bluuebunny/crossref_metadata_2025 huggingface dataset:
On the importance of register in learner writing
Authors: Larsson Tove , Paquot Magali , Biber Douglas
Published: November 2021

The present study explores the relative importance of register in learner writing vis-à-vis
learner-internal factors such as first-language background. Using multi-dimensional analysis, the study looks at learner and
native-speaker student writing from two registers (argumentative essays and research papers), in comparison to published
scientific articles. The results show that while certain differences could be noted across first-language background, the main
differences were found between the registers, stressing its importance as a moderating variable. Specifically, the research
papers and the scientific articles were characterized by topic-focussed, factual descriptions, and the argumentative texts by
a more personal style. The results thus highlight the importance of taking register into consideration in learner corpus
research studies.
Nominalizations in Early Modern English
Authors: Rodríguez-Puente Paula
Published: November 2021

This chapter explores word-based nominalizations in Early Modern English, a crucial period in the
expansion of the English vocabulary. Nine Romance and native suffixes are traced in eighteen registers, thus covering a wide
variety of registers along the formal-informal and speech-written continua. Findings demonstrate that there is a strong
correlation between informal, speech-related registers and a low frequency of nominalizations, although the communicative
purpose of particular registers can also have an effect here. Suffix productivity is also addressed, with results showing
that, the frequency of nominalizations in terms of types and tokens increases over time across registers, except trial
proceedings. However, Romance suffixes are seen chiefly responsible for this, whereas most native suffixes lose productivity
during the period.
Exploring sub-register variation in Victorian newspapers
Authors: Hiltunen Turo
Published: November 2021

This chapter explores sub-register variation in newspaper writing in the 19th century using two corpora
extracted from the British Library Newspapers database, the most comprehensive collection of national and
regional newspapers from the Victorian period. As an ‘agile’ (Hundt & Mair
1999) register, newspaper writing is well suited for tracing language change and investigating the interrelationship
between language and culture. Frequency analysis of select linguistic features identifies systematic patterns of variation,
which can be linked to the communicative functions of sub-registers. The chapter also critically reflects on the value of the
database for corpus-based register analysis, especially on how the findings and interpretations are contingent on what
sampling criteria are used and how the notion of (sub-)register is operationalized.
Additional prognostic value of echocardiographic follow-up in pulmonary hypertension—role of 3D right ventricular area strain
Authors: Moceri Pamela , Duchateau Nicolas , Baudouy Delphine , Squara Fabien , Bun Sok Sithikun , Ferrari Emile , Sermesant Maxime
Published: November 2021

Aims

Outcomes in pulmonary hypertension (PH) are related to right ventricular (RV) function and remodelling. We hypothesized that changes in RV function and especially area strain (AS) could provide incremental prognostic information compared to the use of baseline data only. We therefore aimed to assess RV function changes between baseline and 6-month follow-up and evaluate their prognostic value for PH patients using 3D echocardiography.

Methods and results

Ninety-five PH patients underwent a prospective longitudinal study including ESC/ERS guidelines prognostic assessment and 3D RV echocardiographic imaging at baseline and 6-month follow-up. Semi-automatic software tracked the RV along the cycle, and its output was post-processed to extract 3D deformation patterns. Over a median follow-up of 24.8 (22.1–25.7) months, 21 patients died from PH or were transplanted. Improvements in RV global AS were associated with stable or improving clinical condition as well as survival free from transplant (P < 0.001). The 3D deformation patterns confirmed that the most significant regional changes occurred within the septum. RV global AS change over 6-month by +3.5% identifies patients with a 3.7-fold increased risk of death or transplant. On multivariate COX analysis, changes in WHO class, BNP, and RV global AS were independent predictors of outcomes. Besides, the combination of these three parameters was of special interest to identify high-risk patients [HR 11.5 (1.55–86.06)].

Conclusion

Changes in RV function and especially changes in 3D RV AS are of prognostic importance. Our study underlines that assessing such changes from baseline to follow-up is of additional prognostic value for PH patients.

Clinical Trial Registration

http://clinicaltrials.gov/ct2/show/NCT02799979
Cardiovascular effects of doping substances, commonly prescribed medications and ergogenic aids in relation to sports: a position statement of the sport cardiology and exercise nucleus of the European Association of Preventive Cardiology
Authors: Adami Paolo Emilio , Koutlianos Nikolaos , Baggish Aaron , Bermon Stéphane , Cavarretta Elena , Deligiannis Asterios , Furlanello Francesco , Kouidi Evangelia , Marques-Vidal Pedro , Niebauer Josef , Pelliccia Antonio , Sharma Sanjay , Solberg Erik Ekker , Stuart Mark , Papadakis Michael
Published: November 2021

