bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Changes in Functional Connectivity in Antipsychotic-treated and Antipsychotic-naive Patients with First Episode Psychosis
Authors: Chopra Sidhant , Francey Shona M. , O’Donoghue Brian , Sabaroedin Kristina , Arnatkeviciute Aurina , Cropley Vanessa , Nelson Barnaby , Graham Jessica , Baldwin Lara , Tahtalian Steven , Yuen Hok Pan , Allott Kelly , Alvarez-Jimenez Mario , Harrigan Susy , Pantelis Christos , Wood Stephen J , McGorry Patrick , Fornito Alex
Published: April 2021

Background

Altered functional connectivity (FC) is a common finding in resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotics may influence the temporal evolution of these disturbances, remains unclear. Here, we scanned first episode psychosis (FEP) patients who were and were not exposed to antipsychotic medication during the first six months of illness at baseline, three months, and 12 months, to characterize how FC changes over time and in relation to medication use.

Methods

Sixty-two antipsychotic-naïve patients with FEP received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. A total of 202 rs-fMRI scans were obtained across three timepoints: baseline, 3-months and 12-months. Our primary aim was to differentiate patterns of FC in antipsychotic-treated and antipsychotic-naive patients within the first 3 months of treatment, and to examine associations with clinical and functional outcomes. A secondary aim was to investigate long-term effects at the 12-month timepoint.

Results

At baseline, FEP patients showed widespread functional dysconnectivity in comparison to controls, with reductions predominantly affecting interactions between the default mode network (DMN), limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems, and some of these changes correlated with improved clinical outcomes. Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain. At the 12-month follow-up, antipsychotic treatment was associated with a prolonged increase of FC primarily in the DMN and limbic systems.

Conclusions and Relevance

Antipsychotic-naïve FEP patients show widespread functional dysconnectivity at baseline, followed by an early normalization of DMN and paralimbic dysfunction in patients receiving a psychosocial intervention only. Antipsychotic exposure is associated with distinct FC changes, principally concentrated on thalamo-cortical and limbic networks.
Emergence of the novel SARS-CoV-2 lineage P.4.1 and massive spread of P.2 in South Brazil
Authors: Sant’Anna Fernando Hayashi , Muterle Varela Ana Paula , Prichula Janira , Comerlato Juliana , Comerlato Carolina Baldisserotto , Roglio Vinicius Serafini , Mendes Pereira Gerson Fernando , Moreno Flávia , Seixas Adriana , Márcia Wendland Eliana
Published: April 2021

South Brazil has been the novel epicenter of Coronavirus Disease 2019 (COVID-19) in 2021, accounting for the greatest number of cumulative cases and deaths (per 100 thousand inhabitants in a week) worldwide. In this study, we analyzed 340 whole genomes of SARS-CoV-2, which were sampled between April and November 2020 in 33 cities in South Brazil. We demonstrated the circulation of two novel emergent lineages, described here as P.4 and P.4.1 (provisionally termed VUI-NP13L), and seven lineages that had already been assigned (B.1.1.33, B.1.1.28, P.2, B.1.91, B.1.1.94, B.1.195 and B.1.212). P.2 and P.4.1 demonstrated massive spread from approximately September/October 2020. Constant and consistent genomic surveillance is crucial to identify newly emerging SARS-CoV-2 lineages in Brazil and to guide decision making in the Brazilian Public Healthcare System.
Polygenic Risk for Schizophrenia, Brain Structure and Environmental Risk in UK Biobank
Authors: Zhu Xingxing , Ward Joey , Cullen Breda , Lyall Donald M. , Strawbridge Rona J. , Lyall Laura M. , Smith Daniel J.
Published: April 2021

Schizophrenia is a heritable neurodevelopmental disorder characterized by neuroanatomical changes in the brain but exactly how increased genetic burden for schizophrenia influences brain structure is unknown. Similarly, the impact of environmental risk factors for schizophrenia on brain structure is not fully understood. We investigated how genetic burden for schizophrenia (indexed by a polygenic risk score, PRS-SCZ) was associated with cortical thickness (CT), cortical surface area (SA), cortical volume (CV) and multiple subcortical structures within 18,147 White British ancestry participants from UK Biobank. We also explored whether environmental risk factors for schizophrenia (cannabis use, childhood trauma, low birth weight and Townsend social deprivation index) exacerbated the impact of PRS-SCZ on brain structure. We found that PRS-SCZ was significantly associated with lower CT in the frontal lobe, insula lobe, lateral orbitofrontal cortex, medial orbitofrontal cortex, posterior cingulate cortex and inferior frontal cortex, as well as reduced SA and CV in the supramarginal cortex and superior temporal cortex, but not with differences in subcortical volumes. When models included environmental risk factors as covariates, PRS-SCZ was only associated with lower SA/CV within the supramarginal cortex, superior temporal cortex and inferior frontal cortex. Moreover, no interactions were observed between PRS-SCZ and each of the environmental risk factors on brain structure. Overall, we identified brain structural correlates of PRS-SCZ predominantly within frontal and temporal regions. Some of these associations were independent of environmental risk factors, suggesting that they may represent biomarkers of genetic risk for schizophrenia.
Short selling and stock price crash risk
Authors: Chung Jay M. , Wang Shu-Feng
Published: April 2021

This paper aims to investigate short selling and stock price crash risk. The authors find that short selling is positively associated with one-month-ahead stock price crash risk, consistent with the literature showing that short sellers are informed traders. The authors attribute this prediction ability to the information short sellers receive from foreign investors with high levels of ownership in a firm. The results shed light on policy issues regarding short selling regulation.
Investigating the use of physical restraint of children in emergency departments: A Scandinavian survey
Authors: Aaberg Lauridsen Julie , Lefort Sønderskov Michele , Hetmann Fredrik , Hamilton Annika , Salmi Heli , Wildgaard Kim
Published: April 2021

Aim

The aim of the study is to describe the current frequency of physical restraint and the use of analgesics and sedatives for treating pediatric pain in emergency departments (EDs) in Scandinavia.

