bluuebunny/crossref_metadata_2025 huggingface dataset:
Daily Morning Blue Light Therapy for Post-mTBI Sleep Disruption: Effects on Brain Structure and Function
Authors: Raikes Adam C. , Dailey Natalie S. , Forbeck Brittany , Alkozei Anna , Killgore William D. S.
Published: February 2021

Background: Mild traumatic brain injuries (mTBIs) are associated with novel or worsened sleep disruption. Several studies indicate that daily morning blue light therapy (BLT) is effective for reducing post-mTBI daytime sleepiness and fatigue. Studies demonstrating changes in brain structure and function following BLT are limited. The present study's purpose is to identify the effect of daily morning BLT on brain structure and functional connectivity and the association between these changes and self-reported change in post-mTBI daytime sleepiness.

Methods: A total of 62 individuals recovering from a mTBI were recruited from two US cities to participate in a double-blind placebo-controlled trial. Eligible individuals were randomly assigned to undergo 6 weeks of 30 min daily morning blue or placebo amber light therapy (ALT). Prior to and following treatment all individuals completed a comprehensive battery that included the Epworth Sleepiness Scale as a measure of self-reported daytime sleepiness. All individuals underwent a multimodal neuroimaging battery that included anatomical and resting-state functional magnetic resonance imaging. Atlas-based regional change in gray matter volume (GMV) and region-to-region functional connectivity from baseline to post-treatment were the primary endpoints for this study.

Results: After adjusting for pre-treatment GMV, individuals receiving BLT had greater GMV than those receiving amber light in 15 regions of interest, including the right thalamus and bilateral prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with greater GMV in 74 ROIs, covering many of the same general regions. Likewise, BLT was associated with increased functional connectivity between the thalamus and both prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with increased functional connectivity between attention and cognitive control networks as well as decreased connectivity between visual, motor, and attention networks (all FDR corrected p < 0.05).

Conclusions: Following daily morning BLT, moderate to large increases in both gray matter volume and functional connectivity were observed in areas and networks previously associated with both sleep regulation and daytime cognitive function, alertness, and attention. Additionally, these findings were associated with improvements in self-reported daytime sleepiness. Further work is needed to identify the personal characteristics that may selectively identify individuals recovering from a mTBI for whom BLT may be optimally beneficial.
Wrist Circumference-Dependent Upper Limit of Normal for the Cross-Sectional Area Is Superior Over a Fixed Cut-Off Value in Confirming the Clinical Diagnosis of Carpal Tunnel Syndrome
Authors: Olde Dubbelink Tom B. G. , De Kleermaeker Floriaan G. C. M. , Beekman Roy , Wijntjes Juerd , Bartels Ronald H. M. A. , Meulstee Jan , Verhagen Wim I. M.
Published: February 2021

Introduction: In confirming the clinical diagnosis of carpal tunnel syndrome (CTS), ultrasonography (US) is the recommended first diagnostic test in The Netherlands. One of the most important parameters for an abnormal US result is an increase of the CSA of the median nerve at the carpal tunnel inlet. An earlier study showed that a wrist-circumference dependent cut-off for the upper limit of normal of this CSA might be superior to a fixed cut-off of 11 mm2. In this study we compared three ultrasonography (US) parameters in three large Dutch hospitals.

Methods: Patients with a clinical suspicion of CTS and with reasonable exclusion of other causes of their symptoms were prospectively included. A total number of 175 patients were analysed. The primary goal was to compare the number of wrists with an abnormal US result while using a fixed cut-off of 11 mm2 (FC), a wrist circumference-dependent cut-off (y = 0.88 * x−4, where y = ULN and x = wrist circumference in centimetres; abbreviated as WDC), and an intraneural flow related cut-off (IFC).

Results: The WDC considered more US examinations to be abnormal (55.4%) than the FC (50.3%) did, as well as the IFC (46.9%), with a statistically significant difference of p = 0.035 and p = 0.001, respectively. The WDC detected 12 abnormal median nerves while the FC did not, and 18 while the IFC did not. The wrist circumference of the patients of these subgroups turned out to be significantly smaller (p < 0.001) when compared with the rest of the group.

Conclusion: According to these study results, the wrist-circumference dependent cut-off value for the CSA of the median nerve at the wrist appears to have a higher sensitivity than either a fixed cut-off value of 11 mm2 or cut-off values based on intraneural flow, and may add most value in patients with a smaller wrist circumference.
The Role of Virtual Reality in Screening, Diagnosing, and Rehabilitating Spatial Memory Deficits
Authors: Jonson Miles , Avramescu Sinziana , Chen Derek , Alam Fahad
Published: February 2021

Impairment of spatial memory, including an inability to recall previous locations and navigate the world, is often one of the first signs of functional disability on the road to cognitive impairment. While there are many screening and diagnostic tools which attempt to measure spatial memory ability, they are often not representative of real-life situations and can therefore lack applicability. One potential solution to this problem involves the use of virtual reality (VR), which immerses individuals in a virtually-simulated environment, allowing for scenarios more representative of real-life without any of the associated risks. Here, we review the evidence surrounding the use of VR for the screening and diagnosis of spatial memory impairments, including potential limitations and how it compares to standard neuropsychological tests. We will also discuss the evidence regarding the potential use of VR in the rehabilitation of spatial memory deficits, which has not been well studied, but which could be game-changing if proven successful.
Predictive Factors for Positive Surgical Margins in Patients With Prostate Cancer After Radical Prostatectomy: A Systematic Review and Meta-Analysis
Authors: Zhang Lijin , Zhao Hu , Wu Bin , Zha Zhenlei , Yuan Jun , Feng Yejun
Published: February 2021

Background and Objectives

Previous studies have demonstrated that positive surgical margins (PSMs) were independent predictive factors for biochemical and oncologic outcomes in patients with prostate cancer (PCa). This study aimed to conduct a meta-analysis to identify the predictive factors for PSMs after radical prostatectomy (RP).

