bluuebunny/crossref_metadata_2025 huggingface dataset:
ZmCOI2a and ZmCOI2b redundantly regulate anther dehiscence and gametophytic male fertility in maize
Authors: Qi Xiaolong , Guo Shuwei , Wang Dong , Zhong Yu , Chen Ming , Chen Chen , Cheng Dehe , Liu Zongkai , An Tai , Li Jinlong , Jiao Yanyan , Wang Yuwen , Liu Jinchu , Zhang Yuling , Chen Shaojiang , Liu Chenxu
Published: February 2022

In higher plants, the generation and release of viable pollen from anthers is vital for double fertilization and the initiation of seed development. Thus, the characterization of genes related to pollen development and anther dehiscence in plants is of great significance. The F‐box protein COI1 plays a crucial role in the jasmonate (JA) signaling pathway and interacts with many JAZ family proteins in the presence of jasmonoyl‐isoleucine (JA‐Ile) or coronatine (COR). The mutation of AtCOI1 in Arabidopsis leads to defective anther dehiscence and male sterility (MS), although COI has not been shown to affect fertility in Zea mays (maize). Here we identified two genes, ZmCOI2a and ZmCOI2b, that redundantly regulate gametophytic male fertility. Both ZmCOI2a and ZmCOI2b are highly homologous and constitutively expressed in all tissues tested. Subcellular localization revealed that ZmCOI2a and ZmCOI2b were located in the nucleus. The coi2a coi2b double mutant, generated by CRISPR/Cas9, had non‐dehiscent anthers, delayed anther development and MS. In addition, coi2a coi2b male gametes could not be transmitted to the next generation because of severe defects in pollen germination. The JA content of coi2a coi2b anthers was unaltered compared with those of the wild type, and the exogenous application of JA could not rescue the fertility defects of coi2a coi2b. Transcriptome analysis showed that the expression of genes involving the JA signaling transduction pathway, including ZmJAZ3, ZmJAZ4, ZmJAZ5 and ZmJAZ15, was affected in coi2a coi2b. However, yeast two‐hybrid assays showed that ZmJAZs interacted with ZmCOI1s, but not with ZmCOI2s. In conclusion, ZmCOI2a and ZmCOI2b redundantly regulate anther dehiscence and gametophytic male fertility in maize.
Impact of disasters on blood donation rates and blood safety: A systematic review and meta‐analysis
Authors: Laermans Jorien , O Dorien , Van den Bosch Emma , De Buck Emmy , Compernolle Veerle , Shinar Eilat , Vandekerckhove Philippe
Published: February 2022

Background and Objectives

Timely and adequate access to safe blood forms an integral part of universal health coverage, but it may be compromised by natural or man‐made disasters. This systematic review provides an overview of the best available scientific evidence on the impact of disasters on blood donation rates and safety outcomes.

Materials and Methods

Five databases (The Cochrane Library, MEDLINE, Embase, Web of Science and CINAHL) were searched until 27 March 2020 for (un)controlled studies investigating the impact of disasters on blood donation rates and/or safety. Risk of bias and overall certainty of the evidence were assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Results

Eighteen observational studies were identified, providing very low certainty of evidence (due to high risk of bias, inconsistency and/or imprecision) on the impact of natural (12 studies) and man‐made/technological (6 studies) disasters. The available evidence did not enable us to form any generalizable conclusions on the impact on blood donation rates. Meta‐analyses could not detect any statistically significant changes in transfusion‐transmissible infection (TTI) rates [hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)‐1/2, human T‐lymphotropic virus I and II (HTLV‐I/II) and syphilis] in donated blood after a disaster, either in first‐time or repeat donors, although the evidence is very uncertain.

Conclusion

The very low certainty of evidence synthetized in this systematic review indicates that it is very uncertain whether there is an association between disaster occurrence and changes in TTI rates in donated blood. The currently available evidence did not allow us to draw generalizable conclusions on the impact of disasters on blood donation rates.
Computed tomographic assessment of fracture characteristics and subchondral bone injury in Thoroughbred racehorses with lateral condylar fractures and their relationship to outcome
Authors: Cianci Justine M. , Wulster Kathryn B. , Richardson Dean W. , Stefanovski Darko , Ortved Kyla F.
Published: February 2022

Objective

To investigate the effects of fracture characteristics and concurrent subchondral bone pathology identified with computed tomography (CT) on the racing performance of Thoroughbred racehorses with fractures of the MC3/MT3 lateral condyle.

Study design

Retrospective cohort study.

Sample population

Thoroughbred racehorses (n = 50) with a fracture of the MC3/MT3 lateral condyle, which had preoperative CT and internal fixation performed.

Methods

Medical records were reviewed for age, sex, limb, and surgical treatment. Computed tomography scans were evaluated to determine fracture characteristics including length, whether the fracture was incomplete or complete, and displacement. The presence of subchondral bone injury (SBI), sesamoid bone fracture, articular comminution, and fragmentation in the joint was noted. Racing data was obtained from an online database. Univariable and multivariable analyses determined associations between independent variables and outcomes.

