bluuebunny/crossref_metadata_2025 huggingface dataset:
Privacy-preserving approximate GWAS computation based on homomorphic encryption
Authors: Kim Duhyeong , Son Yongha , Kim Dongwoo , Kim Andrey , Hong Seungwan , Cheon Jung Hee
Published: July 2020

Background

One of three tasks in a secure genome analysis competition called iDASH 2018 was to develop a solution for privacy-preserving GWAS computation based on homomorphic encryption. The scenario is that a data holder encrypts a number of individual records, each of which consists of several phenotype and genotype data, and provide the encrypted data to an untrusted server. Then, the server performs a GWAS algorithm based on homomorphic encryption without the decryption key and outputs the result in encrypted state so that there is no information leakage on the sensitive data to the server.

Methods

We develop a privacy-preserving semi-parallel GWAS algorithm by applying an approximate homomorphic encryption scheme HEAAN. Fisher scoring and semi-parallel GWAS algorithms are modified to be efficiently computed over homomorphically encrypted data with several optimization methodologies; substitute matrix inversion by an adjoint matrix, avoid computing a superfluous matrix of super-large size, and transform the algorithm into an approximate version.

Results

Our modified semi-parallel GWAS algorithm based on homomorphic encryption which achieves 128-bit security takes 30–40 minutes for 245 samples containing 10,000–15,000 SNPs. Compared to the truep-value from the original semi-parallel GWAS algorithm, theF1score of ourp-value result is over 0.99.

Conclusions

Privacy-preserving semi-parallel GWAS computation can be efficiently done based on homomorphic encryption with sufficiently high accuracy compared to the semi-parallel GWAS computation in unencrypted state.
Semi-Parallel logistic regression for GWAS on encrypted data
Authors: Kim Miran , Song Yongsoo , Li Baiyu , Micciancio Daniele
Published: July 2020

Background

The sharing of biomedical data is crucial to enable scientific discoveries across institutions and improve health care. For example, genome-wide association studies (GWAS) based on a large number of samples can identify disease-causing genetic variants. The privacy concern, however, has become a major hurdle for data management and utilization. Homomorphic encryption is one of the most powerful cryptographic primitives which can address the privacy and security issues. It supports the computation on encrypted data, so that we can aggregate data and perform an arbitrary computation on an untrusted cloud environment without the leakage of sensitive information.

Methods

This paper presents a secure outsourcing solution to assess logistic regression models for quantitative traits to test their associations with genotypes. We adapt the semi-parallel training method by Sikorska et al., which builds a logistic regression model for covariates, followed by one-step parallelizable regressions on all individual single nucleotide polymorphisms (SNPs). In addition, we modify our underlying approximate homomorphic encryption scheme for performance improvement.

Results

We evaluated the performance of our solution through experiments on real-world dataset. It achieves the best performance of homomorphic encryption system for GWAS analysis in terms of both complexity and accuracy. For example, given a dataset consisting of 245 samples, each of which has 10643 SNPs and 3 covariates, our algorithm takes about 43 seconds to perform logistic regression based genome wide association analysis over encryption.

Conclusions

We demonstrate the feasibility and scalability of our solution.
Development and preliminary evaluation of the QUALIKO: an observational quality of life instrument for patients with Korsakoff’s syndrome
Authors: ten Klooster Peter M. , Rensen Yvonne C. M. , Postma Jorrit F. , Kessels Roy P. C.
Published: July 2020

Background

To develop a Korsakoff-specific measure of quality of life (QoL), to be rated by professional caregivers, and to field-test its psychometric properties in a sample of patients with Korsakoff’s syndrome (KS) living in a specialized nursing home.

Methods

A research version of the QUALIKO was developed based on an existing instrument for dementia (the QUALIDEM), literature review and two rounds of surveys among expert professionals involved in the care for patients with KS. Next, QoL was independently rated using the preliminary QUALIKO for 77 patients with KS by two primary caregivers.

Results

The research QUALIKO consisted of 48 items describing observable behaviors across ten aspects of QoL relevant to patients with KS. Six items demonstrated poor scalability in the field test. The remaining 42 items all formed subscales with moderate to strong scalability according to Mokken scale analysis. Reliability was acceptable to good across both raters for all subscales (Mokken rho’s = 0.70–0.90), except for the two 2-item subscales of negative affect and positive self-image (Mokken rho’s = 0.47–0.71). Inter-observer agreement was excellent for five subscales (ICCs = 0.75–0.89) and fair to moderate for the other five subscales (ICCs = 0.59–0.72). The multidimensional internal structure was confirmed and all subscales were significantly correlated with primary caregivers’ global ratings of QoL except for positive self-image. Missing item values were low and floor and ceiling effects acceptable for most subscales.

Conclusions

The QUALIKO holds promise as a feasible, reliable, and valid measure of QoL in residential KS patients. Future research in larger samples is needed to confirm the psychometric dimensionality of the instrument, to gather normative data and to examine its test-retest reliability.
What we may learn – and need – from pandemic fiction
Authors: Doherty Jane , Giordano James
Published: July 2020

N/A
POCUS and POCDUS: essential tools for the evaluation and management of carotid artery pseudoaneurysms after a gunshot wound
Authors: Montorfano Lisandro , Sarkissyan Marianna , Wolfers Matthew , Rodríguez Federico , Pla Fernando , Montorfano Miguel
Published: July 2020

Background

Evaluation of asymptomatic penetrating vascular injuries can be done with Point-of-care ultrasound (POCUS) and Point-of-care Doppler ultrasound (POCDUS).

