bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Characterization of Pestalotioid Fungi Causing Leaf Spots on Mango in Southern China
Authors: Shu Juan , Yu Zhihe , Sun Wenxiu , Zhao Jiang , Li Qili , Tang Lihua , Guo Tangxun , Huang Suiping , Mo Jianyou , Hsiang Tom , Luo Shuming
Published: November 2019

Mango is an economically important fruit crop in southern China. However, leaf spots restrict the development of mango trees, reducing the yield and production. Pestalotioid fungi are one of the major agents causing leaf spots on mango. During 2016 and 2017, 21 isolates of pestalotioid fungi associated with leaf spots on mango leaves were collected from five provinces in southern China: Guangxi, Hainan, Yunnan, Guangdong, and Fujian. All 21 isolates were subjected to morphological characterization and DNA sequence analysis. The morphological data were combined with analyses of concatenated sequences of the ITS (internal transcribed spacer), TEF 1-α (translation elongation factor), and TUB2 (β-tubulin) for higher resolution of the species identity of these isolates. The results showed that these isolates belong to Neopestalotiopsis clavispora, Pestalotiopsis adusta, P. anacardiacearum, P. asiatica, P. photinicola, P. saprophyta, P. trachicarpicola, and Pseudopestalotiopsis ampullacea. Pathogenicity test results showed that all these species could cause symptoms. On detached mango leaves (cv. Tainong), early foliar symptoms on leaves were small yellow-to-brown lesions. Later, these spots expanded with uneven borders, turned white to gray, and coalesced to form larger gray patches. To our knowledge, this is the first description of N. clavispora, P. adusta, P. asiatica, P. photinicola, P. saprophyta, P. trachicarpicola, or Ps. ampullacea as causal agents for leaf spots on mango worldwide.
A comparison of the Functional Movement ScreenTM and the Landing Error Scoring System: A cohort study
Authors: Tran Andrew A. , Shen Jennifer , Wernecke Chloe , Gatewood Corey T. , Harris Alex H.S. , Dragoo Jason L.
Published: November 2019

Background:

The Functional Movement Screen (FMSTM) is a nonspecific movement pattern assessment while the Landing Error Scoring System (LESS) is a screen for movement patterns associated with lower extremity injury. The purpose of this study was to determine if the LESS and FMSTM are correlated or if they can be used as complementary assessments of preseason injury risk for anterior cruciate ligament injury.

Methods:

FMSTM and LESS were used to conduct a cohort study of 126 male National Collegiate Athletic Association Division IA football players. One hundred and eleven players met the criteria for inclusion during data review. At risk and not at risk LESS scores of players and FMSTM exercise score status were compared using Welch’s t-test. Associations between FMSTM composites and LESS scores were evaluated using linear regression.

Results:

The average LESS score was 5.51±1.34, and the average composite FMSTM score was 11.77±2.13 (max=15). A poor FMSTM squat score (≤1 or asymmetry present) was associated with a higher LESS score (P<0.001). No other FMSTM individual exercise score was associated with an at-risk LESS score (P>0.05). Composite FMSTM score was loosely associated with the LESS score (R-squared=0.0677, P=0.006). Prior history of an ACL injury and player position were not associated with LESS score on multivariate regression (P>0.05).

Conclusions:

The LESS and FMSTM are not well correlated and may serve as complementary assessments for preseason injury risk.

Level of Evidence:

Level III.
The gut microbiome-joint connection: implications in osteoarthritis
Authors: Favazzo Lacey J. , Hendesi Honey , Villani David A. , Soniwala Sarah , Dar Qurratul-Ain , Schott Eric M. , Gill Steven R. , Zuscik Michael J.
Published: November 2019

Purpose of review

Osteoarthritis is a debilitating disease leading to joint degeneration, inflammation, pain, and disability. Despite efforts to develop a disease modifying treatment, the only accepted and available clinical approaches involve palliation. Although many factors contribute to the development of osteoarthritis, the gut microbiome has recently emerged as an important pathogenic factor in osteoarthritis initiation and progression. This review examines the literature to date regarding the link between the gut microbiome and osteoarthritis.

Recent findings

Studies showing correlations between serum levels of bacterial metabolites and joint degeneration were the first links connecting a dysbiosis of the gut microbiome with osteoarthritis. Further investigations have demonstrated that microbial community shifts induced by antibiotics, a germ-free environment or high-fat are important underlying factors in joint homeostasis and osteoarthritis. It follows that strategies to manipulate the microbiome have demonstrated efficacy in mitigating joint degeneration in osteoarthritis. Moreover, we have observed that dietary supplementation with nutraceuticals that are joint protective may exert their influence via shifts in the gut microbiome.

Although role of the microbiome in osteoarthritis is an area of intense study, no clear mechanism of action has been determined. Increased understanding of how the two factors interact may provide mechanistic insight into osteoarthritis and lead to disease modifying treatments.
Critical Role of p38 in Spinal Cord Injury by Regulating Inflammation and Apoptosis in a Rat Model
Authors: Zhang Heng-Wei , Ding Jian-Dong , Zhang Zeng-Shan , Zhao Si-shun , Duan Kang-ying , Zhu Bao-qi , Zhao Wen-Feng , Chai Zong-Tao , Liu Xiao-Wei
Published: November 2019

Study Design.

