bluuebunny/crossref_metadata_2025 huggingface dataset:
Conjunctival Trichodiscoma of the Lower Eyelid
Authors: Kasturi Nirupama , Chavhan Pratima , Ramakant Ghag Gaurav , Devaraj Athira , Babu K. Ramesh , N.G. Rajesh
Published: October 2019

Trichodiscomas are benign tumors of the skin which develop around a hair follicle. They usually present on the face, neck, or trunk region. The authors report a rare case of a 63-year-old man who presented with a tumor on the left lower eyelid that was histologically proven to be a trichodiscoma of conjunctival origin.

Trichodiscomas are benign tumors of the skin appendage which develop around a hair follicle. Although conjunctival hair follicles are rudimentary and do not give rise to hair, rarely a benign proliferation of these cells can result in trichodiscoma of the conjunctiva.
Emergency bedside ultrasound: benefits as well as caution – part 1. General
Authors: Wong Adrian , Vieillard-Baron Antoine , Malbrain Manu L.N.G.
Published: October 2019

Purpose of review

The use of bedside or point-of-care ultrasound (POCUS) in medical emergencies is rapidly becoming more established as an effective acute diagnostic tool. The purpose of this review is to provide an overview of the various techniques currently used that are readily available, as well as several in development. Possible caveats are also addressed.

Recent findings

Despite its widespread use, definitive studies demonstrating improved patient outcomes are limited. The list of indications for POCUS nonetheless is increasing as practitioners acknowledge clinical benefits, and technological advancement improves diagnostic accuracy and efficiency of use.

We believe that a core level of POCUS should be achievable by practicing clinicians. Ultimately, the integration of POCUS findings into a patient management strategy must be holistic, and hence requires prudent consideration of the clinical scenario.
The outcome of the HCC patients underwent ALPPS
Authors: Peng Chihan , Li Chuan , Liu Chang , Wen Tianfu , Yang Jiayin , Li Bo , Yan Lvnan
Published: October 2019

The complete resection offers the best long-term survival for advanced hepatocellular carcinoma patients. ALPPS as a choice of resection, how is its outcome compared to one-stage resection, liver transplantation and TACE? This retrospective study included 20 ALPPS patients. To minimize the effect of confounding influences of measured covariates, PSM was performed. The overall survival (OS), morbidity, mortality and the increasing rate, KGR were analyzed. The OS in ALPPS group is 27.4 (±3.8 months) moths and the TACE group is 13.5(±1.2 months) (P < .001), LT group is 41.3 (±3.2 months) (P = .048), Resection group is 31.8 (±2.6 months) (P = .368). And the medium increasing volume is 209.5 cm3 (±61.5 cm3) with the increasing ratio 52.4% (+26.9%). The ALPPS is a feasible treatment for HCC patients and it provides a better long-term survival than TACE and it is similar to Resection, less than LT.
Evaluation of the effectiveness of infrared light-emitting diode photobiomodulation in children with sleep bruxism
Authors: Kobayashi Fernanda Yukie , Castelo Paula Midori , Gonçalves Marcela Leticia Leal , Motta Lara Janisky , Mota Ana Carolina da Costa , Altavista Olga Maria , Pinto Marcelo Mendes , Salgueiro Monica Canuto , Ferreira Kristianne Porta Santos , Bussadori Sandra Kalil
Published: October 2019

Background:

Sleep bruxism is a masticatory muscle activity characterized as rhythmic (phasic) or nonrhythmic (tonic). In children and adolescents, etiological factors, such as breathing pattern and sleep quality, have recently been addressed in studies investigating sleep bruxism. New therapies for adults, such as botulinum toxin, have been investigated, but such techniques are not applicable for individuals in the growth and development phase.

Methods:

The participants will be 76 children, which will be randomly allocated to a control group, that is group 1, absence of bruxism; group 2, children with bruxism treated with infrared light-emitting diode (LED); and group 3, bruxism treated with occlusal splint. All participants will be submitted to a clinical evaluation to evaluate muscle activity and salivary biomarkers, before and after treatments. Muscle activity will be verified by electromyography of muscles mastication, masseter and temporal, and salivary biomarkers observed will be cortisol and dopamine levels.

Discussion:

Photobiomodulation therapy has piqued the interest of researchers, as this noninvasive method has demonstrated positive results in problems related to muscle tissues. This document describes the protocol for a proposed study to evaluate morphological and psychosocial aspects in children and adolescents with awake bruxism and their responses to photobiomodulation therapy with infrared LED.

Clinical trials:

https://clinicaltrials.gov/ct2/show/NCT03710174
Predictive role of monocyte-to-lymphocyte ratio in patients with Klebsiella pneumonia infection
Authors: Wang Jia-lu , Lu Xiao-ye , Xu Xin-hui , Zhang Ke-ji , Gong Hao , Lv Dan , Ni Zhu-ang , Zhu Chang-qing
Published: October 2019

The aim of the study is to explore whether monocyte–to-lymphocyte ratio (MLR) provides predictive value of the severity in patients with Klebsiella pneumonia infection (KPI).

