bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of free modified jejunal flaps to reconstruct pharyngoesophageal defects with preservation of the larynx in three cases
Authors: Liu Jifeng , Yu Rong , Wang Ji , Deng Di , Li Linke , Li Bo , Liu Jun , Chen Fei
Published: May 2022

The larynx is often sacrificed in patients with hypopharyngoesophageal cancer before reconstruction using the jejunum to restore the continuity of the digestive tract and allow oral alimentation. We retrospectively collected and analyzed data from three patients who underwent hypopharyngoesophageal reconstruction by partial patch and partial tube free jejunal flap with preservation of laryngeal function. All three flaps survived in patients who underwent the modified jejunal flaps. The larynx was preserved in all three patients. Partial patch and partial tube jejunal flap is a possible option for reconstruction of large and complex defects after pharyngectomy and cervical esophagectomy with larynx preservation.
A large intrathoracic goiter with tracheal stenosis: Complete resection using a robot‐assisted thoracoscopic approach
Authors: Nakamura Ryuji , Okuda Katsuhiro , Chiba Kensuke , Matsui Takuya , Oda Risa , Tatematsu Tsutomu , Yokota Keisuke , Nakanishi Ryoichi
Published: May 2022

Growing intrathoracic goiters may compress surrounding organs and deteriorate the cardiopulmonary function. Treating such cases requires carefully considering how to maintain oxygenation and resect the tumor with minimal invasiveness without complications. We herein report a surgically resected case of a large intrathoracic goiter‐compressed trachea extending from the right lower pole of the thyroid gland to the carina. We secured the airway by intubation preparing for extracorporeal membrane oxygenation and successfully performed surgical complete resection using a robot‐assisted thoracoscopic and cervical approach. Intrathoracic goiter is a tumor with abundant neovascularity, and the right vagus nerve is displaced in the thoracic cavity, but a robot‐assisted thoracoscopic approach using CO2 insufflation improved visualization at the narrow apex area of the thoracic cavity. Robot‐assisted thoracoscopic surgery is a useful surgical procedure enabling safe and minimally invasive surgery without recurrent laryngeal nerve palsy or tracheal injury for intrathoracic giant goiters extending into the thoracic cavity.
Theta oscillatory dynamics of inhibitory control, error processing, and post‐error adjustments: Neural underpinnings and alcohol‐induced dysregulation in social drinkers
Authors: Marinkovic Ksenija , Rosen Burke Q.
Published: May 2022

Background

Alcohol intoxication impairs inhibitory control, resulting in disinhibited, impulsive behavior. The anterior cingulate cortex (ACC) plays an essential role in a range of executive functions and is sensitive to the effects of alcohol, which contributes to the top‐down cognitive dysregulation. This study used a multimodal approach to examine the acute effects of alcohol on the neural underpinnings of inhibitory control, inhibition failures, and neurobehavioral optimization as reflected in trial‐to‐trial dynamics of post‐error adjustments.

Methods

Adult social drinkers served as their own controls by participating in the Go/NoGo task during acute alcohol and placebo conditions in a multi‐session, counterbalanced design. Distributed source modeling of the magnetoencephalographic signal was combined with structural magnetic resonance imaging to characterize the spatio‐temporal dynamics of inhibitory control in the time‐frequency domain.

Results

Successful response inhibition (NoGo) elicited right‐lateralized event‐related theta power (4 to 7 Hz). Errors elicited a short‐latency increase in theta power in the dorsal (dACC), followed by activity in the rostral (rACC), which may underlie an affective “oh, no!” orienting response to errors. Error‐related theta in the dACC was associated with subsequent activity of the motor areas on the first post‐error trial, suggesting the occurrence of post‐error output adjustments. Importantly, a gradual increase of the dACC theta across post‐error trials closely tracked improvements in accuracy under placebo, which may reflect cognitive control engagement to optimize response accuracy. In contrast, alcohol increased NoGo commission errors, dysregulated theta during correct NoGo withholding, and abolished the post‐error theta enhancement of cognitive control.

Conclusions

Confirming the sensitivity of frontal theta to inhibitory control and error monitoring, the results support functional and temporal dissociation along the dorso‐rostral axis of the ACC and the deleterious effects of alcohol on the frontal circuitry subserving top‐down regulation. Over time, alcohol‐induced disinhibition may give rise to compulsive drinking and contribute to alcohol misuse.
Patterns and predictors of alcohol use during the early stages of the COVID‐19 pandemic in Australia: Longitudinal cohort study
Authors: Batterham Philip J. , Shou Yiyun , Farrer Louise M. , Murray Kristen , Morse Alyssa R. , Gulliver Amelia , Slade Tim , Newton Nicola C. , Calear Alison L.
Published: May 2022

Background

The COVID‐19 pandemic has resulted in disruptions across many life domains. The distress associated with the pandemic itself, and with public health efforts to manage the outbreak, could result in increased alcohol use. This study aimed to quantify changes in alcohol use during the early stages of the pandemic and factors associated with different patterns of use.