To evaluate the effect of p38 pathway on spinal cord injury (SCI), a rat model of SCI was performed.

Objective.

We determined the effect of p38 on SCI and SCI related inflammation, apoptosis, and autophagy.

Summary of Background Data.

SCI is a severe clinical problem worldwide. It is difficult to prevent cell necroptosis and promote the survival of residual neurons after SCI. p38, a class of mitogen-activated protein kinases, its effect on SCI and SCI related inflammation, apoptosis, and autophagy have not been studied very well.

Methods.

The rats were randomly divided into the following four groups: the sham-operated (sham) group, the SCI group, the SCI + vehicle group, and the SCI + SB203580 (10 mg/kg) group. The p38 inhibitor SB203580 was administered by oral (10 mg/kg/d) gavage once per day for 14 days. Neurological recovery was assessed using the Basso, Beattie, and Bresnahan locomotion rating scale. Apoptosis, autophagy, and inflammation related proteins were measured by enzyme-linked immunosorbent assay kits or western blotting.

Results.

Our results showed that p38 was upregulated after SCI from day 3, which was paralleled with the levels of its proteins ATF-2, suggesting an increase in p38 activity. Our results showed administration of SB203580 attenuated histopathology and promoted locomotion recovery in rats after SCI. SB203580 administration significantly inhibited inflammatory cytokines levels as well as the inflammation signaling pathway. SB203580 administration also modulated the apoptosis and autophagy signaling pathway.

Conclusion.

Our findings suggest that p38 inhibitor SB203580 treatment alleviates secondary SCI by inhibiting inflammation and apoptosis, thereby promoting neurological and locomoter functional recovery, thus suggest the important role of p38 in neuronal protection after SCI.

Level of Evidence: N/A
Commentary: Why Has Uptake of Pneumococcal Vaccines for Children Been So Slow? The Perils of Undervaluation
Authors: Bloom David E. , Kirby Paige N. , Pugh Sarah , Stawasz Andrew
Published: November 2019

Pediatric pneumococcal disease exacts a substantial burden on global health, much of which is vaccine-preventable. Despite this considerable burden and the demonstrably high efficacy of pneumococcal conjugate vaccines (PCVs), the overall level of PCV uptake remains concerningly low, especially compared with that of other childhood-recommended vaccines, such as tuberculosis and polio. A broad set of plausible explanations exists for this low uptake, including logistical challenges, psychosocial factors and affordability. One additional and systematic cause of low uptake, which is the focus of our discussion, is economists’ and policymakers’ tendency to undervalue vaccination in general by adopting a narrow health sector perspective when performing economic evaluations of vaccines. We present an alternative, societal framework for economic evaluations that encompasses a broader set of socioeconomic benefits in addition to health benefits. Quantifying a more comprehensive taxonomy of PCV’s benefits will help to address potential undervaluation and may be sufficient not only to justify recommendation and reimbursement but also to stimulate efforts and investment toward closing coverage gaps.
Bacterial Reservoirs in the Middle Ear of Otitis-prone Children Are Associated With Repeat Ventilation Tube Insertion
Authors: Seppanen Elke J. , Thornton Ruth B. , North Hannah JD , Corscadden Karli J. , Wiertsema Selma P. , Vijayasekaran Shyan , Coates Harvey L. , Jacoby Peter , Richmond Peter C. , Kirkham Lea-Ann S.
Published: November 2019

Background:

Repeat ventilation tube insertion (VTI) is common in children with recurrent acute otitis media (rAOM). Identifying risk factors associated with repeat surgery will improve clinical management and prevent repeat VTI.

Methods:

Surgical records were assessed at 8 years following VTI surgery for rAOM in children 6–36 months of age. Children were grouped according to detection of bacterial otopathogen in their middle ear effusion (MEE) at the time of VTI, and outcomes for future otorhinolaryngology surgery compared.

Results:

Age, gender, pneumococcal vaccination status, antibiotic usage, day-care attendance, number of siblings and number of AOM episodes were similar between groups. Of the 63 children who had PCR +ve MEE, 58.7% required repeat VTI compared with 31.4% of the 51 children with no otopathogen detected in their MEE (odds ratio = 3.1, 95% confidence interval [1.4–6.8]; P = 0.004). Nontypeable Haemophilus influenzae (NTHi) was the predominant otopathogen in MEE (79% of all PCR +ve MEE). Respiratory virus detection was not associated with repeat VTI.

