bluuebunny/crossref_metadata_2025 huggingface dataset:
A crossover study evaluating the sex‐dependent and sensitizing effects of sleep deprivation using a nociceptive test battery in healthy subjects
Authors: Hijma Hemme , Koopmans Ingrid , Klaassen Erica , Doll Robert Jan , Zuiker Rob , Groeneveld Geert Jan
Published: August 2022

Aim

We assessed whether total sleep deprivation (TSD) in combination with pain tests yields a reliable method to assess altered pain thresholds, which subsequently may be used to investigate (novel) analgesics in healthy subjects.

Methods

This was a two‐part randomized crossover study in 24 healthy men and 24 women. Subjects were randomized 1:1 to first complete a day of nonsleep‐deprived nociceptive threshold testing, followed directly by a TSD night and morning of sleep‐deprived testing, or first complete the TSD night and morning sleep‐deprived testing, returning 7 days later for a day of nonsleep‐deprived testing. A validated pain test battery (heat, pressure, electrical burst and stair, cold pressor pain test and conditioned pain modulation [CPM] paradigm) and sleep questionnaires were performed.

Results

Subjects were significantly sleepier after TSD as measured using sleepiness questionnaires. Cold pressor pain tolerance (PTT, estimate of difference [ED] −10.8%, 95% CI −17.5 to −3.6%), CPM PTT (ED −0.69 mA, 95% CI −1.36 to −0.03 mA), pressure PTT (ED −11.2%, 95% CI −17.5% to −4.3%) and heat pain detection thresholds (ED ‐0.74 °C, 95% CI −1.34 to −0.14 °C) were significantly decreased after TSD compared to the baseline morning assessment in the combined analysis (men + women). Heat hyperalgesia was primarily driven by an effect of TSD in men, whereas cold and pressure hyperalgesia was primarily driven by the effects of TSD observed in women.

Conclusions

TSD induced sex‐dependent hyperalgesia on cold, heat and pressure pain, and CPM response. These results suggest that the TSD model may be suitable to evaluate (novel) analgesics in early‐phase drug studies.
The perceived relevance of design thinking in achieving innovation goals: The individual microfoundations perspective
Authors: Magistretti Stefano , Bellini Emilio , Cautela Cabirio , Dell'Era Claudio , Gastaldi Luca , Lessanibahri Sina
Published: August 2022

Numerous studies highlight that design thinking is being elevated to the strategic level, on the one hand, propelling designers to the top hierarchical level of the organization, on the other hand, making non‐design functions part of design‐based processes. The increasing adoption of design thinking has transformed how firms implement the related processes and techniques, opening areas of research on how managers differently perceive the relevance of design thinking in achieving innovation goals. In considering the individual dimension as our unit of analysis (i.e. managers), our study relies on the microfoundations theoretical lens to delve deeper into the individual design thinking perceptions of leaders/managers/employees. To do so, we conducted a survey of 197 Italian managers to investigate their different perceptions of the potential of design thinking in achieving innovation goals. The findings show that managers associate a new set of goals with design thinking against the paradigmatic view of a user‐centred practice to generate creative solutions. Indeed, market innovation, organizational change and strategic direction are recognized as goals achievable with design thinking. Moreover, as individuals, managers characterized by (i) different organizational functions, (ii) distinct organizational hierarchy and (iii) diverse organizational experiences differently perceive design thinking in terms of its pertinence to achieving specific innovation goals. By deepening the individual microfoundations dimension, this article contributes to the growing design thinking literature.
Recent updates in the development of small molecules as potential clinical candidates for Alzheimer's disease: A review
Authors: Umar Tarana , Meena Rampratap , Mustehasan  , Kumar Pawan , Khan Asim Ali
Published: August 2022

Alzheimer's disease (AD) is one of the prominent causes for disability and lowered quality of life worldwide in elderly population. It has fostered immense burden to AD patients, families and society. Burgeoning progress in the field of pathogenesis over last two decades has persuaded the investigation of novel pharmacological therapeutics that focuses towards the pathophysiological events of AD. Miscellaneous clinical trials, development and testing of interventions aimed at various targets, such as anti‐tau and anti‐amyloid interventions, neurotransmitter modification, neuroprotection and anti‐neuroinflammation interventions, cognitive enhancement and interventions to palliate behavioural symptoms have been carried out. Despite massive efforts to find disease‐modifying therapies, there lingers a vital need for continuing the advancement in progress of the AD research. This review features the new developments of small molecule compounds that will be beneficial in evolution of new AD therapies. In particular, this review briefly describes summary of mechanistic causes chiefly associated with AD and focuses on medicinal approach via small molecule inhibitors that can manage cognitive impairment and dysfunction and may combat Alzheimer's development.
Early pandemic impacts on family environments that shape childhood development and health: A Canadian study
Authors: McIsaac Jessie‐Lee D. , Lamptey De‐Lawrence , Harley Jane , MacQuarrie Madison , Cummings Randi , Rossiter Melissa D. , Janus Magdalena , Turner Joan
Published: August 2022

Objectives

Changes to income and employment are key social determinants of health that have impacted many families during the COVID‐19 pandemic. This research aimed to understand how changes to employment and income influenced family environments that contribute to early childhood development and health.

