bluuebunny/crossref_metadata_2025 huggingface dataset:
On the identifiability of the isoform deconvolution problem: application to select the proper fragment length in an RNA-seq library
Authors: Ferrer-Bonsoms Juan A , Morales Xabier , Afshar Pegah T , Wong Wing H , Rubio Angel
Published: December 2021

Motivation

Isoform deconvolution is an NP-hard problem. The accuracy of the proposed solutions is far from perfect. At present, it is not known if gene structure and isoform concentration can be uniquely inferred given paired-end reads, and there is no objective method to select the fragment length to improve the number of identifiable genes. Different pieces of evidence suggest that the optimal fragment length is gene-dependent, stressing the need for a method that selects the fragment length according to a reasonable trade-off across all the genes in the whole genome.

Results

A gene is considered to be identifiable if it is possible to get both the structure and concentration of its transcripts univocally. Here, we present a method to state the identifiability of this deconvolution problem. Assuming a given transcriptome and that the coverage is sufficient to interrogate all junction reads of the transcripts, this method states whether or not a gene is identifiable given the read length and fragment length distribution. Applying this method using different read and fragment length combinations, the optimal average fragment length for the human transcriptome is around 400–600 nt for coding genes and 150–200 nt for long non-coding RNAs. The optimal read length is the largest one that fits in the fragment length. It is also discussed the potential profit of combining several libraries to reconstruct the transcriptome. Combining two libraries of very different fragment lengths results in a significant improvement in gene identifiability.

Availability and implementation

Code is available in GitHub (https://github.com/JFerrer-B/transcriptome-identifiability).

Supplementary information

Supplementary data are available at Bioinformatics online.
Completing gene trees without species trees in sub-quadratic time
Authors: Mai Uyen , Mirarab Siavash
Published: December 2021

Motivation

As genome-wide reconstruction of phylogenetic trees becomes more widespread, limitations of available data are being appreciated more than ever before. One issue is that phylogenomic datasets are riddled with missing data, and gene trees, in particular, almost always lack representatives from some species otherwise available in the dataset. Since many downstream applications of gene trees require or can benefit from access to complete gene trees, it will be beneficial to algorithmically complete gene trees. Also, gene trees are often unrooted, and rooting them is useful for downstream applications. While completing and rooting a gene tree with respect to a given species tree has been studied, those problems are not studied in depth when we lack such a reference species tree.

Results

We study completion of gene trees without a need for a reference species tree. We formulate an optimization problem to complete the gene trees while minimizing their quartet distance to the given set of gene trees. We extend a seminal algorithm by Brodal et al. to solve this problem in quasi-linear time. In simulated studies and on a large empirical data, we show that completion of gene trees using other gene trees is relatively accurate and, unlike the case where a species tree is available, is unbiased.

Availability and implementation

Our method, tripVote, is available at https://github.com/uym2/tripVote.

Supplementary information

Supplementary data are available at Bioinformatics online.
CACONET: a novel classification framework for microbial correlation networks
Authors: Xu Yuanwei , Nash Katrina , Acharjee Animesh , Gkoutos Georgios V
Published: December 2021

Motivation

Existing microbiome-based disease prediction relies on the ability of machine learning methods to differentiate disease from healthy subjects based on the observed taxa abundance across samples. Despite numerous microbes have been implicated as potential biomarkers, challenges remain due to not only the statistical nature of microbiome data but also the lack of understanding of microbial interactions which can be indicative of the disease.

Results

We propose CACONET (classification of Compositional-Aware COrrelation NETworks), a computational framework that learns to classify microbial correlation networks and extracts potential signature interactions, taking as input taxa relative abundance across samples and their health status. By using Bayesian compositional-aware correlation inference, a collection of posterior correlation networks can be drawn and used for graph-level classification, thus incorporating uncertainty in the estimates. CACONET then employs a deep learning approach for graph classification, achieving excellent performance metrics by exploiting the correlation structure. We test the framework on both simulated data and a large real-world dataset pertaining to microbiome samples of colorectal cancer (CRC) and healthy subjects, and identify potential network substructure characteristic of CRC microbiota. CACONET is customizable and can be adapted to further improve its utility.

Availability and implementation

CACONET is available at https://github.com/yuanwxu/corr-net-classify.

Supplementary information

Supplementary data are available at Bioinformatics online.
How effective is laparoscopic redo-antireflux surgery?
Authors: Fuchs K H , Breithaupt W , Varga G , Babic B , Eckhoff J , Meining A
Published: December 2021

