bluuebunny/crossref_metadata_2025 huggingface dataset:
PERHAPS: Paired-End short Reads-based HAPlotyping from next-generation Sequencing data
Authors: Huang Jie , Pallotti Stefano , Zhou Qianling , Kleber Marcus , Xin Xiaomeng , King Daniel A , Napolioni Valerio
Published: October 2020

The identification of rare haplotypes may greatly expand our knowledge in the genetic architecture of both complex and monogenic traits. To this aim, we developed PERHAPS (Paired-End short Reads-based HAPlotyping from next-generation Sequencing data), a new and simple approach to directly call haplotypes from short-read, paired-end Next Generation Sequencing (NGS) data. To benchmark this method, we considered the APOE classic polymorphism (*1/*2/*3/*4), since it represents one of the best examples of functional polymorphism arising from the haplotype combination of two Single Nucleotide Polymorphisms (SNPs). We leveraged the big Whole Exome Sequencing (WES) and SNP-array data obtained from the multi-ethnic UK BioBank (UKBB, N=48,855). By applying PERHAPS, based on piecing together the paired-end reads according to their FASTQ-labels, we extracted the haplotype data, along with their frequencies and the individual diplotype. Concordance rates between WES directly called diplotypes and the ones generated through statistical pre-phasing and imputation of SNP-array data are extremely high (>99%), either when stratifying the sample by SNP-array genotyping batch or self-reported ethnic group. Hardy-Weinberg Equilibrium tests and the comparison of obtained haplotype frequencies with the ones available from the 1000 Genome Project further supported the reliability of PERHAPS. Notably, we were able to determine the existence of the rare APOE*1 haplotype in two unrelated African subjects from UKBB, supporting its presence at appreciable frequency (approximatively 0.5%) in the African Yoruba population. Despite acknowledging some technical shortcomings, PERHAPS represents a novel and simple approach that will partly overcome the limitations in direct haplotype calling from short read-based sequencing.
Do we need different machine learning algorithms for QSAR modeling? A comprehensive assessment of 16 machine learning algorithms on 14 QSAR data sets
Authors: Wu Zhenxing , Zhu Minfeng , Kang Yu , Leung Elaine Lai-Han , Lei Tailong , Shen Chao , Jiang Dejun , Wang Zhe , Cao Dongsheng , Hou Tingjun
Published: October 2020

Although a wide variety of machine learning (ML) algorithms have been utilized to learn quantitative structure–activity relationships (QSARs), there is no agreed single best algorithm for QSAR learning. Therefore, a comprehensive understanding of the performance characteristics of popular ML algorithms used in QSAR learning is highly desirable. In this study, five linear algorithms [linear function Gaussian process regression (linear-GPR), linear function support vector machine (linear-SVM), partial least squares regression (PLSR), multiple linear regression (MLR) and principal component regression (PCR)], three analogizers [radial basis function support vector machine (rbf-SVM), K-nearest neighbor (KNN) and radial basis function Gaussian process regression (rbf-GPR)], six symbolists [extreme gradient boosting (XGBoost), Cubist, random forest (RF), multiple adaptive regression splines (MARS), gradient boosting machine (GBM), and classification and regression tree (CART)] and two connectionists [principal component analysis artificial neural network (pca-ANN) and deep neural network (DNN)] were employed to learn the regression-based QSAR models for 14 public data sets comprising nine physicochemical properties and five toxicity endpoints. The results show that rbf-SVM, rbf-GPR, XGBoost and DNN generally illustrate better performances than the other algorithms. The overall performances of different algorithms can be ranked from the best to the worst as follows: rbf-SVM > XGBoost > rbf-GPR > Cubist > GBM > DNN > RF > pca-ANN > MARS > linear-GPR ≈ KNN > linear-SVM ≈ PLSR > CART ≈ PCR ≈ MLR. In terms of prediction accuracy and computational efficiency, SVM and XGBoost are recommended to the regression learning for small data sets, and XGBoost is an excellent choice for large data sets. We then investigated the performances of the ensemble models by integrating the predictions of multiple ML algorithms. The results illustrate that the ensembles of two or three algorithms in different categories can indeed improve the predictions of the best individual ML algorithms.
Scool: a new data storage format for single-cell Hi-C data
Authors: Wolff Joachim , Abdennur Nezar , Backofen Rolf , Grüning Björn
Published: October 2020

Motivation

Single-cell Hi-C research currently lacks an efficient, easy to use and shareable data storage format. Recent studies have used a variety of sub-optimal solutions: publishing raw data only, text-based interaction matrices, or reusing established Hi-C storage formats for single interaction matrices. These approaches are storage and pre-processing intensive, require long labour time and are often error-prone.

Results

The single-cell cooler file format (scool) provides an efficient, user-friendly and storage-saving approach for single-cell Hi-C data. It is a flavour of the established cooler format and guarantees stable API support.

Availability and implementation

The single-cell cooler format is part of the cooler file format as of API version 0.8.9. It is available via pip, conda and github: https://github.com/mirnylab/cooler.

