bluuebunny/crossref_metadata_2025 huggingface dataset:
Astrogliosis and compensatory neurogenesis after the first ethanol binge drinking‐like exposure in the adolescent rat
Authors: Vilpoux Catherine , Fouquet Gregory , Deschamps Chloe , Lefebvre Elise , Gosset Philippe , Antol Johann , Zabijak Luciane , Marcq Ingrid , Naassila Mickael , Pierrefiche Olivier
Published: December 2021

Background

Multiple ethanol binge drinking‐like exposures during adolescence in the rat induce neuroinflammation, loss of neurogenesis, and cognitive deficits in adulthood. Interestingly, the first ethanol binge drinking‐like exposure during adolescence also induces short‐ term impairments in cognition and synaptic plasticity in the hippocampus though the cellular mechanisms of these effects are unclear. Here, we sought to determine which of the cellular effects of ethanol might play a role in the disturbances in cognition and synaptic plasticity observed in the adolescent male rat after two binge‐like ethanol exposures.

Methods

Using immunochemistry, we measured neurogenesis, neuronal loss, astrogliosis, neuroinflammation, and synaptogenesis in the hippocampus of adolescent rats 48 h after two binge‐like ethanol exposures (3 g/kg, i.p., 9 h apart). We used flow cytometry to analyze activated microglia and identify the TLR4‐expressing cell types.

Results

We detected increased hippocampal doublecortin immunoreactivity in the subgranular zone (SGZ) of the dentate gyrus (DG), astrogliosis in the SGZ, and a reduced number of mature neurons in the DG and in CA3, suggesting compensatory neurogenesis. Synaptic density decreased in the stratum oriens of CA1 revealing structural plasticity. There was no change in microglial TLR4 expression or in the number of activated microglia, suggesting a lack of neuroinflammatory processes, although neuronal TLR4 was decreased in CA1 and DG.

Conclusions

Our findings demonstrate that the cognitive deficits associated with hippocampal synaptic plasticity alterations that we previously characterized 48 h after the first binge‐like ethanol exposures are associated with hippocampal structural plasticity, astrogliosis, and decreased neuronal TLR4 expression, but not with microglia reactivity.
Is the extractive industries standard still fit for purpose?
Authors: Cortese Corinne , Moerman Lee , Chang Millicent
Published: December 2021

The application of AASB 6 by extractive industries firms is examined to determine the issues and challenges faced by financial statement preparers when applying the standard. The results show that while the area‐of‐interest method is extensively chosen to account for exploration and evaluation costs, there was lack of consistency in its description. Interviews revealed that while preparers reported flexibility in the application of AASB 6, they sought more guidance to reduce reliance on external publications. The findings show that while preparers supported the retention of AASB 6, more guidance on its application was needed, especially in its interaction with new accounting standards and regulations.
A survey study of endometrial receptivity tests and immunological treatments in in vitro fertilisation (IVF)
Authors: Kieu Violet , Lantsberg Daniel , Mizrachi Yossi , Stern Catharyn , Polyakov Alex , Teh Wan Tinn
Published: December 2021

Background

Suboptimal endometrial receptivity is a key factor behind in vitro fertilisation (IVF) implantation failure. Direct clinical tests of the endometrium of natural killer (NK) cells and endometrial receptivity analysis (ERA) are controversial.

Aims

To examine the current practice of endometrial receptivity tests (NK cells and ERA) and immunological treatments (corticosteroids, anticoagulants, antiplatelets, intravenous immunoglobulin, Intralipid, other) among fertility specialists in Australia and New Zealand.

Methods

A prospective 23‐item web‐based survey was distributed by email via the Fertility Society of Australia and New Zealand, between August and October 2020. Data were collected and analysed using Qualtrics.

Results

Of 238 fertility specialists, 90 completed the survey (response rate 37.8%). ERA (48/90, 53.3%) was most commonly ordered, followed by uterine NK (uNK) (36/90, 40.0%) and peripheral blood NK (pNK) (12/90, 13.3%). For all tests, the most common indication was recurrent implantation failure (RIF) (41/48, 22/36, 6/12; 85.4%, 61.1%, and 50.0%, respectively for ERA, uNK and pNK). Of those that did not offer these tests, the main reason cited was insufficient evidence (30/42, 47/54, 68/78; 71.4%, 87.0%, and 87.0%). A third of specialists offered empirical immunological treatment for RIF (30/90, 33.3%): anticoagulants (28/30, 93.3%), antiplatelets (27/30, 90.0%), and corticosteroids (25/30; 83.3%). The majority of specialists (56/90, 62.2%) stated they had refused a patient request for endometrial testing or treatment.