Conclusions:

Presence of bacterial otopathogen, specifically nontypeable H. influenzae, in the middle ear during VTI was a predictor of children at-risk of repeat VTI. Here, we identify a modifiable microbiologic factor for repeat VTI that can be targeted to improve clinical management of rAOM.
Using Lean Performance Improvement for Patient-Centered Medical Home Transformation at an Academic Public Hospital
Authors: Wu Shirley , Brown Christopher , Black Susan , Garcia Michael , Harrington Darrell W.
Published: November 2019

Although Lean performance improvement (PI) has been used in health care for more than 15 years, little is known about how Lean has been used in Patient-Centered Medical Home (PCMH) transformation. We describe our experience implementing Lean in our safety-net, primary care teaching clinic. To advance high value care, a culture of systematic, sustainable PI methods needed to be integrated into primary care and taught to resident physicians. Clinic leadership were trained in Lean methods, protected time was dedicated to PI for a stable, interdisciplinary team, then visual management was introduced, and resident physicians were integrated into the clinic's PI initiatives. Self-assessment using the PCMH Assessment tool demonstrated improvement in core features of the PCMH model. Process outcomes also revealed successful, sustainable integration of Lean into our primary care clinic and resident training, and early findings show improvements in clinical quality outcomes. Patient survey outcomes demonstrate improvement in patient experience. Lean can be used successfully to promote PCMH transformation and create a culture of continuous PI in an academic, safety-net primary care setting.
Clinical Nurse Preparation and Partnership in Antibiotic Stewardship Programs
Authors: Carter Eileen J. , Manning Mary Lou , Pogorzelska-Maziarz Monika
Published: November 2019

OBJECTIVE

Describe clinical nurse involvement in antibiotic stewardship programs (ASPs).

BACKGROUND

The extent to which clinical nurses are supported and integrated into ASPs is unknown.

METHODS

Electronic survey of infection preventionists (IPs) working in acute care hospitals.

RESULTS

A total of 207 IPs nationwide reported on clinical nurses' involvement in their hospital's ASP. Among respondents, 42% reported the presence of a designated nurse executive that championed nurses' involvement in ASPs; 33% reported that the hospital provides antibiotic stewardship education and training to clinical nurses, and only 14% believed that clinical nurses have adequate stewardship knowledge to participate in ASP activities.

CONCLUSIONS

Study findings indicate the need for nurse leaders to improve the preparation and integration of clinical nurses in ASPs. While clinical nurses routinely perform activities that contribute to optimal antibiotic use, the knowledge and competency of clinical nurses in these activities and their formal integration in ASPs are minimal.
Cognitive impairment severity in relation to signs of subclinical Wernicke's encephalopathy in HIV and alcoholism comorbidity
Authors: Le Berre Anne-Pascale , Fama Rosemary , Sassoon Stephanie A. , Zahr Natalie M. , Pfefferbaum Adolf , Sullivan Edith V.
Published: November 2019

Objectives:

The comorbidity of HIV infection and alcoholism (ALC) is prevalent. Wernicke's encephalopathy, a neurological disorder resulting from thiamine depletion, has been generally associated with alcoholism but has also been reported in HIV infection. This study examined whether subclinical Wernicke's encephalopathy signs could contribute to the heterogeneity of cognitive and motor deficits observed in individuals with both disease conditions (HIV+ALC).

Design:

Sixty-one HIV+ALC individuals and 59 controls were assessed on attention and working memory, production, immediate and delayed episodic memory, visuospatial abilities, and upper limb motor function.

Methods:

Using Caine criteria (dietary deficiency, oculomotor abnormality, cerebellar dysfunction, and altered mental state), HIV+ALC individuals were classified by subclinical Wernicke's encephalopathy risk factors.

Results:

Signs of subclinical Wernicke's encephalopathy were present in 20% of the HIV+ALC participants. For attention/working memory, delayed memory, and upper limb motor function, HIV+ALC Caine 2+ (i.e. meeting two or three criteria) demonstrated the most severe deficits, scoring lower than HIV+ALC Caine 1 (i.e. meeting one criterion), HIV+ALC Caine 0 (i.e. meeting no criteria), and controls.

Conclusion:

The high prevalence of subclinical signs of Wernicke's encephalopathy and relevance to performance indicate that this condition should be considered in assessment of HIV-infected individuals, especially when alcoholism comorbidity is known or suspected. Above and beyond clinical factors, such as depression, alcoholism and HIV disease-related variables, AIDS, hepatitis C and drug history known to mediate neuropsychological performance, subclinical Wernicke's encephalopathy signs could partly explain the heterogeneity in patterns and severity of cognitive and motor impairments in HIV-infected individuals with alcoholism comorbidity.
Serum extracellular vesicles expressing bone activity markers associate with bone loss after HIV antiretroviral therapy
Authors: Marques de Menezes Erika G. , Ramallho Janaina , Bucovsky Mariana , Shane Elizabeth , Yin Michael T. , Norris Philip J.
Published: November 2019

Objective:

We tested whether bone-related extracellular vesicle phenotypes changed after initiating antiretroviral therapy (ART) and determined whether changes in levels of extracellular vesicles correlated with changes in bone mineral density (BMD).

Design:

Extracellular vesicle phenotypes were measured in blinded serum samples from 15 adults with HIV at baseline, 1, 3, 6 and 12 months after ART initiation. Not all samples were available at each time point so we averaged early (TP1, 1–3 months) and late (TP2, 6–12 months) time points.

Methods:

Extracellular vesicles were stained for osteocalcin (OC), RANKL (CD254), RANK (CD265), M-CSF (macrophage colony stimulating factor), and CD34. Serum OC, procollagen type I N-terminal propeptide (P1NP), and C-terminal telopeptide of type 1 collagen (CTx) were also measured.

