bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Outcomes of Paediatric and Adult Crohn’s Disease and Association With Emerging Use of Biologics–A Nationwide Study From the Epi-IIRN
Authors: Atia Ohad , Orlanski-Meyer Esther , Lujan Rona , Ledderman Natan , Greenfeld Shira , Kariv Revital , Daher Saleh , Yanai Henit , Loewenberg Weisband Yiska , Gabay Hagit , Matz Eran , Nevo Daniel , Israeli Eran , Schwartz Doron , Chowers Yehuda , Dotan Iris , Turner Dan
Published: November 2021

Background

The effectiveness of biologics for improving long-term outcomes in patients with Crohn’s disease [CD] is still controversial. In this nationwide study, we aimed to evaluate trends of long-term outcomes in all CD patients in Israel during the biologics era.

Methods

Trends of outcomes were analysed using data from the four Israeli health maintenance organisations, covering 98% of the population; joinpoint regression models were used to explore changes of these trends over 2005 to 2019.

Results

A total of 16 936 patients were diagnosed with CD in Israel since 2005 (2932 [17%] paediatric onset, 14 004 [83%] adult onset) with 114 947 person-years of follow-up. The cumulative rate of any CD related surgery was 5%, 9%, 11%, and 14% at 1, 3, 5, and 10 years from diagnosis. The increase in use of biologics was sharp (from 8.9% to 36%; average annual percent change [AAPC], 14.3%), and the time to biologics was shorter in recent years (median time of 4.8 [1.9–8.1] years in those diagnosed in 2005–2008 compared with 0.5 [0.2–1.1] years in those diagnosed in 2015–2018; p < 0.001). A significant decrease was noted in the hazard of hospitalisations (1.3 [0.1–4.6] years compared with 0.2 [0.02–0.9] years; p < 0.001), steroid dependency (1.5 [0.2–5.4] years compared with 0.1 [0.02–0.4] years; p < 0.001), and intestinal surgeries [4.7 [1.6–8.2] years compared with 0.6 [0.2–1.4] years; p < 0.001), but not of perianal surgery (4.2 [1.1–7.7] years compared with 0.6 [0.2–1.4] years; p = 0.2). Outcomes were consistently worse in paediatric onset compared with adults.

Conclusions

The rates of hospitalisations, steroid dependency, and intestinal resections decreased in association with increased use of biologics both in children and in adults, but not the rate of perianal surgeries.
Survivorship and Development of the Invasive Lycorma delicatula (Hemiptera: Fulgoridae) on Wild and Cultivated Temperate Host Plants
Authors: Nixon Laura J , Jones Sharon K , Tang Lisa , Urban Julie , Felton Karen , Leskey Tracy C
Published: November 2021

The invasive spotted lanternfly, Lycorma delicatula, (White Hemiptera: Fulgoridae) continues to spread throughout the Eastern United States. This species exhibits a broad host range, with tree of heaven, Ailanthus altissima (Mill.) Swingle, commonly referred to as the preferred host. Here, we evaluated 2-wk survivorship of early nymphal instars, late nymphal instars, and adult L. delicatula on single diets of ten wild and cultivated hosts: tree of heaven; apple, Malus domestica; peach, Prunus persica; black cherry, P. serotina Ehrh; black locust, Robinia pseudoacacia L.; black walnut, Juglans nigra L.; common hackberry Celtis occidentalis L.; mulberry Morus alba L.; sugar maple Acer saccharum Marshall; white oak, Quercus alba L.. Among them, early and late instars had significantly greater survivorship on tree of heaven and black walnut and adults had greatest survivorship on tree of heaven. Additionally, we evaluated development and survivorship of L. delicatula from newly hatched nymphs to adulthood on single diets of tree of heaven, black walnut, grapevine, apple, and peach, and mixed diets of tree of heaven plus one other host. Single host diets that supported L. delicatula development to adulthood were tree of heaven and black walnut. Interestingly, mixed diets also supported development, and reduced development time to adults by up to 12% compared with the single tree of heaven diet. Our results suggest that within agroecosystems and across landscapes, L. delicatula can develop on single hosts such as tree of heaven, but also on multiple host plants, yielding adults earlier in the growing season.
Arrhythmic CArdiac DEath in MYotonic dystrophy type 1 patients (ACADEMY 1) study: the predictive role of programmed ventricular stimulation
Authors: Russo Vincenzo , Papa Andrea Antonio , Rago Anna , Ciardiello Carmine , Martino Anna Maria , Stazi Alessandra , Golino Paolo , Calò Leonardo , Nigro Gerardo
Published: November 2021

Aims

Myotonic dystrophy type 1 (DM1) predisposes to the development of life-threatening arrhythmias and sudden cardiac death. Our study aimed to evaluate the prognostic value of programmed ventricular stimulation (PVS) in DM1 patients with conduction system disease.

