bluuebunny/crossref_metadata_2025 huggingface dataset:
Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts
Authors: Houston Hamish , Hakki Seran , Pillay Timesh D. , Madon Kieran , Derqui-Fernandez Nieves , Koycheva Aleksandra , Singanayagam Anika , Fenn Joe , Kundu Rhia , Conibear Emily , Varro Robert , Cutajar Jessica , Quinn Valerie , Wang Lulu , Narean Janakan S. , Tolosa-Wright Mica R. , Barnett Jack , Kon Onn Min , Tedder Richard , Taylor Graham , Zambon Maria , Ferguson Neil , Dunning Jake , Deeks Jonathan J. , Lalvani Ajit
Published: November 2021

Background

The success of case isolation and contact tracing for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS),i.e.fever, cough and loss or change in smell or taste, could improve case definitions and accelerate case identification in SARS-CoV-2 contacts.

Methods

Two prospective longitudinal London (UK)-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and area under the receiver operating characteristic curve. Improvements in sensitivity and time to detection were compared with penalties in terms of specificity and number needed to test.

Results

Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion “≥1 of the CS, or ≥2 of the EP” identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than “≥1 of the CS”, with only modest reduction in specificity (5.7%).

Conclusions

Broadening symptom criteria to include individuals with at least two of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time to detection, providing greater opportunities to prevent SARS-CoV-2 transmission.
Simultaneous measurement of inhaled air and exhaled breath by double multicapillary column ion-mobility spectrometry, a new method for breath analysis: results of a feasibility study
Authors: Westhoff Michael , Friedrich Maren , Baumbach Jörg I.
Published: November 2021

The high sensitivity of the methods applied in breath analysis entails a high risk of detecting analytes that do not derive from endogenous production. Consequentially, it appears useful to have knowledge about the composition of inhaled air and to include alveolar gradients into interpretation.

The current study aimed to standardise sampling procedures in breath analysis, especially with multicapillary column ion-mobility spectrometry (MCC-IMS), by applying a simultaneous registration of inhaled air and exhaled breath.

A “double MCC-IMS” device, which for the first time allows simultaneous analysis of inhaled air and exhaled breath, was developed and tested in 18 healthy individuals. For this, two BreathDiscovery instruments were coupled with each other.

Measurements of inhaled air and exhaled breath in 18 healthy individuals (mean age 46±10.9 years; nine men, nine women) identified 35 different volatile organic compounds (VOCs) for further analysis. Not all of these had positive alveolar gradients and could be regarded as endogenous VOCs: 16 VOCs had a positive alveolar gradient in mean; 19 VOCs a negative one. 12 VOCs were positive in >12 of the healthy subjects.

For the first time in our understanding, a method is described that enables simultaneous measurement of inhaled air and exhaled breath. This facilitates the calculation of alveolar gradients and selection of endogenous VOCs for exhaled breath analysis. Only a part of VOCs in exhaled breath are truly endogenous VOCs. The observation of different and varying polarities of the alveolar gradients needs further analysis.
Physiotherapy for large airway collapse: an ABC approach
Authors: Grillo Lizzie J.F. , Housley Georgie M. , Gangadharan Sidhu , Majid Adnan , Hull James H.
Published: November 2021

Large airway collapse (LAC) describes the phenomenon of excessive, abnormal, inward movement of the large airways (
i.e.
trachea and/or main bronchi and/or bronchus intermedius) occurring during the expiratory phase of the respiratory cycle. It is an increasingly well-recognised problem and a prevalent comorbidity in other chronic respiratory conditions (
e.g.
COPD and asthma). LAC is associated with pervasive respiratory features such as a barking cough, exertional dyspnoea and an increased propensity to lower respiratory tract infection. These symptoms are unpleasant, and patients are often limited in their daily life and their function. The pathophysiology of this condition impairs airway clearance and can cause breathlessness and exercise intolerance, due to a loss of airway patency during expiratory flow. Dysfunctional adaptations to breathing and coughing may further amplify symptoms.

This article provides, for the first time, clinically focused physiotherapeutic intervention advice based on our understanding of the pathophysiology of LAC, to support conservative management. It uses the available evidence from LAC, transferable evidence from other conditions and knowledge based on clinical experience. It proposes a practical “ABC model” to ensure physiotherapy assessment and treatments are centred around optimising three key clinical areas: Airways, including airway clearance and cough; Breathing, including breathlessness and breathing pattern; and Capacity for exercise, including an assessment of functional exercise ability.
Long-term bending properties of cross-laminated timber made from Japanese larch under constant environment
Authors: Takanashi Ryuya , Ohashi Yoshinori , Ishihara Wataru , Matsumoto Kazushige
Published: November 2021