Results

Thirty‐three (66%) horses raced after surgery. Horses with sesamoid bone fractures (P = .021), MC3/MT3 comminution (P = .016) and intra‐articular fragmentation (P = .015) were less likely to race postoperatively. Concurrent SBI did not affect outcome. In the final multivariable model, sex (P = .015) and whether a fracture was incomplete or complete (P = .007) were the most significant predictors of racing postoperatively with females and horses with complete fractures being less likely to race.

Conclusion

The prognosis for racing after a lateral condylar fracture is favorable but is decreased in horses with complete fractures and certain concurrent joint pathology.

Clinical significance

Horses presenting with lateral condylar fractures commonly have concurrent joint pathology. Computed tomography can aid in preoperative evaluation and prognostication by enabling more complete fracture assessment.
The effects of Lombard perturbation on speech intelligibility in noise for normal hearing and cochlear implant listeners
Authors: Saba Juliana N. , Hansen John H. L.
Published: February 2022

Natural compensation of speech production in challenging listening environments is referred to as the Lombard effect (LE). The resulting acoustic differences between neutral and Lombard speech have been shown to provide intelligibility benefits for normal hearing (NH) and cochlear implant (CI) listeners alike. Motivated by this outcome, three LE perturbation approaches consisting of pitch, duration, formant, intensity, and spectral contour modifications were designed specifically for CI listeners to combat speech-in-noise performance deficits. Experiment 1 analyzed the effects of loudness, quality, and distortion of approaches on speech intelligibility with and without formant-shifting. Significant improvements of +9.4% were observed in CI listeners without the formant-shifting approach at +5 dB signal-to-noise ratio (SNR) large-crowd-noise (LCN) when loudness was controlled, however, performance was found to be significantly lower for NH listeners. Experiment 2 evaluated the non-formant-shifting approach with additional spectral contour and high pass filtering to reduce spectral smearing and decrease distortion observed in Experiment 1. This resulted in significant intelligibility benefits of +30.2% for NH and +21.2% for CI listeners at 0 and +5 dB SNR LCN, respectively. These results suggest that LE perturbation may be useful as front-end speech modification approaches to improve intelligibility for CI users in noise.
A wearable multi-modal acoustic system for breathing analysis
Authors: Emokpae Lloyd E. , Emokpae Roland N. , Bowry Ese , Bin Saif Jaeed , Mahmud Muntasir , Lalouani Wassila , Younis Mohamed , Joyner Robert L.
Published: February 2022

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide with over 3 × 106 deaths in 2019. Such an alarming figure becomes frightening when combined with the number of lost lives resulting from COVID-caused respiratory failure. Because COPD exacerbations identified early can commonly be treated at home, early symptom detections may enable a major reduction of COPD patient readmission and associated healthcare costs; this is particularly important during pandemics such as COVID-19 in which healthcare facilities are overwhelmed. The standard adjuncts used to assess lung function (e.g., spirometry, plethysmography, and CT scan) are expensive, time consuming, and cannot be used in remote patient monitoring of an acute exacerbation. In this paper, a wearable multi-modal system for breathing analysis is presented, which can be used in quantifying various airflow obstructions. The wearable multi-modal electroacoustic system employs a body area sensor network with each sensor-node having a multi-modal sensing capability, such as a digital stethoscope, electrocardiogram monitor, thermometer, and goniometer. The signal-to-noise ratio (SNR) of the resulting acoustic spectrum is used as a measure of breathing intensity. The results are shown from data collected from over 35 healthy subjects and 3 COPD subjects, demonstrating a positive correlation of SNR values to the health-scale score.
Themis is indispensable for IL-2 and IL-15 signaling in T cells
Authors: Liu Yongchao , Cong Yu , Niu Yujia , Yuan Yin , Tan Fancheng , Lai Qian , Hu Yanyan , Hou Bowen , Li Jian , Lin Chunjie , Zheng Haiping , Dong Junchen , Tang Jian , Chen Qinwei , Brzostek Joanna , Zhang Xueqin , Chen Xiao Lei , Wang Hong-Rui , Gascoigne Nicholas R. J. , Xu Bing , Lin Shu-Hai , Fu Guo
Published: February 2022

To perform their antiviral and antitumor functions, T cells must integrate signals both from the T cell receptor (TCR), which instruct the cell to remain quiescent or become activated, and from cytokines that guide cellular proliferation and differentiation. In mature CD8
+
T cells, Themis has been implicated in integrating TCR and cytokine signals. We investigated whether Themis plays a direct role in cytokine signaling in mature T cells. Themis was required for IL-2– and IL-15–driven CD8
+
T cell proliferation both in mice and in vitro. Mechanistically, we found that Themis promoted the activation of the transcription factor Stat and mechanistic target of rapamycin signaling downstream of cytokine receptors. Metabolomics and stable isotope tracing analyses revealed that Themis deficiency reduced glycolysis and serine and nucleotide biosynthesis, demonstrating a receptor-proximal requirement for Themis in triggering the metabolic changes that enable T cell proliferation. The cellular, metabolic, and biochemical defects caused by Themis deficiency were corrected in mice lacking both Themis and the phosphatase Shp1, suggesting that Themis mediates IL-2 and IL-15 receptor-proximal signaling by restraining the activity of Shp1. Together, these results not only shed light on the mechanisms of cytokine signaling but also provide new clues on manipulating T cells for clinical applications.
Interaction Tolerance Detection Test for Understanding the Killing Efficacy of Directional Antibiotic Combinations
Authors: Liu Jia-Feng , Gefen Orit , Zhang Zi-Yin , Liu Min-Min , Bar-Meir Maskit , Balaban Nathalie Q.
Published: February 2022

