bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of and Factors Associated With the Prescription of Fibrates Among Patients Receiving Lipid-Lowering Drugs in Germany
Authors: Jacob Louis , Greiner Roger-Axel , Luedde Mark , Kostev Karel
Published: October 2021

Little recent data are available about the patterns of prescription for fibrates in patients followed in primary care practices. Therefore, the goal of this study was to analyze the prevalence of and the factors associated with the use of fibrates among patients receiving lipid-lowering drugs in Germany. The study included patients aged ≥18 years with at least 1 visit to 1 of 1070 general practices in Germany between January and December 2019. Lipid-lowering drugs included statins (without and with ezetimibe) and fibrates. The prevalence of the prescription of fibrates corresponded to the number of patients with at least 1 prescription for fibrates divided by the total number of patients receiving lipid-lowering drugs. A logistic regression model was used to assess the relationship between several demographic, clinical, and biological factors and the prescription of fibrates. A total of 111,329 patients were included in this study (mean [SD] age 68.8 [11.5] years; 56.0% of patients were men). The prevalence of the prescription of fibrates was 1.5%. Male sex, hypertension, diabetes mellitus, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and high triglyceride were positively associated with the use of fibrates. By contrast, there was a negative relationship between the odds of receiving fibrates and coronary heart disease, myocardial infarction, peripheral arterial disease, and stroke including transient ischemic attack. Overall, we found that fibrates were infrequently prescribed in general practices in Germany.
Handgrip strength, dynapenia, and related factors in postmenopausal women
Authors: García-Alfaro Pascual , García Sandra , Rodríguez Ignacio , Pérez-López Faustino R.
Published: October 2021

Objective:

This study aimed to evaluate the prevalence of dynapenia and factors related to low dominant handgrip strength (HGS) in postmenopausal women.

Methods:

A cross-sectional study was performed on 249 postmenopausal women aged 50 to 84 years. The following variables were recorded: age, age at menopause, smoking status, and the HGS measured with a digital dynamometer, body mass index, and adiposity assessed by bioelectric impedance. The physical activity level was evaluated by using the International Physical Activity Questionnaire. Bone mineral density was reported as T-scores, and blood biochemical parameters (calcium, phosphorus, vitamin D, and parathormone levels) were measured.

Results:

31.3% of women had dynapenia, and those aged ≥65 years had lower HGS (P < 0.001). Age at menopause was also associated with HGS, with those with menopause < 51 showing lower HGS (P = 0.005). Likewise, fat content ≥ 40%, and osteopenia/osteoporosis were also related to lower strength (P < 0.001). There was no statistically significant difference among HGS with respect to body mass index, smoking status, and plasma levels of vitamin D. A logistic regression model with lower Akaine Information Criterion showed that for every year in age and for each 1% of adiposity, women were more likely to have dynapenia with odd ratio (OR): 1.09; 95% and confidence interval (CI): 1.04 to 1.14 and OR: 1.06; 95% CI: 1.00 to 1.13, respectively. Conversely, women with higher femoral neck T-score were less likely to have dynapenia (OR: 0.53; 95% CI: 0.35-0.78).

Conclusions:

HGS was associated with age at menopause, bone mineral density, and adiposity adjusted by age. The age and adiposity were significantly associated with a higher risk of dynapenia, whereas women with higher femoral neck T-score were less likely to have dynapenia.
Pneumolabyrinth as an Early Computed Tomographic Finding After Cochlear Implantation and its Clinical Significance
Authors: Im Se Yeon , Kim Min-Kyu , Lee Seulgi , Chung Jee-Hye , Choi Jin Woong
Published: October 2021

Objective:

To determine the incidence and volume of pneumolabyrinth using early temporal bone computed tomography (TBCT) findings and evaluate the correlation between pneumolabyrinth and various clinical variables.

Study Design:

Retrospective case review.

Setting:

Tertiary academic center.

Patients:

Fifty-three consecutive adult cochlear implantation (CI) recipients (53 ears) with normal inner ears who underwent high-resolution TBCT within 3 days after CI were included.

Intervention:

Axial TBCT images were used for detection and measurement of pneumolabyrinth.

Main Outcome Measures:

Incidence and volume of pneumolabyrinth were evaluated. In addition, the following clinical variables were analyzed to evaluate the correlation with pneumolabyrinth volume: demographics, implant type, surgical approach, postoperative dizziness, and preservation of functional residual hearing.

Results:

Pneumolabyrinth was present in all patients, and the average volume was 8.496 mm3. Pneumolabyrinth was confined to the cochlea (pneumocochlea) in all patients except for one who also had pneumovestibule. The pneumolabyrinth volume in patients with postoperative dizziness was significantly larger than that in patients without postoperative dizziness (10.435 mm3 vs. 8.016 mm3; p = 0.029). Multivariate analysis showed that a larger volume of pneumolabyrinth was significantly associated with postoperative dizziness (odds ratio, 1.420; 95% confidence interval, 1.114–1.808; p = 0.005).

