bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing batch effects in microbiome data
Authors: Wang Yiwen , LêCao Kim-Anh
Published: October 2019

Microbial communities have been increasingly studied in recent years to investigate their role in ecological habitats. However, microbiome studies are difficult to reproduce or replicate as they may suffer from confounding factors that are unavoidable in practice and originate from biological, technical or computational sources. In this review, we define batch effects as unwanted variation introduced by confounding factors that are not related to any factors of interest. Computational and analytical methods are required to remove or account for batch effects. However, inherent microbiome data characteristics (e.g. sparse, compositional and multivariate) challenge the development and application of batch effect adjustment methods to either account or correct for batch effects. We present commonly encountered sources of batch effects that we illustrate in several case studies. We discuss the limitations of current methods, which often have assumptions that are not met due to the peculiarities of microbiome data. We provide practical guidelines for assessing the efficiency of the methods based on visual and numerical outputs and a thorough tutorial to reproduce the analyses conducted in this review.
Mat_peptide: comprehensive annotation of mature peptides from polyproteins in five virus families
Authors: Larsen Christopher N , Sun Guangyu , Li Xiaomei , Zaremba Sam , Zhao Hongtao , He Sherry , Zhou Liwei , Kumar Sanjeev , Desborough Vince , Klem Edward B
Published: October 2019

Motivation

Sequence repositories have few well-annotated virus mature peptide sequences. Therefore post-translational proteolytic processing of polyproteins into mature peptides (MPs) has been performed in silico, with a new computational method, for over 200 species in 5 pathogenic virus families (Caliciviridae, Coronaviridae, Flaviviridae, Picornaviridae and Togaviridae).

Results

Using pairwise alignment with reference sequences, MPs have been annotated and their sequences made available for search, analysis and download. At publication the method had produced 156 216 sequences, a large portion of the protein sequences now available in https://www.viprbrc.org. It represents a new and comprehensive mature peptide collection.

Availability and implementation

The data are available at the Virus Pathogen Resource https://www.viprbrc.org, and the software at https://github.com/VirusBRC/vipr_mat_peptide.
Effectiveness of Private and Public High Schools: Evidence from Finland
Authors: Kortelainen Mika , Manninen Kalle
Published: October 2019

A number of papers have compared the effectiveness of private and public schools in different institutional settings. However, most of these studies are observational and do not utilize experimental or quasi-experimental design to evaluate the value-added or the effectiveness of private schools in comparison to public schools. This study focuses on private and public high schools in Helsinki, the capital city of Finland. We use two different methods to compare private and public schools, value-added estimation and regression discontinuity design (RDD). Although based on somewhat different assumptions, both methods allow us to evaluate the causal effect of private schools on the exit exam results in high school. We find that private schools perform marginally better than public schools, but the difference in performance is very small and statistically insignificant according to both methods. Various robustness and validity checks strengthen our RDD results and the validity of the discontinuity design.
TreeExp2: An Integrated Framework for Phylogenetic Transcriptome Analysis
Authors: Yang Jingwen , Ruan Hang , Xu Wenjie , Gu Xun
Published: October 2019

Recent innovations of next-generation sequencing such as RNA-seq have generated an enormous amount of comparative transcriptome data, which have shed lights on our understanding of the complexity of transcriptional regulatory systems. Despite numerous RNA-seq analyses, statistical methods and computational tools designed for phylogenetic transcriptome analysis and evolution have not been well developed. In response to this need, we developed software TreeExp2 specifically for RNA-seq data. The R-package TreeExp2 has implemented a suite of advanced, recently developed methods for transcriptome evolutionary analysis. Its main functions include the ancestral transcriptome inference, estimation of the strength of expression conservation, new expression distance, and the relative expression rate test. TreeExp2 provides an integrated, statistically sound framework for phylogenetic transcriptome analysis. It will considerably enhance our analytical capability for exploring the evolution and selection at the transcriptome level. The current version of TreeExp2 is available under GPLv3 license at the Github developer site https://github.com/jingwyang/TreeExp; last accessed November 12, 2019, and its online tutorial which describes the biological theories in details and fully worked case studies with real data can be found at https://jingwyang.github.io/TreeExp-Tutorial; last accessed November 12, 2019.
Redress for Involuntarily Sterilised Trans People in Sweden against Evolving Human Rights Standards: A Critical Appraisal
Authors: Alaattinoğlu Daniela , Rubio-Marín Ruth
Published: October 2019

Involuntary sterilisation is a long-standing practice that has targeted vulnerable and marginalised groups in different historical and geographical contexts. These include transgender and transsexual people who have often had to undergo sterilisation as a requirement for legal gender recognition. During the last decades, the international community has started to recognise involuntary sterilisation as a violation of human rights, with remedial implications flowing from state responsibility. To date, however, no binding remedial human rights standards have been established with reference to trans people specifically. Importantly, in March 2018, the Swedish Parliament approved legislation to compensate sterilised trans people on an ex gratia basis. This article evaluates the new Swedish legislation against developing human rights remedial standards. While pointing out enduring shortcomings, it welcomes the remedial initiative in the Swedish Compensation Act, highlighting the need for equal and coherent international remedial standards concerning involuntarily sterilised persons regardless of their gender identity.
Implementing a hash-based privacy-preserving record linkage tool in the OneFlorida clinical research network
Authors: Bian Jiang , Loiacono Alexander , Sura Andrei , Mendoza Viramontes Tonatiuh , Lipori Gloria , Guo Yi , Shenkman Elizabeth , Hogan William
Published: October 2019

Objective

To implement an open-source tool that performs deterministic privacy-preserving record linkage (RL) in a real-world setting within a large research network.

