bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative lineage analysis identifies a long-term progenitor niche for the hepato-pancreato-biliary organ system
Authors: Willnow David , Benary Uwe , Margineanu Anca , Vignola Maria Lillina , Pongrac Igor M. , Karimaddini Zahra , Vigilante Alessandra , Wolf Jana , Spagnoli Francesca M.
Published: August 2020

Single cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis1–5.

The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts6, 7. Experimental manipulation of various developmental signals in the mouse embryo underscored an important cellular plasticity in this embryonic territory6, 8. This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder6, 8. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established. Here, we combine computational modelling approaches with genetic lineage tracing to assess the tissue dynamics accompanying the ontogeny of the hepato-pancreato-biliary organ system. We show that a long-term multipotent progenitor domain persists at the border between liver and pancreas, even after pancreatic fate is specified, contributing to the formation of several organ derivatives, including the liver. Moreover, using single-cell RNA sequencing we define a specialized niche that possibly supports such long-term cell fate plasticity.
Nitric Oxide Synthase inhibition counteracts the stress-induced DNA methyltransferase 3b expression in the hippocampus of rats
Authors: de Sousa Maciel Izaque , Sales Amanda Juliana , Casarotto Plinio C , Castrén Eero , Biojone Caroline , Joca Sâmia R. L.
Published: August 2020

It has been postulated that activation of NMDA receptors (NMDAr) and nitric oxide (NO) production in the hippocampus is involved in the behavioral consequences of stress. Stress triggers NMDAr-induced calcium influx in limbic areas, such as the hippocampus, which in turn activates neuronal NO synthase (nNOS). Inhibition of nNOS or NMDAr activity can prevent stress-induced effects in animal models, but the molecular mechanisms behind this effect are still unclear. In this study, cultured hippocampal neurons treated with NMDA or dexamethasone showed increased of DNA methyltransferase 3b (DNMT3b) mRNA expression, which was blocked by pre-treatment with nNOS inhibitor nω-propyl-L-arginine (NPA). In rats submitted to the Learned Helplessness paradigm (LH), we observed that inescapable stress increased of DNMT3b mRNA expression at 1h and 24h in the hippocampus. The NOS inhibitors 7-NI and aminoguanidine (AMG) decreased the number of escape failures in LH, and counteracted the changes in hippocampal DNMT3b mRNA induced in this behavioral paradigm. Altogether, our data suggest that NO produced in response to NMDAr activation following stress upregulates DNMT3b in the hippocampus.
Performance of an automated anti-SARS-CoV-2 immunoassay in prepandemic cohorts
Authors: Riester Elena , Krieter Beda , Findeisen Peter , Laimighofer Michael , Schoenfeld Kathrin , Laengin Tina , Niederhauser Christoph
Published: August 2020

Background

The Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide an accurate and reliable method for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the specificity of the Elecsys Anti-SARS-CoV-2 immunoassay in prepandemic sample cohorts across five sites in Germany, Austria and Switzerland.

Methods

Specificity of the immunoassay was evaluated using anonymised, frozen, residual serum and/or plasma samples from blood donors or routine diagnostic testing. All samples were collected before September 2019 and therefore presumed negative for SARS-CoV-2-specific antibodies. Cohorts included samples from blood donors, pregnant women and paediatric patients. Point estimates and 95% confidence intervals (CIs) were calculated.

Results

Overall specificities for the Elecsys Anti-SARS-CoV-2 immunoassay in 9575 samples from blood donors (n = 6714) and diagnostic specimens (n = 2861) were 99.82% (95% CI 99.69-99.91) and 99.93% (95% CI 99.75-99.99), respectively. Among 2256 samples from pregnant women, specificity was 99.91% (95% CI 99.68-99.99). Among 205 paediatric samples, specificity was 100% (95% CI 98.22-100).

Conclusion

The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated a very high specificity across blood donor samples and diagnostic specimens from Germany, Austria and Switzerland. Our findings support the use of the Elecsys Anti-SARS-CoV-2 immunoassay as a potential tool for determination of an immune response following previous exposure to SARS-CoV-2 in the general population, including in blood donors, pregnant women and paediatric populations.
(Z)-N′-[(E)-4-Methoxybenzylidene]-2-(methoxyimino)-2-{2-[(2-methylphenoxy)methyl]phenyl}acetohydrazide
Authors: Shripanavar Chetan Shrimandhar , Butcher Ray J.
Published: August 2020

The title compound, C25H25N3O4, crystallizes with two molecules in the asymmetric unit. In both molecules, the central ethane hydrazide moiety is almost planar. In the crystal, asymmetric, bifurcated N—H...(N,O) hydrogen bonds link the molecules into [100] chains. The packing is consolidated by weak C—H...O interactions.
System identification of flybar-less rotorcraft UAV
Authors: T.K. Khadeeja Nusrath , V.P. Lulu , Singh Jatinder
Published: August 2020

Purpose

This paper aims to build an accurate mathematical model which is necessary for control design and attitude estimation of a miniature unmanned rotorcraft and its subsequent conversion to an autonomous vehicle.

Design/methodology/approach

Frequency-domain system identification of a small-size flybar-less remote controlled helicopter is carried out based on the input–output data collected from flight tests of the instrumented vehicle. A complete six degrees of freedom quasi-steady dynamic model is derived for hover and cruise flight conditions.