Conclusion:

A certain volume of pneumolabyrinth was always present in the early stage after CI, and the volume of pneumolabyrinth measured using early TBCT findings was significantly associated with the occurrence of postoperative dizziness.
Osteoblastoma of the Temporal Bone in a Child
Authors: Gibson Micah , Michalowicz Matthew , Chrisinger John S. A. , Bell Diana , Shah Komal , Demonte Franco , Gidley Paul W.
Published: October 2021

This report describes osteoblastoma of the temporal bone found on a well-child visit. The relevant clinical, radiographic, and histologic features are described. The tumor was completely resected via a transtemporal approach. The differential diagnosis for these tumors include osteoma, giant cell tumor, histiocytosis, aneurysmal bone cyst and sarcoma. Histologic findings are critical for determining the proper diagnosis.
Comparison of Lower Cranial Nerve Function Between Tympanojugular Paraganglioma Class C1/C2 With and Without Intracranial Extension: A Four-Decade Experience
Authors: Grinblat Golda , Sanna Mario , Piccirillo Enrico , Piras Gianluca , Guidi Mariapaola , Shochat Isaac , Munteanu Simona Gloria
Published: October 2021

Objective:

To compare preoperative and postoperative lower cranial nerve (LCN) function between Class C1 and C2 tympanojugular paraganglioma (TJP) with/without intracranial intradural (Di)/extradural (De) extensions, according to the experience of a single surgeon over four decades.

Study Design:

Retrospective review.

Setting:

Quaternary referral center for otology and skull base surgery.

Material and Methods:

A chart review was conducted of all the patients operated for C1/C2 TJPs from September 1983 to December 2018. The tumors were classified as: Limited-Group (C1/C2 without Di/De extensions) and Extended-Group (C1/C2 with Di/De extensions).

Results:

Of 159 patients, 107 (67.3%) were women; the mean age at surgery was 46.5 years. The Limited-Group (56.6%) comprised C1 (41.1%) and C2 (58.9%) tumors; the Extended-Group (43.4%) comprised C1+Di/De (14.5%) and C2+Di/De (85.5%) tumors. The prevalence of preoperative LCN palsy was 11.9 times higher in Extended than Limited tumors: 61.9% versus 4.9% (p < 0.05). The risk for postoperative LCN palsy was 4.7 times greater in Extended than Limited tumors: 29.2% versus 12.9%, p = 0.01.

Conclusion:

Especially in younger patients, complete removal of Limited C1/C2 tumors, before they extend intracranially, reduces the risk of dysfunctionality of LCNs and the burden of residual tumor. The incidence of new tumors increased over four decades. However, new-postoperative LCN palsy did not occur in any Limited C1/C2 tumors operated after the year 2000, and declined to less than 10% of Extended C1/C2 tumors.
Preparedness to Write Items for Nursing Education Examinations
Authors: Moran Vicki , Wade Heather , Moore Leigh , Israel Heidi , Bultas Margaret
Published: October 2021

Background:

Nursing programs in the United States primarily use multiple-choice questions to prepare students for the NCLEX.

Background:

Nursing programs in the United States primarily use multiple-choice questions to prepare students for the NCLEX. Currently, the optional next-generation NCLEX is testing the validity and reliability of situational case studies.

Purpose:

The purpose of this study was to investigate the preparedness and confidence of nurse educators in writing NCLEX-style questions.

Methods:

A descriptive survey design with snowball sampling was used to collect the data and was sent to 1550 deans/directors/coordinators of publicly available email addresses of accredited schools of nursing.

Results:

A total of 300 participants completed the survey from 44 states. When asked about confidence in writing NCLEX-style items, those who received formal education or training reported being somewhat confident (51%), whereas those who did not reported ambivalent or not confident (49%).

Conclusion:

Surveyed nurse educators lack confidence in writing questions and feel unprepared for the new question types instituted by the NCSBN in 2023. Nurse educators need continued education to develop and review NCLEX-style items and examinations.
Perceptions of Teamwork in Schools of Nursing
Authors: Cooke Marcia , Valentine Nancy M.
Published: October 2021

Background:

Characteristics of high-performing teams include shared purpose, clear vision, strong leadership, and the ability to use conflict management when needed. While many individuals who teach in schools of nursing come from the clinical setting where teamwork is normative, that same expectation of teamwork may not be present for the faculty as a whole.

Purpose:

This study assessed perceptions of teamwork among faculty members in schools of nursing in 4 states in the Midwestern region of the United States.

Methods:

Perception of teamwork, related to communication, leadership, team structure, situation monitoring, and mutual support, was examined using a modified TeamSTEPPS Teamwork Perceptions Questionnaire.

Results:

Perceptions of teamwork were highest for team structure and leadership, whereas communication, situation monitoring, and mutual support were lower. In addition, teamwork dimension scores were higher for those who previously participated in teamwork training.

Conclusions:

There are opportunities to improve teamwork in all domains. Teamwork skills are transferrable to different roles and across various situations; therefore once learned and fostered, these can impact the individual as well as improve the organizational climate.
Leveraging Help Desk Reports to Support Faculty Success
Authors: Liwosz Thomas , Abbott Miriam Ruth Bowers , Nininger Jami , Williamson Kathleen
Published: October 2021

Background

The advancement of technological tools fosters constant change in nursing education. Institutional help desk reports classify data sets based on topic and source. These aggregate data may be useful in supporting nursing faculty adaptation to technological change.