Methods

We performed a nation‐wide electronic survey asking nurses in the emergency departments in Denmark, Norway, and Sweden about their experience treating children in pain.

Results

Responses from 103 Danish, Norwegian and Swedish nurses were included (79% response rate). Physical restraint was reported used at 79% [70.0‐85.9] (N = 78) of the surveyed departments (DK: 96%, NO: 67%, SE: 77%) with two participants reporting daily use of physical restraint. Paracetamol was available at all departments and used most frequently. Sedation was available at 88% [78.8‐92.0] of the departments with midazolam as the most recurrent sedative (83%, [74.8‐89.4]). Seventy‐three percent of respondents reported a need for better treatments. Lack of education was the most frequently reported obstacle for providing both pain treatment (29%) and sedation (43%) followed by lack of guidelines.

Conclusion

Physical restraint of children during painful procedures is used in the majority of Scandinavian emergency departments (79%). There appears to be a lack of local guidelines for both pain treatment and sedation.
Vascular inflammation in moderate‐to‐severe atopic dermatitis is associated with enhanced Th2 response
Authors: Villani Axel P. , Pavel Ana B. , Wu Jianni , Fernandes Marie , Maari Catherine , Saint‐Cyr Proulx Etienne , Jack Carolyn , Glickman Jacob , Choi Seulah , He Helen , Ungar Benjamin , Estrada Yeriel , Kameyama Naoya , Zhang Ning , Gonzales Juana , Tardif Jean‐Claude , Krueger James G. , Bissonnette Robert , Guttman‐Yassky Emma
Published: April 2021

Background

In atopic dermatitis (AD), some studies have shown an association with increased cardiovascular disease in certain populations. However, other investigations found modest or no association. Despite conflicting results, molecular profiling studies in both AD skin and blood have demonstrated upregulation of atherosclerosis and cardiovascular risk‐related markers. However, the underlying mechanisms connecting AD to vascular inflammation/atherosclerosis are unknown. In this study, we aim to determine factors associated with vascular inflammation/atherosclerosis in AD patients.

Methods

We used 18‐FDG PET‐CT to characterize vascular inflammation in AD patients and healthy subjects. In parallel, we assessed their skin and blood immune profiles to determine AD‐related immune biomarkers associated with vascular inflammation. We also assessed levels of circulating microparticles, which are known to be associated with increased cardiovascular risk.

Results

We found significant correlations between vascular inflammation and Th2‐related products in skin and blood of AD patients as well as atherosclerosis‐related markers that were modulated by dupilumab. Circulating levels of endothelial microparticles were significantly higher in severe AD patients and tended to correlate with vascular inflammation assessed by PET‐CT.

Conclusion

Vascular inflammation in AD is associated with enhanced Th2 response and clinical severity, which may explain cardiovascular comorbidities observed in select AD populations. Larger prospective studies are needed to further evaluate vascular inflammation and cardiovascular events and mortality in AD patients. Finally, as dupilumab treatment demonstrated significant modulation of atherosclerosis‐related genes in AD patients compared to placebo, these data suggest that modulation of vascular inflammation with systemic treatment should be explored in patients with AD.
Characteristics of tissue–resident ILCs and their potential as therapeutic targets in mucosal and skin inflammatory diseases
Authors: Orimo Keisuke , Tamari Masato , Saito Hirohisa , Matsumoto Kenji , Nakae Susumu , Morita Hideaki
Published: April 2021

Discovery of innate lymphoid cells (ILCs), which are non–T and non–B lymphocytes that have no antigen‐specific receptors, changed the classical concept of the mechanism of allergy, which had been explained mainly as antigen‐specific acquired immunity based on IgE and Th2 cells. The discovery led to dramatic improvement in our understanding of the mechanism of non–IgE‐mediated allergic inflammation. Numerous studies conducted in the past decade have elucidated the characteristics of each ILC subset in various organs and tissues and their ontogeny. We now know that each ILC subset exhibits heterogeneity. Moreover, the functions and activating/suppressing factors of each ILC subset were found to differ among both organs and types of tissue. Therefore, in this review, we summarize our current knowledge of ILCs by focusing on the organ/tissue‐specific features of each subset to understand their roles in various organs. We also discuss ILCs’ involvement in human inflammatory diseases in various organs and potential therapeutic/preventive strategies that target ILCs.
Pharmacist‐led interventions to reduce adverse drug events in older people living in residential aged care facilities: A systematic review
Authors: Ali Sheraz , Salahudeen Mohammed S. , Bereznicki Luke R. E. , Curtain Colin M.
Published: April 2021

Aims

We aimed to investigate the efficacy and effectiveness of pharmacist‐led interventions to reduce adverse drug events (ADEs) in older people living in residential aged care facilities (RACFs).

