bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroanesthesiology Update
Authors: Pasternak Jeffrey J.
Published: January 2020

This review is intended to provide a summary of the literature pertaining to the perioperative care of neurosurgical patients and patients with neurological diseases. General topics addressed in this review include general neurosurgical considerations, stroke, neurological monitoring, and perioperative disorders of cognitive function.
HAIR DYE-INDUCED RETINOPATHY MIMICKING MEK-INHIBITOR RETINOPATHY
Authors: Faure Céline , Salamé Nabil , Cahuzac Armelle , Mauget-Faÿsse Martine , Scemama Claire
Published: January 2020

Purpose:

To report a new toxic retinopathy related to the use of hair dye.

Methods:

Case reports of three patients with follow-up after exposure and until resolution.

Results:

There were three middle-aged women (32–66 year old) all of whom had bilateral moderate to severe vision loss and normal slit-lamp examination at presentation. Fundus examination showed bilateral multiple serous retinal detachments predominantly located in the posterior pole, with some pigment epithelial hypertrophy in chronic cases. Optical coherence tomography showed similar features as in MEK-inhibitor retinopathy. Electrooculogram performed in one patient showed abnormal Arden ratio. During follow-up, visual acuity improved with regression of the serous retinal detachments. The speed of resolution was proportional to the acuteness of the exposure to aromatic amines.

Conclusion:

Hair dyes containing aromatic amines can be responsible for bilateral toxic retinopathy mimicking MEK-inhibitor retinopathy.
Blastic plasmacytoid dendritic cell neoplasm: diagnosis, manifestations, and treatment
Authors: Sweet Kendra
Published: January 2020

Purpose of review

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with historically poor outcomes. It typically manifests as asymptomatic skin lesions and cytopenias, which result from bone marrow involvement. Less commonly, it will present in lymph nodes or visceral organs as well. Although rare, BPDCN has been discussed more frequently in recent years as new drugs have been developed that could be effective at treating this disease.

Recent findings

Until recently, treatment for BPDCN commonly included intensive chemotherapy regimens, which are generally reserved for management of acute myeloid leukemia or acute lymphoblastic leukemia. However, in 2018 tagraxofusp (SL-401) was approved as the only treatment specifically indicated for BPDCN. Additional clinical trials are ongoing evaluating the efficacy of newer agents, which could potentially further improve the long-term outcomes for patients with BPDCN.

This manuscript reviews the diagnosis, manifestations and treatment of BPDCN.
The role of micro-RNAs in management of germ cell tumors: future directions
Authors: Nappi Lucia , Kollmannsberger Christian , Nichols Craig
Published: January 2020

Purpose of review

miRNAs 371 and 302/367 clusters are abundantly secreted in the blood of patients with active germ cell malignancy (aGCM), both seminoma and nonseminoma. The serum concentration of those micro-RNAs correlates with tumor burden and to the activity of specific treatments; therefore, representing attractive biomarkers for the diagnosis and follow-up of patients with germ cell tumors. This review summarizes the most relevant evidence supporting their clinical validity in germ cell tumors.

Recent findings

Several retrospective studies have reported high sensitivity and specificity of those micro-RNAs in identifying aGCM prior to the orchiectomy or in patients with metastatic germ cell tumor prior to or during chemotherapy. Most recently, few prospective studies have confirmed their clinical validity during the follow-up of patients after surgery and/or chemotherapy. Large studies are panned across the spectrum of germ cell tumors to assess their clinical utility and several efforts to identify biomarkers of teratoma are underway.

The integration of those micro-RNAs in the management of germ cell tumors has the potential to refine the therapeutic decision, especially in some clinical situations characterized by high uncertainty, such as clinical stage I, clinical stage IIA with normal tumor markers and residual disease postchemotherapy.
Human papillomavirus vaccination and prevention of intraepithelial neoplasia and penile cancer: review article
Authors: da Costa Nunes João F. , Pires Sanarelly , Chade Daher C.
Published: January 2020

Purpose of review

The objective of the current article is to promote a literature revision of the relationship between the prevention of intraepithelial neoplasms (PeIN) and invasive penile cancer, and human papillomavirus (HPV) vaccination, aiming to enumerate the pros and cons of immunization.

Recent findings

The immunization against the HPV is sufficiently safe and many countries have incorporated the vaccine to their immunization calendar. Compared with men, the sampling size and the evidence quality of scientific researches among the female population are more robust. Some randomized and nonrandomized studies suggest that vaccination reduces the incidence of genital warts and no PeIN and penile cancer cases were developed in the vaccinal group. However, 70% of patients can evolve with the neoplasia despite having been immunized and even among HPV infected patients, only 1% will develop cancer.

The studies about vaccination against HPV and prevention on penile cancer are conflicting and the main academic urology societies still have not incorporated vaccination of men in their guidelines. Future studies are necessary to confirm the efficiency and cost–benefit of the vaccine in men to prevent intraepithelial neoplasms and invasive penile cancer.
Effects of Bovine Lactoferrin on Rat Intestinal Epithelial Cells
Authors: Kong Xiangyong , Yang Mei , Guo Jing , Feng Zhichun
Published: January 2020

Objective:

To determine the effects of bovine lactoferrin (bLF) on cell viability, proliferation, and the protective roles in intestinal epithelial cells‐6 (IEC‐6) treated by lipopolysaccharide (LPS).

