bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing the protocols for the South Australian Emergency Department Admission Blood Psychoactive Testing (EDABPT) programme for drug surveillance
Authors: Partridge Emma , Alfred Sam , Camilleri Andrew , Green Hannah , Haustead Daniel , Kostakis Chris , Mallon Jake , Mason Kerryn , Rivers‐Kennedy April , Stockham Peter
Published: March 2021

Objective

ED presentations because of illicit use of psychotropic drugs and pharmaceuticals result in significant medical harm and resource consumption. Patient assessment is complicated by the regular emergence of new psychoactive substances, difficulties associated with their identification and a lack of information about their effects. Here we report the protocol for the Emergency Department Admission Blood Psychoactive Testing (EDABPT) programme, an observational study utilising clinical data capture and definitive drug identification to assess the medical impact and patterns of illicit drug use in the community, and their geographic and temporal fluctuations. The study provides data to an early warning system targeting an improved public health response to emerging drugs of concern.

Methods

Enrolment of adult patients presenting with suspected illicit drug use occurs at four major EDs in a single urban setting. Clinical and demographic data are collected by treating clinicians. Blood samples are collected at presentation and frozen on site prior to transport to a specialised forensic facility for comprehensive toxicological screening.

Results

Results are fed back to clinicians and disseminated more broadly via an existing local early warning system. Targeted warnings and public health releases are instigated where heightened risk or harm is identified.

Conclusion

The study pairs city‐wide patient enrolment with analytically confirmed toxicology results to allow broad sampling and identification of illicit drugs causing medical harm. It provides a mechanism for the identification of new agents as they emerge in the community, delivers a relevant and reliable source of information for public health agencies and clinicians and supplements existing local early warning mechanisms.
SimBit: A high performance, flexible and easy‐to‐use population genetic simulator
Authors: Matthey‐Doret Remi
Published: March 2021

SimBit is a general purpose, high performance forward‐in‐time population genetics simulator. SimBit can simulate a wide variety of selection scenarios (any selection and dominance coefficients variation, any epistatic interaction, any spatial and temporal changes of selection scenario, etc.), demographic scenarios (any changes in patch sizes, migration rates, realistic demography dependent on fecundity, hard vs. soft selection, exponential vs. logistic growth, gametic or zygotic dispersion, etc.) and mating systems (cloning and selfing rates, hermaphrodites or males and females). SimBit can also track QTLs (with hyperdimensional phenotypes, explicit fitness landscape, plasticity, developmental noise, etc.). Finally, SimBit can simulate multiple species with their ecological relationships. SimBit comes with a R wrapper that simplifies the management of an entire research project from the creation of a grid of parameters and corresponding inputs, running simulations and gathering outputs for analysis. SimBit's performance was extensively benchmarked in comparison to SLiM, Nemo and SFS_CODE, varying population size, recombination rate, mutation rate, and the number of loci. I also reproduced simulations from previous studies, benchmarked QTLs and coalescent tree recording techniques. SimBit was most often the highest performing program with the only notable exception of SLiM outperforming SimBit in scenarios with few loci and low genetic diversity.
Diagnostic value of anti‐citrullinated α‐enolase peptide 1 antibody in patients with rheumatoid arthritis: A systematic review and meta‐analysis
Authors: Li Haolong , Li Liubing , Liu Chenxi , Cheng Linlin , Yan Songxin , Chen Haizhen , Li Yongzhe
Published: March 2021

Aim

To evaluate the diagnostic value of anti‐citrullinated α‐enolase peptide 1 (anti‐CEP 1) antibody in patients with rheumatoid arthritis (RA) by conducting a systematic review and meta‐analysis.

Methods

The PubMed, Web of Science, Embase, Scopus, and Cochrane Library databases were searched for relevant studies published until September 23, 2020. A bivariate mixed‐effects model was used to calculate the diagnostic indices from primary data of eligible studies. We performed meta‐regression and subgroup analysis to explore the sources of heterogeneity.

Results

Twenty‐four articles, with a total of 17 380 patients with RA and 7505 control participants, met the criteria for inclusion in the meta‐analysis. The pooled sensitivity, specificity, and positive and negative likelihood ratios for the anti‐CEP 1 antibody were 44% (95% CI: 38%‐51%), 97% (95% CI: 96%‐98%), and 14.81 (95% CI: 10.66‐20.57) and 0.57 (95% CI: 0.52‐0.64), respectively. The pooled positive and negative predictive values were 0.96 (95% CI: 0.95‐0.97) and 0.53 (95% CI: 0.43‐0.63), respectively. The area under the summary receiver operating characteristic curve was 0.86. Meta‐regression indicated that the anti‐CEP 1 antibody detection method may be a source of heterogeneity. The subgroup analysis of the group in which the anti‐CEP 1 antibody was detected by using a commercial enzyme‐linked immunosorbent assay (ELISA) kit had a sensitivity of 59% (95% CI: 50%‐68%) and a specificity of 93% (95% CI: 85%‐97%).

Conclusions

The anti‐CEP 1 antibody had moderate RA diagnostic value with relatively low sensitivity and high specificity. An ELISA may increase the RA diagnostic sensitivity.
ExpandingTNMfor lung cancer through machine learning
Authors: Hueman Matthew , Wang Huan , Liu Zhenqiu , Henson Donald , Nguyen Cuong , Park Dean , Sheng Li , Chen Dechang
Published: March 2021

Background

Expanding the tumor, lymph node, metastasis (TNM) staging system by accommodating new prognostic and predictive factors for cancer will improve patient stratification and survival prediction. Here, we introduce machine learning for incorporating additional prognostic factors into the conventional TNM for stratifying patients with lung cancer and evaluating survival.

