bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding genotypic and phenotypic spectrums of LTBP3 variants in dental anomalies and short stature syndrome
Authors: Kantaputra Piranit , Guven Yeliz , Kalayci Tugba , Özer Pelin Karaca , Panyarak Wannakamon , Intachai Worrachet , Olsen Bjorn , Carlson Bruce M. , Praditsap Oranud , Tongsima Sissades , Ngamphiw Chumpol , Jatooratthawichot Peeranat , Tucker Abigail S. , Ketudat Cairns James R.
Published: March 2022

Mutations in LTBP3 are associated with Dental Anomalies and Short Stature syndrome (DASS; MIM 601216), which is characterized by hypoplastic type amelogenesis imperfecta, hypodontia, underdeveloped maxilla, short stature, brachyolmia, aneurysm and dissection of the thoracic aorta. Here we report a novel (p.Arg545ProfsTer22) and a recurrent (c.3107‐2A > G) LTBP3 variants, in a Turkish family affected with DASS. The proband, who carried compound heterozygous variant c.3107‐2A > G, p.Arg545ProfsTer22, was most severely affected with DASS. The proband's father, who carried the heterozygous variant c.3107‐2A > G had short stature and prognathic mandible. The mother and brother of the proband carried the heterozygous variant p.Arg545ProfsTer22, but only the mother showed any DASS characteristics. The c.3107‐2A > G and the p.Arg545ProfsTer22 variants are expected to result in abnormal LTPB3 protein, failure of TGFβ‐LAP‐LTBP3 complex formation, and subsequent disruption of TGFβ secretion and activation. This is the first report of heterozygous carriers of LTBP3 variants showing phenotypes. The new findings of DASS found in this family include taurodontism, single‐rooted molars, abnormal dentin, calcified dental pulp blood vessels, prognathic mandible, failure of mandibular tooth eruption, interatrial septal aneurysm, secundum atrial septal defect, tricuspid valve prolapse, and a recurrent glenohumeral joint dislocation.
The relationship between occupational dust exposure and incidence of diabetes in male workers: A retrospective cohort study
Authors: Yun Byungyoon , Sim Juho , Lee Seunghyun , Cho Ara , Oh Juyeon , Kim Seunghan , Yoon Jin‐Ha
Published: March 2022

Aim

Previous studies have focused on the association between ambient particulate matter and diabetes. However, the relationship between subacute exposure to occupational dust and diabetes has not been explored. We aimed to assess this relationship.

Methods

Men who worked in dust‐related process factories between January 2013 and December 2017 were recruited from a Korea Health Worker Examination Common Data Model cohort. A history of physician‐diagnosed diabetes, use of an anti‐diabetic drug, or a fasting blood glucose level of ≥7 mmol/L were considered the criteria to diagnose diabetes. Multivariable time‐dependent Cox analysis estimated hazard ratios (HRs) and 95% CIs for incident diabetes associated with exposure to occupational dust exposure; interactions with lifestyle factors were analysed. Sensitivity analyses used propensity score matching and landmark analysis.

Results

Among 5141 male participants (median follow‐up duration, 3.85 years), 349 participants had diabetes. Occupational dust exposure was related to an increased risk of diabetes in the time‐dependent Cox analysis (entire cohort: HR 1.66 [95% CI 1.25–2.19], matched cohort: HR 1.65 [95% CI 1.22–2.24]). The findings showed the same direction in the landmark analysis (HR 1.42 [95% CI 1.01–1.99]).

Conclusions

A significant relationship exists between occupational dust exposure and increased risk of diabetes in male workers. Further studies should be conducted to confirm that occupational dust exposure is a possible risk factor for diabetes.
Climate change disclosure and the promise of response‐ability and transparency: A synthesizing framework and future research agenda
Authors: Shui Xiaolong , Zhang Minhao , Smart Palie
Published: March 2022

This paper systematically reviews the burgeoning but fragmented body of literature on climate change disclosure in the first two decades of the 21st century. Although there is an increasing trend for organizations to engage in climate change disclosure, the level of transparency, which is the key to allowing organizations to be responsible and accountable, varies significantly. We have synthesized current research findings on disclosure practice, antecedents, and outcomes into an integrative framework. In light of this framework, a more theoretically informed construct of carbon transparency is introduced in this review paper. We further highlight some research gaps supplementing with promising theorizing opportunities to encourage future works that can go beyond the extant scope of inquiry. Given the urgency of the current carbon budget, more studies are encouraged to examine the mechanism under which carbon transparency can lead to enhanced carbon performance in addressing climate change at the micro‐organization level.
Classroom Design and Children's Attention Allocation: Beyond the Laboratory and into the Classroom
Authors: Godwin Karrie E. , Leroux Audrey J. , Scupelli Peter , Fisher Anna V.
Published: March 2022

Prior laboratory research suggests the visual environment can be a source of distraction for children, reducing attention to instructional tasks and learning outcomes. However, systematic research examining how the visual environment relates to attention in genuine classrooms is rare. In addition, it is unknown what specific aspects of the environment pose a challenge for attention regulation. This observational study aims to (1) provide a nuanced examination of specific elements of the classroom visual environment (e.g., visual noise, display quantity, color variability) by analyzing panoramic classroom photographs (N = 58) and (2) investigate whether specific visual environment elements are related to children's rates of on‐task behavior. Results indicate on‐task behavior was lower in classrooms containing greater quantities of visual noise and color variability, and in classrooms with either relatively small or large amounts of displays (controlling for observation session, school type, student gender, grade‐level, and instructional format). Implications for creating more optimal visual learning environments are discussed.
What type of face mask should we choose in coronavirus disease 2019 pandemic considering photoprotective effectiveness?
Authors: Park Sung Jin , Cho Jun Hyuk , Ham Min Seok , Seo Soo Hong , Ahn Hyo Hyun , Kim Dai Hyun
Published: March 2022

Background

Wearing a face mask is one of the most effective personal protective strategies to diminish the spread of coronavirus disease 2019 (COVID‐19). Several dermatological outcomes were reported because of the prolonged use of face masks, especially due to the constant mask‐on policy, but the photoprotective effect of face masks has received less attention.