Methods

We selected eligible studies via the electronic databases, such as PubMed, Web of Science, and EMBASE, from inception to December 2020. The risk factors for PSMs following RP were identified. The pooled estimates of standardized mean differences (SMDs)/odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A fixed effect or random effect was used to pool the estimates. Subgroup analyses were performed to explore the reasons for heterogeneity.

Results

Twenty-seven studies including 50,014 patients with PCa were eligible for further analysis. The results showed that PSMs were significantly associated with preoperative prostate-specific antigen (PSA) (pooled SMD = 0.37; 95% CI: 0.31–0.43; P < 0.001), biopsy Gleason Score (<6/≥7) (pooled OR = 1.53; 95% CI:1.31–1.79; P < 0.001), pathological Gleason Score (<6/≥7) (pooled OR = 2.49; 95% CI: 2.19–2.83; P < 0.001), pathological stage (<T2/≥T3) (pooled OR = 3.90; 95% CI: 3.18–4.79; P < 0.001), positive lymph node (PLN) (pooled OR = 3.12; 95% CI: 2.28–4.27; P < 0.001), extraprostatic extension (EPE) (pooled OR = 4.44; 95% CI: 3.25–6.09; P < 0.001), and seminal vesicle invasion (SVI) (pooled OR = 4.19; 95% CI: 2,87–6.13; P < 0.001). However, we found that age (pooled SMD = 0.01; 95% CI: −0.07–0.10; P = 0.735), body mass index (BMI) (pooled SMD = 0.12; 95% CI: −0.05–0.30; P = 0.162), prostate volume (pooled SMD = −0.28; 95% CI: −0.62–0.05; P = 0.097), and nerve sparing (pooled OR = 0.90; 95% CI: 0.71–1.14; P = 0.388) had no effect on PSMs after RP. Besides, the findings in this study were found to be reliable by our sensitivity and subgroup analyses.

Conclusions

Preoperative PSA, biopsy Gleason Score, pathological Gleason Score, pathological stage, positive lymph node, extraprostatic extension, and seminal vesicle invasion are independent predictors of PSMs after RP. These results may helpful for risk stratification and individualized therapy in PCa patients.
Extracellular Vesicles: An Emerging Nanoplatform for Cancer Therapy
Authors: Ma Yifan , Dong Shiyan , Li Xuefeng , Kim Betty Y. S. , Yang Zhaogang , Jiang Wen
Published: February 2021

Extracellular vesicles (EVs) are cell-derived membrane particles that represent an endogenous mechanism for cell-to-cell communication. Since discovering that EVs have multiple advantages over currently available delivery platforms, such as their ability to overcome natural barriers, intrinsic cell targeting properties, and circulation stability, the potential use of EVs as therapeutic nanoplatforms for cancer studies has attracted considerable interest. To fully elucidate EVs’ therapeutic function for treating cancer, all current knowledge about cellular uptake and trafficking of EVs will be initially reviewed. In order to further improve EVs as anticancer therapeutics, engineering strategies for cancer therapy have been widely explored in the last decade, along with other cancer therapies. However, therapeutic applications of EVs as drug delivery systems have been limited because of immunological concerns, lack of methods to scale EV production, and efficient drug loading. We will review and discuss recent progress and remaining challenges in developing EVs as a delivery nanoplatform for cancer therapy.
Anterior Mediastinal Lesion Segmentation Based on Two-Stage 3D ResUNet With Attention Gates and Lung Segmentation
Authors: Huang Su , Han Xiaowei , Fan Jingfan , Chen Jing , Du Lei , Gao Wenwen , Liu Bing , Chen Yue , Liu Xiuxiu , Wang Yige , Ai Danni , Ma Guolin , Yang Jian
Published: February 2021

Objectives

Anterior mediastinal disease is a common disease in the chest. Computed tomography (CT), as an important imaging technology, is widely used in the diagnosis of mediastinal diseases. Doctors find it difficult to distinguish lesions in CT images because of image artifact, intensity inhomogeneity, and their similarity with other tissues. Direct segmentation of lesions can provide doctors a method to better subtract the features of the lesions, thereby improving the accuracy of diagnosis.

Method

As the trend of image processing technology, deep learning is more accurate in image segmentation than traditional methods. We employ a two-stage 3D ResUNet network combined with lung segmentation to segment CT images. Given that the mediastinum is between the two lungs, the original image is clipped through the lung mask to remove some noises that may affect the segmentation of the lesion. To capture the feature of the lesions, we design a two-stage network structure. In the first stage, the features of the lesion are learned from the low-resolution downsampled image, and the segmentation results under a rough scale are obtained. The results are concatenated with the original image and encoded into the second stage to capture more accurate segmentation information from the image. In addition, attention gates are introduced in the upsampling of the network, and these gates can focus on the lesion and play a role in filtering the features. The proposed method has achieved good results in the segmentation of the anterior mediastinal.