Methods

Data were extracted from SEER. A total of 77 953 patients were analyzed using factors including primary tumor (T), regional lymph node (N), distant metastasis (M), age, and histology type. Ensemble algorithm for clustering cancer data (EACCD) and C‐index were applied to generate prognostic groups and expand the current staging system.

Results

With T, N, and M, EACCD stratified patients into 11 groups, resulting in a significantly higher accuracy in survival prediction than the 10 AJCC stages (C‐index = 0.7346 vs. 0.7247, increase in C‐index = 0.0099, 95% CI: 0.0091–0.0106,p‐value = 9.2 × 10−147). There nevertheless remained a strong association between the EACCD grouping and AJCC staging (rank correlation = 0.9289;p‐value = 6.7 × 10−22). A further analysis demonstrated that age and histological tumor could be integrated with the TNM. Data were stratified into 12 prognostic groups with an even higher prediction accuracy (C‐index = 0.7468 vs. 0.7247, increase in C‐index = 0.0221, 95% CI: 0.0212–0.0231,p‐value <5 × 10−324).

Conclusions

EACCD can be successfully applied to integrate additional factors with T, N, M for lung cancer patients.
Angiomatoid fibrosis histiocytoma in the pulmonary artery: A case report
Authors: Mishima Shuji , Mishima Osamu , Azuhata Koji , Shimojo Hisashi , Ito Nobuo , Misawa Kenji , Shimizu Kimihiro
Published: March 2021

Angiomatoid fibrosis histiocytoma (AFH) is a rare neoplastic disease. Only one report has demonstrated an intraluminal tumor of the pulmonary artery (PA) corresponding to AFH to date. We describe the case of AFH with EWSR1‐CREB1 fusion occurring in the ascending artery. A 42‐year‐old man exhibited an abnormal nodule on chest computed tomography (CT) during checkup. It revealed an intraluminal mass in the ascending artery with significant metabolic uptake in positron emission tomography (PET)/CT. Therefore, right upper lobectomy with wedge resection of the PA trunk was performed. Histologically, the tumor was multinodular and surrounded by a dense lymphoplasmacytic cuff. Each nodule was composed of myxoid stroma and comprised ovoid or spindle cell fascicles with mild atypia. Fluorescent in situ hybridization (FISH) analysis confirmed EWSR1‐CREB1 fusion. A diagnosed as AFH was made. This report widens the spectrum of differential diagnoses of primary tumors occurring in the PA.
Archaeological evidence of an early Islamic monastery in the centre of al‐Qusur (Failaka Island, Kuwait)
Authors: Bonnéric Julie
Published: March 2021

The history of Christianity in the Gulf is still largely unknown since both archaeological and written sources are sparse. Many questions remain about the development and disappearance of Christian communities, as well as their form. A few sites were identified as Christian because of the discovery of churches or crosses. A church was excavated at al‐Qusur (Failaka Island, Kuwait) by the French Mission to Kuwait in 1988–1989. Since 2011, a new French–Kuwaiti Archaeological Mission in Failaka (MAFKF) has aimed to better understand the site’s phasing and organisation. The discovery of a large refectory and a small tripartite building that is most probably a monk’s cell, as well as the reinterpretation of a church‐like building as a structure perhaps dedicated to the spiritual education of monks has demonstrated that at least the central part was a monastery, making it the second Christian settlement in the Gulf to be proven to be a monastery.
Relationship lending and bank loan covenant violations
Authors: Bo Xu Chong , Li Wenyi , Shi Jing , Zheng Yi , Zhou Qing
Published: March 2021

We examine the association between relationship lending and the likelihood of bank loan covenant violations. We find that relationship lending reduces the probability of ex‐post covenant violations. The length of the lending relationships has an inverted U‐shaped effect on the likelihood of covenant violations. The borrowers and lenders both benefit from relationship lending, but long‐term lending relationships weaken the borrower's bargaining power.
Incidence of schizophrenia and influence of prenatal and infant exposure to viral infectious diseases
Authors: Tanskanen Antti , Taipale Heidi , Cannon Mary , Cotter David , Tiihonen Jari
Published: March 2021

Objective

There is conflicting evidence in recent literature about whether the incidence of schizophrenia is increasing or decreasing. A role for prenatal and early childhood viral infections in the aetiology of schizophrenia has also been debated. We examined the incidence of schizophrenia and the catatonic subtype of schizophrenia over a 30‐year period in Finland. We also investigated whether the incidence rate of the catatonic subtype of schizophrenia was linked to changes in exposure to viral infection (polio and measles) during the prenatal or infant period.

Methods

Persons with schizophrenia were identified from the Hospital Discharge Register. Cumulative incidence of schizophrenia from 1956 to 1989 in 4 age groups was calculated with follow‐up from 1972 to 2014. Annual rates of polio and measles were derived from nationwide registers. The association between log‐transformed polio and measles incidence and incidence of schizophrenia, and specifically catatonic schizophrenia, were analysed using linear models.