Methods

A concurrent triangulation mixed method design was used through a cross‐sectional survey on early impacts of the COVID‐19 pandemic involving families with young children in the Canadian Maritime provinces (n = 2158). Analyses included multivariate regression models to examine whether changes to employment and income predicted changes to Family access to resources and social support, parenting Abilities and self‐care at home, and home Routines and Environments (FARE Change Scale). Content analysis was used to identify themes from the open‐ended questions.

Results

Changes to employment and income early in the pandemic like no longer working but continued to receive salary, working fewer hours for the same salary earned before the pandemic, no longer working nor receiving salary, working fewer hours resulting in salary reduction, essential worker status and household income were significant predictors of FARE Change Scale when ethnicity/cultural background and province of residence are controlled (P < .05). Themes provided a description of family impacts, including shifting employment and income, finding time and capacity, feelings of guilt and the creation of new routines.

Conclusion

Our study provides insight on the implications of public health restrictions, such as the importance of increased time for parents (through reduced work hours) and access to resources and social support to support child development and health.
Approach to the patient with a variant of uncertain significance on genetic testing
Authors: Newey Paul J
Published: August 2022

Establishing a genetic diagnosis may lead to major health benefits for the patient and their wider family, but is dependent on the accurate interpretation of test results. The processes of variant interpretation are by their nature imprecise such that the potential for uncertain test results (i.e., variant(s) of uncertain significance [VUS]) are an inevitable consequence of genomic testing. With an increased responsibility for diagnostic testing in the hands of the specialty physician (e.g., endocrinologist) rather than clinical geneticist, it is essential that they are familiar with the possible outcomes of testing including an understanding of the VUS category. While uncertainty is endemic to many aspects of clinical medicine, receiving a VUS result may pose a considerable challenge to both the clinician and the patient. In this article, a framework to support decision‐making when confronted with a VUS variant is provided, focusing on the key components of the genetic testing pathway. This highlights the importance of assessing the VUS result in the context of the clinical presentation and genetic testing strategy, the value of multidisciplinary team working and ensuring good communication with the patient.
Psychiatric genetic counseling for people with copy number variants associated with psychiatric conditions
Authors: Morris Emily , Inglis Angela , Austin Jehannine
Published: August 2022

22q11.2 deletion is one of the most well‐known copy number variants (CNVs) associated with developing a psychiatric condition (e.g., schizophrenia), but there is a growing list of other CNVs which also confer substantial risk for developing psychiatric conditions. With increased use of chromosome microarray and exome sequencing, the frequency with which these CNVs are detected is increasing. While individuals with such CNVs often receive genetic counseling, research shows that associated psychiatric conditions are less often addressed—clinicians tend to focus on the nonpsychiatric manifestations of the CNV. This represents an important service gap for people with these CNVs and their families, as research shows that not only do these families want genetic counseling about psychiatric illness, it can also produce meaningful positive outcomes for people, including increases in empowerment, and self‐efficacy. Therefore, there is a need to ensure that individuals with psychiatric condition‐associated CNVs are being counseled about these manifestations of their condition in a way that can promote the best outcomes. In this paper we describe the process of providing genetic counseling in two clinical scenarios in which a psychiatric susceptibility CNV is identified: (1) in an individual who has not been diagnosed with a psychiatric condition and (2) in an individual with an established psychiatric condition.
Epidemiology and aetiology of chronic rhinosinusitis in Asia—A narrative review
Authors: Chee Jeremy , Pang Khang Wen , Low Terese , Wang De Yun , Subramaniam Somasundaram
Published: August 2022

Background

Despite having a similar prevalence to Western populations, literature on chronic rhinosinusitis (CRS) in the Asian population is sparse. There is limited data on the epidemiology and aetiology of CRS in Asia.

Objectives

To review the current literature on the epidemiology and aetiology of CRS in Asia.

Methods

This is a narrative review of published data on the epidemiology and aetiology of CRS. Studies on CRS in Asian countries, published in English and indexed on PubMed or Google Scholar were reviewed. Where available, data extracted included epidemiology, endotype and cytokine profiles and genetic profiles.

Results and Conclusion

The prevalence of CRS in Asia ranges widely from 2.1% to 28.4%. Type 2 inflammation has been reported in 5%–55% of Asian patients, with lower levels of Type 2 cytokines reported in head to head comparisons of Western versus Asian patients. Notably, there exists marked heterogeneity in criterion of the tissue eosinophilic infiltration for diagnosis of type 2 CRS. Our review suggests that differences in prevalence of CRS and proportion of eosinophilic CRS between Asia and Europe and the Americas requires further study. Large‐scale Asian studies utilising standardised definitions are needed to bridge this gap. Head to head genetic and microbiomal analysis may also be useful in understanding differences in CRS between the Asian and Western populations.
Randomized controlled trial comparing conventional and traction endoscopic submucosal dissection for early colon tumor (CONNECT‐C trial)
Authors: Ichijima Ryoji , Ikehara Hisatomo , Sumida Yorinobu , Inada Taisuke , Nemoto Daiki , Nakajima Yuki , Minagawa Takeyoshi , Sumiyoshi Tetsuya , Inoki Kazuya , Yoshida Naohisa , Inoue Ken , Fukuzawa Masakatsu , Minoda Yosuke , Tsutsumi Koshiro , Esaki Mitsuru , Gotoda Takuji
Published: August 2022

Objectives

Endoscopic submucosal dissection (ESD) is a widely used treatment for early gastrointestinal cancer. However, colon ESD remains challenging. Previous studies on colon ESD using the traction method used a small sample, single‐center design, providing insufficient evidence of this procedure's efficacy. We thus aimed to investigate the efficacy and safety of the traction method in colon ESD in this multicenter randomized trial.