Results:

BMD significantly decreased from baseline to 12 months. Levels of OC+EVs, serum OC, serum P1NP, and CTx were significantly higher at early and late time points compared with baseline. Increases in EVs expressing OC, RANKL, RANK, and CD34 from baseline to TP1 were associated with decreases in total hip BMD from baseline to 12 months. Change in serum OC, P1NP, and CTx from baseline to TP1 or TP2 did not correlate with change in BMD.

Conclusion:

Early changes in extracellular vesicles expressing markers of bone activity were associated with total hip bone loss 12 months after ART initiation. These data suggest that serum extracellular vesicles may serve as novel biomarkers of bone remodeling. Future studies are required to determine if extracellular vesicles contribute to the effects of ART on changes in bone turnover markers and BMD.
Effects of Ketamine Anesthesia on Efficacy, Tolerability, Seizure Response, and Neurocognitive Outcomes in Electroconvulsive Therapy
Authors: Ainsworth Nicholas J. , Sepehry Amir A. , Vila-Rodriguez Fidel
Published: November 2019

Electroconvulsive therapy (ECT) remains the most effective treatment for major depressive disorder. Ketamine is an anesthetic gaining attention for its rapid antidepressant effect. Numerous randomized controlled trials have investigated the effect of ketamine anesthesia in ECT on various clinical outcomes. Previous systematic reviews have not found benefit for overall depression response, although some have found evidence of benefit early in the ECT course. Clear quantitative conclusions have not been established regarding other outcomes, particularly while only using data from high-quality studies. We aimed to examine all data from double-blind randomized controlled trials comparing ketamine to other anesthetics via meta-analysis, to make recommendations regarding ECT practice and future research. Data were extracted for depressive symptoms, seizure duration and electrical dose, neuropsychological performance, and adverse effects. Effect sizes were calculated using Hedge's g and odds ratios. Eighteen studies (n = 915) were included in the meta-analysis. Ketamine was not found to enhance improvement of depressive symptoms, either early in ECT course or at end of study. Ketamine had a large effect on increasing seizure duration both overall (Hedge's g = 0.71, P = 0.038) and in the subgroup receiving ketamine in combination with another anesthetic (Hedge's g = 0.78, P < 0.01), and on decreasing electrical dose (Hedge's g = 1.98, P = 0.039). There was no significant effect of ketamine on any individual neuropsychological domain. Ketamine was not associated with increased adverse effects, except for hypertension in patients receiving ketamine monotherapy. Significant heterogeneity was present for many outcomes, and sensitivity analyses suggested a relation to methodological variation in most cases. This study supports the finding that ketamine does not enhance ECT's antidepressant effect, including on early improvement, but provides substantial evidence for enhancing seizure duration and reducing electrical dose. No significant benefit was found on neurocognitive outcomes, but analysis was limited by small sample sizes and high heterogeneity. Ketamine is generally safe in ECT, particularly as a coanesthetic. Our findings provide meta-analytic support to the recommendations in ECT clinical guidelines for use of coadjuvant ketamine in ECT where seizures are suboptimal. Further studies targeting neurocognitive outcomes are encouraged.
Tooth replacement in early sarcopterygians
Authors: Doeland Mark , Couzens Aidan M. C. , Donoghue Philip C. J. , Rücklin Martin
Published: November 2019

Teeth were an important innovation in vertebrate evolution but basic aspects of early dental evolution remain poorly understood. Teeth differ from other odontode organs, like scales, in their organized, sequential pattern of replacement. However, tooth replacement patterns also vary between the major groups of jawed vertebrates. Although tooth replacement in stem-osteichthyans and extant species has been intensively studied it has been difficult to resolve scenarios for the evolution of osteichthyan tooth replacement because of a dearth of evidence from living and fossil sarcopterygian fishes. Here we provide new anatomical data informing patterns of tooth replacement in the Devonian sarcopterygian fishes
Onychodu
s,
Eusthenopteron
and
Tiktaalik
and the living coelacanth
Latimeria
based on microfocus- and synchrotron radiation-based X-ray microtomography. Early sarcopterygians generated replacement teeth on the jaw surface in a pattern similar to stem-osteichthyans, with damaged teeth resorbed and replacement teeth developed on the surface of the bone. However, resorption grades and development of replacement teeth vary spatially and temporally within the jaw. Particularly in
Onychodus
, where teeth were also shed through anterior rotation and resorption of bone at the base of the parasymphyseal tooth whorl, with new teeth added posteriorly. As tooth whorls are also present in more stem-osteichthyans, and statodont tooth whorls are present among acanthodians (putative stem-chondrichthyans), rotational replacement of the anterior dentition may be a stem-osteichthyan character. Our results suggest a more complex evolutionary history of tooth replacement.
Research on catalytic pyrolysis of algae based on Py-GC/MS
Authors: Zhao Hao , Zhong Zhaoping , Li Zhaoying , Wang Wei
Published: November 2019