Methods

Data were obtained from a longitudinal survey of a representative Australian adult sample (N = 1296, 50% female, Mage = 46.0) conducted from March to June 2020, during the first wave of the COVID‐19 outbreak in Australia. Change in alcohol consumption was examined using Alcohol Use Disorders Identification Test‐Consumption (AUDIT‐C) scores from waves one, three, five, and seven of the study, each 4 weeks apart. Factors associated with alcohol consumption were examined, including depression (PHQ‐9) and anxiety (GAD‐7) symptoms, health risk tolerance, stress and coping, work and social impairment (WSAS), COVID impacts, and sociodemographic variables. We tested changes in alcohol use across the full sample using a mixed effects repeated measure ANOVA model and a multinomial logistic regression to identify factors assessed at wave 1 that were independently associated with alcohol use.

Results

There was no significant change in AUDIT‐C scores across the study. For most participants, alcohol use did not increase during the early phase of the COVID‐19 pandemic in Australia. COVID‐19 exposure, higher perceived coping, depression symptoms, and male gender were associated with greater odds of increasing or elevated levels of alcohol use. Social changes, which included working from home, had mixed effects on alcohol consumption.

Conclusions

Although no evidence was found for increased alcohol use overall during the early months of the pandemic, several factors were associated with alcohol consumption at risky levels. Greater understanding of motivations for drinking across public and private contexts, along with targeted support for high‐risk groups, could assist in reducing harm associated with alcohol consumption.
Hidradenitis suppurativa and Down syndrome in a single‐centre sample: A cross‐sectional study
Authors: Hernández‐Rodríguez Juan‐Carlos , Osorio‐Gómez Guiovana‐Fernanda , Ortiz‐Álvarez Juan , Lebrón‐Martín José‐Antonio , Conejo‐Mir Julián , Pereyra‐Rodríguez José‐Juan
Published: May 2022

Down syndrome (DS) has been related to a higher risk of hidradenitis suppurativa (HS). This cross‐sectional study assessed DS patients with HS in a Spanish single‐centre sample. DS participants presented a lower age of onset, age at diagnosis and time to diagnosis. Also, DS was not associated with the severity of HS measured by baseline IHS4.
PD‐1 mediates decidual γδ T cells cytotoxicity during recurrent pregnancy loss
Authors: Guo Rong , Jiang Silin , Zhang Jianliang , Yang Quanli , Gao Liang , Xia Wei , Tong Lingxia , Feng Peiran , Xu Yan , Zhang Tao , Cheng Hao , Liu CuiPing , Zhang Xueguang , Yin Zhinan , Zhang Hong
Published: May 2022

Problem

Recurrent pregnancy loss (RPL) is one of the big challenges of normal pregnancy. Immune dysregulation has been proposed for the key underline mechanisms of RPL. However, the essential roles of T cells, especially γδ T cells, have not been defined.

Method of study

Decidua were obtained from normal pregnancy women or recurrent pregnancy loss patients and the surface molecules of γδ T cells in decidua were evaluated via flow cytometric analysis. The expression of PD‐1 in clinical samples was analyzed by immunohistochemistry assay. The intracellular cytokines of decidual PD‐1+ and PD‐1‐ γδ T cells were evaluated by flow cytometric analysis. The cytotoxicity of PD‐1‐ γδ T cells were confirmed via an in vitro co‐culture experiment. The specific inhibitors for Erk, p38 and JNK against the MAPK pathway were added to the co‐culture media to evaluate the functions of the Erk, p38 and JNK.

Results

We demonstrated that PD‐1 was significantly decreased on decidual tissue γδ T cells of patients with RPL, resulting in the enhanced cytotoxicity of γδ T cells against trophoblasts. We further elucidated an Erk‐dependent TNF‐α production mediates the γδ T cell cytotoxicity against the trophoblast cells. Finally, the reduced expression of PD‐L1 in the villi tissues of patients with RPL might be the cause of the reduction of PD‐1 on the tissue γδ T cells.

Conclusion

Our study uncovers an important role of PD‐1 expression on decidual γδ T cells in maintaining the normal pregnancy, and may provide a new strategy for immune therapy against RPL.
Expression of antimicrobial peptides in the amniotic fluid of women with cervical insufficiency
Authors: Kim Youngmi , Lee Keun‐Young , Lee Jae Jun , Tak Hyunjin , Park Sung‐Taek , Song Ji‐Eun , Son Ga‐Hyun
Published: May 2022

Problem

Cervical insufficiency (CI) is associated with intra‐amniotic infection or inflammation. Antimicrobial peptides (AMPs) in amniotic fluid may protect the fetus against microbial invasion, giving their broad‐spectrum microbiocidal properties. We evaluated changes in amniotic fluid AMP expression in women with CI and assessed whether these changes are related to their pregnancy outcomes.

Method of Study

We evaluated amniotic fluid human neutrophil peptide 3 (HNP‐3), human β‐defensin‐2 (hBD‐2), and LL‐37 levels in 66 women with CI and 25 normal controls at 16–24 weeks of gestation. The CI group was divided into short cervix and cervical dilation groups, and the cervical dilation group was further divided into preterm and full‐term delivery groups according to the pregnancy outcomes, and AMP expression was analyzed in each group.

Results

: HNP‐3 and hBD‐2 levels were higher in women with CI than in normal controls and in the cervical dilation as compared to the short cervix group. Among women with cervical dilation, 22 delivered at full‐term, and 23 had spontaneous preterm births. The hBD‐2 level in amniotic fluid mid‐pregnancy was higher in the full‐term delivery than in the preterm delivery groups. However, LL‐37 levels in amniotic fluid were low in women with CI and normal controls.