Cross-laminated timber (CLT) has been used extensively in timber construction. CLT panels are typically used in roofs and floors that carry a continuous load, and it is important to examine the long-term loading capacity of CLT. However, studies that focus on the long-term loading capacity of CLT are limited. To this end, we conducted long-term out-of-plane bending tests on seven-layer CLT made from Japanese larch (Larix kaempferi) under constant environmental conditions, investigated creep performance and duration of load, and experimentally analyzed creep rupture behavior. The mean estimated relative creep after 50 years was 1.49. The sample showed a satisfactory resistance to creep as a building material. The duration of load of most of the specimens in this study was shorter than the conventional value of small clear wood specimens. Specimens had a lower duration of load capacity than solid lumber. According to the results of survival analysis, a loading level of 70% or more caused the initial failure of specimens. Creep rupture of most of the specimens occurred at less deflection than displacement at failure in the short-term loading test. Additional studies focusing on the effects of finger joints, transverse layers, and width of a specimen on creep rupture behavior are suggested.
Even experts cannot agree on the optimal use of platelet-rich plasma in lateral elbow tendinopathy: an international Delphi study
Authors: Evans Jonathan P. , Maffulli Nicola , Smith Chris , Watts Adam , Valderas Jose , Goodwin Vicki
Published: November 2021

Background

Platelet-rich plasma (PRP) is widely used in the management of lateral elbow tendinopathy (LET) despite conflicting evidence on its effectiveness. With high levels of user experience, this study aimed to assess consensus amongst experts on its clinical use.

Methods

A three-round international Delphi study was conducted. Participants were invited through national society mailing lists and contact lists derived from a systematic search of the literature on PRP. In round one, a primary working group developed 40 statements on PRP preparation and clinical application. In rounds two and three, an international group of researchers on PRP and clinical users of the device scored their levels of agreement with the statements on a five-point scale. Consensus was defined as an interquartile range of ≤ 1.

Results

Consensus of agreement was only reached for 17/40 (42.5%) statements. For statements on PRP formulation, consensus of agreement was reached in 2/6 statements (33%). Only limited consensus on the contraindications, delivery strategy and delivery technique was achieved.

Conclusion

Experts reached very limited consensus on the use of PRP in LET. High levels of user experience have not resulted in a convergence of opinion on the technical components of PRP formulation and delivery, substantiating the need for further studies and improved trial reporting.
Effect of increased positive end-expiratory pressure on intracranial pressure and cerebral oxygenation: impact of respiratory mechanics and hypovolemia
Authors: Chen Han , Zhou Xiao-Fen , Zhou Da-Wei , Zhou Jian-Xin , Yu Rong-Guo
Published: November 2021

Background

To evaluate the impact of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) in animals with different respiratory mechanics, baseline ICP and volume status.

Methods

A total of 50 male adult Bama miniature pigs were involved in four different protocols (n = 20, 12, 12, and 6, respectively). Under the monitoring of ICP, brain tissue oxygen tension and hemodynamical parameters, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O. Measurements were taken in pigs with normal ICP and normovolemia (Series I), or with intracranial hypertension (via inflating intracranial balloon catheter) and normovolemia (Series II), or with intracranial hypertension and hypovolemia (via exsanguination) (Series III). Pigs randomized to the control group received only hydrochloride instillation while the intervention group received additional chest wall strapping. Common carotid arterial blood flow before and after exsanguination at each PEEP level was measured in pigs with intracranial hypertension and chest wall strapping (Series IV).

Results

ICP was elevated by increased PEEP in both normal ICP and intracranial hypertension conditions in animals with normal blood volume, while resulted in decreased ICP with PEEP increments in animals with hypovolemia. Increasing PEEP resulted in a decrease in brain tissue oxygen tension in both normovolemic and hypovolemic conditions. The impacts of PEEP on hemodynamical parameters, ICP and brain tissue oxygen tension became more evident with increased chest wall elastance. Compare to normovolemic condition, common carotid arterial blood flow was further lowered when PEEP was raised in the condition of hypovolemia.

Conclusions

The impacts of PEEP on ICP and cerebral oxygenation are determined by both volume status and respiratory mechanics. Potential conditions that may increase chest wall elastance should also be ruled out to avoid the deleterious effects of PEEP.
Identification of novel QTL contributing to barley yellow mosaic resistance in wild barley (Hordeum vulgare spp. spontaneum)
Authors: Pan Yuhan , Zhu Juan , Hong Yi , Zhang Mengna , Lv Chao , Guo Baojian , Shen Huiquan , Xu Xiao , Xu Rugen
Published: November 2021

Background

Barley yellow mosaic disease (BYMD) caused by Barley yellow mosaic virus (BaYMV) and Barley mild mosaic virus (BaMMV) seriously threatens the production of winter barley. Cultivating and promoting varieties that carry disease-resistant genes is one of the most powerful ways to minimize the disease’s effect on yield. However, as the BYMD virus mutates rapidly, resistance conferred by the two cloned R genes to the virus had been overcome by new virus strains. There is an urgent need for novel resistance genes in barley that convey sustainable resistance to newly emerging virus strains causing BYMD.