Results

Cumulative incidence of schizophrenia among individuals born 1956–1989 decreased by 23% (from 13 to 10 cases per 1000 live births). The decline was the most prominent in those with onset of schizophrenia diagnosed 16–25 years of age (−41%). The incidence of catatonic schizophrenia declined by 90% over three decades, and there was a significant association between annual polio incidence during the birth year and incidence of catatonic schizophrenia.

Conclusions

The results indicate that the incidence of schizophrenia in Finland has declined for individuals born between 1956 and 1989, and that the decline of catatonic schizophrenia may be partially attributable to eradication of polio.
Contribution of XP‐Endo files to the root canal filling removal: A systematic review and meta‐analysis ofin vitrostudies
Authors: Uzunoglu‐Özyürek Emel , Küçükkaya Eren Selen , Karahan Sevilay
Published: March 2021

This review was designed to analyse whether the supplementary use of XP‐Endo Finisher and XP‐Endo Finisher R contributes to the removal of root canal filling materials. Databases were searched up to November 2020. Studies were critically assessed according to inclusion and exclusion criteria. Risk of bias evaluation was performed. Pooled standardised mean differences (SMD) and 95% confidence intervals (95% CI) were calculated. Ten studies involving 192 teeth were eligible for systematic review and meta‐analysis could be performed with eight of these studies. Strong evidence showed that XP‐Endo Finisher R file contributed significantly to filling material removal from root canals (SMD (95% CI): 0.41 (0.06–0.76)). Although the evidence was conflicting, XP‐Endo Finisher R file was superior than other irrigant activation techniques (SMD (95% CI): 0.47 (0.02–0.93)). The supplementary use of XP‐Endo Finisher and XP‐Endo Finisher R is beneficial in further removal of root canal filling materials from root canal system.
The Welfare Implications of Massive Money Injection: The Japanese Experience from 2013 to 2020
Authors: Watanabe Tsutomu
Published: March 2021

The present paper derives a money demand function that explicitly takes the costs of storing money into account. This function is then used to examine the consequences of the large‐scale money injection conducted by the Bank of Japan since April 2013. The main findings are as follows. First, the opportunity cost of holding money calculated using 1‐year government bond yields has been negative since the fourth quarter of 2014 and most recently (2020:Q2) was −0.2%. Second, the marginal cost of storing money, which was 0.3% in the most recent quarter, exceeds the marginal utility of money, which was 0.1%. Third, the optimal quantity of money, measured by the ratio of M1 to nominal gross domestic product, is 1.2. In contrast, the actual money‐income ratio in the most recent quarter was 1.8. The welfare loss relative to the maximum welfare obtained under the optimal quantity of money in the most recent quarter was 0.2% of nominal gross domestic product. The findings imply that the Bank of Japan needs to reduce M1 by more than 30%, for example through measures that impose a penalty on holding money.
Maternal and neonatal outcomes in planned versus emergency cesarean delivery for placenta accreta spectrum: A multinational database study
Authors: Morlando Maddalena , Schwickert Alexander , Stefanovic Vedran , Gziri Mina M. , Pateisky Petra , Chalubinski Kinga M. , Nonnenmacher Andreas , Morel Olivier , Braun Thorsten , Bertholdt Charline , Van Beekhuizen Heleen J. , Collins Sally L. ,   the International Society for Placenta Accreta Spectrum (IS‐PAS)
Published: March 2021

Introduction

Placenta accreta spectrum (PAS) is a condition often resulting in severe maternal morbidity. Scheduled delivery by an experienced team has been shown to improve maternal outcomes; however, the benefits must be weighed against the risk of iatrogenic prematurity. The aim of this study is to investigate the rates of emergency delivery seen for antenatally suspected PAS and compare the resulting outcomes in the 15 referral centers of the International Society for PAS (IS‐PAS).

Material and methods

Fifteen centers provided cases between 2008 and 2019. The women included were divided into two groups according to whether they had a planned or an emergency cesarean delivery. Delivery was defined as “planned” when performed at a time and date to suit the team. All the remaining cases were classified as “emergency”. Maternal characteristics and neonatal outcomes were compared between the two groups according to gestation at delivery.

Results

In all, 356 women were included. Of these, 239 (67%) underwent a planned delivery and 117 (33%) an emergency delivery. Vaginal bleeding was the indication for emergency delivery in 41 of the 117 women (41%). There were no significant differences in terms of blood loss, transfusion rates or major maternal morbidity between planned and emergency deliveries. However, the rate of maternal intensive therapy unit admission was increased with emergency delivery (45% vs 33%, P = .02). Antepartum hemorrhage was the only independent predictor of emergency delivery (aOR: 4.3, 95% confidence interval 2.4‐7.7). Emergency delivery due to vaginal bleeding was more frequent with false‐positive cases (antenatally suspected but not confirmed as PAS at delivery) and the milder grades of PAS (accreta/increta). The rate of infants experiencing any major neonatal morbidity was 25% at 34+1 to 36+0 weeks and 19% at >36+0 weeks.