The use of substances and medications with potential cardiovascular effects among those practicing sports and physical activity has progressively increased in recent years. This is also connected to the promotion of physical activity and exercise as core aspects of a healthy lifestyle, which has led also to an increase in sport participation across all ages. In this context, three main users’ categories can be identified, (i) professional and amateur athletes using substances to enhance their performance, (ii) people with chronic conditions, which include physical activity and sport in their therapeutic plan, in association with prescribed medications, and (iii) athletes and young individuals using supplements or ergogenic aids to integrate their diet or obtaining a cognitive enhancement effect. All the substances used for these purposes have been reported to have side effects, among whom the cardiovascular consequences are the most dangerous and could lead to cardiac events. The cardiovascular effect depends on the type of substance, the amount, the duration of use, and the individual response to the substances, considering the great variability in responses. This Position Paper reviews the recent literature and represents an update to the previously published Position Paper published in 2006. The objective is to inform physicians, athletes, coaches, and those participating in sport for a health enhancement purpose, about the adverse cardiovascular effects of doping substances, commonly prescribed medications and ergogenic aids, when associated with sport and exercise.
Addressing disparities of care in non-ST-segment elevation myocardial infarction patients without standard modifiable risk factors: insights from a nationwide cohort study
Authors: Moledina Saadiq M , Rashid Muhammad , Nolan James , Nakao Kazuhiro , Sun Louise Y , Velagapudi Poonam , Wilton Stephen B , Volgman Annabelle Santos , Gale Chris P , Mamas Mamas A
Published: November 2021

Aims

The importance of standard modifiable cardiovascular risk factors (SMuRFs) in preventing non-ST-segment elevation myocardial infarction (NSTEMI) is established. However, NSTEMI may present in the absence of SMuRFs, and little is known about their outcomes.

Methods and results

We analysed 176 083 adult (≥18 years) hospitalizations with NSTEMI using data from the United Kingdom (UK) Myocardial Infarction National Audit Project (MINAP). Clinical characteristics and all-cause in-hospital mortality were analysed according to SMuRF status, with 135 223 patients presenting with at least one of diabetes, hypertension, hypercholesterolaemia, or current smoking status and 40 860 patients without any SMuRFs. Those with a history of coronary artery disease were excluded. Patients without SMuRFs were more frequently older (median age 72 year vs. 71 years, P < 0.001), male (62% vs. 61%, P < 0.001), and Caucasian (95% vs. 92%, P < 0.001). Those without SMuRFs less frequently received statins (71% vs. 81%, P < 0.001), had their left ventricular (LV) function recorded (62% vs. 65%, P < 0.001) or for those with moderate or severe LV systolic dysfunction were prescribed angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (80% vs. 85%, P < 0.001). Following propensity score matching the odds of all-cause mortality [odds ratio (OR): 0.85, 95% confidence interval (CI): 0.77–0.93], cardiac mortality (OR: 0.85, 95% CI: 0.76–0.94), and major adverse cardiovascular events (MACE) (OR: 0.85, 95% CI: 0.77–0.93) were lower in patients without SMuRFs.

Conclusion

More than one in five patients presenting with NSTEMI had no SMuRFs, who were less frequently received guideline-recommended management and had lower in-hospital (all-cause and cardiac) mortality and MACE than patients with SMuRFs.
Genome-wide approaches delineate the additive, epistatic, and pleiotropic nature of variants controlling fatty acid composition in peanut (Arachis hypogaeaL.)
Authors: Otyama Paul I , Chamberlin Kelly , Ozias-Akins Peggy , Graham Michelle A , Cannon Ethalinda K S , Cannon Steven B , MacDonald Gregory E , Anglin Noelle L
Published: November 2021

The fatty acid composition of seed oil is a major determinant of the flavor, shelf-life, and nutritional quality of peanuts. Major QTLs controlling high oil content, high oleic content, and low linoleic content have been characterized in several seed oil crop species. Here, we employ genome-wide association approaches on a recently genotyped collection of 787 plant introduction accessions in the USDA peanut core collection, plus selected improved cultivars, to discover markers associated with the natural variation in fatty acid composition, and to explain the genetic control of fatty acid composition in seed oils. Overall, 251 single nucleotide polymorphisms (SNPs) had significant trait associations with the measured fatty acid components. Twelve SNPs were associated with two or three different traits. Of these loci with apparent pleiotropic effects, 10 were associated with both oleic (C18:1) and linoleic acid (C18:2) content at different positions in the genome. In all 10 cases, the favorable allele had an opposite effect—increasing and lowering the concentration, respectively, of oleic and linoleic acid. The other traits with pleiotropic variant control were palmitic (C16:0), behenic (C22:0), lignoceric (C24:0), gadoleic (C20:1), total saturated, and total unsaturated fatty acid content. One hundred (100) of the significantly associated SNPs were located within 1000 kbp of 55 genes with fatty acid biosynthesis functional annotations. These genes encoded, among others: ACCase carboxyl transferase subunits, and several fatty acid synthase II enzymes. With the exception of gadoleic (C20:1) and lignoceric (C24:0) acid content, which occur at relatively low abundance in cultivated peanuts, all traits had significant SNP interactions exceeding a stringent Bonferroni threshold (α = 1%). We detected 7682 pairwise SNP interactions affecting the relative abundance of fatty acid components in the seed oil. Of these, 627 SNP pairs had at least one SNP within 1000 kbp of a gene with fatty acid biosynthesis functional annotation. We evaluated 168 candidate genes underlying these SNP interactions. Functional enrichment and protein-to-protein interactions supported significant interactions (P-value < 1.0E−16) among the genes evaluated. These results show the complex nature of the biology and genes underlying the variation in seed oil fatty acid composition and contribute to an improved genotype-to-phenotype map for fatty acid variation in peanut seed oil.
Pvr and distinct downstream signaling factors are required for hemocyte spreading and epidermal wound closure atDrosophilalarval wound sites
Authors: Tsai Chang-Ru , Wang Yan , Jacobson Alec , Sankoorikkal Niki , Chirinos Josue D , Burra Sirisha , Makthal Nishanth , Kumaraswami Muthiah , Galko Michael J
Published: November 2021