Background: The failure-rate after primary antireflux surgery ranges from 3 to 30%. Reasons for failures are multifactorial. The aim of this study is to gain insight into the complex reasons for, and management of, failure after antireflux surgery. Methods: Patients were selected for redo-surgery after a diagnostic workup consisting of history and physical examination, upper gastrointestinal endoscopy, quality-of-life assessment, screening for somatoform disorders, esophageal manometry, 24-hour-pH-impedance monitoring, and selective radiographic studies such as Barium-sandwich for esophageal passage and delayed gastric emptying. Perioperative and follow-up data were compiled between 2004 and 2017. Results: In total, 578 datasets were analyzed. The patient cohort undergoing a first redo-procedure (n = 401) consisted of 36 patients after in-house primary LF and 365 external referrals (mean age: 62.1 years [25–87]; mean BMI 26 [20–34]). The majority of patients underwent a repeated total or partial laparoscopic fundoplication. Major reasons for failure were migration and insufficient mobilization during the primary operation. With each increasing number of required redo-operations, the complexity of the redo-procedure itself increased, follow-up quality-of-life decreased (GIQLI: 106; 101; and 100), and complication rate increased (intraoperative: 6,4–10%; postoperative: 4,5–19%/first to third redo). After three redo-operations, resections were frequently necessary (morbidity: 42%). Conclusions: Providing a careful patient selection, primary redo-antireflux procedures have proven to be highly successful. It is often the final chance for a satisfying result may be achieved upon performing a second redo-procedure. A third revision may solve critical problems, such as severe pain and/or inadequate nutritional intake. When resection is required, quality of life cannot be entirely normalized.
Natural language processing tool for automatic diseases and drugs recognition from electronic health records in polish- pilot study
Authors: Maciejewski C M , Krajsman M K , Ozieranski K O , Basza M B , Gawalko M G , Lodzinski P L , Opolski G O , Grabowski M G , Cacko A C , Balsam P B
Published: December 2021

Background

An estimate of 80% of data gathered in electronic health records is unstructured, textual information that cannot be utilized for research purposes until it is manually coded into a database. Manual coding is a both cost and time- consuming process. Natural language processing (NLP) techniques may be utilized for extraction of structured data from text. However, little is known about the accuracy of data obtained through these methods.

Purpose

To evaluate the possibility of employing NLP techniques in order to obtain data regarding risk factors needed for CHA2DS2VASc scale calculation and detection of antithrombotic medication prescribed in the population of atrial fibrillation (AF) patients of a cardiology ward.

Methods

An automatic tool for diseases and drugs recognition based on regular expressions rules was designed through cooperation of physicians and IT specialists. Records of 194 AF patients discharged from a cardiology ward were manually reviewed by a physician- annotator as a comparator for the automatic approach.

Results

Median CHA2DS2VASc score calculated by the automatic was 3 (IQR 2–4) versus 3 points (IQR 2–4) for the manual method (p=0.66). High agreement between CHA2DS2VASc scores calculated by both methods was present (Kendall's W=0.979; p<0.001). In terms of anticoagulant recognition, the automatic tool misqualified the drug prescribed in 4 cases.

Conclusion

NLP-based techniques are a promising tools for obtaining structured data for research purposes from electronic health records in polish. Tight cooperation of physicians and IT specialists is crucial for establishing accurate recognition patterns.

Funding Acknowledgement

Type of funding sources: None.
The Influence of Race and Gender on Receiving Assistance With Daily Activities Among Older Americans
Authors: Fabius Chanee D , Parker Lauren J , Thorpe Roland J
Published: December 2021

Background and Objectives

Nearly 8.2 million community-dwelling, older Medicare beneficiaries receive support from long-term services and supports (LTSS) with routine daily activities. Prior work demonstrates disability-related disparities; however, it is unclear whether these patterns persist among LTSS recipients and across specific sets of activities. We examine race and gender differences in receiving help with self-care (e.g., eating), mobility (e.g., getting around the house), and household (e.g., shopping) activities in a nationally representative sample of community-dwelling Medicare beneficiaries receiving LTSS.

Research Design and Methods

Cross-sectional analysis of 1,808 White and Black older adults receiving assistance with routine daily activities in the 2015 National Health and Aging Trends Study. Bivariate statistics were used to describe the sample and provide comparisons of characteristics by race and gender. Logistic regression models examined race and gender differences in receiving assistance with self-care, mobility, and household activities after adjusting for sociodemographic and health characteristics.

Results

Race and gender differences were observed across all sociodemographic and health characteristics, as well as for all forms of assistance. Relative to White men, Black men had lower odds of receiving help with self-care activities. White and black women had higher odds and Black men had lower odds of getting help with mobility activities than White men. Black men and White and Black women all had higher odds of receiving assistance with household tasks compared to White men.

Discussion and Implications

Our findings indicate that, despite prior evidence of disability-related disparities, the receipt of help with self-care, mobility, and household activities varies by race and gender. Findings reveal several target areas for future research. Future work should examine the role of cultural and social preferences for care, as well as the appropriateness of help, as evidenced by health service use and changes in quality of life.
Temporal Changes in the Treatment Paradigm and Long-term Prognosis of Patients With Crohn’s Disease: A Hospital-Based Cohort Study in China
Authors: Yao Lingya , Chen Haotian , Shao Bule , Liu Jing , Wang Chaohui , Zhang Zhou , Cao Qian
Published: December 2021

Background

The temporal trends in medical treatment and long-term outcomes of patients with Crohn’s disease (CD) have not been well elucidated in China over the past 2 decades. Accordingly, we aimed to evaluate the treatment paradigm and long-term clinical course of Chinese patients with CD in a hospital-based cohort.

Methods

All adult patients newly diagnosed with CD (n = 1338) between 1999 and 2019 in the Sir Run Run Shaw Hospital were included in this cohort. Medication utilization, disease outcomes, and risk factors were investigated.