The killing efficacy of antibiotic combinations is rarely measured in the clinical setting. However, in cases where the treatment is required to kill the infecting organism and not merely arrest its growth, the information on the killing efficacy is important, especially when tolerant strains are implicated.
CRP-Like Transcriptional Regulator MrpC Curbs c-di-GMP and 3′,3′-cGAMP Nucleotide Levels during Development in Myxococcus xanthus
Authors: Kuzmich Sofya , Blumenkamp Patrick , Meier Doreen , Szadkowski Dobromir , Goesmann Alexander , Becker Anke , Søgaard-Andersen Lotte
Published: February 2022

The second messenger c-di-GMP is important during both stages of the nutrient-regulated biphasic life cycle of
Myxococcus xanthus
with the formation of predatory swarms in the presence of nutrients and spore-filled fruiting bodies in the absence of nutrients. However, different enzymes involved in c-di-GMP synthesis and degradation are important during distinct life cycle stages.
SARS-CoV-2 Variants Increase Kinetic Stability of Open Spike Conformations as an Evolutionary Strategy
Authors: Yang Ziwei , Han Yang , Ding Shilei , Shi Wei , Zhou Tongqing , Finzi Andrés , Kwong Peter D. , Mothes Walther , Lu Maolin
Published: February 2022

SARS-CoV-2 surface S glycoprotein—the target of antibodies and vaccines—is responsible for binding to the cellular receptor hACE2. The interactions between S and hACE2 trigger structural rearrangements of S from closed to open conformations prerequisite for virus entry.
The Human Nose Organoid Respiratory Virus Model: an
Ex Vivo
Human Challenge Model To Study Respiratory Syncytial Virus (RSV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pathogenesis and Evaluate Therapeutics
Authors: Rajan Anubama , Weaver Ashley Morgan , Aloisio Gina Marie , Jelinski Joseph , Johnson Hannah L. , Venable Susan F. , McBride Trevor , Aideyan Letisha , Piedra Felipe-Andrés , Ye Xunyan , Melicoff-Portillo Ernestina , Yerramilli Malli Rama Kanthi , Zeng Xi-Lei , Mancini Michael A. , Stossi Fabio , Maresso Anthony W. , Kotkar Shalaka A. , Estes Mary K. , Blutt Sarah , Avadhanula Vasanthi , Piedra Pedro A.
Published: February 2022

Preclinical models that recapitulate aspects of human airway disease are essential for the advancement of novel therapeutics and vaccines. Here, we report a versatile airway organoid model, the human nose organoid (HNO), that recapitulates the complex interactions between the host and virus.
Supplemental Material: The “death” of the Sevier-Laramide orogen: Gravitational collapse of the crust or something else?
Authors: Konstantinou Alexandros
Published: February 2022

Appendices S1–S7: Databases and models used to estimate crustal thickness and elevations during the evolution of the Sevier-Laramide orogen and Basin and Range extension
Disparities in cardiometabolic risk profiles and gestational diabetes mellitus by nativity and acculturation: findings from 2016–2017 National Health Interview Survey
Authors: Ogunwole S Michelle , Turkson-Ocran Ruth-Alma N , Boakye Ellen , Creanga Andreea A , Wang Xiaobin , Bennett Wendy L , Sharma Garima , Cooper Lisa A , Commodore-Mensah Yvonne
Published: February 2022

Introduction

Gestational diabetes mellitus (GDM) is a common complication of pregnancy with implications for cardiovascular health. Among reproductive-aged women, less is known about nativity-related disparities in cardiometabolic risk profiles and GDM history. We examined how cardiometabolic risk profiles and GDM history differed by nativity and explored associations between acculturation, cardiometabolic risk profiles and GDM history.

Research design and methods

We analyzed cross-sectional data from the 2016–2017 National Health Interview Survey among reproductive-aged women (18–49 years) who both reported ever being pregnant and answered the question on GDM history. Using multivariable logistic regression, we examined the percentage with GDM history and compared cardiometabolic profiles by nativity status and acculturation (duration of US residence).

Results

Of 9525 women, 22.5% were foreign-born. Also, 11.7% of foreign-born women had a GDM history vs 9.6% of US-born women. Foreign-born women with ≥10 years US residence had the highest age-standardized percentage with GDM history (11.0%) compared with US-born women (9.2%) and foreign-born women with <10 years US residence (6.7%). US-born women had a higher prevalence of hypertension, current smoking, and alcohol use than foreign-born women. Among foreign-born women, those with ≥10 years US residence had a higher prevalence of hypertension, current smoking, and alcohol use than those with <10 years US residence. In the fully adjusted model, foreign-born women with ≥10 years US residence had higher odds of GDM history than US-born women (OR 1.43; 95% CI 1.17 to 1.76) while foreign-born women with <10 years US residence and US-born women has similar odds of GDM history.