Tissue injury is typically accompanied by inflammation. In Drosophila melanogaster larvae, wound-induced inflammation involves adhesive capture of hemocytes at the wound surface followed by hemocyte spreading to assume a flat, lamellar morphology. The factors that mediate this cell spreading at the wound site are not known. Here, we discover a role for the platelet-derived growth factor/vascular endothelial growth factor-related receptor (Pvr) and its ligand, Pvf1, in blood cell spreading at the wound site. Pvr and Pvf1 are required for spreading in vivo and in an in vitro spreading assay where spreading can be directly induced by Pvf1 application or by constitutive Pvr activation. In an effort to identify factors that act downstream of Pvr, we performed a genetic screen in which select candidates were tested to determine if they could suppress the lethality of Pvr overexpression in the larval epidermis. Some of the suppressors identified are required for epidermal wound closure (WC), another Pvr-mediated wound response, some are required for hemocyte spreading in vitro, and some are required for both. One of the downstream factors, Mask, is also required for efficient wound-induced hemocyte spreading in vivo. Our data reveal that Pvr signaling is required for wound responses in hemocytes (cell spreading) and defines distinct downstream signaling factors that are required for either epidermal WC or hemocyte spreading.
The dark industry of data brokers: need for regulation?
Authors: Mishra Shivangi
Published: November 2021

Measuring the impact of harm when the perpetrator is a faceless company operating in the shadows is akin to walking in the dark. You never know what’s awaiting you next! The data brokering industry is one such instance, possessing against you, arguably the strongest weapon today—a secret digital twin or a digital doppelganger of your attributes. In the ever-growing digital economy, is there a need to regulate this industry? This article identifies the lacuna in the law that permits its operation and argues for fixing the loopholes in order to regulate the data brokering industry. Furthermore, it sheds light on India’s missed opportunity to regulate the industry given the inchoate nature of data protection laws in the country. Finally, it raises ethical concerns and argues for a distinction between reasonable and unreasonable inferences building on Prof. Sandra Wachter’s concept of an ex ante right to reasonable inference.
Antimicrobial use in agriculture: critical review of the factors influencing behaviour
Authors: McKernan C , Benson T , Farrell S , Dean M
Published: November 2021

Antimicrobial resistance (AMR) is a global health emergency affecting humans and animals, diminishing the effectiveness of medication used to treat illness. The agri-food sector has attracted increased attention for imprudent antimicrobial use (AMU) and its contribution to AMR. Thus, ascertaining farmers’ and veterinarians’ behaviours surrounding AMU is essential to address imprudent AMU and generate behaviour change within the agri-food sector. Therefore, the aim of this critical review is to investigate, assess and collate the current body of evidence to identify psychosocial factors including knowledge, understanding, perceptions, attitudes and behaviours surrounding AMU. Database searches were limited to articles utilizing qualitative and quantitative methodologies, available in English with no restriction on publication year. Of the 1156 articles identified, 103 were retained for this review. Findings on the psychosocial aspects were thematically analysed. Five key themes emerged from the data: (i) knowledge and awareness of antimicrobials; (ii) attitudes towards antimicrobials; (iii) influential relationships; (iv) resources; and (v) factors influencing AMU. Results indicated that to overcome barriers experienced by key stakeholders, a carefully considered, evidence-based approach, incorporating behaviour change theory, is required when designing intricate interventions/strategies, in order to elicit successful and sustained AMU behaviour change.
I’ve got the power: Saunders v Vautier in the context of massively discretionary trusts
Authors: Morris Rupert , Clark-Jones Jessica
Published: November 2021

In two judgments in 2019 and 2020, the Guernsey Court of Appeal upheld the judgment of the Guernsey Royal Court in Rusnano Capital AG (in liquidation) v Molard International (PTC) Limited and Pullborough International Corp [2019] GRC 011 in relation to the statutory “Saunders v Vautier” provisions under the Trusts (Guernsey) Law, 2007. The position, in Guernsey at least, remains therefore that beneficiaries of a discretionary trust can require trustees to terminate a trust and distribute the trust property, even in circumstances where a broad power to add further (unspecified) beneficiaries exists. This article considers the position, on any view unsettled, in England and Wales (as well as other jurisdictions which still rely on the common law interpretation) of the so-called rule in Saunders v Vautier in light of the somewhat contradictory case law and authorities, particularly in the context of trusts where the dispositive discretions effectively displace the beneficial interests.
Factors Underlying the Prevalence of Pythium Infection of Corn Seeds Following Seed Treatment Application of Tebuconazole
Authors: Tang Xiujun , Chen Shuning , Yan Xiaojing , Wang Zhenying , Yuan Huizhu , Yang Daibin
Published: November 2021