Case presentation

A 21-year-old woman was admitted to the Emergency Department with a small wound and pain on the left side of her neck. The patient stated she was standing outside her home and suddenly felt acute pain in the neck. She denied trauma or being assaulted and reported no significant past medical or surgical history. On physical exam the only positive finding was a small gunshot entry wound on the left side of her neck without hard signs of vascular injury. Bedside POCUS demonstrated soft tissue swelling and a hematoma next to the left carotid artery. A round in shape bullet was visualized in contact with the posterior left common carotid artery wall and two small saccular pseudoaneurysms were seen at left common carotid artery wall. POCDUS showed a patent left carotid artery and turbulent flow in the two saccular aneurysms. A computed tomography angiogram (CTA) was performed confirming the findings and a stent in left carotid artery was placed. The patient tolerated the procedure well and was discharged 4 days after the procedure. At the sixth month follow-up, Doppler ultrasound showed patent stent and resolution of the muscular hematoma.

Conclusions

Penetrating trauma-related vascular injuries are complex cases to handle within an acute setting. POCUS and POCDUS are increasingly being used for the workup and decision-making process of gunshot-related vascular injuries to the neck and are a fundamental part of the follow-up after definitive therapy.
Evaluating flight coordination approaches of UAV squads for WSN data collection enhancing the internet range on WSN data collection
Authors: Olivieri de Souza Bruno José , Endler Markus
Published: July 2020

Wireless sensor networks (WSNs) are an important means of collecting data in a variety of situations, such as the monitoring of large or hazardous areas. The retrieval of WSN data can yield better results through the use of unmanned aerial vehicles (UAVs), for example, concerning the increase in the amount of data collected and the decrease in the time between the collection and use of the data. In particular, disaster areas may be left without communication resources and with high residual risk to humans, at which point a WSN can be quickly launched by air to collect relevant data until other measures can be established. The set of rules of each problem’s component (e.g., number of UAVs, UAVs dislocation control, sensors, communication) is considered the approaches to solve the problem. In this meaning, some studies present approaches for the use of UAVs for the collection of WSN data, focusing primarily on optimizing the path to be covered by a single UAV and relying on long-range communication that is always available; these studies do not explore the possibility of using several UAVs or the limitations on the range of communication. This work describes DADCA, a distributed scalable approach capable of coordinating groups of UAVs in WSN data collection with restricted communication range and without the use of optimization techniques. The results reveal that the amount of data collected by DADCA is similar or superior to path optimization approaches by up to 1%. In our proposed approach, the delay in receiving sensor messages is up to 46% shorter than in other approaches, and the required processing onboard UAVs can reach less than 75% of those using optimization-based algorithms. The results indicate that the DADCA can match and even surpass other presented approaches, since the path optimization is not a focus, while also incorporating the advantages of a distributed approach.
Reference genome and transcriptome informed by the sex chromosome complement of the sample increase ability to detect sex differences in gene expression from RNA-Seq data
Authors: Olney Kimberly C. , Brotman Sarah M. , Andrews Jocelyn P. , Valverde-Vesling Valeria A. , Wilson Melissa A.
Published: July 2020

Background

Human X and Y chromosomes share an evolutionary origin and, as a consequence, sequence similarity. We investigated whether the sequence homology between the X and Y chromosomes affects the alignment of RNA-Seq reads and estimates of differential expression. We tested the effects of using reference genomes and reference transcriptomes informed by the sex chromosome complement of the sample’s genome on the measurements of RNA-Seq abundance and sex differences in expression.

Results

The default genome includes the entire human reference genome (GRCh38), including the entire sequence of the X and Y chromosomes. We created two sex chromosome complement informed reference genomes. One sex chromosome complement informed reference genome was used for samples that lacked a Y chromosome; for this reference genome version, we hard-masked the entire Y chromosome. For the other sex chromosome complement informed reference genome, to be used for samples with a Y chromosome, we hard-masked only the pseudoautosomal regions of the Y chromosome, because these regions are duplicated identically in the reference genome on the X chromosome. We analyzed the transcript abundance in the whole blood, brain cortex, breast, liver, and thyroid tissues from 20 genetic female (46, XX) and 20 genetic male (46, XY) samples. Each sample was aligned twice: once to the default reference genome and then independently aligned to a reference genome informed by the sex chromosome complement of the sample, repeated using two different read aligners, HISAT and STAR. We then quantified sex differences in gene expression using featureCounts to get the raw count estimates followed by Limma/Voom for normalization and differential expression. We additionally created sex chromosome complement informed transcriptome references for use in pseudo-alignment using Salmon. Transcript abundance was quantified twice for each sample: once to the default target transcripts and then independently to target transcripts informed by the sex chromosome complement of the sample.

Conclusions

We show that regardless of the choice of the read aligner, using an alignment protocol informed by the sex chromosome complement of the sample results in higher expression estimates on the pseudoautosomal regions of the X chromosome in both genetic male and genetic female samples, as well as an increased number of unique genes being called as differentially expressed between the sexes. We additionally show that using a pseudo-alignment approach informed on the sex chromosome complement of the sample eliminates Y-linked expression in female XX samples.
Epidemiological study on calf diarrhea and coccidiosis in dairy farms in Bahir Dar, North West Ethiopia
Authors: Tamrat Habtamu , Mekonnen Negesse , Ferede Yeshwas , Cassini Rudi , Belayneh Negus
Published: July 2020

Background

A longitudinal prospective study was conducted from October 2017 to April 2018 on calf diarrhea and coccidiosis in dairy farms in Bahir Dar, North West Ethiopia with the objectives of determining the incidence of calf diarrhea and calf coccidiosis from diarrheic calves, assessing the major risk factors associated with calf diarrhea and coccidiosis and identifying the existing Eimeria species. A total of 237 calves, 86 calves from 52 smallholder dairy farms and 151 calves from 8 large dairy farms, were used for this study. Fresh fecal samples were collected from 86 diarrheic calves for identification of Eimeria species.