Methods

We conducted a prospective, multicenter, randomized, two‐arm controlled trial at 10 facilities in Japan. A 1:1 allocation was conducted for the conventional ESD (C‐ESD) and traction ESD (T‐ESD) groups. The primary end‐point was ESD procedure time.

Results

We included 128 C‐ESD and 123 T‐ESD cases from April 2020 to August 2021. The median procedure times for C‐ESD and T‐ESD were 61 (40–100) and 53 (40–76) min (P = 0.18), respectively, and no significant differences were observed between the groups. Subgroup analysis showed that the median procedure times for patients with a lesion diameter of ≥30 mm in the C‐ESD and T‐ESD groups were 89 (57−80) and 69 (50−104) min (P = 0.05), respectively, and for nonexpert operators were 81 (62−120) and 64 (52−109) min (P = 0.07), respectively.

Conclusions

The traction method did not contribute to a significantly shortened ESD procedure time. However, this method may be useful when the tumor diameter is large or if the procedure is conducted by nonexpert endoscopists.
Activated factor XI is associated with increased factor VIIa – Antithrombin complexes in stable coronary artery disease: Impact on cardiovascular outcomes
Authors: Paszek Elżbieta , Pociask Elżbieta , Ząbczyk Michał , Butenas Saulius , Undas Anetta
Published: August 2022

Background

Coronary artery disease (CAD) is associated with a prothrombotic tendency including increased factor (F) VIIa‐antithrombin (FVIIa‐AT) complexes, a measure of tissue factor (TF) exposure, and activated FXI (FXIa). We investigated whether increased FVIIa–AT complexes are associated with FXIa and active TF and if major adverse clinical outcomes are predicted by the complexes in CAD.

Methods

In 120 CAD patients, we assessed FVIIa–AT complex concentrations and the presence of circulating FXIa and active TF. Levels of 8‐iso‐prostaglandin F2α (8‐iso‐PGF2α), interleukin‐6, high‐sensitivity C reactive protein, prothrombin fragment 1 + 2, and free Tissue Factor Pathway Inhibitor were determined. Myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SE), and cardiovascular (CV) death were recorded separately and as a composite endpoint, during follow‐up.

Results

FVIIa–AT complexes were positively associated with current smoking and multivessel CAD. Elevated FVIIa–AT complexes characterized patients with circulating FXIa and/or active TF in association with increased plasma isoprostanes but not with thrombin generation or inflammatory markers. During a median follow‐up of 106 months (interquartile range 95–119), high baseline levels of FVIIa–AT complexes predicted ischemic stroke/SE (HR 4.61 [95% CI 1.48–18.42]) and a composite endpoint of MI, stroke/SE, and CV death (HR 7.47 [95% CI 2.81–19.87]).

Conclusions

This study is the first to show that high FVIIa–AT complexes characterize advanced CAD patients with detectable FXIa and active TF, which is, in part, driven by oxidative stress. High FVIIa–AT complexes were associated with the risk of ischemic stroke/SE during long‐term follow‐up, highlighting the need for effective antithrombotic agents in CAD.
Incidence and risk factors of posttraumatic epilepsy following pediatric traumatic brain injury: A systematic review and meta‐analysis
Authors: Mariajoseph Frederick P. , Chen Zhibin , Sekhar Praba , Rewell Sarah S. , O'Brien Terence J. , Antonic‐Baker Ana , Semple Bridgette D.
Published: August 2022

Posttraumatic epilepsy (PTE) is a well‐known chronic complication following traumatic brain injury (TBI). Despite some evidence that age at the time of injury may influence the likelihood of PTE, the incidence of PTE in pediatric populations remains unclear. We therefore conducted a systematic review to determine the overall reported incidence of PTE, and explore potential risk factors associated with PTE after pediatric TBI. A comprehensive literature search of the PubMed, Embase, and Web of Science databases was conducted, including randomized controlled trials and cohort studies assessing the incidence of PTE in TBI pediatric patients. We excluded studies with a sample size of <10 patients and those in which a pediatric cohort was not clearly discernable. The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines. We found that the overall incidence of PTE following pediatric TBI was 10% (95% confidence interval [CI] = 5.9%–15%). Subgroup analysis of a small number of studies demonstrated that the occurrence of early seizures (cumulative incidence ratio [CIR] = 7.28, 95% CI = 1.09–48.4, p = .040), severe TBI (CIR = 1.81, 95% CI = 1.23–2.67, p < .001), and intracranial hemorrhage (CIR = 1.60, 95% CI = 1.06–2.40, p = .024) increased the risk of PTE in this population. Other factors, including male sex and neurosurgical intervention, were nonsignificantly associated with a higher incidence of PTE. In conclusion, PTE is a significant chronic complication following childhood TBI, similar to in the adult population. Further standardized investigation into clinical risk factors and management guidelines is warranted. PROSPERO ID# CRD42021245802.
Ultra‐high frequency ultrasound detection of the dermo‐epidermal junction: Its potential role in dermatology
Authors: Granieri Giammarco , Oranges Teresa , Morganti Riccardo , Janowska Agata , Romanelli Marco , Manni Elisabetta , Dini Valentina
Published: August 2022