Conclusions

Greater duration of US residence may be associated with nativity-related disparities in GDM. Acculturation, including changing health-related behaviors may explain the disparities among foreign-born women and should be further investigated to appropriately target interventions to prevent GDM and future cardiometabolic diseases.
Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital
Authors: Burke Hannah , Freeman Anna , O’Regan Paul , Wysocki Oskar , Freitas Andre , Dushianthan Ahilanandan , Celinski Michael , Batchelor James , Phan Hang , Borca Florina , Sheard Natasha , Williams Sarah , Watson Alastair , Fitzpatrick Paul , Landers Dónal , Wilkinson Tom
Published: February 2022

Objectives

COVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19.

Design and setting

This retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England.

Participants

Six hundred and fifty-one patients treated for SARS-CoV-2 between March and September 2020 were included in this analysis. Ethical approval was obtained from the HRA Specific Review Board (REC 20/HRA/2986) for waiver of informed consent.

Results

The majority of patients presented within 1 week of symptom onset. The lowest risk patients had low mortality (1/45, 2%), and most were discharged within 1 week after admission (30/45, 67%). The highest risk patients, as determined by the 4C mortality score predictor, had high mortality (27/29, 93%), with most dying within 1 week after admission (22/29, 76%). Consistent with previous reports, most patients presented with high levels of C reactive protein (CRP) (67% of patients >50 mg/L), D-dimer (98%>upper limit of normal (ULN)), ferritin (65%>ULN), lactate dehydrogenase (90%>ULN) and low lymphocyte counts (81%<lower limit of normal (LLN)). Increases in platelet counts and decreases in CRP, neutrophil:lymphocyte ratio (p<0.001), lactate dehydrogenase, neutrophil counts, urea and white cell counts (all p<0.01) were each associated with discharge.

Conclusions

Serial measurement of routine blood tests may be a useful prognostic tool for monitoring treatment response in hospitalised patients with COVID-19. Changes in other biochemical parameters often included in a ‘COVID-19 bundle’ did not show significant association with outcome, suggesting there may be limited clinical benefit of serial sampling. This may have direct clinical utility in the context of escalating healthcare costs of the pandemic.
Healthcare workers’ perceptions and attitudes towards the UK’s COVID-19 vaccination programme: a rapid qualitative appraisal
Authors: Manby Louisa , Dowrick Anna , Karia Amelia , Maio Laura , Buck Caroline , Singleton Georgina , Lewis-Jackson Sasha , Uddin Inayah , Vanderslott Samantha , Martin Sam , Vindrola-Padros Cecilia
Published: February 2022

Objectives

While there is research relating to perceptions of vaccines among healthcare workers (HCWs), the evidence base in relation to COVID-19 remains limited. The aim of this study was to explore HCWs’ perceptions and attitudes towards vaccines and the COVID-19 vaccination programme in the UK, including their expectations and views on promoting vaccination to others.

Design

This study was designed as a rapid qualitative appraisal, integrating data from a review of UK policies and guidance on COVID-19 vaccination with data from in-depth semistructured telephone interviews with frontline HCWs in the UK. Data were analysed using framework analysis.

Participants

Interviews were carried out with a purposive sample of HCWs from two large London-based hospital Trusts (n=24) and 24 government policies, and guidelines on the vaccination programme were reviewed.

Results

The level of uncertainty about the long-term safety of vaccines and efficacy against mutant strains made it difficult for HCWs to balance the benefits against the risks of vaccination. HCWs felt that government decisions on vaccine rollout had not been supported by evidence-based science, and this impacted their level of trust and confidence in the programme. The spread of misinformation online also impacted HCWs’ attitudes towards vaccination, particularly among junior level and black, Asian and minority ethnic (BAME) HCWs. Most HCWs felt encouraged to promote vaccination to their patients, and the majority said they would advocate vaccination or engage in conversations about vaccination with others when relevant.

Conclusion

In order to improve HCWs’ trust and confidence in the UK’s COVID-19 vaccination programme, there needs to be clarity about what is known and not known about the vaccines and transparency around the evidence-base supporting government decisions on vaccine rollout. Effort is also needed to dispel the spread of vaccine-related misinformation online and to address specific concerns, particularly among BAME and junior-level HCWs.
Protocol for individual participant data meta-analysis of interventions for post-traumatic stress
Authors: Wright Simonne Lesley , Karyotaki Eirini , Bisson Jonathan I , Cuijpers Pim , Papola Davide , Witteveen Anke B , Seedat Soraya , Sijbrandij Marit
Published: February 2022

Introduction

Several evidence-based treatments are effective for post-traumatic stress disorder (PTSD), yet a substantial proportion of patients do not respond or dropout of treatment. We describe the protocol for a systematic review and individual participant data meta-analysis (IPD-MA) aimed at assessing the effectiveness and adverse effects of psychotherapy and pharmacotherapy interventions for treating PTSD. Additionally, we seek to examine moderators and predictors of treatment outcomes.