Results

Overall incidences of calf diarrhea and coccidiosis found in this study were 33.5 and 20.1%, respectively. In total, 19 potential risk factors were investigated for their association with calf diarrhea and coccidiosis from diarrheic calves using Cox regression. Age of calf (HR = 2.057, P = .002), body condition (HR = 1.802, P < .001), house condition (HR = 2.072, P = .004) and age at first colostrum feeding time (HR = 2.107, P = .002) were found significantly (P < 0.05) associated with the risk of diarrhea by multivariate Cox regression. Among the risk factors tested, age (HR = 13.36, P < .001) and sex of calves (HR = 3.500, P = .020) were found significantly (P < 0.05) associated with coccidiosis by multivariate Cox regression. A total of nine Eimeria species were identified. E. bovis (28.6%), E. zuernii (19.0%) and E. auburnensis (14.3%) were the most common Eimeria species encountered.

Conclusion

The incidence of calf diarrhea and coccidiosis was high in the dairy herds in North West Ethiopia. Therefore, sound dairy calf management practices are needed to mitigate risk factors for calf diarrhea and coccidiosis with a view to reducing the incidence of calf diarrhea and coccidiosis in Ethiopian dairy farms.
Correction to: A B-spline finite element method for solving a class of nonlinear parabolic equations modeling epitaxial thin-film growth with variable coefficient
Authors: Qin Dandan , Tan Jiawei , Liu Bo , Huang Wenzhu
Published: July 2020

In the original publication of this article [1] the name of the second author is incorrect. The correct name of the second author is Jiawei Tan rather than John Jiawei Tan. The error in this Correction has been updated in the original article.
Intelligent cloud workflow management and scheduling method for big data applications
Authors: Hu Yannian , Wang Hui , Ma Wenge
Published: July 2020

With the application and comprehensive development of big data technology, the need for effective research on cloud workflow management and scheduling is becoming increasingly urgent. However, there are currently suitable methods for effective analysis. To determine how to effectively manage and schedule smart cloud workflows, this article studies big data from various aspects and draws the following conclusions: Compared with the original JStorm system, the response time is shortened by a maximum of 58.26% and an average of 23.18%, CPU resource utilization is increased by a maximum of 17.96% and an average of 11.39%, and memory utilization increased by a maximum of 88.7% and an average of 71.16%. In terms of optimizing the dynamic combination of web services, the overall performance of both the MOACO and CCA algorithms is better than that of the GA algorithm, and the average performance of the MOACO algorithm is better than that of the CCA algorithm. This paper also proposes a cloud workflow scheduling strategy based on an intelligent algorithm and realizes the two-tier scheduling of cloud workflow tasks by adjusting the combination strategy for cloud service resources. We have studied three representative intelligent algorithms (ACO, PSO and GA) and improved them for scheduling optimization. It can be clearly seen that in the same scenario, the optimal values of the different algorithms vary greatly for different test cases. However, the optimal solution curve is substantially consistent with the trend of the mean curve.
Characterization of a novel endolysin from bacteriophage infecting Vibrio parahaemolyticus, vB_VpaP_KF2
Authors: Lim Jeong-A , Lee Nari , Chun Hyang-Sook , Chang Hyun-Joo
Published: July 2020

The antimicrobial resistance of food-borne pathogenic bacteria, including Vibrio parahaemolyticus, has been reported globally, warranting the need to identify promising alternative antibiotics such as endolysins that originate from bacteriophages. In our previous study, we characterized a bacteriophage infecting V. parahaemolyticus, vB_VpaP_KF2, at the molecular level. In this study, an open reading frame encoding putative endolysin was cloned from the complete genome data and expressed in the Escherichia coli expression system. The recombinant endolysin, vB_VpaP_KF2_Lys, exhibited a novel lytic property against Gram-negative bacteria regardless of pretreatment with an outer-membrane permeabilizer. It was also stable over a wide range of temperatures, pH, and NaCl concentrations, and its hydrolytic spectrum was broader than that of the parent bacteriophage. From the results, vB_VpaP_KF2_Lys could be used as a biocontrol agent against food-borne pathogens in the field of food safety.
Diet induced the change of mtDNA copy number and metabolism in Angus cattle
Authors: Bai Ying , Carrillo José A. , Li Yaokun , He Yanghua , Song Jiuzhou
Published: July 2020

Background

Grass-fed and grain-fed Angus cattle differ in the diet regimes. However, the intricate mechanisms of different beef quality and other phenotypes induced by diet differences are still unclear. Diet affects mitochondrial function and dynamic behavior in response to changes in energy demand and supply. In this study, we examined the mtDNA copy number, mitochondria-related genes expression, and metabolic biomarkers in grass-fed and grain-fed Angus cattle.