Materials and Methods

We learned 2 efficient deterministic linkage rules using publicly available voter registration data. We then validated the 2 rules’ performance with 2 manually curated gold-standard datasets linking electronic health records and claims data from 2 sources. We developed an open-source Python-based tool—OneFL Deduper—that (1) creates seeded hash codes of combinations of patients’ quasi-identifiers using a cryptographic one-way hash function to achieve privacy protection and (2) links and deduplicates patient records using a central broker through matching of hash codes with a high precision and reasonable recall.

Results

We deployed the OneFl Deduper (https://github.com/ufbmi/onefl-deduper) in the OneFlorida, a state-based clinical research network as part of the national Patient-Centered Clinical Research Network (PCORnet). Using the gold-standard datasets, we achieved a precision of 97.25∼99.7% and a recall of 75.5%. With the tool, we deduplicated ∼3.5 million (out of ∼15 million) records down to 1.7 million unique patients across 6 health care partners and the Florida Medicaid program. We demonstrated the benefits of RL through examining different disease profiles of the linked cohorts.

Conclusions

Many factors including privacy risk considerations, policies and regulations, data availability and quality, and computing resources, can impact how a RL solution is constructed in a real-world setting. Nevertheless, RL is a significant task in improving the data quality in a network so that we can draw reliable scientific discoveries from these massive data resources.
Development of optimal genetic evaluations for teat and udder structure in Canadian Angus cattle
Authors: Devani Kajal , Valente Tiago S , Crowley John J , Orsel Karin
Published: October 2019

Despite their heritability and influence on female productivity, there are currently no genetic evaluations for teat and udder structure in Canadian Angus cattle. The objective of this study was to develop optimal genetic evaluations for these traits in the Canadian Angus population. Guidelines recommended by Beef Improvement Federation (BIF) were used to score teat and udder structure in 1,735 Canadian Angus cows from 10 representative herds. Cows scored ranged in parity from 1 to 13; however, >70% of cows were parity ≤4. Scores ranged from 1 (large, bottle shaped) to 9 (very small) for teats and from 1 (very pendulous) to 9 (very tight) for udders. Consistent with parity distribution, >70% of teat and udder scores were ≥6. Teat and udder scores (TS9 and US9, respectively) were modeled using a multiple trait animal model with random effects of contemporary group (herd-year-season) and additive genetic effect, and fixed effects of breed, parity group, and days between calving and scoring. To test good versus poor structure, a binary classification of 1 or 2 (TS2, US2) [comprised of scores 1 to 5 = 1 (poor structure) and scores 6 to 9 = 2 (good structure)] was created. Further, to assess the impact of grouping less frequently observed poor scores, a 1 to 7 scale (TS7, US7) was created by combining teat and udder scores 1 to 3. Analyses for teat and udder scores on scales TS9, US9, TS7, US7, and TS2, US2 were compared. In addition, both threshold and linear animal models were used to estimate variance components for the traits. Data treatment and models were evaluated based on correlation of resulting estimated breeding value (EBV) with corrected phenotypes, Spearman’s rank correlation coefficient, average EBV accuracies (r), and deviance information criteria (DIC). TS9, US9 scales for teat and udder scores and linear models performed best. Estimates of heritability (SE) for teat and udder score were 0.32 (0.06) and 0.15 (0.04), respectively, indicating these traits were moderately heritable and that genetic improvement for teat and udder scores was possible. Estimates of phenotypic and genotypic correlations for teat and udder score were 0.46 (0.02) and 0.71 (0.09), respectively. Estimates of genotypic correlations with birth weight (BW), weaning weight (WW), and yearling weight (YW), ranged from −0.04 (0.10) to −0.20 (0.12), verifying the importance of selecting for improved teat and udder score as individual traits, alongside performance traits.
Utility of index lesion volume assessed by multiparametric MRI combined with Gleason grade for assessment of lymph node involvement in patients with high-risk prostate cancer
Authors: Hatano Koji , Tanaka Junichiro , Nakai Yasutomo , Nakayama Masashi , Kakimoto Ken-ichi , Nakanishi Katsuyuki , Nishimura Kazuo
Published: October 2019

Purpose

We examined the potential predictors of lymph node involvement and evaluated whether index lesion volume assessed using multiparametric magnetic resonance imaging is associated with lymph node involvement among patients with high-risk prostate cancer.

Methods

Extended pelvic lymph node dissection was used to evaluate patients with lymph node involvement. We retrospectively analyzed consecutive 102 patients with high-risk prostate cancer who underwent extended pelvic lymph node dissection at our institution between 2011 and 2017. To evaluate the index lesion volume at multiparametric magnetic resonance imaging (mrV), lesions were manually contoured on each T2-weighted axial slice in combination with diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging and integrated using image analysis software. Logistic regression analysis was performed to identify predictors of lymph node involvement.