Conclusions

: Amniotic fluid HNP‐3 and hBD‐2 levels increased in women with CI compared with normal controls. Moreover, increased amniotic fluid hBD‐2 levels mid‐pregnancy were associated with favorable pregnancy outcomes in women with CI. AMPs in the amniotic fluid may participate in host defense against ascending infection in women with CI.
The evolution of the teledentistry landscape in Australia: A scoping review
Authors: Poirier Brianna , Jensen Emilija , Sethi Sneha
Published: May 2022

Introduction

There has been a recent surge in the use of teledentistry services in Australia that has paralleled the COVID‐19 pandemic. Due to the limited published literature reflecting on this transition, this article employed a systematic scoping review methodology.

Objective

The objective was to explore the role of teledentistry in the provision of clinical dental services in Australia.

Design

Two independent reviewers searched PubMed, Embase, Scopus, Web of Science and grey literature sources to identify literature eligible for inclusion. The search was restricted to Australia and service delivery. Data were categorically synthesised by modalities and reported benefits and limitations; findings were cross‐referenced with the COVID‐19 pandemic timeline.

Findings

The systematic search identified 758 articles, of which 25 met the inclusion criteria. Results highlight a range of service providers and definitions of teledentistry. A shift in modality from asynchronous towards synchronous teledentistry pre‐ and post‐COVID‐19 pandemic is detailed.

Discussion

Whilst highly useful during the COVID‐19 pandemic, teledentistry provides a unique opportunity to continue to increase the accessibility of dental services, especially for patients in rural areas or those who are immunocompromised.

Conclusion

Clinicians and researchers must consider opportunities to merge existing research with the recent clinical uptake of teledentistry for patients that would benefit from teledental services beyond the COVID‐19 pandemic.
Effects of a regional–rural immersion program in Northland, New Zealand, on returning to work in that region
Authors: Connell Charlotte J. W. , Bagg Warwick , Jo Emmanuel , Poole Phillippa
Published: May 2022

Introduction

It is well established that rural workforce outcomes are more likely among medical graduates who spend time training in non‐urban areas; however, fewer studies have assessed whether graduates are more likely to return to the specific area where they undertook rural training.

Objective

This study aimed to determine whether graduates who had undertaken a regional–rural immersion program in Northland, NZ, were more likely to have returned to work in Northland as of mid‐2021, relative to peers who did not participate.

Design

This prospective cohort study used longitudinal tracking survey responses, medical school administrative data and workforce outcome information. A multinomial model, accounting for other covariates, was built to determine the association between graduates practising in Northland (population ⟨ 100 000), which encompasses both rural (population ⟨ 25 000) and regional (25 000 ⟩ population ⟨ 100 000) areas, and having participated in a Northland‐based immersion program during medical school. The study population was University of Auckland domestic medical students graduating between 2009 and 2018, inclusive. Immersion program participants who responded to longitudinal career tracking surveys were included in the study sample.

Findings

The final sample size was 1320 students (80% of population of interest). Graduates who undertook the Northland immersion program (n = 169) were more likely than non‐participants (n = 1151) to be working in Northland as of 2020–2021 (relative risk: 3.2).

Discussion and Conclusion

Regional–rural immersion programs might preferentially build workforces in that specific region; however, further research is required to understand whether these findings are generalizable, and the main reasons for this effect.
Long‐term study on electrophysiological characteristics and catheter ablation of idiopathic ventricular arrhythmias originating from the left ventricular posterior papillary muscles guided by intracardiac ultrasound
Authors: Liu Xiangfei , Wang Jin , Gong Yanwei , Wei Changmin
Published: May 2022

Background

This study aimed to investigate the electrophysiological characteristics of idiopathic ventricular arrhythmias (VAs) originating from the left ventricular posterior papillary muscles (LPPM) and explore the efficiency of catheter ablation using three‐dimensional intracardiac ultrasound technology.

Methods

Twenty‐seven cases of premature ventricular contraction/ventricular tachycardia (PVC/VT) originating from the left ventricular posterior papillary muscles were recorded from July 2015 to June 2019 in the Central Hospital of Shengli Oil Field and the First Affiliated Hospital of Zhengzhou University. Electrophysiological mapping and radiofrequency catheter ablation (RFCA) were performed using three‐dimensional intracardiac ultrasound technology. The characteristics of the body surface and intracavity electrocardiogram were analyzed. All cases were followed up for 24 months after the operation.

Results

The VAs of all 27 cases were successfully eliminated by catheter ablation. QRS complexes were observed with a right bundle branch block (RBBB) pattern and a steep slope in the initial segment. Lead I appeared with an Rs pattern, and inferior leads (lead II, III, and aVF) were usually with an S wave. The lead aVR appeared with a qR pattern, while the R wave was commonly found in aVL. The main wave in leads V1‐V3 was positive but negative in V5 and V6.