Method and analysis

This IPD-MA includes randomised controlled trials comparing psychotherapy and pharmacotherapy interventions for PTSD. PubMed, Embase, PsycINFO, PTSDpubs and CENTRAL will be screened up till the 11th of January 2021. The target population is adults with above-threshold baseline PTSD symptoms on any standardised self-report measure. Trials will only be eligible if at least 70% of the study sample have been diagnosed with PTSD by means of a structured clinical interview. The primary outcomes of this IPD-MA are PTSD symptom severity, and response rate. Secondary outcomes include treatment dropout and adverse effects. Two independent reviewers will screen major bibliographic databases and past reviews. Authors will be contacted to contribute their participant-level datasets. Datasets will be merged into a master dataset. A one-stage IPD-MA will be conducted focusing on the effects of psychological and pharmacological interventions on PTSD symptom severity, response rate, treatment dropout and adverse effects. Subsequent analyses will focus on examining the effect of moderators and predictors of treatment outcomes. These will include sociodemographic, treatment-related, symptom-related, resilience, intervention, trauma and combat-related characteristics. By determining the individual factors that influence the effectiveness of specific PTSD treatments, we will gain insight into personalised treatment options for PTSD.

Ethics and dissemination

Specific ethics approval for an IPD-MA is not required as this study entails secondary analysis of existing anonymised data. The results of this study will be published in peer-reviewed scientific journals and presentations.
Enhanced recovery after surgery management of perioperative period in surgical lung cancer patients: protocol for a systematic review and meta-analysis of randomised controlled trials
Authors: Chen Ting , Wei Huaping , Yue Weigang , Su Yan , Fu Xiaoyan
Published: February 2022

Introduction

Enhanced recovery after surgery (ERAS) has been widely used in the perioperative period of lung cancer surgery. However, there remains a lack of comprehensive and systematic evidence on the effectiveness and safety of ERAS. This study aims to evaluate the efficacy and safety of ERAS in patients with lung cancer.

Methods and analysis

Eight databases (PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP and WANFANG) will be searched from inception to November 2021. Two reviewers will independently screen studies, extract data of interest and assess the risk of bias. The revised risk of bias tool 2 will be used to assess the risk of bias in randomised controlled trials. We will use the Grading of Recommendations, Assessment, Development and Evaluations to assess the certainty of evidence. We will carry out a random-effect meta-analysis focusing on the efficacy and safety variables. All analyses will be conducted using RevMan V.5.3.

Ethics and dissemination

Since the study will be a systematic review and will not involve direct contact with patients or make alterations to patient care, ethical approval and informed consent are not required for this study. The results of this review will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42021250761.
Understanding income-related differences in distribution of child growth, behaviour and development using a cross-sectional sample of a clinical cohort study
Authors: Fuller Anne , Siddiqi Arjumand , Shahidi Faraz V , Anderson Laura N , Hildebrand Vincent , Keown-Stoneman Charles D G , Maguire Jonathon L , Birken Catherine
Published: February 2022

Objectives

Children from low-income households are at an increased risk of social, behavioural and physical health problems. Prior studies have generally relied on dichotomous outcome measures. However, inequities may exist along the range of outcome distribution. Our objective was to examine differences in distribution of three child health outcomes by income categories (high vs low): body mass index (BMI), behaviour difficulties and development.

Design and setting

This was a cross-sectional study using data from a primary care-based research network with sites in three Canadian cities, and 15 practices enrolling participants.

Participants, independent variable and outcomes

The independent variable was annual household income, dichotomised at the median income for Toronto (<$C80 000 or ≥$C80 000). Outcomes were: (1) growth (BMI z-score (zBMI) at 5 years, 1628 participants); (2) behaviour (Strengths and Difficulties Questionnaire (SDQ) at 3–5 years, 649 participants); (3) development (Infant Toddler Checklist (ITC) at 18 months, 1405 participants). We used distributional decomposition to compare distributions of these outcomes for each income group, and then to construct a counterfactual distribution that describes the hypothetical distribution of the low-income group with the predictor profile of the higher-income group.

Results

We included data from 1628 (zBMI), 649 (SDQ) and 1405 (ITC) children. Children with lower family income had a higher risk distribution for all outcomes. For all outcomes, thecounterfactual distribution, which represented the distribution of children with lower-income who were assigned the predictor profile of the higher-income group, was more favourable than their observed distributions.

Conclusion

Comparing the distributions of child health outcomes and understanding different risk profiles for children from higher-income and lower-income groups can offer a deeper understanding of inequities in child health outcomes. These methods may offer an approach that can be implemented in larger datasets to inform future interventions.
Economic evaluations of musculoskeletal physiotherapy: protocol of a systematic review
Authors: Baumbach Linda , König Hans-Helmut , Kretzler Benedikt , Hajek André
Published: February 2022

Introduction

Several economic evaluations of musculoskeletal physiotherapy have been published in the literature. We aim to provide an overview of these existing economic evaluations. This overview will be useful for healthcare funders in identifying studies matching their context. In addition, research gaps as well as literature extensive enough to be combined in a meta-analysis will be identified. This will support researchers in planning relevant research projects.

Methods and analyses

We will search in PubMed, EconLit and NHS-EED for relevant literature. Full economic evaluations of musculoskeletal physiotherapy interventions will be included, regardless of type, and economic evaluation perspective. Initial searches were performed on 7th October 2021. Study selection, data extraction and the quality evaluation will be conducted initially by two independent researchers. If their agreement is sufficient, one reviewer will proceed with the respected process. From the included studies, we will extract information on the publication year, the country of origin, the type of economical evaluation analyses and the specific musculoskeletal condition. An overview will be provided, concerning the distributions of the included studies regarding the extracted information. Furthermore, an evaluation of the individual study quality will be offered.