Conclusions

Emergency delivery in centers of excellence did not increase blood loss, transfusion rates or maternal morbidity. The single greatest risk factor for emergency delivery was antenatal hemorrhage. When adequate expertise and resources are available, to defer delivery in women with no significant antenatal bleeding and no risk factors for pre‐term birth until >36+0 weeks can be considered to improve fetal outcomes. Further studies are needed to investigate this fully.
The All Wales Medicines Strategy Group: 18 years' experience of a national medicines optimisation committee
Authors: Haines Kathryn , Bracchi Robert , Lang Ruth , Samuels Karen , Routledge Philip A.
Published: March 2021

Aims

To review the medicines optimisation activities of the All Wales Medicines Strategy Group (AWMSG), a committee established in 2002 to advise the Welsh Government on “all matters related to prescribing”. Although AWMSG conducts other activities (e.g., health technology appraisal for medicines), we focus here on its role in advising on medicines optimisation.

Methods

Prescribing indicators have been used in Wales to measure change, together with data on volumes and costs of medicines dispensed. A range of improvement strategies have been categorised under the “four Es”, namely educational initiatives, economic incentives, “engineering” and “enforcement”.

Results

AWMSG has helped health professionals in NHS Wales to reduce harm and waste, and to reduce inappropriate local or regional duplication and variation. Specific initiatives include the achievement of major cost savings by supporting increased generic prescribing and an “invest to save” approach related to prescribing of hypnotics and tranquillisers, non‐steroidal anti‐inflammatory drugs (NSAIDs) and proton pump inhibitors. AWMSG also successfully commissioned the introduction of a single national in‐patient medication chart for Wales in 2004. Ongoing priorities include a focus on reducing prescribing of certain medicines deemed “low value for prescribing” and on optimising the use of biosimilar medicines.

Conclusions

Since 2002, AWMSG has acted as a national medicines optimisation committee in Wales. From the outset, pharmacists and clinical pharmacologists have collaborated closely and shared their complementary expertise to make a much greater contribution to the safe, effective and cost‐effective use of medicines than either group could have achieved by working separately.
A safety signal of somnambulism with the use of antipsychotics and lithium: A pharmacovigilance disproportionality analysis
Authors: Gouverneur Amandine , Ferreira Amandine , Morival Camille , Pageot Cécile , Tournier Marie , Pariente Antoine
Published: March 2021

Aims

Antipsychotics and lithium are widely used in psychiatry, particularly in schizophrenia and bipolar disorders. Recently, some cases of somnambulism or sleep‐related eating disorder (SRED) have been reported in patients treated with these drugs. This study investigated the risk of reporting somnambulism or SRED associated with the use of antipsychotics and lithium.

Methods

The World Health Organization pharmacovigilance database (VigiBase), comprising >18 million adverse events, was queried. All somnambulism or SRED reports related to antipsychotics or lithium were identified. The association between antipsychotics or lithium and somnambulism or SRED was computed using the proportional reporting ratio (PRR) and information component.

Results

Among the 5784 cases reporting somnambulism or SRED, 508 suspected at least 1 antipsychotic or lithium. Most patients were aged 18–64 years (62.0%), and 37.0% were men. In most cases (77.6%), antipsychotic or lithium were the only drug class involved, and 53.3% of cases suspected quetiapine. Somnambulism was reported in 88.6% of cases and SRED in 18.1%. A significant association was found for second‐generation antipsychotics (PRR 3.44, 95% confidence interval 3.13) and lithium (PRR 2.03, [1.22; 3.37]), but not for first‐generation antipsychotics (PRR 0.99, [0.68; 1.44]).

Conclusions

We found a significant signal of somnambulism or SRED related to second‐generation antipsychotics and lithium. While case reports mentioned mostly quetiapine and olanzapine, almost all second‐generation antipsychotics were associated with somnambulism or SRED.
Monocyte–macrophage polarization and recruitment pathways in the tumour microenvironment of B‐cell acute lymphoblastic leukaemia
Authors: Dander Erica , Fallati Alessandra , Gulić Tamara , Pagni Fabio , Gaspari Stefania , Silvestri Daniela , Cricrì Giulia , Bedini Gloria , Portale Federica , Buracchi Chiara , Starace Rita , Pasqualini Fabio , D'Angiò Mariella , Brizzolara Lisa , Maglia Oscar , Mantovani Alberto , Garlanda Cecilia , Valsecchi Maria Grazia , Locatelli Franco , Biondi Andrea , Bottazzi Barbara , Allavena Paola , D'Amico Giovanna
Published: March 2021

B‐cell acute lymphoblastic leukaemia (B‐ALL) reprograms the surrounding bone marrow (BM) stroma to create a leukaemia‐supportive niche. To elucidate the contribution of immune cells to the leukaemic microenvironment, we investigated the involvement of monocyte/macrophage compartments, as well as several recruitment pathways in B‐ALL development. Immunohistochemistry analyses showed that CD68‐expressing macrophages were increased in leukaemic BM biopsies, compared to controls and predominantly expressed the M2‐like markers CD163 and CD206. Furthermore, the "non‐classical" CD14+CD16++ monocyte subset, expressing high CX3CR1 levels, was significantly increased in B‐ALL patients' peripheral blood. CX3CL1 was shown to be significantly upregulated in leukaemic BM plasma, thus providing an altered migratory pathway possibly guiding NC monocyte recruitment into the BM. Additionally, the monocyte/macrophage chemoattractant chemokine ligand 2 (CCL2) strongly increased in leukaemic BM plasma, possibly because of the interaction of leukaemic cells with mesenchymal stromal cells and vascular cells and due to a stimulatory effect of leukaemia‐related inflammatory mediators. C5a, a macrophage chemoattractant and M2‐polarizing factor, further appeared to be upregulated in the leukaemic BM, possibly as an effect of PTX3 decrease, that could unleash complement cascade activation. Overall, deregulated monocyte/macrophage compartments are part of the extensive BM microenvironment remodelling at B‐ALL diagnosis and could represent valuable targets for novel treatments to be coupled with classical chemotherapy.
The use of frailty assessments in treating older adults with aggressive lymphomas
Authors: Cordoba Raul , Luminari Stefano , Eyre Toby A.
Published: March 2021