Methods and results

Arrhythmic CArdiac DEath in MYotonic dystrophy type 1 patients (ACADEMY 1) is a double-arm non-randomized interventional prospective study. Myotonic dystrophy type 1 patients with permanent cardiac pacing indication were eligible for the inclusion. The study population underwent to pacemaker (PM) or implantable cardioverter-defibrillator (ICD) implantation according to the inducibility of ventricular tachyarrhythmias at PVS. Primary endpoint of the study was a composite of appropriate ICD therapy and cardiac arrhythmic death. The secondary study endpoint was all-cause mortality. Seventy-two adult-onset DM1 patients (51 ± 12 years; 39 male) were enrolled in the study. A ventricular tachyarrhythmia was induced in 25 patients (34.7%) at PVS (PVS+) who underwent dual chambers ICD implantation. The remaining 47 patients (65.3%) without inducible ventricular tachyarrhythmia (PVS−) were treated with dual-chamber PM. During an average observation period of 44.7 ± 10.2 months, nine patients (12.5%) met the primary endpoint, four in the ICD group (16%) and five (10.6%) in the PM group. Thirteen patients died (18.5%), 2 in the ICD group (8%) and 11 in PM group (23.4%). The Kaplan–Meier analysis did not show a significantly different risk of both primary and secondary endpoint event rates between the two groups.

Conclusions

The inducibility of ventricular tachyarrhythmias has shown a limited value in the arrhythmic risk stratification among DM1 patients.
Disparity and Diversion: Domestic Economic Inequality and MID Initiation
Authors: Long Stephen B , Pickering Jeffrey
Published: November 2021

Scholarship has demonstrated that domestic economic inequality is related to a number of forms of intrastate conflict, such as civil wars and rebellions. There are good reasons to believe that it also has an impact on the initiation of militarized interstate disputes for diversionary reasons. Such use of external force may refocus popular attention and may reinforce the strong nationalist sentiment that tends to prevail in societies with substantial economic inequality. Our empirical results support this contention in democracies but, as expected, not in autocracies. At a time when domestic economic inequality is rising across the world, our findings may be timely.
GPS determined coseismic slip of the 2021Mw7.4 Maduo, China, earthquake and its tectonic implication
Authors: Wang Min , Wang Fan , Jiang Xin , Tian Jianbo , Li Yu , Sun Jiaobao , Shen Zheng-Kang
Published: November 2021

The 2021 Mw7.4 Maduo earthquake occurred on the Jiangcuo fault within the Bayan Har block in eastern Tibet. It is a rather unique event and attests that large earthquakes can occur in the interior of major tectonic blocks within the Tibetan plateau. By processing GPS data observed in the eastern Tibet region, we produce a data set documenting 3-D coseismic displacements of the Maduo earthquake. Using the data set to constrain a coseismic slip model, we find that the earthquake ruptured a nearly vertical fault about 170 km in length, with ∼90% of the moment released in the shallow layer above 20 km depth. The maximum slip of ∼3.6 m occurred near the surface around a bend in the east segment of the fault. The overall seismic moment release is 1.82 × 1020 N m and is equivalent to Mw7.4. Driven by the eastward extrusion of the Tibetan plateau, the deformation field in eastern Tibet is dominated by left-lateral shear, with the strikes of the tectonic faults rotating clockwise from west to east along with the shear stress orientation. This deformation pattern explains the mechanisms of earthquakes along block boundary faults, as well as the ones on faults within the blocks. The Jiangcuo fault is located ∼70 km south of the East Kunlun fault and could be connected to the Kunlun Mountain Pass fault to its WNW that ruptured during the 2001 Kokoxili earthquake, and a seismic gap of ∼240 km long between the two faults is worth special attention for its increased earthquake potential.
Administrative Law
Authors: Endicott Timothy
Published: November 2021

Administrative Law explains the constitutional principles of the subject and their application across the range of twenty-first-century administrative law. The focus on constitutional principles is meant to bring some order to the very diverse topics with which you need to deal if you are to understand this very complex branch of public law. The common law courts, government agencies, and Parliament have developed a wide variety of techniques for controlling the enormously diverse activities of twenty-first-century government. Underlying all that variety is a set of constitutional principles. This book uses the law of judicial review to identify and to explain these principles, and then shows how they ought to be worked out in the private law of tort and contract, in the tribunals system, and in non-judicial techniques such as investigations by ombudsmen, auditors, and other government agencies. The aim is to equip the reader to take a principled approach to the controversial problems of administrative law.
Employment Law
Authors: Taylor Stephen , Emir Astra
Published: November 2021

Employment Law provides an introduction to the issues of employment law and regulation for those studying a variety of subjects including human resource management (HRM) and business management, as well as an easy explanation for students of law. Case exhibits in every chapter illustrate employment law in action, whilst activities test understanding of the law and its application in the real world. In addition, a dedicated, very practical chapter on preparing and presenting a case gives an opportunity to demonstrate understanding using a fictional scenario, through which a greater insight into the challenges faced before an employment tribunal can be gleamed. This fifth edition includes full coverage of the Taylor Report, the Gender Pay Gap Regulations, GDPR/Data Protection Act 2018, the Trade Union Act 2016 and the likely effect of Brexit. The text also encompasses a revision of core legal content including changes to tribunal fees and case law concerning employment status.
Effects of JAK1-Preferential Inhibitor Filgotinib on Circulating Biomarkers and Whole Blood Genes/Pathways of Patients With Moderately to Severely Active Crohn’s Disease
Authors: Roblin Xavier , Serone Adrian , Yoon Oh Kyu , Zhuo, Luting , Grant Ethan , Woo Jacky , Liu Jinfeng , Galien René , D’Haens Geert
Published: November 2021

Background

Pro-inflammatory cytokines are dysregulated in Crohn’s disease (CD) and could serve as surrogate markers to improve diagnostic and therapeutic approaches, potentially addressing an unmet need. We profiled circulating biomarkers and whole blood transcriptional pathway activity to identify those associated with CD using data from the phase 2 FITZROY study with filgotinib, an oral preferential janus kinase-1 inhibitor.