Conclusion

Ventricular arrhythmias originating from the left ventricular posterior papillary muscles have similar electrophysiological characteristics. The origin site was accurately located using three‐dimensional intracardiac ultrasound technology. Catheter ablation effectively eliminated VAs.
Association between complete right bundle branch block and atrial fibrillation development
Authors: Zhang Fu‐Tao , Liu Xiao‐Jie , Zhao Dan‐Qing , Wu Jin‐Tao , Zhang Lei‐Ming , Hu Juan , Fan Xian‐Wei , Yang Hai‐Tao , Yan Li‐Jie , Liu Jing‐Jing , Wang Shan‐Ling
Published: May 2022

Background

Complete right bundle branch block (CRBBB) is an important predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. However, the association between CRBBB and AF development remains unclear.

Methods

We performed a retrospective study of 2639 patients (male, n = 1549; female, n = 1090; mean age, 58 ± 13 years). CRBBB was defined as a late R (R′) wave in lead V1 or V2 with a slurred S wave in lead I and/or lead V6 with a prolonged QRS duration (≥120 ms).

Results

Among the 2639 patients, CRBBB was detected in 40 patients (1.5%), and the prevalence of AF was 7.4% (196/2639). The proportion of patients with AF and CRBBB was higher than the proportion of patients with AF without CRBBB (22.5% vs. 7.2%; p = 0.001). In the forward multivariate logistic analysis, CRBBB (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.350–8.211; p = 0.009), complete left bundle branch block (OR, 2.209; 95% CI, 1.238–3.940; p = 0.007), age (OR, 1.020; 95% CI, 1.005–1.035; p = 0.009), valvular heart disease (OR, 2.332; 95% CI, 1.531–3.552; p < 0.001), left atrial diameter (OR, 1.133; 95% CI, 1.104–1.163; p < 0.001), left ventricular ejection fraction (OR, 1.023; 95% CI, 1.006–1.041; p = 0.007), and class I or III anti‐arrhythmic drug use (OR, 10.534; 95% CI, 7.090–15.651; p < 0.001) were associated with AF.

Conclusion

Complete right bundle branch block was significantly associated with AF development in hospitalized patients with cardiovascular diseases.
Utility and pitfalls of the electrocardiogram in the evaluation of cardiac amyloidosis
Authors: Ng Perryn Lin Fei , Lim Yoke Ching , Evangelista Lauren Kay Mance , Wong Raymond Ching Chiew , Chai Ping , Sia Ching Hui , Loi Hoi Yin , Yeo Tiong Cheng , Lin Weiqin
Published: May 2022

Background

Cardiac amyloidosis is a protein misfolding disorder involving deposition of amyloid fibril proteins in the heart. The associated fibrosis of the conduction tissue results in conduction abnormalities and arrhythmias. “Classical” electrocardiogram (ECG) findings in cardiac amyloidosis include that of low voltage complexes with increased left ventricular wall thickness on echocardiography. However, this “classical” finding is neither sensitive nor specific. As cardiac amyloidosis is associated with a generally poor prognosis, the need for early recognition of this disease is important given the availability of new treatment options. In this review, we highlight 3 cases of patients with cardiac amyloidosis. Although presenting with typical clinical signs and symptoms, ECG for all 3 patients was not consistent with the classical findings described. They underwent further diagnostic tests which clinched the diagnosis of cardiac amyloidosis, allowing patients to receive targeted treatment. Through the review of the literature, we will highlight the different ECG patterns in patients with different types of cardiac amyloidosis and clinical scenarios, as well as the pitfalls of using ECG to identify the condition. Lastly, we also emphasize the current paradigms in diagnosing cardiac amyloidosis through the non‐invasive methods of echocardiography, cardiac magnetic resonance imaging, and nuclear technetium‐pyrophosphate imaging.

Conclusions

Electrocardiogram is often the first investigation used in evaluating many cardiac disorders, including cardiac amyloidosis. However, classical features of cardiac amyloidosis on ECG are often not present. A keen understanding on the ECG features of cardiac amyloidosis and knowledge of the diagnostic workflow is important to diagnose this condition.
Pressure injuries are common in children with myelomeningocele: Results from a follow‐up programme and register
Authors: Stockman Jessica , Westbom Lena , Alriksson‐Schmidt Ann I.
Published: May 2022

Aim

To investigate the occurrence of pressure injuries (PIs) in children with myelomeningocele (MMC) and to investigate the association between PIs and orthoses use by disability‐specific variables.

Methods

Population‐based registry study including participants in the Swedish multidisciplinary follow‐up programme for MMC. Risks of PIs were investigated by birth cohort, country of birth, sex, type of MMC, muscle function level (MFL), and continence status.

Results

Of 180 participants, 29% had PIs recorded. Of the 132 participants with >1 assessment records, 17.4% reported multiple PI occasions. More assessments increased the likelihood of PIs (Odds Ratio [OR] = 1.33, 95% CI 1.15–1.54) and participants born 2015–2018 had a lower OR of PIs than those born 2007–2010 (OR = 0.08, 95% CI = 0.01–0.74). Those at MFL I had lower OR of PIs than those at MFL V (OR = 0.06, 95% CI 0.01–0.64). Of the 73 participants with orthoses on the lower extremities, 47% reported skin irritations/injuries in the last 4 weeks; 30% reported that it made them stop using orthoses.