Microbial communities are essential for soil health, but fungicide application may have significant effects on their structure. It is difficult to predict whether nontarget pathogens of applied fungicides in the soil will cause crop damage. Tebuconazole is a triazole fungicide that can be used as a seed treatment and, thereby, introduced to the soil. However, seed-applied tebuconazole has a potential risk of causing poor emergence of corn (Zea mays) seedlings. Using soil with a history of poor corn seedling emergence, we demonstrate through TA cloning and isolation that the poor emergence of corn seedlings from tebuconazole-coated corn seeds was primarily because of infection by surviving soil pathogens, specifically Pythium species that are not targeted by tebuconazole, rather than the phytotoxic effects of tebuconazole. Bioassay tests on tebuconazole-amended media showed that tebuconazole can suppress soil fungi while allowing Pythium to grow. Pythium species primarily contributing to the corn seed rot were more pathogenic at cooler temperatures. Furthermore, the nontarget biocontrol agent of Trichoderma spp. was strongly inhibited by tebuconazole. Taken together, the nontarget effects of tebuconazole are likely not significant under favorable plant growing conditions but are considerable because of low-temperature stress.
The relationship between intrauterine foetal growth trajectories and blood pressure in young adults
Authors: Yadav Ashish , Beilin Lawrence J. , Huang Rae-Chi , Vlaskovsky Phil , Newnham John P. , White Scott W. , Mori Trevor A.
Published: November 2021

Background:

Previous studies have reported an association between low birthweight and elevated blood pressure (BP) in adulthood, but few have examined the relationship between foetal growth and adult BP.

Method:

The study examined the association between intrauterine growth trajectories determined by serial ultrasound and BP of the adult offspring in the Raine Study. Foetal growth trajectories for abdominal circumference, femur length and head circumference z-scores were developed using group-based trajectory modelling from 1440 women with serial ultrasounds from 15-weeks pregnancy to birth. Seven abdominal circumference, five femur length and five head circumference trajectory groups were identified. Longitudinal linear mixed modelling examined the association between trajectory groups and offspring BP at 20 (n = 487), 22 (n = 419) and 27 (n = 436) years.

Results:

Higher SBP in adulthood significantly associated with two abdominal circumference trajectories, one with the most restricted foetal growth [3.52 mmHg, 95% confidence interval (95% CI) = 1.20–5.83] and the other with sustained low-growth (1.92 mmHg, 95% CI = 0.11–3.73) compared with an average growth trajectory, after adjusting for sex, age, alcohol consumption and BMI. Foetal head circumference trajectories with sustained low-growth or average-to-falling growth significantly associated with higher adult systolic (3.45 mmHg, 95% CI = 1.77–5.14 and 1.54 mmHg, 95% CI = 0.30–2.78, respectively) and diastolic (2.28 mmHg, 95% CI = 0.77–3.78 and 1.47 mmHg, 95% CI = 0.54–2.39, respectively) BP compared with average growth. Low femur length growth associated with higher adult DBP after adjusting for sex, but not after accounting for adult BMI.

Conclusion:

Our results show that restricted foetal head and abdominal circumference associated with higher adult SBP over two decades later, reinforcing the importance of the early intrauterine environment and its influence on adult BP.
Smooth muscle tone alters arterial stiffness: the importance of the extracellular matrix to vascular smooth muscle stiffness ratio
Authors: Pewowaruk Ryan J. , Gepner Adam D.
Published: November 2021

Background:

Recent studies show that vascular smooth muscle (VSM) is more important to elastic artery mechanics than previously believed. It remains unclear whether increased VSM tone increases or decreases arterial stiffness.

Methods and results:

We developed a novel arterial mechanics model based on pressure–diameter relationships that incorporates the contributions of extracellular matrix (ECM) and VSM to arterial stiffness measures. This model is advantageous because it simple enough to use with limited clinical data but has biologically relevant parameters which include ECM stiffness, VSM stiffness, and VSM tone. The model was used to retrospectively analyze the effects of nitroglycerin-induced vasodilation in four clinical studies. Stiffness parameters were modeled for five arterial regions including both elastic and muscular arteries. The model describes complex experimental data with changing VSM tone and blood pressure. Our analysis found that when ECM is less stiff than VSM, increasing VSM tone increases arterial stiffness. The opposite is seen when ECM is stiffer than VSM, increasing VSM tone decreases stiffness. Our results also suggest that VSM tone is a compensatory mechanism for elevated ECM stiffness in hypertensive individuals.

Conclusion:

Based on retrospective analysis of four clinical studies, we propose a simple hypothesis for the role of VSM tone on arterial stiffness: increased VSM tone increases arterial stiffness when VSM is stiffer than ECM and decreases arterial stiffness when ECM is stiffer than VSM. This hypothesis and the methods used in this study could have important implications for understanding arterial physiology in both hypertension and cardiovascular disease and deserve further exploration.
COVID-19 Impact on Students in Physical Therapist and Physical Therapist Assistant Education Programs in New York and New Jersey: Key Issues and Recommended Responses
Authors: Hyland Nannette , Vore Mary Ellen , Chan Clarence , Katz Joanne , Rivers Lynn , Hewson Kyle
Published: November 2021

Introduction.

In March 2020, after the COVID-19 pandemic surged in New York City, higher education had to either halt or immediately convert to fully online education. Physical therapy program directors in New York (NY) State and New Jersey (NJ) immediately recognized a need to understand the new challenges facing students.