Non‐Hodgkin lymphomas (NHL) are most commonly diagnosed among people aged 65–74 years, with a median age at diagnosis of 67 years. The percentage of NHL‐related deaths is highest among people aged 75–84 years, with a median age at death of 76 years from cases between 2014 and 2018. In light of these recent data, attending physicians of patients with NHL will recognize that the majority of their patients will be of advanced age, with many suffering from a spectrum of frailties. The excess rate of death among older adults with NHL may be related to a range of different factors such as more challenging biologic features, undertreatment received due to a patient’s chronology and treatment‐related toxicity. The aim of this review is to provide an updated overview of the knowledge generated over recent years regarding epidemiology, prognosis and treatment options in older adults with lymphoma, focusing on Diffuse Large B‐cell Lymphoma (DLBCL) where the most robust evidence base is available.
Exome sequencing utility in defining the genetic landscape of hearing loss and novel‐gene discovery in Iran
Authors: Mohseni Marzieh , Babanejad Mojgan , Booth Kevin T. , Jamali Payman , Jalalvand Khadijeh , Davarnia Behzad , Ardalani Fariba , Khoshaeen Atefeh , Arzhangi Sanaz , Ghodratpour Fatemeh , Beheshtian Maryam , Jahanshad Faezeh , Otukesh Hasan , Bahrami Fatemeh , Seifati Seyed Morteza , Bazazzadegan Niloofar , Habibi Farkhonde , Behravan Hanieh , Mirzaei Sepide , Keshavarzi Fatemeh , Nikzat Nooshin , Mehrjoo Zohreh , Thiele Holger , Nothnagel Michael , Azaiez Hela , Smith Richard J. , Kahrizi Kimia , Najmabadi Hossein
Published: March 2021

Hearing loss (HL) is one of the most common sensory defects affecting more than 466 million individuals worldwide. It is clinically and genetically heterogeneous with over 120 genes causing non‐syndromic HL identified to date. Here, we performed exome sequencing (ES) on a cohort of Iranian families with no disease‐causing variants in known deafness‐associated genes after screening with a targeted gene panel. We identified likely causal variants in 20 out of 71 families screened. Fifteen families segregated variants in known deafness‐associated genes. Eight families segregated variants in novel candidate genes for HL: DBH, TOP3A, COX18, USP31, TCF19, SCP2, TENM1, and CARMIL1. In the three of these families, intrafamilial locus heterogeneity was observed with variants in both known and novel candidate genes. In aggregate, we were able to identify the underlying genetic cause of HL in nearly 30% of our study cohort using ES. This study corroborates the observation that high‐throughput DNA sequencing in populations with high rates of consanguineous marriages represents a more appropriate strategy to elucidate the genetic etiology of heterogeneous conditions such as HL.
Modeling and understanding social–ecological knowledge diversity
Authors: Schwermer Heike , Aminpour Payam , Reza Caitie , Funk Steffen , Möllmann Christian , Gray Steven
Published: March 2021

The concept of social–ecological knowledge diversity (SEKD) provides a novel way of examining coupled human–environment interactions—it acknowledges differences in knowledge, values, and beliefs of stakeholder groups within social–ecological systems (SES). Thus, understanding and measuring SEKD is an essential component of sustainable management with implications for conflict resolution, collective action and policymaking. However, methods to efficiently define and model knowledge diversity are still underdeveloped. Using a semiquantitative cognitive mapping approach, we collected and analyzed stakeholder‐specific knowledge and perceptions of the Western Baltic cod fishery to model SEKD. Results demonstrate substantial variation in perceptions across different individuals and social groups. SEKD was evident in (a) distinctive meanings attached to social factors relative to ecological factors, (b) causal relationships underlying the understanding of SES dynamics, and (c) social impacts of ecological changes on ecosystems (and vice versa). By identifying and representing knowledge‐specific disparities in SES frameworks, our model explicitly improves the understanding of human–environment interactions with implications that could help reduce conflicts and legitimize management plans.
Late‐onset allograft rejection, cytomegalovirus infection, and renal allograft loss: Is anti‐CMV prophylaxis required following late‐onset allograft rejection?
Authors: Rahimishahmirzadi Mohammadreza , Jevnikar Anthony M. , House Andrew A. , Luke Patrick P. , Humar Atul , Silverman Michael S. , Shalhoub Sarah M. , Hosseini‐Moghaddam Seyed M.
Published: March 2021

Renal transplant recipients remain at risk of delayed‐onset cytomegalovirus (CMV) infection occurring beyond a complete course of prophylaxis. In this retrospective cohort, all 278 patients who received renal allografts from deceased donors from 2014 to 2016 were followed until September 1, 2019. We determined the effect of early–vs late‐onset acute rejection (EAR vs LAR [ie, occurring beyond 12 months after transplantation]) on CMV infection and subsequently long‐term allograft outcome.