Results

We found that the grass-fed group had a higher mtDNA copy number than the grain-fed group. Among different tissues, the mtDNA copy number was the highest in the liver than muscle, rumen, and spleen. Based on the transcriptome of the four tissues, a lower expression of mtDNA-encoded genes in the grass-fed group compared to the grain-fed group was discovered. For the mitochondria-related nuclear genes, however, most of them were significantly down-regulated in the muscle of the grass-fed group and up-regulated in the other three tissues. In which, COX6A2, POLG2, PPIF, DCN, and NDUFA12, involving in ATP synthesis, mitochondrial replication, transcription, and maintenance, might contribute to the alterations of mtDNA copy number and gene expression. Meanwhile, 40 and 23 metabolic biomarkers were identified in the blood and muscle of the grain-fed group compared to a grass-fed group, respectively. Integrated analysis of the altered metabolites and gene expression revealed the high expression level of MDH1 in the grain-fed group might contribute to the mitochondrial NADH oxidation and spermidine metabolism for adapting the deletion mtDNA copy number.

Conclusions

Overall, the study may provide further deep insight into the adaptive and regulatory modulations of the mitochondrial function in response to different feeding systems in Angus cattle.
Gravity stress tibiotalar laxity evaluation with a biomedical gyroscopes device – cadaver study with progressive sectioning of lateral ankle ligaments
Authors: Guerra-Pinto F. , Cunha J. , Sousa L. , Gomes T. M. , Andrade R. , Oliva X. M. , Consciência J. G. , Fernandes P. R.
Published: July 2020

Purpose

Despite the evidence on the role of gravity stress test to access the instability of other ankle injuries, there is limited literature regarding gravity stress on the lateral ankle ligament’s insufficiency. The objective of our study was to objectively measure the tibiotalar angular movement under gravity stress after progressive sectioning of the lateral ankle ligaments.

Methods

We performed sequential sectioning of the anterior talofibular (ATFL), calcaneofibular (CFL), and posterior talofibular ligaments (PTFL) in twelve ankle specimens. Under gravity stress, we measured the angular movement of the talus in relation to the tibia. The measuring device is based on a three-axis gyroscope and accelerometer.

Results

Comparing to the intact condition, the plantar flexion increased on average 1.78° (95% confidence interval [CI] 1.15;2.42), 5.13° (95%CI 3.10;7.16) and 8.63° (95%CI 6.05;11.22), the rotation increased by 1.00° (95 CI -0.51;2.51), 3.68° (95%CI 1.97;5.40) and 15.62° (95%CI 10.09;21.14), and the varus increased 2.89° (95% CI 1.39, 4.39), 8.12° (95% CI 5.16, 11.07) and 11.68° (95% CI 7.91, 15.46), after sectioning the ATFL, CFL, and PTFL, respectively. The overall changes were statistically significant.

Conclusions

There was a significant tibiotalar laxity after sectioning of lateral ankle ligaments when the foot position is influenced only by gravity. The tibiotalar angular displacement was significant when the CFL and PTFL were cut which suggests that the gravity test could be used to assess combined lateral ankle ligament injury. This evidence might be a step forward in the development of lateral ankle ligaments gravity stress tests.

Level of evidence

5 (cadaver study)
Internet-based cognitive behavior therapy for problem gambling in routine care: protocol for a non-randomized pilot and feasibility trial
Authors: Molander Olof , Lindner Philip , Ramnerö Jonas , Bjureberg Johan , Carlbring Per , Berman Anne H.
Published: July 2020

Background

Problem gambling and gambling disorder are major public health concerns worldwide, and awareness of associated negative consequences is rising. In parallel, treatment demand has increased, and Internet interventions offer a promising alternative for providing evidence-based treatment at scale to a low cost.

Method

We developed a novel Internet-delivered cognitive behavioral treatment for gambling, based on qualitative interviews with treatment-seeking gamblers, behavioral research on gambling behavior, and the pathway model for problem gambling. This research protocol describes a non-randomized pilot and feasibility trial conducted in routine addiction care with adult treatment-seeking patients (max N = 25) with problem gambling. The primary aim is to ensure acceptability and safety, measured by satisfaction, credibility, working alliance, and possible negative effects. Secondary aims are feasibility of study procedures in terms of recruitment and measurement procedures as well as potential effectiveness measured weekly by gambling symptoms as primary outcome and gambling behavior, quality of life, symptoms of depression and anxiety, alcohol, and drug use as secondary outcomes. Potential mediators measured weekly are loss of control, verbal rules, and well-being.

Discussion

This study is innovative in several respects, regarding both treatment development and implementation. The results of the study will guide a future randomized controlled trial, as well as the development of the intervention and intervention implementation within ordinary addiction care.

Trial registration

Clinical trials.gov, NCT ID: NCT03946098. Registered 10 May 2019
Freedom to think: the need for thorough assessment and treatment of gender dysphoric children
Authors: Evans Marcus
Published: July 2020

Referrals (particularly natal female) to gender identity clinics have increased significantly in recent years. Understanding the reasons for this increase, and how to respond, is hampered by a politically charged debate regarding gender identity. This article starts with a discussion of the so-called ‘affirmative approach’ to gender dysphoria and considers the implications of the Memorandum of Understanding on conversion therapy. I then say something about the relationship between gender dysphoria and the developmental problems that are characteristic of adolescence. Finally, I outline what changes to the current approach are needed to do our best to ensure these patients receive the appropriate treatment.
Sex, gender and gender identity: a re-evaluation of the evidence
Authors: Griffin Lucy , Clyde Katie , Byng Richard , Bewley Susan
Published: July 2020

In the past decade there has been a rapid increase in gender diversity, particularly in children and young people, with referrals to specialist gender clinics rising. In this article, the evolving terminology around transgender health is considered and the role of psychiatry is explored now that this condition is no longer classified as a mental illness. The concept of conversion therapy with reference to alternative gender identities is examined critically and with reference to psychiatry's historical relationship with conversion therapy for homosexuality. The authors consider the uncertainties that clinicians face when dealing with something that is no longer a disorder nor a mental condition and yet for which medical interventions are frequently sought and in which mental health comorbidities are common.
Prenatal EDCs Impair Mate and Odor Preference and Activation of the VMN in Male and Female Rats
Authors: Hernandez Scudder Morgan E , Weinberg Amy , Thompson Lindsay , Crews David , Gore Andrea C
Published: July 2020