Supplementary information

Supplementary data are available at Bioinformatics online.
Effect of mitophagy in oocytes and granulosa cells on oocyte quality†
Authors: Shen Qiuzi , Liu Yu , Li Honggang , Zhang Ling
Published: October 2020

Mitophagy is the process by which cells selectively remove supernumerary or damaged mitochondria through autophagy, and is crucial for mitochondrial homeostasis and cell survival. Mitochondria play vital roles in determining the developmental competence of oocytes. During the early stages of oogenesis, aberrant mitochondria can be removed by mitophagy. After oocyte formation, mitophagy is not actively initiated to clear damaged mitochondria despite the presence of mitophagy regulators in oocytes, which leads to the transmission of dysfunctional mitochondria from the oocyte to the embryo. However, granulosa cells around oocytes can improve mitochondrial function through mitophagy, thereby improving oocyte developmental capacity. Furthermore, this review discusses recent work on the substances and environmental conditions that affect mitophagy in oocytes and granulosa cells, thus providing new directions for improving oocyte quality during assisted reproductive technology treatment.
What do parents think about statutory child and family social work services in the UK?
Authors: Wilkins David , Forrester Donald
Published: October 2020

Higher levels of ‘service user’ satisfaction are associated with more positive outcomes in many service settings. They are also an important measure of service quality in their own right. In this article, we report the results from a survey of 500 parents in relation to statutory child and family social work services in the UK. Our primary outcome measure was the Client Satisfaction Questionnaire, a valid instrument that has been used in a range of settings and types of service. Parents overall had relatively low levels of satisfaction, compared with research in other settings. Levels of dissatisfaction were higher for parents from lower socio-economic groups and parents of adolescents. The small number of parents in our survey who received short-breaks or residential care for their children gave higher satisfaction ratings. An important limitation of these results is that the sample is not representative. Parents from higher socio-economic groups were over-represented compared with the general population and were therefore very overrepresented compared with the population of families who receive a statutory social work service. These findings nevertheless suggest that parents are likely to be dissatisfied with the services they received and suggest a pressing need for more representative data to understand the experiences of parents across the UK.
Why Are You Backing Such Positions? Types and Trajectories of Social Workers’ Right-Wing Populist Support
Authors: Fazzi Luca , Nothdurfter Urban
Published: October 2020

The rise of right-wing populism and its impact on inclusive welfare and fundamental principles of social work have been discussed mainly as an external challenge to the profession, assuming, implicitly, that social workers are immune to right-wing populist positions because of their professional values and identity. This article questions this assumption, presenting the findings of a qualitative study carried out in the Italian context. The interview study involved a sample of twenty-one social workers recruited to participate via Facebook, where they had published posts and comments supporting right-wing populist parties and positions. The findings indicate different attitudes, experiences and trajectories which are summarised in an interpretative model, reconstructing four ideal-typical profiles of social workers supporting right-wing populist positions. The article suggests abandoning the hypothesis of social workers being immune to populist influences and instead takes seriously the experiences and frustrations that make them turn towards the siren calls of right-wing populism. The article also makes a plea for qualitative in-depth analyses of processes of micro-mobilisation leading to right-wing populist support.
Fetal Rhesus Monkey First Trimester Zika Virus Infection Impacts Cortical Development in the Second and Third Trimesters
Authors: Tarantal Alice F , Hartigan-O’Connor Dennis J , Penna Elisa , Kreutz Anna , Martinez Michele L , Noctor Stephen C
Published: October 2020

Zika virus is a teratogen similar to other neurotropic viruses, notably cytomegalovirus and rubella. The goal of these studies was to address the direct impact of Zika virus on fetal development by inoculating early gestation fetal rhesus monkeys using an ultrasound-guided approach (intraperitoneal vs. intraventricular). Growth and development were monitored across gestation, maternal samples collected, and fetal tissues obtained in the second trimester or near term. Although normal growth and anatomical development were observed, significant morphologic changes were noted in the cerebral cortex at 3-weeks post-Zika virus inoculation including massive alterations in the distribution, density, number, and morphology of microglial cells in proliferative regions of the fetal cerebral cortex; an altered distribution of Tbr2+ neural precursor cells; increased diameter and volume of blood vessels in the cortical proliferative zones; and a thinner cortical plate. At 3-months postinoculation, alterations in morphology, distribution, and density of microglial cells were also observed with an increase in blood vessel volume; and a thinner cortical plate. Only transient maternal viremia was observed but sustained maternal immune activation was detected. Overall, these studies suggest persistent changes in cortical structure result from early gestation Zika virus exposure with durable effects on microglial cells.
Respiratory Syncytial Virus Disease Severity in Young Children
Authors: Haddadin Zaid , Beveridge Stockton , Fernandez Kailee , Rankin Danielle A , Probst Varvara , Spieker Andrew J , Markus Tiffanie M , Stewart Laura S , Schaffner William , Lindegren Mary Lou , Halasa Natasha
Published: October 2020

Background

Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections (ARIs) in hospitalized children. Although prematurity and underlying medical conditions are known risk factors, most of these children are healthy, and factors including RSV load and subgroups may contribute to severity. Therefore, we aimed to evaluate the role of RSV in ARI severity and determine factors associated with increased RSV-ARI severity in young children.