Results

The proposed method was verified on 230 patients, and the anterior mediastinal lesions were well segmented. The average Dice coefficient reached 87.73%. Compared with the model without lung segmentation, the model with lung segmentation greatly improved the accuracy of lesion segmentation by approximately 9%. The addition of attention gates slightly improved the segmentation accuracy.

Conclusion

The proposed automatic segmentation method has achieved good results in clinical data. In clinical application, automatic segmentation of lesions can assist doctors in the diagnosis of diseases and may facilitate the automated diagnosis of illnesses in the future.
The Paradoxical Behavior of microRNA-211 in Melanomas and Other Human Cancers
Authors: Ray Animesh , Kunhiraman Haritha , Perera Ranjan J.
Published: February 2021

Cancer initiation, progression, and metastasis leverage many regulatory agents, such as signaling molecules, transcription factors, and regulatory RNA molecules. Among these, regulatory non-coding RNAs have emerged as molecules that control multiple cancer types and their pathologic properties. The human microRNA-211 (MIR211) is one such molecule, which affects several cancer types, including melanoma, glioblastoma, lung adenocarcinomas, breast, ovarian, prostate, and colorectal carcinoma. Previous studies suggested that in certain tumors MIR211 acts as a tumor suppressor while in others it behaves as an oncogenic regulator. Here we summarize the known molecular genetic mechanisms that regulate MIR211 gene expression and molecular pathways that are in turn controlled by MIR211 itself. We discuss how cellular and epigenetic contexts modulate the biological effects of MIR211, which exhibit pleiotropic effects. For example, up-regulation of MIR211 expression down-regulates Warburg effect in melanoma tumor cells associated with an inhibition of the growth of human melanoma cells in vitro, and yet these conditions robustly increase tumor growth in xenografted mice. Signaling through the DUSP6-ERK5 pathway is modulated by MIR211 in BRAFV600E driven melanoma tumors, and this function is involved in the resistance of tumor cells to the BRAF inhibitor, Vemurafenib. We discuss several alternate but testable models, involving stochastic cell-to-cell expression heterogeneity due to multiple equilibria involving feedback circuits, intracellular communication, and genetic variation at miRNA target sties, to reconcile the paradoxical effects of MIR211 on tumorigenesis. Understanding the precise role of this miRNA is crucial to understanding the genetic basis of melanoma as well as the other cancer types where this regulatory molecule has important influences. We hope this review will inspire novel directions in this field.
Immune Microenvironment: New Insight for Familial Adenomatous Polyposis
Authors: Yang Jun , Wen Zhengqi , Li Wenliang , Sun Xianghua , Ma Junrui , She Xueke , Zhang Hongbin , Tu Changling , Wang Guoqiang , Huang Depei , Shen Xudong , Dong Jian , Zhang Hushan
Published: February 2021

Currently, the main treatment for familial adenomatous polyposis (FAP) is surgery, however, surgery is far from ideal as there are many complications such as uncontrollable bowel movements, pouch inflammation, anastomotic stricture, and secondary fibroids. Therefore, it is necessary to further expand the understanding of FAP and develop new treatments for FAP. The immune microenvironment including immune cells and cytokines, plays an important role in FAP and the progression of FAP to adenocarcinoma, thus it may be a promising treatment for FAP. In the current review, we summarized the recent progress in the immune microenvironment of FAP.
Fetal Intraventricular Hemorrhage Due to Antiphospholipid Syndrome: A Case Report
Authors: Bouw M. C. , Nij Bijvank S. W. A. , Bouwhuis J. W. , Wezel-Meijler G. van
Published: February 2021

Obstetric Antiphospholipid Syndrome (OAPS) is an autoimmune disease characterized by certain pregnancy complications in association with persistent antiphospholipid antibodies. These antibodies are generally known for their prothrombotic characteristics and may affect mother and fetus during the entire pregnancy. The clinical criteria for OAPS, including recurrent fetal loss, intra-uterine growth restriction and premature birth due to severe preeclampsia, all suggest uteroplacental vascular insufficiency. Although rare, thrombotic complications have been described in neonates born to mothers with OAPS, mainly ischemic stroke. We report on the first case of extensive fetal intraventricular hemorrhage related to OAPS. We share our diagnostic search and analysis for this unusual antenatal event, including cranial ultrasound findings and postmortem MRI images. We will also present a short review of the etiology and prognosis of antenatal intraventricular hemorrhage. We suggest that women with severe or early preeclampsia and/or a history of pregnancy loss should be evaluated for OAPS and carefully monitored throughout pregnancy. Further, we advise to test mothers for OAPS in the case of idiopathic fetal hemorrhage.
Epidemiology of Multiple Congenital Anomalies Before and After Implementation of a Nationwide Prenatal Screening Program in Denmark
Authors: Toxværd Marlene E. , Garne Ester
Published: February 2021