Results

A doubled haploid (DH) population derived from a cross of SRY01 (BYMD resistant wild barley) and Gairdner (BYMD susceptible barley cultivar) was used to explore for QTL of resistance to BYMD in barley. A total of six quantitative trait loci (qRYM-1H, qRYM-2Ha, qRYM-2Hb, qRYM-3H, qRYM-5H, and qRYM-7H) related to BYMD resistance were detected, which were located on chromosomes 1H, 2H, 3H, 5H, and 7H. Both qRYM-1H and qRYM-2Ha were detected in all environments. qRYM-1H was found to be overlapped with rym7, a known R gene to the disease, whereas qRYM-2Ha is a novel QTL on chromosome 2H originated from SRY01, explaining phenotypic variation from 9.8 to 17.8%. The closely linked InDel markers for qRYM-2Ha were developed which could be used for marker-assisted selection in barley breeding. qRYM-2Hb and qRYM-3H were stable QTL for specific resistance to Yancheng and Yangzhou virus strains, respectively. qRYM-5H and qRYM-7H identified in Yangzhou were originated from Gairdner.

Conclusions

Our work is focusing on a virus disease (barley yellow mosaic) of barley. It is the first report on BYMD-resistant QTL from wild barley accessions. One novel major QTL (qRYM-2Ha) for the resistance was detected. The consistently detected new genes will potentially serve as novel sources for achieving pre-breeding barley materials with resistance to BYMD.
Instrumental variable estimation for a time-varying treatment and a time-to-event outcome via structural nested cumulative failure time models
Authors: Shi Joy , Swanson Sonja A. , Kraft Peter , Rosner Bernard , De Vivo Immaculata , Hernán Miguel A.
Published: November 2021

Background

In many applications of instrumental variable (IV) methods, the treatments of interest are intrinsically time-varying and outcomes of interest are failure time outcomes. A common example is Mendelian randomization (MR), which uses genetic variants as proposed IVs. In this article, we present a novel application of g-estimation of structural nested cumulative failure models (SNCFTMs), which can accommodate multiple measures of a time-varying treatment when modelling a failure time outcome in an IV analysis.

Methods

A SNCFTM models the ratio of two conditional mean counterfactual outcomes at time k under two treatment strategies which differ only at an earlier time m. These models can be extended to accommodate inverse probability of censoring weights, and can be applied to case-control data. We also describe how the g-estimates of the SNCFTM parameters can be used to calculate marginal cumulative risks under nondynamic treatment strategies. We examine the performance of this method using simulated data, and present an application of these models by conducting an MR study of alcohol intake and endometrial cancer using longitudinal observational data from the Nurses’ Health Study.

Results

Our simulations found that estimates from SNCFTMs which used an IV approach were similar to those obtained from SNCFTMs which adjusted for confounders, and similar to those obtained from the g-formula approach when the outcome was rare. In our data application, the cumulative risk of endometrial cancer from age 45 to age 72 under the “never drink” strategy (4.0%) was similar to that under the “always ½ drink per day” strategy (4.3%).

Conclusions

SNCFTMs can be used to conduct MR and other IV analyses with time-varying treatments and failure time outcomes.
A qualitative study of high-performing primary care practices during the COVID-19 pandemic
Authors: Albert Stephanie L. , Paul Margaret M. , Nguyen Ann M. , Shelley Donna R. , Berry Carolyn A.
Published: November 2021

Background

Primary care practices have remained on the frontline of health care service delivery throughout the COVID-19 pandemic. The purpose of our study was to understand the early pandemic experience of primary care practices, how they adapted care processes for chronic disease management and preventive care, and the future potential of these practices’ service delivery adaptations.

Methods

We interviewed 44 providers and staff at 22 high-performing primary care practices located throughout the United States between March and May 2020. Interviews were transcribed and coded using a modified rapid assessment process due to the time-sensitive nature of the study.

Results

Practices reported employing a variety of adaptations to care during the COVID-19 pandemic including maintaining safe and socially distanced access through increased use of telehealth visits, using disease registries to identify and proactively outreach to patients, providing remote patient education, and incorporating more home-based monitoring into care. Routine screening and testing slowed considerably, resulting in concerns about delayed detection. Patients with fewer resources, lower health literacy, and older adults were the most difficult to reach and manage during this time.

Conclusion

Our findings indicate that primary care structures and processes developed for remote chronic disease management and preventive care are evolving rapidly. Emerging adapted care processes, most notably remote provision of care, are promising and may endure beyond the pandemic, but issues of equity must be addressed (e.g., through payment reform) to ensure vulnerable populations receive the same benefit.
Epidemic size, trend and spatiotemporal mapping of SARS-CoV-2 using geographical information system in Alborz Province, Iran
Authors: Kabir Kourosh , Taherinia Ali , Ashourloo Davoud , Khosravi Ahmad , Karim Hossien , Salehi Shahrabi Hamid , Hedayat Yaghoobi Mojtaba , Soleimani Alireza , Siami Zaynab , Noorisepehr Mohammad , Tajbakhsh Ramin , Maghsoudi Mohammad Reza , Lak Mehran , Mardi Parham , Nouri Behnaz , Mohammadzadeh Mohammad , Azimzadeh Mehdi , Bakhtiyari Mahmood
Published: November 2021

Background

The first confirmed cases of COVID-19 in Iran were reported in Qom city. Subsequently, the neighboring provinces and gradually all 31 provinces of Iran were involved. This study aimed to investigate the case fatility rate, basic reproductive number in different period of epidemic, projection of daily and cumulative incidence cases and also spatiotemporal mapping of SARS-CoV-2 in Alborz province, Iran.