Results

Overall, 48.7%, 35.6%, 67.8%, and 61.6% of patients used 5-aminosalicylates (5-ASA), corticosteroids, thiopurines, and infliximab (IFX), respectively. The cumulative risk of 5-ASA and corticosteroid initiation decreased during follow-up, whereas that of IFX initiation increased. Throughout a median follow-up duration of 26.4 (interquartile range, 12.0–49.2) months, a total of 486 and 300 patients underwent hospitalization and surgery, respectively. Of the 1097 patients with B1/B2 disease behavior at diagnosis, 10.3% experienced phenotype progression. The hospitalization rate decreased after 2015; however, surgery and phenotype progression rates did not significantly change. A Cox regression analysis indicated that IFX use since diagnosis was a contributing factor for lower rates of hospitalization and phenotype progression, whereas thiopurine use was associated with a lower surgery rate.

Conclusions

Infliximab use was observed to increase as 5-ASA and corticosteroid use decreased. Additionally, hospitalization rates decreased following temporal changes in IFX management, yet the surgery and phenotype progression rates remained the same.
Flight and Dietary Antioxidants Influence Antioxidant Expression and Activity in a Migratory Bird
Authors: DeMoranville Kristen J , Carter Wales A , Pierce Barbara J , McWilliams Scott R
Published: December 2021

Synopsis

Ecologically relevant factors such as exercise and diet quality can directly influence how physiological systems work including those involved in maintaining oxidative balance; however, to our knowledge, no studies to date have focused on how such factors directly affect expression of key components of the endogenous antioxidant system (i.e., transcription factors, select antioxidant genes, and corresponding antioxidant enzymes) in several metabolically active tissues of a migratory songbird. We conducted a three-factor experiment that tested the following hypotheses: (H1) Daily flying over several weeks increases the expression of transcription factors NRF2 and PPARs as well as endogenous antioxidant genes (i.e., CAT, SOD1, SOD2, GPX1, GPX4), and upregulates endogenous antioxidant enzyme activities (i.e., CAT, SOD, GPx). (H2) Songbirds fed diets composed of more 18:2n-6 PUFA are more susceptible to oxidative damage and thus upregulate their endogenous antioxidant system compared with when fed diets with less PUFA. (H3) Songbirds fed dietary anthocyanins gain additional antioxidant protection and thus upregulate their endogenous antioxidant system less compared with songbirds not fed anthocyanins. Flight training increased the expression of 3 of the 6 antioxidant genes and transcription factors measured in the liver, consistent with H1, but for only one gene (SOD2) in the pectoralis. Dietary fat quality had no effect on antioxidant pathways (H2), whereas dietary anthocyanins increased the expression of select antioxidant enzymes in the pectoralis, but not in the liver (H3). These tissue-specific differences in response to flying and dietary antioxidants are likely explained by functional differences between tissues as well as fundamental differences in their turnover rates. The consumption of dietary antioxidants along with regular flying enables birds during migration to stimulate the expression of genes involved in antioxidant protection likely through increasing the transcriptional activity of NRF2 and PPARs, and thereby demonstrates for the first time that these relevant ecological factors affect the regulation of key antioxidant pathways in wild birds. What remains to be demonstrated is how the extent of these ecological factors (i.e., intensity or duration of flight, amounts of dietary antioxidants) influences the regulation of these antioxidant pathways and thus oxidative balance.
Applying requisite imagination to safeguard electronic health record transitions
Authors: Sittig Dean F , Lakhani Priti , Singh Hardeep
Published: December 2021

Over the next decade, many health care organizations (HCOs) will transition from one electronic health record (EHR) to another; some forced by hospital acquisition and others by choice in search of better EHRs. Herein, we apply principles of Requisite Imagination, or the ability to imagine key aspects of the future one is planning, to offer 6 recommendations on how to proactively safeguard these transitions. First, HCOs should implement a proactive leadership structure that values communication. Second, HCOs should implement proactive risk assessment and testing processes. Third, HCOs should anticipate and reduce unwarranted variation in their EHR and clinical processes. Fourth, HCOs should establish a culture of conscious inquiry with routine system monitoring. Fifth, HCOs should foresee and reduce information access problems. Sixth, HCOs should support their workforce through difficult EHR transitions. Proactive approaches using Requisite Imagination principles outlined here can help ensure safe, effective, and economically sound EHR transitions.
Novel experimental apparatus for laboratory measurements of phototaxis: A comparison between amphipod species
Authors: Kennedy Melissa D , Barberio Angelo , Connaughton Victoria P
Published: December 2021

Intricate adaptations to visual systems have allowed amphipods to thrive in extreme habitats like caves. In addition to rearranging ocular dioptric elements, adaptations have also been made to photobehaviors to accommodate the environmental conditions of their habitats. Given the prevalence or absence of discernible eyes or photoreceptors across species, phototaxis is a commonly used behavior to assess light sensing mechanisms. Amphipod photobehaviors have increasingly been utilized within neuroethological and ecotoxicological studies but the quality of light used during laboratory experiments is often overlooked. We describe a novel experimental chamber that allows for accurate and efficient measurement of phototaxis under precisely controlled light conditions. We used this experimental chamber to test phototaxis in two related amphipod species, one subterranean (Stygobromus tenuis potomacusHolsinger, 1967) and one surface dwelling (Crangonyx shoemakeriHubricht & Mackin, 1940). Our results confirm that the behaviors of these species are indicative of natural photopreferences and that in certain populations, these preferences vary with light quality. This low cost and efficient method could easily be applied to a variety of animal models and light conditions, allowing for a reproducible and high throughput method to measure phototaxis in laboratory trials.
Bidirectional Predation Between Larvae of the Hoverfly Episyrphus balteatus (Diptera: Syrphidae) and the Fall Armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Li Hui , Wu Kongming
Published: December 2021