Results

The median mrV was 1.4 ml (range 0–30.1 ml), and the median number of resected lymph nodes was 14 (range 7–38). Among 102 patients, 28 (28%) had lymph node involvement. Multivariate analysis identified significant predictors of lymph node involvement as follows: biopsy Gleason-grade group 5 (odds ratio = 17.2; 95% confidence interval, 2.1–299.0; P = 0.005), preoperative mrV (odds ratio = 1.14; 95% confidence interval, 1.02–1.30; P = 0.025) and percentage of positive cores with highest Gleason-grade group (odds ratio = 1.05; 95% confidence interval, 1.01–1.10; P = 0.005). Lymph node involvement was prevalent (69%) among tumors with Gleason-grade group 5 and mrV ≥3.4 ml, but was infrequently (10%) present among tumors with Gleason-grade group ≤4 and mrV <3.4 ml.

Conclusions

The combination of biopsy Gleason-grade and mrV may serve as a useful tool to stratify patients according to their risk of nodal metastases.
Isocitrate dehydrogenase 1 mutant glioblastomas demonstrate a decreased rate of pseudoprogression: a multi-institutional experience
Authors: Mohammadi Homan , Shiue Kevin , Grass G Daniel , Verma Vivek , Engellandt Kay , Daubner Dirk , Schackert Gabriele , Gondim Mercia J , Gondim Dibson , Vortmeyer Alexander O , Kamer Aaron P , Jin William , Robinson Timothy J , Watson Gordon , Yu Hsiang-Hsuan M , Lautenschlaeger Tim
Published: October 2019

Background

Pseudoprogression (psPD) represents false radiologic evidence of tumor progression and is observed in some glioblastoma (GBM) patients after postoperative chemoradiation (CRT) with temozolomide (TMZ). The ambiguity of the psPD diagnosis confounds identification of true progression and may lead to unnecessary interventions. The association between psPD and isocitrate dehydrogenase 1 (IDH1) mutational (mut) status is understudied, and its incidence may alter clinical decision making.

Methods

We retrospectively evaluated 120 patients with IDH1-mut (n = 60) and IDH1–wild-type (IDH-WT; [n = 60]) GBMs who received postoperative CRT with TMZ at 4 academic institutions. Response Assessment in Neuro-Oncology criteria were used to identify psPD rates in routine brain MRIs performed up to 90 days after CRT completion.

Results

Within 90 days of completing CRT, 9 GBM patients (1 [1.7%] IDH1-mut and 8 [13.3%] IDH1-WTs) demonstrated true progression, whereas 17 patients (3 [5%] IDH1-muts and 14 [23.3%] IDH1-WTs) demonstrated psPD (P  =  .004). IDH1-mut GBMs had a lower probability of psPD (hazard ratio: 0.173, 95% CI, 0.047-0.638, P = .008). Among the patients with radiologic signs suggestive of progression (n = 26), psPD was found to be the cause in 3 of 4 (75.0%) of the IDH1-mut GBMs and 14 of 22 (63.6%) of the IDH1-WT GBMs (P = .496). Median overall survival for IDH1-mut and IDH1-WT GBM patients was 40.3 and 23.0 months, respectively (P  < .001).

Conclusions

IDH1-mut GBM patients demonstrate lower absolute rates of psPD expression. Irrespective of GBM subtype, psPD expression was more likely than true progression within 90 days of completing CRT. Continuing adjuvant treatment for IDH1-mut GBMs is suggested if radiologic progression is suspected during this time interval.
#WhyID: Crowdsourcing the Top Reasons to Choose Infectious Diseases in the Age of Twitter
Authors: Cutrell James B
Published: October 2019

Despite lagging compensation and other challenges for the ID specialty, many compelling reasons still exist for why trainees should strongly consider ID as a specialty. Using Twitter as a crowdsourcing tool, the author shares his top 10 reasons for #WhyID.
RE-EVALUATION OF THE AIR KERMA PRIMARY STANDARD OF THE SMU IN 60Co AND 137Cs GAMMA RAY BEAMS
Authors: Durný Norman
Published: October 2019

The primary standard for air kerma of the Slovak Institute of Metrology (SMU) as a part of national standard of dosimetric quantities of gamma radiation NE028/02, based on cylindrical graphite walled cavity ionization chamber was established in 2002 for the 60Co gamma ray beams. Since then the main role of SMU was to continuously maintain, develop and refurbish the standard with related accessory to ensure international equivalence. Since 2002, a re-evaluation of the active volume of the ionizing chamber, correction factors, the key data, due to adoption of ICRU Report 90(1), and changes of the calibrations methods and corrections of the equipment were made to obtain improved parameters. The range was extended for 137Cs gamma ray beams and key comparisons with the Bureau International des Poids et Mesures (BIPM) were performed. ICRU Report 90(1) implementation led to a decrease of the Gray of −0.84% for 60Co and −0.80% for 137Cs.
Facilitatory/inhibitory intracortical imbalance in REM sleep behavior disorder: early electrophysiological marker of neurodegeneration?
Authors: Lanza Giuseppe , Aricò Debora , Lanuzza Bartolo , Cosentino Filomena Irene Ilaria , Tripodi Mariangela , Giardina Floriana , Bella Rita , Puligheddu Monica , Pennisi Giovanni , Ferri Raffaele , Pennisi Manuela
Published: October 2019

Study Objectives

Previous studies found an early impairment of the short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) to transcranial magnetic stimulation (TMS) in Parkinson’s disease. However, very little is known on the TMS correlates of rapid eye movement (REM) sleep behavior disorder (RBD), which can precede the onset of a α-synucleinopathy.

Methods

The following TMS measures were obtained from 14 de novo patients with isolated RBD and 14 age-matched healthy controls: resting motor threshold, cortical silent period, latency and amplitude of the motor evoked potentials, SICI, and ICF. A cognitive screening and a quantification of subjective sleepiness (Epworth Sleepiness Scale [ESS]) and depressive symptoms were also performed.

