bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoantigens and genome instability: impact on immunogenomic phenotypes and immunotherapy response
Authors: Mardis Elaine R. 
Published: November 2019

AbstractThe resurgence of immune therapies in cancer medicine has elicited a corresponding interest in understanding the basis of patient response or resistance to these treatments. One aspect of patient response clearly lies in the genomic alterations that are associated with cancer onset and progression, including those that contribute to genomic instability and the resulting creation of novel peptide sequences that may present as neoantigens. The immune reaction to these unique ‘non-self’ peptides is frequently suppressed by the tumor itself, but the use of checkpoint blockade therapies, personalized vaccines, or a combination of these treatments may elicit a tumor-specific immune response that results in cell death. Massively parallel sequencing, coupled with different computational analyses, provides unbiased identification of the germline and somatic alterations that drive cancer development, and of those alterations that lead to neoantigens. These range from simple point mutations that change single amino acids to complex alterations, such as frameshift insertion or deletion mutations, splice-site alterations that lead to exon skipping, structural alterations that lead to the formation of fusion proteins, and other forms of collateral damage caused by genome instability that result in new protein sequences unique to the cancer. The various genome instability phenotypes can be identified as alterations that impact DNA replication or mismatch repair pathways or by their genomic signatures. This review provides an overview of current knowledge regarding the fundamentals of genome replication and of both germline and somatic alterations that disrupt normal replication, leading to various forms of genomic instability in cancers, to the resulting generation of neoantigens and, ultimately, to immune-responsive and resistant phenotypes.
Hepatic and portal vein Dopplers in the clinical management of patients with right-sided heart failure: two case reports
Authors: Jefkins Matthew , Chan Barry 
Published: November 2019

Abstract

Background
Patients with right heart failure pose significant volume management challenges for hemodynamic optimization. We present two cases in which point of care ultrasound (POCUS) of the hepatic and portal veins contributed to the venous hypertension assessment and decongestive strategy for patients with right-sided heart failure.

Case presentation
Patient A was 91 years old with known pulmonary hypertension and right ventricular systolic dysfunction who presented in septic shock requiring vasopressor support. Hepatic and portal vein Dopplers were consistent with right heart failure and significant venous congestion, therefore, diuresis was initiated which resulted in portal flow normalization, renal recovery, and cessation of vasopressor support. Patient B was 82 years old with severe idiopathic pulmonary fibrosis on home oxygen who presented in decompensated right heart failure. Despite aggressive diuresis, a negative fluid balance was not achieved. The patient continued to deteriorate and prior to their death portal vein, Doppler showed significant flow reversal.

Conclusion
Hepatic and portal vein Doppler ultrasounds are venous hypertension assessment tools that can be readily used at the bedside by clinicians trained in POCUS that may contribute holistically to the hemodynamic profiling for patients with right heart failure and direct therapeutic interventions.
Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway
Authors: Liang Bo , Liang Jia-Ming , Ding Jia-Ning , Xu Jia , Xu Jian-Guang , Chai Yi-Min 
Published: November 2019

Abstract
Background
Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved.

Methods
To investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization.

Results
DMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo.

Conclusions
Low doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.
Extracellular vesicles derived from human Wharton’s jelly mesenchymal stem cells protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers
Authors: Bodart-Santos Victor , de Carvalho Luiza R. P. , de Godoy Mariana A. , Batista André F. , Saraiva Leonardo M. , Lima Luize G. , Abreu Carla Andreia , De Felice Fernanda G. , Galina Antonio , Mendez-Otero Rosalia , Ferreira Sergio T. 
Published: November 2019

AbstractBackgroundMesenchymal stem cells (MSCs) have been explored as promising tools for treatment of several neurological and neurodegenerative diseases. MSCs release abundant extracellular vesicles (EVs) containing a variety of biomolecules, including mRNAs, miRNAs, and proteins. We hypothesized that EVs derived from human Wharton’s jelly would act as mediators of the communication between hMSCs and neurons and could protect hippocampal neurons from damage induced by Alzheimer’s disease-linked amyloid beta oligomers (AβOs).MethodsWe isolated and characterized EVs released by human Wharton’s jelly mesenchymal stem cells (hMSC-EVs). The neuroprotective action of hMSC-EVs was investigated in primary hippocampal cultures exposed to AβOs.ResultshMSC-EVs were internalized by hippocampal cells in culture, and this was enhanced in the presence of AβOs in the medium. hMSC-EVs protected hippocampal neurons from oxidative stress and synapse damage induced by AβOs. Neuroprotection by hMSC-EVs was mediated by catalase and was abolished in the presence of the catalase inhibitor, aminotriazole.ConclusionshMSC-EVs protected hippocampal neurons from damage induced by AβOs, and this was related to the transfer of enzymatically active catalase contained in EVs. Results suggest that hMSC-EVs should be further explored as a cell-free therapeutic approach to prevent neuronal damage in Alzheimer’s disease.
Autofluorescence of NADH is a new biomarker for sorting and characterizing cancer stem cells in human glioma
Authors: Yuan Ye , Yan Zexuan , Miao Jingya , Cai Ruili , Zhang Mengsi , Wang Yanxia , Wang Lihong , Dang Weiqi , Wang Di , Xiang Dongfang , Wang Yan , Zhang Peng , Cui Youhong , Bian Xiuwu , Ma Qinghua 
Published: November 2019