Methods

We systematically searched MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials and PsycINFO from their inceptions to July 2020. We investigated experimental study designs that employed a control group, or quasi‐experimental studies conducted in RACFs.

Results

We screened 3826 records and included 23 studies. We found seven single‐component and 16 multicomponent pharmacist‐led interventions to reduce ADEs in older people living in RACFs. The most frequent single‐component pharmacist‐led intervention was medication review. Medication review and education provision to healthcare professionals were the most common components in many pharmacist‐led multicomponent interventions. Thirteen studies (56%) showed no effect, whereas ten studies (43%) reported significant reductions in ADEs following pharmacist‐led interventions either as a sole intervention or as a part of a multi‐component intervention. Many interventions focused on reducing the incidence of falls (39%).

Conclusions

This systematic review suggests that pharmacist‐led interventions have the potential to reduce the incidence of ADEs in older people living in RACFs. Medication review and educational programmes, particularly academic detailing, either as a single component or as part of multicomponent interventions were the most common approaches to reducing drug‐related harm in older people living in RACFs. The lack of a positive association between interventions and ADE in many studies suggests that targeted and tailored pharmacist‐led interventions are required to reduce ADEs in older people in RACFs.
The wider perspective: cord blood banks and their future prospects
Authors: Querol Sergio , Rubinstein Pablo , Madrigal Alejandro
Published: April 2021

Over the past three decades, cord blood transplantation (CBT) has established its role as an alternative allograft stem cell source. But the future of stored CB units should be to extend their use in updated transplant approaches and develop new CB applications. Thus, CBT will require a coordinated, multicentric, review of transplantation methods and an upgrade and realignment of banking resources and operations. Significant improvements have already been proposed to support the clinical perspective including definition of the cellular threshold for engraftment, development of transplantation methods for adult patients, engraftment acceleration with single cell expansion and homing technologies, personalised protocols to improve efficacy, use of adoptive cell therapy to mitigate delayed immune reconstitution, and further enhancement of the graft‐versus‐leukaemia effect using advanced therapies. The role of CB banks in improving transplantation results are also critical by optimizing the collection, processing, storage and characterization of CB units, and improving reproducibility, efficiency and cost of banking. But future developments beyond transplantation are needed. This implies the extension from transplantation banks to banks that support cell therapy, regenerative medicine and specialized transfusion medicine. This new “CB banking 2.0” concept will require promotion of international scientific and technical collaborations between bank specialists, clinical investigators and transplant physicians.
Pathological and oncological outcomes in patients with sarcomatoid differentiation undergoing cystectomy
Authors: Almassi Nima , Vertosick Emily A. , Sjoberg Daniel D. , Wong Nathan C. , Huang Chun , Pietzak Eugene J. , Cha Eugene K. , Donahue Timothy F. , Dalbagni Guido , Bochner Bernard H. , Iyer Gopa , Rosenberg Jonathan E. , Bajorin Dean F. , Al‐Ahmadie Hikmat , Goh Alvin C.
Published: April 2021

Objective

To evaluate whether urothelial carcinoma (UC) with sarcomatoid differentiation is associated with a lower pathological response rate to neoadjuvant chemotherapy (NAC) and worse oncological outcomes compared to UC without variant histology among patients undergoing radical cystectomy.

Patients and Methods

Patients with UC undergoing cystectomy from 1995 to 2018 at the Memorial Sloan Kettering Cancer Centre were identified. Patients with sarcomatoid differentiation at transurethral resection (TUR) or cystectomy, and patients without variant histology were selected. Downstaging from ≥cT2 to ≤pT1N0 defined partial response and pT0N0 defined complete response. Recurrence‐free, cancer‐specific and overall survival were modelled.

Results

We identified 131 patients with sarcomatoid differentiation and 1722 patients without variant histology, of whom 25 with sarcomatoid histology on biopsy and 313 without variant histology received NAC. Those with sarcomatoid differentiation presented with higher consensus tumour stage (94% ≥T2 vs 62%; P < 0.001) and were, therefore, more likely to receive NAC (29% vs 18%; P = 0.003). We found no evidence to support a difference in partial (24% vs 31%) or complete (20% vs 24%) response between patients with sarcomatoid histology and those with pure UC at TUR (P = 0.6). Among patients with sarcomatoid differentiation, 5‐year recurrence‐free survival was 55% (95% confidence interval [CI] 41–74) among patients receiving NAC and 40% (95% CI 31–52) among patients undergoing cystectomy alone (P = 0.1). Adjusting for stage, nodal involvement, margin status and receipt of NAC, sarcomatoid differentiation was associated with worse recurrence‐free (hazard ratio [HR] 1.82, 95% CI 1.39–2.39), disease‐specific (HR 1.66, 95% CI 1.23–2.22), and overall survival (HR 1.37, 95% CI 1.06–1.78).

