bluuebunny/crossref_metadata_2025 huggingface dataset:
Variable selection in nonlinear function‐on‐scalar regression
Authors: Ghosal Rahul , Maity Arnab
Published: September 2021

We develop a new method for variable selection in a nonlinear additive function‐on‐scalar regression (FOSR) model. Existing methods for variable selection in FOSR have focused on the linear effects of scalar predictors, which can be a restrictive assumption in the presence of multiple continuously measured covariates. We propose a computationally efficient approach for variable selection in existing linear FOSR using functional principal component scores of the functional response and extend this framework to a nonlinear additive function‐on‐scalar model. The proposed method provides a unified and flexible framework for variable selection in FOSR, allowing nonlinear effects of the covariates. Numerical analysis using simulation study illustrates the advantages of the proposed method over existing variable selection methods in FOSR even when the underlying covariate effects are all linear. The proposed procedure is demonstrated on accelerometer data from the 2003–2004 cohorts of the National Health and Nutrition Examination Survey (NHANES) in understanding the association between diurnal patterns of physical activity and demographic, lifestyle, and health characteristics of the participants.
Exploring the association between social behaviour, trust, and its neural correlates in first episode psychosis patients and in individuals at clinical high risk for psychosis
Authors: Wisman‐van der Teen Amanda , Lemmers‐Jansen Imke L. J. , Oorschot Margreet , Krabbendam Lydia
Published: September 2021

Objectives

Psychosis is characterized by paranoid delusions, social withdrawal, and distrust towards others. Trust is essential for successful social interactions. It remains unknown which aspects of social functioning are associated with reduced trust in psychosis. Therefore, we investigated the association between social behaviour, trust, and its neural correlates in a group of individuals with psychotic symptoms (PS‐group), consisting of first episode psychosis patients combined with individuals at clinical high risk.

Methods

We compared 24 PS individuals and 25 healthy controls. Affect and social withdrawal were assessed using the Experience Sampling Method. Trust was measured during functional magnetic resonance imaging (fMRI) scanning, using a trust game with a cooperative and unfair counterpart.

Results

The PS‐group showed lower baseline trust compared to controls and reported less positive and more negative general affect. Social withdrawal did not differ between the groups. Social withdrawal and social reactivity in affect (i.e., changes in affect when with others compared to when alone) were not associated with trust. On the neural level, in controls but not in the PS‐group, social withdrawal was associated with caudate activation during interactions with an unfair partner. An increase in positive social reactivity, was associated with reduced insula activation in the whole sample.

Conclusions

Social withdrawal and social reactivity were not associated with reduced initial trust in the PS‐group. Like controls, the PS‐group showed a positive response in affect when with others, suggesting a decrease in emotional distress. Supporting patients to keep engaging in social interactions, may alleviate their emotional distress.

Practitioner points

Individuals with psychotic symptoms show reduced initial trust towards unknown others.

Trust in others is not associated with social withdrawal and reported affect when with others, nor when alone.

Like controls, individuals with psychotic symptoms showed reduced negative affect and increased positive affect when with others compared to when alone.

We emphasize to support individuals with psychotic symptoms to keep engaging in social interactions, given it may reduce social withdrawal and alleviate their emotional distress.
Myeloma patients with COVID‐19 have superior antibody responses compared to patients fully vaccinated with the BNT162b2 vaccine
Authors: Gavriatopoulou Maria , Terpos Evangelos , Malandrakis Panagiotis , Ntanasis‐Stathopoulos Ioannis , Briasoulis Alexandros , Gumeni Sentiljana , Fotiou Despina , Papanagnou Eleni‐Dimitra , Migkou Magdalini , Theodorakakou Foteini , Eleutherakis‐Papaiakovou Evangelos , Kanellias Nikolaos , Trougakos Ioannis P. , Kastritis Efstathios , Dimopoulos Meletios‐Athanasios
Published: September 2021