Findings

The veracity of the developed model is ascertained by comparing the predicted model responses to the actual responses from flight experiments and from statistical measures. Dynamic stability analysis of the vehicle is carried out using eigenvalues and eigenvectors. The identified model represents the vehicle dynamics very well in the frequency range of interest.

Research limitations/implications

The model needs to be augmented with additional terms to represent the high-frequency dynamics of the vehicle.

Practical implications

Control algorithms developed using the first principles model can be easily reconfigured using the identified model, because the model structure is not altered during identification.

Originality/value

This paper gives a practical solution for model identification and stability analysis of a small-scale flybar-less helicopter. The estimated model can be easily used in developing control algorithms.
Black lives matter…still: moving beyond acknowledging the problem toward effective solutions in graduate training and education
Authors: Thomas Kecia , Ashburn-Nardo Leslie
Published: August 2020

Purpose

The aim of the study is to revisit the importance of Black Lives Matter (BLM) and to encourage more attention to White supremacy in the academy, especially with regards to the development and mentoring of graduate students.

Design/methodology/approach

The study reflects on the urgency of the BLM movement given the death of George Floyd and others.

Findings

The article highlights the ways in which the training and development of graduate students can reinforce systems of exclusion and marginalization while reinforcing existing systems of privilege and the status quo. The essay concludes with recommendations for creating greater systems of inclusion for programs, departments and higher education institutions.

Practical implications

Recommendations are given to initiate culture change.

Originality/value

This is a follow-up to the 2017 special issue.
The influence of soldering process parameters on the optical and thermal properties of power LEDs
Authors: Ptak Przemysław , Górecki Krzysztof , Skwarek Agata , Witek Krzysztof , Tarasiuk Jacek
Published: August 2020

Purpose

This paper aims to present the results of investigations that show the influence of soldering process parameters on the optical and thermal parameters of power LEDs.

Design/methodology/approach

The power LEDs were soldered onto metal core printed circuit board (MCPCB) substrates in different soldering ovens: batch and tunnel types, characterized by different thermal profiles. Three types of solder pastes based on Sn99Ag0.3Cu0.7 with the addition of TiO2 were used. The thermal and optical parameters of the diodes were measured using classical indirect electrical methods. The results of measurements obtained were compared and discussed.

Findings

It was shown that the type of oven and soldering thermal profile considerably influence the effectiveness of the removal of heat generated in the LEDs tested. This influence is characterized by thermal resistance changes. The differences between the values of this parameter can exceed 20%. This value also depends on the composition of the soldering paste. The differences between the diodes tested can exceed 15%. It was also shown that the luminous flux emitted by the diode depends on the soldering process used.

Practical implications

The results obtained could be useful for process design engineers for assembling power LEDs for MCPCBs and for designers of solid-state light sources.

Originality/value

This paper presents the results of investigations into the influence of the soldering profiles and soldering pastes used on the effectiveness of the removal of heat generated in power LEDs. It shows and discusses how the factors mentioned above influence the thermal resistance of the LEDs and optical parameters that characterize the light emitted.
Shifts in ectomycorrhizal exploration types parallel leaf and fine root area with forest age
Authors: Wasyliw Joshua , Karst Justine
Published: August 2020

The abundance of fine roots and leaves in forests typically peaks during mid‐succession and then declines. If fine root area declines more rapidly than leaf area, this could contribute disproportionately to stand decline. However, trees also partner with symbiotic ectomycorrhizal (EcM) fungi that facilitate nutrient acquisition of fine roots. Ectomycorrhizal fungi can use the carbohydrates provided by their plant partners to produce emanating fungal tissues which increase soil exploration potential but may also prove costly. We suggest two competing hypotheses to frame the response of ectomycorrhizas to stand age: (a) the ‘functional offset’ hypothesis posits that the abundance of ectomycorrhizas with emanating tissues (‘Distance’ mycorrhizas) increases with stand age and (b) the ‘energy‐limited’ hypothesis posits that carbon available for root symbionts decreases with stand age resulting in fewer Distance mycorrhizas. In the first hypothesis, EcM functional traits offset root abundance, while in the second, traits parallel root abundance.

To test these competing hypotheses, we sampled fine roots to a depth of 90 cm and used allometric equations to estimate changes in root and leaf area index across a chronosequence of Pinus banksiana stands ranging from 2 to 76 years average tree age. We also examined fine roots microscopically to track changes in the abundance of EcM functional types. We used DNA‐based methods to sequence EcM fungi and confirm roots were of P. banksiana.

Both fine root and leaf area of pine increased for the first 30–36 years (until Mid age) and then plateaued, while the ratio of leaf to fine root area was similar across the age gradient. Also, changes to fine root area with stand age depended on soil depth. The abundance of Distance mycorrhizas was lowest at the youngest plots and increased until Mid age, where it peaked, contrary to the functional offset hypothesis. Instead, the abundance of Distance mycorrhizas paralleled changes to leaf area, aligned with the energy‐limited hypothesis.