Purpose

In an endeavor to identify and address persistent barriers to technological adaptation by nursing faculty, help desk data were reviewed to identify trends and implications of such trends.

Methods

Within the context of a single-purpose, private nursing college, the findings of help desk reports were assessed to identify the source of technological barriers and potential paths toward addressing these barriers.

Results

The help desk reports identify pronounce areas in which faculty frequently seek assistance. In addition, the reports disclose unique tendencies in nursing faculty to collaborate with peers for assistance.

Conclusions

The trends identified within the records provide an evidence-based foundation for efforts to support effective faculty development interventions.
Telehealth Availability and Usage Among Medicare Beneficiaries During the COVID-19 Pandemic, October and November 2020
Authors: Chang Man-Huei , Moonesinghe Ramal , Truman Benedict I.
Published: October 2021

Context:

During the COVID-19 pandemic, demand for telehealth services increased to reduce disease exposure for patients and providers and to meet preexisting demand for physician services in health resource shortage areas.

Objective:

To estimate self-reported telehealth availability, equipment for accessing telehealth, and telehealth usage among Medicare beneficiaries during the COVID-19 pandemic.

Design:

We used data from the 2020 Medicare Current Beneficiary Survey (MCBS) COVID-19 Fall Supplement Public Use File to estimate the weighted percentages of beneficiaries who had (a) access to telehealth before or during COVID-19; (b) equipment for accessing telehealth; and (c) telehealth visits during COVID-19. We used logistic regression to examine sociodemographic factors associated with telehealth usage.

Participants:

Beneficiaries who participated in the MCBS COVID-19 Fall Supplements.

Results:

During October and November 2020, telehealth appointments offered by providers were available to 63.8% (95% confidence interval [CI], 61.8-65.9) of Medicare beneficiaries who had accessed medical care by telephone or video. Among those, only 18.0% (95% CI, 16.1-19.9) had been offered telehealth before the pandemic. The majority of beneficiaries (92.2%; 95% CI, 91.2-93.1) had 1 or more types of equipment available for accessing telehealth, but only 44.9% (95% CI, 43.0-46.9) had had a telehealth visit since July 1, 2020. Older adults, minorities, those with a lower income, and non-English speakers had less availability of telehealth equipment. Patient characteristics were significantly (P < .05) associated with telehealth use, including age, sex, race/ethnicity, and equipment availability.

Conclusion:

Telehealth availability for Medicare beneficiaries increased substantially during the COVID-19 pandemic. Even with the improvement in telehealth offerings and use hastened by the pandemic, gaps in access and use still exist. Effectiveness and implementation research can find ways to close gaps in telehealth services between vulnerable and underrepresented populations and counterparts.
Interpersonal Emotion Dynamics in Couples With Somatic Symptom Disorder: Dyadic Coherence in Facial Temperature During Emotional Interactions
Authors: Okur Güney Zeynep Emine , Cardone Daniela , Sattel Heribert , Ariens Sigert , Witthöft Michael , Merla Arcangelo , Kuppens Peter , Henningsen Peter
Published: October 2021

Objective

Disturbances in emotional processes are commonly reported in patients with a somatic symptom disorder (SSD). Although emotions usually occur in social interactions, little is known about interpersonal emotion dynamics of SSD patients during their actual emotional encounters. This study examined physiological coherence (linkage) between SSD patients and their partners, and in healthy couples during their emotional interactions. Secondarily, we explored group-level relationships between participants’ and their partners’ subjective affect.

Methods

Twenty-nine romantic couples (16 healthy and 13 SSD patient-couples) underwent a dyadic conversation task with neutral and anger-eliciting topics followed by a guided relaxation. Partners’ cutaneous facial temperature was recorded simultaneously by functional infrared thermal imaging. Immediately after each condition, participants reported on their pain intensity, self-affect, and perceived partner-affect.

Results

Emotional conditions and having a partner with an SSD significantly affected coherence amplitude on the forehead (F(2,54) = 4.95, p = .011) and nose tip temperature (F(2,54) = 3.75, p = .030). From baseline to anger condition, coherence amplitude significantly increased in the patient-couples, whereas it decreased in the healthy couples. Correlation changes between partners’ subjective affect comparably accompanied the changes in physiological coherence in healthy and patient-couples.

Conclusions

Inability to reduce emotional interdependence in sympathetic activity and subjective affect during a mutual conflict observed in SSD patient-couples seems to capture emotion co-dysregulation. Interventions should frame patients’ emotional experiences as embodied and social. Functional infrared thermal imaging confirms to be an ecological and reliable method for examining autonomic changes in interpersonal contexts.