Methods

Patients with serum and whole blood samples taken from the induction period were included. Serum cytokines were measured (ELISA), whole blood RNA sequenced, and stool samples taken to measure fecal calprotectin (FC). Spearman’s Rank correlations were assessed between biomarkers and baseline disease activity; post-treatment endoscopic improvement was measured by the Simplified Endoscopy Score for CD (SES-CD), FC and the Crohn’s Disease Activity Index. Effect of filgotinib on circulating biomarkers was also evaluated.

Results

Serum biomarkers (n = 168) and whole blood RNA sequencing (n = 104) were assessed. Moderate correlation between serum analytes with SES-CD and FC was noted; most highly correlated were acute phase proteins CRP (rho = 0.35 [SES-CD] and 0.47 [FC]), serum amyloid A (rho = 0.40 and 0.39, respectively) and pro-inflammatory cytokines interleukin (IL)-6 (rho = 0.31 and 0.30, respectively), IL-22 (rho = 0.36 and 0.35, respectively), and oncostatin M (rho = 0.35 and 0.33, respectively). Filgotinib treatment was associated with reduction of many candidate biomarkers, particularly in patients with treatment response. Early changes in IL-6 and IL-10 may be prognostic for endoscopic response.

Conclusions

Several circulating factors with potential as CD activity biomarkers were identified. Larger studies are necessary to investigate the best utility of these markers for CD.
Effects of Severe Acute Respiratory Syndrome Coronavirus 2 Strain Variation on Virus Neutralization Titers: Therapeutic Use of Convalescent Plasma
Authors: Nguyen Dung , Xiao Julie , Simmonds Peter , Lamikanra Abigail , Odon Valerie , Ratcliff Jeremy , Townsend Alain , Roberts David J , Harvala Heli
Published: November 2021

We compared neutralizing antibody titers of convalescent samples collected before and after the emergence of novel strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), against the wild-type virus and Alpha (B.1.1.7) and Beta (B.1.351) variants. Plasma samples collected in 2020 before emergence of variants showed reduced titers against the Alpha variants, and both sets of samples demonstrated significantly reduced titers against Beta. Comparison of microneutralization titers with those obtained with pseudotype and hemagglutination tests showed a good correlation between their titers and effects of strain variation, supporting the use of these simpler assays for assessing the potency of convalescent plasma against currently circulating and emerging strains of SARS-CoV-2.
Hydroxy-selenomethionine as an organic source of selenium in the diet improves boar reproductive performance in artificial insemination programs
Authors: Pavaneli Ana Paula P , Martinez Cristian H G , Nakasone Denis H , Pedrosa Ana Carolina , Mendonça Maitê V , Martins Simone M M K , Kawai Giulia K V , Nagai Ken K , Nichi Marcilio , Fontinhas-Netto Garros V , Fagundes Naiara S , Alkmin Diego V , de Andrade André F C
Published: November 2021

This study aimed to compare different selenium (Se) sources in the diet on boar's semen quality and fertility. For this, 28 boars aged 8 to 28 months were fed with the following dietary treatments for 95 days: 0.3 mg Se/kg as sodium selenite (SS, n = 14) and 0.3 mg Se/kg as hydroxy-selenomethionine (OH-SeMet, n = 14). During this period, two experiments were carried out. In experiment 1, the semen of all boars was evaluated every 2 weeks. Raw semen was initially evaluated for the processing of seminal doses, which were stored at 17 °C for 72 h, followed by sperm quality assessments. Furthermore, Se concentration and glutathione peroxidase (GPx) activity were measured in the seminal plasma. In experiment 2, 728 females were inseminated weekly with seminal doses from boars of the different experimental groups to further assess in vivo fertility and litter characteristics. Results demonstrated that boars fed OH-SeMet had more Se in their seminal plasma (p < 0.05), showing the greater bioavailability of the organic source in the male reproductive system. Moreover, boars fed OH-SeMet tended (p < 0.10) towards a higher total sperm count in the ejaculate (66.60 vs. 56.57 × 10 9 sperm), and the number of seminal doses (22.11 vs. 18.86; 3 × 10 9 sperm/dose) when compared to those fed SS. No effect of the dietary treatments was observed on GPx activity in seminal plasma (p > 0.05), as well as on raw and stored semen quality (p > 0.05). Under in vivo conditions, seminal doses from boars fed OH-SeMet tended (p < 0.10) towards a higher pregnancy rate at weeks 3, 5, and 8, and also resulted in a higher (p < 0.05) percentage of pregnant females in the overall period (99.30 vs. 97.00). In conclusion, the replacement of SS with OH-SeMet in boars' diet can improve sperm production and results in better reproductive performance for them, bringing greater productivity and profitability to artificial insemination centers and commercial pig farms.
Immune and metabolic effects of rumen-protected methionine during a heat stress challenge in lactating Holstein cows
Authors: Pate Russell T , Luchini Daniel , Cant John P , Baumgard Lance H , Cardoso Felipe C
Published: November 2021