Methods

Children aged <5 years with fever and/or ARI symptoms were recruited from the emergency department (ED) or inpatient settings at Vanderbilt Children’s Hospital. Nasal and/or throat swabs were tested using quantitative reverse-transcription polymerase chain reaction for common respiratory viruses, including RSV. A severity score was calculated for RSV-positive children.

Results

From November 2015 through July 2016, 898 participants were enrolled, and 681 (76%) had at least 1 virus detected, with 191 (28%) testing positive for RSV. RSV-positive children were more likely to be hospitalized, require intensive care unit admission, and receive oxygen compared with children positive for other viruses. Higher viral load, White race, younger age, and higher severity score were independently associated with hospitalization in RSV-positive children. No differences in disease severity were noted between RSV A and RSV B.

Conclusions

RSV was associated with increased ARI severity in young children enrolled from the ED and inpatient settings, but no differences in disease severity were noted between RSV A and RSV B. These findings emphasize the need for antiviral therapy and/or preventive measures such as vaccines against RSV in young children.
Association of 152 Biomarker Reference Intervals with All-Cause Mortality in Participants of a General United States Survey from 1999 to 2010
Authors: Pho Nam , Manrai Arjun K , Leppert John T , Chertow Glenn M , Ioannidis John P A , Patel Chirag J
Published: October 2020

Background

Physicians sometimes consider whether or not to perform diagnostic testing in healthy people, but it is unknown whether nonextreme values of diagnostic tests typically encountered in such populations have any predictive ability, in particular for risk of death. The goal of this study was to quantify the associations among population reference intervals of 152 common biomarkers with all-cause mortality in a representative, nondiseased sample of adults in the United States.

Methods

The study used an observational cohort derived from the National Health and Nutrition Examination Survey (NHANES), a representative sample of the United States population consisting of 6 survey waves from 1999 to 2010 with linked mortality data (unweighted N = 30 651) and a median followup of 6.1 years. We deployed an X-wide association study (XWAS) approach to systematically perform association testing of 152 diagnostic tests with all-cause mortality.

Results

After controlling for multiple hypotheses, we found that the values within reference intervals (10–90th percentiles) of 20 common biomarkers used as diagnostic tests or clinical measures were associated with all-cause mortality, including serum albumin, red cell distribution width, serum alkaline phosphatase, and others after adjusting for age (linear and quadratic terms), sex, race, income, chronic illness, and prior-year healthcare utilization. All biomarkers combined, however, explained only an additional 0.8% of the variance of mortality risk. We found modest year-to-year changes, or changes in association from survey wave to survey wave from 1999 to 2010 in the association sizes of biomarkers.

Conclusions

Reference and nonoutlying variation in common biomarkers are consistently associated with mortality risk in the US population, but their additive contribution in explaining mortality risk is minor.
Interventricular septal haematoma after EXCOR paediatric implantation
Authors: Komori Motoki , Hoashi Takaya , Sakaguchi Heima , Ichikawa Hajime
Published: October 2020

A 3.5-kg boy with dilated cardiomyopathy underwent EXCOR left ventricular assist device implantation, which resulted in right ventricular outflow tract obstruction due to the development of an interventricular septal haematoma (IVSH), which required the implantation of an additional right ventricular assist device. Curettage and haemostasis of the IVSH were successfully performed on postoperative day 17. An 11-kg girl with left ventricular non-compaction also underwent EXCOR left ventricular assist device implantation. An IVSH was initially detected on postoperative day 13 without haemodynamic instability. By decreasing the target-activated partial thromboplastin time, the IVSH completely regressed 2 months later.
Trends in Women’s Relative Earnings Within Couples Across the Transition to Parenthood in Sweden, 1987–2007
Authors: Nylin Anna-Karin , Musick Kelly , Billingsley Sunnee , Duvander Ann-Zofie , Evertsson Marie
Published: October 2020

This article applies a couple perspective to assessing gender inequality in Sweden—a setting with high maternal labour force participation, a long history of family policy investment, and strong norms of gender equality. We address open questions about how couples’ earnings following parenthood have changed over time, and how patterns of inequality in couples’ earnings have played out across educational groups. Our study uses fixed effects methods and register data covering the total population of heterosexual couples giving birth in Sweden between 1987 and 2007 (N = 587,414 couples). It examines change in the female partner’s share of total couple earnings from 2 years before to 8 years after first birth across parent cohorts differentiated by his and her education. Women’s earnings share declines steeply following birth, across all groups. Results show modestly smaller declines among parents in the latest cohort in the year directly following childbirth. Change is most pronounced among couples with a highly educated female partner, and it appears driven by a marked dip in fathers’ earnings that is new to this recent generation of men. Recent movement towards within-couple equality in Sweden appears driven by men’s work adjustments, pointing to an important shift in the allocation of care work within couples.
Diagnostic yield and accuracy in a tertiary referral syncope unit validating the ESC guideline on syncope: a prospective cohort study
Authors: de Jong Jelle S Y , Blok Minou R Snijders , Thijs Roland D , Harms Mark P M , Hemels Martin E W , de Groot Joris R , van Dijk Nynke , de Lange Frederik J
Published: October 2020

Aims 

To assess in patients with transient loss of consciousness the diagnostic yield, accuracy, and safety of the structured approach as described in the ESC guidelines in a tertiary referral syncope unit.