Patients with multiple myeloma (MM) have a suboptimal antibody response following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and lower seroconversion rates following coronavirus disease 2019 (COVID‐19) compared with healthy individuals. In this context, we evaluated the development of neutralising antibodies (NAbs) against SARS‐CoV‐2 in non‐vaccinated patients with MM and COVID‐19 compared with patients after vaccination with two doses of the BNT162b2 vaccine. Serum was collected either four weeks post confirmed diagnosis or four weeks post a second dose of BNT162b2. NAbs were measured with a Food and Drug Administration‐approved enzyme‐linked immunosorbent assay methodology. Thirty‐five patients with COVID‐19 and MM along with 35 matched patients were included. The two groups did not differ in age, sex, body mass index, prior lines of therapy, disease status, lymphocyte count, immunoglobulin levels and comorbidities. Patients with MM and COVID‐19 showed a superior humoral response compared with vaccinated patients with MM. The median (interquartile range) NAb titre was 87·6% (71·6–94%) and 58·7% (21·4–91·8%) for COVID‐19‐positive and vaccinated patients, respectively (P = 0·01).Importantly, there was no difference in NAb production between COVID‐19‐positive and vaccinated patients who did not receive any treatment (median NAb 85·1% vs 91·7%, P = 0·14). In conclusion, our data indicate that vaccinated patients with MM on treatment without prior COVID‐19 should be considered for booster vaccine doses.
THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Introduction and Other Protein Targets
Authors: Alexander Stephen P H , Kelly Eamonn , Mathie Alistair , Peters John A , Veale Emma L , Armstrong Jane F , Faccenda Elena , Harding Simon D , Pawson Adam J , Southan Christopher , Buneman O Peter , Cidlowski John A , Christopoulos Arthur , Davenport Anthony P , Fabbro Doriano , Spedding Michael , Striessnig Jörg , Davies Jamie A , Ahlers‐Dannen Katelin E. , Alqinyah Mohammed , Arumugam Thiruma V. , Bodle Christopher , Dagner Josephine Buo , Chakravarti Bandana , Choudhuri Shreoshi P. , Druey Kirk M. , Fisher Rory A. , Gerber Kyle J. , Hepler John R. , Hooks Shelley B. , Kantheti Havish S. , Karaj Behirda , Layeghi‐Ghalehsoukhteh Somayeh , Lee Jae‐Kyung , Luo Zili , Martemyanov Kirill , Mascarenhas Luke D. , McNabb Harrison , Montañez‐Miranda Carolina , Ogujiofor Osita , Phan Hoa , Roman David L. , Shaw Vincent , Sjogren Benita , Sobey Christopher , Spicer Mackenzie M. , Squires Katherine E. , Sutton Laurie , Wendimu Menbere , Wilkie Thomas , Xie Keqiang , Zhang Qian , Zolghadri Yalda
Published: September 2021

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15537. In addition to this overview, in which are identified ‘Other protein targets’ which fall outside of the subsequent categorisation, there are six areas of focus: G protein‐coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders
Authors: Klausen Mette Kruse , Thomsen Morgane , Wortwein Gitta , Fink‐Jensen Anders
Published: September 2021

Drug, alcohol and tobacco use disorders are a global burden affecting millions of people. Despite decades of research, treatment options are sparse or missing, and relapse rates are high. Glucagon‐like peptide 1 (GLP‐1) is released in the small intestine, promotes blood glucose homeostasis, slows gastric emptying and reduces appetite. GLP‐1 receptor agonists approved for treating Type 2 diabetes mellitus and obesity have received attention as a potential anti‐addiction treatment. Studies in rodents and non‐human primates have demonstrated a reduction in intake of alcohol and drugs of abuse, and clinical trials have been initiated to investigate whether the preclinical findings can be translated to patients. This review will give an overview of current findings and discuss the possible mechanisms of action. We suggest that effects of GLP‐1 in alcohol and substance use disorders is mediated centrally, at least partly through dopamine signalling, but precise mechanisms are still to be uncovered.

LINKED ARTICLES

This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc
Decoding the proregenerative competence of regulatory T cells through complex tissue regeneration in zebrafish
Authors: Gupta Samudra , Adhikary Satadal , Hui Subhra Prakash
Published: September 2021

Regulatory T cells (Tregs) are specific subtype of T cells that play a central role in sustaining self-antigen tolerance and restricting inflammatory tissue damage. More recently, additional direct functions of Tregs in mammalian tissue repair have emerged, but the regenerative potential of Tregs in non-mammalian vertebrates has not been explored despite the latter possessing a highly developed adaptive immune system. Why complex organs such as the caudal fin, heart, brain, spinal cord and retina regenerate in certain non-mammalian vertebrates, but not in mammals, is an interesting but unresolved question in the field of regenerative biology. Inflammation has traditionally been thought to be an impediment to regeneration due to the formation of scars. Regenerative decline in higher organisms has been speculated to be the evolutionary advent of adaptive immunity. Recent studies, however, have shown that the innate inflammatory response in non-mammalian organisms is required for organ regeneration. It has also been found that highly advanced adaptive immunity is no longer incompatible with regeneration and for that, Tregs are important. Zebrafish regulatory T cells (zTregs) migrate rapidly to the injury site in damaged organs, where they facilitate the proliferation of regeneration precursor cells by generating tissue-specific regenerative factors by a process distinct from the canonical anti-inflammatory pathway. We review both reparative and proregenerative roles of Tregs in mammals and zebrafish, respectively, and also give an overview of the forkhead box protein 3 (FoxP3) -dependent immunosuppressive function of Tregs in zebrafish, which makes it a useful model organism for future Treg biology and research.
A practical guide to genetic testing in endocrinology
Authors: Izatt Louise , Owens Martina M. , Pierce Heather , Wilcox Sarah , Park Soo‐Mi
Published: September 2021