Patients in a tertiary medical center with Klebsiella pneumonia infection from 2014 to 2017 were recruited in this study. Patients with Klebsiella pneumonia infection were stratified into two groups based on the National Early Warning Score (NEWS). MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. The area under the curve (AUC) values was determined using the receiver-operating characteristic (ROC) curve. The correlation between the variables was tested with Pearson or Spearman correlation analysis. Ordinal logistic regression analysis was used to assess the relationship between MLR and the severity of Klebsiella pneumonia infection.

One hundred fifty-two patients were finally enrolled for analysis. Among those, 43 (28.29%) cases had severe KPI. MLR was found to be an independent risk factor of the serious Klebsiella pneumonia infection (OR: 23.74, 95% CI: 5.41–104.11, P < .001). Besides, MLR was positively correlated with NEWS score (r = 0.57, P < .001). In the receiver-operating characteristic (ROC) curve analysis, MLR, with an optimal cut-off value of 0.665, predicted the severe coronary lesion with a sensitivity of 79.4% and specificity of 84.4%.

MLR was an independent predictor of the severe Klebsiella pneumonia infection. Compared with neutrophil-to-lymphocyte ratio (NLR), MLR has a better performance to evaluate the severity of Klebsiella pneumonia infection.
Efficacy and safety of electroacupuncture on metabolic syndrome due to olanzapine and risperidone
Authors: Ning Yanzhe , Jia Hongxiao , Chen Pei , Zhu Hong , Yin Dongqing
Published: October 2019

Introduction:

With the second-generation antipsychotics (SGAs) widely applied to treat patients with schizophrenia, adverse effects, especially the metabolic syndrome (MetS), were paid more attention following by the efficacy of SGAs. Several studies have suggested that acupuncture could be an effective and safe intervention for MetS. Here, we present a study protocol to investigate the effect of electroacupuncture on MetS due to olanzapine and risperidone.

Methods:

This study is a prospective, randomized, single-centered, patient-assessor-blinded, parallel-controlled clinical pilot trial. In all, 36 patients will be randomized to an experimental group or control group by a 1:1 ratio. All patients will receive lifestyle interventions. The experimental group will receive electroacupuncture treatment. The control group will receive sham electroacupuncture treatment. The primary outcomes are body mass index (BMI) and waist circumference (WC). The secondary outcome measures include blood pressure (BP), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), leptin, and adiponectin. We will assess at baseline, 8 weeks after intervention and at the end of 3 months’ follow-up.

Discussion:

The results of this trial are expected to provide data on the efficacy and safety of electroacupuncture on MetS due to olanzapine and risperidone, and potential biochemical mechanism.
Uterus-like mass in the right broad ligament
Authors: Liu Lei , Yang Hui , Zhang Shu-Peng
Published: October 2019

Rationale:

Uterus-like masses (ULMs) are rare benign lesions that resemble the uterus.

Patient concerns:

Here, we describe the case of a woman with a ULM in the right broad ligament. A 51-year-old woman with a 2-month history of irregular vaginal bleeding was found to have a mass in the right broad ligament. Imaging studies revealed a solid-cystic lesion, suggestive of an endometrial cyst with malignant transformation.

Interventions:

She underwent prompt surgery for the removal of the mass. Intraoperatively, the uterus and ovaries appeared normal, and an 8-cm-long mass was observed in the right broad ligament without any connection to the uterus or ovaries. The mass was successfully excised.

Diagnoses:

Postoperative histopathological examination showed that the cystic mass was filled with a blackish-brownish fluid and that it had thick walls resembling the uterine myometrium. The cyst center was lined by endometrial glands that were positive for cytokeratin as well as estrogen and progesterone receptors, and by stromal cells that were positive for CD10.

Outcomes:

The patient recovered well and has had no further symptoms during 2 years of follow-up.

Lessons:

We have reported a case of ULM in the right broad ligament in a Chinese woman. Although ULMs are rare, they should be considered in the differential diagnosis for pelvic masses.
Acute blindness as a presenting sign of left atrial myxoma in a pediatric patient
Authors: Yi Seo Yeon , Han Min Jeong , Kong Young Hwa , Joo Chan Uhng , Kim Sun Jun
Published: October 2019

Rationale:

Central retinal artery occlusion (CRAO) due to cardiac myxoma primarily occurs in elderly individuals. Early detection and surgical resection of myxoma are extremely important because CRAO causes complete blindness in most cases. However, due to the extremely low incidence of CRAO caused by cardiac myxoma in the pediatric age group, such condition is rarely reported.

Patient concerns:

A 16-year-old female patient visited our hospital due to sudden onset of vision loss in the left eye, dysarthria, and right-sided hemiplegia.

Diagnoses:

She was diagnosed with CRAO via fundoscopy. Results showed a cherry-red spot, indicating CRAO. Brain magnetic resonance imaging (MRI) revealed multifocal diffusion-restricted foci, particularly in the left frontal lobe. Echocardiography revealed a left atrial mass measuring 4.21 cm × 2.25 cm. The mass was attached to the interseptum and moved along the inflow of the mitral valve. Cardiac computed tomography (CT) revealed an enhanced mass measuring 3 cm × 2.2 cm × 3 cm and with irregular margin on the anterior wall of the left atrium and the border of the fossa ovalis.