Methods

A confirmed case of COVID-19 infection was defined as a case with a positive result of viral nucleic acid testing in respiratory specimens. Serial interval (SI) was fitted by gamma distribution and considered the likelihood-based R0 using a branching process with Poisson likelihood. Seven days average of cases, deaths, doubling times and CFRs used to draw smooth charts. kernel density tool in Arc GIS (Esri) software has been employed to compute hot spot area of the study site.

Results

The maximum-likelihood value of R0 was 2.88 (95%, CI: 2.57–3.23) in the early 14 days of epidemic. The case fatility rate for Alborz province (Iran) on March 10, was 8.33% (95%, CI:6.3–11), and by April 20, it had an increasing trend and reached 12.9% (95%,CI:11.5–14.4). The doubling time has been increasing from about two days and then reached about 97 days on April 20, 2020, which shows the slowdown in the spread rate of the disease. Also, from March 26 to April 2, 2020 the whole Geographical area of Karj city was almost affected by SARS-CoV-2.

Conclusions

The R0 of COVID-19 in Alborz province was substantially high at the beginning of the epidemic, but with preventive measures and public education and GIS based monitoring of the cases,it has been reduced to 1.19 within two months. This reduction highpoints the attainment of preventive measures in place, however we must be ready for any second epidemic waves during the next months.
Automatic differentiation of thyroid scintigram by deep convolutional neural network: a dual center study
Authors: Yang Pei , Pi Yong , He Tao , Sun Jiangming , Wei Jianan , Xiang Yongzhao , Jiang Lisha , Li Lin , Yi Zhang , Zhao Zhen , Cai Huawei
Published: November 2021

Background

99mTc-pertechnetate thyroid scintigraphy is a valid complementary avenue for evaluating thyroid disease in the clinic, the image feature of thyroid scintigram is relatively simple but the interpretation still has a moderate consistency among physicians. Thus, we aimed to develop an artificial intelligence (AI) system to automatically classify the four patterns of thyroid scintigram.

Methods

We collected 3087 thyroid scintigrams from center 1 to construct the training dataset (n = 2468) and internal validating dataset (n = 619), and another 302 cases from center 2 as external validating datasets. Four pre-trained neural networks that included ResNet50, DenseNet169, InceptionV3, and InceptionResNetV2 were implemented to construct AI models. The models were trained separately with transfer learning. We evaluated each model’s performance with metrics as following: accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), recall, precision, and F1-score.

Results

The overall accuracy of four pre-trained neural networks in classifying four common uptake patterns of thyroid scintigrams all exceeded 90%, and the InceptionV3 stands out from others. It reached the highest performance with an overall accuracy of 92.73% for internal validation and 87.75% for external validation, respectively. As for each category of thyroid scintigrams, the area under the receiver operator characteristic curve (AUC) was 0.986 for ‘diffusely increased,’ 0.997 for ‘diffusely decreased,’ 0.998 for ‘focal increased,’ and 0.945 for ‘heterogeneous uptake’ in internal validation, respectively. Accordingly, the corresponding performances also obtained an ideal result of 0.939, 1.000, 0.974, and 0.915 in external validation, respectively.

Conclusions

Deep convolutional neural network-based AI model represented considerable performance in the classification of thyroid scintigrams, which may help physicians improve the interpretation of thyroid scintigrams more consistently and efficiently.
Non-invasive fetal electrocardiography, electrohysterography and speckle-tracking echocardiography in the second trimester: study protocol of a longitudinal prospective cohort study (BEATS-study)
Authors: Nichting T. J. , Frenken M. W. E. , van der Woude D. A. A. , van Oostrum N. H. M. , de Vet C. M. , van Willigen B. G. , van Laar J. O. E. H. , van der Ven M. , Oei S. G.
Published: November 2021

Background

Worldwide, hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR) and preterm birth remain the leading causes of maternal and fetal pregnancy-related mortality and (long-term) morbidity. Fetal cardiac deformation changes can be the first sign of placental dysfunction, which is associated with HDP, FGR and preterm birth. In addition, preterm birth is likely associated with changes in electrical activity across the uterine muscle. Therefore, fetal cardiac function and uterine activity can be used for the early detection of these complications in pregnancy. Fetal cardiac function and uterine activity can be assessed by two-dimensional speckle-tracking echocardiography (2D-STE), non-invasive fetal electrocardiography (NI-fECG), and electrohysterography (EHG). This study aims to generate reference values for 2D-STE, NI-fECG and EHG parameters during the second trimester of pregnancy and to investigate the diagnostic potential of these parameters in the early detection of HDP, FGR and preterm birth.

Methods

In this longitudinal prospective cohort study, eligible women will be recruited from a tertiary care hospital and a primary midwifery practice. In total, 594 initially healthy pregnant women with an uncomplicated singleton pregnancy will be included. Recordings of NI-fECG and EHG will be made weekly from 22 until 28 weeks of gestation and 2D-STE measurements will be performed 4-weekly at 16, 20, 24 and 28 weeks gestational age. Retrospectively, pregnancies complicated with pregnancy-related diseases will be excluded from the cohort. Reference values for 2D-STE, NI-fECG and EHG parameters will be assessed in uncomplicated pregnancies. After, 2D-STE, NI-fCG and EHG parameters measured during gestation in complicated pregnancies will be compared with these reference values.