Methods:

Cell viability and proliferation of IEC‐6 were detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and Brdu assay separately. Cell cycle distribution was analyzed by flow cytometry. Inflammatory cytokines were analysed by real‐time PCR and ELISA. Western blot was utilized to measure the level of MAPK and NF‐κβ nuclear translocation.

Results:

Dose‐dependent effects of bLF on cell viability and proliferation were observed in IEC‐6 cells (both P < 0.05), especially at a dose of 100 μg/ml. The percentage of cells in the G2 and S phase was significantly higher than those of the control group (8.17 ± 0.49% vs 4.72 ± 0.55%, P < 0.01 and 12.75 ± 0.33% vs 9.48 ± 0.33%, P < 0.01, respectively). The mRNA level of IL‐1β, IL‐6 and TNF‐α was decreased by co‐stimulation of bLF and LPS compared with the LPS treatments alone in IEC‐6 cells (all P < 0.001). The secretion of IL‐6 and TNF‐α were also decreased by co‐stimulation of bLF and LPS (both P < 0.01). Bovine lactoferrin treatment at dose of 100 μg/ml could inhibit the activation of MAPK/NF‐κβ signal pathway induced by LPS (both P < 0.001).

Conclusions:

Bovine lactoferrin could promote the cell viability and proliferation, and have anti‐inflammatory effects via inhibition of the activation of MAPK and NF‐κβ nuclear translocation. Supplementation of formula with bLF may be beneficial in preventing NEC in preterm infants.
Meropenem to Children With Febrile Neutropenia Induces Monoresistant Pseudomonas aeruginosa
Authors: Mønster Mette B. , Vissing Nadja H. , Schrøder Henrik , Grosen Dorthe , Rosthøj Steen , Frimodt-Møller Niels , Wang Mikala , Schønheyder Henrik C. , Schmiegelow Kjeld , Justesen Ulrik S. , Nygaard Ulrikka
Published: January 2020

Antimicrobial resistance in Pseudomonas aeruginosa is a threat to children with cancer. We explored the association between P. aeruginosa resistance and previous antibiotic exposure. All children with cancer and P. aeruginosa bacteremia in 2007 to 2016 in Denmark, a country with an overall resistance rate of ∼3%, were included. Twenty percent (10/49) of isolates from children previously exposed to meropenem were meropenem nonsusceptible. The only significant risk factor of meropenem nonsusceptibility was previous meropenem therapy (P=0.03). On the basis of these results, we suggest that meropenem should be reserved as a last resort for children with febrile neutropenia in countries with low antimicrobial resistance.
Multimodal Analgesic Plan for Children Undergoing Chimeric 14.18 Immunotherapy
Authors: Bertolizio Gianluca , Otis Annik , Tam Karen , Aswar Swapnil , Garbin Marta , Ingelmo Pablo
Published: January 2020

Immunotherapy with the chimeric 14.18 anti-GD2 antibody (ch14.18) is associated with severe neuropathic pain. Different analgesic modalities have been employed, but pain management remains challenging and side effects such as desaturation, bradycardia, and hypotension have been reported. We retrospectively analyzed the efficacy of a multimodal regimen based on gabapentin, ketamine, and morphine in controlling pain during ch14.18 chemotherapy. In our cohort, the pain was low, desaturation and hypotension were infrequent, and no episode of bradycardia was reported. Morphine consumption was similar to other studies. Our results suggest that this regimen may be a valid analgesic option in children undergoing ch14.18 infusion.
Educating Ambulatory Care Nurses to Address Substance Use
Authors: Gonzalez Yovan , Kozachik Sharon L. , Finnell Deborah S.
Published: January 2020

Background:

Screening, brief intervention, and referral to treatment (SBIRT) for substance use has an impact on morbidity and mortality and health care cost.

Local Problem:

Nurses in ambulatory care settings may lack knowledge about evidence-based substance use SBIRT.

Methods:

A comparison of pre- and postintervention data was performed to determine whether knowledge improved and to identify facilitators and barriers to SBIRT implementation.

Interventions:

Nurses completed an online self-paced program focusing on alcohol and drug use screening, motivational interviewing used in a brief intervention, and referral to specialty treatment.

Results:

Postintervention knowledge scores increased (P < .001). Facilitator and barrier themes included time, education, resources, receptivity, and interprofessional collaboration.

Conclusions:

The implementation of the SBIRT online program was feasible for nurses to complete during work hours and resulted in increased SBIRT-related knowledge.
NKX3-1 Is a Useful Immunohistochemical Marker of EWSR1-NFATC2 Sarcoma and Mesenchymal Chondrosarcoma
Authors: Yoshida Ken-ichi , Machado Isidro , Motoi Toru , Parafioriti Antonina , Lacambra Maribel , Ichikawa Hitoshi , Kawai Akira , Antonescu Cristina R. , Yoshida Akihiko
Published: January 2020