Surveillance of congenital anomalies is important in order to detect negative influences from environment, medication, or lifestyle as early as possible. Since most teratogens are associated with a spectrum of birth defects rather than a single defect, analysis of the epidemiology of multiple congenital anomalies is important to detect an increase due to environmental or medicine exposure. The aim of the study was to describe changes in prevalence, types of anomalies, and outcome of pregnancies for fetuses and infants with multiple congenital anomalies before and after introduction of the new screening program in the County of Funen, Denmark. The study was based on data from the EUROCAT registry of the County of Funen for the period 1990 to 2014 covering 135,057 births. The registry includes information about livebirths, fetal deaths after 20 weeks of gestation and terminations of pregnancy after prenatal diagnosis of fetal anomalies. All cases with two or more major congenital anomalies in different organ systems, where the pattern of anomalies were not recognized as part of a chromosomal or genetic syndrome or a sequence were included in the study. Overall prevalence of multiple congenital anomalies was 19.7 per 10,000 pregnancies. There was no significant change in prevalence over time. The prenatal detection rate increased from 26 to 57% after introduction of the screening program (p < 0.001). Proportion of terminations of pregnancy increased from 11 to 30% of all cases and 1-week survival for livebirths increased from 64 to 94%. There was no change in combinations of involved organ systems. The implementation of the new screening program in 2004 has led to an increased prenatal detection rate of multiple congenital anomalies followed by an increased rate of termination of pregnancy for the most severe cases and an increased 1-week survival for liveborn infants with multiple congenital anomalies.
Inhaled Antibiotics for the Prevention of Respiratory Tract Infections in Children With a Tracheostomy
Authors: Jutras Camille , Autmizguine Julie , Chomton Maryline , Marquis Christopher , Nguyen The Thanh-Diem , Roumeliotis Nadia , Emeriaud Guillaume
Published: February 2021

Objective: To describe the use of prophylactic inhaled antibiotics in children with a tracheostomy and assess if its use is associated with a reduction in exposition to broad-spectrum antibiotics and a lower risk of acquired respiratory tract infections.

Methods: A case series study was performed in a tertiary care university affiliated hospital. All consecutive children (<18 years old) with a tracheostomy, hospitalized between January 2004 and November 2016, and treated with prophylactic inhaled antibiotics were identified. We analyzed the 3 month- period before and after initiation of prophylactic inhaled antibiotics and described exposure to broad spectrum antibiotics, the number of respiratory tract infections and the associated adverse events.

Results: Six children (median age: 11 months, range: 8–100) were included. One received colimycin, 3 received tobramycin and 2 were treated with both antibiotics in alternance. The median duration of treatment was 74 days (22–173) with one patient still being treated at the end of the study. Patients were exposed to systemic antibiotics for 18 days (2–49) in the 3 months preceding the treatment vs. 2 days (0–15) in the 3 months following the treatment initiation (p = 0.115). The number of respiratory tract infections went from median of 2 (0–3) to 1 (0–1) during the same periods (p = 0.07). Adverse events most commonly reported were cough (n = 2) and increased respiratory secretions post-inhalation (n = 4). Only one new bacterial resistance was observed.

Conclusions: This series of consecutive cases underlines the need for future studies evaluating the potential benefit of prophylactic inhaled antibiotics in children with a tracheostomy.
Modalities and Mechanisms of Treatment for Coronavirus Disease 2019
Authors: Zuo Zhihong , Wu Ting , Pan Liangyu , Zuo Chenzhe , Hu Yingchuo , Luo Xuan , Jiang Liping , Xia Zanxian , Xiao Xiaojuan , Liu Jing , Ye Mao , Deng Meichun
Published: February 2021

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly throughout the world. Although COVID-19 has a relatively low case severity rate compared to SARS and Middle East Respiratory syndrome it is a major public concern because of its rapid spread and devastating impact on the global economy. Scientists and clinicians are urgently trying to identify drugs to combat the virus with hundreds of clinical trials underway. Current treatments could be divided into two major part: anti-viral agents and host system modulatory agents. On one hand, anti-viral agents focus on virus infection process. Umifenovir blocks virus recognizing host and entry. Remdesivir inhibits virus replication. Chloroquine and hydroxychloroquine involve preventing the whole infection process, including virus transcription and release. On the other hand, host system modulatory agents are associated with regulating the imbalanced inflammatory reaction and biased immune system. Corticosteroid is believed to be commonly used for repressing hyper-inflammation, which is one of the major pathologic mechanisms of COVID-19. Convalescent plasma and neutralizing antibodies provide essential elements for host immune system and create passive immunization. Thrombotic events are at high incidence in COVID-19 patients, thus anti-platelet and anti-coagulation are crucial, as well. Here, we summarized these current or reproposed agents to better understand the mechanisms of agents and give an update of present research situation.
Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond
Authors: Di Paolo Antonello , Luci Giacomo
Published: February 2021

The pharmacotherapy of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) has experienced significant progress with the advent of monoclonal antibodies (mABs). As therapeutic proteins, mABs display peculiar pharmacokinetic characteristics that differentiate them from chemical drugs, such as aminosalicylates, antimetabolites (i.e., azathioprine, 6-mercaptopurine, and methotrexate), and immunosuppressants (corticosteroids and cyclosporine). However, clinical trials have demonstrated that biologic agents may suffer from a pharmacokinetic variability that could influence the desired clinical outcome, beyond primary resistance phenomena. Therefore, therapeutic drug monitoring (TDM) protocols have been elaborated and applied to adaptation drug doses according to the desired plasma concentrations of mABs. This activity is aimed at maximizing the beneficial effects of mABs while sparing patients from toxicities. However, some aspects of TDM are still under discussion, including time-changing therapeutic ranges, proactive and reactive approaches, the performance and availability of instrumental platforms, the widely varying individual characteristics of patients, the severity of the disease, and the coadministration of immunomodulatory drugs. Facing these issues, personalized medicine in IBD may benefit from a combined approach, made by TDM protocols and pharmacogenetic analyses in a timeline that necessarily considers the frailty of patients, the chronic administration of drugs, and the possible worsening of the disease. Therefore, the present review presents and discusses the activities of TDM protocols using mABs in light of the most recent results, with special attention on the integration of other actions aimed at exploiting the most effective and safe therapeutic effects of drugs prescribed in IBD patients.
Rapamycin is Effective for Upper but not for Lower Gastrointestinal Crohn’s Disease-Related Stricture: A Pilot Study
Authors: Zhong Min , Cui Bota , Xiang Jie , Wu Xia , Wen Quan , Li Qianqian , Zhang Faming
Published: February 2021