Registration Page: https://osf.io/8eyjr
Cohort Profile Update: The HUNT Study, Norway
Authors: Åsvold Bjørn Olav , Langhammer Arnulf , Rehn Tommy Aune , Kjelvik Grete , Grøntvedt Trond Viggo , Sørgjerd Elin Pettersen , Fenstad Jørn Søberg , Holmen Oddgeir , Stuifbergen Maria C , Vikjord Sigrid Anna Aalberg , Brumpton Ben M , Skjellegrind Håvard Kjesbu , Thingstad Pernille , Sund Erik R , Selbæk Geir , Mork Paul Jarle , Rangul Vegar , Hveem Kristian , Næss Marit , Krokstad Steinar
Published: October 2021

In the HUNT Study, all residents aged ≥20 years in the Nord-Trøndelag region, Norway have been invited to repeated surveys since 1984-86. The study data may be linked to local and national health registries. The HUNT4 survey in 2017-19 included 56 042 participants in Nord-Trøndelag and 107 711 participants in the neighboring Sør-Trøndelag region. The HUNT4 data enable more long-term follow-up, studies of life-course health trajectories, and within-family studies. New measures include body composition analysis using bioelectrical impedance; a one-week accelerometer recording; physical and cognitive testing in older adults; measurements of hemoglobin and blood cell counts, HbA1c and phosphatidylethanol; and genotyping. Researchers can apply for HUNT data access from HUNT Research Centre if they have obtained project approval from the Regional Committee for Medical and Health Research Ethics, seewww.ntnu.edu/hunt/data.
A Computational Approach in Identification of Putative Risk Genes in Parkinsons Disease
Authors: Dave Bhargav , Majumder Prasenjit , Sarkar Shamayeeta
Published: October 2021

This study focussed on identification of risk genes involved in PD through analysis of microarray data. The two methods were applied viz; WGCNA and DEGs Analysis to identify important genes that are downregulated or upregulated in PD. Both methods show high agreement with each other and also with the available biomedical literature available on this neurodegenerative disease. On the basis of their p–value, 20 significantly upregulated and 19 significantly downregulated genes were found to be playing role in the manifestation of motor and non motor symptoms of the disease, as interpreted from the enrichment analysis.

Gene expression dataset of Parkinson’s Disease (PD) used in this study was obtained from the GeneExpression Omnibus namely GSE8397, GSE20164, and GSE20295 (Edgar, 2002). Among the important genes extracted, the top downregulated and upregulated genes were studied using enrichment analysis. Out of the 19 common downregulated genes, 10 were directly associated with neuron development and differentiation. Two of the genes, FGF13 and CDC42 were associated with multiple signalling pathways. The gene NSF was found to be enriched with GABAergic synapse, associated with the predominating inhibitory neurotransmitter in the mammalian CNS. The inhibitory synapses are thought to provide a brake to neural firing.

The upregulated genes DDIT4, HSPB1, NUPR1, GPNMB and CH13L1 were enriched with apoptotic signalling pathway while MT1M, MT1E, MT1F, MT1X were associated with mineral absorption pathways. Genes like CDC42 have already been reported to be potential diagnostic markers of PD in clinic (Chi et al., 2018).
Extreme COVID-19 waves reveal hyperexponential growth and finite-time singularity
Authors: Pavithran Induja , Sujith R. I.
Published: October 2021

Coronavirus disease 2019 (COVID-19) has rapidly spread throughout our planet, bringing human lives to a standstill. Understanding the early transmission dynamics helps plan intervention strategies such as lockdowns that mitigate further spread, minimizing the adverse impact on humanity and the economy1–3. Exponential growth of infections was thought to be the defining feature of an epidemic in its initial growth phase4–7; any variation from an exponential growth was described by adjusting the parameters of the exponential model7,8. Here, we show that, contrary to common belief, early stages of extreme COVID-19 waves display an unbounded growth and finite-time singularity accompanying a hyperexponential power-law. The faster than exponential growth phase is hazardous and would entail stricter regulations. Such a power-law description allows us to characterize COVID-19 waves with single power-law exponents, better than piece-wise exponentials. Furthermore, we identify the presence of log-periodic patterns decorating the power-law growth. These log-periodic oscillations may enable better prediction of the finite-time singularity. We anticipate that our findings of hyperexponential growth and log-periodicity will help model the COVID-19 transmission more accurately.
SARS-COV-2 C.1.2 variant is highly mutated but may possess reduced affinity for ACE2 receptor
Authors: Yang Xiang-Jiao
Published: October 2021

SARS-COV-2 evolution generates different variants and drives the pandemic. As the current main driver, delta variant bears little resemblance to the other three variants of concern (alpha, beta and gamma), raising the question what features the future variants of concern may possess. To address this important question, I searched through the GISAID database for potential clues. While investigating how beta variant has been evolving in South Africa, I noticed a small group of genomes mainly classified as C.1.2 variant, with one-year old boy identified in March 2021 being the index case. Over 80% patients are younger than 60. At the average, there are 46-47 mutations per genome, making this variant one of the most mutated lineages identified. A signature substitution is spike Y449H. Like beta and gamma variants, C.1.2 possesses E484K and N501Y. The genomes are heterogenous and encode different subvariants. Like alpha variant, one such subvariant encodes the spike substitution P681H at the furin cleavage site. In a related genome, this substitution is replaced by P681R, which is present in delta variant. In addition, similar to this variant of concern, three C.1.2 subvariants also encode T478K. Mechanistically, spike Y449 recognizes two key residues of the cell-entry receptor ACE2 and Y449H is known to impair the binding to ACE2 receptor, so C.1.2 variant may show reduced affinity for this receptor. If so, this variant needs other mutations to compensate for such deficiency. These results raise the question whether C.1.2 variant is as virulent as suggested by its unexpected high number of mutations.
Leveraging interindividual variability of regulatory activity refines genetic regulation of gene expression in schizophrenia
Authors: Alver Maris , Lykoskoufis Nikolaos , Ramisch Anna , Ongen Halit , Dermitzakis Emmanouil T.
Published: October 2021