Purpose.

The purpose of this paper was to identify the challenges that students in physical therapist (PT)/physical therapist assistant (PTA) programs in NY and NJ were experiencing and how institutions could respond to those challenges.

Subjects.

Students enrolled in a PT or PTA program in NY or NJ; N = 934 (861 PT and 73 PTA).

Methods.

An online survey was distributed to PT/PTA programs in NY/NJ. The survey consisted of open-ended and closed-ended questions related to academic, financial, and nonacademic issues, transition to online learning, and how institutions could respond to student challenges. Descriptive statistics and thematic analysis were used.

Results.

The most important challenges that students identified were quality/quantity of hands-on experiences, lack of contact with classmates, personal physical and mental health/wellness, and affording tuition and fees. Some differences were found across geographical regions and graduating cohorts. Physical therapist and PTA student cohorts had the same top concerns. Five major themes emerged from open-ended questions: communication; safe return to campus for psychomotor skills; additional academic resources; recognition of students' financial, mental, and physical health concerns; and, financial support.

Discussion and Conclusion.

Students in physical therapy education in NY and NJ faced similar challenges because of COVID-19 as observed by other universities worldwide. Physical therapy education can be stressful, and these additional challenges made this time extremely difficult. The findings of this survey can be used to develop a crisis management plan for university emergencies that require program modifications.
Intravitreal vascular endothelial growth factors hypertension, proteinuria, and renal injury: a concise review
Authors: Hanna Ramy M. , Ahdoot Rebecaa S. , Kim Matthew S. , Jhaveri Kenar D. , Kalantar-Zadeh Kamyar , Kurtz Ira B.
Published: November 2021

Purpose of review

Nearly 20 years ago, vascular endothelial growth factor (VEGF)inhibitors (VEGFi) were adapted from systemic use from antiangiogenesis roles to intravitreal uses. Initially bevacizumab a murine immunoglobulin was injected ‘off label’ as a treatment for diabetic macular edema and age-related macular degeneration. Throughout the following decade aflibercept and finally ranibizumab were adapted and obtained Food and Drug Administration approval for intravitreal use. Initially systemic absorption was thought to be quite low after intravitreal injections and was quoted as being 200-fold lower than levels postulated to induce significant VEGF inhibition. Pharmacodynamic studies obtained in 2014 and again in 2017 revealed significant systemic absorption and detectable VEGF inhibition, this has since been confirmed in multiple subsequent studies.

Recent findings

A few case reports of renal dysfunction and glomerular disease related to VEGFi were initially identified. Mixed findings on effects on blood pressure were noted in studies. More recently, 32 cases of de-novo glomerular disease and/or proteinuria exacerbation were identified. New studies have corroborated increased blood pressure, proteinuria exacerbation in patients with pre-existing nephrotic syndrome, and systemic VEGF depletion. Further, the most common lesion of systemic VEGFi nephrotoxicity, thrombotic microangiopathy, has recently been reported by our group.

We will review the pharmacokinetic, translational, and epidemiological data that year upon year establish the finite-yet real risk of intravitreal VEGFi.
Effectiveness of Vapocoolant Spray on Venipuncture Pain in Young Male Donors: A Randomized Controlled Trial
Authors: Basak Tulay , Aciksoz Semra , Savasci Umit , Yilmaz Soner
Published: November 2021

The aim of this single-blinded, randomized controlled study was to determine the effectiveness of vapocoolant spray in reducing pain related to venipuncture in young, healthy male blood donors. The participants were separated into 2 groups by randomization. The donors in the control group (n = 44) were not given any intervention during the blood collection process. Vapocoolant spray was applied to the donors in the vapocoolant spray group (n = 44). The pain score was 1.90 ± 1.47 for the vapocoolant spray group and 3.23 ± 2.21 for the control group, and the difference between the groups was found to be statistically significant (P = .02). The study result showed that the use of vapocoolant spray for pain management is an effective method of reducing pain related to venipuncture during the process of blood donation in young male donors.
Infusion Center Guidelines for Teprotumumab Infusions: Informed Consent, Safety, and Management of Side Effects
Authors: Kang Julia , Lechuga Maria , Braun Jenna , Kossler Andrea , Douglas Raymond , Cockerham Kimberly
Published: November 2021

Teprotumumab was the first and only medication approved by the US Food and Drug Administration for the treatment of thyroid eye disease in January 2020. Thyroid eye disease is a complex autoimmune inflammatory disease that can be sight-threatening, debilitating, and disfiguring to affected patients. Although biologic therapies are a preferred treatment option for many complex immunologic and oncologic conditions, their use in ophthalmology and endocrinology may be more novel. The goals of this article are to introduce this new therapeutic option; discuss its mechanism of action, indications for use, administration protocol, infusion precautions, and informed consent; and review common side effects and management.
Mycophenolate-Induced Colitis in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Patients
Authors: Schmitt Monica M. , Ferré Elise M. N. , Sampaio De Melo Michelly , Cooper Megan A. , Quezado Martha M. , Heller Theo , Lionakis Michail S.
Published: November 2021

Introduction:

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a prototypic monogenic autoimmune disorder caused by AIRE deficiency-mediated impaired central immune tolerance. Although multiple endocrine and nonendocrine tissues are affected in APECED, the colon is an uncommon target of autoimmune attack. Mycophenolate is a potent immunomodulatory medication that is used to treat autoimmune manifestations in patients with APECED and other autoimmune diseases.