The fall armyworm, Spodoptera frugiperda (J. E. Smith), a newly invasive pest, has natural insect enemies that hold promise as biological control agents. Here we analyzed predation rates between natural enemy insect, the syrphid Episyrphus balteatus (De Geer) and S. frugiperda in all paired combinations of all immature stages for each insect in petri dishes. The 2nd and 3rd instars E. balteatus larvae consumed 1st and 2nd instars S. frugiperda larvae, and 3rd and higher larval instars of S. frugiperda preyed on all instar larvae of E. balteatus. The 2nd and 3rd instars larvae of E. balteatus preyed on 1st and 2nd larval instars of S. frugiperda, consistent with the Holling type III response in petri dishes, with a theoretical maximum predation of 77 and 71 individuals in 24 h. The 5th and 6th instars S. frugiperda larvae consumed E. balteatus larvae, also with the Holling type III response, with a theoretical maximum predation on 1st instar E. balteatus larvae were 29 and 36 individuals, respectively. In a plant cage trial study, predation results were similar to those in petri dishes but with a lower predation number. None of the S. frugiperda larvae that fed on E. balteatus larvae developed to adulthood, and only about 20% of E. balteatus larvae that fed on S. frugiperda larvae became adults which had a significantly shorter lifespan than those who consume aphids. This two-way predation study revealed the complexity of S. frugiperda invasion and provided new insights into relationship between pests and natural enemies.
Economic Injury Levels and Dynamic Action Thresholds forDiuraphis noxia(Hemiptera: Aphididae) in Australian Cereal Crops
Authors: Van Helden Maarten , Heddle Thomas , Umina Paul A , Maino James L
Published: December 2021

The Russian wheat aphid (Diuraphis noxia [Kurdjumov, Hemiptera: Aphididae], RWA) was first detected in Australia in 2016 and is threatening an annual cereal industry valued at nearly 10 billion AUD per annum. Considerable uncertainty surrounds the economic risk of D. noxia to Australian cereals, which limits cost-effective farm management decisions. Through a series of inoculated and non-inoculated field trials in 2018 and 2019 in south-eastern Australia, we generated a range of D. noxia pressure metrics under different growing conditions for barley, wheat, and durum wheat. Relative yield loss was best explained by the ‘percentage of tillers with D. noxia’ (%TwRWA) with 0.28% yield loss per percent of tillers with D. noxia, which is significantly lower than 0.46–0.48% for susceptible winter wheat varieties in dryland conditions in the United States. Highest infestation levels were typically reached around GS40–50. To develop an action threshold, we calculated the rate of increase in the %TwRWA through time at 0.021% per day per %TwRWA (with little variation across sites). This allowed prediction of the expected maximum %TwRWA based on observations post tillering (GS30) and the expected duration before GS50 is reached. For earlier growth stages (<GS30), we were unable to determine yield impact and action thresholds since cereal plants produce many new tillers between GS20 and GS30, which may compensate for feeding damage as reported in other studies. This research should improve the cost-effectiveness of management decisions involving D. noxia in Australian cereal production systems.
The LGBTI Inclusion Index: An Innovative Tool to Incentivize Human Rights and Development Data
Authors: Daly Felicity , Crehan Phil R , Grzywnowicz Micah
Published: December 2021

This article explores the potential of the LGBTI Inclusion Index, an initiative led by the United Nations Development Programme to overcome the paucity of data on the socio-economic status of lesbian, gay, bisexual, trans and intersex (LGBTI) people and other sexual and gender diverse (LGBT+) populations worldwide. Through the participation of LGBTI civil society and other stakeholders, the Index and its Indicators were designed to measure human rights and development dimensions across economic well-being; education; health; personal security and violence; and political and civic participation. The article reviews the development of the Index and shares findings from a limited number of interviews with stakeholders who were involved in conceptualization and/or dissemination of the concept. It discusses limits to intended participation by UN member states and some challenges in state collection and reporting of data disaggregated by sexual orientation, gender identity or expression and sex characteristics (SOGIESC). Utilization of conceptual features of the Index in multilateral reporting and research is also reviewed. The Index offers SOGIESC indicators which may be useful to human rights and development practitioners seeking to generate new data or use secondary data to measure whether development interventions are accessible to LGBTI people. Two case studies outline the adaptation of selected Indicators from the Index in surveys of LGBT+ people planned and/or undertaken by researchers in collaboration with civil society organizations in Africa and the Caribbean. We encourage utilization of the Index and its Indicators to gain greater insight on interventions that deliver socio-economic development and human rights implementation for LGBTI people.
Potential therapeutic effects of adjuvant chemotherapy after neoadjuvant chemotherapy for locally advanced muscle-invasive bladder cancer
Authors: Omura Minami , Kikuchi Eiji , Shigeta Keisuke , Ogihara Koichiro , Hakozaki Kyohei , Hara Satoshi , Shirotake Suguru , Ide Hiroki , Yoshimine Shunsuke , Ohigashi Takashi , Mizuno Ryuichi , Oya Mototsugu
Published: December 2021

Background

Although the administration of neoadjuvant chemotherapy has been associated with improved prognosis in patients with muscle-invasive bladder cancer, the therapeutic effects of adjuvant chemotherapy remain unknown in real-world settings. Therefore, we herein evaluated the clinical outcomes of adjuvant chemotherapy in pT3/4 muscle-invasive bladder cancer patients.