Conclusions

Sarcomatoid differentiation was associated with higher stage at presentation and independently associated with worse survival. Given similar pathological response rates if sarcomatoid differentiation is detected at initial resection, and greater survival among patients receiving NAC, treatment with NAC appears warranted. Other drivers of the poor outcomes of this histology must be investigated.
Analysis of T and NK cell subsets in the Sicilian population from young to supercentenarian: The role of age and gender
Authors: Ligotti Mattia Emanuela , Aiello Anna , Accardi Giulia , Aprile Stefano , Bonura Floriana , Bulati Matteo , Gervasi Francesco , Giammanco Giovanni M , Pojero Fanny , Zareian Nahid , Caruso Calogero , Farzaneh Farzin , Candore Giuseppina
Published: April 2021

Ageing dramatically affects number and function of both innate and adaptive arms of immune system, particularly T cell subsets, contributing to reduced vaccination efficacy, decreased resistance to infections and increased prevalence of cancer in older people. In the present paper, we analysed the age-related changes in the absolute number of lymphocytes in 214 Sicilian subjects, and in the percentages of T and natural killer (NK) cells in a subcohort of donors. We compared these results with the immunophenotype of the oldest living Italian supercentenarian (aged 111 years). The results were also sorted by gender. The correlation between number/percentage of cells and age in all individuals. and separately in males and females, was examined using a simple linear regression analysis. We did not record the increase in the rate of inversion of the CD4/CD8 ratio, frequently reported as being associated with ageing in literature. Our observation was the direct consequence of a flat average trend of CD4+ and CD8+ T cell percentages in ageing donors, even when gender differences were included. Our results also suggest that CD4+ and CD8+ subsets are not affected equally by age comparing females with males, and we speculated that gender may affect the response to cytomegalovirus (CMV) infection. The supercentenarian showed a unique immunophenotypic signature regarding the relative percentages of her T cell subsets, with CD4+ and CD8+ T cell percentages and CD4+ naive T cell values in line with those recorded for the octogenarian subjects. This suggests that the supercentenarian has a naive ‘younger’ T cell profile comparable to that of a >80-year-old female.
Prevalence of biochemical osteomalacia in adults undergoing vitamin D testing
Authors: Bolland Mark J. , Avenell Alison , Grey Andrew
Published: April 2021

Objective

Prolonged severe vitamin D deficiency can cause osteomalacia, but the 25‐hydroxyvitamin D (25OHD) concentration below which this occurs is unknown. We investigated the prevalence of biochemical osteomalacia in adults with a measurement of 25OHD.

Design, Measurement, and Patients

25OHD results between 1/1/2009 and 15/6/2020 were obtained from the regional laboratory database, together with measurements of serum calcium, parathyroid hormone (PTH) and alkaline phosphatase (ALP) within 6 months of the index 25OHD. We defined biochemical osteomalacia as all 3 of: albumin‐adjusted serum calcium (aCa)<2.0 mmol/L, PTH>7.3 pmol/L and ALP>150 IU/L. Possible osteomalacia was 2/3 criteria with the other test not done. 25OHD measurements associated with significant renal impairment, elevated hepatic transaminases or hypercalcaemia were excluded.

Results

110,046 25OHD measurements were identified over the 11.5 years period. After removal of ineligible measurements, 42,171 25OHD measurements from 32,386 individuals with at least 2 of aCa, PTH and ALP were included in analyses. Median 25OHD was 63 nmol/L; 8% were <25 nmol/L, and 33% were <50 nmol/L. Five index 25OHD measurements met the definition of biochemical osteomalacia, and another 11 were possible osteomalacia. After reviewing available clinical records for these 16 episodes, we classified 9 cases as osteomalacia and 7 as other diagnoses. Thus, the prevalence of biochemical osteomalacia was 0.02% (9/42,171) for 25OHD measurements and 0.23% (8/3432) for 25OHD<25 nmol/L. All cases of osteomalacia with 25OHD measurements prior to supplementation had 25OHD≤18 nmol/L.

Conclusion

The prevalence of biochemical osteomalacia is very low, even in individuals with 25OHD<25 nmol/L.
Comprehensive peri‐implant tissue evaluation with ultrasonography and cone‐beam computed tomography: A pilot study
Authors: Siqueira Rafael , Sinjab Khaled , Pan Ying‐Chun , Soki Fabiana , Chan Hsun‐Liang , Kripfgans Oliver
Published: April 2021

Objectives

The aim of the present study was to explore the feasibility of ultrasonography (US) for clinical imaging of peri‐implant tissues.

Material and Methods

Patients with ≥1 implant, a cone‐beam computed tomography (CBCT) scan, an US scan, and clinical photographs taken during the surgery were included. The crestal bone thickness (CBT) and facial bone level (FBL) were measured on both US and CBCT modalities, and direct FBL measurements were also made on clinical images. US measurements were compared with CBCT and direct readings.

Results

A total of eight implants from four patients were included. For FBL measurements, US and direct (r2 = 0.95) as well as US and CBCT (r2 = 0.85) were highly correlated, whereas CBCT correlated satisfactorily with the direct reading (r2 = 0.75). In one implant without facial bone, CBCT was not able to measure CBT and FBL accurately. The estimated bias for CBT readings was 0.17 ± 0.23 mm (p = .10) between US and CBCT. US blood flow imaging was successfully recorded and showed a wide dynamic range among patients with different degrees of clinical inflammation.