Conclusions

Tests for presumed endometrial receptivity pathology are often used in Australia and New Zealand. Immunological treatments for RIF are commonly employed empirically, without strong evidence of their effectiveness or safety. Further studies should focus on education and clinical adherence to evidence‐based guidelines.
Risk factors for systemic reactions in typical cold urticaria: Results from the COLD‐CE study
Authors: Bizjak Mojca , Košnik Mitja , Dinevski Dejan , Thomsen Simon Francis , Fomina Daria , Borzova Elena , Kulthanan Kanokvalai , Meshkova Raisa , Ahsan Dalia Melina , Al‐Ahmad Mona , Altrichter Sabine , Bauer Andrea , Brockstädt Maxi , Costa Célia , Demir Semra , Fachini Criado Roberta , Ensina Luis Felipe , Gelincik Asli , Giménez‐Arnau Ana Maria , Gonçalo Margarida , Gotua Maia , Holm Jesper Grønlund , Inomata Naoko , Kasperska‐Zajac Alicja , Khoshkhui Maryam , Klyucharova Aliya , Kocatürk Emek , Lu Rongbiao , Makris Michael , Maltseva Natalya , Miljković Jovan , Pasali Maria , Paulino Marisa , Pesqué David , Peter Jonny , Ramón German Dario , Ritchie Carla , Rodrigues Valle Solange Oliveira , Rudenko Michael , Sikora Agnieszka , de Souza Lima Eduardo M. , Wagner Nicola , Xepapadaki Paraskevi , Xue Xiaoyang , Zhao Zuotao , Terhorst‐Molawi Dorothea , Maurer Marcus
Published: December 2021

Background

Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold‐induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU.

Methods

An international, cross‐sectional study COLD‐CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold‐induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms.

Results

Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold‐induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes.

Conclusion

ColdA is common in typical ColdU. High‐risk patients require education about their condition and how to use an adrenaline autoinjector.
Adenovirus can be a serious, life‐threatening disease, even in previously healthy children
Authors: Dotan Miri , Zion Elena , Bilavsky Efraim , Nahum Elhanan , Ben‐Zvi Haim , Zalcman Jonatan , Yarden‐Bilavsky Havatzelet , Kadmon Gili
Published: December 2021

Aim

Adenovirus infections are exceedingly common in childhood. However, little is known of the clinical characteristics of children admitted with severe infection to the paediatric intensive care unit (PICU).

Methods

Clinical data on children hospitalised with adenovirus infection between January 2005 and March 2020 were collected. We compared data between children hospitalised in the PICU and those who were not in a 1:2 ratio.

Results

During the study period, 69 children with adenovirus infection were admitted to the PICU, representing 5% of all hospitalised children with adenovirus. Thirty‐four (49%) were previously healthy children. Mortality occurred in 5 patients, and all had an underlying illness. Cidofovir was used in 21 children, including 11 who were previously healthy. No side effects were attributed to the treatment. During 2005–2014, viral co‐infection rates were 42% in the PICU group and 11% in the control group (p = 0.002). However, during 2015–2020, when the viral panel became widespread in our institution, the rates of co‐infection were similar in the two groups (32% and 34%, p = 1.0).

Conclusion

Our findings suggest that adenovirus may present as a serious, life‐threatening disease even in previously healthy children.
Understanding safe water‐carrying practices during pregnancy and postpartum: A mixed‐methods study in Nepal
Authors: Tomberge Vica Marie Jelena , Shrestha Akina , Meierhofer Regula , Inauen Jennifer
Published: December 2021

Daily carrying of heavy loads of domestic water, especially during pregnancy and postpartum, bears a threat to maternal health in low‐income countries. Using an extended health action process approach (HAPA), we examined women's reasons for and psychosocial determinants of safe water‐carrying during pregnancy and postpartum. In a mixed‐methods study, trained local interviewers conducted 1001 quantitative interviews with women of reproductive age (n = 921 analyzed) and 21 qualitative interviews with women of reproductive age, in‐laws, and spouses in rural Nepal. We analyzed the quantitative data with generalized estimating equations to model the HAPA‐based psychosocial determinants of avoiding water‐carrying during pregnancy and postpartum. Subjective perspectives were investigated with thematic analysis. Outcome expectancies (B = 0.24), self‐efficacy (B = 0.20), and injunctive norms (B = 0.23) were significantly associated with the intention to avoid water‐carrying. Self‐efficacy (B = 0.36) and instrumental support (B = 0.05) are related to behavior (all p < 0.05). Women explained water‐carrying during pregnancy by a lack of family support, a shift of health decision‐making power to in‐laws, and low behavioral control. Overall, the necessity of water, family decision‐making structures, and low support make it difficult for women to discontinue water‐carrying. Additionally to infrastructural improvements, behavioral interventions may increase women's self‐efficacy for safe water‐carrying (e.g. reducing weight) and social support.
Prognostic implications of the tumor immune microenvironment and immune checkpoint pathway in primary central nervous system diffuse large B‐cell lymphoma in the North Indian population
Authors: Parkhi Mayur , Chatterjee Debajyoti , Bal Amanjit , Vias Poorva , Yadav Budhi Singh , Prakash Gaurav , Gupta Sunil Kumar , Radotra Bishan Dass
Published: December 2021