Synthesis. Ectomycorrhizas do not offset the function of roots, rather shifts in exploration type likely reflect adjustments to carbon supply from hosts.
Off‐label prescribing of stimulant medication to students: a qualitative study on the general practitioner perspective
Authors: De Bruyn Sara , Wouters Edwin , Ponnet Koen , Tholen Robert , Masquillier Caroline , Remmen Roy , Van Hal Guido
Published: August 2020

Students’ use of prescription stimulants to enhance study performance is increasingly under the spotlight. Medical guidelines discourage general practitioners (GPs) from prescribing stimulants to students without a diagnosis; yet a considerable proportion of students acquire them from GPs. Building on Eisenberg’s theoretical framework on clinical decision‐making and Conrad’s sociological concept of biomedical enhancement, this study examined the social context of GPs’ off‐label prescribing decisions for stimulants, using data from 21 semi‐structured interviews, including vignettes, undertaken with Flemish GPs. Results identified two groups of GPs: (1) hard‐liners who strictly follow medical guidelines and who would only prescribe in case of an appropriate diagnosis and (2) context‐dependent GPs who would prescribe stimulants depending on the patients’ symptoms and extent of need. GPs’ decisions depend on one‐on‐one doctor‐patient interactions (i.e. the extent of empathy from the doctor and the extent of assertiveness from the patient); the extent to which GPs define concentration problems as medical problems; GPs’ interactions with fellow health care workers; as well as GPs’ interaction with the wider community. By disentangling these influences, this paper advances both theoretical and practical understanding of the sociological context in which GPs’ off‐label prescribing behaviour occurs.
Primers to highly conserved elements optimized for qPCR‐based telomere length measurement in vertebrates
Authors: Hudon Stephanie F. , Palencia Hurtado Esteban , Beck James D. , Burden Steven J. , Bendixsen Devin P. , Callery Kathleen R. , Sorensen Forbey Jennifer , Waits Lisette P. , Miller Robert A. , Nielsen Ólafur K. , Heath Julie A. , Hayden Eric J.
Published: August 2020

Telomere length dynamics are an established biomarker of health and ageing in animals. The study of telomeres in numerous species has been facilitated by methods to measure telomere length by real‐time quantitative PCR (qPCR). In this method, telomere length is determined by quantifying the amount of telomeric DNA repeats in a sample and normalizing this to the total amount of genomic DNA. This normalization requires the development of genomic reference primers suitable for qPCR, which remains challenging in nonmodel organism with genomes that have not been sequenced. Here we report reference primers that can be used in qPCR to measure telomere lengths in any vertebrate species. We designed primer pairs to amplify genetic elements that are highly conserved between evolutionarily distant taxa and tested them in species that span the vertebrate tree of life. We report five primer pairs that meet the specificity and reproducibility standards of qPCR. In addition, we demonstrate an approach to choose the best primers for a given species by testing the primers on multiple individuals within a species and then applying an established computational tool. These reference primers can facilitate qPCR‐based telomere length measurements in any vertebrate species of ecological or economic interest.
Meta‐analysis of differentially expressed microRNAs in systemic sclerosis
Authors: Zhang Lian , Wu Haijing , Zhao Ming , Lu Qianjin
Published: August 2020

Objective

Emerging evidence suggests a possible role of microRNAs (miRNAs) that can regulate gene expression in the pathogenesis of systemic sclerosis (SSc). However, contradictory results have been reported on miRNA expression in SSc. We performed a meta‐analysis to identify the consistently differentially expressed miRNAs in SSc across studies.

Methods

We performed a systematic search in PubMed using the terms “microRNAs OR Circulating MicroRNA OR miRNAs” AND “systemic sclerosis OR systemic scleroderma” to identify full‐text English publications until 1 August, 2019. After quality assessment using Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2), we utilized RevMan 5.3 and Meta‐Disc 1.4 to assess heterogeneity (I2 index and Q test P values) and perform effect size modeling.

Results

From 120 publications in the initial search, 16 studies on miRNA expression profiles in blood and/or dermal fibroblasts were selected after publication screening. The median number of samples in these studies was 36 (interquartile range 19‐59, range 10‐119). Meta‐analysis revealed 8 differentially expressed miRNAs, of which miR‐21 in blood, miR‐29a, miR‐155, and miR‐196a in dermal fibroblasts, and let‐7a in both serum and dermal fibroblast samples were most consistent across studies. These miRNAs have been implicated in immune activation, vascular damage, and fibroblast activation, which could potentially lead to the overproduction of collagen and extracellular protein.

Conclusion

Studies of miRNA expression in SSc are limited and have used a relatively small number of samples. A meta‐analysis of these reports reveals a cluster of differentially expressed miRNAs implicated in immune activation, vascular damage, and fibroblast activation that could play roles in SSc pathogenesis and serve as potential biomarkers.
Treatment and toxic effects of prophylactic cranial irradiation in stage II–III non–small cell lung cancer: A meta‐analysis
Authors: Li Meng , Wang Taifang , Wen Ping , Wang Xiang , Wu Chunli
Published: August 2020

Objective

To determine the role of prophylactic cranial irradiation (PCI) in non–small cell lung cancer (NSCLC) patients using meta‐analysis.

Methods

PubMed, Embase, the Cochrane Database of Systematic Review and the China National Knowledge Infrastructure databases were systematically searched for studies published between 1 January 1980 and 31 March 2019. Search terms included “non–small cell lung cancer,” “prophylactic cranial irradiation” and “clinical trials.” The research data extracted from above studies was analyzed by Review Manager 5.3 and Stata12.0 software. The outcomes included development of brain metastases (BMs), overall survival (OS), disease‐free survival (DFS), BMs for different diagnoses, toxicity, quality of life (QoL).