Multiparous, lactating Holstein cows (n = 32) were randomly assigned to one of two dietary treatments [TMR with rumen-protected Met (RPM) or TMR without RPM (CON)], and within each dietary treatment group cows were randomly assigned to one of two environmental treatment groups in a split-plot crossover design. In phase 1 (9 d), all cows were fed ad libitum and in thermoneutral conditions (TN). In phase 2 (9 d), group 1 (n = 16) was exposed to a heat stress (HS) challenge (HSC). Group 2 cows (n = 16) were pair-fed (PFTN) to HSC counterparts and remained in TN. After a 21-d washout period, the study was repeated (period 2) and the environmental treatments were inverted relative to treatments from phase 2 of period 1, while dietary treatments remained the same for each cow. During phase 1, cows in RPM had greater plasma Met concentration compared with cows in CON (59 and 30 µM, respectively; P < 0.001). Cows in PFTN had a greater decrease (P < 0.05) in plasma insulin than cows in HSC at 4 h (−2.7 µIU/mL vs. −0.7 µIU/mL) and 8 h (−7.7 µIU/mL vs. −0.4 µIU/mL) during phase 2. Compared with cows in PFTN, cows in HSC had an increase (P < 0.05) in plasma serum amyloid A (−59 µg/mL vs. +58 µg/mL), serum haptoglobin (−3 µg/mL vs. +33 µg/mL), plasma lipopolysaccharide binding protein (−0.27 and +0.11 µg/mL), and plasma interleukin-1β (−1.9 and +3.9 pg/mL) during phase 2. In conclusion, HSC elicited immunometabolic alterations; however, there were limited effects of RPM on cows in HSC.
My plate, not thine—copyright infringement of Würtz utensils
Authors: Kohli Vishv Priya , Teilmann-Lock Stina
Published: November 2021

Danish Maritime and Commercial Court (Sø-og Handelsret), K.H. Würtz v/Kasper Heie Würtz v. F&H and Christain Bitz, Case number BS 1370/2016-SHR, 25 March 2020; and Court of Appeal of Eastern Denmark (Østre Landsret) F&H and Christain Bitz v.K.H. Würtz v/Kasper Heie Würtz Case Number BS - 1594/2020-OLR, 27 May 2021

The Danish Maritime Court and the High Court clarified the meaning of Article 2 of the Danish Copyright Act concerning exculsive rights of authors.
Cashew-Induced Oxalate Nephropathy: A Rare Cause of Acute Renal Failure
Authors: Lee Oliver , Park Katherine , Sun Kelly , O’Shea John-Paul , Gordon Sarah
Published: November 2021

We present a rare case of cashew-induced oxalate nephropathy in a 69 year old veteran male with history of type 2 diabetes mellitus, nephrolithiasis, and undiagnosed chronic kidney disease (CKD). Oxalate nephropathy is a rare cause of acute renal failure with poor prognosis. The various causes of oxalate nephropathy are categorized as primary or secondary hyperoxaluria. Primary hyperoxaluria is caused by genetic mutation in genes involved in the metabolism of glyoxylate. Secondary hyperoxaluria is caused by mal-absorptive state, excessive intake of oxalate-rich diet, inflammatory diseases, and medications such as orlistat and antibiotics. Diet-induced oxalate nephropathy is often identified after unexplained acute kidney injury in patients with underlying CKD. Definitive diagnosis requires renal biopsy as laboratory tests are non-specific. A simple dietary history in CKD patients during routine primary care visit may lead to early diagnosis and lead to prevention of acute renal failure and progression of renal disease.
Gynecologic Surgery and Obstetrics Leadership Roles in Academic Military Treatment Facilities by Subspecialty and Gender
Authors: Foglia Lisa M , Batig Alison L
Published: November 2021

Introduction

Gender distribution in academic ob-gyn leadership positions has previously been examined in the civilian sector, but not in military medicine.

Objective

To characterize the distribution of department-level leadership positions by gender and subspecialty in academic military facilities in comparison to those reported in the civilian sector.

Methods

This is an observational cross-sectional study. We queried military obstetrics and gynecology (ob-gyn) specialty consultants, for title and gender of personnel assigned to academic military treatment facilities. Roles were characterized by gender and subspecialty, and the proportion of female leaders was compared to published civilian leadership data.

Results

Women comprised 25% of Department Chairs, 45% of Assistant Chairs, and 42% of Division Directors. In educational leadership roles, women comprised 25% of Residency Program Directors, 0% of Fellowship Directors, and 62% of medical Student Clerkship Directors. Female department chairs were most often uro-gynecologists (44%) followed by specialists in ob-gyn (37%). Most female residency program directors were specialists in general obstetrics and gynecology. The proportion of women in leadership roles in military departments was not different than in the civilian sector.

Conclusion

In contrast to civilian academic leadership positions, Department Chairs were most likely to be uro-gynecologists. Similar to civilian programs, women remain underrepresented as chairs, Assistant Chairs, Fellowship Directors, and Division Directors and similarly represented as Residency Program Directors. Despite a smaller pool of women available to fill academic leadership positions in military ob-gyn departments, the proportion of women in leadership roles reaches parity with the civilian sector. This suggests that a greater proportion of women rise to leadership positions in military academic ob-gyn departments than in the civilian sector.
Reproducibility of Assessment Tests Addressing Body Structure and Function and Activity in Older Adults With Dementia: A Systematic Review
Authors: de Oliveira Marcos Paulo Braz , da Silva Serrão Paula Regina Mendes , de Medeiros Takahashi Anielle Cristhine , Pereira Natalia Duarte , de Andrade Larissa Pires
Published: November 2021

Objective

The purpose of this study was to analyze the relative and absolute reliability of assessment tests addressing body structure and function and activity in older adults with dementia.