Discussion

This will be the a large prospective study investigating new technologies that could potentially have a high impact on antepartum fetal monitoring.

Trial registration

Registered on 26 March 2020 in the Dutch Trial Register (NL8769) via https://www.trialregister.nl/trials and registered on 21 October 2020 to the Central Committee on Research Involving Human Subjects (NL73607.015.20) via https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm.
Effect of self-regulatory behaviour change techniques and predictors of physical activity maintenance in cancer survivors: a 12-month follow-up of the Phys-Can RCT
Authors: Mazzoni Anne-Sophie , Brooke Hannah L. , Berntsen Sveinung , Nordin Karin , Demmelmaier Ingrid
Published: November 2021

Background

Current knowledge about the promotion of long-term physical activity (PA) maintenance in cancer survivors is limited. The aims of this study were to 1) determine the effect of self-regulatory BCTs on long-term PA maintenance, and 2) identify predictors of long-term PA maintenance in cancer survivors 12 months after participating in a six-month exercise intervention during cancer treatment.

Methods

In a multicentre study with a 2 × 2 factorial design, the Phys-Can RCT, 577 participants with curable breast, colorectal or prostate cancer and starting their cancer treatment, were randomized to high intensity exercise with or without self-regulatory behaviour change techniques (BCTs; e.g. goal-setting and self-monitoring) or low-to-moderate intensity exercise with or without self-regulatory BCTs. Participants’ level of PA was assessed at the end of the exercise intervention and 12 months later (i.e. 12-month follow-up), using a PA monitor and a PA diary. Participants were categorized as either maintainers (change in minutes/week of aerobic PA ≥ 0 and/or change in number of sessions/week of resistance training ≥0) or non-maintainers. Data on potential predictors were collected at baseline and at the end of the exercise intervention. Multiple logistic regression analyses were performed to answer both research questions.

Results

A total of 301 participants (52%) completed the data assessments. A main effect of BCTs on PA maintenance was found (OR = 1.80, 95%CI [1.05–3.08]) at 12-month follow-up. Participants reporting higher health-related quality-of-life (HRQoL) (OR = 1.03, 95%CI [1.00–1.06] and higher exercise motivation (OR = 1.02, 95%CI [1.00–1.04]) at baseline were more likely to maintain PA levels at 12-month follow-up. Participants with higher exercise expectations (OR = 0.88, 95%CI [0.78–0.99]) and a history of tobacco use at baseline (OR = 0.43, 95%CI [0.21–0.86]) were less likely to maintain PA levels at 12-month follow-up. Finally, participants with greater BMI increases over the course of the exercise intervention (OR = 0.63, 95%CI [0.44–0.90]) were less likely to maintain their PA levels at 12-month follow-up.

Conclusions

Self-regulatory BCTs improved PA maintenance at 12-month follow-up and can be recommended to cancer survivors for long-term PA maintenance. Such support should be considered especially for patients with low HRQoL, low exercise motivation, high exercise expectations or with a history of tobacco use at the start of their cancer treatment, as well as for those gaining weight during their treatment. However, more experimental studies are needed to investigate the efficacy of individual or combinations of BCTs in broader clinical populations.

Trial registration

NCT02473003 (10/10/2014).
The effect of hypoxia on PD-L1 expression in bladder cancer
Authors: Smith Vicky , Mukherjee Debayan , Lunj Sapna , Choudhury Ananya , Hoskin Peter , West Catharine , Illidge Tim
Published: November 2021

Introduction

Recent data has demonstrated that hypoxia drives an immunosuppressive tumour microenvironment (TME) via various mechanisms including hypoxia inducible factor (HIF)-dependent upregulation of programmed death ligand 1 (PD-L1). Both hypoxia and an immunosuppressive TME are targetable independent negative prognostic factors for bladder cancer. Therefore we sought to investigate whether hypoxia is associated with upregulation of PD-L1 in the disease.

Materials and methods

Three human muscle-invasive bladder cancer cell lines (T24, J82, UMUC3) were cultured in normoxia (20% oxygen) or hypoxia (1 and 0.1% oxygen) for 24 h. Differences in PD-L1 expression were measured using Western blotting, quantitative polymerase chain reaction (qPCR) and flow cytometry (≥3 independent experiments). Statistical tests performed were unpaired t tests and ANOVA. For in silico work an hypoxia signature was used to apply hypoxia scores to muscle-invasive bladder cancers from a clinical trial (BCON; n = 142) and TCGA (n = 404). Analyses were carried out using R and RStudio and statistical tests performed were linear models and one-way ANOVA.