Environmental endocrine-disrupting chemicals (EDCs) disrupt hormone-dependent biological processes. We examined how prenatal exposure to EDCs act in a sex-specific manner to disrupt social and olfactory behaviors in adulthood and underlying neurobiological mechanisms. Pregnant rat dams were injected daily from embryonic day 8 to 18 with 1 mg/kg Aroclor 1221 (A1221), 1 mg/kg vinclozolin, or the vehicle (6% DMSO in sesame oil). A1221 is a mixture of polychlorinated biphenyls (weakly estrogenic) while vinclozolin is a fungicide (anti-androgenic). Adult male offspring exposed to A1221 or vinclozolin, and females exposed to A1221, had impaired mate preference behavior when given a choice between 2 opposite-sex rats that differed by hormone status. A similar pattern of impairment was observed in an odor preference test for urine-soaked filter paper from the same rat groups. A habituation/dishabituation test revealed that all rats had normal odor discrimination ability. Because of the importance of the ventrolateral portion of the ventromedial nucleus (VMNvl) in mate choice, expression of the immediate early gene product Fos was measured, along with its co-expression in estrogen receptor alpha (ERα) cells. A1221 females with impaired mate and odor preference behavior also had increased neuronal activation in the VMNvl, although not specific to ERα-expressing neurons. Interestingly, males exposed to EDCs had normal Fos expression in this region, suggesting that other neurons and/or brain regions mediate these effects. The high conservation of hormonal, olfactory, and behavioral traits necessary for reproductive success means that EDC contamination and its ability to alter these traits has widespread effects on wildlife and humans.
Influence of Cinnamon on Glycemic Control in Individuals With Prediabetes: A Randomized Controlled Trial
Authors: Romeo Giulio R , Lee Junhee , Mulla Christopher M , Noh Youngmin , Holden Casey , Lee Byung-Cheol
Published: July 2020

Context

The identification of adjunct safe, durable, and cost-effective approaches to reduce the progression from prediabetes to type 2 diabetes (T2D) is a clinically relevant, unmet goal. It is unknown whether cinnamon’s glucose-lowering properties can be leveraged in individuals with prediabetes.

Objective

The objective of this work is to investigate the effects of cinnamon on measures of glucose homeostasis in prediabetes.

Design, Setting, Participants, and Intervention

This double-blind, placebo-controlled, clinical trial randomly assigned adult individuals meeting any criteria for prediabetes to receive cinnamon 500 mg or placebo thrice daily (n = 27/group). Participants were enrolled and followed at 2 academic centers for 12 weeks.

Main Outcome Measures

Primary outcome was the between-group difference in fasting plasma glucose (FPG) at 12 weeks from baseline. Secondary end points included the change in 2-hour PG of the oral glucose tolerance test (OGTT), and the change in the PG area under the curve (AUC) derived from the OGTT.

Results

From a similar baseline, FPG rose after 12 weeks with placebo but remained stable with cinnamon, leading to a mean between-group difference of 5 mg/dL (P < .05). When compared to the respective baseline, cinnamon, but not placebo, resulted in a significant decrease of the AUC PG (P < .001) and of the 2-hour PG of the OGTT (P < .05). There were no serious adverse events in either study group.

Conclusions

In individuals with prediabetes, 12 weeks of cinnamon supplementation improved FPG and glucose tolerance, with a favorable safety profile. Longer and larger studies should address cinnamon’s effects on the rate of progression from prediabetes to T2D.
E-cigarette, or Vaping, Product Use-Associated Lung Injury—Lessons Learned: A Case Series
Authors: Helm Cole , Labovsky Kristen , Thakrar Pooja D. , Diaz Christina D.
Published: July 2020

E-cigarette, or vaping, product use has been declared an epidemic, and a new disease has emerged from their use. We describe 4 patients with significant acute lung injury related to e-cigarette use who underwent bronchoscopy and bronchoalveolar lavage. All cases posed anesthetic challenges, including increased airway reactivity, hypoxia, increasing oxygen requirements, and, in 2 severe cases, the need for continued postprocedural mechanical ventilatory support. It is imperative that all members of the treating team are aware of the disproportionate risk of respiratory complications to anticipate the possible need for increased postprocedural respiratory support.
Adverse Drug Reaction: Midazolam-Induced Extrapyramidal Symptoms: A Case Report
Authors: McConn Margaux M. , Gundy Joseph T. , Karan Suzanne B. , Lindenmuth Danielle M.
Published: July 2020

Midazolam is commonly used for sedation during procedures because of its relative safety and predictability. Still, some rare undesirable medication reactions have been described. We report a case in which midazolam given before a peripheral nerve block caused acute onset dyskinetic extrapyramidal symptoms. These symptoms ultimately resolved following reversal of the midazolam with flumazenil. Given the widespread and multidisciplinary use of midazolam, practitioners should be aware of the potential for rare adverse reactions and be prepared to manage these scenarios.
Innovative Use of High-Fidelity Lung Simulators to Test a Ventilator Splitter Device
Authors: Boyer Tanna J. , Mitchell Sally A. , Cartwright Johnny F. , Ahmed Rami A.
Published: July 2020