Objective

The aim of this study was to provide guidance in the use of face masks by comparing the photoprotective effects of routinely used masks.

Methods

A total of 12 frequently used face masks were tested, including certified respirators, Korea filter (KF)94, KF‐anti‐droplet (KF‐AD), and KF80. The amount of light that penetrates each face mask was measured using a light sensor that can quantify Ultraviolet A (UVA), visible light (VL), and infrared A (IR‐A) rays.

Results

Black‐colored KF94 masks and surgical masks reduced penetration of UVA, VL, and IR‐A by approximately 100%. The UVA penetration decreased on average by 95.51%, 90.97%, 85.06%, and 86.41% with white‐colored KF94, KF‐AD, KF80, and surgical masks, respectively. The VL and IR‐A were blocked by approximately 75.58%, 66.16%, 59.18%, and 64.48% with white‐colored KF94, KF‐AD, KF80, and surgical masks, respectively.

Conclusion

In conclusion, the different photoprotective effectiveness of face masks was mainly determined by colors, and therefore, black‐colored, multi‐layered respirators can be recommended in terms of photoprotection in the COVID‐19 pandemic. The quantified comparative results will be helpful to the person with pre‐existing photo‐aggravated dermatosis, especially in the season of the high intensity of sunlight.
Influence of narrow‐band ultraviolet B therapy on sirtuin 1 expression in lesional skin of patients with chronic plaque psoriasis: Relation to clinical improvement and interferon‐γ expression
Authors: Eid Amira Abulfotooh , Aly Rania Gaber , Elkholy Shaimaa Abd Elkarim , Sorour Osama Ahmed
Published: March 2022

Background

Reduced sirtuin 1 (Sirt1) expression in psoriasis was previously reported, and its activation was associated with disease improvement. Narrow‐band ultraviolet B (NB‐UVB) downregulates several pro‐inflammatory cytokines such as interferon‐γ (IFN‐γ) and influences keratinocyte differentiation in psoriasis.

Objectives

The aim of this study was to study the in vivo influence NB‐UVB treatment on Sirt1 expression in psoriatic skin in relation to disease improvement and IFN‐γ expression.

Methods

Twenty‐six patients with chronic plaque psoriasis were evaluated, and psoriasis area severity index (PASI) was calculated. Skin biopsies were taken from lesional skin of the patients before and after 3 months of treatment with NB‐UVB and from 26 controls, where the distribution and immunohistochemistry (IHC) scores of Sirt1 and IFN‐γ were determined.

Results

After 3 months of treatment, Sirt1 distribution and epidermal IHC score were significantly higher, whereas Sirt1 dermal IHC score and IFN‐γ distribution, epidermal and dermal IHC scores were significantly lower than the pre‐treatment values. Before and after 3 months of NB‐UVB therapy, PASI showed a significant negative correlation with Sirt1 distribution and epidermal IHC score; and a significant positive correlation with interferon‐γ distribution and epidermal IHC score. Moreover, Sirt1 distributions were negatively correlated with the corresponding interferon‐γ distributions.

Conclusions

The detected upregulation of epidermal Sirt1 following NB‐UVB therapy possibly represents another mechanism by which NB‐UVB can act in psoriasis and also highlights the role of Sirt1 upregulation in psoriasis treatment.
Epistemic entitlement, epistemic risk and leaching
Authors: Moretti Luca , Wright Crispin
Published: March 2022

One type of argument to sceptical paradox proceeds by making a case that a certain kind of metaphysically “heavyweight” or “cornerstone” proposition is beyond all possible evidence and hence may not be known or justifiably believed. Crispin Wright has argued that we can concede that our rational acceptance of these propositions is evidentially risky though we still remain rationally entitled to those of our ordinary knowledge claims that are seemingly threatened by that concession. A problem for Wright's proposal is the so‐called Leaching Worry: if we are merely rationally entitled to accept the cornerstones without evidence, how can we achieve evidence‐based knowledge of the multitude of quotidian propositions that we think we know, which require the cornerstones to be true? This paper presents a rigorous, novel explication of this worry within a Bayesian framework, and offers the Epistemic Entitlement theorist two distinct responses.
Coordination of autonomic and endocrine stress responses to the Trier Social Stress Test in adolescence
Authors: Glier Sarah , Campbell Alana , Corr Rachel , Pelletier‐Baldelli Andrea , Yefimov Mae , Guerra Carina , Scott Kathryn , Murphy Louis , Bizzell Joshua , Belger Aysenil
Published: March 2022