Crohn’s disease (CD)-related fibrotic stricture remains a clinical challenge because of no effective treatments. This study aimed to evaluate the potential efficacy of rapamycin in patients with CD-related strictures in different locations in gastrointestinal tract. A pilot prospective study on using rapamycin for CD-related stricture was performed from April 2015 to August 2020 in a single center in China. Fifteen patients were enrolled into the study. The clinical efficacy was evaluated by diet score and gastrointestinal obstruction symptoms score. Clinical responses were defined as the ability to tolerate the regular diet with vegetable fiber combined with a reduction of ≥75% in overall target score and a score of less than two points for each item. Three patients discontinued rapamycin for less than 1-month due to intolerance to adverse events, then, 12 patients received ≥1 dose of the rapamycin and provided ≥1 post-baseline target score after baseline were included for intent-to-treat (ITT) analysis. 100% (5/5) of patients with upper gastrointestinal strictures achieved clinical response after using rapamycin. However, no clinical response was observed in those patients with CD lesions in lower gastrointestinal tract. Adverse events occurred in 40% (6/15) of patients. No death or serious opportunistic infections were observed in the present study. This study firstly reported that rapamycin might be effective for CD-related stricture in the upper, but not in lower gastrointestinal tract.
Comparing the Prevalence of Polypharmacy and Potential Drug-Drug Interactions in Nursing Homes and in the Community Dwelling Elderly of Emilia Romagna Region
Authors: Burato Sofia , Leonardi Luca , Antonazzo Ippazio Cosimo , Raschi Emanuel , Ajolfi Chiara , Baraghini Manuela , Chiarello Antonella , Delmonte Valentina , Di Castri Lucio , Donati Monia , Fadda Antonella , Fedele Daniela , Ferretti Alessandra , Gabrielli Laura , Gobbi Silvia , Lughi Sereno , Mazzari Martina , Pieraccini Fabio , Renzetti Alessandro , Russi Elsa , Scanelli Chiara , Zanetti Barbara , Poluzzi Elisabetta
Published: February 2021

Backround: We aimed at assessing the prevalence of polypharmacy and potential drug-drug interactions (DDIs) with clinical relevance in elderly patient on Emilia Romagna area. Both outpatients and residents in nursing homes were assessed, with only partially overlapping strategies.

Methods: We defined a list of 190 pairs of potentially interacting drugs, based on literature appraisal and availability of therapeutic alternatives. January-June 2018 data on drug use in patients over 65 years-old were collected from nine Local Health Authorities of Emilia Romagna: data on community-dwelling subjects were extracted from archives of reimbursed prescriptions, while drug use in a sample of nursing homes was recorded from clinical charts in one index day within the same semester. The frequency of polypharmacy (at least five or at least 10 concurrent drugs) and of each DDI was calculated.

Results: In line with different rates of polypharmacy (80% vs 16%), the risk of exposure to at least one interaction was 53.7% in nursing homes and 26.4% in outpatients. Among DDIs, in nursing homes antidepressants—anxiolytics (11.9%) ranked first, followed by antidepressants—aspirin (7.4%). In outpatients, ACE-inhibitors—non-steroidal anti-inflammatory drugs (NSAIDs) reached 7.2% followed by the calcium channel blockers—α-blockers (2.4%).

Discussion: Polypharmacy and risk of DDIs appeared very different in the two settings, due to both technical and clinical reasons. In order to reduce use of benzodiazepines, NSAIDs, antidepressants and relevant DDIs, 1) defining alternative options for pain relief in elderly outpatients, and 2) implementing non-pharmacological management of insomnia and anxiety in nursing homes should be prioritized.
Reduction of Neuroinflammation by δ-Opioids Via STAT3-Dependent Pathway in Chronic Glaucoma Model
Authors: Husain Shahid , Zaidi Syed A. H. , Singh Sudha , Guzman Wendy , Mehrotra Shikhar
Published: February 2021