AbstractBackgroundThe existing cell surface markers used for sorting glioma stem cells (GSCs) have obvious limitations, such as vulnerability to the enzymatic digestion and time-consuming labeling procedure. Reduced nicotinamide adenine dinucleotide (NADH) as a cellular metabolite with property of autofluorescence has the potential to be used as a new biomarker for sorting GSCs.MethodsA method for sorting GSCs was established according to the properties of the autofluorescence of NADH. Then, the NADHhighand NADHlowsubpopulations were sorted. The stem-like properties of the subpopulations were evaluated by qRT-PCR, western blot analyses, limiting dilution assay, cell viability assay, bioluminescence imaging, and immunofluorescence analysis in vitro and in vivo. The relationship between CD133+/CD15+cells and NADHhighsubpopulation was also assessed.ResultsNADHhighcells expressed higher stem-related genes, formed more tumor spheres, and harbored stronger pluripotency in vitro and higher tumorigenicity in vivo, compared to NADHlowsubpopulation. NADHhighglioma cells had the similar stemness with CD133+or CD15+GSCs, but the three subpopulations less overlaid each other. Also, NADHhighglioma cells were more invasive and more resistant to chemotherapeutic drug temozolomide (TMZ) than NADHlowcells. In addition, the autofluorescence of NADH might be an appropriate marker to sort cancer stem cells (CSCs) in other cancer types, such as breast and colon cancer.ConclusionOur findings demonstrate that intracellular autofluorescence of NADH is a non-labeling, sensitive maker for isolating GSCs, even for other CSCs.
Heart to spine measurements to detect left atrial enlargement in dogs with mitral insufficiency
Authors: Sánchez Salguero Xavier , Prandi David , Llabrés-Díaz Francisco , Manzanilla Edgar G. , Badiella Llorenç , Bussadori Claudio 
Published: November 2019

Abstract
Background
Radiography is useful to determine left atrial (LA) size when echocardiography is not available. Recently, the authors have described Radiographic Left Atrial Dimension (RLAD) as a new radiographic measurement to assess LA size. The objective of this study was to assess the clinical usefulness of 2 new radiographic measurements to detect and quantify left atrial enlargement (LAE) compared to RLAD and using left atrium to aortic root (LA/Ao) ratio as gold standard. These new measurements, bronchus-to-spine (Br-Spine) and RLAD-to-spine (RLAD-Spine) may be more precise in cases were LA boundaries are not well defined. Fifty dogs, 25 with and 25 without LAE were recruited. Reference LA/Ao ratio was assessed by 2D echocardiography and LAE was considered if LA/Ao > 1.6. Br-spine was measured as a straight vertical line from the main stem bronchus to the ventral border of the vertebra situated immediately dorsal to the heart base. RLAD-Spine was measured from RLAD endpoint perpendicularly to spine. The correlation of RLAD, Br-Spine and RLAD-Spine methods with LA/Ao and their sensitivity and specificity for detecting LAE were calculated. Receiver Operating Characteristic (ROC) curves were used to estimate the optimal cut-off for each method.

Results
Correlations between Br-Spine, RLAD-Spine, RLAD and LA/Ao ratio were − 0.66, − 0.76 and 0.89 respectively (P < 0.001). Sensitivity at the optimal cut-off values for detecting LAE were 32.0, 64.0 and 96.0%, respectively. Specificity was 96.0% in all cases.