Schizophrenia is a polygenic psychiatric disorder with limited understanding about the mechanistic changes in gene expression regulation. To elucidate on this, we integrate interindividual variability of regulatory activity with gene expression and genotype data captured from the prefrontal cortex of 272 cases and controls. We show that regulatory element activity is structured into 10,936 and 10,376 cis-regulatory domains in cases and controls, respectively, which display distinct regulatory element coordination structures in both states. By studying the interplay among genetic variants, gene expression and cis-regulatory domains, we ascertain that changes in coordinated regulatory activity tag alterations in gene expression levels (p=8.62e-06, OR=1.60), unveil case-specific QTL effects, and identify regulatory machinery changes for genes affecting synaptic function and dendritic spine morphology in schizophrenia. Altogether, we show that accounting for coordinated regulatory activity provides a novel mechanistic approach to reduce the search space for unveiling genetically perturbed regulation of gene expression in schizophrenia.
Conflicts of interest and physicians’ attitudes towards hydroxychloroquine as a treatment against COVID-19 A replication and extension of Roussel & Raoult (2020)
Authors: Freget Louis , Mulot Matthieu , Rochoy Michael , Ruggeri Valentin , Schöpfer Céline , Cova Florian
Published: October 2021

Hydroxychloroquine (HCQ) and its use as a treatment against COVID-19 have been at the center of heated debates. Some claim that physicians’ hostility towards HCQ was partly orchestrated by rival pharmaceutical companies seeking to promote their own treatment. In favor of this hypothesis, Roussel and Raoult (2020) have presented the results of a study in which they find a perfect positive correlation (ρ = 1.00) between French physicians’ attitudes towards HCQ and their conflict of interest with Gilead Sciences - the company that has promoted Remdesivir (REM) as a treatment against COVID-19. However, Roussel and Raoult’s study suffers from serious methodological shortcomings, among which is the fact that the statistical methods they employed might tend to artificially inflate correlations. In this study, we use a similar method and sample, but correct for their study’s original shortcomings: we provide a detailed, pre-registered method for collecting and coding data, computer inter-rater agreement and use a wide array of appropriate statistical methods to achieve a more reliable estimate the association between conflicts of interest and physicians’ attitudes towards HCQ. We conclude that Roussel and Raoult’s conclusion was misguided and that financial conflicts of interest were not the main predictors of the attitudes of physicians when compared to other factors, such as academic affiliation. Moreover, compared to other pharmaceutical companies, there was no specific link between attitudes towards HCQ and conflicts of interest with Gilead Sciences.
BioThings SDK: a toolkit for building high-performance data APIs in biomedical research
Authors: Lelong Sebastien , Zhou Xinghua , Afrasiabi Cyrus , Qian Zhongchao , Cano Marco Alvarado , Tsueng Ginger , Xin Jiwen , Mullen Julia , Yao Yao , Avila Ricardo , Taylor Greg , Su Andrew I , Wu Chunlei
Published: October 2021

To meet the increased need of making biomedical resources more accessible and reusable, Web APIs or web services have become a common way to disseminate knowledge sources. The BioThings APIs are a collection of high-performance, scalable, annotation as a service APIs that automate the integration of biological annotations from disparate data sources. This collection of APIs currently includes MyGene.info, MyVariant.info, and MyChem.info for integrating annotations on genes, variants, and chemical compounds, respectively. These APIs are used by both individual researchers and application developers to simplify the process of annotation retrieval and identifier mapping. Here, we describe the BioThings Software Development Kit (SDK), a generalizable and reusable toolkit for integrating data from multiple disparate data sources and creating high-performance APIs. This toolkit allows users to easily create their own BioThings APIs for any data type of interest to them, as well as keep APIs up-to-date with their underlying data sources.

Availability and implementation

The BioThings SDK is built in Python and released via PyPI (https://pypi.org/project/biothings/).