Primary central nervous system‐diffuse large B‐cell lymphoma (PCNS‐DLBCL) is a rare, extranodal malignant lymphoma carrying poor prognosis. The prognostic impact of tumor microenvironment (TME) composition and the PD‐1/PD‐L1 immune checkpoint pathway are still undetermined in PCNS‐DLBCL. We aimed to quantify the tumor‐infiltrating lymphocytes (TILs), tumor‐associated macrophages (TAMs), and PD‐L1 expression in the PCNSL and evaluated their prognostic significance. All patients with histopathologically diagnosed PCNS‐DLBCL over a period of 7 years were recruited. Immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, PD‐1, and PD‐L1 was performed on the tissue microarray. Forty‐four cases of PCNS‐DLBCL, who satisfied the selection criteria, were included with mean age of 55 ± 12.3 years and male‐to‐female ratio of 0.91:1. The mean overall survival (OS) and disease‐free survival (DFS) was 531.6 days and 409.8 days, respectively. Among TILs, an increased number of CD3+ T cells showed better OS and DFS, without achieving statistical significance. CD4 positive T‐cells were significantly associated with the longer OS (p = 0.037) and DFS (p = 0.023). TAMs (68CD and CD163 positive) showed an inverse relationship with OS and DFS but did not reach statistical significance (p > 0.05). Increased PD‐L1 expression in immune cells, but not in tumor cells, was associated with significantly better DFS (p = 0.037). The TME plays a significant role in the prognosis of PCNS‐DLBCL. Increased number of CD4+ T cells and PD‐L1–expressing immune cells is associated with better prognosis in PCNS‐DLBCL. Further studies with larger sample size are required to evaluate the role of targeted therapy against the TME and immune check point inhibitors in this disease.
Clinicopathological and molecular characteristics of the alpha‐fetoprotein–producing gastric cancer: emphasis on two major subtypes
Authors: Lu Jun , Jin Mulan , Zhou Xiang , Chen Xin , Shao Yang , Jiang Xingran
Published: December 2021

Alpha‐fetoprotein–producing gastric cancer (AFPGC) is associated with high invasion and poor prognosis, but has not been well‐documented due to its rarity. To develop the understanding of AFPGC, and further facilitate its clinical decision‐making and treatment, we performed clinicopathological and molecular characterization of AFPGC and its two major subtypes, namely, gastric adenocarcinoma with enteroblastic differentiation (GAED) and hepatoid adenocarcinoma (HAC). The clinicopathological and molecular characteristics of AFPGC patients (n = 54) were mainly investigated by immunohistochemistry and next‐generation sequencing (NGS) approaches. AFPGC exhibited a higher incidence of lymphatic and vascular invasion than conventional gastric adenocarcinoma (CGA). Despite various morphological patterns, there was mostly no evident difference in clinicopathological characteristics between the GAED and HAC subtypes. Target‐enriched NGS profiling of disease mutation landscapes discovered 17 differentially mutated genes between AFPGC and CGA. The AFPGC patients carrying ZNF217 mutations had poorer overall survival than the ZNF217 wildtype. Furthermore, ATR showed a significantly higher mutation rate in GAED than in HAC. Overall, our study of clinicopathological characteristics shed light on the differences between CGA and AFPGC, as well as the relationships between the GAED and HAC subtypes of AFPGC. Furthermore, mutation landscape profiling revealed potential diagnostic and prognostic markers for AFPGC and its two subtypes.
Procrastinate at work, sleep badly at night: How job autonomy matters
Authors: Song Baihe , Wang Bin , Qian Jing , Zhang Yue
Published: December 2021

Despite the well‐documented deleterious effects of poor sleep quality on procrastination, limited efforts have been devoted to examining whether procrastination can hurt sleep quality. To address this theoretical gap, this study aims to reveal how and when individuals' procrastination at work influences their subsequent sleep quality. Building upon cognitive appraisal theory, the current research employs experience‐sampling methodology to investigate mediators of rumination (as a cognitive pathway) and negative affect (as an affective pathway), explaining within‐person fluctuations in sleep quality resulting from daily procrastination. Furthermore, job autonomy is proposed to be a cross‐level moderator in the relationship between daily procrastination and rumination/negative affect. The results of 2026 daily data records from 213 employees across 10 consecutive workdays supported the mediation effect of rumination and moderation effects of job autonomy but did not support the mediation effect of negative affect. Specifically, daily procrastination was negatively related to subsequent sleep quality through the cognitive pathway of rumination. Our results also reveal that the positive relationships between daily procrastination and rumination/negative affect were stronger for employees with higher levels of job autonomy. Finally, we discuss the implications and limitations of this paper as well as future directions.
Outcome predictors for maternal red blood cell alloimmunisation with anti‐K and anti‐D managed with intrauterine blood transfusion
Authors: Vlachodimitropoulou Evangelia , Garbowski Maciej , Anne Solomon Shelley , Abbasi Nimrah , Seaward Gareth , Windrim Rory , Keunen Johannes , Kelly Edmond , Van Mieghem Tim , Shehata Nadine , Ryan Greg
Published: December 2021

