expressed reduced desire to utilize residential long-term care homes, some caregivers found that passive remote monitoring technology was particularly useful within the COVID-19 context. Our results provide important insights into the ways the older adults and their caregivers have been affected during the COVID-19 context and how to better support them in the future.
Combination of mesenchymal stem cells and nicorandil: an emerging therapeutic challenge against COVID-19 infection-induced multiple organ dysfunction
Authors: Safari Anahid , Lionetti Vicenzo , Razeghian-Jahromi Iman
Published: July 2021

The recent COronaVIrus Disease (COVID)-19 pandemic has placed an unprecedented burden on the drug development opportunity to prevent the onset of multi-organ failure.

Emerging experimental reports have highlighted the beneficial effects of mesenchymal stem cell (MSC) administration against COVID-19. MSCs and their derived exosomes may attenuate SARS-CoV-2-induced inflammatory response through managing the immune cell function and cytokine expression. Although these are promising results, the exposure of MSCs to chemical compounds with pharmacological activities may further improve their homing, survival, and paracrine machinery.

Nicorandil (N-[2-hydroxyethyl]-nicotinamide nitrate), an established adenosine triphosphate-sensitive potassium channel opener, is recently hypothesized to modulate inflammation as well as cell injury and death in COVID-19-affected lungs through inhibiting reactive oxygen species levels and apoptosis. Since it also exerts protective effects against hypoxia-induced MSC apoptosis, we assumed that transplanted MSCs combined to long-term nicorandil administration may survive longer in a severely inflamed microenvironment and have more beneficial effects in the treatment of SARS-CoV-2 infection than MSCs alone.
In situ transplantation of adipose-derived stem cells via photoactivation improves glucose metabolism in obese mice
Authors: Zhu Luochen , Feng Ziqian , Shu Xin , Gao Qian , Wu Jiaqi , Du Zuoqin , Li Rong , Wang Liqun , Chen Ni , Li Yi , Luo Mao , Wu Jianbo
Published: July 2021

Background

Accumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. However, therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches.

Methods

We demonstrate that the effect of a combined application of photoactivation and adipose-derived stem cells (ASCs) using transplantation into visceral epididymal adipose tissue (EAT) in obesity. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND).

Results

In diet-induced obesity, implantation of light-treated ASCs improved glucose tolerance and ameliorated systemic insulin resistance. Intriguingly, compared with non-light-treated ASCs, light-treated ASCs reduced monocyte infiltration and the levels of ATMs in EAT. Moreover, implantation of light-treated ASCs exerts more anti-inflammatory effects by suppressing M1 polarization and enhancing macrophage M2 polarization in EAT. Mass spectrometry revealed that light-treated human obese ASCs conditioned medium retained a more complete secretome with significant downregulation of pro-inflammatory cytokines and chemokines.

Conclusions

These data suggest that the combined application of photoactivation and ASCs using transplantation into dysfunctional adipose tissue contribute to selective suppression of inflammatory responses and protection from insulin resistance in obesity and type 2 diabetes.
BioVerbNet: a large semantic-syntactic classification of verbs in biomedicine
Authors: Majewska Olga , Collins Charlotte , Baker Simon , Björne Jari , Brown Susan Windisch , Korhonen Anna , Palmer Martha
Published: July 2021

Background

Recent advances in representation learning have enabled large strides in natural language understanding; However, verbal reasoning remains a challenge for state-of-the-art systems. External sources of structured, expert-curated verb-related knowledge have been shown to boost model performance in different Natural Language Processing (NLP) tasks where accurate handling of verb meaning and behaviour is critical. The costliness and time required for manual lexicon construction has been a major obstacle to porting the benefits of such resources to NLP in specialised domains, such as biomedicine. To address this issue, we combine a neural classification method with expert annotation to create BioVerbNet. This new resource comprises 693 verbs assigned to 22 top-level and 117 fine-grained semantic-syntactic verb classes. We make this resource available complete with semantic roles and VerbNet-style syntactic frames.

Results

We demonstrate the utility of the new resource in boosting model performance in document- and sentence-level classification in biomedicine. We apply an established retrofitting method to harness the verb class membership knowledge from BioVerbNet and transform a pretrained word embedding space by pulling together verbs belonging to the same semantic-syntactic class. The BioVerbNet knowledge-aware embeddings surpass the non-specialised baseline by a significant margin on both tasks.

Conclusion

This work introduces the first large, annotated semantic-syntactic classification of biomedical verbs, providing a detailed account of the annotation process, the key differences in verb behaviour between the general and biomedical domain, and the design choices made to accurately capture the meaning and properties of verbs used in biomedical texts. The demonstrated benefits of leveraging BioVerbNet in text classification suggest the resource could help systems better tackle challenging NLP tasks in biomedicine.