Its source code is hosted at its github repository (https://github.com/biothings/biothings.api).
Novel genetic sex markers reveal unexpected lack of, and similar susceptibility to, sex reversal in free-living common toads in both natural and anthropogenic habitats
Authors: Nemesházi Edina , Sramkó Gábor , Laczkó Levente , Balogh Emese , Szatmári Lajos , Vili Nóra , Ujhegyi Nikolett , Üveges Bálint , Bókony Veronika
Published: October 2021

Anthropogenic environmental changes are affecting biodiversity and microevolution worldwide. Ectothermic vertebrates are especially vulnerable, since their sexual development can be disrupted by environmental changes, which can cause sex reversal, a mismatch between genetic and phenotypic sex, potentially leading to sex-ratio distortion and population decline. Despite these implications, we have scarce empirical knowledge on the incidence of sex reversal in nature. Populations in anthropogenic environments may experience sex reversal more frequently, or alternatively, they may adapt to resist sex reversal. To test these alternative hypotheses, we developed PCR-based genetic sex markers for the common toad (Bufo bufo). We assessed the prevalence of sex reversal in wild populations living in natural, agricultural and urban habitats, and the susceptibility of the same populations to two ubiquitous estrogenic pollutants in a common-garden experiment. We found negligible sex-reversal frequency in free-living adults despite the presence of various endocrine-disrupting pollutants in their breeding ponds. Individuals from different habitat types showed similar susceptibility to sex reversal in the laboratory: all genetic males developed female phenotype when exposed to 1 µg/L 17α- ethinylestradiol (EE2) during larval development, whereas no sex reversal occurred in response to 1 ng/L EE2 and a glyphosate-based herbicide with 3 µg/L or 3 mg/L glyphosate. The latter results do not support that populations in anthropogenic habitats would have either increased propensity for or higher tolerance to chemically induced sex reversal. Thus, the surprisingly low sex-reversal frequency in wild toads compared to other ectothermic vertebrates studied before might indicate idiosyncratic, potentially species-specific resistance to sex reversal.
FindZX: an automated pipeline for detecting and visualising sex chromosomes using whole-genome sequencing data
Authors: Sigeman Hanna , Sinclair Bella , Hansson Bengt
Published: October 2021

Sex chromosomes have evolved numerous times, as revealed by recent genomic studies. However, large gaps in our knowledge of sex chromosome diversity across the tree of life remain. Filling these gaps, through the study of novel species, is crucial for improved understanding of why and how sex chromosomes evolve. Characterization of sex chromosomes in already well-studied organisms is also important to avoid misinterpretations of population genomic patterns caused by undetected sex chromosome variation. Here we present findZX, an automated Snakemake-based computational pipeline for detecting and visualizing sex chromosomes through differences in genome coverage and heterozygosity between males and females. FindZX is user-friendly and scalable to suit different computational platforms and works with any number of male and female samples. An option to perform a genome coordinate lift-over to a reference genome of another species allows users to inspect sex-linked regions over larger contiguous chromosome regions, while also providing important between-species synteny information. To demonstrate its effectiveness, we applied findZX to publicly available genomic data from species belonging to widely different taxonomic groups (mammals, birds, reptiles, fish, and insects), with sex chromosome systems of different ages, sizes, and levels of differentiation. We also demonstrate that the lift-over method is robust over large phylogenetic distances (>80 million years of evolution).
A method for independent estimation of false localisation rate for phosphoproteomics
Authors: Ramsbottom Kerry A , Prakash Ananth , Riverol Yasset Perez , Camacho Oscar Martin , Martin Maria , Vizcaíno Juan Antonio , Deutsch Eric W , Jones Andrew R
Published: October 2021

Phosphoproteomics methods are commonly employed in labs to identify and quantify the sites of phosphorylation on proteins. In recent years, various software tools have been developed, incorporating scores or statistics related to whether a given phosphosite has been correctly identified, or to estimate the global false localisation rate (FLR) within a given data set for all sites reported. These scores have generally been calibrated using synthetic data sets, and their statistical reliability on real datasets is largely unknown. As a result, there is considerable problem in the field of reporting incorrectly localised phosphosites, due to inadequate statistical control.

In this work, we develop the concept of using scoring and ranking modifications on a decoy amino acid, i.e. one that cannot be modified, to allow for independent estimation of global FLR. We test a variety of different amino acids to act as the decoy, on both synthetic and real data sets, demonstrating that the amino acid selection can make a substantial difference to the estimated global FLR. We conclude that while several different amino acids might be appropriate, the most reliable FLR results were achieved using alanine and leucine as decoys, although we have a preference for alanine due to the risk of potential confusion between leucine and isoleucine amino acids. We propose that the phosphoproteomics field should adopt the use of a decoy amino acid, so that there is better control of false reporting in the literature, and in public databases that re-distribute the data. Data are available via ProteomeXchange with identifier PXD028840.
GoMi - A new gold standard corpus for miRNA Named Entity Recognition to test dictionary, rule-based and machine-learning approaches
Authors: Frericks-Zipper Anika , Stepath Markus , Schork Karin , Marcus Katrin , Turewicz Michael , Eisenacher Martin
Published: October 2021