Conclusion

US is a feasible method to evaluate peri‐implant facial crestal bone dimensions. Additional US features, for example, functional blood flow imaging, may be useful to estimate the extent and severity of inflammation.
A Computational Evaluation of Two Models of Retrieval Processes in Sentence Processing in Aphasia
Authors: Lissón Paula , Pregla Dorothea , Nicenboim Bruno , Paape Dario , van het Nederend Mick L. , Burchert Frank , Stadie Nicole , Caplan David , Vasishth Shravan
Published: April 2021

Can sentence comprehension impairments in aphasia be explained by difficulties arising from dependency completion processes in parsing? Two distinct models of dependency completion difficulty are investigated, the Lewis and Vasishth (2005) activation‐based model and the direct‐access model (DA; McElree, 2000). These models' predictive performance is compared using data from individuals with aphasia (IWAs) and control participants. The data are from a self‐paced listening task involving subject and object relative clauses. The relative predictive performance of the models is evaluated using k‐fold cross‐validation. For both IWAs and controls, the activation‐based model furnishes a somewhat better quantitative fit to the data than the DA. Model comparisons using Bayes factors show that, assuming an activation‐based model, intermittent deficiencies may be the best explanation for the cause of impairments in IWAs, although slowed syntax and lexical delayed access may also play a role. This is the first computational evaluation of different models of dependency completion using data from impaired and unimpaired individuals. This evaluation develops a systematic approach that can be used to quantitatively compare the predictions of competing models of language processing.
A single dose of pre‐operative pregabalin reduces post‐operative opioid use after orthotopic liver transplantation
Authors: Knorr John P. , Barlow Ashley , Reinaker Travis S. , Zaki Radi F.
Published: April 2021

Multimodal pain management strategies including pregabalin (PGB) have been shown to reduce pain and opioid use after many types of surgeries. This was a single‐center, retrospective study aimed to determine whether a single pre‐operative dose of PGB reduces opioid requirements and post‐operative pain after orthotopic liver transplantation (OLT). Outcomes included the mean morphine milligram equivalents used; the proportion of patients with no pain documented; and the maximum level of pain documented within the first 24h and in the 24‐72h following OLT. A total of 44 patients received PGB vs 57 who received standard of care. Baseline demographics were comparable between groups. Patients who received PGB required 70% and 54% less opioids within the first 24h and subsequent 24‐72h post‐OLT, respectively (p‐values < .001). In the first 24h post‐OLT, there were more patients with no documented pain, and fewer with severe pain in the PGB group, but these were not significant. A greater proportion in the PGB group reported a maximum of mild pain (p = .039). This study demonstrated that a single dose of pre‐operative PGB significantly reduced opioid use in the first 72 h after OLT. Larger studies will help determine the safety and efficacy of PGB in this setting.
Immunoglobulin, nucleos(t)ide analogues and hepatitis B virus recurrence after liver transplant: A meta‐analysis
Authors: Lai Quirino , Mennini Gianluca , Giovanardi Francesco , Rossi Massimo , Giannini Edoardo G.
Published: April 2021

Background

Prophylaxis with hepatitis B immunoglobulin (HBIG) represents an efficient strategy for reducing the risk of hepatitis B virus (HBV) recurrence after liver transplantation (LT). Unfortunately, the long‐term use of HBIG presents high costs. Therefore, the use of prophylaxis based only on nucleos(t)ide analogues (NUC) has been recently postulated. The present meta‐analysis aimed to evaluate the impact of HBIG ± NUC vs HBIG alone or NUC alone in post‐LT HBV recurrence prophylaxis.

Materials and methods

A systematic literature search was performed using PubMed and Cochrane databases. The primary outcome investigated was the HBV recurrence after LT. Three analyses were done comparing the effect of (a) HBIG + NUC vs HBIG alone; (b) HBIG+NUC vs NUC alone; and (c) HBIG alone vs NUC alone. Sub‐analyses were also performed investigating the effect of low and high genetic barrierto‐recurrence NUC.

Results

Fifty‐one studies were included. The summary OR (95%CI) showed a decreased risk with the combination of HBIG + NUC vs HBIG alone for HBV recurrence, being 0.36 (95% CI = 0.22‐0.61; P < .001). HBIG + NUC combined treatment reduced HBV reappearance respect to NUC alone (OR = 0.22; 95% CI = 0.16‐0.30; P < .0001). Similarly, HBIG alone was significantly better than NUC alone in preventing HBV recurrence (OR = 0.20; 95% CI = 0.09‐0.44; P < .0001).

Conclusions

Prophylaxis with HBIG is relevant in preventing post‐LT HBV recurrence. Its combination with NUC gives the best results in terms of protection. The present results should be considered in light of the fact that also old studies based on lamivudine use were included. Studies exploring in detail high genetic barrier‐to‐recurrence NUC and protocols with definite use of HBIG are needed.
NDNF is selectively expressed by neocortical, but not habenular neurogliaform cells
Authors: Webster Jack F. , Vroman Rozan , Beerens Sanne , Sakata Shuzo , Wozny Christian
Published: April 2021

The lateral habenula (LHb) is a brain structure which is known to be pathologically hyperactive in depression, whereby it shuts down the brains' reward systems. Interestingly, inhibition of the LHb has been shown to have an antidepressant effect, hence making the LHb a fascinating subject of study for developing novel antidepressant therapies. Despite this however, the exact mechanisms by which inhibitory signalling is processed within the LHb remain incompletely understood. Some studies have proposed the existence of locally targeting inhibitory interneuron populations within the LHb. One such population is believed to be akin to neocortical neurogliaform cells, yet specific molecular markers for studying these neurons are sparse and hence their function remains elusive. Recently, neuron‐derived neurotrophic factor (NDNF) has been proposed as one such marker for neocortical neurogliaform cells. Using a combination of histological, physiological and optogenetic tools, we hence sought to first validate if NDNF was selectively expressed by such inhibitory neurons within the neocortex, and then if it was confined to a similar population within the LHb. While we report this to be true for the neocortex, we find no such evidence within the LHb; rather that NDNF is expressed without restriction to a particular neuronal subpopulation. These results hence indicate that molecular markers can represent broadly diverse populations of neurons on a region‐to‐region basis and that therefore each population as defined by molecular marker expression should be validated in each brain structure.
What changes in prescription patterns of antiemetic medications in pregnant women in France?
Authors: Hurault‐Delarue Caroline , Araujo Mélanie , Vabre Clémentine , Benevent Justine , Damase‐Michel Christine , Lacroix Isabelle
Published: April 2021

Background

In France, few data are available on the prescription patterns of antiemetic medications in pregnant women.