Rapid advances in sequencing technology have led to significant improvements in genomic analysis, resulting in increased understanding of the molecular basis of many endocrine conditions. Genomic testing for rare disease is being integrated into everyday clinical practice, as the importance of confirming a genetic diagnosis earlier in a patient's pathway helps direct their clinical care and specialized management. In England, the new nationally commissioned Genomic Medicine Service has started to deliver testing for rare and inherited disease and cancer somatic tissue via seven Genomic Laboratory Hubs. The range of genetic tests, technology employed and eligibility criteria for patient testing are all defined in the National Genomic Test Directory. This review provides practical guidance on how to access genomic testing for endocrine disease, how to interpret and relay results, and details how genetic counselling can help integrate results into ongoing care of the individual and their family. This article discusses general principles as well as specifics related to the process of genomic testing in England. We illustrate mainstream genetic testing with a clinical scenario involving an individual with inherited endocrine neoplasia, followed by a generic description of the different steps involved, including informed consent to proceed to diagnostic testing. Most genetic tests analyse multiple genes simultaneously by next‐generation sequencing, and variant interpretation may yield not only pathogenic explanatory results, but also ambiguous outcomes, with variants of unknown significance or incidental findings. Delivery of results and posttest genetic counselling are therefore key components of integrating genetic testing into routine endocrine care.
Accuracy of fine‐needle aspiration of lymph nodes: A cancer center’s experience
Authors: Bueno Adriana Passos , Palu Rafael Felipe , Dalcin José Francisco , Moraes Lucas Neves , da Silva Eveline Cristina , Novaes Silva Tulio , Saieg Mauro Ajaj
Published: September 2021

Introduction

Lymph node fine needle aspiration (LN‐FNA) is a minimally invasive method of evaluating lymphadenopathy. Nonetheless, its use is not widely accepted due to the lack of guidelines and a cytopathological categorisation that directly relates to management. We report our experience with LN FNA at a large Cancer Center in Latin America.

Methods

We retrospectively collected cytological cases of lymph node FNA from the department of pathology at AC Camargo Cancer Center performed over a 2‐year period. Data extracted included LN location, age, sex and final cytological diagnosis. Patients that had undergone neoadjuvant chemotherapy and/or cases for which the surgery specimen location was not clearly reported were excluded. For those cases with surgical reports, risk of malignancy was calculated for each diagnostic category, along with overall performance of cytology. False positive cases were reviewed to assess any possible misinterpretation or sampling errors.

Results

A total of 1730 LN‐FNA were distributed as follows: 62 (3.5%) non‐diagnostic (ND); 1123 (64.9%) negative (NEG), 19 (1.1%) atypical (ATY), 53 (3.1%) suspicious for malignancy (SUS), and 473 (27.3%) positive (POS). Surgical reports were available for 560 cases (32.4%). Risk of malignancy (ROM) for each category was 33.3% for ND, 29.9% for NEG, 25% for ATY, 74.2% for SUS and 99.6% for POS. Overall sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were 78.5%, 99.4%, 70.2% and 99.6%, respectively.

Conclusion

Lymph node FNA is a very specific and accurate exam, which is reliable in the detection of lymph node metastasis and other causes of lymphadenopathy.
Towards establishment of an endoscopic treatment strategy for pancreatic fluid collection in the era of the lumen‐apposing metal stent
Authors: Mukai Shuntaro , Itoi Takao
Published: September 2021

This Editorial refers to the article by J.Y. Bang et al., p 612‐621 of this issue.
Chronotype and well‐being in adults with established type 2 diabetes: A cross‐sectional study
Authors: Quinn Lauren M. , Hadjiconstantinou Michelle , Brady Emer M. , Bodicoat Danielle H. , Henson Joseph J. , Hall Andrew P. , Davies Melanie J.
Published: September 2021

Aims

‘Chronotype’ describes an individual's sleep–wake schedule, and can be classified into morning, intermediate or evening types. Evening chronotype has been widely associated with increased cardiometabolic risk and mortality in people with type 2 diabetes. We explored associations between chronotype and markers of well‐being in people with type 2 diabetes.

Methods

Participants of the ‘Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control’ (CODEC) observational study completed questionnaires to determine chronotype (Morningness–Eveningness Questionnaire, MEQ) and concurrent measures of well‐being (Diabetes‐related Distress scale, Patient Health Questionnaire‐9 to measure depression, and Self‐Compassion Scale), as a secondary endpoint of the study. Adjusted generalised linear models were used to compare well‐being between chronotype subgroups in this cohort.

Results

Of the 808 individuals included in the CODEC study, from convenience sampling, 476 individuals completed the psychosocial questionnaire substudy. Of these, 67% (n = 321) were male, and 86% (n = 408) were white European. From the MEQ, 24% (n = 114) were morning chronotype, 24% (n = 113) were evening and 52% (n = 249) were intermediate chronotype. Diabetes‐related distress was significantly higher in evening chronotypes (exponentiated adjusted coefficient = 1.18 (CI: 1.05–1.32)), compared to morning (padjusted = 0.005) and intermediate chronotypes (padjusted = 0.039). Similarly, depression was significantly higher in evening chronotypes (exponentiated adjusted coefficient = 1.84 (CI: 1.28–2.65)) compared to morning (padjusted = 0.001) and intermediate chronotypes (padjusted = 0.016).

Discussion

Evening chronotype in people with type 2 diabetes may be associated with higher levels of diabetes‐related distress and depression. These findings warrant further investigation to establish causality and evidence‐based interventions that negate the effects of evening chronotype in people with type 2 diabetes.
3‐Dimensional simulations and student learning in orthodontic education
Authors: Ho Angus Cheuk Hin , Liao Chongshan , Lu Jiajing , Shan Zhiyi , Gu Min , Bridges Susan M. , Yang Yanqi
Published: September 2021

Introduction

The electronic dental model (e‐model) is an example of a digital 3‐dimensional technology to support inquiry‐based learning in undergraduate dental education. As student perceptions of and engagement with e‐models vary, it is uncertain whether these perceptions have implications for their learning processes and outcomes.