Results

Neurological examination, global cognitive functioning, and mood status were normal in all participants. ESS score was higher in patients, although not suggestive of diurnal sleepiness. Compared to controls, patients exhibited a significant decrease of ICF (median 0.8, range 0.5–1.4 vs. 1.9, range 1.4–2.3; p < 0.01) and a clear trend, though not significant, towards a reduction of SICI (median 0.55, range 0.1–1.4 vs. 0.25, range 0.1–0.3), with a large effect size (Cohen’s d: −0.848). REM Sleep Atonia Index significantly correlated with SICI.

Conclusions

In still asymptomatic patients for a parkinsonian syndrome or neurodegenerative disorder, changes of ICF and, to a lesser extent, SICI (which are largely mediated by glutamatergic and GABAergic transmission, respectively) might precede the onset of a future neurodegeneration. SICI was correlated with the muscle tone alteration, possibly supporting the proposed RBD model of retrograde influence on the cortex from the brainstem.
A Lighter Shade of Brown? Racial Formation and Gentrification in Latino Los Angeles
Authors: Huante Alfredo
Published: October 2019

Conventional gentrification literature has meaningfully demonstrated how economic inequality is perpetuated in urban settings, but there has been a limited understanding of how racial inequality is maintained. Drawing from participant observation, interviews, and digital ethnography in the barrio of Boyle Heights in Los Angeles that were collected over five years, this study examines how gentrification functions as a racial project and supports new forms of racialization to maintain uneven development along racial lines. Examining the ways that racial formation processes unfurl at the local scale expands conventional understanding of racial formation theory and practice while, simultaneously, illustrating the centrality of place in race-making. This study finds new race and class formations are developed by casting the barrio itself and significant portions of the Mexican American population as “honorary white.” Despite colorblind and post-racial ideologies espoused in majority-minority cities like Los Angeles, this landscape fostered emerging racial formations alongside gentrification processes which have increased racial, political, and economic inequality.
Pathogenicity and Distribution of Fusarium solani Isolates Associated with Erythrina Decline in Japan
Authors: Takashina Kuya , Chuma Izumi , Kajimura Hisashi , Kameyama Norikazu , Goto Chiaki , Kuroda Keiko
Published: October 2019

Erythrina spp. trees have been declining since the 2000s worldwide, and fungi belonging to Fusarium solani species complex (FSSC) have been suggested to be a causal factor of decline and mortality of Erythrina variegata trees in Okinawa Island, Japan. In addition to the FSSC isolate grouped as “it-1” based on ITS sequence data (previously called strain A), we conducted an inoculation experiment with two isolates grouped as “it-2” (previously strain B), which is genetically close to it-1. Two it-2 isolates originating from two islands showed pathogenicity to E. variegata with the same symptoms as those caused by it-1 isolate. We also found the isolates of it-1 and it-2 were widely distributed, including on Ishigaki Island, ∼400 km south of Okinawa Island across the ocean. All isolates of it-1 and it-2 belong to the ambrosia Fusarium clade of the FSSC, a group of symbionts of ambrosia beetles, including the pathogens of Fusarium dieback in avocados and teas. The detection of ambrosia beetles Euwallacea spp. from our specimens provided information on the vectors of the pathogens. Our present results suggest the fungi of the FSSC could be responsible for the Erythrina decline in other areas with damage.
Genotyping-by-Sequencing for the Study of Genetic Diversity inPuccinia triticina
Authors: Aoun Meriem , Kolmer James A. , Breiland Matthew , Richards Jonathan , Brueggeman Robert S. , Szabo Les J. , Acevedo Maricelis
Published: October 2019

Leaf rust, caused by Puccinia triticina Erikss., is globally the most widespread rust of wheat. Populations of P. triticina are highly diverse for virulence, with many different races found annually. The genetic diversity of P. triticina populations has been previously assessed using different types of DNA markers. Genotyping technologies that provide a higher density of markers distributed across the genome will be more powerful for analysis of genetic and phylogenetic relationships in P. triticina populations. In this study, we utilized restriction-associated DNA (RAD) genotyping-by-sequencing (GBS) adapted for the Ion Torrent sequencing platform for the study of population diversity in P. triticina. A collection of 102 isolates, collected mainly from tetraploid and hexaploid wheat, was used. The virulence phenotypes of the isolates were determined on 20 lines of Thatcher wheat near isogenic for leaf rust resistance genes. Seven races were found among 57 isolates collected from tetraploid wheat, and 21 races were observed among 40 hexaploid wheat type isolates. This is the first study to report durum wheat virulent races to Lr3bg in Tunisia, Lr14a in Morocco, and Lr3bg and Lr28 in Mexico. Ethiopian isolates with high virulence to durum wheat but avirulent on Thatcher (hexaploid wheat) were tested for virulence on a set of durum (tetraploid) differentials. A subset of 30 isolates representing most of the virulence phenotypes in the 102 isolates were genotyped using RAD-GBS. Phylogenetic analysis of 30 isolates using 2,125 single nucleotide polymorphism (SNP) markers showed nine distinct clusters. There was a general correlation between virulence phenotypes and SNP genotypes. The high bootstrap values between clusters of isolates in the phylogenetic tree indicated that RAD-GBS can be used as a new genotyping tool that is fast, simple, high throughput, cost effective, and provides a sufficient number of markers for the study of genetic diversity in P. triticina.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Use of Botanicals to Suppress Different Stages of the Life Cycle of Fusarium graminearum
Authors: Drakopoulos Dimitrios , Luz Carlos , Torrijos Raquel , Meca Giuseppe , Weber Pascal , Bänziger Irene , Voegele Ralf T. , Six Johan , Vogelgsang Susanne
Published: October 2019