NK3 homeobox 1 (NKX3-1) is widely accepted as a highly sensitive and specific marker for prostatic adenocarcinoma. Prompted by published transcriptome data showing upregulation of NKX3-1 mRNA expression in EWSR1-NFATC2 sarcoma, we explored the utility of NKX3-1 immunohistochemistry in sarcoma diagnosis. We applied NKX3-1 immunohistochemistry to 11 EWSR1-NFATC2 sarcomas and 168 mimics using whole tissue sections. All EWSR1-NFATC2 sarcomas consisted of uniform small round or ovoid cells, all except 1 showing at least focally the typical growth pattern of nests, cords, or trabeculae within a fibrous/myxoid background. A variable eosinophilic infiltrate was common. NKX3-1 was expressed in 9 of 11 (82%) EWSR1-NFATC2 sarcomas, often diffuse and of moderate or strong intensity. All 12 mesenchymal chondrosarcomas tested were also positive for NKX3-1, with over half showing diffuse staining and moderate or strong intensity. The positive staining was seen only in the primitive small round cell component, whereas the cartilaginous component was mostly negative. Although 1 of 30 osteosarcomas showed focal NKX3-1 positivity, all the remaining 155 cases tested, including 20 Ewing sarcomas, 20 myoepithelial tumors, 11 ossifying fibromyxoid tumors, and 1 FUS-NFATC2 sarcoma were negative for NKX3-1. Our study provides the first evidence that EWSR1-NFATC2 sarcoma and Ewing sarcoma could be distinguished immunohistochemically, adding to the accumulating data that these tumors are phenotypically distinct. We suggest that NKX3-1 may have a diagnostic utility in the evaluation of sarcoma and we also call attention to potential pitfalls in the use of this well-known marker of prostatic adenocarcinoma.
Evaluation of Cognitive Function in Relation to Progression of Parkinson Disease
Authors: Yamawaki Rie , Nankaku Manabu , Kusano Yusuke , Tajima Ayumi , Ikeguchi Ryosuke , Matsuda Shuichi
Published: January 2020

Objective

Cognitive impairments are among the nonmotor symptoms in patients with Parkinson disease. Understanding the cognitive impairments in patients with Parkinson disease may be critical for developing effective rehabilitation interventions. The aims of this study were to assess cognitive function in patients with Parkinson disease using the Wechsler Adult Intelligence Scale Third Edition, and the Wechsler Memory Scale Revised and to investigate how cognitive impairments relate to progression of disease in patients with Parkinson disease according to the Hoehn and Yahr stages.

Design

Seventy-eight patients with Parkinson disease participated in the present study. Our study consisted of patients in the following Hoehn and Yahr groups: 1 (no disability, n = 11), 2 (mild, n = 34), 3 (moderate, n = 26), and 4 and 5 (severe, n = 7). Cognitive function was assessed using the Wechsler Adult Intelligence Scale Third Edition, and the Wechsler Memory Scale Revised.

Results

The verbal memory was significantly higher in group 1 (106.4 ± 12.0) than in the other groups (2: 90.5 ± 14.0, 3: 89.9 ± 16.9, 4 and 5: 89.6 ± 11.4). Visual memory and delayed recall were similar to the results seen with verbal memory; however, the differences between groups were not statistically significant. The full-scale IQ was not significantly different (1: 107.3 ± 8.1, 2: 96.9 ± 18.2, 3: 96.7 ± 14.8, 4 and 5: 91.7 ± 9.5).

Conclusions

These results suggest that a comprehensive assessment focused on memory impairments is important for applying the appropriate interventions in patients with early-stage Parkinson disease.
Local Recurrence After Transanal Total Mesorectal Excision for Rectal Cancer
Authors: Roodbeen Sapho Xenia , Spinelli Antonino , Bemelman Willem A. , Di Candido Francesca , Cardepont Maylis , Denost Quentin , D’Hoore Andre , Houben Bert , Knol Joep J. , Martín-Pérez Beatriz , Rullier Eric , Sands Dana , Setton Ilana , Van de Steen Katrien , Tanis Pieter J. , Wexner Steven D. , Hompes Roel , Wolthuis Albert M.
Published: January 2020

Objective:

This study aimed to determine local recurrence (LR) rate and pattern after transanal total mesorectal excision (TaTME) for rectal cancer.

Background:

TaTME for mid- and low rectal cancer has known a rapid and worldwide adoption. Recently, concerns have been raised on the oncological safety in light of reported high LR rates with a multifocal pattern.

Methods:

This was a multicenter observational cohort study in 6 tertiary referral centers. All consecutive TaTME cases for primary rectal adenocarcinoma from the first TaTME case in every center until December 2018 were included for analysis. Patients with benign tumors, malignancies other than adenocarcinoma and recurrent rectal cancer, as well as exenterative procedures, were excluded. The primary endpoint was 2-year LR rate. Secondary endpoints included patterns and treatment of LR and histopathological characteristics of the primary surgery.

Results:

A total of 767 patients were identified and eligible for analysis. Resection margins were involved in 8% and optimal pathological outcome (clear margins, (nearly) complete specimen, no perforation) was achieved in 86% of patients. After a median follow-up of 25.5 months, 24 patients developed LR, with an actuarial cumulative 2-year LR rate of 3% (95% CI 2–5). In none of the patients, a multifocal pattern of LR was observed. Thirteen patients had isolated LR (without systemic disease) and 10/13 could be managed by salvage surgery of whom 8 were disease-free at the end of follow-up.

Conclusions and Relevance:

This study shows good loco regional control after TaTME in selected cases from tertiary referral centers and does not indicate an inherent oncological risk of the surgical technique.
Improving health care worker’s compliance with traceability by recording the nursing process at the point of care using a personal digital assistant with a barcode
Authors: Florea Olga , Dufour Jean Charles , Magnin Chloe , Brouqui Philippe , Boudjema Sophia
Published: January 2020

Background

Adverse events are serious and frequent complications most often linked to the quality of nursing care.

Purpose

We evaluated the compliance to traceability of nursing care at bedside using the Patient Smart Reader®, a personal digital assistant with a barcode.