Materials and Methods

Third‐year dental students (N = 40) completed a questionnaire to identify their perceptions of and preferences for model modalities. They were divided into three groups based on their preference: Preferring plaster models (Group 1); Preferring e‐models (Group 2); No preference (Group 3). Students from three groups (N = 9) attended a hands‐on digital occlusion evaluation workshop, and then completed a case‐based diagnostic evaluation test using digital occlusion evaluation software. Camtasia Studio™ recorded real‐time and on‐screen data of the number of mouse‐clicks and time spent.

Results

Students reported positive feedbacks on the use of e‐models, and 72.5% of the students preferred combination use of e‐models and plaster models. After attending the hands‐on digital dental occlusion evaluation workshop, Group 2 scored higher on the diagnostic evaluation test (p < .05) and registered more mouse‐clicks than Group 1 when evaluating the arch symmetry (p < .05). Group 2 registered fewer mouse‐clicks than Group 3 during tooth size measurement (p < .05). There was no significant difference regarding the time used to answer the knowledge questions amongst the three groups.

Conclusion

Undergraduate dental students indicated a generally high acceptance of e‐models for their learning in orthodontics, and more prefer a blended approach. Students preferring e‐models presented higher performance outcomes, which supports cognitive load theory regarding prior exposure to simulation‐based environments.
Relationship between primary stroke center volume and time to endovascular thrombectomy in acute ischemic stroke
Authors: van Meenen Laura C. C. , den Hartog Sanne J. , Groot Adrien E. , Emmer Bart J. , Smeekes Martin D. , Siegers Arjen , Kommer Geert Jan , Majoie Charles B. L. M. , Roos Yvo B. W. E. M. , van Es Adriaan C. G. M. , Dippel Diederik W. , van der Worp H. Bart , Lingsma Hester F. , Roozenbeek Bob , Coutinho Jonathan M. ,   the MR CLEAN Registry Investigators
Published: September 2021

Background and purpose

We investigated whether the annual volume of patients with acute ischemic stroke referred from a primary stroke center (PSC) for endovascular treatment (EVT) is associated with treatment times and functional outcome.

Methods

We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) registry (2014–2017). We included patients with acute ischemic stroke of the anterior circulation who were transferred from a PSC to a comprehensive stroke center (CSC) for EVT. We examined the association between EVT referral volume of PSCs and treatment times and functional outcome using multivariable regression modeling. The main outcomes were time from arrival at the PSC to groin puncture (PSC‐door‐to‐groin time), adjusted for estimated ambulance travel times, time from arrival at the CSC to groin puncture (CSC‐door‐to‐groin time), and modified Rankin Scale (mRS) score at 90 days after stroke.

Results

Of the 3637 patients in the registry, 1541 patients (42%) from 65 PSCs were included. Mean age was 71 years (SD ± 13.3), median National Institutes of Health Stroke Scale score was 16 (interquartile range [IQR]: 12–19), and median time from stroke onset to arrival at the PSC was 53 min (IQR: 38–90). Eighty‐three percent had received intravenous thrombolysis. EVT referral volume was not associated with PSC‐door‐to‐groin time (adjusted coefficient: −0.49 min/annual referral, 95% confidence interval [CI]: −1.27 to 0.29), CSC‐door‐to‐groin time (adjusted coefficient: −0.34 min/annual referral, 95% CI: −0.69 to 0.01) or 90‐day mRS score (adjusted common odds ratio: 0.99, 95% CI: 0.96–1.01).

Conclusions

In patients transferred from a PSC for EVT, higher PSC volumes do not seem to translate into better workflow metrics or patient outcome.
Potential of intraoperative ultrasonographic assessment of the spinal cord central echo complex in predicting postoperative neurological recovery of degenerative cervical myelopathy
Authors: Chen Guoliang , Wu Huachuan , Chen Ningning , Wang Meng , Shi Liangyu , Li Jiachun , Wei Fuxin , Xu Zuofeng , Liu Xizhe , Liu Shaoyu
Published: September 2021

Background and purpose

The spinal cord central echo complex (SCCEC) is a special ultrasonography‐based intramedullary structure, but its clinical significance in degenerative cervical myelopathy (DCM) is undefined. This study aimed to explore the potential of the SCCEC in predicting postoperative neurological recovery in DCM.

Methods

Thirty‐two DCM patients who underwent intraoperative ultrasonography‐guided French‐door laminoplasty were prospectively enrolled. The modified Japanese Orthopaedic Association (mJOA) score was evaluated preoperatively and 12 months postoperatively. SCCEC width (SCCEC‐W), and anteroposterior diameter (APD) and transverse diameter (TD) of the spinal cord were measured on transverse ultrasonographic images, while the tissue widths from anterior and posterior borders of the spinal cord to the SCCEC were measured on sagittal ultrasonographic images. The APD of the spinal cord and occupying rate of the spinal canal were measured on preoperative magnetic resonance imaging (MRI).