Methods and results 

Prospective cohort study including 264 consecutive patients (≥18 years) referred with at least one self-reported episode of transient loss of consciousness and presenting to the syncope unit between October 2012 and February 2015. The study consisted of three phases: history taking (Phase 1), autonomic function tests (AFTs) (Phase 2), and after 1.5-year follow-up with assessment by a multidisciplinary committee (Phase 3). Diagnostic yield was assessed after Phases 1 and 2. Empirical diagnostic accuracy was measured for diagnoses according to the ESC guidelines after Phase 3. The diagnostic yield after Phase 1 (history taking) was 94.7% (95% CI: 91.1–97.0%, 250/264 patients) and increased to 97.0% (93.9–98.6%, 256/264 patients) after Phase 2. The overall diagnostic accuracy (as established in Phase 3) of the Phases 1 and 2 diagnoses was 90.6% (95% CI: 86.2–93.8%, 232/256 patients). No life-threatening conditions were missed. Three patients died, two unrelated to the cause of transient loss of consciousness, and one whom remained undiagnosed.

Conclusion 

A clinical work-up at a tertiary syncope unit using the ESC guidelines has a high diagnostic yield, accuracy, and safety. History taking (Phase 1) is the most important diagnostic tool. Autonomic function tests never changed the Phase 1 diagnosis but helped to increase the certainty of the Phase 1 diagnosis in many patients and yield additional diagnoses in patients who remained undiagnosed after Phase 1. Diagnoses were inaccurate in 9.4%, but no serious conditions were missed. This is adequate for clinical practice.
Impact of guidelines on antibiotic prescribing approach in primary care—a 10-year study
Authors: Radošević Quadranti Nives , Vlahović-Palčevski Vera , Popović Branislava , Diminić-Lisica Ines
Published: October 2020

Background

Publication and implementation of clinical guidelines is an important educational measure that considerably helps physicians in choosing appropriate antimicrobial drug.

Objectives

To evaluate long-term changes in antimicrobial prescribing habits before and after publishing the guidelines and to determine the factors that influence physician’s decision to prescribe an antimicrobial drug.

Methods

The study among general practitioners in Primorsko-Goranska County was conducted in three periods (January 2009, January 2011 and April 2019) by using a structured questionnaire that included general data about the physician, questions about their habits in antibiotic prescribing, criteria that influenced decision to prescribe antibiotics and antimicrobial agent(s) preferred in treating common infections.

Results

Concomitant chronic (non-pulmonary) disease was the most important factor influencing decision to prescribe an antimicrobial drug. Over 88% of physicians that completed the survey declared themselves as rational prescribers of antimicrobials but more than half of them (53.3%) sometimes prescribed an antibiotic even though it was not indicated compared to 75% of self-reported non-rational prescribers (P ˂ 0.05). Self-reported adherence to the guidelines increased from 34.6% in 2011 to 51.8% in 2019.

Conclusion

The research showed improvement in physicians’ knowledge in choosing the right antibiotic based on the analysis of answers but indicated the necessity for improving communication skills and empowering physicians not to prescribe antibiotics ‘just in case’ because of diagnostic uncertainty or patient demand. Further qualitative research is needed to understand physicians’ prescribing behaviour and decision-making processes in order to develop interventions that will effectively improve the use of antibiotics.
Volunteering, Self-Perceptions of Aging, and Mental Health in Later Life
Authors: Huo Meng , Miller Lisa M Soederberg , Kim Kyungmin , Liu Siwei
Published: October 2020

Background and Objectives

Scholars argue that volunteering enhances social, physical, and cognitive activities that are increasingly valued as people age, which in turn improves older adults’ well-being via a host of psychosocial and neurobiological mechanisms. This study explicitly tested older adults’ self-perceptions of aging as a mechanism underlying the mental health benefits of volunteering.

Research Design and Methods

Using 2-wave data from the Health and Retirement Study (2008/2010 for Wave 1 and 2012/2014 for Wave 2), we analyzed reports from a pooled sample of older adults aged 65 or older (N = 9,017). Participants reported on demographic characteristics, volunteer work (did not volunteer, 1–99 h/year, 100+ h/year), self-perceptions of aging, and depressive symptoms. We estimated an autoregressive cross-lagged panel model.

Results

Volunteering for 100 h or more per year was associated with older adults’ more positive and less negative self-perceptions of aging in the subsequent wave (i.e., 4 years later), which in turn predicted fewer depressive symptoms.