Methods

We compared paper record forms, specific computer software in the hospital information system and the Patient Smart Reader®.

Results

The Patient Smart Reader enhanced the recording of 90% of nursing care surveyed. Regarding the insertion of blood catheters, compliance rates increased from 44.19 % to 100%, and blood catheter monitoring has risen from 29.64% to 80.74%. Urinary catheter monitoring and insertion recording increased from 10.23% to 55.43% and from 16.67% to 100 % respectively.

Conclusions

Providing to caregivers a nursing record system using barcoded implements at the point of care in real time significantly improved traceability of the nursing care.
Prognostic and predictive factors for primary chemotherapy in locally advanced breast cancer
Authors: Borges Clara , Almeida Daniela , Damasceno Margarida
Published: January 2020

Background

Complete pathologic response (pCR) to neoadjuvant chemotherapy in breast cancer is associated to a better locoregional disease control and better long-term prognosis. Our purpose is to identify clinical and pathologic characteristics that influence treatment response, relapse risk and overall survival.

Methods

We analyzed 341 women with breast cancer submitted to primary chemotherapy between 2004 and 2017. We compared clinical response, pathologic response and conservative surgery rate, among different tumor and patient features. We assessed survival and relapse rate, according to complete pathologic response and histologic characteristics.

Results

Among 341 women who underwent neoadjuvant treatment, 34% obtained pCR and 94,4% expressed a pathologic response.

Patients who achived pCR had better overall survival (HR 0,68, CI95% 0,53-0,87, p=0.002) and better progression free survival (HR 0,78, CI95%, 0,61-1,00, p=0,05). pCR was significantly influenced by histologic grade (0% G1, 18,9% G2 vs 41,5% G3, p-value <0,001), HER2 over-expression (56% vs 22,8%, p-value<0,001), cytokeratin 19 expression (38,6% vs 30,8%, p-value 0,047) and cytokeratin 5 (44% vs 32,4%, p-value 0,002).

Instead, presence of bilateral breast cancer (34,7% vs 0%, p-value 0,007) and hormone receptor expression (20,2% vs 54,3%, p-value <0,001) negatively influenced pCR.

Additionally, overall survival was negatively influenced by cytokeratin 19 expression (HR 0,14, CI95% 0,10-0,20, p<0,001) and presence of inflammatory breast cancer (HR 0,26, CI95% 0,11-0,64, p=0.003).

Conclusions

Cytokeratin 19 expression, cytokeratin 5 expression, histologic grade, molecular subtypes and bilaterality are independent predictors for pCR to primary chemotherapy.

pCR influences positively overall survival and progression free survival. However, inflammatory carcinoma and cytokeratin 19 expression are independent predictors for a worse prognosis.
Evolutionary causes of lifespan extension by dietary restriction: linking theory and mechanisms
Authors: Travers Laura M. , Carlsson Hanne , Duxbury Elizabeth M. L. , Maklakov Alexei A.
Published: January 2020

Dietary restriction (DR), reduced food intake without malnutrition, increases lifespan across a broad range of taxa, but the evolutionary underpinning of this phenomenon is poorly understood. The resource reallocation hypothesis proposes that dietary restricted animals divert resources from reproduction to somatic maintenance to increase survival in times of nutrient scarcity in favour of future reproduction. The “longevity by-product” hypothesis proposes instead that dietary restricted animals increase nutrient recycling via autophagy to maximise immediate reproduction, thereby reducing cellular toxic waste and leading to longer lifespan as an unselected by-product. The “longevity by-product” hypothesis makes a unique prediction that blocking autophagy in DR animals will simultaneously reduce lifespan and reproduction. To test the adaptive value of autophagy under dietary restriction, we inhibited autophagy usingbec-1RNAi knockdown in DR and fully-fedCaenorhabditis elegansnematodes. Our findings confirm that autophagic inhibition results in a significantly shorter lifespan under DR, suggesting that autophagy is important for survival in times of famine. Remarkably, we also show that inhibiting autophagy throughout adult life significantly increases reproduction in both dietary restricted and fully fed worms. Moreover, this did not come at a transgenerational cost to offspring fitness. Our results suggest that autophagy is an energetically costly process that reduces resources available for reproduction, but is necessary for survival during famine, and are thus consistent with the resource reallocation hypothesis.
Salamander retinal ganglion cell responses to rich stimuli
Authors: Sadeghi Kolia , Berry Michael J.
Published: January 2020

The retina’s phenomenological function is often considered to be well-understood: individual retinal ganglion cells are sensitive to a projection of the light stimulus movie onto a classical center-surround linear filter. Recent models elaborating on this basic framework by adding a second linear filter or spike histories, have been quite successful at predicting ganglion cell spikes for spatially uniform random stimuli, and for random stimuli varying spatially with low resolution. Fitting models for stimuli with more finely grained spatial variations becomes difficult because of the very high dimensionality of such stimuli. We present a method of reducing the dimensionality of a fine one dimensional random stimulus by using wavelets, allowing for several clean predictive linear filters to be found for each cell. For salamander retinal ganglion cells, we find in addition to the spike triggered average, 3 identifiable types of linear filters which modulate the firing of most cells. While some cells can be modeled fairly accurately, many cells are poorly captured, even with as many as 4 filters. The new linear filters we find shed some light on the nonlinearities in the retina’s integration of temporal and fine spatial information.
Rituximab in the treatment of multiple sclerosis in the Hospital District of Southwest Finland
Authors: Airas Laura , Nylund Marjo , Mannonen Iina , Matilainen Markus , Sucksdorff Marcus , Rissanen Eero
Published: January 2020

Background

There are already numerous B-cell depleting monoclonal anti-CD20 antibodies which have been used to reduce the inflammatory burden associated with multiple sclerosis (MS). We describe here our experience of treating MS-patients with B-cell depleting rituximab.