Red blood cell (RBC) alloimmunisation with anti‐D and anti‐K comprise the majority of cases of fetal haemolytic disease requiring intrauterine red cell transfusion (IUT). Few studies have investigated which haematological parameters can predict adverse fetal or neonatal outcomes. The aim of the present study was to identify predictors of adverse outcome, including preterm birth, intrauterine fetal demise (IUFD), neonatal death (NND) and/or neonatal transfusion. We reviewed the records of all pregnancies alloimmunised with anti‐K and anti‐D, requiring IUT over 27 years at a quaternary fetal centre. We reviewed data for 128 pregnancies in 116 women undergoing 425 IUTs. The median gestational age (GA) at first IUT was significantly earlier for anti‐K than for anti‐D (24·3 vs. 28·7 weeks, P = 0·004). Women with anti‐K required more IUTs than women with anti‐D (3·84 vs. 3·12 mean IUTs, P = 0·036) and the fetal haemoglobin (Hb) at first IUT was significantly lower (51.0 vs. 70.5 g/l, P = 0·001). The mean estimated daily decrease in Hb did not differ between the two groups. A greater number of IUTs and a slower daily decrease in Hb (g/l/day) between first and second IUTs were predictive of a longer period in utero. Earlier GA at first IUT and a shorter interval from the first IUT until delivery predicted IUFD/NND. Earlier GA and lower Hb at first IUT significantly predicted need for phototherapy and/or blood product use in the neonate. In the anti‐K group, a greater number of IUTs was required in women with a higher titre. Furthermore, the higher the titre, the earlier the GA at which an IUT was required in both groups. The rate of fall in fetal Hb between IUTs decreased, as the number of transfusions increased. Our present study identified pregnancies at considerable risk of an unfavourable outcome with anti‐D and anti‐K RBC alloimmunisation. Identifying such patients can guide pregnancy management, facilitates patient counselling, and can optimise resource use. Prospective studies can also incorporate these characteristics, in addition to laboratory markers, to further identify and improve the outcomes of these pregnancies.
Theoretical study of myriocin‐binding mechanism targeting serine palmitoyltransferase
Authors: Yu Li , Jiang Yingmin , Xu Lei , Jin Jian , Pei Zejun , Zhu Jingyu
Published: December 2021

Sphingolipids (SLs) are vital for cells as forming membrane and transducing signals. The first step for de novo biosynthesis of SLs is catalyzed by the pyridoxal‐5′‐phosphate (PLP)‐dependent enzyme serine palmitoyltransferase (SPT), which has been proven to be a promising drug target for treating various diseases. However, there are few SPT‐specific inhibitors have been identified so far. Myriocin, a natural fungal product, is confirmed as the most potent inhibitor of SPT and has been widely used, but studies of its molecular mechanism are still underway. Besides, there is no intact co‐crystal structure of SPT‐binding myriocin until now. Aiming to uncover the interaction mechanism between SPT‐ and PLP‐binding myriocin at the molecular level, a systematic computational strategy was performed in this present study. Firstly, covalent docking was implemented to preliminarily predict the binding pose SPT/PLP‐myriocin aldimine and its structurally similar intermediate SPT/PLP‐β‐ketoacid aldimine. Secondly, two binding complexes were treated as initial structures to perform molecular dynamics simulations and binding free energy calculations. The calculated docking scores and predicted binding energies were consistent with the reported bioactivities. Finally, the binding mechanism of myriocin binding with SPT was meticulously described, and the key residues making favorable contributions were highlighted. Taken together, the current study could provide some important information and valuable guidance for further rational screening, design, and modification of potent specific SPT inhibitors.
Recent advances and perspectives of postoperative neurological disorders in the elderly surgical patients
Authors: Liu Biying , Huang Dan , Guo Yunlu , Sun Xiaoqiong , Chen Caiyang , Zhai Xiaozhu , Jin Xia , Zhu Hui , Li Peiying , Yu Weifeng
Published: December 2021

Postoperative neurological disorders, including postoperative delirium (POD), postoperative cognitive dysfunction (POCD), postoperative covert ischemic stroke, and hemorrhagic stroke, are challenging clinical problems in the emerging aged surgical population. These disorders can deteriorate functional outcomes and long‐term quality of life after surgery, resulting in a substantial social and financial burden to the family and society. Understanding predisposing and precipitating factors may promote individualized preventive treatment for each disorder, as several risk factors are modifiable. Besides prevention, timely identification and treatment of etiologies and symptoms can contribute to better recovery from postoperative neurological disorders and lower risk of long‐term cognitive impairment, disability, and even death. Herein, we summarize the diagnosis, risk factors, prevention, and treatment of these postoperative complications, with emphasis on recent advances and perspectives.
Observed elevated donor‐derived cell free DNA in orthotopic heart transplant recipients without clinical evidence of rejection
Authors: Afzal Aasim , Alam Amit , van Zyl Johanna S. , Zafar Hira , Felius Joost , Hall Shelley A. , Carey Sandra A.
Published: December 2021

Donor‐derived cell free DNA (dd‐cfDNA) has rapidly become part of rejection surveillance following orthotopic heart transplantation. However, some patients show elevated dd‐cfDNA without clinical evidence of rejection. With the aim to provide a clinical description of this subpopulation, we retrospectively analyzed 35 cardiac transplant recipients at our center who experienced elevated (≥.20%) dd‐cfDNA in the absence of clinical rejection, out of a total 106 recipients who had dd‐cfDNA results available during the first year. The median time to first elevated dd‐cfDNA level was 46 days, and the highest dd‐cfDNA recorded within 1 year was .31% [inter‐quartile range, .23–.45]. Twenty‐two (63%) patients experienced infections (cytomegalovirus (CMV) or other), and 16 (46%) presented with de novo donor‐specific antibodies. Cluster analysis revealed four distinct groups characterized by (a) subclinical rejection with 50% CMV (n = 16), (b) non‐CMV infections and the longest time to first elevated dd‐cfDNA (187 days) (n = 8), (c) right ventricular dysfunction (n = 6), and (d) women who showed the youngest median age (45 years) and highest median dd‐cfDNA (.50%) (n = 5). Continued prospective analysis is needed to determine if these observations warrant changes in patient management to optimize the utilization of this vital non‐invasive graft surveillance tool.
Common diseases of the nail: Diagnosis and therapy
Authors: Löser Christoph R. , Nenoff Pietro , Mainusch Oliver , Dippel Edgar , Balakirski Galina
Published: December 2021