Materials and Methods

Among 587 bladder cancer patients who underwent radical cystectomy, 200 with a pathological T3 or higher muscle-invasive bladder cancer were included in the present analysis. Recurrence-free survival and cancer-specific survival were assessed by multivariate Cox regression analysis.

Results

Median age was 73 years, and the median follow-up duration was 17 months. The 5-year cancer-specific survival rate was 53.6% in 66 patients treated with adjuvant chemotherapy, which was significantly higher than that in those without adjuvant chemotherapy (34.0%, P = 0.025). The absence of adjuvant chemotherapy (hazard ratio = 2.114, P = 0.004) and lymphovascular invasion (hazard ratio = 2.203, P = 0.011) was identified as independent prognostic indicators for cancer-specific death. In patients treated without neoadjuvant chemotherapy (n = 143), the absence of adjuvant chemotherapy (hazard ratio:1.887, P = 0.030) remained an independent indicator for cancer-specific death. For those treated with adjuvant chemotherapy without neoadjuvant chemotherapy, three or more adjuvant chemotherapy cycles were independently associated with favourable outcome (hazard ratio = 0.240, P = 0.009). In contrast, for neoadjuvant chemotherapy-treated patients (N = 57), adjuvant chemotherapy was not independently associated with disease recurrence or cancer-specific death.

Conclusion

Adjuvant chemotherapy was associated with improvements in the prognosis of patients, even in those with pT3 or higher muscle-invasive bladder cancer. Although three or more cycles of adjuvant chemotherapy were effective for muscle-invasive bladder cancer patients treated without neoadjuvant chemotherapy, no therapeutic advantages were observed with additional adjuvant chemotherapy in patients treated with neoadjuvant chemotherapy.
Sequential stabilization of RNF220 by RLIM and ZC4H2 during cerebellum development and Shh-group medulloblastoma progression
Authors: Li Yuwei , Yang Chencheng , Wang Huishan , Zhao Ling , Kong Qinghua , Cang Yu , Zhao Shuhua , Lv Longbao , Li Yan , Mao Bingyu , Ma Pengcheng
Published: December 2021

Sonic hedgehog (Shh) signaling is essential for the proliferation of cerebellar granule neuron progenitors (CGNPs), and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma (MB). During vertebrate neural development, RNF220, a ubiquitin E3 ligase, is involved in spinal cord patterning by modulating the subcellular location of glioma-associated oncogene homologs (Glis) through ubiquitination. RNF220 is also required for full activation of Shh signaling during cerebellum development in an epigenetic manner through targeting embryonic ectoderm development. ZC4H2 was reported to be involved in spinal cord patterning by acting as an RNF220 stabilizer. Here, we provided evidence to show that ZC4H2 is also required for full activation of Shh signaling in CGNP and MB progression by stabilizing RNF220. In addition, we found that the ubiquitin E3 ligase RING finger LIM domain-binding protein (RLIM) is responsible for ZC4H2 stabilization via direct ubiquitination, through which RNF220 is also thus stabilized. RLIM is a direct target of Shh signaling and is also required for full activation of Shh signaling in CGNP and MB cell proliferation. We further provided clinical evidence to show that the RLIM‒ZC4H2‒RNF220 cascade is involved in Shh-group MB progression. Disease-causative human RLIM and ZC4H2 mutations affect their interaction and regulation. Therefore, our study sheds light on the regulation of Shh signaling during cerebellar development and MB progression and provides insights into neural disorders caused by RLIM or ZC4H2 mutations.
Genetic Counseling Considerations for Military Beneficiaries
Authors: Hellwig Lydia D , Krokosky Alyson , Vargason Ashlee , Turner Clesson
Published: December 2021

Genetic counseling for military beneficiaries poses unique challenges and counseling opportunities. In order to fully meet the needs of this population, genetic counseling involves critical ethical and psychosocial considerations. This article reviews some elements of genetic counseling that must be considered when working with beneficiaries in the military health system.
Investigation of Aerobic and Muscular Fitness and Concussion Among Service Academy Cadets at the United States Air Force Academy: Results from the CARE Consortium
Authors: Van Pelt Kathryn L , Wolff Laura , Campbell Darren E , McGinty Gerald , Zupan Michael , Jackson Jonathan C
Published: December 2021

Introduction

Concussion has become the signature injury facing the U.S. military. However, little is understood about the relationship between military fitness and concussion recovery. The current study examined the recoveries of cadets at a U.S. Service Academy to determine whether preinjury physical fitness improved recovery and whether recovery was associated with post-injury physical fitness measures.