The coronavirus disease 2019 (COVID-19) pandemic has rapidly exposed health care system inadequacies. Hospital ventilator shortages in Italy compelled US physicians to consider creative solutions, such as using Y-pieces or T-pieces, to preclude the need to make decisions of life or death based on medical equipment availability. We add to current knowledge and testing capacity for ventilator splitters by reporting the ability to examine the functionality of ventilator splitters by using 2 high-fidelity lung simulators. Data obtained by the high-fidelity lung simulators included: tidal volume, respiratory rate, minute ventilation, peak inspiratory pressure, peak plateau pressure, and positive end-expiratory pressure.
Management of Coronavirus Disease 2019 Intubation Teams
Authors: Patel Gaurav P. , Collins Jeremy S. , Sullivan Cinnamon L. , Winters Bradford D. , Pustavoitau Aliaksei , Margulies Susan S. , Lynde Grant C.
Published: July 2020

Some patients infected with the Coronavirus Disease 2019 (COVID-19) require endotracheal intubation, an aerosol-generating procedure that is believed to result in viral transmission to personnel performing the procedure. Additionally, donning and doffing personal protective equipment can be time consuming. In particular, doffing requires strict protocol adherence to avoid exposure. We describe the Emory Healthcare intubation team approach during the COVID-19 pandemic. This structure resulted in only 1 team member testing positive for COVID-19 despite 253 patient intubations over a 6-week period with 153 anesthesia providers on service.
The structure and symmetry of the radial spoke protein complex in Chlamydomonas flagella
Authors: Poghosyan Emiliya , Iacovache Ioan , Faltova Lenka , Leitner Alexander , Yang Pinfen , Diener Dennis R. , Aebersold Ruedi , Zuber Benoit , Ishikawa Takashi
Published: July 2020

The radial spoke is a key element in a transducer apparatus controlling the motility of eukaryotic cilia. The transduction biomechanics is a long-standing question in cilia biology. The radial spoke has three regions – a spoke head, a bifurcated neck and a stalk. Although the neck and the stalk are asymmetric, twofold symmetry of the head has remained controversial. In this work we used single particle cryo-electron microscopy (cryo-EM) analysis to generate a 3D structure of the whole radial spoke at unprecedented resolution. We show the head region at 15 Å (1.5 nm) resolution and confirm twofold symmetry. Using distance constraints generated by cross-linking mass spectrometry, we locate two components, RSP2 and RSP4, at the head and neck regions. Our biophysical analysis of isolated RSP4, RSP9, and RSP10 affirmed their oligomeric state. Our results enable us to redefine the boundaries of the regions and propose a model of organization of the radial spoke component proteins.
The ubiquitin-like modifier FAT10 – much more than a proteasome-targeting signal
Authors: Aichem Annette , Groettrup Marcus
Published: July 2020

Human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10) also called ubiquitin D (UBD) is a member of the ubiquitin-like modifier (ULM) family. The FAT10 gene is localized in the MHC class I locus and FAT10 protein expression is mainly restricted to cells and organs of the immune system. In all other cell types and tissues, FAT10 expression is highly inducible by the pro-inflammatory cytokines interferon (IFN)-γ and tumor necrosis factor (TNF). Besides ubiquitin, FAT10 is the only ULM which directly targets its substrates for degradation by the 26S proteasome. This poses the question as to why two ULMs sharing the proteasome-targeting function have evolved and how they differ from each other. This Review summarizes the current knowledge of the special structure of FAT10 and highlights its differences from ubiquitin. We discuss how these differences might result in differential outcomes concerning proteasomal degradation mechanisms and non-covalent target interactions. Moreover, recent insights about the structural and functional impact of FAT10 interacting with specific non-covalent interaction partners are reviewed.
Prognostic Value of Leg Muscle Strength in Acute Heart Failure Syndrome
Authors: YOUN JONG-CHAN , CHOI SUK-WON , LEE HYE SUN , HAN SEONGWOO , SHIN EUI-CHEOL , BAEK SANG HONG , KANG SEOK-MIn
Published: July 2020

Introduction

Leg muscle strength (LMS) may be useful as a frailty index in patients with heart failure. However, LMS, until recently, has been indirectly estimated, and its prognostic value in acute heart failure syndrome (AHFS) is unclear. Therefore, we evaluated the prognostic value of direct LMS assessment and its relationship with proinflammatory mediators in patients with AHFS.

Methods

We directly measured LMS at predischarge using a dynamometer in 110 prospectively and consecutively enrolled patients with AHFS (75 male; 60 ± 14 yr; mean ejection fraction, 29.9% ± 14.6%). The primary end point was cardiovascular (CV) events, defined as CV mortality, cardiac transplantation, or rehospitalization due to heart failure aggravation. Patients were divided into impaired and preserved LMS groups according to Contal and O’Quigley’s method.

Results

CV events occurred in 28 patients (25.5%) (including 5 CV deaths and 6 cardiac transplantations) during follow-up (median, 246 d; range = 11–888 d). Impaired LMS was associated with significantly higher levels of serum monokine induced by gamma interferon and poor clinical outcomes (P < 0.001). Multivariable Cox proportional hazard analysis (controlling for age, sex, body mass index, heart failure type, hemoglobin level, N-terminal pro-b-type natriuretic peptide level, and beta-blocker use) revealed LMS as an independent predictor of CV events (P = 0.017).