Dysregulations in autonomic and endocrine stress responses are linked to the emergence of psychopathology in adolescence. However, most studies fail to consider the interplay between these systems giving rise to conflicting findings and a gap in understanding adolescent stress response regulation. A multisystem framework—investigation of parasympathetic (PNS), sympathetic (SNS), and hypothalamic pituitary adrenal (HPA) axis components and their coordination—is necessary to understand individual differences in stress response coordination which contribute to stress vulnerabilities. As the first investigation to comprehensively evaluate these three systems in adolescence, the current study employed the Trier Social Stress Test in 72 typically developing adolescents (mean age = 13) to address how PNS, SNS, and HPA stress responses are coordinated in adolescence. Hypotheses tested key predictions of the Adaptive Calibration Model (ACM) of stress response coordination. PNS and SNS responses were assessed via heart rate variability (HRV) and salivary alpha amylase (sAA) respectively. HPA responses were indexed by salivary cortisol. Analyses utilized piecewise growth curve modeling to investigate these aims. Supporting the ACM theory, there was significant hierarchical coordination between the systems such that those with low HRV had higher sAA and cortisol reactivity and those with high HRV had low‐to‐moderate sAA and cortisol responsivity. Our novel results reveal the necessity of studying multisystem dynamics in an integrative fashion to uncover the true mechanisms of stress response and regulation during development. Additionally, our findings support the existence of characteristic stress response profiles as predicted by the ACM model.
Genomes, repeatomes and interphase chromosome organization in the meadowfoam family (Limnanthaceae, Brassicales)
Authors: Zuo Sheng , Mandáková Terezie , Kubová Michaela , Lysak Martin A.
Published: March 2022

The meadowfoam family (Limnanthaceae) is one of the smallest and genomically underexplored families of the Brassicales. The Limnanthaceae harbor about seven species in the genus Limnanthes (meadowfoam) and Floerkea proserpinacoides (false mermaidweed), all native to North America. Because all Limnanthes and Floerkea species have only five chromosome pairs, i.e., a chromosome number rare in Brassicales and shared with Arabidopsis thaliana (Arabidopsis), we examined the Limnanthaceae genomes as a potential model system. Using low‐coverage whole‐genome sequencing data, we reexamined phylogenetic relationships and characterized the repeatomes of Limnanthaceae genomes. Phylogenies based on complete chloroplast and 35S rDNA sequences corroborated the sister relationship between Floerkea and Limnanthes and two major clades in the latter genus. The genome size of Limnanthaceae species ranges from 1.5 to 2.1 Gb, apparently due to the large increase in DNA repeats, which constitute 60–70% of their genomes. Repeatomes are dominated by long terminal repeat retrotransposons, while tandem repeats represent only less than 0.5% of the genomes. The average chromosome size in Limnanthaceae species (340–420 Mb) is more than 10 times larger than in Arabidopsis (32 Mb). A three‐dimensional fluorescence in situ hybridization analysis demonstrated that the five chromosome pairs in interphase nuclei of Limnanthes species adopt the Rabl‐like configuration.
Reviewer Acknowledgements
Authors: Oscar William
Published: March 2022

International Journal of Contemporary Education (IJCE) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether IJCE publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 5, Number 1 Ahmad Suradi, State Islamic Institute of Bengkulu, IndonesiaAurora Q. Pestano, University of San Jose Recoletos, PhilippinesBožić-Lenard Dragana, University of Osijek Croatia, CroatiaDina Radeljas, Mohawk Valley Community College, USAEdward Bolden, Case Western Reserve University, USAFederica Cornali, University of Turin, ItalyGiuseppe Maugeri, University of Urbino, ItalyInaad M Sayer, University of Human Development, IraqIvan Lenard, Elementary School Ladimirevci, CroatiaMatthew Schatt, University of Florida, USANesrin Ozturk, Ege University, TurkeyQiu Yuan, Gannan Normal University, ChinaSaid K. Juma, State University of Zanzibar, TanzaniaVassiliki Pliogou, Metropolitan College of Thessaloniki, GreeceVassilios Papadimitriou, University of Thessaly, Greece William OscarEditorial AssistantInternational Journal of Contemporary Education------------------------------------------------------------Redfame Publishing9450 SW Gemini Dr. #99416Beaverton, OR 97008, USATel: 1-503-828-0536 ext. 509Fax: 1-503-828-0537E-mail 1: ijce@redfame.comE-mail 2: ijce@redfame.orgURL: http://ijce.redfame.com
β-Lactam Resistance in
Azospirillum baldaniorum
Sp245 Is Mediated by Lytic Transglycosylase and β-Lactamase and Regulated by a Cascade of RpoE7→RpoH3 Sigma Factors
Authors: Pandey Parul , Dubey Ashutosh P. , Mishra Shivangi , Singh Vijay Shankar , Singh Chhaya , Tripathi Anil K.
Published: March 2022

Antimicrobial resistance is a global health problem that requires a better understanding of the mechanisms that bacteria use to resist antibiotics. Bacteria inhabiting the plant rhizosphere are a potential source of antibiotic resistance, but their mechanisms controlling antibiotic resistance are poorly understood.
A. baldaniorum
Sp245 is a rhizobacterium that is known for its characteristic resistance to ampicillin.
Linking the Gulf of Mexico and Coast Mountains batholith during late Paleocene time: Insights from Hf isotopes in detrital zircons
Authors: Pecha* Mark E. , Blum Michael D. , Gehrels George E. , Sundell Kurt E. , Karlstrom Karl E. , Gonzales David A. , Malone David H. , Mahoney J. Brian
Published: March 2022