Objectives

The purpose of this study was to describe antiemetic medication prescriptions and trends over time. Can we observe significant changes in pregnant woman prescriptions in recent years?

Methods

We conducted a drug utilization study among pregnant women using data from the EFEMERIS database, including 135 574 pregnant women who had a pregnancy outcome between 2004 and 2017 in Haute‐Garonne (France).

Results

During the study period, 40 028 women (29.5%) received at least one antiemetic prescription during pregnancy. Metoclopramide (56.6%), domperidone (34.9%), and metopimazine (28.5%) were the most commonly prescribed antiemetics, whatever the trimester of pregnancy. Prescriptions of ondansetron only concerned 53 women (0.1%). The prevalence of women who received at least one prescription for an antiemetic decreased from 32.5% in 2010 to 21.6% in 2017. This decline mainly concerned domperidone prescriptions (from 13.1% in 2010 to 1.2% in 2017). Metoclopramide prescriptions also decreased slightly (18.3% in 2010 and 14.0% in 2017). Metopimazine prescriptions increased lowly (8.0% in 2010 and 9.0% in 2017).

Conclusion

This study showed a decrease of antiemetic prescriptions between 2010 and 2017, linked to the sharp decrease in domperidone use from 2011, probably related to warnings about the risk of cardiovascular adverse effects following exposure to domperidone. We could not observe real switches to other antiemetic medications. No switches to ondansetron could be noted either, with only rare exposure during pregnancy, contrary to other countries, like the United States.
Mitochondrial sirtuins in stem cells and cancer
Authors: Jaiswal Amit , Xudong Zhu , Zhenyu Ju , Saretzki Gabriele
Published: April 2021

The mammalian sirtuin family consists of seven proteins, three of which (SIRT3, SIRT4, and SIRT5) localise specifically within mitochondria and preserve mitochondrial function and homeostasis. Mitochondrial sirtuins are involved in diverse functions such as deacetylation, ADP‐ribosylation, demalonylation and desuccinylation, thus affecting various aspects of cell fate. Intriguingly, mitochondrial sirtuins are able to manage these delicate processes with accuracy mediated by crosstalk between the nucleus and mitochondria. Previous studies have provided ample information about their substrates and targets, whereas less is known about their role in cancer and stem cells. Here, we review and discuss recent advances in our understanding of the structural and functional properties of mitochondrial sirtuins, including their targets in cancer and stem cells. These advances could help to improve the understanding of their interplay with signalling cascades and pathways, leading to new avenues for developing novel drugs for sirtuin‐related disease treatments. We also highlight the complex network of mitochondrial sirtuins in cancer and stem cells, which may be important in deciphering the molecular mechanism for their activation and inhibition.
Validation of the FibroScan‐aspartate aminotransferase score by vibration‐controlled transient and B‐mode ultrasound elastography
Authors: Hirooka Masashi , Koizumi Yohei , Yano Ryo , Sunago Kotarou , Watanabe Takao , Yoshida Osamu , Tokumoto Yoshio , Abe Masanori , Hiasa Yoichi
Published: April 2021

Aim

The FibroScan‐aspartate aminotransferase (FAST) score comprises an easy and feasible method for identifying advanced non‐alcoholic steatohepatitis. Recently, shear‐wave elastography and attenuation coefficient measurement on B‐mode ultrasound (US) have become widely utilized. We investigated the diagnostic accuracy of the FAST score as calculated using US‐elastography compared with that using vibration‐controlled transient elastography (VCTE).

Methods

Patients with chronic liver disease who underwent VCTE, point‐shear‐wave elastography with attenuation coefficient measurement, and liver biopsy on the same day between January 2015 and September 2020 were retrospectively reviewed.

Results

Of 189 patients, 94 underwent VCTE using both M and XL probes. The C‐statistics were similar for VCTE (0.846) and US‐elastography (0.814; p = 0.251), and for M (0.857) and XL probes (0.833; p = 0.412). Scatter and Bland–Altman plots showed good reproducibility for the FAST score. For VCTE, a cut‐off of ≤0.35 had a sensitivity of 92.3%, negative predictive value of 85.5%, and negative likelihood ratio of 0.14, and a cut‐off of ≥0.67 had a specificity of 90.6%, positive predictive value of 88.1%, and positive likelihood ratio of 6.03, for ruling out and in advanced non‐alcoholic steatohepatitis, respectively. For US‐elastography, a cut‐off of ≤0.35 had a sensitivity of 90.4%, negative predictive value of 83.3%, and negative likelihood ratio of 0.16, and a cutoff of ≥0.67 had a specificity of 91.8%, positive predictive value of 85.1%, and positive likelihood ratio of 4.67, for ruling out and in advanced non‐alcoholic steatohepatitis, respectively.