Methods:

We reviewed the clinical, laboratory, genetic, histological, and treatment data of mycophenolate-induced colitis in our cohort of 104 APECED patients.

Results:

Among 10 mycophenolate-treated APECED patients, 4 (40%) developed reversible biopsy-proven mycophenolate-induced colitis characterized by an inflammatory bowel disease-like and/or graft-versus-host disease-like histological pattern.

Conclusion:

Mycophenolate-induced colitis appears to be a common complication in patients with APECED for which clinicians should maintain a high index of suspicion.
Sex differences in type 2 diabetes mellitus prevalence among persons with HIV
Authors: Birabaharan Morgan , Strunk Andrew , Kaelber David C. , Smith Davey M. , Martin Thomas C.S.
Published: November 2021

Objective:

To examine whether type 2 diabetes mellitus (T2DM) is more common among women with HIV (WWH) than men with HIV (MWH).

Design:

A cross-sectional analysis of a demographically heterogenous population-based sample of more than 64 million patients in the United States.

Methods:

Using the Explorys (IBM) database, compare the prevalence of T2DM among men and women without HIV and influence of HIV on T2DM by sex controlling for confounding factors.

Results:

From 19 182 775 persons included in the study, 39 485 were with HIV. Rates of obesity was higher among WWH than MWH (58 vs. 35%). Prevalence of T2DM among WWH was 23% compared with 16% among MWH (P < 0.001). In sex-stratified adjusted analysis, WWH had 1.31 [95% confidence interval (CI), 1.24–1.38] times the odds of having T2DM than women without HIV. Women with HIV was associated with T2DM across all demographic subgroups. In contrast, no association between HIV and T2DM was observed among men (OR 1.01; 95% CI 0.98–1.05).

Conclusion:

These data suggest that HIV confers a sex-specific increase in odds of T2DM among women but not men.
Paenihalocynthiibacter styelae gen. nov., sp. nov., isolated from stalked sea squirt Styela clava
Authors: Kim Young-Ok , Noh Jae Koo , Kim Dong-Gyun , Park In-Suk , Park Sooyeon , Yoon Jung-Hoon
Published: November 2021

A Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacterial strain, MYP1-1T, was isolated from the intestine of a stalked sea squirt (Styela clava) of the South Sea in the Republic of Korea. The neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain MYP1-1T clustered with the type strains of

Halocynthiibacter

species and

Pseudohalocynthiibacter aestuariivivens

. Strain MYP1-1T exhibited 16S rRNA gene sequence similarity values of 97.0–97.6 % to the type strains of

Halocynthiibacter namhaensis

,

Halocynthiibacter arcticus

and

P. aestuariivivens

. The phylogenetic tree based on genomic sequences showed that strain MYP1-1T formed a distinct branch separating it from the type strains of two

Halocynthiibacter

species and

P. aestuariivivens

and other taxa. The DNA G+C content of strain MYP1-1T from its genomic sequence was 55.0 mol%. Strain MYP1-1T contained Q-10 as the predominant ubiquinone and C18 : 1
 ω7c as the major fatty acid. The major polar lipids of strain MYP1-1T were phosphatidylcholine, phosphatidylglycerol, one unidentified lipid and one unidentified aminolipid. The differences in fatty acid and polar lipid profiles and other differential phenotypic properties made it reasonable to distinguish strain MYP1-1T from the genera

Halocynthiibacter

and

Pseudohalocynthiibacter

. On the basis of the polyphasic taxonomic investigations, we conclude that strain MYP1-1T constitutes a new genus and species within the class

Alphaproteobacteria

, for which the name Paenihalocynthiibacter styelae gen. nov., sp. nov. is proposed. The type strain is MYP1-1T (=KCTC 82143T=NBRC 114355T).
Streptomyces spirodelae sp. nov., isolated from duckweed
Authors: Saimee Yuparat , Duangmal Kannika
Published: November 2021

A novel actinobacterium, designated strain DW4-2T, was isolated from duckweed (Spirodela sp.) collected from an agricultural pond in Kasetsart University, Bangkok, Thailand. The morphological, chemotaxonomic and phylogenetic characteristics were consistent with its classification in the genus

Streptomyces

. Strain DW4-2T showed the highest 16S rRNA gene sequence similarity values to

Streptomyces qinglanensis

DSM 42035T (98.5 %), S

treptomyces smyrnaeus

DSM 42105T (98.4 %) and

Streptomyces oryzae

S16-07T (98.4 %). Digital DNA–DNA hydridization and average nucleotide identity values between the genome sequences of strain DW4-2T with

S. qinglanensis

DSM 42035T (29.8 and 87.8 %),

S. smyrnaeus

DSM 42105T (33.1 and 89.0 %) and

S. oryzae

S16-07T (33.0 and 88.9 %) were below the thresholds of 70 and 95–96 % for prokaryotic conspecific assignation. Chemotaxonomic data revealed that strain DW4-2T possessed MK-9(H6) and MK-9(H8) as the predominant menaquinones. It contained
ll