Patients and methods

All MS-patients (n=72) who had received rituximab treatment for at least six months by January 2019 were identified from the patient charts at the Turku University Hospital. Information about MS disease subtype, disease severity, MR-imaging outcomes and B-cell counts were collected from the charts.

Results

Rituximab was well received and well tolerated by the patients. There were no serious infusion-related side effects. The most serious adverse event that led to treatment discontinuation was neutropenia. Our study confirms the usability of rituximab treatment for MS in the Finnish health care environment.

Conclusions

Off-label rituximab-treatment can be successfully used to reduce MS disease burden for the benefit of MS patients.
Association between temperature and back pain among lumbar disc herniation patients
Authors: Chen Cai , Wang Dandan , Liu Fanjie , Qin Hao , Li Xiyuan , Bu Fan , Li Wei , Shi Bin , Cao Shengnan , An Jianpeng , Meng Xiangwei , Ma Zhixiang , Dong Leilei , Zhang Qinghao , Wang Tao
Published: January 2020

Purpose

This paper was designed to critically provide empirical evidence for the relationship between temperature and intensity of back pain among people with lumbar disc herniation (LDH).

Methods

Distributed lag linear and non-linear models (DLNM) was used to evaluate the relationship between lag-response and exposure to ambient temperature. Stratification was based on age and gender.

Results

When daily average temperature was on the rage of 15-23□, the risk of hospitalization was at the lowest level for men group. About below 10□, risk for male hospitalization could keep increase when lag day were during lag0-lag5 and lag20-lag28. 40<age≤50 group was little affected when they exposed to ambient temperature.
Higher polygenic risk scores for schizophrenia may be suggestive of treatment non-response in major depressive disorder
Authors: Fanelli Giuseppe , Benedetti Francesco , Kasper Siegfried , Kautzky Alexander , Zohar Joseph , Souery Daniel , Montgomery Stuart , Albani Diego , Ferentinos Panagiotis , Rujescu Dan , Mendlewicz Julien , Serretti Alessandro , Fabbri Chiara
Published: January 2020

Background

Up to 60% of patients with major depressive disorder (MDD) do not respond to the first treatment with antidepressants. Response to antidepressants is a polygenic trait, although its underpinning genetics has not been fully clarified. This study aimed to investigate if Polygenic Risk Scores (PRSs) for major psychiatric disorders and neuroticism were associated with non-response or resistance to antidepressants in MDD.

Methods

PRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) were computed in 1148 MDD patients recruited by the European Group for the Study of Resistant Depression. Summary statistics from largest meta-analyses of genome-wide association studies were used as base data. Patients were classified as responders, non-responders to one treatment, non-responders to two or more treatments (treatment-resistant depression or TRD). Regression analyses were adjusted for population stratification and recruitment sites.

Results

PRSs did not predict either non-response or TRD after Bonferroni correction. However, SCZ-PRS was nominally associated with non-response (p=0.003). Patients in the highest SCZ-PRS quintile were more likely to be non-responders than those in the lowest quintile (OR=2.23, 95% CI=1.21-4.10, p=0.02). Patients in the lowest SCZ-PRS quintile showed higher response rates when they did not receive augmentation with second-generation antipsychotics (SGAs), while those in the highest SCZ-PRS quintile had a poor response independently from the treatment strategy (p=0.009).

Conclusions

A higher genetic liability to SCZ may reduce responsiveness to pharmacological treatment in MDD. From a clinical point of view, our results suggest that MDD patients with low SCZ-PRS do not benefit from augmentation with SGAs.
Validity of intraoperative imageless navigation (Naviswiss™) for component positioning accuracy in primary total hip arthroplasty: Protocol for a prospective observational cohort study in a single-surgeon practice
Authors: Ektas Nalan , Scholes Corey , Ruiz Alejandro M , Ireland John
Published: January 2020

Introduction

Optimal outcomes in total hip arthroplasty are dependent on appropriate placement of femoral and acetabular components, with technological advances providing a platform for guiding component placement to reduce the risk of malpositioned components during surgery. This study will validate the intraoperative data captured using a handheld imageless THA navigation system against postoperative measurements of acetabular inclination, anteversion, leg length, and femoral offset on CT radiographs.

Methods and analysis

This is a prospective observational cohort study conducted within a single-centre, single-surgeon private practice. Data will be collected for 35 consecutive patients (>18years) undergoing elective THA surgery, from the research registry established at the surgeon’s practice. The primary outcome is the agreement between intraoperative component positioning data captured by the navigation system compared to postoperative measurements using computed tomography (CT). A total of ten CT scans will be re-assessed for inter- and intra-observer reliability. The influence of patient and surgical factors on the accuracy of component position will also be examined with multivariable linear regression.

Ethics and dissemination

Ethics approval for this study was provided through a certified ethics committee (Bellberry HREC approval number 2017-07-499). The results of this study will be disseminated through peer-reviewed journals and conference presentations.