Methods

Participants were enrolled in a longitudinal study of concussion. Aerobic Fitness Test (AFT) and Physical Fitness Test (PFT) data were used to estimate cadet fitness. Survival analysis evaluated significant estimators of concussion recovery time. Linear regression models were used to explore the relationship between recovery duration and change in physical fitness scores.

Results

Between 2014 and 2017, 307 (n = 70; 22.80% Women) cadets who had sustained a concussion were enrolled. Preinjury physical fitness was not significantly associated with recovery duration (P > .05). Men and intercollegiate cadets took fewer days to reach recovery milestones. Compared to women, men had greater decrements in the Aerobic Fitness Test total score (P < .05) and increased 1.5-mile time postconcussion (P < .05). Women had greater decreases in push-ups postconcussion compared to males (P < .05). There was a trend for a negative association between days until asymptomatic and change in the Physical Fitness Test score (P = .07).

Conclusion

Preconcussion physical fitness levels do not appear to impact concussion recovery time among a highly physically fit cohort. Possible methods to reduce the effect of symptom duration on strength-related physical fitness should be investigated along with evaluating reductions in strength as a possible mechanism for postconcussion injury risk.
Black hole to breakout: 3D GRMHD simulations of collapsar jets reveal a wide range of transients
Authors: Gottlieb Ore , Lalakos Aretaios , Bromberg Omer , Liska Matthew , Tchekhovskoy Alexander
Published: December 2021

We present a suite of the first 3D GRMHD collapsar simulations, which extend from the self-consistent jet launching by an accreting Kerr black hole (BH) to the breakout from the star. We identify three types of outflows, depending on the angular momentum, l, of the collapsing material and the magnetic field, B, on the BH horizon: (i) subrelativistic outflow (low l and high B), (ii) stationary accretion shock instability (SASI; high l and low B), (iii) relativistic jets (high l and high B). In the absence of jets, free-fall of the stellar envelope provides a good estimate for the BH accretion rate. Jets can substantially suppress the accretion rate, and their duration can be limited by the magnetization profile in the star. We find that progenitors with large (steep) inner density power-law indices (≳ 2), face extreme challenges as gamma-ray burst (GRB) progenitors due to excessive luminosity, global time evolution in the light curve throughout the burst and short breakout times, inconsistent with observations. Our results suggest that the wide variety of observed explosion appearances (supernova/supernova + GRB/low-luminosity GRBs) and the characteristics of the emitting relativistic outflows (luminosity and duration) can be naturally explained by the differences in the progenitor structure. Our simulations reveal several important jet features: (i) strong magnetic dissipation inside the star, resulting in weakly magnetized jets by breakout that may have significant photospheric emission and (ii) spontaneous emergence of tilted accretion disc-jet flows, even in the absence of any tilt in the progenitor.
Tidal modulations and the habitability of exoplanetary systems
Authors: Lingam Manasvi , Pryor Samantha , Ginsburg Idan
Published: December 2021

The Earth currently experiences rich tidal modulations by virtue of the fact that the tidal forces generated by the Sun and the Moon are approximately a factor of 2 removed from each other. This datum has been adduced by some scientists as one of the major drivers of the origin and evolution of (complex) life on the Earth (e.g. evolution of tetrapods). In this paper, we investigate the conditions under which terrestrial planets in the habitable zone can undergo strong tidal modulations akin to those documented on the Earth. By using an analytical model, we show that higher mass stars are more conducive to hosting potentially habitable planets with such moons, and that late-type M-dwarfs with masses $\lesssim 0.1\, {\rm M}_\odot$ might not host temperate Earth-analogues that fulfil the aforementioned criterion regarding tidal modulations. We also find that the Moon may perhaps be close to the maximal allowed mass limit compatible with producing large tidal modulations.
Extremely strong DLAs at high redshift: gas cooling and H2 formation
Authors: Telikova K N , Balashev S A , Noterdaeme P , Krogager J-K , Ranjan A
Published: December 2021

We present a spectroscopic investigation with the Very Large Telescope/X-shooter of seven candidate extremely strong damped Lyman-α absorption systems [ESDLAs, N(H i) ≥ 5 × 1021 cm−2] observed along quasar sightlines. We confirm the extremely high column densities, albeit slightly (0.1 dex) lower than the original ESDLA definition for four systems. We measured low-ionization metal abundances and dust extinction for all systems. For two systems, we also found strong associated H$\rm _2$ absorption $\log N(\rm{H\rm _2})\,\text{(cm$^{-2}$)}=18.16\pm 0.03$ and 19.28 ± 0.06 at z = 3.26 and 2.25 towards J2205+1021 and J2359+1354, respectively, while for the remaining five we measured conservative upper limits on the H$\rm _2$ column densities of typically $\log N(\rm{H\rm _2})\,\text{(cm$^{-2}$)}\,\lt\, 17.3$. The increased H2 detection rate (10–55 per cent at 68 per cent confidence level) at high H i column density compared with the overall damped Lyman-α population (∼5–10 per cent) confirms previous works. We find that these seven ESDLAs have similar observed properties as those previously studied towards quasars and γ-ray burst afterglows, suggesting they probe inner regions of galaxies. We use the abundance of ionized carbon at the excited fine-structure level to calculate the cooling rates through the C ii λ158 μm emission, and compare them with the cooling rates from damped Lyman-α systems in the literature. We find that the cooling rate distribution of ESDLAs also presents the same bimodality as previously observed for the general (mostly lower H i column density) damped Lyman-α population.
Consciousness as a multidimensional phenomenon: implications for the assessment of disorders of consciousness
Authors: Walter Jasmine
Published: December 2021