Traditional high‐frequency ultrasound (HFUS; 20 MHz) is a non‐invasive method used to study skin in vivo but is not able to measure skin thickness accurately and to identify the dermal‐epidermal junction (DEJ). Ultra‐high frequency ultrasound (UHFUS; 70–100 MHz) has sub‐millimetre resolution comparable to histology. The aim of this study was to identify, by UHFUS, the DEJ and to describe skin differences in healthy individuals by providing a measure of skin thickness, based on age and gender. We also described the bullous pemphigoid lesion. We enrolled 42 patients divided into 2 groups: A and B. Group A included 32 healthy volunteers aged 22–74 years. Group B consisted of 10 patients with bullous pemphigoid. For each patient in group A, 8 ultrasound (US) clips by 70 MHz probe were performed at forehead, cheek, nose, forearm, abdomen, chest, back and leg. For each patient in group B, 5 US images were acquired at blisters roofs and edges. In each US image, we measured thickness of stratum corneum (α‐β), epidermis (α‐γ) and epidermis plus dermis (α‐δ). In both groups, we found the presence of 4 lines delimiting: the stratum corneum (the layer between α‐line and β‐line), the epidermis (distance between α‐ and γ‐line), and the boundary between dermis and subcutis (δ‐line). The γ‐line corresponds to the point of detachment of the bullae. The abdominal α‐β layer was thicker in males (p = 0.019) and α‐δ thickness at cheeks (p < 0.001), chest (p = 0.007), back (p = 0.025) and forearm (p < 0.001). In females, α‐γ thickness of the back was greater (p = 0.005). In old people compared to young, we noticed an increase of α‐β layer at forehead and chest (p = 0.014), an increase of α‐γ layer at forearm (p = 0.001), back (p = 0.024) and leg (p = 0.010) and an increase of α‐δ layer at forehead (p = 0.001) and nose (p = 0.049). UHFUS is an advanced imaging technique that can detect both the DEJ and the boundary between dermis and subcutaneous tissue so that epidermal and dermal thickness can be measured with good accuracy. Regarding gender and age, skin differences obtained with UHFUS were comparable to other non‐invasive methods.
The global decline in the sensitivity of vegetation productivity to precipitation from 2001 to 2018
Authors: Zeng Xiang , Hu Zhongmin , Chen Anping , Yuan Wenping , Hou Guolong , Han Daorui , Liang Minqi , Di Kai , Cao Ruochen , Luo Dengnan
Published: August 2022

The sensitivity of vegetation productivity to precipitation (Sppt) is a key metric for understanding the variations in vegetation productivity under changing precipitation and predicting future changes in ecosystem functions. However, a comprehensive assessment of Sppt over all the global land is lacking. Here, we investigated spatial patterns and temporal changes of Sppt across the global land from 2001 to 2018 with multiple streams of satellite observations. We found consistent spatial patterns of Sppt with different satellite products: Sppt was highest in dry regions while low in humid regions. Grassland and shrubland showed the highest Sppt, and evergreen needle‐leaf forest and wetland showed the lowest. Temporally, Sppt showed a generally declining trend over the past two decades (p < .05), yet with clear spatial heterogeneities. The decline in Sppt was especially noticeable in North America and Europe, likely due to the increase in precipitation. In central Russia and Australia, however, Sppt showed an increasing trend. Biome‐wise, most ecosystem types exhibited significant decrease in Sppt, while grassland, evergreen broadleaf forest, and mixed forest showed slight increases or non‐significant changes in Sppt. Our finding of the overall decline in Sppt implies a potential stabilization mechanism for ecosystem productivity under climate change. However, the revealed Sppt increase for some regions and ecosystem types, in particular global grasslands, suggests that grasslands might be increasingly vulnerable to climatic variability with continuing global climate change.
Near‐net‐size preparation of porous mullite matrix ceramics with in situ formed 3D mullite whisker network
Authors: Yan Hao , Chen Shile , Lang Ying , Wei Hongkang , Tian Chuanjin , Wang Chang‐An
Published: August 2022

Porous mullite matrix ceramics have excellent thermal and mechanical properties suitable for applications such as in thermal insulation. However, their applications are limited by processing defects from nonuniform sintering shrinkage and the trade‐off between high porosity (preferred for low thermal conductivity) and high mechanical strength. Herein, we seek to minimize the sintering shrinkage by near‐net‐size preparation and improve the strength by in situ formed whisker network structure. Gelcasting forming technology and pressureless sintering were used to prepare porous mullite matrix ceramics using kyanite and α‐Al2O3 powders as the starting materials and using MoO3 to promote the growth of mullite whiskers. The results showed that the sintering shrinkage could be compensated by the volume expansion from solid‐state reaction during reaction sintering. The in situ formed three‐dimensional (3D) whisker network further reduced sintering shrinkage and effectively improved the strength of the ceramics. An ultralow sintering shrinkage of .78% was achieved. The near‐net‐shape porous mullite matrix ceramics strengthened by 3D whisker network had a high porosity of 63.9%, a high compressive strength of 83.8 MPa and a high flexural strength of 53.5 MPa.
Population‐based hospitalization burden estimates for respiratory viruses, 2015–2019
Authors: Zimmerman Richard K. , Balasubramani G. K. , D'Agostino Helen E. A. , Clarke Lloyd , Yassin Mohamed , Middleton Donald B. , Silveira Fernanda P. , Wheeler Nicole D. , Landis Jonathan , Peterson Alanna , Suyama Joe , Weissman Alexandra , Nowalk Mary Patricia
Published: August 2022