Discussion and Implications

This study suggests the promising role of volunteering in shaping older adults’ self-perceptions of aging on a sustained basis and refines our understanding of the benefits volunteering brings. Findings shed light on future interventions aimed at improving older adults’ adjustment to age-related changes and lessening ageism in society.
A simultaneous calibration and data assimilation (C/DA) to improve NRLMSISE00 using thermospheric neutral density (TND) from space-borne accelerometer measurements
Authors: Forootan E , Farzaneh S , Kosary M , Schmidt M , Schumacher M
Published: October 2020

Improving thermospheric neutral density (TND) estimates is important for computing drag forces acting on low-Earth-orbit (LEO) satellites and debris. Empirical thermospheric models are often used to compute TNDs for the precise orbit determination experiments. However, it is known that simulating TNDs are of limited accuracy due to simplification of model structure, coarse sampling of model inputs and dependencies to the calibration period. Here, we apply TND estimates from accelerometer measurements of the Challenging Minisatellite Payload (CHAMP) and the Gravity Recovery and Climate Experiment (GRACE) missions as observations to improve the NRLMSISE-00 model, which belongs to the mass spectrometer and incoherent scatter family of models. For this, a novel simultaneous calibration and data assimilation (C/DA) technique is implemented that uses the ensemble Kalman filter and the ensemble square-root Kalman filter as merger. The application of C/DA is unique because it modifies both model-derived TNDs, as well as the selected model parameters. The calibrated parameters derived from C/DA are then used to predict TNDs in locations that are not covered by CHAMP and GRACE orbits, and forecasting TNDs of the next day. The C/DA is implemented using daily CHAMP- and/or GRACE-TNDs, for which compared to the original model, we find 27 per cent and 62 per cent reduction of misfit between model and observations in terms of root mean square error and Nash coefficient, respectively. These validations are performed using the observations along the orbital track of the other satellite that is not used in the C/DA during 2003 with various solar activity. Comparisons with another empirical model, that is, Jacchia-Bowman, indicate that the C/DA results improve these quality measurements on an average range of 50 per cent and 60 per cent, respectively.
NMIHBA results from hypomorphic PRUNE1 variants that lack short-chain exopolyphosphatase activity
Authors: Nistala Harikiran , Dronzek John , Gonzaga-Jauregui Claudia , Chim Shek Man , Rajamani Saathyaki , Nuwayhid Samer , Delgado Dennis , Burke Elizabeth , Karaca Ender , Franklin Matthew C , Sarangapani Prasad , Podgorski Michael , Tang Yajun , Dominguez Melissa G , Withers Marjorie , Deckelbaum Ron A , Scheonherr Christopher J , Gahl William A , Malicdan May C , Zambrowicz Brian , Gale Nicholas W , Gibbs Richard A , Chung Wendy K , Lupski James R , Economides Aris N
Published: October 2020

Neurodevelopmental disorder with microcephaly, hypotonia and variable brain anomalies (NMIHBA) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by global developmental delay and severe intellectual disability. Microcephaly, progressive cortical atrophy, cerebellar hypoplasia and delayed myelination are neurological hallmarks in affected individuals. NMIHBA is caused by biallelic variants in PRUNE1 encoding prune exopolyphosphatase 1. We provide in-depth clinical description of two affected siblings harboring compound heterozygous variant alleles, c.383G > A (p.Arg128Gln), c.520G > T (p.Gly174*) in PRUNE1. To gain insights into disease biology, we biochemically characterized missense variants within the conserved N-terminal aspartic acid-histidine-histidine (DHH) motif and provide evidence that they result in the destabilization of protein structure and/or loss of exopolyphosphatase activity. Genetic ablation of Prune1 results in midgestational lethality in mice, associated with perturbations to embryonic growth and vascular development. Our findings suggest that NMIHBA results from hypomorphic variant alleles in humans and underscore the potential key role of PRUNE1 exopolyphoshatase activity in neurodevelopment.
The Elusive History of the Pan-African Congress, 1919–27
Authors: Hodder Jake
Published: October 2020

This paper considers the meetings of the interwar Pan-African Congress movement. It examines the Congress in the context of how conferencing became a dominant mode of international politics in the 1920s and the opportunities this offered to non-state actors. The Congress exemplified the hope which race reformers placed in the new international system established after the First World War, and in the League of Nations specifically. The paper considers three key conferencing elements in turn: delegates, venues, and resolutions. In each case, organizers mobilized the framework of conferencing to validate their political demands within this international system whilst, also in each case, their constrained circumstances required them to be strategically ambiguous with the facts of their meetings. As such, the paper encourages a broader methodological reflection on how historians approach seemingly unreliable historical sources. I argue that inconsistencies in reports of the Congress are themselves important historical artefacts of the political manoeuvres undertaken by race reformers. Foregrounding these strategies allows us to consider how political authority was circumscribed in the past, the resourcefulness of those on the political margins, and the promise and failure of international governance on the race question in the 1920s.
A Unified Proof of Conjectures on Cycle Lengths in Graphs
Authors: Gao Jun , Huo Qingyi , Liu Chun-Hung , Ma Jie
Published: October 2020

In this paper, we prove a tight minimum degree condition in general graphs for the existence of paths between two given endpoints whose lengths form a long arithmetic progression with common difference one or two. This allows us to obtain a number of exact and optimal results on cycle lengths in graphs of given minimum degree, connectivity or chromatic number.