Results

Fifteen trials (nine RCTs and six non‐RCTs) involving 2418 NSCLC patients met the inclusion criteria. There was a significant reduction in the risk of developing BM in patients who received PCI compared with those who did not (95% CI, 0.20–0.37; P < 0.00001). PCI significantly reduced the BM of squamous cell carcinoma (P = 0.02), but not for adenocarcinoma (P = 0.07) and other pathological types (P = 0.29). There was a significant increase in DFS for the PCI compared to the non‐PCI group (P = 0.006); however, OS did not significantly differ (P = 0.15). In addition, fatigue significantly increased in the PCI group (P = 0.0002). Cognitive disturbance showed no significant difference between PCI and non‐PCI groups (P = 0.06).

Conclusion

This study showed that, compared with non‐PCI, PCI significantly decreased the incidence of NSCLC BM and improved the DFS of patients, and reduced the BM rate from squamous cell carcinoma. However, it showed no effect on OS and the BM rate of adenocarcinoma and other pathological types of tumors. There were limited data concerning PCI‐related toxicity and QoL.
Cognitive and behavioural strategies employed to overcome “lapses” and prevent “relapse” among weight‐loss maintainers and regainers: A qualitative study
Authors: Lawlor Emma R , Hughes Carly A , Duschinsky Robbie , Pountain Gillian D , Hill Andrew J , Griffin Simon J , Ahern Amy L
Published: August 2020

While many behavioural weight management programmes are effective in the short‐term, post‐programme weight regain is common. Overcoming “lapses” and preventing “relapse” has been highlighted as important in weight‐loss maintenance, but little is known on how this is achieved. This study aimed to compare the cognitive and behavioural strategies employed to overcome “lapses” and prevent “relapse” by people who had regained weight or maintained weight‐loss after participating in a weight management programme. By investigating differences between groups, we intended to identify strategies associated with better weight‐loss maintenance. Semi‐structured interviews were conducted with 26 participants (58% female) recruited from the 5‐year follow‐up of the Weight Loss Referrals for Adults in Primary Care (WRAP) trial (evaluation of a commercial weight‐loss programme). Participants who had lost ≥5% baseline weight during the active intervention were purposively sampled according to 5‐year weight trajectories (n = 16 'Regainers', n = 10 'Maintainers'). Interviews were audio‐recorded, transcribed verbatim, and analysed thematically. Key differences in strategies were that Maintainers continued to pay attention to their dietary intake, anticipated and planned for potential lapses in high‐risk situations, and managed impulses using distraction techniques. Regainers did not report making plans, used relaxed dietary monitoring, found distraction techniques to be ineffective and appeared to have difficulty navigating food within interpersonal relationships. This study is one of the longest qualitative follow‐ups of a weight loss trial to date, offering unique insights into long‐term maintenance. Future programmes should emphasize strategies focusing on self‐monitoring, planning and managing interpersonal relationships to help participants successfully maintain weight‐loss in the longer‐term.
COVID‐19 and immunological regulations – from basic and translational aspects to clinical implications
Authors: Schön Michael P. , Berking Carola , Biedermann Tilo , Buhl Timo , Erpenbeck Luise , Eyerich Kilian , Eyerich Stefanie , Ghoreschi Kamran , Goebeler Matthias , Ludwig Ralf J. , Schäkel Knut , Schilling Bastian , Schlapbach Christoph , Stary Georg , von Stebut Esther , Steinbrink Kerstin
Published: August 2020

The COVID‐19 pandemic caused by SARS‐CoV‐2 has far‐reaching direct and indirect medical consequences. These include both the course and treatment of diseases. It is becoming increasingly clear that infections with SARS‐CoV‐2 can cause considerable immunological alterations, which particularly also affect pathogenetically and/or therapeutically relevant factors.

Against this background we summarize here the current state of knowledge on the interaction of SARS‐CoV‐2/COVID‐19 with mediators of the acute phase of inflammation (TNF, IL‐1, IL‐6), type 1 and type 17 immune responses (IL‐12, IL‐23, IL‐17, IL‐36), type 2 immune reactions (IL‐4, IL‐13, IL‐5, IL‐31, IgE), B‐cell immunity, checkpoint regulators (PD‐1, PD‐L1, CTLA4), and orally druggable signaling pathways (JAK, PDE4, calcineurin). In addition, we discuss in this context non‐specific immune modulation by glucocorticosteroids, methotrexate, antimalarial drugs, azathioprine, dapsone, mycophenolate mofetil and fumaric acid esters, as well as neutrophil granulocyte‐mediated innate immune mechanisms.

From these recent findings we derive possible implications for the therapeutic modulation of said immunological mechanisms in connection with SARS‐CoV‐2/COVID‐19. Although, of course, the greatest care should be taken with patients with immunologically mediated diseases or immunomodulating therapies, it appears that many treatments can also be carried out during the COVID‐19 pandemic; some even appear to alleviate COVID‐19.
Y‐chromosome haplotypes are associated with variation in size and age at maturity in male Chinook salmon
Authors: McKinney Garrett J. , Seeb James E. , Pascal Carita E. , Schindler Daniel E. , Gilk‐Baumer Sara E. , Seeb Lisa W.
Published: August 2020