Median (IQR) duration of follow‐up was 1186.0 (904.7‐1531.2) days. Seventy patients including 49 patients with EAR and 21 with LAR received augmented immunosuppression. In the same interval, 40 patients developed CMV infection (36 patients beyond 90 days after transplantation [90%]). In logistic regression analysis, D+/R‐ CMV serostatus (OR: 5.5, 95% CI: 2.5‐12.2) and LAR (OR: 7.9, 95% CI: 2.8‐22.2) significantly increased the risk of CMV infection. In Cox proportional hazard model, delayed‐onset CMV infection (HR: 2.51, 95% CI: 1.08‐5.86) and LAR (HR: 5.46, 95% CI: 2.26‐13.14) significantly increased the risk of allograft loss.

Patients with LAR are at risk of late‐onset CMV infection. Post‐LAR, targeted prophylaxis may reduce the risk of CMV infection and subsequently allograft loss. Further studies are required to demonstrate the effect of targeted prophylaxis following LAR.
Cholesterotic fibrous histiocytoma: Case report and literature review
Authors: Lukach Alexis J. , Adams Alison K. , Werling Robert W.
Published: March 2021

Cholesterotic fibrous histiocytoma is a particularly rare variant of dermatofibroma that is distinguished histopathologically by the presence of prominent cholesterol deposits within the lesion. We report the case of a 54‐year‐old male with poorly controlled hyperlipidemia who presented with a firm violaceous papule on the right shin, diagnosed as a cholesterotic fibrous histiocytoma. We also review and summarize the existing literature on this uncommon entity.
Effects of stomach content on the breath alcohol concentration‐transdermal alcohol concentration relationship
Authors: Saldich Emily B. , Wang Chunming , Rosen I. Gary , Bartroff Jay , Luczak Susan E.
Published: March 2021

Introduction

Wearable devices that obtain transdermal alcohol concentration (TAC) could become valuable research tools for monitoring alcohol consumption levels in naturalistic environments if the TAC they produce could be converted into quantitatively‐meaningful estimates of breath alcohol concentration (eBrAC). Our team has developed mathematical models to produce eBrAC from TAC, but it is not yet clear how a variety of factors affect the accuracy of the models. Stomach content is one factor that is known to affect breath alcohol concentration (BrAC), but its effect on the BrAC‐TAC relationship has not yet been studied.

Methods

We examine the BrAC‐TAC relationship by having two investigators participate in four laboratory drinking sessions with varied stomach content conditions: (i) no meal, (ii) half and (iii) full meal before drinking, and (iv) full meal after drinking. BrAC and TAC were obtained every 10 min over the BrAC curve.

Results

Eating before drinking lowered BrAC and TAC levels, with greater variability in TAC across person‐device pairings, but the BrAC‐TAC relationship was not consistently altered by stomach content. The mathematical model calibration parameters, fit indices, and eBrAC curves and summary score outputs did not consistently vary based on stomach content, indicating that our models were able to produce eBrAC from TAC with similar accuracy despite variations in the shape and magnitude of the BrAC curves under different conditions.

Discussion and Conclusions

This study represents the first examination of how stomach content affects our ability to model estimates of BrAC from TAC and indicates it is not a major factor.
Screening marker sensitivity: Optimizing eDNA‐based rare species detection
Authors: Xia Zhiqiang , Zhan Aibin , Johansson Mattias L. , DeRoy Emma , Haffner Gordon Douglas , MacIsaac Hugh J.
Published: March 2021

Aim

Environmental DNA (eDNA)‐based techniques are useful tools in disciplines such as conservation biogeography at local to global scales since they provide promising methods to locate organisms at low abundance. Here, we raise a largely overlooked issue that the marker (primer pairs and/or probes) sensitivity of eDNA‐based detection should be optimized and reported to improve detection performance and result interpretation.

Location

Global.

Methods

We analysed 250 articles published between 2008 and 2019 that sought to detect animals from environmental water samples using species‐specific markers to identify effort required.

Results

Most (66.0%) studies used newly designed markers, and real‐time quantitative PCR dominated the studies (72.4% of articles). The use of quantitative PCR increased significantly over time (p = .016), while conventional PCR decreased significantly (p = .005). In 82.4% of studies using newly designed markers, researchers did not screen their chosen markers for sensitivity, and 46.7% of these studies did not report the limit of detection (LoD). Limited knowledge of sensitivity screening and LoD was also found among aquatic species on the list of the world's worst alien invasive species, and many studies used published markers without such knowledge, potentially propagating errors.

Main conclusions

The rapidly growing use of eDNA‐based detection of low‐abundance species requires well‐designed protocols to improve sensitivity. Knowledge of the limits of eDNA technology is imperative, particularly when applied to conservation biogeography studies for detecting non‐indigenous or endangered species. Our results highlight the currently inadequate sensitivity screening of genetic markers used in most studies, contrasting the transition to highly sensitive PCR methods. Along with ongoing calls for standardization in the eDNA methods, we add that newly designed markers be screened to determine and optimize sensitivity before use to reduce the uncertainty of detection and benefit future applications within or beyond areas of their development.
Peroral endoscopic tumor resection of a granular cell tumor arising from the 4th layer: Case report with video
Authors: Scaffidi Michael A. , Hurlbut David , Bechara Robert
Published: March 2021