Background

Acute respiratory infections (ARIs) result in millions of illnesses and hundreds of thousands of hospitalizations annually in the United States. The responsible viruses include influenza, parainfluenza, human metapneumovirus, coronaviruses, respiratory syncytial virus (RSV), and human rhinoviruses. This study estimated the population‐based hospitalization burden of those respiratory viruses (RVs) over 4 years, from July 1, 2015 to June 30, 2019, among adults ≥18 years of age for Allegheny County (Pittsburgh), Pennsylvania.

Methods

We used population‐based statewide hospital discharge data, health system electronic medical record (EMR) data for RV tests, census data, and a published method to calculate burden.

Results

Among 26,211 eligible RV tests, 67.6% were negative for any virus. The viruses detected were rhinovirus/enterovirus (2552; 30.1%), influenza A (2,299; 27.1%), RSV (1082; 12.7%), human metapneumovirus (832; 9.8%), parainfluenza (601; 7.1%), influenza B (565; 6.7%), non‐SARS‐CoV‐2 coronavirus (420; 4.9% 1.5 years of data available), and adenovirus (136; 1.6%). Most tests were among female (58%) and White (71%) patients with 60% of patients ≥65 years, 24% 50–64 years, and 16% 18–49 years. The annual burden ranged from 137–174/100,000 population for rhinovirus/enterovirus; 99–182/100,000 for influenza A; and 56–81/100,000 for RSV. Among adults <65 years, rhinovirus/enterovirus hospitalization burden was higher than influenza A; whereas the reverse was true for adults ≥65 years. RV hospitalization burden increased with increasing age.

Conclusions

These virus‐specific ARI population‐based hospital burden estimates showed significant non‐influenza burden. These estimates can serve as the basis for several areas of research that are essential for setting funding priorities and guiding public health policy.
Risk for intellectual disability populations in inpatient forensic settings in the United Kingdom: A literature review
Authors: Quinn Sam , Rhynas Sarah , Gowland Susan , Cameron Lois , Braid Nicola , O′Connor Siobhán
Published: August 2022

Background

People with an intellectual disability who commit a criminal offence can be detained, by a court, in a forensic inpatient facility. There is limited understanding of how inpatients with an intellectual disability and their nurses navigate risk in U.K. forensic services.

Methods

A traditional literature review design was followed to map evidence (2000–2021) around the forensic and health and wellbeing risks faced by inpatients with an intellectual disability, nurses' perceptions of managing risk, and patient experiences of informing risk assessment and management. Papers were analysed thematically.

Results

Findings suggest that restrictive measures to mitigate forensic risks (e.g., violence) can exacerbate the risk of poor health and wellbeing outcomes. There was some limited evidence of direct patient involvement in risk assessment and management.

Conclusion

Further research is required to explore how forensic inpatients with an intellectual disability can have input in care planning, risk assessment and management.
Hoisted with his own petard: How sex‐ratio meiotic drive in Drosophila affinis creates resistance alleles that limit its spread
Authors: Ma Wen‐Juan , Knoles Emma M. , Patch Kistie B. , Shoaib Murtaza M. , Unckless Robert L.
Published: August 2022

Meiotic drivers are selfish genetic elements that tinker with gametogenesis to bias their own transmission into the next generation of offspring. Such tinkering can have significant consequences on gametogenesis and end up hampering the spread of the driver. In Drosophila affinis, sex‐ratio meiotic drive is caused by an X‐linked complex that, when in males with a susceptible Y chromosome, results in broods that are typically more than 95% female. Interestingly, D. affinis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons—effectively reversing the sex‐ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 750X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex‐ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex‐ratio X chromosome, and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex‐chromosome turnover indirectly.
Otoliths suggest lifespans more than 30 years for free‐living bowfin Amia calva: Implications for fisheries management in the bowfishing era
Authors: Lackmann Alec R. , Bielak‐Lackmann Ewelina S. , Butler Malcolm G. , Clark Mark E.
Published: August 2022

The bowfin Amia calva is an amiid (Amiiformes) relict native to North America. It is the last surviving member of the Halecomorphi, a group of fishes that evolved more than 250 million years ago. Despite the phylogenetic significance of the amiids in vertebrate evolution, little has been published about their age and growth. Recreational bowfin harvest is currently unregulated throughout most of the USA, yet new recreational fisheries are emerging. As such, bowfin are increasingly harvested by sport bowfishing without limit, in addition to their growing commercial harvest for caviar. From 2017 to 2021 we studied a total of 81 bowfin from 11 populations across the east–west gradient of Minnesota within a narrow latitudinal margin (<50 km) of the 46th parallel north. We compared the allometry and translucence of bowfin asteriscus, lapillus and sagittal otoliths and found the lapillus otoliths provide consistent readability for age estimation despite being the smallest of the set. Size‐at‐age data derived from otoliths indicated that bowfin are sexually dimorphic in asymptotic length and may live up to 33 years, which is 15 years longer than previously estimated in wild populations, but comparable to what has been reported in captivity. Overall, 28% of the otolith‐aged fish were estimated as older than the previously reported maximum age for wild bowfin populations. Our findings suggest that the bowfin life history may exhibit slower growth, greater longevity, and more variable recruitment than previously recognized, which sets the stage for more otolith‐derived population demographics across their range and age validation study. Our results have direct implications for conservation of bowfin, especially amidst the increasing rates of exploitation during the bowfishing era.
Addressing social and institutional vulnerabilities in the context of flood risk mitigation
Authors: Alves Priscila B. R. , Djordjević Slobodan , Javadi Akbar A.
Published: August 2022