Fusarium head blight (FHB) is one of the most important cereal diseases worldwide, causing yield losses and contamination of harvested products with mycotoxins. Fusarium graminearum is one of the most common FHB-causing species in wheat and barley cropping systems. We assessed the ability of different botanical extracts to suppress essential stages of the fungal life cycle using three strains of F. graminearum (FG0410, FG2113, and FG1145). The botanicals included aqueous extracts from white mustard (Sinapis alba) seed flour (Pure Yellow Mustard [PYM] and Tillecur [Ti]) as well as milled Chinese galls (CG). At 2% concentration (wt/vol), PYM and Ti completely inhibited growth of mycelium of all F. graminearum strains whereas, at 1%, CG reduced the growth by 65 to 83%, depending on the strain. While PYM and Ti reduced the germination of both conidia and ascospores at 2% (wt/vol), CG was only effective in reducing conidia germination. Perithecia formation of FG0410 but not FG2113 was suppressed by all botanicals. Moreover, application of botanicals on mature perithecia led to a two- to fourfold reduction in discharge of ascospores. Using liquid chromatography (LC) with diode array detection, we quantified the principal glucosinolate component sinalbin of PYM and Ti. LC time-of-flight mass spectrometry was used to demonstrate that the bioactive matrix of CG contains different gallotannins as well as gallic and tannic acids. Possible antifungal mechanisms of the botanical matrices are discussed. The results of this study are promising and suggest that PYM, Ti, and CG should be explored further for efficacy at managing FHB.

[Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Academic Advocacy: Opportunities to Influence Health and Science Policy Under U.S. Lobbying Law
Authors: Fernandez Lynch Holly , Bateman-House Alison , Rivera Suzanne M.
Published: October 2019

Medical school faculty and their colleagues in schools of nursing, public health, social work, and elsewhere often research issues of critical importance to health and science policy. When academics engage with government policymakers to advocate for change based on their research, however, they may find themselves engaged in “lobbying,” thereby entering a complex environment of legal requirements and institutional policies that they may not fully understand. To promote academic advocacy, this article explains what is and is not legally permitted when it comes to engaging with policymakers and encourages academic institutions to facilitate permissible advocacy activities.

U.S. law permits academic researchers to conduct certain types of policy-focused advocacy without running afoul of legal restrictions on lobbying. Academics acting in their personal capacities and with their own resources may freely engage with policymakers in any branch of government to provide their expertise and advocate for desired outcomes. When acting in their professional capacities, academics are free to engage in most advocacy activities directed to the executive and judicial branches, and they also may advocate to influence legislation and legislators within certain limits that are particularly relevant to academic work. In all cases, academics must take care to not use restricted funds for lobbying.

Academic researchers have an important role to play in advancing evidence-based health and science policy. They should familiarize themselves with legal restrictions and opportunities to influence policy based on their research, and their institutions should actively support them in doing so.
Effect of General Anesthetics on Caspase-3 Levels in Patients With Aneurysmal Subarachnoid Hemorrhage: A Preliminary Study
Authors: Balasubramanian Mukilan , Kuberan Aswini , Rawat Amit , Dhandapani Sivashanmugam , Panda Nidhi , Kumar Ajay , Sahoo Asish K. , Kumar Munish , Sharma Tanavi , Garcia Paul S. , Bhagat Hemant
Published: October 2019

Background:

General anesthesia has been associated with neuronal apoptosis and activation of caspases. Apoptosis is a crucial factor in early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). We conducted a double-blind, prospective, randomized pilot study to evaluate the effect of 4 anesthetic agents on cerebrospinal fluid (CSF) and serum caspase-3 levels in aSAH patients.

Materials and Methods:

A total of 44 good-grade aSAH patients with preoperative lumbar drain scheduled for surgical clipping or endovascular coiling were randomized to receive maintenance of anesthesia with propofol, isoflurane, sevoflurane, or desflurane. Caspase-3 levels were measured in CSF and serum samples collected at baseline, 1 hour after induction, and 1 hour after cessation of anesthesia.

Results:

Compared with baseline, there was a decrease in CSF caspase-3 levels and an increase in serum caspase-3 levels 1 hour after exposure to all 4 anesthetic agents; levels returned to baseline values after cessation of anesthesia. Median CSF caspase-3 levels at baseline, 1 hour after anesthesia exposure, and 1 hour after cessation of anesthesia were 0.0679, 0.0004, and 0.0689 ng/mL, respectively (P<0.05). Median serum caspase-3 levels at baseline, 1 hour after anesthesia exposure, and 1-hour after cessation of anesthesia were 0.0028, 0.0682, and 0.0044 ng/mL, respectively (P<0.05).