This review focuses on nail changes that do not belong to the group of benign or malignant nail tumors. These common afflictions of the nail include structural changes in and under the nail plate as well as inflammation around and in the nail bed. They include onychomycoses, nail psoriasis, onychodystrophies, subungual hematoma, paronychia, ingrown nails and pincer nails. Due to the peculiar anatomy and physiological growth conditions of the nail, the pathology does not necessarily stem from the site of the clinical problem and calls for careful inspection and interpretation.
Sperm associated antigen 7 is activated by T3 during Xenopus tropicalis metamorphosis via a thyroid hormone response element within the first intron
Authors: Fu Liezhen , Crawford LaTaijah , Tong Andrew , Luu Nga , Tanizaki Yuta , Shi Yun‐Bo
Published: December 2021

Thyroid hormone (T3) affects many diverse physiological processes such as metabolism, organogenesis, and growth. The two highly related frog species, diploid Xenopus tropicalis and pseudo tetraploid Xenopus laevis, have been used as models for analyzing the effects of T3 during vertebrate development. T3 regulates T3‐inducible gene transcription through T3 receptor (TR)‐binding to T3‐response elements (TREs). We have previously identified sperm associated antigen 7 (spag7) as a candidate T3 target gene that is potentially involved in adult stem cell development and/or proliferation during intestinal metamorphosis. To investigate whether T3 regulates spag7 directly at the transcriptional level via TR, we first conducted qRT‐PCR to analyze its expression during natural and T3‐induced metamorphosis and found that spag7 was up‐regulated during natural metamorphosis in the intestine, tail, brain and hindlimb, peaking at the climax of metamorphosis in all those organs, and upon T3 treatment of premetamorphic tadpoles. Next, we demonstrated that an intronic TRE in spag7, first identified through bioinformatic analysis, could bind to TR in vitro and in vivo during metamorphosis. A dual luciferase assay utilizing a reconstituted frog oocyte transcription system showed that the TRE could mediate promoter activation by liganded TR. These results indicate that spag7 expression is directly regulated by T3 through the TRE in the first intron during metamorphosis, implicating a role for spag7 early during T3‐regulated tissue remodeling and resorption.
Use of intermittently scanned continuous glucose monitoring in young people with high‐risk type 1 diabetes—Extension phase outcomes following a 6‐month randomized control trial
Authors: Rose Shelley , Styles Sara E. , Wiltshire Esko J. , Stanley James , Galland Barbara C. , de Bock Martin I. , Tomlinson Paul A. , Rayns Jenny A. , MacKenzie Karen E. , Wheeler Benjamin J.
Published: December 2021

Aims

To describe the impact of a 12‐month intervention using intermittently scanned continuous glucose monitoring (isCGM) on glycaemic control and glucose test frequency in adolescents and young adults with type 1 diabetes (T1D) and high‐risk glycaemic control (HbA1c ≥75 mmol/mol [≥9.0%]).

Methods

In total, 64 young people (aged 13–20 years, 16.6 ± 2.1 years; 48% female; 41% Māori or Pacific ethnicity; mean diabetes duration 7.5 ± 3.8 years) with T1D were enrolled in a 6‐month, randomized, parallel‐group study comparing glycaemic outcomes from the isCGM intervention (n = 33) to self monitoring blood glucose (SMBG) controls (n = 31). In this 6‐month extension phase, both groups received isCGM; HbA1c, glucose time‐in‐range (TIR), and combined glucose test frequency were assessed at 9 and 12 months.

Results

At 12 months, the mean difference in HbA1c from baseline was −4 mmol/mol [−0.4%] (95% confidence interval, CI: −8, 1 mmol/mol [−0.8, 0.1%]; p = 0.14) in the isCGM intervention group, and −7 mmol/mol [−0.7%] (95% CI: −16, 1 mmol/mol [−1.5, 0.1%]; p = 0.08) in the SMBG control group. No participants achieved ≥70% glucose TIR (3.9–10.0 mmol/L). The isCGM intervention group mean rate of daily glucose testing was highest at 9 months, 2.4 times baseline rates (p < 0.001), then returned to baseline by 12 months (incidence rate ratio = 1.4; 95% CI: 0.9, 2.1; p = 0.091).

Conclusions

The use of isCGM in young people with high‐risk T1D resulted in transient improvements in HbA1c and glucose monitoring over a 9‐month time frame; however, benefits were not sustained to 12 months.
Choosing the duration of continuous glucose monitoring for reliable assessment of time in range: A new analytical approach to overcome the limitations of correlation‐based methods
Authors: Camerlingo Nunzio , Vettoretti Martina , Sparacino Giovanni , Facchinetti Andrea , Mader Julia K. , Choudhary Pratik , Del Favero Simone ,   the Hypo‐RESOLVE Consortium
Published: December 2021

Aims

Reliable estimation of the time spent in different glycaemic ranges (time‐in‐ranges) requires sufficiently long continuous glucose monitoring. In a 2019 paper (Battelino et al., Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range. Diabetes Care. 2019;42:1593‐1603), an international panel of experts suggested using a correlation‐based approach to obtain the minimum number of days for reliable time‐in‐ranges estimates. More recently (in Camerlingo et al., Design of clinical trials to assess diabetes treatment: minimum duration of continuous glucose monitoring data to estimate time‐in‐ranges with the desired precision. Diabetes Obes Metab. 2021;23:2446‐2454) we presented a mathematical equation linking the number of monitoring days to the uncertainty around time‐in‐ranges estimates. In this work, we compare these two approaches, mainly focusing on time spent in (70‐180) mg/dL range (TIR).