Ethics and dissemination

No ethical approval will be required for this systematic review, since no human participants are involved. We aim to distribute the findings of this review in a peer-reviewed journal, on national and international conferences, as well as via social media.
The German Gestational Diabetes Study (PREG), a prospective multicentre cohort study: rationale, methodology and design
Authors: Fritsche Louise , Hummel Julia , Wagner Robert , Löffler Dorina , Hartkopf Julia , Machann Jürgen , Hilberath Johannes , Kantartzis Konstantinos , Jakubowski Peter , Pauluschke-Fröhlich Jan , Brucker Sara , Hörber Sebastian , Häring Hans-Ulrich , Roden Michael , Schürmann Annette , Solimena Michele , de Angelis Martin Hrabe , Peter Andreas , Birkenfeld Andreas L , Preissl Hubert , Fritsche Andreas , Heni Martin
Published: February 2022

Introduction

Even well-treated gestational diabetes mellitus (GDM) might still have impact on long-term health of the mother and her offspring, although this relationship has not yet been conclusively studied. Using in-depth phenotyping of the mother and her offspring, we aim to elucidate the relationship of maternal hyperglycaemia during pregnancy and adequate treatment, and its impact on the long-term health of both mother and child.

Methods

The multicentre PREG study, a prospective cohort study, is designed to metabolically and phenotypically characterise women with a 75-g five-point oral glucose tolerance test (OGTT) during, and repeatedly after pregnancy. Outcome measures are maternal glycaemia during OGTTs, birth outcome and the health and growth development of the offspring. The children of the study participants are followed up until adulthood with developmental tests and metabolic and epigenetic phenotyping in the PREG Offspring study. A total of 800 women (600 with GDM, 200 controls) will be recruited.

Ethics and dissemination

The study protocol has been approved by all local ethics committees. Results will be disseminated via conference presentations and peer-reviewed publications.

Trial registration number

The PREG study and the PREG Offspring study are registered with Clinical Trials (ClinicalTrials.gov identifiers:NCT04270578,NCT04722900).
Potential of four definitions of metabolic syndrome to discriminate individuals with different 10-year cardiovascular disease risk scores: a cross-sectional analysis of an Iranian cohort
Authors: Zibaeenezhad Mohammad Javad , Sayadi Mehrab , Karimi-Akhormeh Ali , Ardekani Ali , Parsa Nader , Razeghian-Jahromi Iman
Published: February 2022

Objective

We aimed to reveal the potential of four different metabolic syndrome (Mets) definitions to differentiate subjects according to 10-year risk of cardiovascular disease.

Design

A cross-sectional analysis of a prospective cohort.

Setting

This study used baseline data from the Shiraz Heart Study, a prospective cohort study in Shiraz, Iran. Participants were screened against Mets definitions including modified WHO, National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), American Heart Association (AHA) and International Diabetes Federation (IDF). Also, Framingham risk score (FRS) and atherosclerotic cardiovascular disease (ASCVD) risk score were determined for each participant.

Participants

A total number of 7225 participants of both genders entered the study. They were selected through defined family physician centres in different geographical areas. Urban residents with no migration plan were included. Those who were far from study centres or with disabilities that made them incapable to cooperate were excluded.

Results

Participants were 47.68% (N=3445) male with the mean age of 52.13±8.00 years. The number of subjects with Mets identified by WHO was the lowest (N=1676), while the percentage of subjects with high risk score was the highest, 17.1% (N=282) in FRS and 9.8% (N=162) in ASCVD risk score. There were statistically significant differences in the mean risk scores between participants with and without Mets according to AHA, WHO and NCEP ATP III definitions (p<0.001). In IDF definition, the risk scores of subjects with Mets were not statistically different compared with peers without Mets, neither based on FRS (p=0.247) nor ASCVD risk score (p=0.193).

Conclusions

IDF was not the appropriate definition for discrimination of subjects with Mets and/or those at high risk of future cardiovascular events. AHA, WHO and NCEP ATP III definitions were effective to discriminate subjects with Mets from peers without Mets.
Serious Illness Care Programme—contextual factors and implementation strategies: a qualitative study
Authors: Paladino Joanna , Sanders Justin , Kilpatrick Laurel B , Prabhakar Ramya , Kumar Pallavi , O'Connor Nina , Durieux Brigitte , Fromme Erik K , Benjamin Evan , Mitchell Suzanne
Published: February 2022

Objectives

The Serious Illness Care Programme (SICP) is a multicomponent evidence-based intervention that improves communication about patients’ values and goals in serious illness. We aim to characterise implementation strategies for programme delivery and the contextual factors that influence implementation in three ‘real-world’ health system SICP initiatives.

Methods

We employed a qualitative thematic framework analysis of field notes collected during the first 1.5 years of implementation and a fidelity survey.

Results

Analysis revealed empiric evidence about implementation and institutional context. All teams successfully implemented clinician training and an electronic health record (EHR) template for documentation of serious illness conversations. When training was used as the primary strategy to engage clinicians, however, clinician receptivity to the programme and adoption of conversations remained limited due to clinical culture-related barriers (eg, clinicians’ attitudes, motivations and practice environment). Visible leadership involvement, champion facilitation and automated EHR-based data feedback on documented conversations appeared to improve adoption. Implementing these strategies depended on contextual factors, including leadership support at the specialty level, champion resources and capacity, and EHR capabilities.