In order to improve the quality of catalysis products of algae, composite molecular sieve catalyst was prepared by digestion and crystallization of HZSM-5 to reduce the oxygen content of the catalytic products. According to the analysis of the pyrolysis products, the best preparation conditions were chosen of tetra propylammonium hydroxide (TPAOH) solution 2.0 mol l
−1
, cetyltrimethylammonium bromide (CTAB) solution 10 wt%, crystallization temperature 110°C, digestion–crystallization time: 24–24 h. The results indicate that the main function of catalysts is to promote the conversion of alcohols into hydrocarbons by reducing energy barriers. Catalysed by the composite molecular sieve, the content of alcohols in the pyrolysis products decreased from more than 30% to less than 10%, the content of hydrocarbons increased from 20% to nearly 60%, while all the adverse components remained at a low level, which indicates that the catalytic pyrolysis products are of high quality. The great deoxidation effect of composite molecular sieves is not only due to the expansion of the range of organic matter during re-pyrolysis, but also the increasing of the residence time of pyrolysis products inside the structure for the external mesoporous structure.
Pure shear deformation and its induced mechanical responses in metallic glasses
Authors: Zhou Zhukun , Wang Hao , Li Mo
Published: November 2019

Shear is a basic deformation mode governing yielding, plasticity and fracture in metallic solids. For amorphous metals, due to various constraints, little work is available in addressing directly shear deformation and shear-induced mechanical property changes which are vital to the mechanistic understanding of this new class of disordered materials. Here, by using a finite deformation theory, we examine the pure shear deformation in a bulk metallic glass in a large range of shear strains. With the continuum approach, we show systematically for the first time the detailed shear deformation behaviours, shear-induced normal stress and strain relations, softening in the elastic constants, volume dilatation and free energy change induced by the shear deformation. These results point to two major consequences from the shear deformation, one is the mechanical degradations and the other material degradation which is responsible for the changes in the mechanical properties of the disordered materials.
An observation-driven time-dependent basis for a reduced description of transient stochastic systems
Authors: Babaee H.
Published: November 2019

We present a variational principle for the extraction of a time-dependent orthonormal basis from random realizations of transient systems. The optimality condition of the variational principle leads to a closed-form evolution equation for the orthonormal basis and its coefficients. The extracted modes are associated with the most transient subspace of the system, and they provide a reduced description of the transient dynamics that may be used for reduced-order modelling, filtering and prediction. The presented method is matrix free; it relies only on the observables of the system and ignores any information about the underlying system. In that sense, the presented reduction is purely observation driven and may be applied to systems whose models are not known. The presented method has linear computational complexity and memory storage requirement with respect to the number of observables and the number of random realizations. Therefore, it may be used for a large number of observations and samples. The effectiveness of the proposed method is tested on four examples: (i) stochastic advection equation, (ii) stochastic Burgers equation, (iii) a reduced description of transient instability of Kuramoto–Sivashinsky, and (iv) a transient vertical jet governed by the incompressible Navier–Stokes equation. In these examples, we contrast the performance of the time-dependent basis versus static basis such as proper orthogonal decomposition, dynamic mode decomposition and polynomial chaos expansion.
Is there an oxidative cost of acute stress? Characterization, implication of glucocorticoids and modulation by prior stress experience
Authors: Majer Ariana D. , Fasanello Vince J. , Tindle Kailey , Frenz Brian J. , Ziur Alexis D. , Fischer Chelsea P. , Fletcher Kelsey L. , Seecof Olivia M. , Gronsky Sarah , Vassallo Brian G. , Reed Wendy L. , Paitz Ryan T. , Stier Antoine , Haussmann Mark F.
Published: November 2019

Acute rises in glucocorticoid hormones allow individuals to adaptively respond to environmental challenges but may also have negative consequences, including oxidative stress. While the effects of chronic glucocorticoid exposure on oxidative stress have been well characterized, those of acute stress or glucocorticoid exposure have mostly been overlooked. We examined the relationship between acute stress exposure, glucocorticoids and oxidative stress in Japanese quail (
Coturnix japonica
). We (i) characterized the pattern of oxidative stress during an acute stressor in two phenotypically distinct breeds; (ii) determined whether corticosterone ingestion, in the absence of acute stress, increased oxidative stress, which we call glucocorticoid-induced oxidative stress (GiOS); and (iii) explored how prior experience to stressful events affected GiOS. Both breeds exhibited an increase in oxidative stress in response to an acute stressor. Importantly, in the absence of acute stress, ingesting corticosterone caused an acute rise in plasma corticosterone and oxidative stress. Lastly, birds exposed to no previous acute stress or numerous stressful events had high levels of GiOS in response to acute stress, while birds with moderate prior exposure did not. Together, these findings suggest that an acute stress response results in GiOS, but prior experience to stressors may modulate that oxidative cost.
Effects of a male meiotic driver on male and female transcriptomes in the house mouse
Authors: Lindholm Anna , Sutter Andreas , Künzel Sven , Tautz Diethard , Rehrauer Hubert
Published: November 2019