Strengths and limitations of this study

This study will assess the accuracy of an imageless THA navigation system for measurement of component positioning against postoperative computed tomography analysis as gold standard.

A sample size of n=35 participants will ensure adequate power to detect differences between intraoperative navigation results and postoperative CT measurements.

A sample size of n=10 will provide adequate confidence to establish intra and inter-observer reliability of postoperative measurements of component positioning via CT analysis.

This study will enable a mechanism to detect potential discrepancies between the component positioning measurement methods intrinsic to the Naviswiss™ device and postoperative CT analysis method and identify any corrective factors required for direct comparison of the two methods.
Association between inflammatory bowel disease and prostate cancer: A large-scale, prospective, population-based study
Authors: Meyers Travis J. , Weiner Adam B. , Graff Rebecca E. , Desai Anuj S. , Cooley Lauren Folgosa , Catalona William J. , Hanauer Stephen B. , Wu Jennifer D. , Schaeffer Edward M. , Abdulkadir Sarki A. , Kundu Shilajit D. , Witte John S.
Published: January 2020

Background

Inflammatory bowel disease (IBD) is an established risk factor for colorectal cancer. Recent reports suggesting IBD is also a risk factor for prostate cancer (PC) require further investigation.

Objective

To test the association between IBD with incident PC.

Design, setting, and participants

We studied 218,084 men in the population-based UK Biobank cohort, aged 40-69 at study entry between 2006 and 2010, with follow-up through mid-2015.

Outcome measurements and statistical analysis

We assessed the association between IBD and subsequent PC using multivariable Cox regression analyses, adjusting for age at assessment, ethnic group, UK region, smoking status, alcohol drinking frequency, body mass index, Townsend Deprivation Index, family history of prostate cancer, and previous prostate-specific antigen testing.

Results and limitations

Mean age at study entry was 56 years, 94% of the men were white, and 1.1% (n=2,311) had a diagnosis of IBD. After a median follow-up of 78 months, men with IBD had an increased risk of PC (adjusted hazards ratio [aHR] = 1.31, 95% Confidence interval [CI] = 1.03-1.67, p = 0.029). Separately analyzing the IBD subtypes of ulcerative colitis (UC) and Crohn’s disease (CD), the association with PC was only among men with the former (UC; aHR = 1.47, 95% CI = 1.11-1.95, p=0.0070), and not the latter (CD; aHR 1.06, 95% CI = 0.63-1.80, p = 0.82). Results are limited by lack of data on frequency of health care interactions.

Conclusions

In a large-scale, prospective cohort study, we detected an association between IBD, and UC specifically, with incident PC diagnosis.

Patient summary

This study of over 200,000 men in the UK suggests that men with inflammatory bowel disease may be at a higher risk of prostate cancer than the general population.
Personalised prediction of daily eczema severity scores using a mechanistic machine learning model
Authors: Hurault Guillem , Domínguez-Hüttinger Elisa , Langan Sinéad M. , Williams Hywel C. , Tanaka Reiko J.
Published: January 2020

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease with periods of flares and remission. Designing personalised treatment strategies for AD is challenging, given the apparent unpredictability and large variation in AD symptoms and treatment responses within and across individuals. Better prediction of AD severity over time for individual patients could help to select optimum timing and type of treatment for improving disease control.

Objective

We aimed to develop a mechanistic machine learning model that predicts the patient-specific evolution of AD severity scores on a daily basis.

Methods

We designed a probabilistic predictive model and trained it using Bayesian inference with the longitudinal data from two published clinical studies. The data consisted of daily recordings of AD severity scores and treatments used by 59 and 334 AD children over 6 months and 16 weeks, respectively. Internal and external validation of the predictive model was conducted in a forward-chaining setting.

Results

Our model was able to predict future severity scores at the individual level and improved chance-level forecast by 60%. Heterogeneous patterns in severity trajectories were captured with patient-specific parameters such as the short-term persistence of AD severity and responsiveness to topical steroids, calcineurin inhibitors and step-up treatment.

Conclusion

Our proof of principle model successfully predicted the daily evolution of AD severity scores at an individual level, and could inform the design of personalised treatment strategies that can be tested in future studies.
E-Cigarette Use and Subclinical Cardiac Effects
Authors: Rader Florian , Rashid Mohamad A. , Nguyen Trevor Trung , Luong Eric , Kim Andy , Kim Elizabeth H. , Elashhoff Robert , Davoren Katherine , Moy Norma B. , Nafeh Fida , Bairey Merz C. Noel , Ebinger Joseph E. , Hamburg Naomi M. , Lindner Jonathan R. , Cheng Susan
Published: January 2020

BACKGROUND

Electronic (e-) cigarettes are marketed as a safer alternative to conventional tobacco cigarettes. Although e-cigarettes contain a lower level of nicotine, the delivery method involves delivering an aerosolized bolus of poorly-characterized ultrafine particles that have unknown cardiovascular effects.

METHODS

We studied apparently adult volunteers, free of any chronic disease, including: non-smoking controls, chronic e-cigarette users, and chronic tobacco cigarette smokers. After overnight abstinence, we used myocardial contrast echocardiography to measure acute increases in myocardial blood flow (MBF)induced by ischemic rhythmic handgrip stress, which causes sympathetically-mediated increases in myocardial work and oxygen demand and, in turn, shear stress, nitric oxide production, and coronary endothelial-dependent vasodilation.