Methods

The first 100 and 150 days of data were extracted from study A (148 subjects, ~180 days), and the first 100, 150, 200, 250 and 300 days of data from study B (45 subjects, ~365 days). For each of these data windows, the minimum monitoring duration was computed using correlation‐based and equation‐based approaches. The suggestions were compared for the windows of different durations extracted from the same study, and for the windows of equal duration extracted from different studies.

Results

When changing the dataset duration, the correlation‐based approach produces inconsistent results, ranging from 23 to 64 days, for TIR. The equation‐based approach was found to be robust versus this issue, as it is affected only by the characteristics of the population being monitored. Indeed, to grant a confidence interval of 5% around TIR, it suggests 18 days for windows from study A, and 17 days for windows from study B. Similar considerations hold for other time‐in‐ranges.

Conclusions

The equation‐based approach offers advantages for the design of clinical trials having time‐in‐ranges as final end points, with focus on trial duration.
Assessment of radiology baseline knowledge of freshman North American dental students prior to any formal instruction
Authors: Mupparapu Mel , Kulkarni Roopali
Published: December 2021

Introduction

There is a wide variation in the knowledge related to oral radiology. This study aims to assess the prior knowledge of radiology amongst freshman dental students prior to beginning any formal dental school instruction.

Materials and Methods

A total of 139 newly matriculated freshman dental students were asked to complete a 7‐question radiology, take‐home survey regarding their prior knowledge. The questionnaire was built within their course site and was presented prior to beginning the radiology lectures.

Results

The responses were varied for all seven questions based on previous experiences and existing knowledge. Significant variation was noted in responses to Q4, Q6 and Q7 as opposed to Qs 1–3 and 5. Many students believed that the acquisition of radiographs should be selective. The acquisition of radiographs in pregnant women yielded comments in line with the belief that dose and frequency of radiation exposure would impact the health of the pregnant woman and developing foetus. Additionally, many students agreed with the statement regarding orthodontists over‐radiating children as reported in the New York Times. Perceptions based on social media and news outlets need to be addressed and changed in a dental school setting based on evidence.

Conclusion

Dental school instruction must use the cues from surveys similar to that used in this research and structure their instruction to increase the critical teaching of radiology. The eventual goal of such an instruction would be to have a scientifically accurate information and remove the perceptions that the students came with when they began their dental education.
Systematic review of survival outcomes for relapsed or refractory adult T‐cell leukemia‐lymphoma
Authors: Nosaka Kisato , Crawford Bruce , Yi Jingbo , Kuan William , Matsumoto Tomoko , Takahashi Takeshi
Published: December 2021

Introduction

Adult T‐cell leukemia‐lymphoma (ATL) is a mature T‐cell lymphoproliferative neoplasm caused by human T‐cell leukemia virus type‐1 infection. There is no standard treatment for relapsed or refractory (r/r) ATL, and clinical outcomes are poor. This systematic review examined the survival outcomes for r/r ATL treated with various systemic therapies.

Methods

EMBASE and PubMed were searched for studies on r/r ATL, published between January 2010 and January 2020. The main outcome of interest was overall survival (OS). Median OS and an exploratory 30% OS time were assessed based on published data and Kaplan‐Meier curves.

Results

There were 21 unique treatment subgroups (from 14 studies), that met the eligibility criteria. Nine subgroups were mogamulizumab treatment, two were mogamulizumab prior to allogenic hematopoietic stem cell transplantation (allo‐HSCT), five were allo‐HSCT, and five were other chemotherapy. Respectively, the median OS and 30% OS varied considerably in range for mogamulizumab treatment (2.2–17.6 months and 8.7–27.1 months), allo‐HSCT (3.8–6.2 months and 7.5–19.8 months), and other chemotherapy arms (4.1–20.3 months and 7.1–17.0 months).

Conclusion

Mogamulizumab was the most frequently studied treatment regimen and can potentially provide longer survival compared with chemotherapy alone. Future comparisons with synthetic or historical control arms may enable clearer insights into treatment efficacy.
Transcriptional regulation of neuronal identity
Authors: Sousa Erick , Flames Nuria
Published: December 2021

Neuronal diversity is an intrinsic feature of the nervous system. Transcription factors (TFs) are key regulators in the establishment of different neuronal identities; how are the actions of different TFs coordinated to orchestrate this diversity? Are there common features shared among the different neuron types of an organism or even among different animal groups? In this review, we provide a brief overview on common traits emerging on the transcriptional regulation of neuron type diversification with a special focus on the comparison between mouse and Caenorhabditis elegans model systems. In the first part, we describe general concepts on neuronal identity and transcriptional regulation of gene expression. In the second part of the review, TFs are classified in different categories according to their key roles at specific steps along the protracted process of neuronal specification and differentiation. The same TF categories can be identified both in mammals and nematodes. Importantly, TFs are very pleiotropic: Depending on the neuron type or the time in development, the same TF can fulfil functions belonging to different categories. Finally, we describe the key role of transcriptional repression at all steps controlling neuronal diversity and propose that acquisition of neuronal identities could be considered a metastable process.
Smoke and heat can increase germination of common wildflowers and grasses—implications for conservation and restoration of critically endangered grassy ecosystems
Authors: Hodges Joshua A. , Price Jodi N. , Nicotra Adrienne B. , Guja Lydia K.
Published: December 2021