Not all genetic loci follow Mendel's rules, and the evolutionary consequences of this are not yet fully known. Genomic conflict involving multiple loci is a likely outcome, as restoration of Mendelian inheritance patterns will be selected for, and sexual conflict may also arise when sexes are differentially affected. Here, we investigate effects of thethaplotype, an autosomal male meiotic driver in house mice, on genome-wide gene expression patterns in males and females. We analysed gonads, liver and brain in adult same-sex sibling pairs differing in genotype, allowing us to identifyt-associated differences in gene regulation. In testes, only 40% of differentially expressed genes mapped to the approximately 708 annotated genes comprising thethaplotype. Thus, much of the activity of thethaplotype occurs intrans, and as upregulation. Sperm maturation functions were enriched among bothcisandtransactingthaplotype genes. Within thethaplotype, we observed more downregulation and differential exon usage. In ovaries, liver and brain, the majority of expression differences mapped to thethaplotype, and were largely independent of the differences seen in the testis. Overall, we found widespread transcriptional effects of this male meiotic driver in the house mouse genome.
Cerebral blood flow rates in recent great apes are greater than in
Australopithecus
species that had equal or larger brains
Authors: Seymour Roger S. , Bosiocic Vanya , Snelling Edward P. , Chikezie Prince C. , Hu Qiaohui , Nelson Thomas J. , Zipfel Bernhard , Miller Case V.
Published: November 2019

Brain metabolic rate (MR) is linked mainly to the cost of synaptic activity, so may be a better correlate of cognitive ability than brain size alone. Among primates, the sizes of arterial foramina in recent and fossil skulls can be used to evaluate brain blood flow rate, which is proportional to brain MR. We use this approach to calculate flow rate in the internal carotid arteries

(

Q
˙

ICA

)

, which supply most of the primate cerebrum.

Q
˙

ICA

is up to two times higher in recent gorillas, chimpanzees and orangutans compared with 3-million-year-old australopithecine human relatives, which had equal or larger brains. The scaling relationships between

Q
˙

ICA

and brain volume (
V
br
) show exponents of 1.03 across 44 species of living haplorhine primates and 1.41 across 12 species of fossil hominins. Thus, the evolutionary trajectory for brain perfusion is much steeper among ancestral hominins than would be predicted from living primates. Between 4.4-million-year-old
Ardipithecus
and
Homo sapiens
,
V
br
increased 4.7-fold, but

Q
˙

ICA

increased 9.3-fold, indicating an approximate doubling of metabolic intensity of brain tissue. By contrast,

Q
˙

ICA

is proportional to
V
br
among haplorhine primates, suggesting a constant volume-specific brain MR.
A pilot biomonitoring study of cumulative phthalates exposure among Vietnamese American nail salon workers
Authors: Varshavsky Julia R. , Morello-Frosch Rachel , Harwani Suhash , Snider Martin , Petropoulou Syrago-Styliani E. , Park June-Soo , Petreas Myrto , Reynolds Peggy , Nguyen Tuan , Quach Thu
Published: November 2019

Background

Many California nail salon workers are low-income Vietnamese women of reproductive age who use nail products daily that contain androgen-disrupting phthalates which may increase risk of male reproductive tract abnormalities during pregnancy. Yet, few studies have characterized phthalate exposures among this workforce.

Objective

To characterize individual metabolites and cumulative phthalates exposure among a potentially vulnerable occupational group of nail salon workers.

Study Design

We collected 17 post-shift urine samples from Vietnamese workers at six San Francisco Bay Area nail salons in 2011, which were analyzed for four primary phthalate metabolites: mono-n-butyl-, mono-isobutyl-, mono(2-ethylhexyl)-, and monoethyl phthalates (MnBP, MiBP, MEHP, and MEP, respectively) (μg/L). Phthalate metabolite concentrations and a potency-weighted sum of parent compound daily intake (Σandrogen-disruptor, μg/kg/day) were compared to 203 Asian Americans from the 2011– 12 National Health and Nutritional Examination Survey (NHANES) using Student’s t-test and Wilcoxin signed rank test.

Results

Creatinine-corrected MnBP, MiBP, MEHP (μg/g), and cumulative phthalates exposure (Σandrogen-disruptor, μg/kg/day) levels were 2.9 (p< 0.0001), 1.6 (p= 0.015), 2.6 (p< 0.0001), and 2.0 (p< 0.0001) times higher, respectively, in our nail salon worker population compared to NHANES Asian Americans. Levels exceeded the NHANES 95thor 75thpercentiles among some workers.

Conclusion

This pilot study suggests that nail salon workers are disproportionately exposed to multiple phthalates, a finding that warrants further investigation to assess their potential health significance.
Distinct single cell gene expression in peripheral blood monocytes correlates with tumor necrosis factor inhibitor treatment response groups defined by type I interferon in rheumatoid arthritis
Authors: Muskardin Theresa L. Wampler , Fan Wei , Jin Zhongbo , Jensen Mark A. , Dorschner Jessica M. , Ghodke-Puranik Yogita , Dicke Betty , Vsetecka Danielle , Wright Kerry , Mason Thomas , Persellin Scott , Michet Clement J. , Davis John M. , Matteson Eric , Niewold Timothy B.
Published: November 2019