Paleocene Lower Wilcox Group sedimentation rates are three times the Cenozoic average for the Gulf of Mexico region and are attributed to Laramide tectonism within the Laramide–Rocky Mountains region. These increased rates likely represent the erosion of easily weathered Phanerozoic strata that blanketed the Laramide-age basement-cored uplifts. Geologic observations and U-Pb geochronology are not sufficient to fully address this hypothesis alone, so we conducted 439 Lu-Hf isotopic analyses on detrital zircons from eight samples from the San Juan Basin and five samples from the Gulf of Mexico Basin. Focusing on the zircons younger than 300 Ma allowed us to make direct comparisons to the eight principal components that comprise the North American Cordilleran magmatic arc: (1) Coast Mountains batholith; (2) North Cascades Range; (3) Idaho batholith; (4) Sierra Nevada batholith; (5) Laramide porphyry copper province; (6) Transverse Ranges; (7) Peninsular Ranges; and (8) Sierra Madre Occidental. The εHf(t) results range from +8.9 to –27.0 for the San Juan Basin samples and from +13.0 to –26.6 for the Gulf of Mexico samples. Using the San Juan Basin samples as a proxy for the eroded Mesozoic cover that was shed from the Laramide uplifts, we show that much of the sediment entering the Gulf of Mexico through the Houston and Mississippi embayments during the late Paleocene was derived from reworked cover from the greater Laramide–Rocky Mountains region. However, the Gulf of Mexico samples also include a distinct juvenile suite (εHf[t] ranging from +13 to +5) of zircons ranging in age from ca. 220 to 55 Ma that we traced to the Coast Mountains batholith in British Columbia, Canada. This transcontinental connection indicates an extension to the headwaters of the previously defined paleo-Mississippi drainage basin from ca. 58 to 56 Ma. Therefore, we propose a through-going fluvial system (referred to here as the “Coast Mountains River”) that was routed from the Coast Mountains batholith to the Gulf of Mexico. This expands the previously defined paleo-Mississippi drainage basin area by an estimated 280,000 km2. Our comprehensive Hf isotopic compilation of the North American Cordilleran magmatic arc also provides a benchmark εHf(t) versus U-Pb age plot, which can be used to determine provenance of detrital zircons (85–50 Ma) at the scale of specific region(s) within the Cordillera based on their εHf(t) values.
Iodinated contrast media induced Kounis syndrome during coronary angiogram: a life-threatening clinical dilemma
Authors: Bonnet Romain , Mahmoudi Allal , Carrel Guillaume , Cook Stephane
Published: March 2022

Kounis syndrome (KS) is a well-documented hypersensitivity vasospastic reaction induced by a variety of triggers. Clinical presentation ranges from non-specific symptoms such as dizziness and nausea to myocardial infarction. Many cases of KS were reported after the use of iodinated contrast media, mainly during radiological procedures. This report describes the case of a 46-year-old man developing coronary vasospasm and anaphylactic shock at the end of percutaneous coronary intervention. Occurrence of such pathology while performing coronary angiogram is a tricky situation for the invasive cardiologist. It requires recognising a rare syndrome and interrupting the procedure to avoid extra use of contrast media even in presence of severe coronary lesions due to vasospasm. Every interventionalist should be aware of such a presentation to recognise and react promptly when facing a potentially life-threatening clinical dilemma.
Pompholyx as a side effect of intravenous immunoglobulin (IVIg)
Authors: Doyle Claire , Eustace Karen
Published: March 2022

Intravenous immunoglobulin (IVIg) is increasingly used across multiple specialties for the treatment of inflammatory and autoimmune diseases. Cutaneous reactions to IVIg are generally minor. Pompholyx is a common eruption of small vesicles on the palms, soles, and/or lateral aspects of the fingers. It has a multifactorial aetiology but is rarely attributed to being a drug-related side effect. We describe a 43-year-old woman presenting with peripheral sensory neuropathy who developed pompholyx eczema on both palms following treatment with IVIg.
Epidemiological status quo of hypertension in elderly population in Changchun, China: a cross-sectional study
Authors: Ren Yaxuan , Shi Jikang , Qiao Yichun , Gu Yulu , Li Yong , Liu Yunkai , Cheng Yi , Liu Yawen
Published: March 2022

Objectives

To investigate the epidemiological status quo of hypertension in elderly population in Changchun, China, and provide a reference for the prevention and control strategies of hypertension of elderly population in this region.

Design

A cross-sectional study, as a part of a comprehensive project in Northeast China, was designed to perform in 10 districts in Changchun.

Participants and setting

A total of 6846 participants who were ≥60 years old were selected using a random sampling method.

Main outcome measures

The epidemiological status quo of hypertension.

Results

The prevalence of hypertension in Changchun was 52.6%. Among participants with hypertension enrolled in this study, 87.6% of the participants had been diagnosed with hypertension before the study, 69.1% was taking antihypertensive medications and 66.9% had effective blood pressure control. Obesity, widower/widow, history of diseases and family history of hypertension were risk factors of hypertension (all p<0.05). Participants with obesity, a personal history of heart coronary disease, or a family history of hypertension were susceptible to realising risks of hypertension (all p<0.05). However, participants with diabetes, hyperlipidaemia, or a family history of hypertension were difficult to control blood pressure within the normal range (all p<0.05). In addition, 92.6% participants taking antihypertensive medications used a single medication, and calcium channel blockers was the most commonly used antihypertensive medications in monotherapy.