Variation in size and age at maturity is an important component of life history that is influenced by both environmental and genetic factors. In salmonids, large size confers a direct reproductive advantage through increased fecundity and egg quality in females, while larger males gain a reproductive advantage by monopolizing access to females. In addition, variation in size and age at maturity in males can be associated with different reproductive strategies; younger smaller males may gain reproductive success by sneaking among mating pairs. In both sexes, there is a trade‐off between older age and increased reproductive success and increased risk of mortality by delaying reproduction. We identified four Y‐chromosome haplogroups that showed regional‐ and population‐specific variation in frequency using RADseq data for 21 populations of Alaska Chinook salmon. We then characterized the range‐wide distribution of these haplogroups using GT‐seq assays. These haplogroups exhibited associations with size at maturity in multiple populations, suggesting that lack of recombination between X and Y‐chromosomes has allowed Y‐chromosome haplogroups to capture different alleles that influence size at maturity. Ultimately, conservation of life history diversity in Chinook salmon may require conservation of Y‐chromosome haplotype diversity.
Quantifying cellular forces: Practical considerations of traction force microscopy for dermal fibroblasts
Authors: De La Pena Abigail , Mukhtar Marah , Yokosawa Ryosuke , Carrasquilla Santiago , Simmons Chelsey S.
Published: August 2020

Traction force microscopy (TFM) is a well‐established technique traditionally used by biophysicists to quantify the forces adherent biological cells exert on their microenvironment. As image processing software becomes increasingly user‐friendly, TFM is being adopted by broader audiences to quantify contractility of (myo)fibroblasts. While many technical reviews of TFM’s computational mechanics are available, this review focuses on practical experimental considerations for dermatology researchers new to cell mechanics and TFM who may wish to implement a higher throughput and less expensive alternative to collagen compaction assays. Here, we describe implementation of experimental methods, analysis using open‐source software and troubleshooting of common issues to enable researchers to leverage TFM for their investigations into skin fibroblasts.
Red king crab larval advection in Bristol Bay: Implications for recruitment variability
Authors: Daly Benjamin , Parada Carolina , Loher Timothy , Hinckley Sarah , Hermann Albert J. , Armstrong David
Published: August 2020

Recruitment variability is poorly understood for Bering Sea crab stocks. The nearshore area in southwest Bristol Bay (Alaska, USA) is hypothesized as having historically (i.e., prior to ~ 1980) been the most important spawning ground for Bristol Bay red king crab (Paralithodes camtschaticus) because post‐larvae are thought to have been most likely to reach optimal settlement habitat along the Alaska Peninsula when hatched from this area as part of an endless‐belt reproductive strategy. We coupled a biophysical and oceanographic circulation model to test this hypothesis, investigate larval connectivity of more recent female spatial distributions, and evaluate the importance of climate variability on larval advection trajectories. Predicted settlement success varied through changes in larval pelagic duration and oceanographic circulation patterns: Shorter advective distance was associated with warmer conditions, causing higher rates of local retention relative to cold conditions. Contrary to earlier models, most larvae hatched in southwest Bristol Bay were advected offshore away from good habitat, whereas larvae hatched in central and nearshore Bristol Bay were retained in or advected to good habitat along the Alaska Peninsula. Our results suggest contemporary spatial distributions can supply settlement‐competent larvae to nurseries along the Alaska Peninsula and that under certain conditions, larvae may reach the Pribilof Islands when hatched from southwest Bristol Bay. Our study informs the role of environmental variability on larval transport and provides context within which to structure future investigations of recruitment mechanisms.
Associations of DXA‐measured abdominal adiposity with cardio‐metabolic risk and related markers in early adolescence in Project Viva
Authors: Wu Allison J. , Rifas‐Shiman Sheryl L. , Taveras Elsie M. , Oken Emily , Hivert Marie‐France
Published: August 2020

Background

Increased visceral adipose tissue (VAT) precedes development of insulin resistance and dyslipidemia in adults. The associations of abdominal adiposity derived from dual‐energy X‐ray absorptiometry (DXA), including VAT, subcutaneous abdominal adipose tissue (SAAT) and total abdominal adipose tissue (TAAT) with cardio‐metabolic risk in adolescents are understudied.

Objectives

We examined the cross‐sectional associations of DXA‐measured abdominal adiposity with cardio‐metabolic risk and related markers in early adolescence (mean [SD] age 13.0 [0.7] years).

Methods

We collected data from 740 adolescents (374 girls and 366 boys) in Project Viva, a U.S. pre‐birth cohort. We used DXA estimates of VAT, SAAT and TAAT area. We conducted overall and sex‐stratified linear regression models, adjusting for age, sex (in overall models), race/ethnicity, puberty score and body mass index (BMI) z‐score.

Results

Mean BMI z‐score was 0.59 (1.28). After adjustment, greater VAT (per 1 SD score) was associated with higher metabolic risk z‐score (β 0.14 units; 95% CI 0.08, 0.20), higher log high‐sensitivity C‐reactive protein (β 0.51 mg/L; 0.36, 0.66) and log leptin (β 0.36 ng/mL; 0.27, 0.44), and lower log adiponectin (β −0.08 ug/mL; −0.13, −0.02). SAAT and TAAT showed similar associations as VAT with comparable or greater effect sizes.