Conclusion

Impaired LMS, which might be used as a marker of frailty, is associated with increased levels of a proinflammatory chemokine and independently predicts clinical outcomes in patients with AHFS. The direct measurement of LMS is simple and feasible and might have important implications for the risk stratification of patients with AHFS.
HRR and V˙O2R Fractions Are Not Equivalent: Is It Time to Rethink Aerobic Exercise Prescription Methods?
Authors: FERRI MARINI CARLO , SISTI DAVIDE , LEON ARTHUR S. , SKINNER JAMES S. , SARZYNSKI MARK A. , BOUCHARD CLAUDE , ROCCHI MARCO B. L. , PICCOLI GIOVANNI , STOCCHI VILBERTO , FEDERICI ARIO , LUCERTINI FRANCESCO
Published: July 2020

Introduction

According to current guidelines, the intensity of health-enhancing aerobic exercise should be prescribed using a percentage of heart rate reserve (%HRR), which is considered to be more closely associated (showing a 1:1 relation) with the percentage of oxygen uptake reserve (%V˙O2R) rather than with the percentage of maximal oxygen uptake (%V˙O2max) during incremental exercise. However, the associations between %HRR and %V˙O2R and between %HRR and %V˙O2max are under debate; hence, their actual relationships were investigated in this study.

Methods

Data from each stage of a maximal incremental exercise test performed by 737 healthy and physically inactive participants of the HERITAGE Family Study were screened and filtered then used to calculate the individual linear regressions between %HRR and either %V˙O2R or %V˙O2max. For each relationship, the mean slope and intercept of the individual linear regression were compared with 1 and 0 (i.e., the identity line), respectively, using one-sample t-tests. The individual root mean square errors of the actual versus the 1:1 predicted %HRR were calculated for both relationships and compared using a paired-sample t-test.

Results

The mean slopes (%HRR–%V˙O2R, 0.972 ± 0.189; %HRR–%V˙O2max, 1.096 ± 0.216) and intercepts (%HRR–%V˙O2R, 8.855 ± 16.022; %HRR–%V˙O2max, −3.616 ± 18.993) of both relationships were significantly different from 1 and 0, respectively, with high interindividual variability. The average root mean square errors were high and revealed that the %HRR–%V˙O2max relationship was more similar to the identity line (P < 0.001) than the %HRR–%V˙O2R relationship (7.78% ± 4.49% vs 9.25% ± 5.54%).

Conclusions

Because both relationships are different from the identity line and using a single equation may not be appropriate to predict exercise intensity at the individual level, a rethinking of the relationships between the intensity variables may be necessary to ensure that the most suitable health-enhancing aerobic exercise intensity is prescribed.
Serum Acylglycerols Inversely Associate with Muscle Oxidative Capacity in Severe COPD
Authors: LI RONGSONG , ADAMI ALESSANDRA , CHANG CHIH-CHIANG , TSENG CHI-HONG , HSIAI TZUNG K. , ROSSITER HARRY B.
Published: July 2020

Purpose

Chronic obstructive pulmonary disease (COPD) is associated with altered metabolism and body composition that accompany poor outcomes. We aimed to determine whether metabolic derangements in COPD are associated with skeletal muscle deconditioning and/or physical inactivity, independent of pulmonary obstruction.

Methods

We characterized serum metabolites associated with muscle oxidative capacity or physical activity in 44 COPD patients (forced expiratory volume in 1 s [FEV1] = 61% ± 4% predicted) and 63 current and former smokers with normal spirometry (CON) (FEV1 = 93% ± 2% predicted). Medial gastrocnemius oxidative capacity was assessed at rest from the recovery rate constant (k) of muscle oxygen consumption using near-infrared spectroscopy. Step counts and physical activity (average vector magnitude units [VMU] per minute) were measured over 5–7 d using triaxial accelerometry. Untargeted prime and lipid metabolites were measured using liquid chromatography and mass spectrometry.

Results

Muscle k (1.12 ± 0.05 vs 1.68 ± 0.06 min−1, P < 0.0001, d = 1.58) and VMU per minute (170 ± 26 vs 450 ± 50 VMU per minute, P = 0.004, d = 1.04) were lower in severe COPD (FEV1 < 50% predicted, n = 14–16) compared with CON (n = 56–60). A total of 129 prime metabolites and 470 lipids with known identity were quantified. Using sex as a covariate, lipidomics revealed 24 differentially expressed lipids (19 sphingomyelins) in COPD, consequent to a diminished sex difference of sphingomyelins in COPD (false discovery rate [FDR] < 0.05, n = 44). Total, and some individual, fatty acid concentrations were greater in severe COPD than CON (FDR < 0.05, n = 16, d = 0.56–1.02). After adjusting for FEV1% predicted, we observed that grouped diacylglycerides (ρ = −0.745, FDR = 0.03) and triacylglycerides (ρ = −0.811, FDR = 0.01) were negatively associated with muscle oxidative capacity, but not physical activity, in severe COPD (n = 14).

Conclusion

Strong negative associations relate impaired mitochondrial function to the accumulation of serum aclyglycerides in severe COPD.
Altered Position Sense after Submaximal Eccentric Exercise–inducing Central Fatigue
Authors: DA SILVA FLAVIO , MONJO FLORIAN , ZGHAL FIRAS , CHORIN FRÉDÉRIC , GUÉRIN OLIVIER , COLSON SERGE S.
Published: July 2020

Purpose

The purpose of this study was to concomitantly investigate the acute and delayed effects of a submaximal eccentric-induced muscle fatigue on the position sense and the neuromuscular function of the right knee extensor muscles.