Interventions:

The patient underwent surgical excision under general anesthesia. Intraoperative finding showed a huge, jelly-like, and extremely friable mass. Pathological examination confirmed myxoma.

Outcomes:

During a follow-up of 2 years after diagnosis, she did not present with other neurological deficits and no residual mass was observed on echocardiography. However, visual impairment of the left eye persisted.

Lessons:

Most patients with CRAO may present with other mild symptoms that are often be neglected before CRAO development. We recommend that patients who present with frequent syncopal attack or symptoms of transient ischemic attack should undergo echocardiography.
Identification of gene and microRNA changes in response to smoking in human airway epithelium by bioinformatics analyses
Authors: Huang Jizhen , Jiang Wanli , Tong Xiang , Zhang Li , Zhang Yuan , Fan Hong
Published: October 2019

Smoking is a substantial risk factor for many respiratory diseases. This study aimed to identify the gene and microRNA changes related to smoking in human airway epithelium by bioinformatics analysis.

From the Gene Expression Omnibus (GEO) database, the mRNA datasets GSE11906, GSE22047, GSE63127, and microRNA dataset GSE14634 were downloaded, and were analyzed using GEO2R. Functional enrichment analysis of the differentially expressed genes (DEGs) was enforced using DAVID. The protein–protein interaction (PPI) network and differentially expressed miRNAs (DEMs)- DEGs network were executed by Cytoscape.

In total, 107 DEGs and 10 DEMs were determined. Gene Ontology (GO) analysis revealed that DEGs principally enriched in oxidation-reduction process, extracellular space and oxidoreductase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that DEGs were principally enriched in metabolism of xenobiotics by cytochrome P450 and chemical carcinogenesis. The PPI network revealed 15 hub genes, including NQO1, CYP1B1, AKR1C1, CYP1A1, AKR1C3, CEACAM5, MUCL1, B3GNT6, MUC5AC, MUC12, PTGER4, CALCA, CBR1, TXNRD1, and CBR3. Cluster analysis showed that these hub genes were associated with adenocarcinoma in situ, squamous cell carcinoma, cell differentiation, inflammatory response, oxidative DNA damage, oxidative stress response and tumor necrosis factor. Hsa-miR-627-5p might have the most target genes, including ITLN1, TIMP3, PPP4R4, SLC1A2, NOVA1, RNFT2, CLDN10, TMCC3, EPHA7, SRPX2, PPP1R16B, GRM1, HS3ST3A1, SFRP2, SLC7A11, and KLHDC8A.

We identified several molecular changes induced by smoking in human airway epithelium. This study may provide some candidate genes and microRNAs for assessing the risk of lung diseases caused by smoking.
Weight status in individuals with autism spectrum disorder
Authors: Xie Xue-Ni , Li Yong-Jiang , Lei Xue , Li Ya-Min
Published: October 2019

Background:

Weight status and autism spectrum disorder (ASD) are rising public health concerns. An increasing number of reports indicate that individuals with ASD may have unhealthy weight status, but the evidence is mixed. To understand the weight status in individuals with ASD and provide strategies for prevention and intervention, we describe the protocol for a systematic review and meta-analysis aimed at assessing the prevalence of obesity, overweight, and underweight in ASD.

Methods:

A broad range of key bibliographic databases including MEDLINE (PubMed), Embase, Cochrane, and ISI Web of Science will be searched to identify studies reporting the prevalence of obesity, overweight, and underweight in patients with ASD. Retrieved records will be independently screened by 2 authors and relevant estimates will be extracted from studies reporting data on obesity, overweight, and underweight prevalence among individuals with ASD. The assessment of study quality will be conducted primarily using the Newcastle–Ottawa scale and checklist proposed by the Joanna Briggs Institute. Prevalence estimates of obesity and overweight will be separately pooled using random-effects model. The pooled estimates will be summarized and presented by regional groupings. Subgroup analysis will be conducted for variables (such as study setting, participants’ age, and geographical region) across studies, depending on data availability. Between-study heterogeneity will be assessed using the I
2 statistic and explored through subgroup analyses. This systematic review and meta-analysis will be reported following the preferred reporting items for systematic reviews and meta-analyses checklist and the meta-analysis of observational studies in epidemiology statements guidelines for meta-analysis and systematic reviews of observational studies.

Results:

In this study, we will outline details of the aims and methods on the meta-analysis of weight status of individuals with ASD.

Conclusion:

The results of this study will summarize the current data of weight status of individuals with ASD.

Registration:

PROSPERO-National Institute of Health Research (NIHR) Prospective Register of Systematic Reviews (CRD42019130790).
Nurse-Reported Bullying and Documented Adverse Patient Events
Authors: Arnetz Judith E. , Neufcourt Leo , Sudan Sukhesh , Arnetz Bengt B. , Maiti Tapabrata , Viens Frederi
Published: October 2019

Background:

Negative nurse work environments have been associated with nurse bullying and poor nurse health. However, few studies have examined the influence of nurse bullying on actual patient outcomes.

Purpose:

The purpose of the study was to examine the association between nurse-reported bullying and documented nursing-sensitive patient outcomes.

Methods:

Nurses (n = 432) in a large US hospital responded to a survey on workplace bullying. Unit-level data for 5 adverse patient events and nurse staffing were acquired from the National Database of Nursing Quality Indicators. Generalized linear models were used to examine the association between bullying and adverse patient events. A Bayesian regression analysis was used to confirm the findings.