Conclusion

The rates of awareness, treatment and control of hypertension are greater in Changchun than those in China, indicating that the prevention and control of hypertension in Changchun are effective. However, the prevalence of hypertension in the elderly population in China is lower than that in Changchun, also rendering Changchun a substantial challenge for the supervision of hypertension.
Efficacy of the Gelstix nucleus augmentation device for the treatment of chronic discogenic low back pain: protocol for a randomised, sham-controlled, double-blind, multicentre trial
Authors: Koetsier Eva , van Kuijk Sander M J , Maino Paolo , Dukanac Jasmina , Scascighini Luca , Cianfoni Alessandro , Scarone Pietro , Kuhlen Dominique E , Hollman Markus W , Kallewaard Jan-Willem
Published: March 2022

Introduction

Discogenic pain is the cause of pain in 26%–40% of patients with for low back pain. Consensus about treatment of chronic discogenic low back pain is lacking and most treatment alternatives are supported by limited evidence. The percutaneous implantation of hydrogels into the nucleus pulposus represents a promising regenerative intradiscal therapy. The hydrogel ‘GelStix’ is composed primarily of hydrolyzed polyacrylonitrile and acts as a reservoir of hydration, producing increased pressure and improved pH balance, potentially leading to disc preservation. We hypothesise that treatment with GelStix will lead to greater reduction in pain intensity at 6 months post-treatment compared with patients receiving sham treatment.

Methods and analysis

This is a parallel group, randomised sham-controlled double-blind, multicentre trial to assess whether the GelStix device is superior to sham in reducing pain intensity in patients with chronic discogenic low back pain. The study will be conducted in two regional hospitals in Europe. Seventy-two participants will be randomised in a 1:1 ratio. The primary outcome will be the change in pain intensity between preoperative baseline and at 6 months postintervention. Secondary outcomes were disability, quality of life, the patient’s global impression of change scale, the use of pain medication and the disc degeneration process assessed by means of MRI. For change in pain intensity, disability, health-related quality of life and disc height, mean values will be compared between groups using linear regression analysis, adjusted for treatment centre.

Ethics and dissemination

Ethics approval was obtained from the Ethics Committee of the Canton Ticino, Switzerland (CE2982) and by the Medical Ethical Committee Arnhem-Nijmegen, the Netherlands (2016-2944). All patients that agree to participate will be asked to sign an informed consent form. Results will be disseminated through international publications in peer-reviewed journals, in addition to international conference presentations.

Trial registration number

NCT02763956.

Protocol version

7.1, 18 November 2020.
Validation of type 2 diabetes subgroups by simple clinical parameters: a retrospective cohort study of NHANES data from 1999 to 2014
Authors: Xie Jing , Shao Hua , Shan Tao , Jing Shenqi , Shi Yaxiang , Wang Junjie , Hu Jie , Li Yong , Huang Ruochen , Liu Naifeng , Liu Yun
Published: March 2022

Objectives

To verify whether a simplified method based on age, body mass index (BMI) and glycated haemoglobin (HbA1c) is feasible in classifying patients with type 2 diabetes (T2D), and evaluate the predictive ability of subgroups in several health and mortality outcomes.

Design

Retrospective cohort study.

Setting

The National Health and Nutrition Examination Survey 1999–2014 cycle.

Participants

A total of 1960 participants with diabetes and the age at diagnosis greater than 30.

Primary and secondary outcome measures

Participants with T2D were assigned to previously defined (by Ahlqvist) subgroups based on five variables: age, BMI, HbA1c, homoeostasis model assessment (HOMA) 2 estimates of β-cell function (HOMA2-B), and insulin resistance (HOMA2-IR), and on three variables: age, BMI and HbA1c. The classification performances of the three variables were evaluated based on 10-fold cross validation, with accuracy, precision and recall as evaluation criteria. Outcomes were assessed using logistic regression and Cox regression analysis.

Results

Without HOMA measurements, it is difficult to identify severe insulin-resistant diabetes, but other subgroups can be ideally identified. There is no significant difference between the five variables and the three variables in the ability to predict the prevalence of poor cardiovascular health (CVH), chronic kidney disease, non-alcoholic fatty liver disease and advanced liver fibrosis, and the risk of all-cause, cardiovascular disease and cancer-related mortality (p>0.05), except the prevalence of poor CVH in mild age-related diabetes (p<0.05).

Conclusions

A simple classification based on age, BMI and HbA1c could be used to identify T2D with several health and mortality risks, which is accessible in most individuals with T2D. Due to its simplicity and practicality, more patients with T2D can benefit from subgroup specific treatment paradigms.
Efficacy and safety of an orally administered DGAT2 inhibitor alone or coadministered with a liver-targeted ACC inhibitor in adults with non-alcoholic steatohepatitis (NASH): rationale and design of the phase II, dose-ranging, dose-finding, randomised, placebo-controlled MIRNA (Metabolic Interventions to Resolve NASH with fibrosis) study
Authors: Amin Neeta B , Darekar Amanda , Anstee Quentin M , Wong Vincent Wai-Sun , Tacke Frank , Vourvahis Manoli , Lee Douglas S , Charlton Michael , Alkhouri Naim , Nakajima Atsushi , Yunis Carla
Published: March 2022

Introduction

Small molecule inhibitors of the terminal step in intrahepatic triglyceride synthesis (diacylglycerol acyltransferase 2 inhibitor (DGAT2i, PF-06865571, ervogastat)) and upstream blockade ofde novolipogenesis via acetyl-coenzyme A carboxylase inhibitor (ACCi, PF-05221304, clesacostat) showed promise in reducing hepatic steatosis in early clinical trials. This study assesses efficacy and safety of these metabolic interventions to resolve non-alcoholic steatohepatitis (NASH) with fibrosis.