The main objective of this study was to determine the inhibition of pro-inflammatory cytokines and their associated signaling molecules by δ-opioid receptor activation by a selective ligand, SNC-121 in chronic rat glaucoma model. Intraocular pressure was raised in rat eyes by injecting 2 M hypertonic saline into the limbal veins. SNC-121 (1 mg/kg; i. p) or Stattic (5 mg/kg; i. p) was administered in Brown Norway rats daily for 7 days. The mRNA expression of IL-1β, TNF-α, Fas, IL-6, leukemia inhibitory factor, and IFN-γ was increased significantly in the retina of ocular hypertensive animals at day 7, post injury. Administration of SNC-121 (1 mg/kg; i. p. injection) for 7 days (once a day) completely inhibited the increase in the mRNA and protein expression of pro-inflammatory cytokines. Mechanistically, we provide data showing a significant increase in the phosphorylation of STAT3 at tyrosine 705 whereas a moderate but significant increase in the total STAT3 protein expression was also seen in the retina of ocular hypertensive animals. Data illustrated that SNC-121 administration completely abrogated ocular hypertension-induced increase in STAT3Y705phosphorylation. Interestingly, acetylation of STAT3 at lysine 685 (AcK685) was reduced in ocular hypertensive animals and subsequently increased significantly by SNC-121 treatment. Stattic, a selective STAT3 inhibitor, administration resulted in a complete attenuation in the production of IL-1β and IL-6 in ocular hypertensive animals. In conclusion, δ-opioid receptor activation suppressed the phosphorylation of STAT3 at tyrosine 705 and increased acetylation at lysine 686 and these posttranslational modifications can regulate the production of some but not all pro-inflammatory cytokines in response to glaucomatous injury.
An Optimized K-Edge Signal Extraction Method for K-Edge Decomposition Imaging Using a Photon Counting Detector
Authors: Zhang Zhidu , Zhang Xiaomei , Hu Jinming , Xu Qiong , Li Mohan , Wei Cunfeng , Wei Long , Wang Zhe
Published: February 2021

In K-edge decomposition imaging for the multienergy system with the photon counting detectors (PCDs), the energy bins significantly affect the intensity of the extracted K-edge signal. Optimized energy bins can provide a better K-edge signal to improve the quality of the decomposition images and have the potential to reduce the amount of contrast agents. In this article, we present the Gaussian spectrum selection method (GSSM) for the multienergy K-edge decomposition imaging which can extract an optimized K-edge signal by optimizing energy bins compared with the conventional theoretical attenuation selection method (TASM). GSSM decides the width and locations of the energy bins using a simple but effective model of the imaging system, which takes the degraded energy resolution of the detector and the continuous x-ray spectrum into consideration. Besides, we establish the objective function, difference of attenuation to relative standard deviation ratio (DAR), to determine the optimal energy bins which maximize the K-edge signal. The results show that GSSM gets a better K-edge signal than TASM especially at the lower concentration level of contrast agents. The new method has the potential to improve the contrast and reduce the amount of contrast agents.
Usefulness of NGS for Diagnosis of Dominant Beta-Thalassemia and Unstable Hemoglobinopathies in Five Clinical Cases
Authors: Rizzuto Valeria , Koopmann Tamara T. , Blanco-Álvarez Adoración , Tazón-Vega Barbara , Idrizovic Amira , Díaz de Heredia Cristina , Del Orbe Rafael , Pampliega Miriam Vara , Velasco Pablo , Beneitez David , Santen Gijs W. E. , Waisfisz Quinten , Elting Mariet , Smiers Frans J. W. , de Pagter Anne J. , Kerkhoffs Jean-Louis H. , Harteveld Cornelis L. , Mañú-Pereira Maria del Mar
Published: February 2021

Unstable hemoglobinopathies (UHs) are rare anemia disorders (RADs) characterized by abnormal hemoglobin (Hb) variants with decreased stability. UHs are therefore easily precipitating, causing hemolysis and, in some cases, leading to dominant beta-thalassemia (dBTHAL). The clinical picture of UHs is highly heterogeneous, inheritance pattern is dominant, instead of recessive as in more prevalent major Hb syndromes, and may occur de novo. Most cases of UHs are not detected by conventional testing, therefore diagnosis requires a high index of suspicion of the treating physician. Here, we highlight the importance of next generation sequencing (NGS) methodologies for the diagnosis of patients with dBTHAL and other less severe UH variants. We present five unrelated clinical cases referred with chronic hemolytic anemia, three of them with severe blood transfusion dependent anemia. Targeted NGS analysis was performed in three cases while whole exome sequencing (WES) analysis was performed in two cases. Five different UH variants were identified correlating with patients’ clinical manifestations. Four variants were related to the beta-globin gene (Hb Bristol—Alesha, Hb Debrousse, Hb Zunyi, and the novel Hb Mokum) meanwhile one case was caused by a mutation in the alpha-globin gene leading to Hb Evans. Inclusion of alpha and beta-globin genes in routine NGS approaches for RADs has to be considered to improve diagnosis’ efficiency of RAD due to UHs. Reducing misdiagnoses and underdiagnoses of UH variants, especially of the severe forms leading to dBTHAL would also facilitate the early start of intensive or curative treatments for these patients.
A Multi-OMICs Approach Sheds Light on the Higher Yield Phenotype and Enhanced Abiotic Stress Tolerance in Tobacco Lines Expressing the Carrot lycopene β-cyclase1 Gene
Authors: Moreno Juan C. , Martinez-Jaime Silvia , Kosmacz Monika , Sokolowska Ewelina M. , Schulz Philipp , Fischer Axel , Luzarowska Urszula , Havaux Michel , Skirycz Aleksandra
Published: February 2021