Biomarkers have been the focus of research for more than 30 years [REF1]. Paone et al. were among the first scientists to use the term biomarker in the course of a comparative study dealing with breast carcinoma [REF2]. In recent years, in addition to proteins and genes, miRNA or micro RNAs, which play an essential role in gene expression, have gained increased interest as valuable biomarkers. As a result, more and more information on miRNA biomarkers can be extracted via text mining approaches from the increasing amount of scientific literature. In the late 1990s the recognition of specific terms in biomedical texts has become a focus of bioinformatic research to automatically extract knowledge out of the increasing number of publications. For this, amongst other methods, machine learning algorithms are applied. However, the recognition (classification) capability of terms by machine learning or rule based algorithms depends on their correct and reproducible training and development. In the case of machine learning-based algorithms the quality of the available training and test data is crucial. The algorithms have to be tested and trained with curated and trustable data sets, the so-called gold or silver standards. Gold standards are text corpora, which are annotated by expertes, whereby silver standards are curated automatically by other algorithms. Training and calibration of neural networks is based on such corpora. In the literature there are some silver standards with approx. 500,000 tokens [REF3]. Also there are already published gold standards for species, genes, proteins or diseases. However, there is no corpus that has been generated specifically for miRNA. To close this gap, we have generated GoMi, a novel and manually curated gold standard corpus for miRNA. GoMi can be directly used to train ML-methods to calibrate or test different algorithms based on the rule-based approach or dictionary-based approach. The GoMi gold standard corpus was created using publicly available PubMed abstracts.

GoMi can be downloaded here: https://github.com/mpc-bioinformatics/mirnaGS---GoMi.
Trivial Excitation Energy Transfer to Carotenoids is an Unlikely Mechanism for Non-Photochemical Quenching in LHCII
Authors: Gray Callum , Wei Tiejun , Polívka Tomáš , Daskalakis Vangelis , Duffy Christopher D. P.
Published: October 2021

Higher plants defend themselves from bursts of intense light via the mechanism of Non-Photochemical Quenching (NPQ). It involves the Photosystem II (PSII) antenna protein (LHCII) adopting a conformation that favours excitation quenching. In recent years several structural models have suggested that quenching proceeds via energy transfer to the optically forbidden and short-lived S1 states of a carotenoid. It was proposed that this pathway was controlled by subtle changes in the relative orientation of a small number of pigments. However, quantum chemical calculations of S1 properties are not trivial and therefore its energy, oscillator strength and lifetime are treated as rather loose parameters. Moreover, the models were based either on a single LHCII crystal structure or Molecular Dynamics (MD trajectories) about a single minimum. Here we try and address these limitations by parameterizing the vibronic structure and relaxation dynamics of lutein in terms of observable quantities, namely linear absorption (LA) transient absorption (TA) and two-photon excitation (TPE) spectra. We also analyze a number of minima taken from an exhaustive meta-dynamical search of the LHCII potential energy surface. We show that trivial, Coulomb-mediated energy transfer to S1 is an unlikely quenching mechanism. Pigment movements are insufficient to switch the system between quenched and unquenched states. Modulation of S1 energy level as a quenching switch is similarly unlikely. Moreover, the quenching predicted by previous models is likely an artefact of quantum chemical over-estimation of S1 oscillator strength and the real mechanism likely involves non-trivial inter-molecular states.
Human placental bed transcriptomic profiling reveals inflammatory activation of endothelial cells in preeclampsia
Authors: Brouwers Laura , Wienke Judith , Mokry Michal , Nikkels Peter GJ , Vogelvang Tatjana E. , Franx Arie , van Wijk Femke , van Rijn Bas B.
Published: October 2021

Rationale

Functional characteristics of endothelial cells (ECs) within the human placental bed are unknown and may provide insight into the adaptive biology of ECs in disorders of vascular remodelling like preeclampsia.

Objective

To determine transcriptional profiles of human placental bed ECs and systemic biomarker profiles in women with normal pregnancy, and women with preeclampsia, a condition characterized by extensive EC dysfunction, poor development of spiral arteries underlying the placenta and long-term susceptibility to atherosclerosis and hypertension.

Methods & results

We obtained biopsy samples from the uterine placental bed, of five women with preeclampsia with fetal growth restriction (FGR) due to impaired spiral artery development and four controls undergoing Caesarean section. CD31+CD146+ ECs were isolated and sorted by flow cytometry for RNA-sequencing using CEL-Seq2 protocol. Data were analyzed by unsupervised clustering, gene set enrichment (GSEA) and pathway analysis. 67 circulating biomarkers of EC function and inflammation were measured in 20 women with preeclampsia with FGR and 20 controls by multiplex immunoassay. Transcriptional profiling showed various differentially expressed genes (FDR<0.05) in placental bed ECs of preeclampsia patients, with enhanced activity of pathways associated with vasoconstriction, platelet activation and innate immunity. GSEA was suggestive of a VEGF- and PlGF deprived state of preeclampsia-derived ECs. Moreover, the transcriptomic profile was similar to that of human umbilical vein endothelial cells (HUVECs) treated with plasma from preeclampsia patients, pointing towards a central role for circulating factors in EC dysfunction. Unsupervised clustering of subjects by EC-related circulating factors identified distinct profiles for healthy pregnancy and preeclampsia, in particular for those women with low platelets and elevated liver enzymes, which was predominantly driven by sFLT-1, endoglin, PlGF, leptin, SAA-1 and sICAM-1.