Methods

Medline, Embase, Web of Science, The Cochrane Library, and Scielo were searched from inception until March 2021. Two independent reviewers performed the selection process based on titles, abstracts, and full text. Reliability studies of assessment tests in older adults with dementia were included. Methodological quality of the studies was evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments Risk of Bias checklist. Relative reliability was analyzed using the intraclass correlation coefficient (ICC) interpreted based on Munro classification. Absolute reliability was analyzed using the minimal detectable change (MDC) and standard error of measurement.

Results

Fifteen studies involving a total of 560 older adults with dementia were included. Nineteen assessment tests were identified: 13 addressing body structure and function (muscle strength, postural balance, cardiorespiratory fitness) and 6 addressing activity (walking and mobility). Studies determined test–retest and interrater reliability. Fifteen studies evaluated relative reliability using the ICC, with values ranging from no or small correlation to very high correlations. Ten studies evaluated absolute reliability using the MDC or standard error of measurement or both.

Conclusion

Relative reliability of the assessment tests for body structure and function and activity was high to very high based on ICCs, demonstrating good reproducibility. Regarding absolute reliability, the analysis of the MDC values revealed the need for substantial change to determine that a real change had occurred. Future investigations should consider the type of dementia and standardization of verbal encouragement during the assessment.

Impact

This review identified the good reproducibility of assessment tests of body structure and function (muscle strength, postural balance, cardiorespiratory fitness) and activity (walking and mobility) domains in older adults with dementia. Clinically important values may differ when older adults with dementia of diverse etiologies are analyzed together and older adults specifically with Alzheimer disease. Identifying the type of dementia, analyzing types of dementia separately, and standardizing verbal commands during the execution of tests is of considerable clinical importance for this population of older adults.
Different Evolutionary Pathways Lead to Incomplete Convergence of Elongate Body Shapes in Carnivoran Mammals
Authors: Law Chris J
Published: November 2021

Although convergence is often recognized as a ubiquitous feature across the Tree of Life, whether the underlying traits also exhibit similar evolutionary pathways towards convergent forms puzzles biologists. In carnivoran mammals, “elongate,” “slender,” and “long” are often used to describe and even to categorize mustelids (martens, polecats, and weasels), herpestids (mongooses), viverrids (civets and genets), and other carnivorans together. But just how similar these carnivorans are and whether there is convergence in the morphological component that contribute to elongation has never been assessed. Here, I found that these qualitatively described elongate carnivorans exhibited incomplete convergence towards elongate bodies compared to other terrestrial carnivorans. In contrast, the morphological components underlying body shape variation do not exhibit convergence despite evidence that these components are more elongate in elongate carnivorans compared to nonelongate carnivorans. Furthermore, these components also exhibited shorter but different phylogenetic half-lives towards more elongate adaptive peaks, indicating that different selective pressures can create multiple pathways to elongation. Incorporating the fossil record will facilitate further investigation of whether body elongation evolved adaptively or if it is simply a retained ancestral trait.[Axial skeleton; body elongation; convergent evolution; macroevolution; phylogenetic comparative methods; thoracolumbar vertebrae.]
Combined phylogeny and new classification of catsharks (Chondrichthyes: Elasmobranchii: Carcharhiniformes)
Authors: Soares Karla D A , Mathubara Kleber
Published: November 2021

This is the first study to combine morphological and molecular characters to infer the phylogenetic relationships among catsharks. All currently valid genera classified in the family Scyliorhinidae s.l. and representatives of other carcharhinoid families plus one lamnoid and two orectoloboids were included as terminal taxa. A total of 143 morphological characters and 44 NADH2 sequences were analysed. Parsimony analyses under different weighting schemes and strengths were used to generate hypotheses of phylogenetic relationships. The phylogenetic analysis of 78 terminal taxa, using the combined dataset and weighting each column separately (SEP; k = 3) resulted in one most-parsimonious cladogram of 4441 steps with the greatest internal resolution of clades and strongest support. The main changes in nomenclature and classification are the revised definition and scope of Scyliorhinidae, Apristurus and Pentanchus and the revalidation of Atelomycteridae. The monophyly of Pentanchidae is supported, as is that of most catshark genera. Two new subfamilies of the family Pentanchidae are defined: Halaelurinae subfam. nov. and Galeinae subfam. nov. Our analysis emphasizes the relevance of morphological characters in the inference of evolutionary history of carcharhinoids and sheds light on the taxonomic status of some genera in need of further exploration.
Written-Based Progress Testing: A Scoping Review
Authors: Dion Vincent , St-Onge Christina , Bartman Ilona , Touchie Claire , Pugh Debra
Published: November 2021

Purpose

Progress testing is an increasingly popular form of assessment in which a comprehensive test is administered to learners repeatedly over time. To inform potential users, this scoping review aimed to document barriers, facilitators, and potential outcomes of the use of written progress tests in higher education.