Results:

After controlling for nurse staffing and qualification, nurse-reported bullying was significantly associated with the incidence of central-line-associated bloodstream infections (P < .001).

Conclusions:

Interventions to address bullying, a malleable aspect of the nurse practice environment, may help to reduce adverse patient events.
Advance Care Planning in Home Health
Authors: Bigger Sharon , Haddad Lisa
Published: October 2019

The purpose of this article is to synthesize the evidence on advance care planning (ACP), determine what is applicable to the home health (HH) setting, and find where gaps in knowledge may exist. An integrative review methodology was chosen. Although there is ample literature on the topic of ACP, most research has been conducted in the acute care, outpatient, and general community settings. There is limited literature regarding ACP with patients living with chronic cardiovascular and pulmonary illnesses, who comprise the majority of the HH population. Some literature has been published regarding the interprofessional team’s role in ACP in the HH setting. A gap in knowledge exists regarding ACP in HH, and recommendations for future research are provided.
Online End-of-Life Nursing Education Consortium Core Curriculum for Staff Nurses
Authors: Bishop Caitlin Tabler , Mazanec Polly , Bullington Jessica , Craven Heather , Dunkerley Melissa , Pritchett Jessica , Coyne Patrick J.
Published: October 2019

Because of the growing population of patients with serious illness, the demand for specialty palliative care exceeds the resources available. Nurses must be prepared to provide primary palliative care to fill the gap in the availability of specialized palliative care providers. However, meeting the educational needs of a vast number of practicing nurses poses a significant challenge. Often, institutions are limited in the financial and staffing support that they can contribute for continuing nursing education, especially when the training requires staff to spend substantial time away from work. In order to address this issue, one large medical center conducted a study to examine the educational and clinical practice outcomes of offering an online version of the End-of-Life Nursing Education Consortium Core Curriculum to nearly 100 nurses. The participants were divided into 2 groups. Group 1 received online education only, whereas the other group received the online education plus a 3-hour face-to-face training session. Both groups reported statistically significant improvements in symptom management and communication skills, with no significant difference between the pedagogical approaches. Most importantly, the education resulted in a statistically significant impact on the nurses’ clinical practice. The results of this study demonstrate that online education can be used as an effective and efficient strategy to provide primary palliative care education to a large number of nurses.
Recent Penile Sexual Contact Is Associated With an Increased Odds of High-Risk Cervical Human Papillomavirus Infection in Transgender Men
Authors: Deutsch Madeline B. , Reisner Sari L. , Peitzmeier Sarah , Potter Jennifer , Pardee Dana , Hughto Jaclyn M.W.
Published: October 2019

Background

Transgender men (TM) have a male, masculine, or nonfemale gender identity, yet were assigned female sex at birth on the basis of their external genitalia. The majority of TM are at risk of infection with one of several high-risk strains of the human papillomavirus (hr-HPV), acquired primarily through sexual contact, that cause 99.7% of cervical cancers. This study aimed to explore the association between sexual behaviors and current cervical hr-HPV infection in TM with a cervix.

Methods

The primary aim of this analysis was to test for an association between participant self-report of sexual contact with a penis in the past 1 year and current infection with cervical hr-HPV as measured by provider-collected cervical HPV DNA assay. This is a secondary analysis of a bio-behavioral sexual health study conducted at a health center in Boston, MA from 2015 to 2016. Analysis was conducted using logistic regression with significance level set at P less than 0.05; the primary analysis was adjusted for self-reported age, current tobacco use, years of testosterone use, and HPV vaccination status.

Results

Overall prevalence of hr-HPV was 15.9%. In adjusted analyses, participants reporting receptive penile vaginal sex with any of their most recent 3 sexual partners in the past 12 months had more than 5 times greater odds of current hr-HPV infection than those reporting no penile sex of any kind during this timeframe (odds ratio, 5.23; 95% confidence interval, 1.61–17.02).

Conclusions

Vaginal-receptive penile sex in the last 12 months was associated with a 5-fold increased odds of cervical high-risk HPV infection among TM. Findings can inform future population level study of associations between sexual behaviors and hr-HPV risk, which could lead to more individualized approaches to screening.
Implementation of pharmacist consultations as part of a multidisciplinary consultation program for patients with oral anticancer agent
Authors: Streicher Caroline , Daulange Annick
Published: October 2019

Introduction:

In this study we describe the implementation in a hospital setting of pharmacist consultations, by oncology pharmacists, as part of a multidisciplinary consultation program (MCP) established for patients before they start a new oral anticancer treatment.

Methods:

Pharmacist consultations consisted of 3 steps in the MCP. (1) The first one was the preparation of the medication assessment with the realization of an accurate patient medication list. (2) The second step was the pharmacist consultation with the patient. The oncology pharmacist assessed the ability of the patient to self-manage their therapy at home and gave information about the new drug. To prevent potential drug, herbs, and food interactions, individual medication plans were also performed. (3) Finally, the oncology pharmacist completed and sent the multidisciplinary report to the community pharmacists with a satisfaction survey.