Conclusions

Health systems need multifaceted implementation strategies to move beyond the limited impact of clinician training in driving improvement in serious illness conversations. These include EHR-based data feedback, involvement of specialty leaders to message the programme and align incentives, and local champions to problem-solve frontline challenges longitudinally. Implementation of these strategies depended on a favourable institutional context. Greater attention to the influence of contextual factors and implementation strategies may enable sustained improvements in serious illness conversations at scale.
Association of physical activity trajectories with major cardiovascular diseases in elderly people
Authors: Barbiellini Amidei Claudio , Trevisan Caterina , Dotto Matilde , Ferroni Eliana , Noale Marianna , Maggi Stefania , Corti Maria Chiara , Baggio Giovannella , Fedeli Ugo , Sergi Giuseppe
Published: February 2022

Introduction

Cardiovascular benefits deriving from physical activity are well known, but it is unclear whether physical activity trajectories in late life are associated with different risks of cardiovascular diseases.

Methods

Progetto Veneto Anziani (Pro.V.A.) is a cohort study of 3099 Italians aged ≥65 years with baseline assessment in 1995–1997 and follow-up visits at 4 and 7 years. Surveillance was extended to 2018 by linkage with hospital and mortality records. Prevalent and incident cardiovascular diseases (coronary heart disease, heart failure and stroke) were identified through clinical examination, questionnaire, or hospital records. Moderate to vigorous physical activity was considered as a time-varying variable. Physical activity trajectories were categorised as: stable-low, high-decreasing, low-increasing and stable-high. Exposure was also assessed at 70, 75, 80 and 85 years.

Results

Overall, physical activity was associated with lower rates of incident cardiovascular diseases. A significant risk reduction was present among men and was stronger earlier in late life (70–75 years). Trajectories of stable-high physical activity were associated with a significantly lower risk of cardiovascular outcomes among men (HR 0.48, 95% CI 0.27 to 0.86) compared with those with stable-low trajectories (p for trend 0.002). No significant association was found with stroke. The greatest cardiovascular risk reduction was observed for >20 min/day of physical activity, and was more marked at 70 years.

Conclusion

Increasingly active trajectories of physical activity were associated with lower rates of cardiovascular diseases and overall mortality. Promoting at least 20 min/day of physical activity early in late life seems to provide the greatest cardiovascular benefits.
Compound computer vision workflow for efficient and automated immunohistochemical analysis of whole slide images
Authors: Lee Michael Kyung Ik , Rabindranath Madhumitha , Faust Kevin , Yao Jennie , Gershon Ariel , Alsafwani Noor , Diamandis Phedias
Published: February 2022

Aims

Immunohistochemistry (IHC) assessment of tissue is a central component of the modern pathology workflow, but quantification is challenged by subjective estimates by pathologists or manual steps in semi-automated digital tools. This study integrates various computer vision tools to develop a fully automated workflow for quantifying Ki-67, a standard IHC test used to assess cell proliferation on digital whole slide images (WSIs).

Methods

We create an automated nuclear segmentation strategy by deploying a Mask R-CNN classifier to recognise and count 3,3′-diaminobenzidine positive and negative nuclei. To further improve automation, we replaced manual selection of regions of interest (ROIs) by aligning Ki-67 WSIs with corresponding H&E-stained sections, using scale-invariant feature transform (SIFT) and a conventional histomorphological convolutional neural networks to define tumour-rich areas for quantification.

Results

The Mask R-CNN was tested on 147 images generated from 34 brain tumour Ki-67 WSIs and showed a high concordance with aggregate pathologists’ estimates (n=3assessors;y=0.9712x−1.945,r=0.9750). Concordance of each assessor’s Ki-67 estimates was higher when compared with the Mask R-CNN than between individual assessors (ravg=0.9322 vs 0.8703; p=0.0213). Coupling the Mask R-CNN with SIFT-CNN workflow demonstrated ROIs can be automatically chosen and partially sampled to improve automation and dramatically decrease computational time (average: 88.55–19.28 min; p<0.0001).

Conclusions

We show how innovations in computer vision can be serially compounded to automate and improve implementation in clinical workflows. Generalisation of this approach to other ancillary studies has significant implications for computational pathology.
Endovascular thrombectomy beyond 24 hours from ischemic stroke onset: a propensity score matched cohort study
Authors: Dhillon Permesh Singh , Butt Waleed , Podlasek Anna , Barrett Emma , McConachie Norman , Lenthall Robert , Nair Sujit , Malik Luqman , James Martin A , Dineen Robert A , England Timothy J
Published: February 2022

Background

The safety and functional outcome of endovascular thrombectomy (EVT) in the very late (VL; >24 hours) time window from ischemic stroke onset remains undetermined.

Methods

Using data from a national stroke registry, we used propensity score matched (PSM) individual level data of patients who underwent EVT, selected with CT perfusion or non-contrast CT/CT angiography, between October 2015 and March 2020. Functional and safety outcomes were assessed in both late (6–24 hours) and VL time windows. Subgroup analysis was performed of imaging selection modality in the VL time window.