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Case of bile duct coil embolization for broncho‐biliary fistula after radiofrequency ablation (with video)
Authors: Suzuki Eisuke , Fujita Yuji , Matsuhashi Nobuyuki
Published: March 2021

Watch a video of this article.
Colonoscopy screening and surveillance guidelines
Authors: Saito Yutaka , Oka Shiro , Kawamura Takuji , Shimoda Ryo , Sekiguchi Masau , Tamai Naoto , Hotta Kinichi , Matsuda Takahisa , Misawa Masashi , Tanaka Shinji , Iriguchi Yosuke , Nozaki Ryoichi , Yamamoto Hironori , Yoshida Masahiro , Fujimoto Kazuma , Inoue Haruhiro
Published: March 2021

The Colonoscopy Screening and Surveillance Guidelines were developed by the Japan Gastroenterological Endoscopy Society as basic guidelines based on the scientific methods. The importance of endoscopic screening and surveillance for both detection and post‐treatment follow‐up of colorectal cancer has been recognized as essential to reduce disease mortality. There is limited high‐level evidence in this field; therefore, we had to focus on the consensus of experts. These clinical practice guidelines consist of 20 clinical questions and eight background knowledge topics that have been determined as the current guiding principles.
Effectiveness of two biopesticides against the invasive tomato pest Tuta absoluta
Authors: Sarr Oumar Mal , Bal Amadou Bocar , Fossati‐Gaschignard Odile , Gauthier Nathalie
Published: March 2021

Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) is among the most devastating pests worldwide of solanaceous plants, particularly of tomato (Solanum lycopersicum L.). Since its recent introduction into sub‐Saharan Africa, it has become an additional widespread tomato pest throughout the region. When no control measures are taken, yield losses caused by T. absoluta larvae can reach 100%. Chemical control remains the primary management option despite its many adverse effects and increasing inefficiency due to the species’ endophytic habits and ability to develop insecticide resistance. Safer and more effective alternatives are therefore urgently required. Here, we investigated the effectiveness of two bioinsecticides compared to that of a widely used deltamethrin‐based synthetic insecticide, in preventing damage caused by T. absoluta larvae to tomato leaves and fruits, thereby affecting tomato yield. A field trial was conducted in 2018 and 2019 in northwestern Senegal using a randomized complete block design. Damage caused by T. absoluta affected approximately 65% of total leaf area and 3–24% of the fruits. Damage to the leaves caused by other insect species or other factors was less significant. At the dose applied, the chemical insecticide did not significantly reduce the surface area of leaflets affected by T. absoluta or other causal agents, the number of T. absoluta mines on the leaflets, or the proportion of fruits damaged. In contrast, the azadirachtin and Bacillus thuringiensis (Bt) formulations rapidly and significantly reduced damage to both leaves and fruits. The proportion of fruits damaged was reduced by a factor two and the total tomato yield was improved, particularly when the Bt formulation was used. In addition to their effectiveness in reducing damage caused by T. absoluta larvae to tomato leaves and fruit, and increasing the yield of marketable fruits, the viability of these organic alternatives was shown. The scope of our results is discussed in the context of T. absoluta control, in particular in integrated pest management programmes for tomato crops.
Effects of light and nutrients on intraspecific competition among midges from a shallow eutrophic lake
Authors: Wetzel Rebecca L. , McCormick Amanda R. , Phillips Joseph S. , Ives Anthony R.
Published: March 2021

1. Intraspecific competition for food may affect the development, survival, and fecundity of organisms. However, environmental variation in abiotic conditions can influence resource quality and/or quantity, thereby modifying the strength of intraspecific competition.

2. This study focuses on intraspecific competition among Tanytarsus gracilentus (Chironomidae: Diptera) larvae. In Lake Mývatn, Iceland, T. gracilentus undergoes large population fluctuations, and evidence suggests that these fluctuations are governed by consumer‐resource interactions between the larvae and benthic diatoms. In two experiments, we studied (i) the effects of larval density on individual development and survival, and (ii) how light and nutrients (nitrogen and phosphorus) mediate the strength of intraspecific competition across a density gradient.

3. Survival declined with increasing larval density in both experiments, although not significantly in the first experiment in which we manipulated only density. In the second experiment, enhancement of either light or phosphorus mitigated the negative effect of larval density on survival. In both experiments, density had a negative effect on individual development. In the first experiment, fewer larvae progressed to the final fourth instar at higher densities. In the second experiment, larvae were smaller in high density treatments, and this effect was most pronounced in the treatments without light or phosphorus supplementation.

4. These results highlight the potential for environmental factors to influence the strength of density‐dependent competition. Environmental variation that affects resource quantity or quality may influence the overall dynamics of our study organism and other populations whose dynamics are controlled by consumer‐resource relationships.
Defibrotide in hematopoietic stem cell transplantation: A multicenter survey study of the Spanish Hematopoietic Stem Cell Transplantation Group (GETH)
Authors: González Vicent Marta , Díaz de Heredia Cristina , González de Pablo Jesús , Molina Blanca , Regueiro Alexandra , Pérez Martinez Antonio , Palomo Pilar , López Corral Lucía , García Estefanía , Fernández José María , Pérez Ariadna , Jiménez María José , Guerreiro Manuel , Vallejo Carlos , Gallardo Ana Isabel , López Oriana , Benito Ana , Marsal Julia , Duarte Mónica , Bento Leyre , Badell Isabel , Pedraza Alexandra , Jiménez Ubieto Ana , González Pedro , Gómez Centurión Ignacio , Costilla Lissette , Beléndez Cristina , Esquirol Albert , Espigado Ildefonso , Lavilla Esperanza , Díaz Miguel Ángel
Published: March 2021

Background

Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant‐associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT.