-diaminopimelic acid as the diagnostic diamino acid and glucose, ribose and trace amount of madurose in whole-cell sugars. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, an unidentified aminolipid, an unidentified lipid and an unidentified phospholipid. The predominant cellular fatty acids were anteiso-C17 : 0, anteiso-C15 : 0 and iso-C16 : 0. The genomic DNA size of the strain DW4-2T was 7 310 765 bp with DNA G+C content 71.0 mol%. Genomic analysis of the genome indicated that the strain DW4-2T had the potential to produce bioactive compounds. On the basis of these genotypic and phenotypic data, it is supported that strain DW4-2T represents a novel species of the genus

Streptomyces

, for which the name Streptomyces spirodelae sp. nov. is proposed. The type strain is strain DW4-2T (=TBRC 13095T=NBRC 114803T).
DOCKGROUND Membrane Protein-Protein Set
Authors: Kotthoff Ian , Kundrotas Petras J. , Vakser Ilya A.
Published: November 2021

Membrane proteins play essential role in cellular mechanisms. Despite that and the major progress in experimental structure determination, they are still significantly underrepresented in Protein Data Bank. Thus, computational approaches to protein structure determination, which are important in general, are especially valuable in the case of membrane proteins and protein-protein assemblies. Due to a number of reasons, not the least of which is much greater availability of structural data, the main focus of structure prediction techniques has been on soluble proteins. Structure prediction of protein-protein complexes is a well-developed field of study. However, because of the differences in physicochemical environment in the membranes and the spatial constraints of the membranes, the generic protein-protein docking approaches are not optimal for the membrane proteins. Thus, specialized computational methods for docking of the membrane proteins must be developed. Development and benchmarking of such methods requires high-quality datasets of membrane protein-protein complexes. In this study we present a new dataset of 456 non-redundant alpha helical binary complexes. The set is significantly larger and more representative than previously developed ones. In the future, this set will become the basis for the development of docking and scoring benchmarks, similar to the ones developed for soluble proteins in the DOCKGROUND resource http://dockground.compbio.ku.edu.
The Immune Signatures Data Resource: A compendium of systems vaccinology datasets
Authors: Diray-Arce Joann , Miller Helen E.R. , Henrich Evan , Gerritsen Bram , Mulè Matthew P. , Fourati Slim , Gygi Jeremy , Hagan Thomas , Tomalin Lewis , Rychkov Dmitry , Kazmin Dmitri , Chawla Daniel G. , Meng Hailong , Dunn Patrick , Campbell John ,   The Human Immunology Project Consortium (HIPC), Sarwal Minnie , Tsang John S. , Levy Ofer , Pulendran Bali , Sekaly Rafick , Floratos Aris , Gottardo Raphael , Kleinstein Steven H. , Suárez-Fariñas Mayte
Published: November 2021

Vaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern ‘omic profiling techniques and computational modeling to promote rapid and transformative advances in vaccinology and vaccine discovery. The NIH/NIAID Human Immunology Project Consortium (HIPC) has leveraged systems immunology approaches to identify molecular signatures associated with the immunogenicity of many vaccines, including those targeting seasonal influenza, yellow fever, and hepatitis B. These data are made available to the broader scientific community through the ImmuneSpace data portal and analysis engine leveraging the NIH/NIAID ImmPort repository1,2. However, a barrier to progress in this area is that comparative analyses have been limited by the distributed nature of some data, potential batch effects across studies, and the absence of multiple relevant studies from non-HIPC groups in ImmPort. To support comparative analyses across different vaccines, we have created the Immune Signatures Data Resource, a compendium of standardized systems vaccinology datasets. This data resource is available through ImmuneSpace, along with code to reproduce the processing and batch normalization starting from the underlying study data in ImmPort and the Gene Expression Omnibus (GEO). The current release comprises 1405 participants from 53 cohorts profiling the response to 24 different vaccines and includes transcriptional profiles and antibody response measurements. This novel systems vaccinology data release represents a valuable resource for comparative and meta-analyses that will accelerate our understanding of mechanisms underlying vaccine responses.
Distribution And Population Of Chukar Partrigde (Alectoris chukar) In District Bajuar, KPK, Pakistan
Authors: Shahwar Durr e , Kawan Atufa , Mukhtar Hina , Ullah Inam
Published: November 2021

The Chukar Partridge (Alectoris chukar) is a wild bird of the Phasianidae family. In Pakistan, it occurs in a wide range of rugged, sloping and dry areas, rising to the interior of the Himalayas, the western Himalayas and plains, the higher piedmont valleys on the dry slopes of the Baluchistan provinces and Punjab and Sindh provinces. It is the “national bird” of Pakistan, however, little is known about its ecology and reproduction in the northern part of the country. This study investigated the existence, distribution and population of birds in the Bajaur region of Khyber Pakhtunkhwa (KP) Province from December 2019 to August 2020. Usually in the early morning (5 to 78 AM) and evening (4 to 9 pm). The areas occupied by Alectoris chukar mainly include Mulberry, Ficus banyan, Gum arabic, Arabian acacia, Barberes lycium, Dilberia sisso, Melia azedarach, Ailanthus, Alalthus altissima, Zanthoxylum alatum, Olea europaea, Olea europaea, Ingres, Celtis eriocarpa and Pinus wallichiana. Habitat destruction (overgrazing, mowing and landslides) caused by hunting, shooting, capture, explosives, excavation, and road construction is the main threat to existing wildlife (including Alectoris chukar).
Structural basis of main proteases of coronavirus bound to drug candidate PF-07321332
Authors: Li Jian , Lin Cheng , Zhou Xuelan , Zhong Fanglin , Zeng Pei , Yang Yang , Zhang Yuting , Yu Bo , Fan Xiaona , McCormick Peter J. , Fu Rui , Fu Yang , Jiang Haihai , Zhang Jin
Published: November 2021