RESULTS

In non-smoking controls, handgrip stress increased myocardial blood flow, reflecting normal endothelial function. Chronic tobacco cigarette smokers demonstrated stress-induced blunting in myocardial blood flow change, when compared to non-smoking controls. Chronic e-cigarette smokers demonstrated a decrease, rather than increase, in myocardial blood flow change.

CONCLUSION

Chronic e-cigarette users demonstrated substantially impaired coronary microvascular endothelial function, even more pronounced than that seen in chronic tobacco cigarette users. These findings suggest that chronic e-cigarette use leads to measurable and persistent adverse vascular effects that are not directly related to nicotine.
Ethical Considerations When Creating Evidence from Real World Digital Health Data
Authors: Nebeker C. , Leavy Victoria , Roitmann Eva , Steinhubl Steven
Published: January 2020

Background

Personal health data (PHD) are collected using digital self-tracking technologies and present opportunities to increase self-knowledge and, also biometric surveillance. PHD become “big” data and are used in health-related research studies. We surveyed consumers regarding expectations regarding consent and sharing of PHD for biomedical research.

Methods

Data sharing preferences were assessed via an 11-item survey. The survey link was emailed to 89539 English-speaking Withings product users. Responses were accepted for 5 weeks.

Descriptive statistics were calculated using Excel and qualitative data were analyzed to provide additional context.

Results

Nearly 1640 people or 5.7% of invitees responded representing 62 countries with 80% identifying as Caucasian, 75% male with 78% being college educated. The majority were agreeable to having their data shared with researchers to advance knowledge and improve health care.

Participants responding to open ended items (N=247) appeared unaware that the company had access to their personal health data.

Conclusions

While the majority of respondents were in favor of data sharing, individuals expressed concerns about the ability to de-identify data and associated risks of re-identification as well as an interest in having some control over the use of “their” data. Given consumer misconception about data ownership, access and use, efforts to increase transparency when interacting with individual digital health data must be prioritized. Moreover, the basic ethical principle of “respect for persons” demonstrated via the informed consent process will be critical in advancing the adoption of digital technologies that create real-world evidence and advance opportunities for N-of-1 self-study.
Religious Belief and Cognitive Conflict Sensitivity: A Preregistered fMRI Study
Authors: Hoogeveen Suzanne , Snoek Lukas , van Elk Michiel
Published: January 2020

In the current preregistered fMRI study, we investigated the relationship between religiosity and behavioral and neural mechanisms of conflict processing, as a conceptual replication of the study by Inzlicht et al. (2009). Participants (N= 193) performed a gender-Stroop task and afterwards completed standardized measures to assess their religiosity. As expected, the task induced cognitive conflict at the behavioral level and at a neural level this was reflected in increased activity in the anterior cingulate cortex (ACC). However, individual differences in religiosity were not related to performance on the Stroop task as measured in accuracy and interference effects, nor to neural markers of response conflict (correct responses vs. errors) or informational conflict (congruent vs. incongruent stimuli). Overall, we obtained moderate to strong evidence in favor of the null hypotheses that religiosity is unrelated to cognitive conflict sensitivity. We discuss the implications for the neuroscience of religion and emphasize the importance of designing studies that more directly implicate religious concepts and behaviors in an ecologically valid manner.
Substrate-dependent accessibility changes in the Na+-dependent C4-dicarboxylate transporter, VcINDY, suggest differential substrate effects in a multistep mechanism
Authors: Sampson Connor D. D. , Stewart Matthew J. , Mindell Joseph A. , Mulligan Christopher
Published: January 2020

Members of thedivalentanionsodiumsymporter (DASS) family (SLC13 in humans) play critical roles in metabolic homeostasis, influencing many processes including fatty acid synthesis, insulin resistance, adiposity, and lifespan determination. DASS transporters catalyse the Na+-driven concentrative uptake of Krebs cycle intermediates and sulfate into cells; disrupting their function can protect against age-related metabolic diseases and can extend lifespan. An inward-facing crystal structure and an outward-facing model of a bacterial DASS family member, VcINDY fromVibrio cholerae, predict an elevator-like transport mechanism involving a large rigid body movement of the substrate binding site. How substrate binding influences the conformational state of VcINDY is currently unknown. Here, we probe the interaction between substrate binding and VcINDY conformation using a site-specific alkylation strategy to probe the solvent accessibility of several broadly distributed positions in VcINDY in the presence and absence of substrates (Na+and succinate). Our findings reveal that accessibility to all positions tested can be modulated by the presence of substrates, with the majority becoming less accessible in the presence of Na+. Mapping these solvent accessibility changes onto the known structures of VcINDY suggests that Na+binding drives the transporter into an as-yet-unidentified intermediate state. We also observe substantial, separable effects of Na+and succinate binding at several amino acid positions suggesting distinct effects of the two substrates. Furthermore, analysis of a solely succinate-sensitive residue indicates that VcINDY binds its substrate with a low affinity and proceeds via an ordered process in which one or more Na+ions must bind prior to succinate. These findings provide insight into the mechanism of VcINDY, which is currently the only structural-characterised representative of the entire DASS family.
Cortical tracking of speech in noise accounts for reading strategies in children
Authors: Destoky Florian , Bertels Julie , Niesen Maxime , Wens Vincent , Vander Ghinst Marc , Leybaert Jacqueline , Lallier Marie , Ince Robin A. A. , Gross Joachim , De Tiège Xavier , Bourguignon Mathieu
Published: January 2020