Results

When T24 cells were seeded at < 70% confluence, there was decreased PD-L1 protein (p = 0.009) and mRNA (p < 0.001) expression after culture in 0.1% oxygen. PD-L1 protein expression decreased in both 0.1% oxygen and 1% oxygen in a panel of muscle-invasive bladder cancer cells: T24 (p = 0.009 and 0.001), J82 (p = 0.008 and 0.013) and UMUC3 (p = 0.003 and 0.289). Increasing seeding density decreased PD-L1 protein (p < 0.001) and mRNA (p = 0.001) expression in T24 cells grown in both 20 and 1% oxygen. Only when cells were 100% confluent, were PD-L1 protein and mRNA levels higher in 1% versus 20% oxygen (p = 0.056 and p = 0.037). In silico analyses showed a positive correlation between hypoxia signature scores and PD-L1 expression in both BCON (p = 0.003) and TCGA (p < 0.001) cohorts, and between hypoxia and IFNγ signature scores (p < 0.001 for both).

Conclusion

Tumour hypoxia correlates with increased PD-L1 expression in patient derived bladder cancer tumours. In vitro PD-L1 expression was affected by cell density and decreased PD-L1 expression was observed after culture in hypoxia in muscle-invasive bladder cancer cell lines. As cell density has such an important effect on PD-L1 expression, it should be considered when investigating PD-L1 expression in vitro.
Mental health professionals’ perceived barriers and enablers to shared decision-making in risk assessment and risk management: a qualitative systematic review
Authors: Ahmed Nafiso , Barlow Sally , Reynolds Lisa , Drey Nicholas , Begum Fareha , Tuudah Elizabeth , Simpson Alan
Published: November 2021

Background

Risk assessment and risk management are fundamental processes in the delivery of safe and effective mental health care, yet studies have shown that service users are often not directly involved or are unaware that an assessment has taken place. Shared decision-making in mental health systems is supported by research and advocated in policy. This systematic review (PROSPERO: CRD42016050457) aimed to explore the perceived barriers and enablers to implementing shared decision-making in risk assessment and risk management from mental health professionals’ perspectives.

Methods

PRISMA guidelines were followed in the conduct and reporting of this review. Medline, CINAHL, EMBASE, PsycINFO, AMED and Internurse were systematically searched from inception to December 2019. Data were mapped directly into the Theoretical Domains Framework (TDF), a psychological framework that includes 14 domains relevant to behaviour change. Thematic synthesis was used to identify potential barriers and enablers within each domain. Data were then matched to the three components of the COM-B model: Capability, Opportunity, and Motivation.

Results

Twenty studies met the eligibility criteria. The findings of this review indicate that shared decision-making is not a concept commonly used in mental health services when exploring processes of risk assessment and risk management. The key barriers identified were ‘power and best interest’ (social influences) and ‘my professional role and responsibility’ (social/professional role and identity). Key enablers were ‘therapeutic relationship’ (social influences) and ‘value collaboration’ (reinforcement). The salient barriers, enablers and linked TDF domains matched COM-B components ‘opportunity’ and ‘motivation’.

Conclusion

The review highlights the need for further empirical research to better understand current practice and mental health professionals’ experiences and attitudes towards shared decision-making in risk assessment and risk management.
Determining what constitutes an effective psychosocial ‘return to work’ intervention: a systematic review and narrative synthesis
Authors: Venning Anthony , Oswald Tassia K. , Stevenson Jeremy , Tepper Nicci , Azadi Leva , Lawn Sharon , Redpath Paula
Published: November 2021

Purpose

Work can offer a myriad of social and health benefits. Long-term sick leave can be detrimental to employers, individuals, families, and societies. The burden of long-term sick leave has motivated the development of return to work (RTW) interventions. This study sought to determine what constitutes an effective psychosocial RTW intervention, which included exploring whether the level of intervention intensity and intervention characteristics matter to RTW outcomes.

Methods

A systematic review and narrative synthesis were undertaken. Studies were identified through six databases (Ovid Medline, CINAHL (EBSCOhost), PsycInfo (Ovid), ProQuest, Scopus, and Google Scholar) between 2011 and 3 September 2019. Randomised controlled trials (RCTs) or reviews published in English were eligible for inclusion if they targeted adults who were on sick leave/unemployed trying to return to full-capacity employment, had at least one structured psychosocial RTW intervention, and assessed RTW. Study quality was assessed using checklists from the Joanna Briggs Institute.

Results

Database searching yielded 12,311 records. Eighteen RCTs (comprising 42 intervention/comparison groups), seven reviews (comprising 153 studies), and five grey literature documents were included. Included studies were of moderate-to-high quality. Research was primarily conducted in Europe and focused on psychological or musculoskeletal problems. RTW outcomes included RTW status, time until RTW, insurance claims, and sick days. Participating in a RTW program was superior to care-as-usual. RTW outcomes were similar between diverse interventions of low, moderate, and high intensity. Common foundational characteristics seen across effective RTW interventions included a focus on RTW, psychoeducation, and behavioural activation.