More precisely, we prove the following statements by a unified approach: 1. Every graph $G$ with minimum degree at least $k+1$ contains cycles of all even lengths modulo $k$; in addition, if $G$ is $2$-connected and non-bipartite, then it contains cycles of all lengths modulo $k$. 2. For all $k\geq 3$, every $k$-connected graph contains a cycle of length zero modulo $k$. 3. Every $3$-connected non-bipartite graph with minimum degree at least $k+1$ contains $k$ cycles of consecutive lengths. 4. Every graph with chromatic number at least $k+2$ contains $k$ cycles of consecutive lengths. The 1st statement is a conjecture of Thomassen, the 2nd is a conjecture of Dean, the 3rd is a tight answer to a question of Bondy and Vince, and the 4th is a conjecture of Sudakov and Verstraëte. All of the above results are best possible.
Clinical and Immunologic Predictors of Mycobacterium avium Complex Immune Reconstitution Inflammatory Syndrome in a Contemporary Cohort of Patients With Human Immunodeficiency Virus
Authors: Breglio Kimberly F , Vinhaes Caian L , Arriaga María B , Nason Martha , Roby Gregg , Adelsberger Joseph , Andrade Bruno B , Sheikh Virginia , Sereti Irini
Published: October 2020

Background

People with human immunodeficiency virus (HIV) can present with new or worsening symptoms associated with Mycobacterium avium complex (MAC) infection shortly after antiretroviral therapy (ART) initiation as MAC immune reconstitution inflammatory syndrome (MAC-IRIS). In this study, we assessed the utility of several laboratory tests as predictors of MAC-IRIS.

Methods

People with HIV with clinical and histologic and/or microbiologic evidence of MAC-IRIS were identified and followed up to 96 weeks post–ART initiation within a prospective study of 206 ART-naive patients with CD4 <100 cells/µL.

Results

Fifteen (7.3%) patients presented with MAC-IRIS within a median interval of 26 days after ART initiation. Patients who developed MAC-IRIS had lower body mass index, lower hemoglobin levels, higher alkaline phosphatase (ALP), and increased CD38 frequency and mean fluorescence intensity on CD8+ T cells at the time of ART initiation compared with non-MAC IRIS patients. A decision tree inference model revealed that stratifying patients based on levels of ALP and D-dimer could predict the likelihood of MAC-IRIS. A binary logistic regression demonstrated that higher levels of ALP at baseline were associated with increased risk of MAC-IRIS development.

Conclusions

High ALP levels and increased CD8+ T-cell activation with low CD4 counts at ART initiation should warrant suspicion for subsequent development of MAC-IRIS.
Neutralizing Antibody Responses in COVID-19 Convalescent Sera
Authors: Lee William T , Girardin Roxanne C , Dupuis Alan P , Kulas Karen E , Payne Anne F , Wong Susan J , Arinsburg Suzanne , Nguyen Freddy T , Mendu Damodara Rao , Firpo-Betancourt Adolfo , Jhang Jeffrey , Wajnberg Ania , Krammer Florian , Cordon-Cardo Carlos , Amler Sherlita , Montecalvo Marisa , Hutton Brad , Taylor Jill , McDonough Kathleen A
Published: October 2020

Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31–35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.
Provider–patient communication and hospital ratings: perceived gaps and forward thinking about the effects of COVID-19
Authors: Belasen Alan T , Oppenlander Jane , Belasen Ariel R , Hertelendy Attila J
Published: October 2020

Objectives

To highlight clinical and operational issues, identify factors that shape patient responses in Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) and test the correlations between composite measures and overall hospital ratings.

Design

Responses to HCAHPS surveys were used in a partial correlation analysis to ascertain those HCAHPS composite measures that most relate to overall hospital ratings. The linear mean scores for the composite measures and individual and global items were analyzed with descriptive analysis and correlation analysis via JMP and SPSS statistical software.

Setting

HCAHPS is a patient satisfaction survey required by the Centers for Medicare and Medicaid Services for hospitals in the USA. The survey is for adult inpatients, excluding psychiatric patients.

Participants

3382 US hospitals.

Intervention

None.

Main Outcome Measure

Pearson correlation coefficients for the six composite measures and overall hospital rating.

Results

The partial correlations for overall hospital rating and three composite measures are positive and moderately strong for care transition (0.445) and nurse communication (0.369) and weak for doctor communication (0.066).

Conclusions

From a health policy standpoint, it is imperative that hospital administrators stress open and clear communication between providers and patients to avoid problems ranging from misdiagnosis to incorrect treatment. Additional research is needed to determine how the coronavirus of 2019 pandemic influences patients’ perceptions of quality and willingness to recommend hospitals at a time when nurses and physicians show symptoms of burnout due to heavy workloads and inadequate personal protective equipment.
Drug Positivity Findings from a Universal Umbilical Cord Tissue Drug Analysis Program in Appalachia
Authors: Yossuck Panitan , Tacker Danyel H
Published: October 2020

Background

West Virginia has high rates of opioid-related health crises and deaths that extend to pregnant women and newborns. Our institutional screening approach has included universal umbilical cord tissue drug analysis (UCTDA) since 2013. The objective of this study was to retrospectively report incidence of in utero drug exposure using UCTDA data.

Methods

Two sequential UCTDA data sets (October 2013 to September 2015, and October 2016 to September 2018) represent interrupted epochs given changes in interfaced data availability. UCTDA positivity (by drug class and parent drug) and numbers of drugs detected in each specimen were retrospectively analyzed. THC was removed from the analysis because of discontinuous testing, and 4 opioids were separated from the data set given the potential for both therapeutic and illicit use.