Results:

Ninety patients, enrolled in the MCP, received pharmacist consultations. Oncology pharmacists reported that 24% (n = 22) of the patients were not able to take their medicine by themselves and that information for the home caregiver was needed. The realization of the best possible medication history highlighted drug interactions in 36% (n = 32) of patients and required, for 4 patients, discontinuation of 1 drug of their regular medicines. With the information delivered by oncology pharmacists, 83% of the community pharmacists contacted were able to better advise the patient at the time of the oral anticancer agent dispensing.

Conclusions:

The implementation of the MCP with pharmacist consultations allowed us to better support patients who start new oral anticancer treatment and shows us how crucial the expertise of oncology pharmacists is. They contribute to limit drug-related problems especially by identifying drug, herbs, and food interactions but also by identifying the patients unable to self-manage their therapy at home. The collaboration established with the community pharmacists allowed us to improve patient management by sharing information and knowledge.
Evidence for individual discrimination and numerical assessment in collective antipredator behaviour in wild jackdaws (
Corvus monedula
)
Authors: Coomes Jenny R. , McIvor Guillam E. , Thornton Alex
Published: October 2019

Collective responses to threats occur throughout the animal kingdom but little is known about the cognitive processes underpinning them. Antipredator mobbing is one such response. Approaching a predator may be highly risky, but the individual risk declines and the likelihood of repelling the predator increases in larger mobbing groups. The ability to appraise the number of conspecifics involved in a mobbing event could therefore facilitate strategic decisions about whether to join. Mobs are commonly initiated by recruitment calls, which may provide valuable information to guide decision-making. We tested whether the number of wild jackdaws responding to recruitment calls was influenced by the number of callers. As predicted, playbacks simulating three or five callers tended to recruit more individuals than playbacks of one caller. Recruitment also substantially increased if recruits themselves produced calls. These results suggest that jackdaws use individual vocal discrimination to assess the number of conspecifics involved in initiating mobbing events, and use this information to guide their responses. Our results show support for the use of numerical assessment in antipredator mobbing responses and highlight the need for a greater understanding of the cognitive processes involved in collective behaviour.
Central thalamus modulates consciousness by controlling layer-specific cortical interactions
Authors: Redinbaugh Michelle J. , Phillips Jessica M. , Kambi Niranjan A. , Mohanta Sounak , Andryk Samantha , Dooley Gaven L. , Afrasiabi Mohsen , Raz Aeyal , Saalmann Yuri B.
Published: October 2019

Consciousness is the capacity to experience one’s environment and internal states. The minimal mechanisms sufficient to produce this experience, the neural correlates of consciousness (NCC), are thought to involve thalamocortical and intracortical interactions, but the key operations and circuit paths are unclear. We simultaneously recorded neural activity in central thalamus and across layers of fronto-parietal cortex in awake, sleeping and anesthetized macaques. Spiking activity was selectively reduced in deep cortical layers and thalamus during unconsciousness, as were intracolumnar and interareal interactions at alpha and gamma frequencies. Gamma-frequency stimulation, when focused on the central lateral thalamus of anesthetized macaques, counteracted these neural changes and restored consciousness. These findings suggest that the NCC involve both corticocortical feedforward and feedback pathways coordinated with intracolumnar and thalamocortical loops.

Stimulation of central lateral thalamus counters anesthesia to restore wake cortical dynamics and consciousness.
Apical restriction of the planar cell polarity component VANGL in pancreatic ducts is required to maintain epithelial integrity
Authors: Flasse Lydie , Yennek Siham , Cortijo Cédric , Barandiaran Irene Seijo , Kraus Marine R-C , Grapin-Botton Anne
Published: October 2019

Cell polarity is essential for the architecture and function of numerous epithelial tissues. Here we show how planar cell polarity (PCP), so far studied principally in flat epithelia, is deployed during the morphogenesis of a tubular organ. Using the mammalian pancreas as a model, we report that components of the core PCP pathway such as the transmembrane protein Van Gogh-like (VANGL), are progressively apically-restricted. VANGL expression becomes asymmetrically localized at the apical surface of ductal cells, revealing a planar polarization of the pancreatic duct. We further show that restricting VANGL to these discrete sites of expression is crucial for epithelial integrity. Expansion of expression on basolateral membranes of the progenitors leads to their death and extrusion from the epithelium, as previously observed for perturbations of apico-basal polarity. Using organoids andin vivoanalyses, we show that cell elimination is induced by a decrease of Rock activityviaDishevelled.
Selective Ablation of Cancer Cells with Low Intensity Pulsed Ultrasound
Authors: Mittelstein David R. , Ye Jian , Schibber Erika F. , Roychoudhury Ankita , Martinez Leyre Troyas , Fekrazad M. Houman , Ortiz Michael , Lee Peter P. , Shapiro Mikhail G. , Gharib Morteza
Published: October 2019