Conclusions:

Propofol, isoflurane, sevoflurane, or desflurane have similar effects on CSF and serum caspase-3. The reduction of intraoperative CSF caspase-3 levels suggests a possible role for general anesthesia in neuroresuscitation by slowing the neuronal apoptotic pathway.
Clinical Course, Associated Factors, and Blood Pressure Profile of Delayed-Onset Postpartum Preeclampsia
Authors: Redman Emily K. , Hauspurg Alisse , Hubel Carl A. , Roberts James M. , Jeyabalan Arun
Published: October 2019

OBJECTIVE:

To identify clinical risk factors associated with development of delayed-onset postpartum preeclampsia, and to characterize management and subsequent risk of cardiovascular disease.

METHODS:

This is a case–control study of women admitted to the hospital with delayed-onset postpartum preeclampsia (defined as a new diagnosis of preeclampsia presenting between 48 hours and 6 weeks postpartum) compared with women with full-term, uncomplicated pregnancies without a hypertensive diagnosis or diabetes. Included women delivered between January 2014 and June 2018 at a single tertiary care center. Women with an antenatal diagnosis of preeclampsia or chronic hypertension were excluded. Univariate analysis was used to identify risk factors associated with delayed-onset postpartum preeclampsia and to compare rates of hypertension and antihypertensive medication use, with follow-up beyond 3 months postpartum among a subset of women in the control group who were matched 2:1 with women in the case group. Multivariable logistic regression was performed and included covariates identified in a backward stepwise approach.

RESULTS:

Compared with women in the control group (n=26,936), women with delayed-onset postpartum preeclampsia (n=121) were significantly more likely to be of non-Hispanic black race (31.4% vs 18.0%), obese (39.7% vs 20.1%), and deliver by cesarean (40.5% vs 25.8%), all P<.01. For women diagnosed with delayed-onset postpartum preeclampsia, the median postpartum day of presentation was 7.0 (interquartile range 5.0–9.0), with 93.4% presenting secondary to symptoms, which was most commonly a headache. A majority (73.6%) underwent imaging studies, and 49.6% received intravenous antihypertensive agents. A total of 86 (71.0%) women with delayed-onset postpartum preeclampsia and 169 (72.8%) women in the control group had longer term information available, with a median follow-up time of 1.5 years (interquartile range 0.8–2.8). Delayed-onset postpartum preeclampsia was associated with higher blood pressures at 3 months postpartum or later (median systolic 130 mm Hg vs 112 mm Hg and median diastolic 80 mm Hg vs 70 mm Hg, P<.001).

CONCLUSION:

Delayed-onset postpartum preeclampsia is associated with variable management strategies. There is substantial overlap between the clinical risk factors for delayed-onset postpartum preeclampsia and antepartum preeclampsia. Our findings suggest that delayed-onset postpartum preeclampsia is also associated with an increased risk of progression to chronic hypertension.
Telemedicine Companies Providing Prescription-Only Medications
Authors: Hariton Eduardo , Tracy Erin E.
Published: October 2019

In the past few years, there has been a significant increase in the number of direct-to-consumer telehealth companies offering prescription medications to women. Leveraging technology, these companies have the potential to improve access to care and ensure that women have access to prescription-only medications in a convenient fashion. However, it is important to ensure that they are doing so in a safe, patient-centered way that observes evidence-based prescribing guidelines. In this article, we discuss the pros and cons of direct-to-consumer telehealth companies offering prescription medicine and suggest several guidelines to ensure that women are being cared for in an appropriate way.
Self-Removal of a Urinary Catheter After Urogynecologic Surgery
Authors: Shatkin-Margolis Abigail , Yook Eunsun , Hill Austin M. , Crisp Catrina C. , Yeung Jennifer , Kleeman Steven , Pauls Rachel N.
Published: October 2019

OBJECTIVE:

To evaluate whether self-discontinuation of a transurethral catheter is noninferior to office discontinuation in patients requiring indwelling catheterization for postoperative urinary retention after pelvic reconstructive surgery.

METHODS:

In this randomized noninferiority trial, patients with postoperative urinary retention after pelvic reconstructive surgery were assigned to self-discontinuation or office discontinuation of their catheter 1 week after surgery. The primary outcome was a noninferiority comparison of postoperative urinary retention at 1 week. Self-discontinuation patients were instructed on home catheter removal on postoperative day 7. Office discontinuation patients underwent a standard voiding trial on postoperative day 6–8. Postoperative urinary retention at 1 week was defined as continued catheterization on postoperative day 6–8. Secondary outcomes included urinary tract infections (UTI), residual volume at 2 weeks, duration of catheter use, recurrent postoperative urinary retention, number of patient encounters, and visual analog scales (VAS) regarding patient experience. Given a known incidence of postoperative urinary retention at 1 week (16%) and 15% noninferiority margin, a sample size of 74 per group (n=148) was planned.

RESULTS:

From January 2017 through March 2019, 217 women were screened and 157 were analyzed: 78 self-discontinuation and 79 office discontinuation. Demographic characteristics and surgeries performed were similar. Eleven patients in each group experienced postoperative urinary retention at 1 week (14.1% self-discontinuation vs 13.9% office discontinuation, P=.97), establishing noninferiority (difference 0.2%, 95% CI: −1.00, 0.10). There were significantly fewer patient encounters with self-discontinuation (42/78, 53.8% vs 79/79, 100%). Self-discontinuation patients demonstrated better VAS scores regarding pain, ease, disruption, and likelihood to use the same method again (all P<.05). Though the rate of UTI was high, there was no difference between groups (59.0% self-discontinuation vs 66.7% office discontinuation, P=.32). Residual volume at 2 weeks, recurrent postoperative urinary retention, and duration of catheter use were also similar.