Conclusion

In early adolescence, DXA‐measured VAT, SAAT and TAAT are associated with cardio‐metabolic risk and related markers, independent of current BMI. Among two adolescents with the same BMI, there is an associated higher cardio‐metabolic risk in the adolescent with greater DXA‐measured abdominal adiposity.
Science and art of anticancer drug dosing: nine steps to personalised therapy
Authors: Ackland Stephen P. , Michael Michael , de Souza Paul , Martin Jennifer H. , Clarke Stephen J. , Francis Kay , Karapetis Christos S. , Gurney Howard
Published: August 2020

Cancer medicine is a challenging field with an increasing range of promising therapies and combinations. Increasingly, personalised medicine shows promise to improve cancer outcomes – response, symptom control, survival and cure. However, optimal dosing is an under‐appreciated aspect of personalised anticancer therapy, with few clinical trials addressing this specific issue. This position paper aims to inform various health professionals about the principles that guide anticancer drug dose selection and modifications. We discuss the available evidence base for personalised dosing, as well as the professional judgement required by experienced oncology physicians to determine the most appropriate dose for each patient. We provide nine steps to guide clinicians and trainees in this process, based on: pharmacology of each agent (absorption, distribution, metabolism, elimination and mechanism of action); scientific evidence for recommended doses; professional knowledge of patients' unique phenotype (adiposity, comorbidities, etc.); previous drug tolerance; individual dose adjustment in combination therapy; communication and documentation, with the added need for ongoing monitoring and adjustment. We strongly propose professional education and future research towards optimal dosing.
What came first, the virus or the egg: Innate immunity during viral coinfections
Authors: Rippee‐Brooks Meagan D. , Marcinczyk Riley N. , Lupfer Christopher R.
Published: August 2020

Infections with any pathogen can be severe and present with numerous complications caused by the pathogen or the host immune response to the invading microbe. However, coinfections, also called polymicrobial infections or secondary infections, can further exacerbate disease. Coinfections are more common than is often appreciated. In this review, we focus specifically on coinfections between viruses and other viruses, bacteria, parasites, or fungi. Importantly, innate immune signaling and innate immune cells that facilitate clearance of the initial viral infection can affect host susceptibility to coinfections. Understanding these immune imbalances may facilitate better diagnosis, prevention, and treatment of such coinfections.
Horses for courses? Assessing the potential value of a surrogate, point‐of‐care test for SARS‐CoV‐2 epidemic control
Authors: Ismail Sharif A. , Huntley Catherine , Post Nathan , Rigby Samuel , Shrotri Madhumita , Williams Sarah V. , Peacock Sharon J.
Published: August 2020

Point‐of‐care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID‐19 by providing timely information to guide decision‐making, but data on real‐world performance are in short supply. Besides SARS‐CoV‐2‐specific tests, there is growing interest in the role of surrogate (non‐specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza‐like illnesses. This short report assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS‐CoV‐2‐specific POCTs. While FebriDx shows some potential in supporting triage for early‐stage infection in acute care settings, this is dependent on SARS‐CoV‐2 being the most likely cause for influenza‐like illnesses, with reduction in discriminatory power when COVID‐19 case numbers are low, and when co‐circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts, and further evaluation is needed. Reliable SARS CoV2‐specific POCTs—when they become available—are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide.
“Tomorrow, I’ll Be Fine”: Impacts and coping mechanisms in adolescents and young adults with primary dysmenorrhoea
Authors: Allyn Katherine , Evans Subhadra , Seidman Laura C. , Payne Laura A.
Published: August 2020

Aims

To understand the experiences of adolescents and young adults with primary dysmenorrhoea through the lens of structured frameworks extant in contemporary pain literature.

Design

Descriptive qualitative study.

Methods

Thirty‐nine adolescents and young adults (ages 16–24 years) with primary dysmenorrhoea participated in semi‐structured in‐person interviews. Transcripts of the interviews were analysed using deductive thematic analysis from November 2018 to April 2019.

Results

Two overarching themes, each with subthemes, were identified. The first theme, primary dysmenorrhoea impacts the whole person, contained the following subthemes: biological, social, and psychological. The second theme, coping mechanisms of women with primary dysmenorrhoea, contained the following subthemes: primary, secondary, and passive coping.

Conclusion

Women experience several primary dysmenorrhoea‐related impacts on their biological, social, and psychological functioning. Women employ a variety of coping mechanisms to manage their primary dysmenorrhoea pain.

Impact

This study emphasizes the significant effects of primary dysmenorrhoea on nearly every aspect of women's lives and contributes to an understanding of the ways women cope with this pain. The findings of this study underscore the need for continued consideration of primary dysmenorrhoea as a debilitating pain process as well as the need for additional interventions to help women manage this condition.
Genetic parameter estimation and gene association analyses for meat quality traits in open‐air free‐range Iberian pigs
Authors: Fernández‐Barroso Miguel Á. , Silió Luis , Rodríguez Carmen , Palma‐Granados Patricia , López Adrián , Caraballo Carmen , Sánchez‐Esquiliche Fernando , Gómez‐Carballar Fernando , García‐Casco Juan M. , Muñoz María
Published: August 2020