Critically endangered grasslands and grassy woodlands were once widespread across south‐eastern Australia. However, more than 200 years of European land use means less than 1% of their pre‐European extent remains today. Conservation and restoration of these ecosystems involves reintroducing fire to periodically reduce competition and allow smaller species to establish. Furthermore, seeds of native species are sown – but often fail to establish as many forbs and grasses are hard‐to‐germinate. Therefore, data on how these species respond to fire‐related germination cues, such as smoke and heat, can benefit our understanding of both how species respond to fire and identify treatments which can be used to increase germination. We conducted a germination trial to determine if smoke and heat cues increase percent germination and germination speed of 55 common grassy ecosystem species. Fire cues increased germination speed and/or percent germination of 44 of the 55 study species. These results have three implications for grassy ecosystem conservation and restoration: (i) fire may aid conservation by maximizing germination of native species; (ii) pre‐treating seed with smoke and/or heat prior to sowing may increase germination when restoring these ecosystems via direct seeding; and (iii) smoke and heat can be used to increase germination when growing seedlings for plantings.
Perspectives on research protocols on Indigenous conservation lands: Outcomes from a talking circle
Authors: Preece Noel , Locke John , Turpin Gerry
Published: December 2021

Ecological field researchers mostly work on other people's lands. Agreements to do this work are standard practice, but the way that researchers must approach and determine agreements is changing rapidly. The rise in agency of Indigenous peoples and the massive increase in Indigenous‐owned and managed lands, coupled with the rise in other private‐ and corporate‐owned conservation lands, have had direct impacts on researchers. Most of these impacts are beneficial to researchers, and benefit sharing has now become the norm wherein Indigenous people and private conservation landholders expect equitable beneficial returns from the research. Likewise, research questions are more frequently driven by landholders. New rules about engaging with Indigenous people and other private landholders need to be understood by researchers, because these rules can determine the outcomes of applications to work on other people's lands and the research conducted. This article presents some experience and observations from Indigenous landholders who have worked with research protocols and other people who have worked on Indigenous lands. Some learned principles that can benefit researchers are presented.

Implications for managers Research protocols determine if and how research is to be conducted, how landholders are to be engaged and acknowledged and what and how research outcomes are to be published and reported Agreements must be reached between researchers and landholders before research is conducted Agreements are becoming more legally binding Joint authorship is becoming more common, and this may influence how the scientific methods and process are understood Cultural and social matters are core to research protocol negotiation in many instances and may require researchers to think differently from the ways in which they have been educated.
Evaluating predictors of Ptunarra Brown Butterfly Oreixenica ptunarra abundance on a conservation reserve to refine future monitoring
Authors: Kutt Alex S. , Dickson Catherine R. , Quarmby Joseph , Kingdom Denna , Hamer Rowena P.
Published: December 2021

Grasslands are globally threatened ecosystems and provide habitat for multiple threatened species. For this reason, grassland management must employ strategies which can protect multiple species of conservation significance. We reviewed surveillance monitoring data collected on a private conservation reserve in Tasmania between 2014 and 2021 for the endangered Ptunarra Brown Butterfly (Oreixenica ptunarra) to identify the landscape scale predictors of abundance. The data suggested that elevation (lower), time since fire (longer) and highland grassy sedgeland and subalpine Diplarrena latifolia rushland habitats were preferred. These data provide information on how to target future monitoring of this species more effectively. Conservation management on this reserve needs to develop strategies that account for the ecological requirements of other threatened species in the reserve, which may have different and possibly conflicting management requirements.
“Do I still have epilepsy?” Epilepsy identity 15–20 years after anterior temporal lobectomy
Authors: Coleman Honor , McIntosh Anne , Wilson Sarah J.
Published: December 2021

Objective

Identity is a multifaceted construct, comprising personal identity (sense of being a unique individual) and social identity (the sense‐of‐self derived from membership of social groups). Social identity involves explicit identification with a group (“I am …”) and implicit behaviors or attitudes associated with group membership. Following successful treatment with surgery, patients with epilepsy can undergo a complex and lasting change in personal identity. To date, there has been no research into postoperative social epilepsy identity (SEI). We sought to examine SEI 15–20 years post‐surgery, and the relationship between SEI and satisfaction with surgery, psychosocial improvements, mood, and health‐related quality of life (HRQoL).

Methods

Thirty‐two patients who underwent anterior temporal lobectomy (ATL; 19 female) were recruited, with a median follow‐up of 18 years (interquartile range [IQR] = 2.5). Using a novel interactive online program, we collected data on SEI, satisfaction with surgery, and perceived psychosocial improvements, alongside standardized measures of mood (Neurological Disorders Depressio Inventory‐Epilepsy; Patient Health Questionnaire‐Generalised Anxiety Disorder‐7 item) and HRQoL (Quality of Life in Epilepsy‐31 item). Non‐parametric analyses were used to analyse the data.