Ultrasound can be focused into deep tissues with millimeter precision to perform non-invasive ablative therapy for diseases such as cancer. In most cases, this ablation uses high intensity ultrasound to deposit non-selective thermal or mechanical energy at the ultrasound focus, damaging both healthy bystander tissue and cancer cells. Here we describe an alternative low intensity pulsed ultrasound approach that leverages the distinct mechanical properties of neoplastic cells to achieve inherent cancer selectivity. We show that when applied at a specific frequency and pulse duration, focused ultrasound selectively disrupts a panel of breast, colon, and leukemia cancer cell models in suspension without significantly damaging healthy immune or red blood cells. Mechanistic experiments reveal that the formation of acoustic standing waves and the emergence of cell-seeded cavitation lead to cytoskeletal disruption, expression of apoptotic markers, and cell death. The inherent selectivity of this low intensity pulsed ultrasound approach offers a potentially safer and thus more broadly applicable alternative to non-selective high intensity ultrasound ablation.
Rapid ordering of barcoded transposon insertion libraries of anaerobic bacteria
Authors: Shiver Anthony L. , Culver Rebecca , Deutschbauer Adam M. , Huang Kerwyn Casey
Published: October 2019

Commensal bacteria from the human intestinal microbiota play important roles in health and disease. Research into the mechanisms by which these bacteria exert their effects is hampered by the complexity of the microbiota and by the strict growth requirements of the individual species. The assembly of ordered transposon insertion libraries, in which nearly all nonessential genes have been disrupted and the strains stored as independent monocultures, would be a transformative resource for research into many microbiota members. However, assembly of these libraries must be fast and inexpensive in order to empower investigation of the large number of species that typically compose gut communities. The methods used to generate ordered libraries must also be adapted to the anaerobic growth requirements of most intestinal bacteria. We have developed a protocol to assemble ordered libraries of transposon insertion mutants that is fast, cheap, and effective for even strict anaerobes. The protocol differs from currently available methods by making use of cell sorting to order the library and barcoded transposons to facilitate the localization of ordered mutations in the library. By tracking transposon insertions using barcode sequencing, our approach increases the accuracy and reduces the time and effort required to locate mutants in the library. Ordered libraries can be sorted and characterized over the course of two weeks using this approach. We expect this protocol will lower the barrier to generating comprehensive, ordered mutant libraries for many species in the human microbiota, allowing for new investigations into genotype-phenotype relationships within this important microbial ecosystem.
The role of genomic vs. epigenomic variation in shaping patterns of convergent transcriptomic variation across continents in a young species complex
Authors: Rougeux Clément , Laporte Martin , Gagnaire Pierre-Alexandre , Bernatchez Louis
Published: October 2019

Repeated adaptive divergence in replicates of phenotypic diversification offers a propitious context to identify the molecular bases associated to adaptive divergence. A currently hotly debated topic pertains to the relative role of genomic vs. epigenomic variation in shaping patterns of phenotypic variation at the gene expression level. Here, we combined genomic, epigenomic and transcriptomic information from 64 individuals in order to quantify the relative role of SNPs and DNA methylation variation in the repeated evolution of four limnetic-benthic whitefish species pairs from Europe and North America. We first found evidence for 149 convergent differentially methylated regions (DMRs) between species across continents, which significantly influenced levels of gene expression. Hyper-methylated DMRs in the limnetic species were globally associated to an expression repression relatively to benthic species, and inversely. Furthermore, we identified 108 convergent genetic variants (eQTLs) associated to gene expression differences between species. Gene expression differences were more pronounced in genes harbouring eQTL compared to those associated with DMRs, thus revealing a greater effect of eQTLs on gene expression. Multivariate analyses allowed partitioning the relative contribution of epi-/genomic changes and their association to gene expression variation. Most of the gene expression variation was significantly explained by genomic (4.1%) and putatively genomic-epigenomic interactive variation (46.7%), while “pure” epigenomic variation explained marginally 2.3% of the gene expression variation across continents. This study provides a rare qualitative and quantitative documentation of the relative role of genomic, DNA methylation and their interaction in shaping patterns of convergent gene expression during the process of ecological speciation.
Prefrontal High Gamma in ECoG tags periodicity of musical rhythms in perception and imagination
Authors: Herff S. A. , Herff C. , Milne A. J. , Johnson G. D. , Shih J. J. , Krusienski D. J.
Published: October 2019

Rhythmic auditory stimuli are known to elicit matching activity patterns in neural populations. Furthermore, recent research has established the particular importance of high-gamma brain activity in auditory processing by showing its involvement in auditory phrase segmentation and envelope-tracking. Here, we use electrocorticographic (ECoG) recordings from eight human listeners, to see whether periodicities in high-gamma activity track the periodicities in the envelope of musical rhythms during rhythm perception and imagination. Rhythm imagination was elicited by instructing participants to imagine the rhythm to continue during pauses of several repetitions. To identify electrodes whose periodicities in high-gamma activity track the periodicities in the musical rhythms, we compute the correlation between the autocorrelations (ACC) of both the musical rhythms and the neural signals. A condition in which participants listened to white noise was used to establish a baseline. High-gamma autocorrelations in auditory areas in the superior temporal gyrus and in frontal areas on both hemispheres significantly matched the autocorrelation of the musical rhythms. Overall, numerous significant electrodes are observed on the right hemisphere. Of particular interest is a large cluster of electrodes in the right prefrontal cortex that is active during both rhythm perception and imagination. This indicates conscious processing of the rhythms’ structure as opposed to mere auditory phenomena. The ACC approach clearly highlights that high-gamma activity measured from cortical electrodes tracks both attended and imagined rhythms.
Genetic meta-analysis of obsessive-compulsive disorder and self-report compulsive symptoms
Authors: Smit Dirk J.A. , Cath Danielle , Zilhão Nuno R. , Ip Hill F. , Denys Damiaan , den Braber Anouk , de Geus Eco J.C. , Verweij Karin J.H , Hottenga Jouke-Jan , Boomsma Dorret I.
Published: October 2019