Methods and analysis

This phase II, randomised, dose-ranging, dose-finding study evaluates DGAT2i 25–300 mg two times per day (BID) or 150–300 mg once a day, DGAT2i 150–300 mg BID+ACCi 5–10 mg BID coadministration or matching placebo in a planned 450 adults with biopsy-confirmed NASH and liver fibrosis stages 2–3 from approximately 220 sites in 11 countries across North America, Europe and Asia. A triage approach including double-confirmation via non-invasive markers is included prior to screening/baseline liver biopsy. On confirmation of histological diagnosis, participants enter a ≥6-week run-in period, then a 48-week double-blind, double-dummy dosing period. The primary endpoint is the proportion of participants achieving histological NASH resolution without worsening fibrosis, ≥1 stage improvement in fibrosis without worsening NASH, or both, assessed by central pathologists. Other endpoints include assessment of hepatic steatosis (imaging substudy), overall safety and tolerability, and evaluation of blood-based biomarkers and quantitative ultrasound parameters over time.

Ethics and dissemination

Metabolic Interventions to Resolve NASH with fibrosis (MIRNA) is conducted in accordance with the Declaration of Helsinki and Council for International Organisations of Medical Sciences (CIOMS) International Ethical Guidelines, International Council on Harmonisation Good Clinical Practice guidelines, applicable laws and regulations, including privacy laws. Local independent review board/ethics committees (IRB/ECs) review/approve the protocol, any amendments, informed consent and other forms. Participants provide written informed consent. Details of all IRB/ECs, as well as results, will be published in a peer-reviewed journal and publicly disclosed through ClinicalTrials.gov, EudraCT, and/orwww.pfizer.comand other public registries as per applicable local laws/regulations.

Trial registration number

NCT04321031.
Protocol for a randomised controlled trial investigating an intervention to boost decentering in response to distressing mental experiences during adolescence: the decentering in adolescence study (DECADES)
Authors: Bennett Marc P , Knight Rachel Clare , Dunning Darren , Archer-Boyd Alan , Blakemore Sarah-Jayne , Dalmaijer Edwin , Ford Tamsin , Williams J Mark G , Clegg Hannah , Kuyken Willem , So Tierney , Wright Gemma , Lenaert Bert , Vainre Maris , Watson Peter ,   MYRIAD Team, Dalgleish Tim
Published: March 2022

Introduction

Decentering describes the ability to voluntarily adopt an objective self-perspective from which to notice internal, typically distressing, stressors (eg, difficult thoughts, memories and feelings). The reinforcement of this skill may be an active ingredient through which different psychological interventions accrue reductions in anxiety and/or depression. However, it is unclear if decentering can be selectively trained at a young age and if this might reduce psychological distress. The aim of the current trial is to address this research gap.

Methods and analysis

Adolescents, recruited from schools in the UK and Ireland (n=57 per group, age range=16–19 years), will be randomised to complete 5 weeks of decentering training, or an active control group that will take part in a combination of light physical exercise and cognitive training. The coprimary training outcomes include a self-reported decentering inventory (ie, the Experiences Questionnaire) and the momentary use of decentering in response to psychological stressors, using experience sampling. The secondary mental health outcomes will include self-reported inventories of depression and anxiety symptoms, as well as psychological well-being. Initial statistical analysis will use between-group analysis of covariance to estimate the effect of training condition on self-rated inventories, adjusted for baseline scores. Additionally, experience sampling data will be examined using hierarchical linear models.

Ethics and dissemination

This study was approved by the Cambridge Psychology Research Ethics Committee, University of Cambridge (PRE.2019.109). Findings will be disseminated through typical academic routes including poster/paper presentations at (inter)national conferences, academic institutes and through publication in peer-reviewed journals.

Trial registration number

ISRCTN14329613.
Worldwide prevalence, risk factors and psychological impact of infertility among women: a systematic review and meta-analysis
Authors: Nik Hazlina Nik Hussain , Norhayati Mohd Noor , Shaiful Bahari Ismail , Nik Muhammad Arif Nik Ahmad
Published: March 2022

Objectives

To assess the prevalence, risk factors and psychological impact of infertility among females. This review summarises the available evidence, effect estimates and strength of statistical associations between infertility and its risk factors.

Study design

Systematic review and meta-analysis.

Data sources

MEDLINE, CINAHL and ScienceDirect were searched through 23 January 2022.

Eligibility criteria

The inclusion criteria involved studies that reported the psychological impact of infertility among women. We included cross-sectional, case–control and cohort designs, published in the English language, conducted in the community, and performed at health institution levels on prevalence, risk factors and psychological impact of infertility in women.

Data extraction and synthesis

Two reviewers independently extracted and assess the quality of data using the Joanna Briggs Institute Meta-Analysis. The outcomes were assessed with random-effects model and reported as the OR with 95% CI using the Review Manager software.