Conclusion

Pressure injuries are common even in young children with MMC. Many have recurring skin irritations. Inspecting for PIs should be part of a daily routine and tools to increase compliance are needed.
Optimising homeothermy in neonates: A systematic review and clinical guidelines from the French Neonatal Society
Authors: Tourneux Pierre , Thiriez Gérard , Renesme Laurent , Zores Claire , Sizun Jacques , Kuhn Pierre ,   The Group of Reflection and Evaluation of the Environment of Newborns (GREEN) study group of the French Neonatology Society
Published: May 2022

Aim

Thermal instability is harmful on the newborn infant. We sought to draw up practical guidelines on maintaining homeothermy alongside skin‐to‐skin contact.

Methods

A systematic analysis of the literature identified relevant studies between 2000 and 2021 in the PubMed database. Selected publications were evaluated, and their level of evidence was graded, in order to underpin the development of clinical guidelines.

Results

We identified 7 meta‐analyses and 64 clinical studies with a focus on newborn infants homeothermy. Skin‐to‐skin contact is the easiest and most rapidly implementable method to prevent body heat loss. Alongside skin‐to‐skin contact, monitoring the newborn infant's body temperature with a target of 37.0°C is essential. For newborn infants <32 weeks of gestation, a skullcap and a polyethylene bag should be used in the delivery room or during transport. To limit water loss, inhaled gases humidification and warming is recommended, and preterm infants weighing less than 1600 g should be nursed in a closed, convective incubator. With regard to incubators, there are no clear benefits for single‐ versus double‐wall incubators as well as for air versus skin servo control.

Conclusion

Alongside skin‐to‐skin contact, a bundle of practical guidelines could improve the maintenance of homeothermy in the newborn infant.
Clinical trials and outcome reporting in congenital diaphragmatic hernia overlook long‐term health and functional outcomes—A plea for core outcomes
Authors: Lewis Leonie , Sinha Ian , Losty Paul D.
Published: May 2022

Aim

To review the selection, measurement and reporting of outcomes in studies of interventions in Congenital Diaphragmatic Hernia (CDH).

Methods

We searched the Cochrane Central Register of Controlled Trials from 2000–2020 for randomised trials and observational studies. Outcomes reported were classified into seven key domains modelled on the patient journey.

Results

Our search yielded 118 papers; 27 were eligible. The most frequent domains measured were ‘short‐term markers of disease activity’ (17/27), whereas long‐term outcomes (3/27) and outcomes relating to functional health status (8/27) were reported infrequently. There was heterogeneity in the methods and timing of outcome reporting. Primary outcomes were varied and not always clearly stated.

Conclusion

Long‐term health and functional outcomes involving interventional studies in CDH are infrequently reported, which hinders the process of shared decision‐making and evidence‐based healthcare. A CDH core outcome set is needed to standardise outcome reporting that is relevant to both families and healthcare teams.
Review article: current and emerging therapies for acute alcohol‐associated hepatitis
Authors: Rattan Puru , Shah Vijay H.
Published: May 2022

Background

Alcohol‐associated hepatitis is an acute manifestation of alcohol‐associated liver disease (ALD) and is associated with 30%–40% mortality at 28 days. Abstinence and corticosteroids are the mainstays of treatment, but the latter only improves short‐term mortality, so new and improved therapies remain an unmet need.

Aims

The aim was to review the pathophysiology of alcohol‐associated hepatitis and how various targets can be used by current and emerging therapies as treatment.

Methods

A thorough literature review was conducted on acute alcohol‐associated hepatitis, current therapies and therapies under investigation.

Results

With the increasing prevalence of alcohol use disorder and ALD, the burden of alcohol‐associated hepatitis is also expected to rise. The current understanding of alcohol‐associated hepatitis pathophysiology has led to clinical trials of several therapies involving IL‐1 antagonism, modification of the gut microbiome and liver regeneration.

Conclusions

Corticosteroid therapy for alcohol‐associated hepatitis is restricted in its applicability and has limited efficacy. Developing multidisciplinary, patient‐centred care models based on digital health technologies, in combination with continued discovery of novel therapies using multiomics data and computational biology techniques will be necessary to tackle the increasing burden of alcohol‐associated hepatitis.
Pharmacokinetics of free and total mycophenolic acid in paediatric and adult renal transplant recipients: Exploratory analysis of the effects of clinical factors and gene variants
Authors: Liu Yan , Zhang Huanxi , Li Jun , Liu Longshan , Wu Chenglin , Fu Qian , Huang Min , Chen Xiao , Wang Changxi , Chen Pan
Published: May 2022

Clinical and genetic influencing factors on free fraction of mycophenolic acid (MPA) have rarely been discussed. The present study investigated whether the clinical and genetic factors could explain the variability in the pharmacokinetics of free MPA (fMPA) and total MPA (tMPA) in Chinese paediatric and adult renal transplant recipients. Twenty‐eight paediatric and 31 adult patients were enrolled, and the concentrations of tMPA and fMPA were determined at 0 h (predose) and 0.5, 1, 1.5, 2, 4, 5, 8, 9, 10 and 12 h after mycophenolate mofetil administration. Genetic polymorphisms of UGTs (rs671448, rs1042597, rs2741049, rs62298861, rs7439366, rs12233719) and ABCC2 (rs717620) were simultaneously determined. The clinical and genetic data were analysed and reported. tMPA and fMPA concentrations adjusted for dose per body weight were consistently higher in adults than in paediatric patients. In the paediatric group, only albumin and time after transplantation correlated significantly with the MPA‐free fraction variation, which could explain 32.4% of the variability. Besides, ABCC2 polymorphism, albumin and time after transplantation correlated significantly with the MPA‐free fraction variation in adults, which could explain 56.9% of the variability. The influencing factors in the paediatric group are different from those in adults, which may be due to age‐related transporter expression.
Closed Testing with Globaltest, with Application in Metabolomics
Authors: Xu Ningning , Solari Aldo , Goeman Jelle J.
Published: May 2022