Results

UCTDA specimens that were positive for drugs (22% overall) decreased between Epochs 1 and 2, from 25% to 20%. Increased positivity was noted for hydrocodone (+407%), oxycodone (+240%), amphetamines (+506%), and cocaine (+417%). Fentanyl and morphine positivity decreased by 75% and 18%, respectively, whereas buprenorphine detection increased 195%. Most positive specimens (80% overall) had 1 drug present, but specimens positive for 2 to 6 discrete drugs were found.

Conclusion

Universal UCTDA allows for unbiased assessment of drug exposure in infants. With the additional knowledge of therapeutic indications for drug use, UCTDA may allow for analysis of trends in illicit drug use and the impact of interventions to curb neonatal abstinence syndrome.
Rotigotine: A Review of Analytical Methods for the Raw Material, Pharmaceutical Formulations, and Its Impurities
Authors: Mendes Thamara de Carvalho , Pinto Eduardo Costa , Cabral Lucio Mendes , de Sousa Valeria Pereira
Published: October 2020

Background

Rotigotine is a dopaminergic agonist developed for the treatment of Parkinson’s disease and restless leg syndrome. The pure levorotatory enantiomer is marketed in several countries as a transdermal patch. Reports of oxidation and instability in a previous formulation indicate the need to evaluate impurities in both the raw material and pharmaceutical dosage forms of rotigotine to ensure product quality.

Objective

This review examines the main analytical methods for analyzing rotigotine in raw material and its transdermal patches with the aim of assisting the development of new pharmaceutical formulations and stability studies.

Methods

Analytical methods based on high-performance liquid chromatography for rotigotine from pharmacopoeias and literature were evaluated. A comparison was made between the methods found in the literature and official rotigotine monographs described by the United States, European, and British Pharmacopoeias, including a discussion of their acceptance limits for impurities related to the drug. The different impurities from the synthesis processes and degradation studies of rotigotine were also evaluated, as well as the main articles that describe methods for assessing their chiral purity.

Results

Qualified and unofficial official impurities found in forced degradation studies were verified. The methods presented show adequate specificity and selectivity in determining the drug in the presence of its impurities.

Conclusions

The approached methods are promising, but more detailed studies on the stability of rotigotine are still lacking, mainly in the pharmacokinetic and toxicological characterization of its impurities.
Cross-Sectional Assessment of Burn Center and Nonburn Center Patient Care: A Multi-Database Comparison
Authors: Prindeze Nicholas J , Marano Michael A , Shupp Jeffrey W , Johnson Laura S
Published: October 2020

The practice of burn care is complex and continues to be a rapidly evolving field. To assess how differences in management affect hospital stay characteristics and outcomes, the authors sought to compare outcomes data from two sources, such as burn center and nonburn center data. The National Burn Repository (NBR, version 8) and the 2014 Nationwide Readmission Database (NRD) were compared based on ICD-9 948-series burn-related diagnosis codes, generating a total of 83,068 and 14,131 burn patients from the NBR and NRD, respectively. Patients were stratified by burn size and compared based on demographic factors and hospital stay characteristics. t-Test and chi-squared statistics were performed with SAS, version 9.4. Burn patient populations from the NBR and NRD databases, when stratified by patient demographic factors, were found to have similar sex distributions, 68% and 64% male, respectively. The average age was significantly higher in the NRD data at 39.5 ± 23.6 compared with 30.9 ± 22.3 years. Hospital stay characteristics, including length of stay and mortality, were not found to differ significantly. Differences were identified in the number of trips to the OR, which was significantly greater in the NBR population as well as the total cost of care, which was significantly less in the NBR population at $92k compared with $125k. This study has shown through the interpretation of multiple databases that not only do demographics differ between burn and nonburn center populations, but also do management strategies, particularly in operative intervention and cost.
Bargain Hunting for Buffered Lidocaine: A Collaborative Discovery of Cost-saving Strategies That Can Improve Patient Care
Authors: Simmons Curtis L , Harper Laura K , Holst Kathryn J , Brinkman Nathan J , Lee Christine U
Published: October 2020

Buffered lidocaine is a local anesthetic option during percutaneous needle-directed procedures in the breast. At our institution, sodium bicarbonate (the buffer) is dispensed in volumes that frequently lead to medical waste and shortages. In this study, we describe how moving the buffering of lidocaine from the procedure room to our clinical hospital pharmacy results in a reduction in costs and improves satisfaction across the breast radiology department. While cost savings are difficult to tease out in practices that opt for bundled payments, we were able to access pricing and supply data and coordinate with our pharmacy to change our practice. Making these changes saves our practice $26 000 a year and allows us to continue to offer buffered lidocaine even during sodium bicarbonate shortages. This manuscript describes how these changes came about and their economic impact.
Two new species of the freshwater-crab genusDemaniettaBott, 1966 (Decapoda: Brachyura: Potamidae) from southern Myanmar
Authors: Shi Bo-Yang , Chen Xiao-Yong , Sun Hong-Ying
Published: October 2020