Results

All patients achieved improvements in mJOA scores, with an average recovery rate (RR) of 68.69 ± 20.22%. Spearman correlation analysis revealed that SCCEC‐W, and ratios between the SCCEC‐W and APD/TD based on ultrasonography, correlated moderately with mJOA score RR, with coefficients of −0.527, −0.605 and −0.514, respectively. The ratio between SCCEC‐W and ultrasonographic TD correlated moderately with preoperative APD of the spinal cord. The MRI measurements and ultrasonography‐based tissue widths showed no significant correlation with mJOA score RR.

Conclusions

The SCCEC may have predictive potential as an intraoperative indicator of neurological recovery in treating DCM. SCCEC‐W may be related to spinal cord compression in DCM.
Perceived and Actual Knowledge Gain among Juvenile Drug Treatment Court Team Members: A Pre‐Post Analysis of On‐Site Training and Technical Assistance
Authors: Idrogo Jasmine Victoria , Yelderman Logan A. , Blomquist Martha‐Elin , Broadus Angela D.
Published: September 2021

Juvenile drug treatment courts (JDTCs), in large part, are a product of the therapeutic jurisprudence movement. When they were established in 1993 in the U.S., JDTCs were initially modeled after adult drug treatment courts but insufficiently addressed unique characteristics of adolescence. In 2003, recommended practices, known as the 16 Strategies, for JDTCs working with adolescent offenders with substance use disorders were introduced to the field by the National Drug Court Institute (NDCI) and the National Council of Juvenile and Family Court Judges (NCJFCJ). Recently, the Office of Juvenile Justice and Delinquency Prevention (OJJDP) and the American Institute of Research (AIR), proposed a set of evidence‐based, recommended practices outlined in the Juvenile Drug Treatment Court Guidelines (JDTC Guideline). However, little research examines the effectiveness of training and technical assistance on recommended, evidence‐based practices for JDTC teams. The current study uses a pre/post‐training survey design to examine perceived and actual knowledge gain of JDTC practitioners who receive targeted training and technical assistance on recommended practices for JDTCs. The data demonstrate significantly higher perceived knowledge gain, post‐training, on the topics of recommended practice (as outlined in the 16 Strategies and JDTC Guidelines). Implications are discussed.
Targeting long‐term depression of excitatory synaptic transmission for the treatment of neuropathic pain
Authors: Wang Jing‐Hua , Wu Cheng , Lian Yan‐Na , Liu Li , Li Xiang‐Yao
Published: September 2021

Injury or disease in the somatosensory nervous system may cause broad molecular changes and lead to neuropathic pain. Excitatory synaptic transmission in somatosensory pathways conveys the somatosensory information from the peripheral to the central nervous system. Long‐term effects of excitatory synaptic transmission on the pain pathway contribute to neuropathic pain hypersensitivity. Synaptic strength is dynamically regulated and undergoes bidirectional changes, manifested by two primary forms of synaptic plasticity, long‐term potentiation and long‐term depression (LTD), which are mediated by insertion and endocytosis of amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPARs), respectively. Molecular mechanisms of LTP have been extensively studied; on the other hand, the role of AMPAR endocytosis in the pain‐related synaptic enhancement is less well known. Recent research in the anterior cingulate cortex reveals that loss of LTD contributes to the maintenance of neuropathic pain, which provides the novel perspective of the mechanism of LTD also being critical for maintaining neuropathic pain. More importantly, exploring the molecular mechanism of LTD may help with the development of novel analgesic strategies to manage neuropathic pain.
APOBEC3C, a nucleolar protein induced by genotoxins, is excluded from DNA damage sites
Authors: Constantin Daniel , Dubuis Gilles , Conde‐Rubio María del Carmen , Widmann Christian
Published: September 2021

The human genome contains 11 APOBEC (apolipoprotein B mRNA editing catalytic polypeptide‐like) cytidine deaminases classified into four families. These proteins function mainly in innate antiviral immunity and can also restrict endogenous retrotransposable element multiplication. The present study focuses on APOBEC3C (A3C), a member of the APOBEC3 subfamily. Some APOBEC3 proteins use their enzymatic activity on genomic DNA, inducing mutations and DNA damage, while other members facilitate DNA repair. Our results show that A3C is highly expressed in cells treated with DNA‐damaging agents. Its expression is regulated by p53. Depletion of A3C slightly decreases proliferation and does not affect DNA repair via homologous recombination or nonhomologous end joining. The A3C interactomes obtained from control cells and cells exposed to the genotoxin etoposide indicated that A3C is a nucleolar protein. This was confirmed by the detection of either endogenous or ectopic A3C in nucleoli. Interestingly, we show that A3C is excluded from areas of DNA breaks in live cells. Our data also indicate that the C‐terminal part of A3C is responsible for its nucleolar localization and exclusion from DNA damage sites.
Neoproterozoic syn‐glacial carbonate precipitation and implications for a snowball Earth
Authors: Hood Ashleigh v. S. , Penman Donald E. , Lechte Maxwell A. , Wallace Malcolm W. , Giddings Jonathan A. , Planavsky Noah J.
Published: September 2021