Results

We included 1150 patients (late window: 1046 (208 after PSM); VL window: 104 (104 after PSM)). Compared with EVT treatment initiation between 6 and 24 hours, patients treated in the VL window had similar modified Rankin Scale (mRS) scores at discharge (ordinal shift; common OR=1.08, 95% CI 0.69 to 1.47, p=0.70). No significant differences in achieving good functional outcome (mRS ≤2 at discharge; 28.8% (VL) vs 29.3% (late), OR=0.97, 95% CI 0.58 to 1.64, p=0.93), successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b–3) (p=0.77), or safety outcomes of symptomatic intracranial hemorrhage (p=0.43) and inhospital mortality (p=0.23) were demonstrated. In the VL window, there was no significant difference in functional outcome among patients selected with perfusion versus those selected without perfusion imaging (common OR=1.38, 95% CI 0.81 to 1.76, p=0.18).

Conclusion

In this real world study, EVT beyond 24 hours from stroke onset or last known well appeared to be feasible, with comparable safety and functional outcomes to EVT initiation between 6 and 24 hours. Randomized trials assessing the efficacy of EVT in the VL window are warranted, but may only be feasible with a large international collaborative approach.
Appropriate use of transthoracic echocardiography in the investigation of general medicine patients presenting with syncope or presyncope
Authors: Simos Peter , Scott Ian
Published: February 2022

Study purpose

Routine transthoracic echocardiography (TTE) in patients with syncope or presyncope is resource-intensive. We assessed if risk thresholds defined by a validated risk score may identify patients at low risk of cardiac abnormality in whom TTE is unnecessary.

Study design

We conducted a retrospective study of all general medicine patients with syncope/presyncope presenting to a tertiary hospital between July 2016 and September 2020 and who underwent TTE. The Canadian Syncope Risk Score (CSRS) was used to categorise patients as low to very low risk (score −3 to 0) or moderate to high risk (score ≥1) for serious adverse events at 30 days. A cut-point of 0 was used to calculate the sensitivity, specificity, positive and negative predictive values (PPV and NPV) for CSRS and the odds ratio (OR) of a clinically significant finding on TTE in patients with CSRS ≥1 compared with all patients.

Results

Among 157 patients, the CSRS categorised 69 (44%) as very low to low risk in whom TTE was normal. In 88 patients deemed moderate to high risk, TTE detected a cardiac abnormality in 24 (27%). A CSRS ≥1 yielded a sensitivity of 100% (95% CI 85.7% to 100%), specificity of 51.1% (95% CI 42.3% to 59.8%), PPV of 26.5% (95% CI 26.3% to 30.1%) and NPV of 100% (95% CI 92.5% to 100%) for cardiac abnormalities and doubled the odds of an abnormality (OR = 2.05, 95% CI 1.08 to 3.87, p = 0.028).

Conclusion

In general medicine patients with syncope/presyncope, using the CSRS to stratify risk of a cardiac abnormality on TTE can almost halve TTE use.
Glueballs at high temperature within the hard-wall holographic model
Authors: Rinaldi Matteo , Vento Vicente
Published: February 2022

In this investigation an holographic description of the deconfined phase transition of scalar and tensor glueballs is presented within the so called hard-wall model. The spectra of these bound states of gluons have been calculated from the linearized Einstein equations for a graviton propagating from a thermal $$AdS_5$$

A
d

S
5

space to an AdS Black-Hole. In this framework, the deconfined phase is reached via a two steps mechanism. We propose that the transition between the AdS thermal sector to the BH is described via a first order phase transition, with discontinuous masses at the critical temperature, which has been determined by Herzog’s method of regulating the free energy densities. Then, the glueball masses diverge with increasing T in the BH phase and thus lead to deconfined states à la Hagedorn.
A high-resolution, variable-energy electron beam from a Penning–Malmberg (Surko) buffer-gas trap
Authors: Machacek J. R. , Gay T. J. , Buckman Stephen J. , Hodgman Sean S.
Published: February 2022

We describe the production of a high-resolution electron beam using a Penning–Malmberg buffer-gas trap, or Surko trap as they have become known. A high-flux beam with an energy width of ~ 30 meV (FWHM) is readily achieved and the efficiency of production is considerably higher than that for positrons in a similar trap configuration. The reasons for this become apparent when one considers the molecular collisions and the respective selection rules involved, for electrons and positrons. We demonstrate the production of the beam and the capacity that it realises for absolute scattering measurements and for high-resolution electron spectroscopy.

Graphical abstract
Numerical treatment for processing the effect of convective thermal condition and Joule heating on Casson fluid flow past a stretching sheet
Authors: Mahdy Amr M. S. , Babatin M. M. , Khader M. M.
Published: February 2022

In this work, an approximate analytical solution for the problem of non-Newtonian Casson fluid flow past a porous exponentially stretching sheet with Joule heating and convective boundary condition is obtained using a relatively new technique; He’s homotopy perturbation (HPM). The major feature of HPM is that it does not need the small parameters in the equations, and hence the determination of classical perturbation can be discarded. Due to the complete efficiency of the HPM, it becomes practically well suited for use in this field of study. Also, the obtained solutions for both the velocity and temperature field are graphically sketched. The results reveal that the method is very effective, convenient and quite accurate to systems of nonlinear equations.