There are different perspectives of what constitutes disaster risk. Among the “hazards”‐tradition research, more focus is given to modelling hazards, and less effort is made to understand the vulnerabilities. Considering vulnerabilities as the inherent characteristics of the place that create the potential to harm, this paper highlights the importance of understanding the vulnerabilities of the place before defining actions for flood risk mitigation (FRM). In this sense, a participatory approach, the Project PLANEJEEE, was developed to understand the social and institutional vulnerabilities of FRM in Campina Grande, Brazil. Data was collected with the collaboration with 199 stakeholders through surveys, workshop and focus groups. The results reflect the analysis of risk perception and coping capacity of communities at risk (n = 172), and the institutional context with the involvement with policymakers and local specialists (n = 27). Although results confirm that individuals faced severe flood risk cases previously, they still need resources for increasing their coping capacity and their own risk protection. Institutional vulnerabilities are shown with the contrast between challenges and actions for FRM. Findings show that multiple challenges in social and institutional contexts should be systematically addressed to propose actions to reduce flood risk vulnerability, and increase resilience.
Need for improvement in the evaluation of pre‐malignant upper gastro‐intestinal lesions in India: Results of a nationwide survey
Authors: Madhu Deepak , Krishnamurthy Veeraraghavan , Natarajan Thirumoorthi , Lakhtakia Sundeep
Published: August 2022

Background and Aim

Gastric and esophageal cancers are associated with high morbidity in India. In the absence of formal screening programs in India, it is essential that all elective esophago‐gastro‐duodenoscopies (EGDs), irrespective of indication, be also considered an opportunity to screen for premalignant lesions. With this premise, we tried to assess the adherence to best practices in the detection of premalignant upper gastro‐intestinal lesions (PMUGIL) among endoscopists in India. We also evaluated the adequacy of training, availability of appropriate facilities, and differences between teaching and non‐teaching centers.

Methods

We disbursed a survey among endoscopists working in India, through the membership database of the Society of Gastrointestinal Endoscopists of India, by email and instant messaging. The responses were collected and subsequently analyzed.

Results

We obtained a total of 422 eligible responses. The adherence to best practices assessed was lower than the set threshold in all except one parameter in both teaching centers and non‐teaching centers. Only 58.5% of endoscopists had received training in the detection of PMUGIL. Appropriate image enhanced endoscopy (IEE) facilities were available to only 58.05% of surveyed endoscopists.

Conclusions

Strategies to improve detection of PMUGIL should be directed at improving adherence to best practices, ensuring adequate training of endoscopists in the evaluation of PMUGIL and improving infrastructure.
The impact of branched‐chain amino acid supplementation on measures of glucose homeostasis in individuals with hepatic disorders: A systematic review of clinical studies
Authors: Prokopidis Konstantinos , Kirwan Richard P. , Giannos Panagiotis , Triantafyllidis Konstantinos K. , Kechagias Konstantinos S. , Forbes Scott C. , Candow Darren G.
Published: August 2022

Background

Branched chain amino acid (BCAA) supplementation may influence glucose metabolism in individuals with an impaired glyceamic profile. This systematic review investigated the effects of isolated BCAA supplementation on measures of glucose homeostasis in individuals with hepatic disorders.

Methods

We searched PubMed, Web of Science, Cochrane Library and Scopus for published clinical trials that investigated the effects of isolated BCAA supplementation on measures of glucose homeostasis, including serum glucose and insulin, glycated haemoglobin (HbA1c) levels and homeostatic model assessment for insulin resistance (HOMA‐IR) scores.

Results

Eleven trials met the inclusion criteria. Only one study revealed a decrease in serum glucose from BCAA supplementation compared to three studies that showed increases. Five studies demonstrated no significant changes in serum glucose, and two studies displayed no changes in HbA1c following BCAA supplementation. Serum levels of insulin were decreased in three studies, remained unchanged in one, and increased in the remaining three studies. BCAA supplementation reduced HOMA‐IR scores in two studies, increased HOMA‐IR scores in another two, or resulted in no changes in two other studies.