Disorders of consciousness (DoCs) pose a significant clinical and ethical challenge because they allow for complex forms of conscious experience in patients where intentional behaviour and communication are highly limited or non-existent. There is a pressing need for brain-based assessments that can precisely and accurately characterize the conscious state of individual DoC patients. There has been an ongoing research effort to develop neural measures of consciousness. However, these measures are challenging to validate not only due to our lack of ground truth about consciousness in many DoC patients but also because there is an open ontological question about consciousness. There is a growing, well-supported view that consciousness is a multidimensional phenomenon that cannot be fully described in terms of the theoretical construct of hierarchical, easily ordered conscious levels. The multidimensional view of consciousness challenges the utility of levels-based neural measures in the context of DoC assessment. To examine how these measures may map onto consciousness as a multidimensional phenomenon, this article will investigate a range of studies where they have been applied in states other than DoC and where more is known about conscious experience. This comparative evidence suggests that measures of conscious level are more sensitive to some dimensions of consciousness than others and cannot be assumed to provide a straightforward hierarchical characterization of conscious states. Elevated levels of brain complexity, for example, are associated with conscious states characterized by a high degree of sensory richness and minimal attentional constraints, but are suboptimal for goal-directed behaviour and external responsiveness. Overall, this comparative analysis indicates that there are currently limitations to the use of these measures as tools to evaluate consciousness as a multidimensional phenomenon and that the relationship between these neural signatures and phenomenology requires closer scrutiny.
Involvement of platelet-derived VWF in metastatic growth of melanoma in the brain
Authors: Robador Jose R , Feinauer Manuel J , Schneider Stefan W , Mayer Frank T , Gorzelanny Christian , Sacharow Artur , Liu Xiaobo , Berghoff Anna , Brehm Maria A , Hirsch Daniela , Stadler Julia , Vidal-y-Si Sabine , Wladykowski Ewa , Asong Marisse , Nowak Kai , Seiz-Rosenhagen Marcel , Umansky Viktor , Mess Christian , Pantel Klaus , Winkler Frank , Bauer Alexander T
Published: December 2021

Background

The prognosis of patients with brain metastases (BM) is poor despite advances in our understanding of the underlying pathophysiology. The high incidence of thrombotic complications defines tumor progression and the high mortality rate. We, therefore, postulated that von Willebrand factor (VWF) promotes BM via its ability to induce platelet aggregation and thrombosis.

Methods

We measured the abundance of VWF in the blood and intravascular platelet aggregates of patients with BM, and determined the specific contribution of endothelial and platelet-derived VWF using in vitro models and microfluidics. The relevance for the brain metastatic cascade in vivo was demonstrated in ret transgenic mice, which spontaneously develop BM, and by the intracardiac injection of melanoma cells.

Results

Higher levels of plasma VWF in patients with BM were associated with enhanced intraluminal VWF fiber formation and platelet aggregation in the metastatic tissue and peritumoral regions. Platelet activation triggered the formation of VWF multimers, promoting platelet aggregation and activation, in turn enhancing tumor invasiveness. The absence of VWF in platelets, or the blocking of platelet activation, abolished platelet aggregation, and reduced tumor cell transmigration. Anticoagulation and platelet inhibition consistently reduced the number of BM in preclinical animal models.

Conclusions

Our data indicate that platelet-derived VWF is involved in cerebral clot formation and in metastatic growth of melanoma in the brain. Targeting platelet activation with low-molecular-weight heparins represents a promising therapeutic approach to prevent melanoma BM.
Manual Lymph Drainage With Progressive Arm Exercises for Axillary Web Syndrome After Breast Cancer Surgery: A Randomized Controlled Trial
Authors: Torres-Lacomba María , Prieto-Gómez Virginia , Arranz-Martín Beatriz , Ferrandez Jean Claude , Yuste-Sánchez María José , Navarro-Brazález Beatriz , Romay-Barrero Helena
Published: December 2021

Objective

This study aimed to determine the effectiveness of a physical therapist–designed program tailored to axillary web syndrome (AWS) in women after breast cancer surgery.

Methods

A prospective, single-center, assessor-blinded, randomized controlled trial was conducted at the Physiotherapy in Women’s Health Research Unit of the Alcalá University (Madrid, Spain). Ninety-six women with AWS were assigned to the physical therapy group (manual lymph drainage [MLD] using resorption strokes and arm exercises as if performing median nerve neurodynamic glide exercises with no neural loading; n = 48) or the control group (standard arm exercises; n = 48), with both groups receiving treatment 3 times a week for 3 weeks. Both interventions included an educational component.

Results

Compared with the control group, the physical therapy group showed significant and clinically relevant improvements in the primary outcome (self-reported pain intensity) at the primary and 3-month follow-ups. Significant and clinically relevant differences between groups were also found in the secondary outcomes (shoulder active range of motion, shoulder disability, and physical and functional aspects of health-related quality of life) at the primary follow-up and in the secondary outcomes as well as the trial outcome index at the 3-month follow-up. No significant differences were found at the 6-month follow-up in either primary or secondary outcomes.