Method

The authors followed Arksey and O’Malley’s scoping review methodology to identify and summarize the literature on progress testing. They searched 6 databases (Academic Search Complete, CINAHL, ERIC, Education Source, MEDLINE, and PsycINFO) on 2 occasions (May 22, 2018, and April 21, 2020) and included articles written in English or French and pertaining to written progress tests in higher education. Two authors screened articles for the inclusion criteria (90% agreement), then data extraction was performed by pairs of authors. Using a snowball approach, the authors also screened additional articles identified from the included reference lists. They completed a thematic analysis through an iterative process.

Results

A total of 104 articles were included. The majority of progress tests used a multiple-choice and/or true-or-false question format (95, 91.3%) and were administered 4 times a year (38, 36.5%). The most documented source of validity evidence was internal consistency (38, 36.5%). Four major themes were identified: (1) barriers and challenges to the implementation of progress testing (e.g., need for additional resources); (2) established collaboration as a facilitator of progress testing implementation; (3) factors that increase the acceptance of progress testing (e.g., formative use); and (4) outcomes and consequences of progress test use (e.g., progress testing contributes to an increase in knowledge).

Conclusions

Progress testing appears to have a positive impact on learning, and there is significant validity evidence to support its use. Although progress testing is resource- and time-intensive, strategies such as collaboration with other institutions may facilitate its use.
Technology-Assisted Supplemental Work Among Rural Medical Providers: Impact on Burnout, Stress, and Job Satisfaction
Authors: Terry Danielle L. , Mathews David P.
Published: November 2021

EXECUTIVE SUMMARY

Burnout among healthcare providers has been identified as a national public health concern. The purpose of this study was to (a) examine technology usage outside the workplace among rural medical providers, (b) examine whether technology usage is associated with perceived stress and burnout, and (c) examine the impact of technology usage and perceived usefulness of technology on job satisfaction. Results indicated that supplemental technology usage was associated with perceived stress and burnout. Years in practice, supplemental technology usage, and perceived usefulness of technology were all correlated with whether providers would recommend their organization to those considering working there. Findings expand upon past research on physician burnout and indicate that perception of the usefulness of technology is correlated with job satisfaction and whether one would recommend that others work at one’s organization. Finding ways to increase positive perceptions of technology usage in a technology-driven medical system may increase the likelihood of retaining or recruiting staff.
Indwelling Pleural Catheter (IPC) for the Management of Hepatic Hydrothorax
Authors: Avula Akshay , Acharya Sudeep , Anwar Shamsuddin , Narula Naureen , Chalhoub Michel , Maroun Rabih , Thapa Sakura , Friedman Yelena
Published: November 2021

Background:

Hepatic hydrothorax (HH) is described as pleural effusion secondary to liver cirrhosis after ruling out other etiologies. We aim to assess the efficacy of an indwelling pleural catheter (IPC) placement in refractory HH in this systematic review and meta-analysis.

Methods:

A comprehensive search of literature was performed from inception to December 2020. The authors reviewed, selected, and abstracted the data from eligible studies into Covidence, a systematic review software. Cochrane criteria was used to rate each study for the risk of bias. The data abstracted were described using a random-effects model. Heterogeneity was evaluated using the I
2 test.

Results:

Ten studies involving a total of 269 patients were included. The studies were analyzed for the proportion of pleurodesis achieved, the average time to pleurodesis, total complication rate, pleural infection rate, and mortality. A proportion of 47% of the total subjects included achieved spontaneous pleurodesis in an average duration of 104.3 days. The frequency of total complication rate was noted to be 30.36%. The incidence of pleural cavity infection was described to be 12.4% and death resulting from complications of IPC was 3.35%.

Conclusion:

The current management options for the refractory pleural effusion in HH include repeated thoracenteses, transjugular intrahepatic portosystemic shunt, surgical repair of defects in the diaphragm, and liver transplantation. However, the cost, eligibility, and availability can be some of the major concerns with these treatment modalities. With this meta-analysis, we conclude that IPCs can provide an alternative therapeutic option for spontaneous pleurodesis.
Structural Syndemics and Antiretroviral Medication Adherence Among Black Sexual Minority Men Living With HIV
Authors: Holloway Ian W. , Beltran Raiza , Shah Saanchi V. , Cordero Luisita , Garth Gerald , Smith Terry , Wilson Bianca D. M. , Ochoa Ayako M.
Published: November 2021

Background:

Although HIV antiretroviral treatment (ART) access and uptake have increased among racial/ethnic minority individuals, lower rates of ART adherence and viral suppression persist, especially among Black men who have sex with men (BMSM) compared with their White counterparts.

Setting:

Black men who have sex with men living with HIV (BMSM+) residing in Los Angeles County (N = 124) were recruited in-person (eg, clinic) and online (eg, social networking apps).

Methods:

Participants completed a cross-sectional survey measuring demographic characteristics, structural syndemics (poverty, criminal justice involvement, and housing instability), and psychosocial syndemics (mental health and substance use). A text message survey assessed missed doses of ART over the past week. Zero-inflated Poisson regression models were used to evaluate variables associated with the number of missed doses of ART.

Results:

On average, participants missed 1.30 doses of ART (SD = 2.09) and reported structural syndemics: poverty (56.1%), criminal justice involvement (36.6%), housing instability (26.3%), and psychosocial syndemics: childhood sexual abuse (51.8%), intimate partner violence (16.9%), depression (39%), and problem alcohol use (15.5%). After controlling for employment, age, education, and psychosocial syndemics, participants with a one-point increase in structural syndemic indicators were found to be 1.63 times more likely to have missed a dose of ART.