The Globaltest is a powerful test for the global null hypothesis that there is no association between a group of features and a response of interest, which is popular in pathway testing in metabolomics. Evaluating multiple feature sets, however, requires multiple testing correction. In this paper, we propose a multiple testing method, based on closed testing, specifically designed for the Globaltest. The proposed method controls the familywise error rate simultaneously over all possible feature sets, and therefore allows post hoc inference, that is, the researcher may choose feature sets of interest after seeing the data without jeopardizing error control. To circumvent the exponential computation time of closed testing, we derive a novel shortcut that allows exact closed testing to be performed on the scale of metabolomics data. An R package ctgt is available on comprehensive R archive network for the implementation of the shortcut procedure, with applications on several real metabolomics data examples.
Does product market competition discipline managers? Evidence from an exogenous trade shock and corporate acquisitions
Authors: Alimov Azizjon
Published: May 2022

Research question/issue

This study uses the 1989 Canada‐United States Free Trade Agreement (FTA) to study the effect of increased foreign competition on the efficiency of major corporate investment decisions. The analysis builds on the disciplining theories of competition that suggest that managers facing greater competition should make better investment decisions, resulting in more wealth created for shareholders.

Research findings/insights

Using a sample of more than 2000 mergers and acquisitions, the study finds that acquirers exposed to greater increases in foreign competition experience better acquisition performance. The positive impact of increased competition is stronger in acquirers with relatively higher agency costs prior to the FTA. Managers of acquirers exposed to greater foreign competition are more likely to be terminated following value‐destroying acquisitions.

Theoretical/academic implications

This study provides novel empirical evidence showing that increased foreign competition results in better investment decisions and that the result is likely due to the disciplining effects of competition. This evidence adds to a growing body of work on the disciplining role of competition and on the effects of increased foreign competition on corporate decision‐making.

Practitioner/policy implications

This study is relevant to policymakers because the extent of competition can be influenced by policy decisions. For regulators, it is worth considering that reducing import tariffs and other entry barriers into product markets may lower agency costs and increase the efficiency of corporate investment. This is a topical issue due to the increase in globalization and ongoing debates about further liberalization of trade relations.
Does proxy voting really promote corporate sustainability?
Authors: Bernard Julie , Boiral Olivier , Guillaumie Laurence , Brotherton Marie‐Christine
Published: May 2022

Research question/issue

This study explores the challenges faced by responsible investment and shareholder activism practitioners in integrating sustainability by means of proxy voting as shareholder engagement strategy.

Research findings/insights

Proxy voting guidelines that sometimes include sustainability provisions are applied in a very elastic and inconsistent way. Proxy voting agents are expected to follow the guidelines; they explain their non‐compliance by pointing out the guidelines' vagueness, the opacity of current proxy voting practices, and portfolio managers not necessarily aligned with their clients' stated sustainability commitments, along with their perceptions of what is in the best interest of the clients.

Theoretical/academic implications

This study sheds new light on processes underlying proxy voting practices for sustainability, which have been largely overlooked in the literature. By opening the “black box” of proxy voting processes, this study challenges the dominant optimism in this area and raises serious concerns regarding the effectiveness of current shareholder activism practices. This paper also contributes to the critical literature on corporate sustainability and neo‐institutional approaches by showing that the use of proxy voting guidelines in this area can be considered as a rational myth based on symbolic commitments divorced from substantial change in the dominant financial logic.

Practitioner/policy implications

This paper has important practical implications for institutional investors, organizations involved in proxy voting practices, and stakeholders in general. Among other things, this article shows the importance of clarifying the commitments included in proxy voting procedures, monitoring their application, and providing training on ESG issues to the actors involved in implementing the guidelines.
Spatial non‐stationary effects of explanatory variables on soil bulk density in the critical zone of the Chinese Loess Plateau
Authors: Liu Shaozhen , Wang Yunqiang , Zhou Zixuan , Zhang Pingping , Zhao Yali , Xu Lan , Qi Lijun , Sun Hui , Zhou Jingxiong , An Zhisheng
Published: May 2022