Recently, we published a set of tobacco lines expressing the Daucus carota (carrot) DcLCYB1 gene with accelerated development, increased carotenoid content, photosynthetic efficiency, and yield. Because of this development, DcLCYB1 expression might be of general interest in crop species as a strategy to accelerate development and increase biomass production under field conditions. However, to follow this path, a better understanding of the molecular basis of this phenotype is essential. Here, we combine OMICs (RNAseq, proteomics, and metabolomics) approaches to advance our understanding of the broader effect of LCYB expression on the tobacco transcriptome and metabolism. Upon DcLCYB1 expression, the tobacco transcriptome (~2,000 genes), proteome (~700 proteins), and metabolome (26 metabolites) showed a high number of changes in the genes involved in metabolic processes related to cell wall, lipids, glycolysis, and secondary metabolism. Gene and protein networks revealed clusters of interacting genes and proteins mainly involved in ribosome and RNA metabolism and translation. In addition, abiotic stress-related genes and proteins were mainly upregulated in the transgenic lines. This was well in line with an enhanced stress (high light, salt, and H2O2) tolerance response in all the transgenic lines compared with the wild type. Altogether, our results show an extended and coordinated response beyond the chloroplast (nucleus and cytosol) at the transcriptome, proteome, and metabolome levels, supporting enhanced plant growth under normal and stress conditions. This final evidence completes the set of benefits conferred by the expression of the DcLCYB1 gene, making it a very promising bioengineering tool to generate super crops.
Genetic Variation for Nitrogen Use Efficiency Traits in Global Diversity Panel and Parents of Mapping Populations in Pearl Millet
Authors: Pujarula Vijayalakshmi , Pusuluri Madhu , Bollam Srikanth , Das Roma Rani , Ratnala Rambabu , Adapala Gopikrishna , Thuraga Vishnukiran , Rathore Abhishek , Srivastava Rakesh K. , Gupta Rajeev
Published: February 2021

Nitrogen (N) is one of the primary macronutrients required for crop growth and yield. This nutrient is especially limiting in the dry and low fertility soils where pearl millet [Pennisetum glaucum (L.) R. Br] is typically grown. Globally, pearl millet is the sixth most important cereal grown by subsistence farmers in the arid and semi-arid regions of sub-Saharan Africa and the Indian subcontinent. Most of these agro-ecologies have low N in the root zone soil strata. Therefore, there is an immense need to identify lines that use nitrogen efficiently. A set of 380 diverse pearl millet lines consisting of a global diversity panel (345), parents of mapping populations (20), and standard checks (15) were evaluated in an alpha-lattice design with two replications, 25 blocks, a three-row plot for 11 nitrogen use efficiency (NUE) related traits across three growing seasons (Summer 2017, Rainy 2017, and Summer 2018) in an N-depleted precision field under three different N levels (0%-N0, 50%-N50, 100%-N100 of recommended N, i.e., 100 kg ha–1). Analysis of variance revealed significant genetic variation for NUE-related traits across treatments and seasons. Nitrogen in limited condition (N0) resulted in a 27.6 and 17.6% reduction in grain yield (GY) and dry stover yield (DSY) compared to N50. Higher reduction in GY and DSY traits by 24.6 and 23.6% were observed under N0 compared to N100. Among the assessed traits, GY exhibited significant positive correlations with nitrogen utilization efficiency (NUtE) and nitrogen harvest index (NHI). This indicated the pivotal role of N remobilization to the grain in enhancing yield levels. Top 25 N-insensitive (NIS-top grain yielders) and N-sensitive (NS-poor grain yielders) genotypes were identified under low N conditions. Out of 25 NIS lines, nine genotypes (IP 10820, IP 17720, ICMB 01222-P1, IP 10379, ICMB 89111-P2, IP 8069, ICMB 90111-P2, ICMV IS89305, and ICMV 221) were common with the top 25 lines for N100 level showing the genotype plasticity toward varying N levels. Low N tolerant genotypes identified from the current investigation may help in the identification of genomic regions responsible for NUE and its deployment in pearl millet breeding programs through marker-assisted selection (MAS).
Segregation and Life Satisfaction
Authors: Montero Rodrigo , Vargas Miguel , Vásquez Diego
Published: February 2021

Our aim is to cast light on socioeconomic residential segregation effects on life satisfaction (LS). In order to test our hypothesis, we use survey data from Chile (Casen) for the years 2011 and 2013. We use the Duncan Index to measure segregation based on income at the municipality level for 324 municipalities. LS is obtained from the CASEN survey, which considers a question about self-reported well-being. Segregation’s impact upon LS is not clear at first glance. On one hand, there is evidence telling that segregation’s consequences are negative due to the spatial concentration of poverty and all the woes related to it. On the other hand, segregation would have positive effects because people may feel stress, unhappiness, and alienation when comparing themselves to better-off households. Additionally, there is previous evidence regarding the fact that people prefer to neighbor people of a similar socioeconomic background. Hence, an empirical test is needed. In order to implement it, we should deal with two problems, first, the survey limited statistical significance at the municipal level, hence we use the small area estimation (SAE) methodology to improve the estimations’ statistic properties, and second, the double causality between segregation and LS; to deal with the latter, we include lagged LS as a regressor. Our findings indicate that socioeconomic segregation has a positive effect on LS. This result is robust to different econometric specifications.
Employable as We Age? A Systematic Review of Relationships Between Age Conceptualizations and Employability
Authors: De Lange Annet H. , Van der Heijden Beatrice , Van Vuuren Tinka , Furunes Trude , De Lange Christiane , Dikkers Josje
Published: February 2021