Results

Thirty-two studies with low risk of bias involving 124 556 women were included. The findings indicated the overall pooled prevalence to be 46.25% and 51.5% for infertility and primary infertility, respectively. Smoking was significantly related to infertility, with the OR of 1.85 (95% CI 1.08 to 3.14) times higher than females who do not smoke. There was a statistical significance between infertility and psychological distress among females, with the OR of 1.63 (95% CI 1.24 to 2.13). A statistical significance was noted between depression and infertility among females, with the OR of 1.40 (95% CI 1.11 to 1.75) compared with those fertile.

Conclusions

The study results highlight an essential and increasing mental disorder among females associated with infertility and may be overlooked. Acknowledging the problem and providing positive, supportive measures to females with infertility ensure more positive outcomes during the therapeutic process. This review is limited by the differences in definitions, diagnostic cut points, study designs and source populations.

PROSPERO registration number

CRD42021226414.
Patients presenting to an acute general hospital with acute mental health needs: a retrospective observational cohort study
Authors: Cann Johnathon , Barter Reece , Battle Joseph , Schwenck Jonas , Anakwe Raymond
Published: March 2022

Objectives

To examine the numbers and patterns of patients presenting to an urban acute general hospital with acute mental health presentations and to further investigate any variation related to the COVID-19 pandemic.

Design

Retrospective observational cohort study.

Setting

An urban acute general hospital in London, UK, comprising of five sites and two emergency departments. The hospital provides tertiary level general acute care but is not an acute mental health services provider. There is an inpatient liaison psychiatry service.

Participants

358 131 patients attended the emergency departments of our acute general hospital during the study period. Of these, 14 871 patients attended with an acute mental health presentation. A further 14 947 patients attending with a physical illness were also noted to have a concurrent recorded mental health diagnosis.

Results

Large numbers of patients present to our acute general hospital with mental health illness even though the organisation does not provide mental health services other than inpatient liaison psychiatry. There was some variation in the numbers and patterns of presentations related to the COVID-19 pandemic. Patient numbers reduced to a mean of 9.13 (SD 3.38) patients presenting per day during the first ‘lockdown’ compared with 10.75 (SD 1.96) patients per day in an earlier matched time period (t=3.80, p<0.01). Acute mental health presentations following the third lockdown increased to a mean of 13.84 a day.

Conclusions

Large numbers of patients present to our acute general hospital with mental health illness. This suggests a need for appropriate resource, staffing and training to address the needs of these patients in a non-mental health provider organisation and subsequent appropriate transfer for timely treatment. The COVID-19 pandemic and the resulting lockdowns have resulted in variation in the numbers and patterns of patients presenting with acute mental health illness but these presentations are not new. Considerable work is still needed to provide integrated care which addresses the physical and mental healthcare needs of patients presenting to acute and general hospitals.
Accuracy of telephone triage for predicting adverse outcomes in suspected COVID-19: an observational cohort study
Authors: Marincowitz Carl , Stone Tony , Bath Peter , Campbell Richard , Turner Janette Kay , Hasan Madina , Pilbery Richard , Thomas Benjamin David , Sutton Laura , Bell Fiona , Biggs Katie , Hopfgartner Frank , Mazumdar Suvodeep , Petrie Jennifer , Goodacre Steve
Published: March 2022

Objective

To assess accuracy of telephone triage in identifying need for emergency care among those with suspected COVID-19 infection and identify factors which affect triage accuracy.

Design

Observational cohort study.

Setting

Community telephone triage provided in the UK by Yorkshire Ambulance Service NHS Trust (YAS).

Participants

40 261 adults who contacted National Health Service (NHS) 111 telephone triage services provided by YAS between 18 March 2020 and 29 June 2020 with symptoms indicating COVID-19 infection were linked to Office for National Statistics death registrations and healthcare data collected by NHS Digital.

Outcome

Accuracy of triage disposition was assessed in terms of death or need for organ support up to 30 days from first contact.

Results

Callers had a 3% (1200/40 261) risk of serious adverse outcomes (death or organ support). Telephone triage recommended self-care or non-urgent assessment for 60% (24 335/40 261), with a 1.3% (310/24 335) risk of adverse outcomes. Telephone triage had 74.2% sensitivity (95% CI: 71.6 to 76.6%) and 61.5% specificity (95% CI: 61% to 62%) for the primary outcome. Multivariable analysis suggested respiratory comorbidities may be overappreciated, and diabetes underappreciated as predictors of deterioration. Repeat contact with triage service appears to be an important under-recognised predictor of deterioration with 2 contacts (OR 1.77, 95% CI: 1.14 to 2.75) and 3 or more contacts (OR 4.02, 95% CI: 1.68 to 9.65) associated with false negative triage.

Conclusion

Patients advised to self-care or receive non-urgent clinical assessment had a small but non-negligible risk of serious clinical deterioration. Repeat contact with telephone services needs recognition as an important predictor of subsequent adverse outcomes.
Optimising GPs’ communication of advice to facilitate patients’ self-care and prompt follow-up when the diagnosis is uncertain: a realist review of ‘safety-netting’ in primary care
Authors: Friedemann Smith Claire , Lunn Hannah , Wong Geoff , Nicholson Brian D
Published: March 2022

Background

Safety-netting has become best practice when dealing with diagnostic uncertainty in primary care. Its use, however, is highly varied and a lack of evidence-based guidance on its communication could be harming its effectiveness and putting patient safety at risk.

Objective

To use a realist review method to produce a programme theory of safety-netting, that is, advice and support provided to patients when diagnosis or prognosis is uncertain, in primary care.