Conclusions:

Structural syndemic were associated with ART nonadherence among BMSM+ after adjusting for demographic and psychosocial factors. HIV treatment interventions that incorporate financial incentives, legal support, and housing may help improve ART adherence among BMSM+. Findings suggest that key priorities to ending the HIV epidemic must include structural interventions that alleviate poverty, eliminate disproportionate policing and criminalization, and end homelessness.
Cytoskeletal assembly in axonal outgrowth and regeneration analyzed on the nanoscale
Authors: Hofmann Max , Biller Lucas , Michel Uwe , Bähr Mathias , Koch Jan Christoph
Published: November 2021

The axonal cytoskeleton is organized in a highly periodic structure, the membrane-associated periodic skeleton (MPS), which is essential to maintain the structure and function of the axon. Here, we use stimulated emission depletion microscopy (STED) of primary rat cortical neurons in microfluidic chambers to analyze the temporal and spatial sequence of MPS formation at the distal end of growing axons and during regeneration after axotomy. We demonstrate that the MPS does not extend continuously into the growing axon but develops from patches of periodic β-spectrin II arrangements that grow and coalesce into a continuous scaffold. We estimate that the underlying sequence of nucleation, elongation, and subsequent coalescence of periodic β-spectrin II patches takes around 15 hours. Strikingly, we find that development of the MPS occurs faster in regenerating axons after axotomy and note marked differences in the morphology of the growth cone and adjacent axonal regions between regenerating and unlesioned axons. Moreover, we find that inhibition of the spectrin-cleaving enzyme calpain accelerates MPS formation in regenerating axons and increases the number of regenerating axons after axotomy. Taken together, we provide here a detailed nanoscale analysis of MPS development in growing axons.
A high-throughput, automated, cell-free expression and screening platform for antibody discovery
Authors: Hunt Andrew C. , Vögeli Bastian , Kightlinger Weston K. , Yoesep Danielle J. , Krüger Antje , Jewett Michael C.
Published: November 2021

Antibody discovery is bottlenecked by the individual expression and evaluation of antigen-specific hits. Here, we address this gap by developing an automated workflow combining cell-free DNA template generation, protein synthesis, and high-throughput binding measurements of antibody fragments in a process that takes hours rather than weeks. We apply this workflow to 119 published SARS-CoV-2 neutralizing antibodies and demonstrate rapid identification of the most potent antibody candidates.
Waning, Boosting and a Path to Endemicity for SARS-CoV-2
Authors: Keeling Matt J. , Thomas Amy , Hill Edward M. , Thompson Robin N. , Dyson Louise , Tildesley Michael J. , Moore Sam
Published: November 2021

In many countries, an extensive vaccination programme has substantially reduced the public-health impact of SARS-CoV-2, limiting the number of hospital admissions and deaths compared to an unmitigated epidemic. Ensuring a low-risk transition from the current situation to one in which SARS-CoV-2 is endemic requires maintenance of high levels of population immunity. The observed waning of vaccine efficacy over time suggests that booster doses may be required to maintain population immunity especially in the most vulnerable groups. Here, using data and models for England, we consider the dynamics of COVID-19 over a two-year time-frame, and the role that booster vaccinations can play in mitigating the worst effects. We find that boosters are necessary to suppress the imminent wave of infections that would be generated by waning vaccine efficacy. Projecting further into the future, the optimal deployment of boosters is highly sensitive to their long-term action. If protection from boosters wanes slowly (akin to protection following infection) then a single booster dose to the over 50s may be all that is needed over the next two-years. However, if protection wanes more rapidly (akin to protection following second dose vaccination) then annual or even biannual boosters are required to limit subsequent epidemic peaks an reduce the pressure on public health services.
Turnover in life-strategies recapitulates marine microbial succession colonizing model particles
Authors: Pascual-García Alberto , Schwartzman Julia , Enke Tim N. , Iffland-Stettner Arion , Cordero Otto X. , Bonhoeffer Sebastian
Published: November 2021

Particulate organic matter (POM) in the ocean sustains diverse communities of bacteria that mediate the remineralization of organic complex matter. However, the variability of these particles and of the environmental conditions surrounding them present a challenge to the study of the ecological processes shaping particle-associated communities and their function. In this work, we utilise data from experiments in which coastal water communities were grown on synthetic particles to ask which are the most important ecological drivers of their assembly and associated traits. Combining 16S rRNA amplicon sequencing with shotgun metagenomics, together with an analysis of the full genomes of a subset of isolated strains, we were able to identify two-to-three distinct community classes, corresponding to early vs. late colonizers. We show that these classes are shaped by environmental selection (early colonizers) and facilitation (late colonizers), and find distinctive traits associated with each class. While early colonizers have a larger proportion of genes related to uptake of nutrients, motility and environmental sensing with few pathways enriched for metabolism, late colonizers devote a higher proportion of genes for metabolism, comprising a wide array of different pathways including metabolism of carbohydrates, amino acids and xenobiotics We find evidence in selected metabolic pathways for the existence of a trophic-chain topology connecting both classes. The interpretation of these traits suggests a distinction between early and late colonizers analogous to other classifications found in the literature, and we discuss connections with the classical distinction between r- and K-strategists.
A truncated reverse transcriptase enhances prime editing by split AAV vectors
Authors: Gao Zongliang , Haldrup Jakob , Ravendran Sujan , Mikkelsen Nanna S. , Mikkelsen Jacob Giehm , Bak Rasmus O.
Published: November 2021