We investigated whether obsessive compulsive (OC) symptoms from a population-based sample could be analyzed to detect genetic variants influencing OCD. We performed a GWAS on the obsession (rumination and impulsions) and compulsion (checking, washing, and ordering/precision) subscales of an abbreviated version of the Padua Inventory (N=8267 with genome-wide genotyping and phenotyping). The compulsion subscale showed a substantial and significant positive genetic correlation with an OCD case-control GWAS (rG=0.61, p=0.017) previously published by the Psychiatric Genomics Consortium (PGC-OCD). The obsession subscale and the total Padua score showed no significant genetic correlations (rG=–0.02 and rG=0.42, respectively). A meta-analysis of the compulsive symptoms GWAS with the PGC-OCD revealed no genome-wide significant SNPs (combined N=17992, indicating that the power is still low for individual SNP effects). A gene-based association analysis, however, yielded two novel genes (WDR7 and ADCK1). The top 250 genes in the gene-based test also showed significant increase in enrichment for psychiatric and brain-expressed genes. S-Predixcan testing showed that for genes expressed in hippocampus, amygdala, and caudate nucleus significance increased in the meta-analysis with compulsive symptoms compared to the original PGC-OCD GWAS. Thus, inclusion of dimensional symptom data in genome-wide association on clinical case-control GWAS of OCD may be useful to find genes for OCD if the data are based on quantitative indices of compulsive behavior. SNP-level power increases were limited, but aggregate, gene-level analyses showed increased enrichment for brain-expressed genes related to psychiatric disorders, and increased association with gene-expression in brain tissues with known emotional, reward processing, memory, and fear-formation functions.
GLP-1(9-36) mediates the glucagonostatic effect of GLP-1 by promiscuous activation of the glucagon receptor
Authors: Guida Claudia , Miranda Caroline , Asterholm Ingrid Wernstedt , Basco Davide , Benrick Anna , Chanclon Belen , Chibalina Margarita V. , Harris Matthew , Kellard Joely , McCulloch Laura J. , Real Joana , Rorsman Nils J.G. , Yeung Ho Yan , Reimann Frank , Shigeto Makoto , Clark Anne , Thorens Bernard , Rorsman Patrik , Ladds Graham , Ramracheya Reshma
Published: October 2019

The incretin hormone glucagon-like peptide 1(7-36) (GLP-1(7-36)) stimulates insulin and inhibits glucagon secretion. The mechanisms by which GLP-1 suppresses glucagon release are unclear as glucagon-secreting α-cells express GLP-1 receptors (GLP-1Rs) at very low levels. Here, we examine the underlying mechanisms. We find that both GLP-1(7-36) and its degradation product GLP-1(9-36) inhibit glucagon secretion at physiological (pM) concentrations. Whereas the effect of GLP-1(7-36) is sensitive to PKA inhibition, GLP-1(9-36) exerts its effect by a PKA-independent mechanism sensitive to pretreatment with pertussis. The glucagonostatic effects of both GLP-1(7-36) and (9-36) are retained in islets fromGlp1rknockout mice but only GLP-1(9-36) remains glucagonostatic in the presence of the DPP-4 (the peptidase catalyzing the formation of GLP-1(9-36)) inhibitor sitagliptin. Glucagon receptor (GCGR) antagonism specifically prevents the inhibitory effects of GLP-1(9-36) whilst not affecting that of GLP-1(7-36). We conclude that GLP-1(7-36) and GLP-1(9-36) regulate glucagon secretion via interaction with GLP-1R and GCGR, respectively.

Highlights

GLP-1(7-36) and GLP-1(9-36) inhibit glucagon secretion from alpha-cells

GLP-1(7-36) and (9-36) retain glucagonostatic effect in Glp1r-/-islets

GLP-1(7-36) and (9-36) activate distinct signal transduction mechanisms

GLP-1(7-36) acts via GLP-1R and GLP-1(9-36) via GCGR
Dynamics of genetic variation in Transcription Factors and its implications for the evolution of regulatory networks in Bacteria
Authors: Ali Farhan , Narain Seshasayee Aswin Sai
Published: October 2019

The evolution of bacterial regulatory networks has largely been explained at macroevolutionary scales through lateral gene transfer and gene duplication. Transcription factors (TF) have been found to be less conserved across species than their target genes (TG). This would be expected if TFs accumulate mutations faster than TGs. This hypothesis is supported by several lab evolution studies which found TFs, especially global regulators, to be frequently mutated. Despite these studies, the contribution of point mutations in TFs to the evolution of regulatory network is poorly understood. We tested if TFs show greater genetic variation than their TGs using whole-genome sequencing data from a large collection of E coli isolates. We found TFs to be less diverse, across natural isolates, due to their regulatory roles. TFs were enriched in mutations in multiple adaptive lab evolution studies but not in mutation accumulation. However, over long-term evolution, relative frequency of mutations in TFs showed a gradual decay after a rapid initial burst. Our results suggest that point mutations, conferring large-scale expression changes, may drive the early stages of adaptation but gene regulation is subjected to stronger purifying selection post adaptation.
Symbolic Information Flow Measurement (SIFM): A Software for Measurement of Information Flow Using Symbolic Analysis
Authors: Nebiu Dhurata , Kamberaj Hiqmet
Published: October 2019