Methods

Five electronic databases, web searches, and grey literature were searched for studies assessing outcomes related to understanding and communicating safety-netting advice or risk communication, or the ability of patients to self-care and re-consult when appropriate. Characteristics of included documents were extracted into an Excel spreadsheet, and full texts uploaded into NVivo and coded. A random 10% sample was independently double -extracted and coded. Coded data wasere synthesised and itstheir ability to contribute an explanation for the contexts, mechanisms, or outcomes of effective safety-netting communication considered. Draft context, mechanism and outcome configurations (CMOCs) were written by the authors and reviewed by an expert panel of primary care professionals and patient representatives.

Results

95 documents contributed to our CMOCs and programme theory. Effective safety-netting advice should be tailored to the patient and provide practical information for self-care and reconsultation. The importance of ensuring understanding and agreement with advice was highlighted, as was consideration of factors such as previous experiences with healthcare, the patient’s personal circumstances and the consultation setting. Safety-netting advice should be documented in sufficient detail to facilitate continuity of care.

Conclusions

We present 15 recommendations to enhance communication of safety-netting advice and map these onto established consultation models. Effective safety-netting communication relies on understanding the information needs of the patient, barriers to acceptance and explanation of the reasons why the advice is being given. Reduced continuity of care, increasing multimorbidity and remote consultations represent threats to safety-netting communication.
Changes in heart failure management and long-term mortality over 10 years: observational study
Authors: Bottle Alex , Newson Roger , Faitna Puji , Hayhoe Benedict , Cowie Martin R
Published: March 2022

Objectives

To estimate the long-term survival of two cohorts of people diagnosed with heart failure 10 years apart and to assess differences in patient characteristics, clinical guideline compliance and survival by diagnosis setting.

Methods

Data for patients aged 18 and over with a new diagnosis of heart failure in the Clinical Practice Research Datalink in 2001–2002 (5966 patients in 156 practices) and 2011–2012 (12 827 patients in 331 practices). Survival rates since diagnosis were described using Kaplan-Meier plots. Compliance with national guidelines was summarised.

Results

2011/2012 patients were older than those diagnosed a decade before, with lower blood pressure and cholesterol but more comorbidity and healthcare contacts. For those diagnosed in 2001/2002, the 5-year survival was 40.0% (40.2% in the 2011/2012 cohort), 10-year survival was 20.8%, and 15-year survival 11.1%. Improvement in survival between the two time periods was seen only in those diagnosed in primary care (5-year survival 46.0% vs 57.4%, compared with 33.9% and 32.6% for hospital-diagnosed patients).

Beta-blocker use rose from 24.3% to 39.1%; renin–angiotensin system blockers rose from 31.8% to 54.3% (both p<0.001). There was little change for loop diuretics and none for thiazide diuretics. For the 9963 patients with symptoms recorded by their general practitioner before diagnosis, brain natriuretic peptide (BNP) testing was low, but echocardiogram use rose from 8.3% to 19.3%, and specialist referral rose from 7.2% to 24.6% (all p<0.001).

Conclusions

The 10 years saw some long-term survival gains but only modest improvement in national clinical guideline compliance, from a low baseline, despite the introduction of national initiatives.
Rationale and design of a stepped wedge cluster randomised trial to improve acute reperfusion treatment quality for stroke: IMPROVE stroke care in China
Authors: Li Zixiao , Wang Chunjuan , Zhang Xinmiao , Zong Lixia , Zhou Hongyu , Gu Hongqiu , Jiang Yong , Pan Yuesong , Meng Xia , Zhou Qi , Zhao Haifen , Yang Xin , Wang Meng , Xiong Yunyun , Zhao Xingquan , Wang Yilong , Liu Liping , Ma Xudong , Morgan Louise , Xian Ying , Schwamm Lee H , Wang Yongjun
Published: March 2022

Background

Reperfusion therapy is the most effective treatment for acute ischaemic stroke (AIS) but remains underutilised in China. There is an urgent need to develop tailored strategies to increase adherence to intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) within the guideline-recommended time window for eligible patients.

Aims

This study aims to investigate the efficacy of a comprehensive quality improvement intervention on adherence to guideline-recommended reperfusion therapy for patients with AIS in China.

Design

The Improve Acute Reperfusion Treatment Quality for Stroke in China (IMPROVE Stroke Care in China) trial is designed as a stepped wedge cluster randomised trial within 51 hospitals. We developed the comprehensive intervention ‘STEP’ (Strategies, Toolkit, Exploration, Paradigm) to promote the reconstruction of workflow in stroke centres and shorten in-hospital delay of reperfusion treatment for patients with AIS. The participating hospitals (clusters) were randomised to three groups (cohorts) for different predefined steps to intervention implementation. The primary outcome was the adherent rate of IVT or EVT for eligible patients within the time window. The sample size was estimated to be 7644, and was determined by the number of cases to be enrolled in five study periods to detect a relative increase of 30% (from 19% to 25%) with 90% power and intraclass correlation coefficient of 0.03. All efficacy analyses will be conducted based on the intention-to-treat principle. The primary outcome will be analysed using a mixed-effects logistic regression with a random effect for the cluster (hospital), and a fixed effect for the strategy and period.

Conclusions

If the efficacy is well established, this targeted comprehensive intervention STEP will inform national strategies to increase adherence to guideline-recommended performance on reperfusion therapy.

Trial registration number

clinicaltrials.gov Identifier:NCT003578107