The Neoproterozoic ‘snowball Earth’ hypothesis suggests that a runaway ice–albedo feedback led to two intense glaciations around 717–635 million years ago, and this global ice cover would have drastically impacted biogeochemical cycles. Testing the predictions of this hypothesis against the rock record is key to understanding Earth’s surface evolution in the Neoproterozoic. A central tenet of the snowball Earth hypothesis is that extremely high atmospheric CO2 levels—supplied by volcanic degassing over millions of years—would be required to overcome a strong ice–albedo feedback and trigger deglaciation. This requires severely diminished continental weathering (and associated CO2 drawdown) during glaciation, and implies that carbonate minerals would not precipitate from syn‐glacial seawater due to a lack of alkalinity influxes into ice‐covered oceans. In this scenario, syn‐glacial seawater chemistry should instead be dominated by chemical exchange with the oceanic crust and volcanic systems, developing low pH and low Mg/Ca ratios. However, sedimentary rocks deposited during the Sturtian glaciation from the Adelaide Fold Belt—and contemporaneous successions globally—show evidence for syn‐sedimentary dolomite precipitation in glaciomarine environments. The dolomitic composition of these syn‐glacial sediments and post‐glacial ‘cap carbonates’ implies that carbonate precipitation and Mg cycling must have remained active during the ~50 million‐year Sturtian glaciation. These syn‐glacial carbonates highlight a gap in our understanding of continental weathering—and therefore, the carbon cycle—during snowball Earth. In light of these observations, a Precambrian global biogeochemical model (PreCOSCIOUS) was modified to explore scenarios of syn‐glacial chemical weathering, ocean chemistry and Sturtian carbonate mineralogy. Modelling results suggest that a small degree of chemical weathering during glaciation would have been capable of maintaining high seawater Mg/Ca ratios and carbonate precipitation throughout the Sturtian glaciation. This is consistent with a severe ice age during the Sturtian, but challenges predictions of biogeochemical cycling during the endmember ‘hard snowball’ models. A small degree of continental weathering might also help explain the extreme duration of the Sturtian glaciation, which appears to have been the longest ice age in Earth history.
Ocean warming threatens key trophic interactions supporting a commercial fishery in a climate change hotspot
Authors: Holland Owen J. , Young Mary A. , Sherman Craig D. H. , Tan Mun Hua , Gorfine Harry , Matthews Ty , Miller Adam D.
Published: September 2021

Worldwide, rising ocean temperatures are causing declines and range shifts in marine species. The direct effects of climate change on the biology of marine organisms are often well documented; yet, knowledge on the indirect effects, particularly through trophic interactions, is largely lacking. We provide evidence of ocean warming decoupling critical trophic interactions supporting a commercially important mollusc in a climate change hotspot. Dietary assessments of the Australian blacklip abalone (Haliotis rubra) indicate primary dependency on a widespread macroalgal species (Phyllospora comosa) which we show to be in state of decline due to ocean warming, resulting in abalone biomass reductions. Niche models suggest further declines in P. comosa over the coming decades and ongoing risks to H. rubra. This study highlights the importance of studies from climate change hotspots and understanding the interplay between climate and trophic interactions when determining the likely response of marine species to environmental changes.
Academic mothers with disabilities: Navigating academia and parenthood during COVID‐19
Authors: Wagner Kathryn , Pennell Summer Melody , Eilert Meike , Lim Stacey R.
Published: September 2021

Academic mothers (including nonbinary, trans, and genderqueer parents) have always faced challenges in their profession due to systemic barriers and a “motherhood tax”; however, COVID‐19 has exacerbated already existing inequalities (Oleschuk, 2020). This study examines how the pandemic has affected academic mothers with mental health and physical disabilities, as these voices often remain hidden and unheard in academia despite increased awareness of their presence (Brown & Leigh, 2018; Kelly & Senior, 2020). Here, we share the voices of 23 participants using a qualitative methodology drawing from social justice and feminist theories to highlight the lived experience of academic mothers with mental and/or physical disabilities and their experiences as a scholar and parent during COVID‐19. Understanding the lived experience of this intersectional population can provide invaluable insights into ableist privilege within higher education, especially in the context of COVID‐19 which has substantially disrupted work and homelife routines.
Cutaneous manifestations in children with SARS‐CoV‐2 infection and/or COVID‐19: what do we know after 10 months under this pandemic?
Authors: Li Hongxin , Zhao Yong , Zhou Lin
Published: September 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global crisis. However, cutaneous manifestations in children with SARS‐CoV‐2 infection have received little attention.

Objective

Our study was aimed to present clinical and cutaneous manifestations of children with SARS‐CoV‐2 and to provide the basis for early diagnosis.

Methods

We analyzed the clinical data of COVID‐19 infected (CI) children worldwide from December 2019 to October 6, 2020, by using search terms “COVID‐19,” “SARS‐CoV‐2,” “Coronavirus” in combination with “cutaneous,” “lesion,” “rash,” “skin,” “dermatology,” “epidermis,” “dermis,” “multisystem inflammatory syndrome.” We collected and analyzed the general information, clinical symptoms, cutaneous manifestations, laboratory examination results, history of close contact with CI patients or suspected CI patients, and outcome in CI children.