Humans’ propensity to acquire literacy relates to several factors, among which, the ability to understand speech in noise (SiN). Still, the nature of the relation between reading and SiN perception abilities remains poorly understood. Here, we dissect the interplay between (i) reading abilities, (ii) classical behavioral predictors of reading (phonological awareness, phonological memory and lexical access), and (iii) electrophysiological markers of SiN perception in 99 elementary school children (26 with dyslexia). We demonstrate that cortical representation of phrasal content of SiN relates to the development of the lexical (but not sublexical) reading strategy. In contrast, classical behavioral predictors of reading abilities and the ability to benefit from visual speech to represent the syllabic content of SiN account for global reading performance (i.e., speed and accuracy of lexical and sublexical reading). Finally, we found that individuals with dyslexia properly integrate visual speech information to optimize processing of syntactic information, but not to sustain acoustic/phonemic processing. These results clarify the nature of the relation between SiN perception and reading abilities in typical and dyslexic child readers, and identified novel electrophysiological markers of emergent literacy.
Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility
Authors: Hiltpold Maya , Niu Guanglin , Kadri Naveen Kumar , Crysnanto Danang , Fang Zih-Hua , Spengeler Mirjam , Schmitz-Hsu Fritz , Fuerst Christian , Schwarzenbacher Hermann , Seefried Franz R. , Seehusen Frauke , Witschi Ulrich , Schnieke Angelika , Fries Ruedi , Bollwein Heinrich , Flisikowski Krzysztof , Pausch Hubert
Published: January 2020

Cattle are ideally suited to investigate the genetics of male reproduction, because semen quality and fertility are recorded for all ejaculates of artificial insemination bulls. We analysed 26,090 ejaculates of 794 Brown Swiss bulls to assess ejaculate volume, sperm concentration, sperm motility, sperm head and tail anomalies and insemination success. The heritability of the six semen traits was between 0 and 0.26. Genome-wide association testing on 607,511 SNPs revealed a QTL on bovine chromosome 6 that was associated with sperm motility (P = 2.5 × 10−27), head (P = 2.0 × 10−44) and tail anomalies (P = 7.2 × 10−49) and insemination success (P = 9.9 × 10−13). The QTL harbors a recessive allele that compromises semen quality and male fertility. We replicated the effect of the QTL on fertility (P = 7.1 × 10−32) in an independent cohort of 2481 Brown Swiss bulls. The analysis of whole-genome sequencing data revealed that a synonymous variant (BTA6:58373887C>T, rs474302732) inWDR19encoding WD repeat-containing protein 19 was in linkage disequilibrium with the fertility-associated haplotype. WD repeat-containing protein 19 is a constituent of the intraflagellar transport complex that is essential for the physiological function of motile cilia and flagella. Bioinformatic and transcription analyses revealed that the BTA6:58373887 T-allele activates a cryptic exonic splice site that eliminates three evolutionarily conserved amino acids from WDR19. Western blot analysis demonstrated that the BTA6:58373887 T-allele decreases protein expression. We make the remarkable observation that, in spite of negative effects on semen quality and bull fertility, the BTA6:58373887 T-allele has a frequency of 24 % in the Brown Swiss population. Our findings are the first to uncover a variant that is associated with quantitative variation in semen quality and male fertility in cattle.

Author summary

In cattle farming, artificial insemination is the most commonly used method of breeding. To ensure high fertilization rates, ejaculate quality and insemination success are closely monitored in artificial insemination bulls. We analyse semen quality, insemination success and microarray-called genotypes at more than 600,000 genome-wide SNP markers in 794 bulls to identify a recessive allele that compromises semen quality. We take advantage of whole-genome sequencing to pinpoint a variant in the coding sequence ofWDR19encoding WD repeat-containing protein 19 that activates a novel exonic splice site. Our results indicate that cryptic splicing inWDR19is associated with reduced male reproductive performance. This is the first report of a variant that contributes to quantitative variation in bovine semen quality.
In silicocharacterization of mechanisms positioning costimulatory and checkpoint complexes in immune synapses
Authors: Siokis Anastasios , Robert Philippe A. , Demetriou Philippos , Kvalvaag Audun , Valvo Salvatore , Mayya Viveka , Dustin Michael L. , Meyer-Hermann Michael
Published: January 2020

Integrin and small immunoglobulin superfamily (sIGSF) adhesion complexes function physiologically in human immunological synapses (IS) wherein sIGSF complexes form a corolla of microdomains around an integrin ring and secretory core. The corolla recruits and retains the major costimulatory and checkpoint complexes that regulate the response to T cell receptor (TCR) engagement, making forces that govern corolla formation of particular interest. We developed a phenomenological agent-based model in order to test different hypotheses concerning the mechanisms underlying molecular reorganization during IS formation. The model showed that sIGSF complexes are passively excluded to the distal aspect of the IS as long as their interaction with the ramified F-actin transport network is absent or weaker than that of integrins. An attractive force between sIGSF adhesion and costimulatory/checkpoint complexes relocates the latter from the centre of the IS to the corolla. The simulations suggest that size based sorting interactions with large glycocalyx components as well as a short-range self-attraction between sIGSF complexes explain the corolla “petals”. These molecular and mechanistic features establish a general model that can recapitulate complex pattern formation processes observed in cell-bilayer and cell-cell interfaces.

One Sentence Summary

Computer simulations of immunological synapses reveal the localization mechanisms of immunoglobulin superfamily adhesion and costimulatory/checkpoint complexes.