Methods

Thirteen young and physically active participants performed a unilateral isokinetic eccentric exercise of their right lower limb until a decrease in maximal voluntary isometric contraction (MVIC) of 20% was reached. Neuromuscular (i.e., MVIC, voluntary activation (VA) level, and evoked contractile properties [DB100 and DB10]) and psychophysical evaluations (i.e., bilateral position-matching task, perceived muscle soreness, and perceived fatigue) were performed at four time points: before (PRE), immediately after (POST), 24 (POST24), and 48 (POST48) the exercise.

Results

The acute 20% MVIC reduction (P < 0.001) was associated with both central (i.e., −13% VA decrease, P < 0.01) and peripheral (i.e., −18% and −42% reduction of DB100 and DB10, respectively, P < 0.001) fatigue. In the following days (POST24 and POST48), VA levels had recovered despite the presence of a persisting peripheral fatigue and delayed-onset muscle soreness. Knee position sense, as revealed by position errors, was significantly altered only at POST (P < 0.05) with participants overestimating the length of their knee extensor. Position errors and VA deficits were significantly correlated at POST (r = −0.60, P = 0.03). Position errors returned to nonsignificant control values in the following days.

Conclusion

The acute central fatigue induced by the eccentric exercise contributes to the position sense disturbances. Central fatigue might lead to alterations in the sensory structures responsible for the integration and the processing of position-related sensory inputs.
Accelerated Muscle Recovery in Baseball Pitchers Using Phase Change Material Cooling
Authors: MULLANEY MICHAEL J. , MCHUGH MALACHY P. , KWIECIEN SUSAN Y. , IOVIERO NEIL , FINK ANDREW , HOWATSON GLYN
Published: July 2020

Purpose

The purpose of this study was to document recovery after a pitching performance and determine whether prolonged postgame phase change material (PCM) cooling of the shoulder and forearm accelerates recovery.

Methods

Strength, soreness, and serum creatine kinase (CK) activity were assessed before and on the 2 d after pitching performances in 16 college pitchers. Pitchers were randomized to receive either postgame PCM cooling packs on the shoulder and forearm or no cooling (control). PCM packs were applied inside compression shirts and delivered cooling at a constant temperature of 15°C for 3 h. Strength was assessed for shoulder internal rotation (IR), external rotation (ER), empty can (EC) test, and grip.

Results

Total pitch count was 60 ± 16 for 23 PCM cooling games and 62 ± 17 for 24 control games (P = 0.679). On the days after pitching, IR strength (P = 0.006) and grip strength (P = 0.036) were higher in the PCM cooling group versus control. One day after pitching, IR strength was 95% ± 14% of baseline with PCM cooling versus 83% ± 13% for control (P = 0.008, effect size d = 0.91) and 107% ± 9% versus 95% ± 10% for grip strength (P = 0.022, effect size d = 1.29). There was a trend for greater ER strength with PCM cooling (P = 0.091, effect size d = 0.51). The EC strength was not impaired after pitching (P = 0.147) and was therefore unaffected by PCM cooling (P = 0.168). Elevations in soreness and CK were not different between treatments (treatment–time CK P = 0.139, shoulder soreness P = 0.885, forearm soreness P = 0.206).

Conclusion

This is one of the first studies to document impairments in muscle function on the days after baseball pitching, and the first study showing a novel cryotherapy intervention that accelerates recovery of muscle function in baseball pitchers after a game.
Muscle Glycogen Utilization during Exercise after Ingestion of Alcohol
Authors: SMITH HARRY A. , HENGIST AARON , BONSON DRUSUS JOHNSON , WALHIN JEAN-PHILIPPE , JONES ROBERT , TSINTZAS KOSTAS , AFMAN GREGG H. , GONZALEZ JAVIER T. , BETTS JAMES A.
Published: July 2020

Purpose

Ingested ethanol (EtOH) is metabolized gastrically and hepatically, which may influence resting and exercise metabolism. Previous exercise studies have provided EtOH intravenously rather than orally, altering the metabolic effects of EtOH. No studies to date have investigated the effects of EtOH ingestion on systemic and peripheral (e.g., skeletal muscle) exercise metabolism.

Methods

Eight men (mean ± SD; age = 24 ± 5 yr, body mass = 76.7 ± 5.6 kg, height = 1.80 ± 0.04 m, V˙O2peak = 4.1 ± 0.2 L·min−1) performed two bouts of fasted cycling exercise at 55% V˙O2peak for 2 h, with (EtOH) and without (control) prior ingestion of EtOH 1 h and immediately before exercise (total dose = 0.1 g·kg lean body mass−1·h−1; 30.2 ± 1.1 g 40% ABV Vodka; fed in two equal boluses) in a randomized order, separated by 7–10 d.

Results

Muscle glycogen use during exercise was not different between conditions (mean [normalized 95% confidence interval]; EtOH, 229 [156–302] mmol·kg dm−1, vs control, 258 [185–331] mmol·kg dm−1; P = 0.67). Mean plasma glucose concentrations during exercise were similar (control, 5.26 [5.22–5.30], vs EtOH, 5.34 [5.30–5.38]; P = 0.06). EtOH ingestion resulted in similar plasma nonesterified fatty acid concentrations compared with rest (control, 0.43 [0.31–0.55] mmol·L−1, vs EtOH, 0.30 [0.21–0.40] mmol·L−1) and during exercise. Plasma lactate concentration was higher during the first 30 min of rest after EtOH consumption (mean concentration; control, 0.83 [0.77–0.90] mmol·L−1, vs EtOH, 1.00 [0.93–1.07] mmol·L−1), but the response during exercise was similar between conditions.

Conclusions

Muscle glycogen utilization was similar during exercise with or without prior EtOH ingestion, reflected in similar total whole-body carbohydrate oxidation rates observed.