Prime editing is a new CRISPR-based genome editing technology that relies on the prime editor (PE), a fusion protein of Cas9-nickase and M-MLV reverse transcriptase (RT), and a prime editing guide RNA (pegRNA) that serves both to target PE to the desired genomic locus and to carry the edit to be introduced. Here, we make advancements to the RT moiety to improve prime editing efficiencies and truncations to mitigate issues with AAV viral vector size limitations, which currently do not support efficient delivery of the large prime editing components. These efforts include RT variant screening, codon optimization, and PE truncation by removal of the RNase H domain and further trimming. This led to a codon-optimized and size-minimized PE that has an expression advantage (1.4× fold) and size advantage (621 bp shorter). In addition, we optimize the split intein PE system and identify Rma-based Cas9 split sites (573-574 and 673-674) that combined with the truncated PE delivered by dual AAVs result in superior AAV titer and prime editing efficiency. This novel minimized PE provides great value to AAV-based delivery applications in vivo.
Number and proportion of P.falciparumgametocytes vary from acute infection to chronic parasite carriage despite unaltered sexual commitment rate
Authors: van Dijk Hannah , Kampmann Martin , Lima Nathalia F , Gabel Michael , Dabbas Usama , Doumbo Safiatou , Cisse Hamidou , Li Shanping , Jeninga Myriam , Thomson-Luque Richard , Doumtabe Didier , Petter Michaela , Kayentao Kassoum , Ongoiba Aissata , Bousema Teun , Crompton Peter D , Traore Boubacar , Graw Frederik , Portugal Silvia
Published: November 2021

Plasmodium falciparuminfections persist through long dry seasons at low parasitaemia without causing malaria symptoms and thus remain untreated. In asymptomatic children, increased circulation of infected erythrocytes without adhering to the vascular endothelium is observed during the dry months, compared to febrile malaria in the wet season. However, alterations of parasite sexual commitment and gametocytogenesis have not been investigated. Here, we compared the expression of genes related to sexual commitment and gametocytogenesis, the proportion and density ofP. falciparumgametocytes, and the blood concentration of phospholipids in dry season asymptomatic individuals versus symptomatic subjects in the wet season. Additionally, we adapted a within-host mathematical model considering asexual and sexually-committed parasites and gametocytes to understand the dynamics of gametocyte number and proportion as infections progress. Compared to clinical malaria cases, transcripts of late-stage gametocytes were predominantly upregulated in the dry season, associating with increased proportions of mature gametocytes; while transcription of genes related to parasite sexual commitment was unaltered throughout the year. Our data suggest that gametocyte density and proportion diverge as infections progress from recent transmission to chronic carriage, without alterations in the sexual commitment rate over time.
Design, construction and optimization of a synthetic RNA polymerase operon in Escherichia coli
Authors: Houkes Joep , Olivi Lorenzo , Paquet Zacharie , Claassens Nico J. , van der Oost John
Published: November 2021

Prokaryotic genes encoding functionally related proteins are often clustered in operons. The compact structure of operons allows for co-transcription of the genes, and for co-translation of the polycistronic messenger RNA to the corresponding proteins. This leads to reduced regulatory complexity and enhanced gene expression efficiency, and as such to an overall metabolic benefit for the protein production process in bacteria and archaea. Interestingly, the genes encoding the subunits of one of the most conserved and ubiquitous protein complexes, the RNA polymerase, are not clustered in a single operon. Rather, its genes are scattered in all known prokaryotic genomes, generally integrated in different ribosomal operons. To analyze the impact of this genetic organization on the fitness of Escherichia coli, we constructed a bacterial artificial chromosome harboring the genes encoding the RNA polymerase complex in a single operon. Subsequent deletion of the native chromosomal genes led to a reduced growth on minimal medium. However, by using adaptive laboratory evolution the growth rate was restored to wild-type level. Hence, we show that a highly conserved genetic organization of core genes in a bacterium can be reorganized by a combination of design, construction and optimization, yielding a well-functioning synthetic genetic architecture.
Discovery of imidazole-based inhibitors of P. falciparum cGMP-dependent protein kinase
Authors: Yadav Bheemanaboina Rammohan R. , de Souza Mariana Laureano , Gonzalez Mariana Lozano , Mahmood Shams Ul , Eck Tyler , Kreiss Tamara , Aylor Samantha O. , Roth Alison , Lee Patricia , Pybus Brandon S. , Colussi Dennis J. , Childers Wayne E. , Gordon John , Siekierka John J. , Bhanot Purnima , Rotella David P.
Published: November 2021

The discovery of new targets for treatment of malaria and in particular those aimed at the pre-erythrocytic stage in the life cycle, advanced with the demonstration that orally administered inhibitors of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) could clear infection in a murine model. This enthusiasm was tempered by unsatisfactory safety and/or pharmacokinetic issues found with these chemotypes. To address the urgent need for new scaffolds, this manuscript presents initial structure-activity relationships in an imidazole scaffold at four positions, representative in vitro ADME, hERG characterization and cell-based anti-parasitic activity. This series of PfPKG inhibitors has good in vitro PfPKG potency, low hERG activity and cell-based anti-parasitic activity against multiple Plasmodium species that appears to correlate with in vitro potency.