We describe two new species of the freshwater-crab genus Demanietta  Bott, 1966 from Tanintharyi (Tenasserim) division, southern Myanmar (Burma), Demanietta liui  sp. nov. and Demanietta lenya  sp. nov.  Demanietta liui  sp. nov. is morphologically most similar to D. thagatensis  Rathbun, 1904 and D. khirikhan  Yeo, Naiyanetr & Ng, 1999; D. lenya  sp. nov. appears close to D. manii  Rathbun, 1904, D. merguensis  Bott, 1966, and D. nakhonsi  Yeo, Naiyanetr & Ng, 1999. The two new species are easily distinguished from their most similar congeners in the shape of the external orbital tooth, epibranchial tooth, and male first gonopod. Molecular analysis based on partial mitochondrial 16S rDNA also supports the systematic position of the new taxa.
Effects of Bt Cry78Ba1 Toxin on Larvae and Adults of Apis mellifera (Hymenoptera: Apidae)
Authors: Han Bo , Cao Beibei , Yang Yang , Wang Xinling , Geng Lili , Diao Qingyun , Dai Pingli
Published: October 2020

Cry78Ba1 is Bacillus thuringiensis Berliner (Bacillales: Bacillaceae) (Bt) protein found with high insecticidal activity against the piercing–sucking insect Laodelphax striatellus Fallén (Homoptera: Delphacidae) and has broad application prospects for control of the rice planthopper. As honey bees may be exposed to Bt Cry78Ba1 rice pollen by feeding, we evaluated the risk of Bt Cry78Ba1 toxin to Apis mellifera L. workers. A dietary exposure experiment was conducted on worker larvae and adults under controlled laboratory conditions to examine the effects of Cry78Ba1 toxin on honey bees. Worker bee larvae were fed a diet containing Cry78Ba1 toxin (0.01, 0.1, 1, and 10 mg/liter) on day 2 through day 5 after grafting, and adults were exposed to syrup containing Cry78Ba1 for up to 16 d. Negative control (no test substance added), solvent control (1 mM Tris–HCl), and positive control (dimethoate 45 mg/liter for the larva test, 1 and 45 mg/liter for the adult test) groups were established. Compared with the negative control, larvae and adults that consumed food containing Cry78Ba1 toxin exhibited no significant differences in survival, larval weight, or pollen or syrup consumption. This result indicates that chronic oral exposure to Cry78Ba1 toxin has no negative effects on honey bees at the maximum tested concentration.
The ‘China Shock’ revisited: insights from value added trade flows
Authors: Jakubik Adam , Stolzenburg Victor
Published: October 2020

We exploit a decomposition of gross trade flows into their value added components to reassess the relationship between increased imports from China and manufacturing jobs in US local labour markets following the seminal paper of Autor, Dorn, and Hanson (2013, ADH). Decomposed trade flows enable us to address identification and measurement issues inherent to gross trade data. In particular, it allows us to remove US value added in Chinese exports from the exposure measure which is mechanically correlated with the dependent variable and overstates the volume of the trade shock. In addition, the decomposition permits to correct for double counting, to remove primary and services inputs in manufacturing exports, and to assign competition to the upstream industry that supplied the value added rather than the final exporting industry. This further reduces the volume of the shock and improves the accuracy of the import exposure measure. Consequently, we find considerable differences in the pattern of regions that are most affected by the trade shock and show that imports from China can explain less of the decline in US manufacturing than what gross trade data would suggest. We then separate the shock into a China-driven domestic reform and a third-country-driven value chain component, and find in line with ADH that the smaller, but still negative labour market effects are indeed China driven. Finally, we observe that the negative effects identified in ADH are not present in the 2008–2014 period, which is in line with the hypothesis that labour market adjustment has largely concluded.
The conserved brassinosteroid-related transcription factor BIM1a negatively regulates fruit growth in tomato
Authors: Mori Kentaro , Lemaire-Chamley Martine , Jorly Joana , Carrari Fernando , Conte Mariana , Asamizu Erika , Mizoguchi Tsuyoshi , Ezura Hiroshi , Rothan Christophe
Published: October 2020

Brassinosteroids (BRs) are steroid hormones that play key roles in plant development and defense. Our goal is to harness the extensive knowledge of the Arabidopsis BR signaling network to improve productivity in crop species. This first requires identifying components of the conserved network and their function in the target species. Here, we investigated the function of SlBIM1a, the closest tomato homolog of AtBIM1, which is highly expressed in fruit. SlBIM1a-overexpressing lines displayed severe plant and fruit dwarfism, and histological characterization of different transgenic lines revealed that SlBIM1a expression negatively correlated with fruit pericarp cell size, resulting in fruit size modifications. These growth phenotypes were in contrast to those found in Arabidopsis, and this was confirmed by the reciprocal ectopic expression of SlBIM1a/b in Arabidopsis and of AtBIM1 in tomato. These results determined that BIM1 function depends more on the recipient species than on its primary sequence. Yeast two-hybrid interaction studies and transcriptomic analyses of SlBIM1a-overexpressing fruit further suggested that SlBIM1a acts through its interaction with SlBZH1 to govern the transcriptional regulation of growth-related BR target genes. Together, these results suggest that SlBIM1a is a negative regulator of pericarp cell expansion, possibly at the crossroads with auxin and light signaling.