Methods

This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON).

Results

Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%‐91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%‐86%) and 62% (95% CI, 59%‐65%), respectively (P = .0015). With a longer follow‐up, median of 2 years (4 months–7 years), OS was 63% (95% CI, 59%‐67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%‐61%) and 26% (95% CI, 22%‐30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%).

Conclusions

Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long‐term survival, as can be concluded from our study.
Synergistic effect of sleep depth and seizures correlates with postictal heart rate
Authors: Schomer Andrew C. , Lynch Morgan , Lowenhaupt Stephanie , Leonardo Juliana , Baljak Valentina , Clark Matthew , Kapur Jaideep , Quigg Mark
Published: March 2021

Our objective was to determine the effect of sleep on heart rate following a recorded seizure. We prospectively acquired heart rate data in hospitalized epilepsy monitoring unit patients. We analyzed heart rate trends for multiple seizures (n = 101) in patients (n = 42) with electroencephalographically confirmed events. The patient's sleep state was scored for the 5 min preceding each seizure and correlated with the postictal nadir heart rate (PINHR). The depth of sleep during the 5 min before a seizure correlated (correlation coefficient [CC] = −.229, p < .05) with PINHR. This result was more significant and strengthened (CC = −.272, 95% confidence interval = −.392 to −.152, p < .001) when adjusted for covariates of age, generalized tonic–clonic seizures, and baseline heart rate. Sleep depth is an independent predictor of the change in heart rate following a seizure. Diminished heart rate following a seizure in the setting of sleep is likely secondary to non‐rapid eye movement sleep's synergistic effect on parasympathetic tone.
Magnetic resonance‐guided laser interstitial thermal therapy: Correlations with seizure outcome
Authors: Kang Joon Y. , Pickard Allyson A. , Bronder Jay , Yenokyan Gayane , Chen Mo , Anderson William S. , Sperling Michael R. , Nei Maromi
Published: March 2021

Objective

This study was undertaken to identify clinical factors associated with seizure freedom after magnetic resonance‐guided laser interstitial thermal therapy (MRgLiTT) in temporal lobe epilepsy patients with unilateral mesial temporal sclerosis (MTS).

Methods

We identified 56 patients with magnetic resonance imaging‐defined MTS who underwent MRgLiTT with at least 1 year of follow‐up. Primary outcome was seizure freedom at 1 year. We examined the association of seizure freedom and the following clinical factors: age at surgery, gender, history of febrile seizures, history of focal to bilateral tonic–clonic seizures, duration of epilepsy at the time of surgery, frequency of interictal epileptiform discharges (IEDs), seizure frequency, and presence of bilateral IEDs.

Results

Thirty‐five (62.5%) patients were seizure‐free at 1 year. The presence of bilateral IEDs and age at surgery were associated with 1‐year seizure freedom after MRgLiTT. The presence of bilateral IEDS was associated with lower odds of seizure freedom (odds ratio [OR] = .05, 95% confidence interval [CI] = .01–.46, p = .008), whereas increasing age at surgery was associated with increased odds of seizure freedom (OR = 1.10, 95% CI = 1.03–1.19, p = .009).

Significance

This study demonstrates associations between presence of bilateral IEDs and age at surgery and seizure freedom at 1 year after MRgLiTT.
Whole genome genotyping reveals discrete genetic diversity in north‐east Atlantic maerl beds
Authors: Jenkins Tom L. , Guillemin Marie‐Laure , Simon‐Nutbrown Cornelia , Burdett Heidi L. , Stevens Jamie R. , Peña Viviana
Published: March 2021

Maerl beds are vital habitats for a diverse array of marine species across trophic levels, but they are increasingly threatened by human activities and climate change. Furthermore, little is known about the genetic diversity of maerl‐forming species and the population structure of maerl beds, both of which are important for understanding the ability of these species to adapt to changing environments and for informing marine reserve planning. In this study, we used a whole genome genotyping approach to explore the population genomics of Phymatolithon calcareum, a maerl‐forming red algal species, whose geographical distribution spans the north‐east Atlantic, from Norway to Portugal. Our results, using 14,150 genome‐wide SNPs (single nucleotide polymorphisms), showed that P. calcareum maerl beds across the north‐east Atlantic are generally structured geographically, a pattern likely explained by low dispersal potential and limited connectivity between regions. Additionally, we found that P. calcareum from the Fal Estuary, south‐west England, is genetically distinct from all other P. calcareum sampled, even from The Manacles, a site located only 13 km away. Further analysis revealed that this finding is not the result of introgression from two closely related species, Phymatolithon purpureum or Lithothamnion corallioides. Instead, this unique diversity may have been shaped over time by geographical isolation of the Fal Estuary maerl bed and a lack of gene flow with other P. calcareum populations. The genomic data presented in this study suggest that P. calcareum genetic diversity has accumulated over large temporal and spatial scales, the preservation of which will be important for maximizing the resilience of this species to changes in climate and the environment. Moreover, our findings underline the importance of managing the conservation of maerl beds across western Europe as distinct units, at a site‐by‐site level.