Results

Among 90 CI children, there were 46 boys (59%) and 32 girls (41%). Erythema was the most frequent lesion, followed by conjunctivitis, and edematous lesions. Face was the most commonly affected location including lips, conjunctivae, tongue, eyes, and eyelids. Sixty‐three (73.3%) patients had multisystem inflammatory syndrome (MIS‐C). As for clinical symptoms, 70 (81.4%) CI children suffered fever, and 34 (39.5%) patients had lung involvement. Meanwhile, 65.1% of patients had cardiac involvement, 4.7% of patients were asymptomatic, and 71.6% of patients received intravenous immunoglobulin, as well as 31.1% of CI children received systemic corticosteroids. Three children were dead. The most frequent route of infection was familial clustering. As silent virus carriers of CI children, it is important to find out the clinical and cutaneous manifestations in CI children to prevent and control COVID‐19 transmission.
The role of interleukin‐17 (IL‐17) in the pathogenesis of discoid lupus erythematosus and lichen planopilaris: is immunohistochemistry for IL‐17 a promising way to differentiate these entities?
Authors: Shahidi Dadras Mohammad , Rakhshan Azadeh , Dadkhahfar Sahar , Barat Tara
Published: September 2021

Background

Interleukin‐17 (IL‐17) is a pro‐inflammatory mediator which its excess secretion by immune cells is found in many chronic autoimmune diseases. This survey is aimed to compare the amount and pattern of distribution of IL‐17 positive cells in lichen planopilaris (LPP) and discoid lupus erythematosus (DLE) which are of the most frequent causes of primary cicatricial alopecia (CA).

Methods

Biopsies of lesional scalp skin from adult LPP (n = 30), DLE patients (n = 19), and control scalp skin (n = 18) were analyzed by immunohistochemistry (IHC) method using rabbit polyclonal antibody against IL‐17. Cells stained positive for IL‐17 and their pattern of distribution were assessed and compared between these groups.

Results

The mean of IL‐17 positive cell counts per high power field (HPF) in both LPP and DLE groups was significantly higher in comparison with the control group (both p < .0001). The LPP group had higher values of IL‐17 positive cell counts per HPF (47.56 ± 13.37) compared to the DLE group (22.21 ± 11.06) (p < .0001). More than 30 IL‐17 positive cell counts in IHC have a sensitivity of 90% and a specificity of 78% for differentiating LPP from DLE.

Conclusions

Our findings suggest that IL‐17 is effective in the pathogenesis of DLE and LPP and its role is more prominent in LPP. IL‐17 positive cells in IHC can distinguish DLE from LPP with satisfactory sensitivity and specificity.
Trends and safety of robot‐assisted partial nephrectomy during the initial 2‐year period after government approval in Japan: A nationwide database study from 2016 to 2018
Authors: Yokoyama Minato , Ishioka Junichiro , Toba Mikayo , Fukushima Hiroshi , Tanaka Hajime , Yoshida Soichiro , Matsuoka Yoh , Ai Masumi , Fushimi Kiyohide , Fujii Yasuhisa
Published: September 2021

Objectives

To evaluate the trends and safety of robot‐assisted partial nephrectomy during the initial 2‐year period after government approval for this type of procedure in April 2016.

Methods

This nationwide retrospective study included 3722 received robot‐assisted partial nephrectomy cases carried out from April 2016 to March 2018 in 124 participating institutions. The institutions were divided into lower‐ and higher‐volume institutions according to the median of 19 robot‐assisted partial nephrectomy cases during the study period. Surgical outcomes between 616 cases from lower‐volume institutions and 3106 cases from higher‐volume institutions were compared using propensity score matching.

Results

During the study period, both the number of robot‐assisted partial nephrectomy surgeries and the number of institutions in which the surgery was carried out steadily increased. Overall, the median anesthesia time was 217 min, the median postoperative length of stay was 9 days, and the proportion of blood transfusions, complications and readmissions were 0.8%, 5.1% and 1.0%, respectively. There were no significant differences in anesthesia time, incidence of blood transfusions, and complication rates between the lower‐volume and higher‐volume institutions. However, a slightly, but significantly, longer postoperative length of stay and a lower incidence of readmission were observed in lower‐volume institutions both before and after propensity score matching.

Conclusions

Robot‐assisted partial nephrectomy has become widespread during the initial 2‐year period after government approval with an acceptable safety profile, regardless of the institutional caseloads. This technique has become a standard of care for stage 1 renal cancer patients in Japan.
Survey study of trends in adult nephrology advanced training in Australia and New Zealand
Authors: Yaxley Julian , Campbell Scott B. , Gray Nicholas A. , Viecelli Andrea K.
Published: September 2021

Background

There has been considerable growth in nephrology advanced trainee numbers in Australia and New Zealand, with uncertain effects on clinical experience, competence and employment outcomes.

Aims

To review the perceived adequacy and temporal trends of advanced training in nephrology in Australia and New Zealand by evaluating training experiences, personal views on important aspects of training and nephrology, career paths and early employment outcomes.