Meat quality of Iberian pigs is defined by the combination of their genetic characteristics and the particular production system. To carry out a genetic analysis of the main meat quality traits, we estimated their heritabilities, genetic correlations and the association effects of 32 selected SNPs of 12 candidate genes. A total of ten traits were measured in longissimus dorsi samples from 1,199 Iberian pigs fattened in the traditional free‐range system: water holding capacity (thawing, cooking and centrifuge force water losses), instrumental colour (lightness L*, redness a* and yellowness b*), myoglobin content, shear force on cooked meat, and shear force and maximum compression force on dry‐cured loin. Estimated heritability values were low to moderate (0.01 to 0.43) being the lowest for L* and the highest for cooking loss. Strong genetic correlations between water holding capacity traits (0.93 to 0.96) and between myoglobin content and a* (0.94) were observed. The association analyses revealed 19 SNPs significantly associated with different traits. Consistent and strong effects were observed between PRKAG3 SNPs (rs319678464G > C and rs330427832C > T), MYH3_rs81437544T > C, CASP3_rs319658214G > T and CTSL_rs332171512A > G and water losses. Also for CAPN1_rs81358667G > A and CASP3_rs319658214G > T and shear force. The SNPs mapping on PRKAG3 showed the highest effects on Minolta colour traits. Genotyping of these SNPs could be useful for the selection of Iberian young boars with similar estimated breeding values for productive traits.
Optimal blood pressure for the prevention of hypertensive nephropathy in nondiabetic hypertensive patients in Taiwan
Authors: Kao Ting‐Wei , Huang Chin‐Chou , Chen Jaw‐Wen
Published: August 2020

Hypertension is a global health burden. However, clinical reference for the adequate management of blood pressure (BP) to prevent renal injury has yet to be established. Thus, this study aimed to investigate whether optimal control and maintenance of BP at < 140/90, < 130/80, or < 120/70 mmHg could prevent hypertensive nephropathy in nondiabetic hypertensive patients. A single‐center observational study of 351 nondiabetic hypertensive patients was conducted in Taiwan. The average age of the participants was 64.0 years, and approximately 57.8% of the participants were men. Kidney function was assessed using estimated glomerular filtration rate (eGFR). The baseline eGFR was 83.8 ± 19.8 mL/min/1.73 m2. All patients were followed up every 3 months and underwent office BP measurement and blood sampling. Renal events were defined as> 25% and> 50% decline in eGFR. During an average follow‐up period of 4.2 ± 2.3 years, a> 25% and> 50% decline in eGFR was noted in 49 and 11 patients, respectively. The Cox regression analysis revealed that a baseline BP ≥ 140/90 mmHg (hazard ratio [HR]: 1.965; 95% confidence interval [CI]: 1.099–3.514, P = 0.023) and ≥ 130/80 mmHg (HR: 2.799; 95% CI: 1.286–6.004, P = 0.009) increased the risk of> 25% decline in eGFR. Moreover, a baseline BP ≥ 140/90 mmHg (HR: 8.120; 95% CI: 1.650–39.956, P = 0.010) and follow‐up BP ≥ 140/90 mmHg (HR: 6.402; 95% CI: 1.338–30.637, P = 0.020) increased the risk of> 50% decline in eGFR. In conclusion, a stringent baseline BP < 130/80 mmHg and a follow‐up BP < 140/90 mmHg can be considered optimal cutoff values for clinical practice to prevent hypertensive nephropathy.
Chronopharmacology of simvastatin on hyperlipidaemia in high‐fat diet‐fed obese mice
Authors: Li Huan , Rabearivony Anjara , Zhang Wenxiang , Chen Siyu , An Xiaofei , Liu Chang
Published: August 2020

The chronopharmacology refers to the utilization of physiological circadian rhythms to optimize the administration time of drugs, thus increasing their efficacy and safety, or reducing adverse effects. Simvastatin is one of the most widely prescribed drugs for the treatment of hypercholesterolaemia, hyperlipidemia and coronary artery disease. There are conflicting statements regarding the timing of simvastatin administration, and convincing experimental evidence remains unavailable. Thus, we aimed to examine whether different administration times would influence the efficacy of simvastatin. High‐fat diet‐fed mice were treated with simvastatin at zeitgeber time 1 (ZT1) or ZT13, respectively, for nine weeks. Simvastatin showed robust anti‐hypercholesterolaemia and anti‐hyperlipidemia effects on these obese mice, regardless of administration time. However, simvastatin administrated at ZT13, compared to ZT1, was more functional for decreasing serum levels of total cholesterol, triglycerides, non‐esterified free fatty acids and LDL cholesterol, as well as improving liver pathological characteristics. In terms of possible mechanisms, we found that simvastatin did not alter the expression of hepatic circadian clock gene in vivo, although it failed to change the period, phase and amplitude of oscillation patterns in Per2::Luc U2OS and Bmal1::Luc U2OS cells in vitro. In contrast, simvastatin regulated the expression of Hmgcr, Mdr1 and Slco2b1 in a circadian manner, which potentially contributed to the chronopharmacological function of the drug. Taken together, we provide solid evidence to suggest that different administration times affect the lipid‐lowering effects of simvastatin.
Determining the minimal important difference of the Oral Health Impact Profile for Chronic Periodontitis
Authors: He Song‐lin , Hou Hai‐juan , Wang Jin‐hua
Published: August 2020

Aim

Building on previous psychometric work, we aimed to further assess the minimally important difference (MID) of the Oral Health Impact Profile for Chronic Periodontitis (OHIP‐CP).

Methods

In total, 240 consecutive patients with chronic periodontitis were recruited in the study. The OHIP‐CP was completed at baseline and after six weeks. Methodology testing included the confirmatory factor analysis (CFA) and MID. Confirmatory factor analysis (CFA) was performed to assess the fit of the previously proposed three‐factor model. The MID of this questionnaire was determined by applying anchor‐based and distribution‐based approaches.