The high mutation rate of COVID-19 and the prevalence of multiple variants strongly support the need for pharmacological options to complement vaccine strategies. One region that appears highly conserved among different genus of coronaviruses is the substrate binding site of the main protease (Mpro or 3CLpro), making it an attractive target for the development of broad-spectrum drugs for multiple coronaviruses. PF-07321332 developed by Pfizer is the first orally administered inhibitor targeting the main protease of SARS-CoV-2, which also has shown potency against other coronaviruses. Here we report three crystal structures of main protease of SARS-CoV-2, SARS-CoV and MERS-CoV bound to the inhibitor PF-07321332. The structures reveal a ligand-binding site that is conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, providing insights into the mechanism of inhibition of viral replication. The long and narrow cavity in the cleft between domains I and II of main protease harbors multiple inhibitor binding sites, where PF-07321332 occupies subsites S1, S2 and S4 and appears more restricted compared with other inhibitors. A detailed analysis of these structures illuminated key structural determinants essential for inhibition and elucidated the binding mode of action of main proteases from different coronaviruses. Given the importance of main protease for the treatment of SARS-CoV-2 infection, insights derived from this study should accelerate the design of safer and more effective antivirals.
A Descriptive Analysis of Chairs of Academic Neurology Departments in the United States
Authors: Patel Kajol K. , Patel Parth A.
Published: November 2021

There remains a limited understanding of the characteristics of academic leaders within neurology departments, despite similar research in other fields. This investigation characterized the demographics, academic background, and scholarly productivity of United States (U.S.) neurology department chairs. Here, 131 chairs at Accreditation Council for Graduate Medical Education (ACGME)-certified neurology programs were identified. Publicly accessible demographic and academic data available online were collected in March 2021. Among the 131 neurology chairs analyzed, 84.7% were male. On average, these faculty were 60.5 years old and were appointed at a mean age of 52.0 years. 74.8% of chairs graduated from an American medical school, although a notable proportion of department heads received medical training internationally. A substantial cohort also acquired an additional graduate degree, of which Doctor of Philosophy (PhD; 22.1%) and master’s degree (21.4%) were most common. 82.4% completed a post-residency fellowship, which were most frequently in vascular neurology (24.1%) and clinical neurophysiology (17.6%). The mean h-index, m-quotient, and lifetime NIH grant funding received were 39.2 ± 29.4, 1.2 ± 0.8, and $20,021,594 ± $31,861,816, respectively. No between-gender differences were observed. Overall, neurology chairs are predominantly male, most often completing fellowships in vascular neurology or clinical neurophysiology. Research productivity is a notable component of these chairs’ careers, although certain programs place less emphasis on these metrics. Finally, substantial effort remains to address disparities in female representation at this leadership position. These findings serve as a benchmark to evaluate demographic trends among neurology department chairs.
An interactome landscape of SARS-CoV-2 virus-human protein-protein interactions by protein sequence-based multi-label classifiers
Authors: Lee Ho-Joon
Published: November 2021

The new coronavirus species, SARS-CoV-2, caused an unprecedented global pandemic of COVID-19 disease since late December 2019. A comprehensive characterization of protein-protein interactions (PPIs) between SARS-CoV-2 and human cells is a key to understanding the infection and preventing the disease. Here we present a novel approach to predict virus-host PPIs by multi-label machine learning classifiers of random forests and XGBoost using amino acid composition profiles of virus and human proteins. Our models harness a large-scale database of Viruses.STRING with >80,000 virus-host PPIs along with evidence scores for multi-level evidence prediction, which is distinct from predicting binary interactions in previous studies. Our multi-label classifiers are based on 5 evidence levels binned from evidence scores. Our best model of XGBoost achieves 74% AUC and 68% accuracy on average in 10-fold cross validation. The most important amino acids are cysteine and histidine. In addition, our model predicts experimental PPIs with higher accuracy than text mining-based PPIs by 4% despite their smaller data size by more than 6-fold. We then predict evidence levels of ∼2,000 SARS-CoV-2 virus-human PPIs from public experimental proteomics data. Interactions with SARS-CoV-2 Nsp7b show high evidence. We also predict evidence levels of all pairwise PPIs of ∼550,000 between the SARS-CoV-2 and human proteomes to provide a draft virus-host interactome landscape for SARS-CoV-2 infection in humans in a comprehensive and unbiased wayin silico. Most human proteins from 140 highest evidence predictions interact with SARS-CoV-2 Nsp7, Nsp1, and ORF14, with significant enrichment in the top 2 pathways of vascular smooth muscle contraction (CALD1, NPR2, CALML3) and Myc targets (CBX3, PES1). Our prediction also suggests that histone H2A components are targeted by multiple SARS-CoV-2 proteins.