Conclusions

BCAA supplementation in isolation had no effect on overall glucose homeostasis in individuals with hepatic disorders, although some improvements on serum insulin levels and HOMA‐IR scores were observed. Overall, there is little evidence to support the utilisation of BCAA supplementation as a potential nutritional strategy for improving measures of glucose homeostasis in individuals with hepatic disorders.
Respiratory and systemic monocytes, dendritic cells, and myeloid‐derived suppressor cells in COVID‐19: Implications for disease severity
Authors: Falck‐Jones Sara , Österberg Björn , Smed‐Sörensen Anna
Published: August 2022

Since the beginning of the SARS‐CoV‐2 pandemic in 2020, researchers worldwide have made efforts to understand the mechanisms behind the varying range of COVID‐19 disease severity. Since the respiratory tract is the site of infection, and immune cells differ depending on their anatomical location, studying blood is not sufficient to understand the full immunopathogenesis in patients with COVID‐19. It is becoming increasingly clear that monocytes, dendritic cells (DCs), and monocytic myeloid‐derived suppressor cells (M‐MDSCs) are involved in the immunopathology of COVID‐19 and may play important roles in determining disease severity. Patients with mild COVID‐19 display an early antiviral (interferon) response in the nasopharynx, expansion of activated intermediate monocytes, and low levels of M‐MDSCs in blood. In contrast, patients with severe COVID‐19 seem to lack an early efficient induction of interferons, and skew towards a more suppressive response in blood. This is characterized by downregulation of activation markers and decreased functional capacity of blood monocytes and DCs, reduced circulating DCs, and increased levels of HLA‐DRloCD14+ M‐MDSCs. These suppressive characteristics could potentially contribute to delayed T‐cell responses in severe COVID‐19 cases. In contrast, airways of patients with severe COVID‐19 display hyperinflammation with elevated levels of inflammatory monocytes and monocyte‐derived macrophages, and reduced levels of tissue‐resident alveolar macrophages. These monocyte‐derived cells contribute to excess inflammation by producing cytokines and chemokines. Here, we review the current knowledge on the role of monocytes, DCs, and M‐MDSCs in COVID‐19 and how alterations and the anatomical distribution of these cell populations may relate to disease severity.
Analysis of differentially expressed microRNAs in bovine mammary epithelial cells treated with lipoteichoic acid
Authors: Shen Puxiu , Yu Jingcheng , Yan Chenbo , Yang Dexin , Tong Chao , Wang Xinzhuang
Published: August 2022

Mastitis is one of the most common diseases of dairy cattle and can be caused by physical stress, chemicals and microbial infection. Staphylococcus aureus is the most common pathogens that induce mastitis in dairy cattle. In this study, bovine mammary epithelial cells (BMECs) were treated either with lipoteichoic acid (LTA, 30 µg/ml) or 1 × phosphate‐buffer saline (PBS, control) and RNA‐Seq was applied to explore the effect of LTA on the expression microRNAs (miRNAs) in BMECs. Compared to the control group, 43 miRNAs were significantly up‐regulated and eight miRNAs were significantly down‐regulated. Additionally, 724 genes were significantly up‐regulated and 13 genes were significantly down‐regulated in LTA group relative to the control group. Bta‐miR‐196a, bta‐miR‐2285aj‐5p, bta‐miR‐143, bta‐miR‐2433, bta‐miR‐2284f and bta‐miR‐2368‐3p were selected from 51 differentially expressed miRNAs and are discussed in this manuscript. Target gene prediction revealed that the target genes of these six miRNAs were all differentially expressed, including MT1E, SPDYA, FGL1, TLR2, PAPOLG, ZDHHC17 and SMC4. Subsequently, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the target genes with differentially expressed miRNAs were enriched in mitogen‐activated protein kinase (MAPK) signalling pathway, rheumatoid arthritis and cancer. Therefore, the results of this study provided new evidences for the molecular mechanism of LTA‐induced mastitis, which may provide new targets for the diagnosis and treatment of mastitis in dairy cattle.
Warm ears, a red flag for sleepiness?
Authors: Schinkelshoek Mink S. , Fronczek Rolf , de Boer Anke F. J. , de Wit Kay , Tannemaat Martijn R. , Lammers Gert J.
Published: August 2022

Core body and skin temperatures are intimately linked to sleep and alertness. The distal‐to‐proximal skin temperature gradient has been described as a good physiological predictor for sleep onset. Increased ear skin temperature is often caused by increased blood flow reflected in redness, which is commonly noticed in people who are sleepy, especially anecdotally in children. Nonetheless, no prior study investigated the possible relation between sleepiness and ear skin temperature as a separate measurement. We assessed the relation between ear skin temperature and sleepiness in patients undergoing regular electroencephalographic examinations, because of suspicion of epilepsy, both without and after sleep deprivation. Subjective sleepiness was measured using the Stanford Sleepiness Scale, and objective sleepiness by determining sleep onset with electroencephalography. Distal, proximal and ear skin temperature were measured repeatedly using wireless measurement devices (iButtons). Forty‐four adult patients were included. Ear skin temperature correlates weakly with distal skin temperature (r = 0.174, p < 0.001) and distal‐to‐proximal gradient (r = 0.160, p < 0.001), but not with proximal skin temperature (r = −0.001, p = 0.975). Ear skin temperature increased significantly in a subgroup of 13 patients, between 5 and 1 min before sleep onset (p = 0.002; η2 = 0.059), even though this increase was also associated with supine posture. iButtons is a valid method to measure ear skin temperature, which appears to function partly like a distal and partly like a proximal skin temperature measurement. Change in ear skin temperature is associated with sleep onset and supine posture.
Changes in alcohol use during hepatitis C treatment in persons who inject drugs
Authors: Martin Madhuri , Roth Prerana J. , Niu Jiajing , Pericot‐Valverde Irene , Heo Moonseong , Padi Akhila , Norton Brianna L. , Akiyama Matthew J. , Litwin Alain H.
Published: August 2022