Results

The CFA supported a three‐factor model for the OHIP‐CP with acceptable fit to the data. The fit indices were χ2/df = 2.231, GFI = 0.935, TLI = 0.969 and CFI = 0.976, RMSEA = 0.076. The OHIP‐CP scores showed significant improvements after treatment (p < .001). The anchor‐based MIDs of OHIP‐CP for “oral function restriction,” “oral pain” and “psychological and social impact,” and total score were 2, 1, 4 and 7 points, respectively. The effect sizes (ES) and standardized response mean (SRM) for the OHIP‐CP were moderate to large.

Conclusions

The MID of the OHIP‐CP is recommended for interpreting clinically meaningful change in oral health‐related quality of life (OHRQoL) over time.
ABNORMAL SHOOT 6 interacts with KATANIN 1 and SHADE AVOIDANCE 4 to promote cortical microtubule severing and ordering in Arabidopsis
Authors: Li Yuanfeng , Deng Meng , Liu Haofeng , Li Yan , Chen Yu , Jia Min , Xue Hui , Shao Jingxia , Zhao Jun , Qi Yafei , An Lijun , Yu Fei , Liu Xiayan
Published: August 2020

Plant interphase cortical microtubules (cMTs) mediate anisotropic cell expansion in response to environmental and developmental cues. In Arabidopsis thaliana, KATANIN 1 (KTN1), the p60 catalytic subunit of the conserved MT‐severing enzyme katanin, is essential for cMT ordering and anisotropic cell expansion. However, the regulation of KTN1‐mediated cMT severing and ordering remains unclear. In this work, we report that the Arabidopsis IQ67 DOMAIN (IQD) family gene ABNORMAL SHOOT 6 (ABS6) encodes a MT‐associated protein. Overexpression of ABS6 leads to elongated cotyledons, directional pavement cell expansion, and highly ordered transverse cMT arrays. Genetic suppressor analysis revealed that ABS6‐mediated cMT ordering is dependent on KTN1 and SHADE AVOIDANCE 4 (SAV4). Live imaging of cMT dynamics showed that both ABS6 and SAV4 function as positive regulators of cMT severing. Furthermore, ABS6 directly interacts with KTN1 and SAV4 and promotes their recruitment to the cMTs. Finally, analysis of loss‐of‐function mutant combinations showed that ABS6, SAV4, and KTN1 work together to ensure the robust ethylene response in the apical hook of dark‐grown seedlings. Together, our findings establish ABS6 and SAV4 as positive regulators of cMT severing and ordering, and highlight the role of cMT dynamics in fine‐tuning differential growth in plants.
Christian Mainline Protestant Pastors’ Beliefs About the Practice of Conversion Therapy: Reflections for Family Therapists
Authors: McGeorge Christi R. , Coburn Katelyn O. , Walsdorf Ashley A.
Published: August 2020

Efforts to change the sexual orientation of lesbian, gay, and bisexual (LGB) individuals to heterosexual are referred to as conversion therapy. Given the religious groundings that support the practice of conversion therapy, we sought to explore the beliefs of Christian religious leaders about this practice and what they want family therapists to know about the practice of conversion therapy. Twenty‐one pastors from diverse Mainline Christian Protestant traditions were interviewed. Queer theory‐informed thematic analysis revealed four themes that reflect the participants’ perspectives on conversion therapy: (a) Conversion Therapy Is an Abomination, (b) Conversion Therapy Is Similar to Other Abusive Practices, (c) Conversion Therapy Represents A Misuse of Religion, and (d) Ethical Concerns About Therapists Who Practice Conversion Therapy. Implications of this study include a need for self‐of‐the‐therapist work to address religious biases and heteronormative assumptions in order to examine beliefs that support practicing conversion therapy.
UNC‐5 netrin receptor B regulates adipogenesis of human adipose–derived stem cells through JNK pathway
Authors: Hu Xinyi , Liu Xuejiao , Lv Longwei , Zhang Xiao , Liu Yunsong , Zhang Ping , Zhou Yongsheng
Published: August 2020

Background

There is a balance between adipogenic differentiation and osteogenic differentiation of human adipose–derived stem cells (hASCs). It is essential to explore the mechanism of hASCs lineage commitment. In our previous study, UNC‐5 netrin receptor B (UNC5B) was identified as a positive regulator for osteogenesis.

Objective

To further explore the potential roles and mechanisms of UNC5B during adipogenic differentiation and to provide a new method to regulate adipogenesis and osteogenesis of hASCs.

Methods

Lentivirus containing UNC5B shRNA was used for UNC5B knockdown. Plasmids overexpressing UNC5B gene were used for UNC5B upregulation. To investigate the role of UNC5B in adipogenesis in vitro and in vivo, Oil Red O staining, RT‐qPCR and transplantation into nude mice were performed. Western blotting analyses were performed to explore the mechanisms of UNC5B in adipogenic differentiation.

Results

UNC5B expression in hASCs was significantly increased during adipogenic differentiation. Knockdown of UNC5B enhanced adipogenic differentiation in vitro. Both H&E staining and Oil Red O staining showed more adipose tissue–like constructs in UNC5B‐knockdown cells in vivo. Upregulation of UNC5B significantly impaired adipogenic differentiation in vitro. Downregulation of UNC5B could increase phosphorylation of JNK in hASCs. JNK inhibitors reduced adipogenic differentiation of hASCs.

Conclusion

Our findings showed that UNC5B inhibited adipogenesis of hASCs through JNK signalling. As a whole, UNC5B regulates both adipogenesis and osteogenesis of hASCs.