Conclusions

Evidence suggests that a low intensity approach to RTW interventions may be an appropriate first option before investment in high intensity, and arguably more expensive interventions, as the latter appear to provide limited additional benefit. More high-quality RCTs, from diverse countries, are needed to provide stronger evidence.
Immune infiltration landscape and immune-marker molecular typing of pulmonary fibrosis with pulmonary hypertension
Authors: Cai Haomin , Liu Hongcheng
Published: November 2021

Background

Pulmonary arterial hypertension (PH) secondary to pulmonary fibrosis (PF) is one of the most common complications in PF patients, it causes severe disease and usually have a poor prognosis. Whether the combination of PH and PF is a unique disease phenotype is unclear. We aimed to screen the key modules associated with PH–PF immune infiltration based on WGCNA and identify the hub genes for molecular typing.

Method

Using the gene expression profile GSE24988 of PF patients with or without PH from the Gene Expression Omnibus (GEO) database, we evaluated immune cell infiltration using Cibersortx and immune cell gene signature files. Different immune cell types were screened using the Wilcoxon test; differentially expressed genes were screened using samr. The molecular pathways implicated in these differential responses were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses. A weighted co-expression network of the differential genes was constructed, relevant co-expression modules were identified, and relationships between modules and differential immune cell infiltration were calculated. The modules most relevant to this disease were identified using weighted correlation network analysis. From these, we constructed a co-expression network; using the STRING database, we integrated the values into the human protein–protein interaction network before constructing a co-expression interaction subnet, screening genes associated with immunity and unsupervised molecular typing, and analyzing the immune cell infiltration and expression of key genes in each disease type.

Results

Of the 22 immune cell types from the PF GEO data, 20 different immune cell types were identified. There were 1622 differentially expressed genes (295 upregulated and 1327 downregulated). The resulting weighted co-expression network identified six co-expression modules. These were screened to identify the modules most relevant to the disease phenotype (the green module). By calculating the correlations between modules and the differentially infiltrated immune cells, extracting the green module co-expression network (46 genes), extracting 25 key genes using gene significance and module-membership thresholds, and combining these with the 10 key genes in the human protein–protein interaction network, we identified five immune cell-related marker genes that might be applied as biomarkers. Using these marker genes, we evaluated these disease samples using unsupervised clustering molecular typing.

Conclusion

Our results demonstrated that all PF combined with PH samples belonged to four categories. Studies on the five key genes are required to validate their diagnostic and prognostic value.
Individualized 3D printing-assisted repair and reconstruction of neoplastic bone defects at irregular bone sites: exploration and practice in the treatment of scapular aneurysmal bone cysts
Authors: Luo Guochen , Zhang Yao , Wang Xiahua , Chen Shuaishuai , Li Dongyi , Yu Mingyang
Published: November 2021

Background

The irregular anatomical shape and complex structures of irregular bones make it more difficult to repair and reconstruct bone defects in irregular bones than in the long bones of the extremities. Three-dimensional (3D) printing technology can help to overcome the technical limitations of irregular bone repair by generating simulations that enable structural integration of the lesion area and bone structure of the donor site in all directions and at multiple angles. Thus, personalized and accurate treatment plans for restoring anatomical structure, muscle attachment points, and maximal function can be made. The present study aimed to investigate the ability of 3D printing technology to assist in the repair and reconstruction of scapular aneurysmal ABC defects.

Methods

The study included seven patients with ABCs of the scapula. Based on computed tomography (CT) data for the patient, the scapula (including the defect) and pelvis were reconstructed using Mimics Medical software. The reconstructed scapula model was printed using a 3D printer. Before the operation, the model was used to design the surgical approach and simulate the operation process, to determine the length and radius of the plate and the number and direction of screws, and to determine the bone mass of the ilium and develop reasonable strategies for segmentation and distribution. The operation time, amount of bleeding, length and radius of the plate, and direction and number of screws were recorded.

Results

The average duration of follow-up was 25.6 months, and none of the seven patients experienced recurrence during the follow-up period. The surgical approach, the length and radius of internal fixation, and the number and direction of screws were consistent with the designed operation plan. Patients gradually recovered the anatomical structure of the scapula and function of the shoulder joint.

Conclusions

In the treatment of bone defects caused by irregular bone tumors, 3D printing technology combined with surgery has the advantages of less trauma, short operation time, less bleeding and reducing the difficulty of operation, which can reduce the waste of bone graft, and more complete reconstruction of the anatomical structure of the defective bone.
Exploring healthcare staff narratives to understand the role of quality improvement methods in innovative practices during COVID-19
Authors: Khurshid Zuneera , McAuliffe Eilish , De Brún Aoife
Published: November 2021

Background

COVID-19 has impacted the context in which healthcare staff and teams operate and this has implications for quality improvement (QI) work. Contrary to the usual ambivalent relationship staff have with QI work, there have been examples of unprecedented staff engagement in implementing rapid changes during the pandemic indicating a change in important underlying factors that impact staff involvement in QI. The purpose of this study is to explore staff perspectives about how experience and skills of QI methods supported them in implementing innovative practices during COVID-19.

Methods

This is a qualitative narrative study based on narrative interviews to collect healthcare staff stories of implementing rapid change. The stories were identified through social media (Twitter) and a national health magazine issued by the Irish health service. Twenty staff members participated in the interviews. Interviews were audio recorded, transcribed, and anonymised. A four-step thematic analysis was conducted.