Conclusion

The physical therapy program tailored to AWS was found to be effective for AWS symptoms in women after breast cancer surgery, both immediately after the program and after 3 months.

Impact

To our knowledge, this is the first appropriately designed study to demonstrate the effectiveness of MLD with progressive arm exercises for AWS. Clinicians and health service providers should consider how to provide survivors of breast cancer with AWS the opportunity to participate in physical therapy programs, including MLD with progressive arm exercises.

Lay Summary

For axillary web syndrome following breast cancer surgery, a physical therapist can design a treatment program including manual lymph drainage and progressive arm exercises, which has been shown to result in reduced pain and improved motion compared with standard arm exercises.
Stand Up for Indigenous Health: A Simulation to Educate Residents About the Social Determinants of Health Faced by Indigenous Peoples in Canada
Authors: Sauvé Amanda , Cappelletti Adriana , Murji Latif
Published: December 2021

Problem

In Canada, Indigenous peoples face significant health disparities. To improve health outcomes of and provide culturally safe care to Indigenous patients, medical learners must receive training on the social determinants of health (SDOH) driving these health inequities. The authors developed Stand Up for Indigenous Health (SU4IH), an immersive 2-hour simulation where participants navigate a series of scenarios as an Indigenous person. The objective of this pilot study was to assess whether SU4IH promotes intercultural empathy and enhances medical learners’ knowledge of Indigenous SDOH.

Approach

The authors partnered with 4 Indigenous communities in Ontario, Canada, from urban, rural, and remote settings to develop the scenarios for SU4IH between June 2015 and March 2016. During each SU4IH simulation, learners experience 14 scenarios using the Stand Up for Health mobile app, which automatically calculates each individual’s financial balance and stress levels as the simulation unfolds. The authors conducted a pre–post intervention study of SU4IH in January 2019 with family medicine residents recruited from 2 training sites in Ontario (n = 29). Residents completed pre- and postsurveys assessing change in empathy toward Indigenous patients (primary outcome), knowledge of Indigenous SDOH (secondary outcome), and motivation to engage with Indigenous patients in a culturally safe manner (secondary outcome).

Outcomes

Residents’ empathy scores significantly increased after participating in SU4IH (P < .001), as did residents’ knowledge of Indigenous SDOH (P < .001) and motivation to engage with Indigenous patients in a culturally safe manner (P = .031).

Next Steps

The authors are working to expand their capacity to implement this learning tool across Canada, which has involved relationship building with medical learners and faculty outside of Ontario who will need to partner with Indigenous communities in their region to develop region-specific scenarios. SU4IH is also being redesigned for small-group and virtual formats to facilitate its expansion.
The Effects of Leadership Curricula With and Without Implicit Bias Training on Graduate Medical Education: A Multicenter Randomized Trial
Authors: Hansen Matt , Harrod Tabria , Bahr Nathan , Schoonover Amanda , Adams Karen , Kornegay Josh , Stenson Amy , Ng Vivienne , Plitt Jennifer , Cooper Dylan , Scott Nicole , Chinai Sneha , Johnson Julia , Conlon Lauren Weinberger , Salva Catherine , Caretta-Weyer Holly , Huynh Trang , Jones David , Jorda Katherine , Lo Jamie , Mayersak Ryanne , Paré Emmanuelle , Hughes Kate , Ahmed Rami , Patel Soha , Tsao Suzana , Wang Eileen , Ogburn Tony , Guise Jeanne-Marie
Published: December 2021

Purpose

To determine whether a brief leadership curriculum including high-fidelity simulation can improve leadership skills among resident physicians.

Method

This was a double-blind, randomized controlled trial among obstetrics–gynecology and emergency medicine (EM) residents across 5 academic medical centers from different geographic areas of the United States, 2015–2017. Participants were assigned to 1 of 3 study arms: the Leadership Education Advanced During Simulation (LEADS) curriculum, a shortened Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) curriculum, or as active controls (no leadership curriculum). Active controls were recruited from a separate site and not randomized to limit any unintentional introduction of materials from leadership curricula. The LEADS curriculum was developed in partnership with the Council on Resident Education in Obstetrics and Gynecology and Council of Residency Directors in Emergency Medicine as a novel way to provide a leadership toolkit. Both LEADS and the abbreviated TeamSTEPPS were designed as six 10-minute interactive web-based modules.

The primary outcome of interest was the leadership performance score from the validated Clinical Teamwork Scale instrument measured during standardized high-fidelity simulation scenarios. Secondary outcomes were 9 key components of leadership from the detailed leadership evaluation measured on 5-point Likert scales. Both outcomes were rated by a blinded clinical video reviewer.

Results

One hundred ten obstetrics–gynecology and EM residents participated in this 2-year trial. Participants in both LEADS and TeamSTEPPS had statistically significant improvement in leadership scores from “average” to “good” ranges both immediately and at the 6-month follow-up, while controls remained unchanged in the “average” category throughout the study. There were no differences between LEADS and TeamSTEPPS curricula with respect to the primary outcome.

Conclusions

Residents who participated in a brief structured leadership training intervention had improved leadership skills that were maintained at 6-month follow-up.