Symbolic Information Flow Measurement software is used to compute the information flow between different components of a dynamical system or different dynamical systems using symbolic transfer entropy. Here, the time series represents the time evolution trajectory of a component of the dynamical system. Different methods are used to perform a symbolic analysis of the time series based on the coarse-graining approach by computing the so-called embedding parameters. Information flow is measured in terms of the so-called average symbolic transfer entropy and local symbolic transfer entropy. Besides, a new measure of mutual information is introduced based on the symbolic analysis, called symbolic mutual information.
Angular momentum regulation may dictate the slip severity in young adults
Authors: Nazifi Mohammad Moein , Beschorner Kurt , Hur Pilwon
Published: October 2019

Falls vastly affect the economy and the society with their high cost, injuries, and mortalities. Slipping is the main trigger for falling. Yet, individuals differ in their ability to recover from slips. Mild slippers can accommodate slips without falling, whereas severe slippers indicate inadequate or slow pre-or post-slip control that make them more prone to fall after a slip. Knowing the discrepancies in different kinematic and kinetic variables in mild and severe slippers helps pinpoint the adverse control responsible for severe slipping and falling. This study examined Center of Mass (COM) height, sagittal angular momentum (H), upper body kinematics, and the duration of single/double phase in mild and severe slippers for both normal walking and slipping to identify their differences and possible relationships. Possible causality of such relationships were also studied by observing the time-lead of the deviations. Twenty healthy young adults walked in a long walkway for several trials and were slipped unexpectedly. They were classified into mild and severe slippers based on their slip severity. No inter-group differences were observed in the upper extremity kinematics. It was found that mild and severe slippers do not differ in the studied variables during normal gait; however, they do show significant differences through slipping. Compared to mild slippers, sever slippers lowered their COM height following a slip, presented higherH, and shortened their single support phase (p-value<0.05 for all). Based on the time-lead observed inHover all other variables suggests that angular momentum may be the key variable in controlling slips.
Mutational load and the functional fraction of the human genome
Authors: Galeota-Sprung Benjamin , Sniegowski Paul , Ewens Warren
Published: October 2019

The fraction of the human genome that is functional is a question of both evolutionary and practical importance. Studies of sequence divergence have suggested that the functional fraction of the human genome is likely to be no more than ∼15%. In contrast, the ENCODE project, a systematic effort to map regions of transcription, transcription factor association, chromatin structure, and histone modification, assigned function to 80% of the human genome. In this paper we examine whether and how an analysis based on mutational load might set a limit on the functional fraction. In order to do so, we characterize the distribution of fitness of a large, finite, diploid population at mutation-selection equilibrium. In particular, if mean fitness is ∼1, the fitness of the fittest individual likely to occur cannot be unreasonably high. We find that at equilibrium, the distribution of log fitness has variance nus, where u is the per-base deleterious mutation rate, n is the number of functional sites (and hence incorporates the functional fraction f), and s is the selection coefficient of deleterious mutations. In a large (N = 109) reproducing population, the fitness of the fittest individual likely to exist is . These results apply to both additive and recessive fitness schemes. Our approach is different from previous work that compared mean fitness at mutation-selection equilibrium to the fitness of an individual who has no deleterious mutations; we show that such an individual is exceedingly unlikely to exist. We find that the functional fraction is not very likely to be limited substantially by mutational load, and that any such limit, if it exists, depends strongly on the selection coefficients of new deleterious mutations.
Comparative single-cell transcriptomics of complete insect nervous systems
Authors: Cocanougher Benjamin T. , Wittenbach Jason D. , Long Xi Salina , Kohn Andrea B. , Norekian Tigran P. , Yan Jinyao , Colonell Jennifer , Masson Jean-Baptiste , Truman James W. , Cardona Albert , Turaga Srinivas C. , Singer Robert H. , Moroz Leonid L. , Zlatic Marta
Published: October 2019

Molecular profiles of neurons influence information processing, but bridging the gap between genes, circuits, and behavior has been very difficult. Furthermore, the behavioral state of an animal continuously changes across development and as a result of sensory experience. How behavioral state influences molecular cell state is poorly understood. Here we present a complete atlas of theDrosophilalarval central nervous system composed of over 200,000 single cells across four developmental stages. We developpolyseq, a python package, to perform cell-type analyses. We use single-molecule RNA-FISH to validate our scRNAseq findings. To investigate how internal state affects cell state, we optogentically altered internal state with high-throughput behavior protocols designed to mimic wasp sting and over activation of the memory system. We found nervous system-wide and neuron-specific gene expression changes. This resource is valuable for developmental biology and neuroscience, and it advances our understanding of how genes, neurons, and circuits generate behavior.