Conclusions

The FAST score is highly reproducible, even when different echo equipment or probes are used.
Objective assessment of Platelet‐Rich Plasma (PRP) potentiality in the treatment of Chronic leg Ulcer: RCT on 80 patients with Venous ulcer
Authors: Helmy Yasser , Farouk Nehal , Ali Dahy Asmaa , Abu‐Elsoud Ahmed , Fouad khattab Rania , Elshahat Mohammed Sahar , Abdullbary Gad Lamia , Altramsy Ayman , Hussein Emad , Farahat Ayman
Published: April 2021

Background

Chronic venous leg ulcer reduces the patients’ activities and their overall quality of life. Platelet‐rich plasma (PRP) was previously investigated as promising less invasive management for leg ulcers.

This study aims

To re‐assess the efficacy and safety of PRP in the management of chronic leg ulcers due to venous factors.

Patients/Methods

RCT enrolled 80 patients who clinically presented with chronic venous leg ulcers. Forty patients were allocated randomly for the treatment with autologous platelet‐rich plasma (PRP). Intradermal and subdermal injection of PRP by 27guage syringe weekly, in all edges and in the granular floor of the ulcer for 4–6 sessions. Another 40 patients managed by conventional treatment by compression and dressing for the same period were allocated as Group B. Objective assessment achieved by the percentage of reduction of the size of the ulcer area, rate of healing, incidence of recurrence, and if side effects have been reported.

Results

PRP therapy showed better results and high p value significance when compared to conventional therapy.

Conclusion

This study shows that PRP is effective and significant in promoting the wound healing process in chronic leg venous ulcers. PRP is simple, safe, and has a short learning curve technique.
An improved method for selection of wheat genotypes for tolerance to crown rot caused by Fusarium pseudograminearum
Authors: Kelly Alison , Macdonald Bethany , Percy Cassandra , Davies Philip
Published: April 2021

Achieving genetic gain when selecting for genotypes with favourable grain production traits in the presence of the fungal pathogen Fusarium pseudograminearum can involve potentially competitive objectives of breeding for tolerance and breeding for resistance. A method for the selection of genotypes for both tolerance and resistance to crown rot in wheat, caused by this fungal pathogen, is presented through a combined analysis of grain yield and symptoms of disease severity across inoculated and uninoculated treatments. The symptoms of disease severity are measured as basal stem browning in the plant, and this trait provides a measure of resistance in this study. The measurement of grain yield in uninoculated and inoculated treatments provides a measure of yield potential and yield in the presence of disease, respectively. Interpretation of analysis results through the regression inherent in the statistical model allows us to derive and select for three traits of interest. Firstly, yield retention can be derived from a random regression of yield of genotypes in inoculated versus uninoculated treatments, independently of yield potential in that environment. Secondly, severity of disease symptoms in inoculated treatments can be used to select genotypes with superior resistance. Finally, a tolerance measure can be derived from the yield retention, when it is assessed independently of the disease severity measured as stem browning. In theory, this method is superior to traditional approaches of forming a yield difference or a percentage yield loss calculation. In practice, genetic gain can be made for tolerance through accurate phenotyping of the trait, independently of resistance in that environment.
Mental health nursing and autism: I am a mental health nurse so why did it take me so long to realize I’m autistic?
Authors: Sweetmore Victoria
Published: April 2021

Accessible Summary

What is known on the subject?

Women with autistic spectrum disorder are likely to be diagnosed with other mental health needs and to have experienced trauma.

Mental health nurses are likely to encounter women who possibly fit the criteria for a autistic spectrum diagnosis, but who have not been offered appropriate support or signposting.

What the paper adds to existing knowledge

Using my own lived experience as a late diagnosed woman with autism and as a mental health nurse, I identify some of the gaps in training and knowledge that mental health nurses have.

What are the implications for practice?

Suggestions are made as to how improvements in mental health nurses’ knowledge of autistic spectrum disorder in women could enhance mental wellbeing for this group of people.
Variability in molecular characteristics of Hepatitis E virus quasispecies could modify viral surface properties and transmission
Authors: Hartard Cédric , Fenaux Honorine , Gentilhomme Alexis , Murray John M. , Akand Elma , Laugel Elodie , Berger Sibel , Maul Armand , de Rougemont Alexis , Jeulin Hélène , Remen Thomas , Bensenane Mouni , Bronowicki Jean‐Pierre , Gantzer Christophe , Bertrand Isabelle , Schvoerer Evelyne
Published: April 2021