CONCLUSION:

Self-discontinuation of a transurethral catheter was noninferior to office-based discontinuation in the setting of postoperative urinary retention after pelvic reconstructive surgery. Self-discontinuation resulted in fewer patient encounters and improved patient experience.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02996968.
Adverse Childhood Experiences Among Gynecology Patients With Chronic Pelvic Pain
Authors: Krantz Tessa E. , Andrews Nicholas , Petersen Timothy R. , Dunivan Gena C. , Montoya Maria , Swanson Naomi , Wenzl Cynthia K. , Zambrano Julissa R. , Komesu Yuko M.
Published: October 2019

OBJECTIVE:

To compare adverse childhood experiences (ACEs) in women with chronic pelvic pain with a control group, and describe occurrence of specific ACEs in women with chronic pelvic pain.

METHODS:

This case-control study examined the relationship between history of ACEs, traumatic events occurring during childhood as defined by the Centers for Disease Control and Prevention (CDC), and chronic pelvic pain. Patients diagnosed with chronic pelvic pain (n=60) were age-matched to a control group of women without chronic pelvic pain (n=60). All participants completed validated measures to detect for presence of any of the 11 ACEs as identified by the CDC's Behavioral Risk Factor Surveillance System ACE Module.

RESULTS:

Mean participant age was 40 (±11 years). Total numbers of ACEs were elevated in chronic pelvic pain participants compared with a control group (median 4 [interquartile range 2–6] vs median 1 [interquartile range 0–4], P<.001) and 53% of chronic pelvic pain participants had four or more ACEs, compared with 27% of the control group (odds ratio [OR] 3.14; 95% CI 1.46–6.75). All categories of abuse were more prevalent in chronic pelvic pain compared with the control group: physical (43% vs 15%, OR 4.3; 95% CI 1.8–10.4; P=.001), sexual (55% vs 23%, OR 4.0; 95% CI 1.8–8.8; P<.001) and verbal or emotional (62% vs 33%, OR 3.2; 95% CI 1.5–6.8; P=.003). Regarding household challenges, the subcategory most prevalent in chronic pelvic pain participants compared with the control group was that of witnessed domestic violence (35% vs 8%, OR 5.9; 95% CI 2.1–17.1, P<.001).

CONCLUSION:

Chronic pelvic pain participants had a greater than threefold odds of having a history of childhood abuse and having witnessed domestic violence during childhood compared with the control group. Women with chronic pelvic pain had increased numbers of ACEs and 53% had four or more ACEs, crossing a threshold that others have found to predict poor overall health outcomes.
Clinical and Genetic Contributors to New-Onset Atrial Fibrillation in Critically Ill Adults*
Authors: Kerchberger V. Eric , Huang Yi , Koyama Tatsuki , Shoemaker M. Benjamin , Darbar Dawood , Bastarache Julie A. , Ware Lorraine B. , Shaver Ciara M.
Published: October 2019

Objectives:

New-onset atrial fibrillation during critical illness is an independent risk factor for mortality. The ability to identify patients at high risk for new-onset atrial fibrillation is limited. We hypothesized that genetic susceptibility contributes to risk of new-onset atrial fibrillation in the ICU.

Design:

Retrospective sub-study of a prospective observational cohort study.

Setting:

Medical and general surgical ICUs in a tertiary academic medical center.

Patients:

One-thousand three-hundred sixty-nine critically ill patients admitted to the ICU for at least 2 days with no known history of atrial fibrillation who had DNA available for genotyping.

Interventions:

None.

Measurements and Main Results:

We genotyped 21 single-nucleotide polymorphisms associated with atrial fibrillation in ambulatory studies using a Sequenom platform (San Diego, CA). We collected demographics, medical history, and development of new-onset atrial fibrillation during the first four days of ICU admission. New-onset atrial fibrillation occurred in 98 patients (7.2%) and was associated with age, male sex, coronary artery disease, and vasopressor use. Single-nucleotide polymorphisms associated with new-onset atrial fibrillation were rs3853445 (nearPITX2,p= 0.0002), rs6838973 (nearPITX2,p= 0.01), and rs12415501 (inNEURL,p= 0.03) on univariate testing. When controlling for clinical factors, rs3853445 (odds ratio, 0.47; 95% CI, 0.30–0.73;p= 0.001) and rs12415501 (odds ratio, 1.72; 95% CI, 1.27–2.59;p= 0.01) remained significantly associated with new-onset atrial fibrillation. The addition of genetic variables to clinical factors improved new-onset atrial fibrillation discrimination in a multivariable logistic regression model (C-statistic 0.82 vs 0.78;p= 0.0009).

Conclusions:

We identified several single-nucleotide polymorphisms associated with new-onset atrial fibrillation in a large cohort of critically ill ICU patients, suggesting there is genetic susceptibility underlying this common clinical condition. This finding may provide new targets for future mechanistic studies and additional insight into the application of genomic information to identify patients at elevated risk for a common and important condition in the ICU.
Novel molecular targets for the treatment of lung cancer
Authors: Rosell Rafael , Karachaliou Niki , Arrieta Oscar
Published: October 2019

Purpose of review

The mutational landscape in lung adenocarcinoma (LADC) is broadly recognized, particularly regarding the presence of the epidermal growth factor receptor (EGFR) mutation in non-smokers. However, even in the EGFR canonical-mutant LADC, other accompanying alterations surface which may have a major impact in prognosis and open possibilities to explore new therapeutic approaches.