Bulk density (BD) is one of the most important soil physical properties in the hydrological processes of Earth's Critical Zone (CZ). The heterogeneity and related controlling factors of surface BD have received extensive research attention. However, it is unclear whether the effects of controlling factors on BD are homogeneous or vary spatially. This study quantified topsoil BD with a high‐density sampling strategy (10 m × 10 m; n = 1134) across the ShuangChaGou watershed in the critical zone of the Chinese Loess Plateau (CLP‐CZ). Stepwise multiple linear regression (SMLR), regression kriging (RK), random forest (RF) and geographically weighted regression (GWR) were established as modelling approaches to (i) compare the performance of these four models in explaining BD variation, (ii) assess the main factors driving BD, and (iii) evaluate the spatial non‐stationary relationship between BD and its explanatory variables. GWR explained the BD variation to the same extent as the RK model (35%), outperforming both the SMLR (15%) and RF models (19%). The variation in topsoil BD depended mainly on: soil organic carbon (SOC) content, normalised difference vegetation index (NDVI), plan curvature, and slope length. The spatial distribution of the local R2, regression coefficient magnitude, significance and sign calculated by GWR revealed that the effects of variables accounting for variation in BD varied spatially. The explanatory power of these variables in terms of BD variation was strongest in northern and northeastern areas of the watershed and weakest in southern areas of the watershed. Both significant negative and positive correlations between BD and silt content, NDVI, and plan curvature were found. This study enriched traditional research linked to the complicated relationships between BD and controlling factors by incorporating spatial non‐stationarity, which is useful for improving the accuracy of hydrological modelling in the CLP‐CZ and in similar CZs worldwide.

Highlights

Non‐stationary relationships between BD (N = 1134) and its explanatory variables were captured at the watershed scale.

GWR model performed on par with the RK and better than the SMLR or RF model.

Silt content, NDVI, and plan curvature showed both significant negative and positive effects on BD.

Spatial non‐stationarity of BD should be considered for improving the performance of hydrological modeling.
The influence of genetic architecture on responses to selection under drought in rice
Authors: Ćalić Irina , Groen Simon C. , Choi Jae Young , Joly‐Lopez Zoé , Hamann Elena , Natividad Mignon A. , Dorph Katherine , Cabral Carlo Leo U. , Torres Rolando O. , Vergara Georgina V. , Henry Amelia , Purugganan Michael D. , Franks Steven J.
Published: May 2022

Accurately predicting responses to selection is a major goal in biology and important for successful crop breeding in changing environments. However, evolutionary responses to selection can be constrained by such factors as genetic and cross‐environment correlations, linkage, and pleiotropy, and our understanding of the extent and impact of such constraints is still developing. Here, we conducted a field experiment to investigate potential constraints to selection for drought resistance in rice (Oryza sativa) using phenotypic selection analysis and quantitative genetics. We found that traits related to drought response were heritable, and some were under selection, including selection for earlier flowering, which could allow drought escape. However, patterns of selection generally were not opposite under wet and dry conditions, and we did not find individual or closely linked genes that influenced multiple traits, indicating a lack of evidence that antagonistic pleiotropy, linkage, or cross‐environment correlations would constrain selection for drought resistance. In most cases, genetic correlations had little influence on responses to selection, with direct and indirect selection largely congruent. The exception to this was seed mass under drought, which was predicted to evolve in the opposite direction of direct selection due to correlations. Because of this indirect effect on selection on seed mass, selection for drought resistance was not accompanied by a decrease in seed mass, and yield increased with fecundity. Furthermore, breeding lines with high fitness and yield under drought also had high fitness and yield under wet conditions, indicating that there was no evidence for a yield penalty on drought resistance. We found multiple genes in which expression influenced both water use efficiency (WUE) and days to first flowering, supporting a genetic basis for the trade‐off between drought escape and avoidance strategies. Together, these results can provide helpful guidance for understanding and managing evolutionary constraints and breeding stress‐resistant crops.
Male frequency in Caenorhabditis elegans increases in response to chronic irradiation
Authors: Quevarec Loïc , Réale Denis , Dufourcq‐Sekatcheff Elizabeth , Car Clément , Armant Olivier , Dubourg Nicolas , Adam‐Guillermin Christelle , Bonzom Jean‐Marc
Published: May 2022

Outcrossing can be advantageous in a changing environment because it promotes the purge of deleterious mutations and increases the genetic diversity within a population, which may improve population persistence and evolutionary potential. Some species may, therefore, switch their reproductive mode from inbreeding to outcrossing when under environmental stress. This switch may have consequences on the demographic dynamics and evolutionary trajectory of populations. For example, it may directly influence the sex ratio of a population. However, much remains to be discovered about the mechanisms and evolutionary implications of sex ratio changes in a population in response to environmental stress. Populations of the androdioecious nematode Caenorhabditis elegans, are composed of selfing hermaphrodites and rare males. Here, we investigate the changes in the sex ratio of C. elegans populations exposed to radioactive pollution for 60 days or around 20 generations. We experimentally exposed populations to three levels of ionizing radiation (i.e., 0, 1.4, and 50 mGy.h−1). We then performed reciprocal transplant experiments to evaluate genetic divergence between populations submitted to different treatments. Finally, we used a mathematical model to examine the evolutionary mechanisms that could be responsible for the change in sex ratio. Our results showed an increase in male frequency in irradiated populations, and this effect increased with the dose rate. The model showed that an increase in male fertilization success or a decrease in hermaphrodite self‐fertilization could explain this increase in the frequency of males. Moreover, males persisted in populations after transplant back into the control conditions. These results suggested selection favoring outcrossing under irradiation conditions. This study shows that ionizing radiation can sustainably alter the reproductive strategy of a population, likely impacting its long‐term evolutionary history. This study highlights the need to evaluate the impact of pollutants on the reproductive strategies of populations when assessing the ecological risks.
Melatonin as a complementary and prophylactic agent against COVID‐19 in high‐risk populations: A narrative review of recent findings from clinical and preclinical studies
Authors: Hosseini Abdolkarim , Badri Taleb , Esmaeili Gouvarchin Ghaleh Hadi , Hassanpour Kazem , Alishiri Gholamhossein , Akbariqomi Mostafa , Farnoosh Gholamreza
Published: May 2022