Hepatitis E virus (HEV) usually causes self‐limited liver diseases but can also result in severe cases. Genotypes 1 (G1) and 2 circulate in developing countries are human‐restricted and waterborne, while zoonotic G3 and G4 circulating in industrialized countries preferentially infect human through consumption of contaminated meat. Our aims were to identify amino acid patterns in HEV variants that could be involved in pathogenicity or in transmission modes, related to their impact on antigenicity and viral surface hydrophobicity. HEV sequences from human (n = 37) and environmental origins (wild boar [n = 3], pig slaughterhouse effluent [n = 6] and urban wastewater [n = 2]) were collected for the characterization of quasispecies using ultra‐deep sequencing (ORF2/ORF3 overlap). Predictive and functional assays were carried out to investigate viral particle antigenicity and hydrophobicity. Most quasispecies showed a major variant while a mixture was observed in urban wastewater and in one chronically infected patient. Amino acid signatures were identified, as a rabbit‐linked HEV pattern in two infected patients, or the S68L (ORF2) / H81C (ORF3) residue mostly identified in wild boars. By comparison with environmental strains, molecular patterns less likely represented in humans were identified. Patterns impacting viral hydrophobicity and/or antigenicity were also observed, and the higher hydrophobicity of HEV naked particles compared with the enveloped forms was demonstrated. HEV variants isolated from human and environment present molecular patterns that could impact their surface properties as well as their transmission. These molecular patterns may concern only one minor variant of a quasispecies and could emerge under selective pressure.
A novel urine cell‐free DNA preservation solution and its application in kidney transplantation
Authors: Zhou Qiang , Liu Feng , Guo Luoying , Chen Ruoyang , Yuan Xiaodong , Li Chao , Shu Liping , Liu Haitao , Zhou Yang , Wu Yu , Shi Haifeng , Zhao Hongwen , Jiang Tingya
Published: April 2021

Aim

Urine cell‐free DNA (cfDNA) is a new type of liquid biopsy biomarker used in tumours and allograft injury detection but is highly susceptible to degradation by the high nuclease activity of urine. This study presents a newly developed urine cfDNA preservation solution (AlloU), efficient for examining allograft injury in kidney transplant recipients (KTx).

Methods

We established urine‐preserve solution called AlloU based on the response‐surface methodology, with two commercial collection reagents (Streck and K2 EDTA preservation solution) included for analysis. A total of 120 urine samples from KTx patients, including morning, nocturnal and random urine from specific storage time were subjected to investigation. The urine total cfDNA concentration was quantified by fluorometry, fragment distribution was analysed by qPCR, and donor‐derived cfDNA (ddcfDNA) was detected by next‐generation sequencing.

Results

Urine total cfDNA concentration and fragment size of samples preserved with AlloU and Streck did not change significantly within 5 days whereas the ddcfDNA also did not change significantly within 7 days. However, compared with EDTA, the total cfDNA concentration increased significantly on the third day. When compare with different urine types, it was found that samples preserved with AlloU showed no significant differences in total cfDNA concentration, fragment size, and ddcfDNA concentration, however, the SD for morning urine was significantly smaller in total cfDNA and ddcfDNA concentration.

Conclusion

To the best of our knowledge, this is the first report to verify the dynamics of urine cfDNA in KTx, especially in the analysis impact of different urine types on cfDNA detection.
Rhodocybe cistetorum (Basidiomycota, Entolomataceae), a new species from the Colchic ecoregion of Turkey
Authors: Sesli Ertugrul
Published: April 2021

Based on both morphological and molecular data, Rhodocybe cistetorum sp. nov., found under Cistus creticus, is described as a new species from the Black Sea coast of Turkey. ITS and LSU rDNA sequences obtained from the type specimen did not find any close match in public databases, but the new taxon is phylogenetically nested within Rhodocybe based on the analysis of LSU data from the new species as well as LSU, SSU, rpb2 and tef1 sequences from species of Clitocella, Clitopilus, Clitopilopsis, Rhodocybe and Rhodophana. The new species is well distinguished by a small, slightly umbilicate, creamy to beige pileus, decurrent, whitish to creamy lamellae and somewhat angular to broadly ellipsoid basidiospores. A full description of the species is provided with field photos, micromorphological illustrations, a phylogenetic tree and a short discussion.
Corneal thickness changes in myopic children during and after short‐term orthokeratology lens wear
Authors: Wan Kin , Yau Hing Tuen , Cheung Sin Wan , Cho Pauline
Published: April 2021

Purpose

To evaluate thickness changes in the central and mid‐peripheral cornea (CCT and mPCT), corneal epithelium (CET and mPET) and stroma (CST and mPST) of myopic children during and after short‐term orthokeratology (ortho‐k) lens wear, with conventional (CCF, 0.75 D) and increased compression factors (ICF, 1.75 D).

Methods

This was a self‐controlled case series study. Subjects wore a CCF lens in one eye and an ICF lens in the other. Anterior segment optical coherence tomography images were captured weekly for 1 month during lens wear and for 2 weeks after discontinuing lens wear. CCT and CET (central 3‐mm cornea) and mPCT and mPET (within a 4–6 mm diameter annulus) were measured. Stromal thickness (ST) was determined by subtracting epithelium thickness (ET) from corneal thickness (CT). The repeatability of the analytical software was also investigated on age‐matched spectacle‐wearing subjects (n = 98).

Results

Excluding three outliers (>3 S.D.s), the coefficient of repeatability and intraclass correlation coefficients of 98 spectacle‐wearing subjects ranged from 2.63 to 4.64 μm and from 0.90 to 0.99, respectively. For the weekly‐change study, CCT and CET in both eyes were significantly thinner after lens wear (p < 0.001) and CET thinning in the ICF eyes were significantly higher (p < 0.02). CCT changes were mainly contributed by CET. CST, mPCT, mPET and mPST changes were not significant (p > 0.20) in either eye. CT (all sublayers) rebounded to baseline values 2 weeks after discontinuing lens wear (0.99 > p > 0.12).

Conclusions

Significant reductions in CT and ET, but not ST, were observed within 1 month of ortho‐k lens wear. Wearing ICF lenses resulted in a higher reduction in CET. Corneal thickness changes were reversible after discontinuing lens wear.