Recent findings

Complex genomic rearrangements, including chromothripsis and chromoplexy, are the origin of most-known fusion oncogenes, including echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, Cluster of Differentiation 74-c-ros oncogene 1, and kinesin-1 heavy chain- rearranged during transfection. Quite often LADCs driven by fusion oncogenes are accompanied by SET domain containing 2 (SETD2) mutations. SETD2 mutations have been described in renal cancer and have been related to cisplatin resistance in LADCs. Suppression of the SETD2 function inhibits the signal transducer and transcription activator function and the interferon-signaling pathway, which could partially explain the lack of effectiveness of immunotherapy in LADCs driven by fusion oncogenes.

Targeted next-generation sequencing of DNA in the tumor tissue or in the circulating plasma of LADC is becoming indispensable for the accurate classification of LADCs that can receive appropriate targeted therapy. It is unquestionable that additional techniques, like RNA sequencing or the nCounter technology, can accomplish accurate assessment of an ample array of fusion oncogenes involved in LADCs.
Hard-wired Epimysial Recordings from Normal and Reinnervated Muscle Using a Bone-anchored Device
Authors: Lancashire Henry T. , Al Ajam Yazan , Dowling Robert P. , Pendegrass Catherine J. , Blunn Gordon W.
Published: October 2019

Background:

A combined approach for prosthetic attachment and control using a transcutaneous bone-anchored device and implanted muscle electrodes can improve function for upper-limb amputees. The bone-anchor provides a transcutaneous feed-through for muscle signal recording. This approach can be combined with targeted muscle reinnervation (TMR) to further improve myoelectric control.

Methods:

A bone-anchored device was implanted trans-tibially in n = 8 sheep with a bipolar recording electrode secured epimysially to the peroneus tertius muscle. TMR was carried out in a single animal: the peroneus tertius was deinnervated and the distal portion of the transected nerve to the peroneus muscle was coapted to a transected nerve branch previously supplying the tibialis anterior muscle. For 12 weeks (TMR) or 19 weeks (standard procedure), epimysial muscle signals were recorded while animals walked at 2 km·h−1.

Results:

After 19 weeks implantation following standard procedure, epimysial recording signal-to-noise ratio (SNR) was 18.7 dB (± 6.4 dB, 95% CI) with typical recordings falling in the range 10–25 dB. Recoveries in gait and muscle signals were coincident 6 weeks post-TMR; initial muscle activity was identifiable 3 weeks post-TMR though with low signal amplitude and signal-to-noise ratio compared with normal muscle recordings.

Conclusions:

Following recovery, muscle signals were recorded reliably over 19 weeks following implantation. In this study, targeted reinnervation was successful in parallel with bone-anchor implantation, with recovery identified 6 weeks after surgery.
Novel Surface Anatomic Landmarks of the Jowl to Guide Treatment with ATX-101
Authors: Shridharani Sachin M.
Published: October 2019

Facial appearance is critical to physical attractiveness, and maintaining a youthful face and neck is a major motivation for individuals seeking facial cosmetic procedures. A strong mandibular border without prominent jowls is one sign of a youthful face as jowling occurs with age, contributing to squaring of the face and loss of jawline definition. Excess jowl fat has traditionally been reduced with surgical liposuction when jowling is caused by fat flow across the mandible. The approval of ATX-101 (deoxycholic acid injection) for submental fat reduction provides a minimally invasive technique that may also be suitable for jowl fat reduction. The author has developed novel facial markings that consistently isolate the jowl fat area of concern at the mandible for treatment with ATX-101. The current work refreshes physicians on important jowl anatomical structures, defines the facial markings that consistently isolate the jowl, and describes an injection technique to safely treat excess jowl fat with ATX-101.
Measurement of Quality of Life in Keratoconus
Authors: Kandel Himal , Pesudovs Konrad , Watson Stephanie L.
Published: October 2019

Purpose:

To identify and assess the quality of questionnaires used to measure quality of life in keratoconus and guide selection of the most appropriate questionnaire for evaluating the impact of keratoconus.

Methods:

A literature search was carried out in Scopus, Web of Science, PubMed, MEDLINE, Cochrane, and PsycINFO databases. Articles that described a questionnaire to measure quality of life in keratoconus were included. Information on psychometric properties and validity was extracted and analyzed based on a set of quality criteria. Finally, the impact of keratoconus and its management methods on quality of life was reviewed.

Results:

The search yielded 331 publications, of which 45 articles describing 18 (12 ophthalmic including 2 keratoconus-specific and 6 generic) questionnaires were reviewed. Most of the articles (40, 88.9%) described ophthalmic questionnaires not specific to keratoconus. The National Eye Institute Visual Function Questionnaire was the most frequently used questionnaire (n = 26). Only 4 articles provided information on psychometric properties. The Keratoconus Outcomes Research Questionnaire, the only validated keratoconus-specific questionnaire, had the most superior psychometric properties. However, it consists of items on only 2 domains of quality of life (activity limitation and symptoms). Overall, keratoconus management methods (spectacles, contact lenses, and cross-linking in early stages, corneal transplantation in late stages) improved quality of life. The quality of life scores were associated with clinical measures including visual acuity, corneal topography, pachymetry, and keratoconus severity.

Conclusions:

There is a need for a comprehensive and high-quality patient-reported outcome measure in keratoconus. A questionnaire should be chosen based on the purpose and the quality of the questionnaire. This review guides selection of an appropriate questionnaire.