The coronavirus disease 2019 (COVID‐19) pandemic has been going on around the world for more than a year and has cost a lot, as well as affected the quality of life of many. The psychological stress like delirium and sleep disturbances caused by the COVID‐19 has affected many people in direct or indirect way by the disease. Insomnia and sleep deprivation have a negative effect on the immune system as well as disorders of the hormonal system, including the production and secretion of melatonin, known as the sleep hormone. Melatonin is a known anti‐inflammatory and antioxidant agent in addition to its role in regulating circadian rhythms. In this review, we investigated the relationship between the effect of psychological stress caused by COVID‐19 on patients, their families, health care workers, and occupations as well as how melatonin might act as a prophylactic agent with sedative effects and sleep enhancement potential. Search terms “melatonin” and “COVID‐19” were manually searched on PubMed or other electronic database and relevant articles were included. Based on the review of scholarly articles, it can be inferred that melatonin, as an endogenous hormone controlling and regulating sleep and wakefulness in various researches, has a good potential due to its antioxidant and anti‐inflammatory with minimal side effects. These beneficial effects highlight the impact of melatonin as an adjuvant and a potential alternative for the better management of SARS‐CoV‐2 infection in high‐risk populations.
The broiler chicken and the Anthropocene: Using critical nexus thinking to unpack the geographies of Gallus gallus domesticus
Authors: Coles Ben
Published: May 2022

A key scientific publication demonstrates that the bio‐physical composition of the broiler chicken (Gallus gallus domesticus) represents a signal of the Anthropocene. This finding contributes to a wider body of evidence that locates the beginning of the Anthropocene in the mid‐20th century, and is part of a broader intellectual project that seeks to establish and demarcate the Anthropocene as a new geological era. This paper takes a different tack. Treating Gallus gallus as an objective corollary for the Anthropocene, it positions the broiler chicken and the Anthropocene as an ontologically emergent nexus comprised of social–spatial relations, materialities, and practices. The paper then adopts critical nexus thinking to trace out the key relations and materialities, and their points of convergence, and underpinning extractivist ontologies that assemble into the chicken's body. Relations of particular concern include the processes that embody surplus value into the corporality of the chicken; the rationalisation and transformation of territories and landscapes into productive units of space, and the tightly coupled, interconnected flows of relations, materials, and coordinating technologies that comprise the ‘supply chain’. It argues that by using critical nexus thinking to identify and articulate these relations that assemble into Gallus gallus, it renders the Anthropocene legible. Such legibility in turn fosters geographical awareness and responsibility that might lead to the changes necessary to address the large‐scale spatial inequalities from which the era stems and redress the consequences that the era might otherwise engender.
Comprehensive study of nine novel cases of TFEB‐amplified renal cell carcinoma: an aggressive tumour with frequent PDL1 expression
Authors: Kammerer‐Jacquet Solène‐Florence , Gandon Camille , Dugay Frederic , Laguerre Brigitte , Peyronnet Benoit , Mathieu Romain , Verhoest Grégory , Bensalah Karim , Leroy Xavier , Aubert Sebastien , Vermaut Catherine , Escande Fabienne , Verkarre Virginie , Compérat Eva , Ambrosetti Damien , Pedeutour Florence , Belaud‐Rotureau Marc‐Antoine , Rioux‐Leclercq Nathalie ,   the members of CARARE French network (Rare Renal Carcinoma in Adults) of the INCa (National Institut of Cancer, France)
Published: May 2022

Aims

First described in 2014, renal cell carcinoma (RCC) with TFEB amplification (6p21) is a rare molecular subgroup whose diagnosis is challenging. The prognosis and therapeutic implications remain unclear.

Methods

We report here the clinical, histological, immunohistochemical, and genetic features of nine novel cases. The pathological and immunohistochemical features were centrally reviewed by expert uropathologists. Fluorescence in situ hybridisation (FISH) confirmed the diagnosis and comparative genomic hybridisation (CGH) was performed to determine quantitative genomic alterations. We also performed an exhaustive review of the literature and compiled our data.

Results

TFEB‐amplified RCC were locally advanced, with initial lymph node involvement in one case and liver metastasis in another case. They were high‐grade eosinophilic tumours with papillary/pseudopapillary architecture, frequent positivity for melanocytic markers, and frequent PDL1 expression. FISH demonstrated high‐level TFEB amplification in six cases. One case showed concomitant TFEB translocation. CGH analysis identified complex alterations with frequent losses of 1p, 2q, 3p, 6p, and frequent 6p and 8q gains. VEGFA coamplification was identified in all cases with a lower level than TFEB. The prognosis was poor, with five patients having lymph node or distant metastases.

Conclusion

TFEB‐amplified RCC is a rare molecular subgroup with variable morphology whose diagnosis is confirmed by FISH analysis. The complex alterations identified by CGH are consistent with an aggressive clinical behaviour. The coamplification of VEGFA and the expression of PDL1 could suggest a potential benefit from antiangiogenics and targeted immunotherapy in combination for these aggressive tumours.