Methods

An online survey was distributed to members of the Australian and New Zealand Society of Nephrology through email in December 2020. Responses were sought from current trainees and from nephrologists qualifying since 2014. Likert scale proportions were calculated and group comparisons made using the Chi‐squared test.

Results

A total of 88 participants returned the survey yielding a response rate of 32%, with a representative sample of trainees and consultants from across Australia and New Zealand. Training was reported as adequate in most aspects of clinical nephrology, although 88% of respondents felt poorly prepared for entering private practice and 61% reported inadequate training in kidney histopathology. Exposure to clinical procedures was variable, with adequate training in percutaneous kidney biopsy, but mostly inadequate training in dialysis access insertion. Sixty‐nine percent of nephrologists completed their advanced training entirely in large urban centres and 85% worked in an urban area after training. Only 23% of consultants were engaged in full‐time clinical employment in their first‐year post‐training and 78% were undertaking at least one of dual specialty training or a higher degree by research. Demand for subspecialty fellowships was high.

Conclusion

Trainees and nephrologists in Australia and New Zealand are currently satisfied with their training in most aspects of nephrology; however, some clinical experiences are perceived as inadequate and early career paths after advanced training are increasingly diverse.
Prostaglandin E2 directly inhibits the conversion of inducible regulatory T cells through EP2 and EP4 receptors via antagonizing TGF‐β signalling
Authors: Goepp Marie , Crittenden Siobhan , Zhou You , Rossi Adriano G , Narumiya Shuh , Yao Chengcan
Published: September 2021

Regulatory T (Treg) cells are essential for control of inflammatory processes by suppressing effector T‐cell functions. The actions of PGE2 on the development and function of Treg cells, particularly under inflammatory conditions, are debated. In this study, we employed pharmacological and genetic approaches to examine whether PGE2 had a direct action on T cells to modulate de novo differentiation of Treg cells. We found that TGF‐β‐induced Foxp3 expression and iTreg cell differentiation in vitro is markedly inhibited by PGE2, which was mediated by the receptors EP2 and EP4. Mechanistically, PGE2‐EP2/EP4 signalling interrupts TGF‐β signalling during iTreg differentiation. Moreover, EP4 deficiency in T cells impaired iTreg cell differentiation in vivo. Thus, our results demonstrate that PGE2 negatively regulates iTreg cell differentiation through a direct action on T cells, highlighting the potential for selectively targeting the PGE2‐EP2/EP4 pathway to control T cell‐mediated inflammation.
Retrospective screening for SARS‐CoV‐2 among influenza‐like illness hospitalizations: 2018–2019 and 2019–2020 seasons, Valencia region, Spain
Authors: Mira‐Iglesias Ainara , Mengual‐Chuliá Beatriz , Cano Laura , García‐Rubio Javier , Tortajada‐Girbés Miguel , Carballido‐Fernández Mario , Mollar‐Maseres Juan , Schwarz‐Chavarri Germán , García‐Esteban Sandra , Puig‐Barberà Joan , Díez‐Domingo Javier , López‐Labrador F. Xavier
Published: September 2021

On 9 March 2020, the World Health Organization (WHO) Global Influenza Programme (GIP) asked participant sites on the Global Influenza Hospital Surveillance Network (GIHSN) to contribute to data collection concerning severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). We re‐analysed 5833 viral RNA archived samples collected prospectively from hospital admissions for influenza‐like illness (ILI) in the Valencia Region of Spain by the Valencia Hospital Surveillance Network for the Study of Influenza and Other Respiratory Viruses (VAHNSI) network (four hospitals, catchment area population 1 118 732) during the pre‐pandemic 2018/2019 (n = 4010) and pandemic 2019/2020 (n = 1823) influenza seasons for the presence of SARS‐CoV‐2. We did not find evidence for community‐acquired SARS‐CoV‐2 infection in hospital admissions for ILI in our region before early March 2020.
Determining the disordered nanostructure of calcium silicate hydrate (C‐S‐H) from broad X‐ray diffractograms
Authors: Basquiroto de Souza Felipe , Sagoe‐Crentsil Kwesi , Duan Wenhui
Published: September 2021

Calcium silicate hydrate (C‐S‐H), the main binder of Portland cement, is one of the most complex nanostructured materials, making the retrieval of its highly defective atomic arrangement a long‐standing challenge. This drawback prevents the development of realistic molecular models to guide the optimization of the physicochemical properties of Portland cement materials. Here, we applied Debye function analysis (DFA), an ab initio X‐ray diffraction (XRD) analysis method suitable to disordered nanostructured materials, to identify the atomic and nanoscale structural‐disorder features that dictate C‐S‐H's scattering properties. By examining the DFA theoretical calculations of C‐S‐H with different sizes, crystal defects, and stacking faults, we discovered that random layer rotations are a critical feature in the C‐S‐H phases, which has been largely overlooked by other XRD analysis methods. Moreover, the DFA calculations disclosed that C‐S‐H consists of layered, plate‐like nanoparticles with ∼10 nm in lateral size and defined crystal defects, in agreement with previous neutron scattering and spectroscopic studies. These findings may not only enable the construction of more accurate nanoscale models of hydrated cement but have potential wider application to similar complex layered structures, such as phyllosilicates, in ceramic and geological materials.