Results

Twenty‐five percent of patients were free of disabling seizures since surgery, yet 65% stated they no longer had epilepsy and >90% reported satisfaction with surgery. Explicitly discarding SEI was positively associated with HRQoL at long‐term follow‐up, over and above seizure outcome. Implicit SEI was expressed as (a) acceptance of epilepsy, (b) a sense of belonging to the epilepsy community, and (c) difficulty disclosing and discussing epilepsy. Difficulty disclosing and discussing epilepsy was associated with increased anxiety and lower HRQoL.

Significance

At long‐term follow‐up, over half of our patients reported an explicit change in SEI, which could promote better HRQoL. In contrast, difficulty with disclosure of epilepsy was associated with increased anxiety and reduced HRQoL, possibly reflecting the ongoing effects of stigma. These findings highlight the importance of understanding changes in patient social identity for promoting long‐term well‐being after surgery.
Receptor binding mechanisms of Clostridioides difficile toxin B and implications for therapeutics development
Authors: Chen Peng , Jin Rongsheng
Published: December 2021

Clostridioides difficile is classified as an urgent antibiotic resistance threat by the Centers for Disease Control and Prevention (CDC). C. difficile infection (CDI) is mainly caused by the C. difficile exotoxin TcdB, which invades host cells via receptor‐mediated endocytosis. However, many natural variants of TcdB have been identified including some from the hypervirulent strains, which pose significant challenges for developing effective CDI therapies. Here, we review the recent research progress on the molecular mechanisms by which TcdB recognizes Frizzed proteins (FZDs) and chondroitin sulfate proteoglycan 4 (CSPG4) as two major host receptors. We suggest that the receptor‐binding sites and several previously identified neutralizing epitopes on TcdB are ideal targets for the development of broad‐spectrum inhibitors to protect against diverse TcdB variants.
Motif‐driven protein binder design towards transferrin receptor helical domain
Authors: Sjöström Dick J. , Mohlin Camilla , Ambrosetti Elena , Garforth Scott J. , Teixeira Ana I. , Bjelic Sinisa
Published: December 2021

Human transferrin receptor 1 (TfR) is necessary for the delivery of the iron carrier protein transferrin into cells and can be utilized for targeted delivery across cellular membranes. Binding of transferrin to the receptor is regulated by hereditary hemochromatosis protein (HFE), an iron regulatory protein that partly shares a binding site with transferrin on TfR. Here, we derived essential binding interactions from HFE and computationally grafted these into a library of small protein scaffolds. One of the designed proteins, TB08, was further optimized computationally and experimentally to identify variants with improved binding to TfR. The optimized variant, TB08 S3.1, expressed well in the E. coli expression system and had an affinity to TfR in the low micromolar range, Kd ≈ 1 μm, as determined by surface plasmon resonance. A binding competition assay with transferrin further confirmed the interaction of the evolved variant to TfR at the shared binding surface. Additionally, the GFP‐tagged evolved variant of TB08 demonstrated cellular internalization as determined by fluorescent and confocal microscopy in HeLa cells. The designed protein is small, allows for robust cargo tagging, and interacts specifically with TfR, thus making it a valuable tool for the characterization of TfR‐mediated cellular transport mechanisms and for the assessment of engineering strategies for cargo delivery across cell membranes.
Freshwater disease hotspots: Drivers of fine‐scale spatial heterogeneity in trematode parasitism in streams
Authors: Falke Landon P. , Preston Daniel L.
Published: December 2021

Populations of stream organisms often show large heterogeneity in space, which can substantially influence community dynamics and ecosystem functioning. However, few studies have examined spatial heterogeneity of parasites in lotic ecosystems, especially at fine spatial scales (e.g., within stream reaches).

We quantified parasite infections in 3,255 host snails (Juga plicifera) at 1‐m intervals along three second‐order stream reaches to examine relationships between trematode parasite infections, fine‐scale heterogeneity in host characteristics (density and size), and the stream environment (depth, allochthonous materials, flow velocity, and substrate rugosity). We then conducted a field experiment to specifically test the effect of resource heterogeneity in the form of leaf litter on trematode densities (i.e., infected snails per unit area), which represents a measure of local disease risk to secondary hosts. We hypothesised that variation in bottom‐up effects of host resources to snail hosts to parasites would drive spatial heterogeneity in trematode density.

In the field surveys, trematode density ranged from 0 to 80 infected snails/m2 and showed spatial autocorrelation within two of three stream reaches. Trematode density increased with snail density, which was positively related with the amount of allochthonous materials but negatively related to steam depth. Individual host infection probability increased with snail size, which was positively related to both allochthonous materials and stream depth.

In the experiment, host snail and trematode densities increased by 3‐fold and 4‐fold, respectively, in the leaf addition treatments relative to controls. The experiment therefore provided mechanistic understanding of patterns from the surveys by demonstrating a bottom‐up effect from high quality resources to host space use to trematode density.

Our results demonstrate a strong role of within‐reach variation in allochthonous resources and habitat (depth) in driving spatial heterogeneity of stream parasites, which probably creates fine‐scale hotspots of disease transmission to downstream hosts. More broadly, our findings help integrate parasites into our understanding of how environmental heterogeneity influences community structure and ecosystem processes (e.g., disease risk) in streams.