Previously, we demonstrated that type I IFN (IFNβ/α) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of TNFi non-response in monocytes from RA patients. We compared single cell gene expression in purified classical (CL, n=342) and non-classical (NC, n=359) monocytes. RA patients were grouped according to their pre-TNFi IFNβ/α activity: those likely to have EULAR no response (non-response group, IFNβ/α 0 or >1.3, n=9) and those likely to have EULAR moderate or good response (response group, IFNβ/α > 0 and ≤1.3, n=6). Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the non-response group were unlikely to expressJAK1andIFI27(p <0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression ofIFNAR1, IRF1, TNFA, TLR4(p ≤0.0001 for each) and others was enriched. Interestingly,JAK1expression was absent in CL and NC monocytes from 9 patients. This pattern strongly associated with the non-response IFNβ/α group, suggesting a major biological difference betweenJAK1expressors and non-expressors. The type I IFN activity that was previously found to predict TNFi response associated with changes in gene expression in monocytes that suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. This work could suggest mechanisms for TNFi non-response, and potential therapeutic strategies for those patients unlikely to respond to TNFi.
Re-evaluating the evidence for fecal microbiota transplantation “super-donors” in inflammatory bowel disease
Authors: Olesen Scott W. , Gerardin Ylaine
Published: November 2019

Background

Fecal microbiota transplantation (FMT) is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions like inflammatory bowel disease (IBD). Previous FMT clinical trials have considered the possibility of a “donor effect”, that is, that FMT material from different donors has different clinical efficacies.

Aim & Methods

Here we re-evaluate evidence for donor effects in published FMT clinical trials for IBD.

Results

In 7 of 9 published studies, no statistically significant donor effect was detected when rigorously re-evaluating the original analyses. One study had statistically significant separation of microbiota composition of pools of donor stool when stratified by patient outcome. One study reported a significant effect but did not have underlying data available for re-evaluation. When quantifying the uncertainty on the magnitude of the donor effect, confidence intervals were large, including both zero donor effect and very substantial donor effects.

Conclusion

Although we found very little evidence for donor effects, the existing data also cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are likely necessary to determine if donor effects are clinically relevant for IBD.
Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data
Authors: Bean Daniel M. , Teo James , Wu Honghan , Oliveira Ricardo , Patel Raj , Bendayan Rebecca , Shah Ajay M. , Dobson Richard J. B. , Scott Paul A.
Published: November 2019

Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs.

The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing.

AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N=10,030, 64.6% male, average age 75.3 ± 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients.

Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts).

In high-risk patients (CHA2DS2-VASc ≥2) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%).

Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely-collected EHR data can replicate findings from large-scale curated registries.
Evaluation of the Hospital Readmissions Reduction Program
Authors: Khera Rohan , Wang Yongfei , Bernheim Susannah M. , Lin Zhenqiu , Normand Sharon-Lise T. , Krumholz Harlan M.
Published: November 2019

Background

There is conflicting evidence about whether the Hospital Readmission Reduction Program (HRRP) is associated with an increase in mortality.

Methods

In a cohort of Medicare beneficiaries hospitalized with heart failure (HF), we compared two published approaches to evaluating the association of HRRP and risk-adjusted 30-day mortality, including changes in average mortality across periods and changes in slope of monthly mortality rates across discrete periods. We also tested various methods with simulated data that was designed with an inflection in mortality.

Results

We identified 4,313,523 hospitalizations for HF, 1,788,219 for AMI, and 3,758,111 for pneumonia. Monthly slope-change models identified an increase in mortality for HF and pneumonia in the pre-HRRP period (P<.001 for slope-change). The changes in average mortality across the four time periods model found an increase in mortality for HF and pneumonia in the HRRP anticipation period (post-announcement, pre-implementation) as well as following HRRP implementation. However, under those conditions, our simulations reveal that method errs in identifying the timing of a change. Varying the data sources and risk-adjustment strategies had no significant effect on the results.

Conclusion

A national policy incentivizing efforts to reduce readmission did not increase the risk of mortality.
Evaluation of the concentration and profile of serum proteins and immunoglobulins in Mexican patients with advanced gastric cancer
Authors: y Orea María Alicia Díaz , Díaz Hernández Héctor Adrián , Lopez Rogelio Gonzalez , Conde Eduardo Gómez , Cárdenas Perea Maria Elena , Montaño Mónica Heredia , de los Ángeles Tapia Roldán María José , Juarez Alvarado Emmanuel Marcelino
Published: November 2019

Introduction

Gastric cancer remains an important health problem. It’s molecular mechanisms and interactions with the immune system are still not well elucidated. Therefore, we aimed to evaluate the concentration and profile of serum proteins and immunoglobulins in Mexican patients with advanced gastric cancer.

Materials and methods

We performed a descriptive study. Adult patients from both sexes were included. The problem group was formed of patients with advanced gastric cancer and the control group was formed of healthy subjects. Demographic data, gastric cancer histological type and stage of tumor node metastasis (TNM) system were recorded. The profile and concentration of serum proteins and immunoglobulins was determined and analyzed in different subgroups classified by sex, histologic type and stage of TNM system. To compare the concentrations of serum proteins and immunoglobulins the ANOVA test was performed. A p <0.05 was considered statistically significant.

Results

We included 88 patients with advanced gastric cancer and 74 healthy controls. There were no differences in demographic data among the groups, and the most common gastric cancer type was the diffuse (67.04%). Women with gastric cancer from any type presented higher levels of immunoglobulin G (IgG) compared with the control group (p <0.001) and men with gastric cancer of intestinal type in TNM stage III presented higher levels of IgG compared with it’s counterpart of diffuse type (p <0.001). Also, patients with intestinal type gastric cancer presented higher concentrations of alpha-1 globulins compared with patients with the diffuse type (p <0.05). Finally, patients with diffuse gastric cancer TNM stage IV presented the lowest albumin/globulin ratios.