This systematic review aimed to provide an overview of earlier research on the relationships between age conceptualizations (i.e., calendar age, organizational age, lifespan age, psychosocial age, and functional age) and indicators of employability. We have conducted a systematic literature search using PsycINFO, Academic Search Premier, Business Source Complete, CINAHL, ERIC, MEDLINE, and Science Direct. Two raters evaluated the articles and subsequently distinguishedk= 41 studies that met the inclusion criteria for this systematic review. Our review revealed that many researchers adopted different operationalizations to measure employability (15 studies were based on an input- or competence-based measure of employability, 23 studies included an output- or labor market-based measure of employability, and three studies included a combination of both measures). Moreover, most studies included calendar age (40 studies, 97.6%) as indicator of aging at work, and were based on a cross-sectional design (34 studies, 82.9%; 17.1% a longitudinal design). Based on the Standardized Index of Convergence (SIC) method, different types of evidence were found for the relationships between age and the employability measures. For relationships between psychosocial age and lifespan age, on the one hand, and employability measures, on the other hand, too few studies were found to draw conclusions. Yet, for relationships between calendar age and labor market-based measures strong consistent negative relationships were found across the studies, and moderately strong positive relationships were found for functional age and labor market- based measures. For organizational age and both competence-based as well as labor market-based measures moderately strong negative relationships were found. We discuss the implications of these results and propose a research agenda for future studies.
Adaptability and Social Support: Examining Links With Psychological Wellbeing Among UK Students and Non-students
Authors: Holliman Andrew J. , Waldeck Daniel , Jay Bethany , Murphy Summayah , Atkinson Emily , Collie Rebecca J. , Martin Andrew
Published: February 2021

The purpose of this multi-study article was to investigate the roles of adaptability and social support in predicting a variety of psychological outcomes. Data were collected from Year 12 college students (N= 73; Study 1), university students (N= 102; Study 2), and non-studying members of the general public (N= 141; Study 3). Findings showed that, beyond variance attributable to social support, adaptability made a significant independent contribution to psychological wellbeing (life satisfaction, psychological wellbeing, flourishing, and general affect) and psychological distress across all studies. Beyond the effects of adaptability, social support was found to make a significant independent contribution to most wellbeing outcomes (but not psychological distress in university students). In a multi-group analysis comparing predictors of psychological wellbeing in university students and non-studying adults, where the same outcome measures were used (Study 4;N= 243), it was found that adaptability played a stronger role (relative to social support) for university students, whereas social support played a stronger role for non-studying adults. Finally, (contrary to expectations) there was no evidence of an interaction between adaptability and social support predicting psychological outcomes—adaptability and social support operated as independent main effects. These findings demonstrate the importance of adaptability and social support in uniquely predicting psychological wellbeing in different sample groups. It is argued here that these two factors, should be given greater consideration in discussions of psychological wellbeing, and are relevant to psychological wellbeing at different major developmental life stages.
Linezolid Resistance in Enterococcus faecalis Associated With Urinary Tract Infections of Patients in a Tertiary Hospitals in China: Resistance Mechanisms, Virulence, and Risk Factors
Authors: Ma Xiaoyu , Zhang Fan , Bai Bing , Lin Zhiwei , Xu Guangjian , Chen Zhong , Sun Xiang , Zheng Jinxin , Deng Qiwen , Yu Zhijian
Published: February 2021

Background:Enterococcus faecalis has been commonly considered as one of the major pathogens of the urinary tract infection (UTI) in human host worldwide, whereas the molecular characteristics of E. faecalis clinical isolates from the patients with UTI in China remains seldomly reported. This study aimed to investigate the resistance mechanism, molecular characteristics and risk factors of E. faecalis clinical isolates from patients with UTI in China.

Methods: A total of 115 non-duplicated E. faecalis clinical isolates from patients with UTI were retrospectively collected in a tertiary hospital in China and their clinical data was further analyzed. The linezolid and tedizolid susceptibility were determined by agar dilution. The resistance genes, including erm(A), erm(B), erm(C), tet(M), optrA, cfr, cfr(B), poxtA, and MLST-based housekeeping genes were investigated by PCR.

Results: In 115 non-duplicated E. faecalis clinical isolates from the patients with UTI in this hospital setting, the frequency of linezolid or tedizolid-resistant/intermediate isolates were 22.61 and 13.04%, respectively, and the frequency of linezolid-resistant/intermediate E. faecalis clinical isolates carrying with erm(A) were 86%. Among the five linezolid-resistant E. faecalis strains found in this study, three optrA-positive isolates and the other two linezolid-resistant strains were G2576U genetic mutations in the V domain of the 23S rRNA genes. The ST clonality analysis indicated that 31.42% (11/35) of ST16 E. faecalis UTI isolates were not susceptible to linezolid. Moreover, the univariable analysis indicated that the high risk factors of linezolid-resistant/intermediate E. faecalis infections involved the indwelling catheter, trachea cannula catheter and the carriage of erm(A) or optrA. Furthermore, the indwelling catheter and trachea cannula catheter were demonstrated as the independent predictors of linezolid-resistant/intermediate E. faecalis strains in patients with UTI by multivariable analysis.

Conclusion: Linezolid-resistant/intermediate E. faecalis associated with urinary tract infections of patients in this hospital setting from China might be explained by the high carriage frequency of optrA genes and moreover, indwelling catheter and trachea cannula should be considered as the independent predictors of linezolid-resistant/intermediate E. faecalis infections. The transmission mechanism of linezolid-resistant/intermediate E. faecalis in this hospital setting should be further studied.