Results

The analysis revealed the transformational journey of healthcare staff from the initial shock and anxiety caused by COVID-19 to making sense of the situation, implementing rapid changes, and acknowledging COVID as a learning experience. Six themes were evident from the analysis: COVID anxiety and fear, emotional supports and coping mechanisms, person-centric changes, COVID as a ‘forcing function’ for change, a collective way of working and looking back and thinking ahead.

Conclusions

While most rapid changes during COVID-19 did not represent a systematic and explicit QI application, QI principles were evident throughout the stories and actions taken, including making small changes, testing changes, learning, reflecting as a team, and improving. Many staff members were able to retrospectively identify the relevance of QI principles. COVID-19 eliminated some traditional barriers to change leading to efficient solutions, thus highlighting a need to sustain these positive changes into routine practice to develop an adaptive healthcare system receptive to QI.
Effect of blood lipid variability on mortality in patients with type 2 diabetes: a large single-center cohort study
Authors: Wang Mu-Cyun , Li Chia-Ing , Liu Chiu-Shong , Lin Chih-Hsueh , Yang Shing-Yu , Li Tsai-Chung , Lin Cheng-Chieh
Published: November 2021

Background

Dyslipidemia is a major cardiovascular risk factor and common in diabetes patients. Most guidelines focus on optimal lipid levels, while variation of lipid profiles is far less discussed. This study aims to investigate the association of visit-to-visit variability in blood lipids with all-cause, cardiovascular, and non-cardiovascular mortality in patients with type 2 diabetes.

Methods

We identified 10,583 type 2 diabetes patients aged ≥ 30 years with follow-up ≥ 3 years and who participated in the Diabetes Care Management Program at a medical center in Taiwan. Variability in lipid profiles within 3 years after entry was calculated using coefficient of variation. Cox proportional hazard models were used to evaluate lipid variability in relation to subsequent mortality.

Results

Over a mean follow-up of 6.4 years, 1838 all-cause deaths (809 cardiovascular deaths) were observed. For each 10% increase in variability in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol, the hazard ratios (95% confidence intervals) of all-cause mortality were 1.30 (1.22–1.37), 1.05 (1.01–1.09), and 1.10 (1.03–1.16), respectively; those of cardiovascular mortality were 1.27 (1.16–1.39), 1.08 (1.02–1.15), and 1.16 (1.07–1.27), respectively. Each 10% increase in high-density lipoprotein cholesterol variability conveyed 31% greater risk of non-cardiovascular mortality. High variability in total cholesterol and low-density lipoprotein cholesterol increased all-cause mortality in subgroups of nonsmoking, regular exercising, non-dyslipidemia, and more severe status of diabetes at baseline.

Conclusions

Blood lipid variability except for triglyceride variability was associated with all-cause and cardiovascular mortality in patients with type 2 diabetes.
Characterization of a novel glucocorticoid-resistant human B-cell acute lymphoblastic leukemia cell line, with AMPK, mTOR and fatty acid synthesis pathway inhibition
Authors: Li Yuanyuan , Zuo Chuan , Gu Ling
Published: November 2021

Background

Acquired glucocorticoid (GC) resistance remains the main obstacle in acute lymphoblastic leukemia (ALL) therapy. The aim of the present study was to establish a novel GC-resistant B-ALL cell line and investigate its biological characteristics.

Methods

A cell culture technique was used to establish the GC-resistant cell line from the parental cell, NALM-6. Molecular and cellular biological techniques including flow cytometry, MTT assay, western blotting, DNA fingerprinting analysis and whole transcriptome sequencing (WTS) were used to characterize the GC-resistant cell lines. Nude mice were used for xenograft studies.

Results

The GC-resistant cell line, NALM-6/HDR, was established by culturing NALM-6 cells under hypoxia for 5 weeks with a single dexamethasone (Dex) treatment. We subcloned the NALM-6/HDR cell lines, and got 6 monoclone Dex-resistant cell lines, NALM-6/HDR-C1, C3, C4, C5, C6 and C9 with resistance index (RI) ranging from 20,000–50,000. NALM-6/HDR and its monoclone cell line, NALM-6/HDR-C5, exhibited moderate (RI 5–15) to high resistance (RI > 20) to Ara-c; low or no cross-resistance to L-Asp, VCR, DNR, and MTX (RI < 5). STR analysis confirmed that NALM-6/HDR and NALM-6/H were all derived from NALM-6. All these cells derived from NALM-6 showed similar morphology, growth curves, immunophenotype, chromosomal karyotype and tumorigenicity. WTS analysis revealed that the main metabolic differences between NALM-6 or NALM-6/H (GC-sensitive) and NALM-6/HDR (GC-resistant) were lipid and carbohydrates metabolism. Western blotting analysis showed that NALM-6/HDR cells had a low expression of GR and p-GR. Moreover, AMPK, mTORC1, glycolysis and de novo fatty acid synthesis (FAS) pathway were inhibited in NALM-6/HDR when compared with NALM-6.

Conclusions

NALM-6/HDR cell line may represent a subtype of B-ALL cells in patients who acquired GC and Ara-c resistance during the treatment. These patients may get little benefit from the available therapy target of AMPK, mTORC1, glycolysis and FAS pathway.