Conclusion

There is a greater concentration of serum IgG in some subgroups of patients with advanced gastric cancer, the concentration of alpha-1 globulins is different between the intestinal and diffuse types and the albumin/globulin ratio is lower in the diffuse type.
Prevalence of erectile dysfunction patients with diabetes mellitus and its association with body mass index and glycated hemoglobin in Africa: a systematic review and meta-analysis
Authors: Shiferaw Wondimeneh Shibabaw , Akalu Tadesse Yirga , Aynalem Yared Asmare
Published: November 2019

Background

Mortality and morbidity in patients with diabetes mellitus (DM) is attributed to both the micro-vascular and macro-vascular complications. Variation among primary studies was seen on the prevalence of erectile dysfunction in Africa. Therefore, this study was aimed to estimate the pooled prevalence of erectile dysfunction patients with diabetes mellitus and its association with body mass index and glycated hemoglobin in Africa.

Methods

PubMed, Web of Science, Cochrane library, Scopus, Psyinfo, Africa online journal and Google Scholar were searched. A funnel plot and Egger’s regression test were used to see publication bias. I-squared statistic was used to check heterogeneity of studies. DerSimonian and Laird random-effects model was applied to estimate the pooled effect size. The subgroup and Meta regression analysis were conducted by country, sample size, and year of publication. Sensitivity analysis was deployed to see the effect of single study on the overall estimation. STATA version 14 statistical software was used for meta-analysis.

Result

A total of 20 studies with 5,177 study participants were included to estimate the pooled prevalence. The pooled prevalence of erectile dysfunction patients with diabetes mellitus was 61.62% (95% CI: 48.35–74.9). BMI ≥ 30kg/m2(AOR = 1.26; 95% CI: 0.73 –2.16), and glycated hemoglobin ≥ 7% (AOR = 0.93; 95% CI: 0.5–5.9), were identified factors though not statistically significant associated with erectile dysfunction.

Conclusions

The prevalence of erectile dysfunction in Africa remains high. Therefore, situation based interventions and country context specific preventive strategies could be developed to reduce the magnitude of erectile dysfunction among patients with diabetes mellitus.
Gonad transcriptome of golden musselLimnoperna fortuneireveals potential sex differentiation genes
Authors: Afonso Luana Ferreira , Americo Juliana Alves , Soares-Souza Giordano Bruno , Torres André Luiz Quintanilha , Wajsenzon Inês Julia Ribas , de Freitas Rebelo Mauro
Published: November 2019

The golden musselLimnoperna fortuneiis an Asian invasive bivalve that threats aquatic biodiversity and causes economic damage, especially to the hydroelectric sector in South America. Traditional control methods have been inefficient to stop the advance of the invasive mollusk, which currently is found in 40% of Brazilian hydroelectric power plants. In order to develop an effective strategy to stop golden mussel infestations, we need to better understand its reproductive and sexual mechanisms. In this study, we sequenced total RNA samples from male and female golden mussel gonads in the spawning stage. A transcriptome was assembled resulting in 200,185 contigs with 2,250 bp N50 and 99.3% completeness. Differential expression analysis identified 3,906 differentially expressed transcripts between the sexes. We searched for genes related to the sex determination/differentiation pathways in bivalves and model species and investigated their expression profiles in the transcriptome of the golden mussel gonads. From a total of 187 genes identified in the literature, 131 potential homologs were found in theL. fortuneitranscriptome, of which 15 were overexpressed in males and four in females. To this group belong gene families relevant to sexual development in various organisms, from mammals to invertebrates, such as Dmrt (doublesex and mab3-related-transcription factor), Sox (SRY-related HMG-box) and Fox (forkhead box).
Privacy-preserving quality control of neuroimaging datasets in federated environment
Authors: Saha D. K. , Calhoun V. D. , Du Y. , Fu Z. , Panta S. R. , Kwon S. , Sarwate A. D. , Plis S. M.
Published: November 2019

Privacy concerns for rare disease data, institutional or IRB policies, access to local computational or storage resources or download capabilities are among the reasons that may preclude analyses that pool data to a single site. A growing number of multi-site projects and consortia were formed to function in the federated environment to conduct productive research under constraints of this kind. In this scenario, a quality control tool that visualizes decentralized data in its entirety via global aggregation of local computations is especially important, as it would allow the screening of samples that cannot be jointly evaluated otherwise. To solve this issue, we present two algorithms: decentralized data stochastic neighbor embedding, dSNE, and its differentially private counterpart, DP-dSNE. We leverage publicly available datasets to simultaneously map data samples located at different sites according to their similarities. Even though the data never leaves the individual sites, dSNE does not provide any formal privacy guarantees. To overcome that, we rely on differential privacy: a formal mathematical guarantee that protects individuals from being identified as contributors to a dataset. We implement DP-dSNE with AdaCliP, a method recently proposed to add less noise to the gradients per iteration. We introduce metrics for measuring the embedding quality and validate our algorithms on these metrics against their centralized counterpart on two toy datasets. Our validation on six multi-site neuroimaging datasets shows promising results for the quality control tasks of visualization and outlier detection, highlighting the potential of our private, decentralized visualization approach.