Conclusions

We revealed inflammatory activation of EC and a key role for systemic factors in EC dysfunction in women with preeclampsia associated with impaired spiral artery development.
New adaptive peaks for crops – an example from improvement of drought-resilience of sorghum in Ethiopia
Authors: Birhan Techale , Dong Hongxu , Abajebel Nezif , Wakjira Misganu , Lemke Cornelia , Vadez Vincent , Paterson Andrew H. , Bantte Kassahun
Published: October 2021

As the center of diversity for sorghum [Sorghum bicolor (L.) Moench], elite cultivars selected in Ethiopia are of central importance to sub-Saharan food security. Despite being presumably well adapted to their center of diversity, elite Ethiopian sorghums nonetheless experience constraints to productivity, for example associated with shifting rainfall patterns associated with climate change.

A sorghum backcross nested association mapping (BC-NAM) population developed by crossing thirteen diverse lines pre-identified to have various drought resilience mechanisms, with an Ethiopian elite cultivar, Teshale, was tested under three rain-fed environments in Ethiopia.

27, 15, and 15 QTLs with predominantly small additive effects were identified for days to flowering, days to maturity, and plant height, respectively. Many associations detected in this study corresponded closely to known or candidate genes or previously mapped QTLs, supporting their validity. Field tests show drought resilience to be improved by incorporation of adaptations from the diverse donor lines.

The expectation that genotypes such as Teshale from near the center of diversity tend to have a history of strong balancing selection, with novel variations more likely to persist in small marginal populations, was strongly supported in that for these three traits, nearly equal numbers of alleles from the donor lines conferred increases and decreases in phenotype relative to the Teshale allele. Such rich variation provides a foundation for selection to traverse a ‘valley’ of reduced yield and arrive at a new ‘adaptive peak’, exemplifying the nature of efforts that may be necessary to adapt many crops to new climate extremes.

Societal Impact Statement

In Ethiopia, agriculture is the largest economic sector and contributes 48% of the nation’s GDP, and sorghum provides more than one third of the cereal diet and is widely grown for food, feed, brewing, and construction purposes. With a worldwide water crisis looming, developing drought tolerant sorghum is vital in rain-fed environments, particularly in sub-Saharan Africa. Addressing such issues often requires a far-reaching approach to identify and incorporate new traits into a gene pool, followed by a period of selection to re-establish an overall adaptive phenotype. This study revealed that with the enormous altitudinal variation of a country such as Ethiopia, somewhat different lines may be needed for different locales.
Mechanical compressive forces increase PI3K output signaling in breast and pancreatic cancer cells
Authors: Di-Luoffo M. , Schmitter C. , Barrere E.C. , Therville N. , Chaouki M. , D’Angelo R. , Arcucci S. , Thibault B. , Delarue M. , Guillermet-Guibert J.
Published: October 2021

Context

Mechanical stresses, including compression, arise during cancer progression. In solid cancer, especially breast and pancreatic cancers, the rapid tumor growth and the environment remodeling explain their high intensity of compressive forces. However, the sensitivity of compressed cells to targeted therapies remains poorly known.

Results

In breast and pancreatic cancer cells, pharmacological PI3K inactivation decreased cell number and induced apoptosis. These effects were accentuated when we applied 2D compression forces in mechanically responsive cells. Compression selectively induced overexpression of PI3K isoforms and PI3K/AKT pathway activation. Further, transcriptional effects of PI3K inhibition and compression converged to control the expression of an autophagy regulator, GABARAP, which level was inversely associated with PI3K inhibitor sensitivity under compression. Compression alone blocked autophagy flux in all tested cells, while inactivation of basal PI3K activity restored autophagy flux only in mechanically non-responsive compressed cells.

Conclusion

This study provides direct evidence for the role of PI3K/AKT pathway in compression-induced mechanotransduction. PI3K inhibition promotes apoptosis or autophagy, explaining PI3K importance to control cancer cell survival under compression.
The relative speed of the glucorticoid stress response varies independently of scope and is predicted by environmental variability and longevity across birds
Authors: Taff Conor C. , Wingfield John C. , Vitousek Maren N.
Published: October 2021

The acute glucocorticoid response is a key mediator of the coordinated vertebrate response to unpredictable challenges. Rapid glucocorticoid increases initiate changes that allow animals to cope with stressors. The scope of the glucocorticoid response — defined here as the absolute increase in glucocorticoids — is associated with individual differences in performance and varies across species with environment and life history. In addition to varying in scope, responses can differ enormously in speed; however, relatively little is known about whether speed and absolute glucocorticoid levels covary, how selection shapes speed, or what aspects of speed are important. We used corticosterone samples collected at 5 time points from 1,750 individuals of 60 species of birds to ask i) how the speed and scope of the glucocorticoid response covary and ii) whether variation in absolute or relative speed is predicted by environmental context or life history. As predicted by a recent model, faster absolute glucocorticoid responses were strongly associated with a larger scope. Despite this covariation, the relative speed of the glucocorticoid response (standardized within species) varied independently of absolute scope, suggesting that selection could operate on both features independently. Species with faster relative glucocorticoid responses lived in locations with more variable temperature and had shorter lifespans. Our results suggest that rapid changes associated with the speed of the glucocorticoid response, such as those occurring through non-genomic receptors, might be an important determinant of coping ability and we emphasize the need for studies designed to measure speed independently of absolute glucocorticoid levels.