People who inject drugs (PWID) are a vulnerable population at high risk for acquiring hepatitis C virus (HCV) and frequently suffer from comorbid alcohol use. This study examines the characteristics and correlates of alcohol use among study participants, the association between alcohol consumption and sustained virologic response (SVR) in patients receiving HCV treatment, changes in drinking behaviours during HCV treatment and associations of drinking over time with specific models of HCV treatment. Participants were 150 PWID with HCV who were receiving opioid agonist therapy (OAT) and enrolled in a randomized clinical trial exploring the effectiveness of three models of care for HCV treatment. The addiction severity index was the primary measure of alcohol consumption. Days of alcohol intake were evaluated longitudinally and across three treatment groups. At baseline, 31% (47/150) reported having at least one drink in the last 30 days including 24% (36/150) who reported drinking to intoxication in the last 30 days. There was no difference in SVR rates between groups. There was a significant decrease in overall days of drinking from baseline (7.78 ± 7.86) to follow‐up at Week 24 (5.78 ± 8.83) (p = 0.041), but there were no significant changes among those who drank to intoxication; modified directly observed therapy (mDOT) was the only group with a significant decline in days of alcohol consumption (p = 0.041). In this cohort of PWID on OAT, baseline alcohol consumption did not affect SVR rates. HCV treatment was overall associated with decreased alcohol consumption. In particular, mDOT was associated with decreased alcohol consumption. Given the additive effect of alcohol and HCV on the development of cirrhosis, studies should be done to investigate the complimentary effects of the mDOT model of care on alcohol cessation.
Genome‐wide DNA methylation patterns harbour signatures of hatchling sex and past incubation temperature in a species with environmental sex determination
Authors: Bock Samantha L. , Smaga Christopher R. , McCoy Jessica A. , Parrott Benjamin B.
Published: August 2022

Conservation of thermally sensitive species depends on monitoring organismal and population‐level responses to environmental change in real time. Epigenetic processes are increasingly recognized as key integrators of environmental conditions into developmentally plastic responses, and attendant epigenomic data sets hold potential for revealing cryptic phenotypes relevant to conservation efforts. Here, we demonstrate the utility of genome‐wide DNA methylation (DNAm) patterns in the face of climate change for a group of especially vulnerable species, those with temperature‐dependent sex determination (TSD). Due to their reliance on thermal cues during development to determine sexual fate, contemporary shifts in temperature are predicted to skew offspring sex ratios and ultimately destabilize sensitive populations. Using reduced‐representation bisulphite sequencing, we profiled the DNA methylome in blood cells of hatchling American alligators (Alligator mississippiensis), a TSD species lacking reliable markers of sexual dimorphism in early life stages. We identified 120 sex‐associated differentially methylated cytosines (DMCs; FDR < 0.1) in hatchlings incubated under a range of temperatures, as well as 707 unique temperature‐associated DMCs. We further developed DNAm‐based models capable of predicting hatchling sex with 100% accuracy (in 20 training samples and four test samples) and past incubation temperature with a mean absolute error of 1.2°C (in four test samples) based on the methylation status of 20 and 24 loci, respectively. Though largely independent of epigenomic patterning occurring in the embryonic gonad during TSD, DNAm patterns in blood cells may serve as nonlethal markers of hatchling sex and past incubation conditions in conservation applications. These findings also raise intriguing questions regarding tissue‐specific epigenomic patterning in the context of developmental plasticity.
Burnout, wellbeing and how they relate: A qualitative study in general practice trainees
Authors: Prentice Shaun , Elliott Taryn , Dorstyn Diana , Benson Jill
Published: August 2022

Purpose

Although research has explored burnout risk factors among medical trainees, there has been little exploration of the personal experiences and perceptions of this phenomenon. Similarly, there has been little theoretical consideration of trainee wellbeing and how this relates to burnout. Our study aimed to conceptualise both constructs.

Method

We situated this study within a post‐positivist epistemology using grounded theory to guide the research process. Participants were recruited from one Australian General Practice training organisation. Fourteen trainees completed interviews, while a further five focus groups explored the views of 33 supervisors, educators and training coordinators. Data collection and analysis occurred concurrently, drawing upon constant comparison and triangulation. Template analysis, using an iterative process of coding, was employed to generate conceptual models of the phenomena of interest.

Results

Participants described burnout as an insidious syndrome lying on a spectrum, with descriptions coalescing under seven themes: altered emotion, compromised performance, disengagement, dissatisfaction, exhaustion, overexertion and feeling overwhelmed. Wellbeing was perceived to comprise personal and professional domains that interacted and were fuelled by an underlying ‘reservoir’. Both constructs were linked by the degree of a trainee's value fulfilment, with burnout occurring when a trainee's wellbeing reservoir was depleted.

Conclusions

Participants in this study characterised burnout and wellbeing as multifaceted, connected constructs. Given the complexity of these constructs, preventive interventions should target both person and workplace‐focused factors, with value fulfilment proposed as the basic change mechanism. A novel model that synthesises and advances previous research is offered based on these findings.