Conclusion
Br-Spine and RLAD-Spine were less sensitive radiographic measurements than RLAD in detecting LAE in dogs. Both Br-Spine and RLAD-Spine may not be good alternatives to RLAD.
The anti-virulence effect of cranberry active compound proanthocyanins (PACs) on expression of genes in the third-generation cephalosporin-resistant Escherichia coli CTX-M-15 associated with urinary tract infection
Authors: Samarasinghe Shivanthi , Reid Ruth , AL-Bayati Majid 
Published: November 2019

Abstract
Background
Urinary tract infections (UTIs) are one of the most common infections found in humans, with uropathogenic Escherichia coli (UPEC) being the most common cause. Prevention of UTI is a major global concern due to its recurrent nature, medical cost, and most importantly, the increased antimicrobial resistance among UPEC. The resistance in UPEC is mainly due to the Extended-Spectrum β-lactamases (ESBL), particularly the E. coli CTXM-15 type which is known for its rapid dissemination worldwide. Treatment options for E. coli CTXM-15 have become limited over recent years because of their multi-drug resistance, hence anti-virulent strategies based on herbal remedies, have considered as a viable option. The cranberry product, Cysticlean® capsules, contain 240 mg of proanthocyanins (PACs), which have been shown to significantly inhibit E. coli adherence, both in vitro and ex vivo, to uroepithelial cells.

Method
In this study, the cephalosporin-resistant E. coli isolate NCTC 1553 (E. coli CTXM-15) was analysed by qRT-PCR (quantitative Reverse Transcriptase -Polymerase Chain Reaction) for the expression of virulence factors after treatment with Cysticlean®. qRT-PCR was carried out to detect virulence determinants encoding for toxins SAT, and USP, the iron acquisition system ChuA, the protectins SoxS, KPSM, TraT and RecA, the antibiotic resistance gene CTX-M (encode β-lactamases), and the transporters IdfB and HcaT.

Results
Cysticlean® significantly reduced the expression of all ten selected genes encoding for virulence factors and β-lactamases.

Conclusion
Cranberry product Cysticlean® could represent a practicable alternative option for the prevention of recurrent UTI caused by multi-drug resistant E. coli CTXM-15, as the product acts on multiple bacterial targets.
Effect of straw incorporation on methane emission in rice paddy: conversion factor and smart straw management
Authors: Song Hyeon Ji , Lee Jin Ho , Jeong Hyun-Cheol , Choi Eun-Jung , Oh Taek-Keun , Hong Chang-Oh , Kim Pil Joo 
Published: November 2019

AbstractStraw incorporation is strongly recommended in rice paddy to improve soil quality and mitigate atmospheric carbon dioxide (CO2), via increasing soil organic carbon (SOC) stock. However, straw application significantly increased methane (CH4) emission during rice cultivation, and then its incorporation area was not expanded effectively. To find the reasonable straw management practice which can reduce CH4 emission without productivity damage, the effect of straw incorporation season and method on CH4 emission was investigated at six different textured paddy fields in South Korea for 2 years. A straw was applied right after rice harvesting in autumn, and the other right before rice transplanting in spring. In the autumn application, straw was applied with two different methods: spreading over soil surface or mixing with soil. Straw application significantly increased seasonal CH4 flux by average 28–122% over 197–590 kg CH4 ha−1 of the no-straw, but its flux showed big difference among straw applications. Fresh straw application before transplanting increased seasonal CH4 flux by approximately 120% over the no-straw, but the autumn application reduced its CH4 flux by 24–43% over 509–1407 kg CH4 ha−1 of the spring application. In particular, the seasonal CH4 flux was approximately 24% lower in straw mixing with soil after autumn harvesting than 423–855 kg CH4 ha−1 in straw spreading over surface. However, CH4 fluxes were not significantly discriminated by soil and meteorological properties in the selected condition. Straw application slightly increased rice grain yield by approximately 4% over the no-straw, but rice productivity was not statistically different among straw applications. Spring straw application increased CH4 intensity which means seasonal CH4 flux per grain yield by the maximum 220% over the no-straw. Autumn straw application significantly decreased CH4 intensity by average 24–65% over the spring straw application. In particular, CH4 intensity in straw mixing with soil treatment was not statistically different with the no-straw. Therefore, autumn straw application with mixing inner soil could be a reasonable straw management practice to decrease CH4 emission impact with improving soil productivity.
Performance of an adapted household food insecurity access scale in measuring seasonality in household food insecurity in rural Ethiopia: a cohort analysis
Authors: Kabalo Bereket Yohannes , Gebreyesus Seifu Hagos , Loha Eskindir , Lindtjørn Bernt 
Published: November 2019

Abstract
Background
Seasonality poses a considerable food security challenge in Ethiopia. Yet, measuring seasonal variations in food insecurity, particularly the dimension of food access, lacks an adequately validated tool. We therefore evaluated the performance of an adapted Household Food Insecurity Access Scale (HFIAS) to estimate seasonal variations in food insecurity (FI) among subsistence villagers in Ethiopia.

Methods
We employed a cohort study design using a panel of four repeated measurements taken in June, September, and December in the year 2017, and in March 2018. The study recruited 473 villagers from the drought-affected Wolaita area in southwest Ethiopia. The performance of the HFIAS was evaluated via internal consistency (Chronbach’s alpha values) and criterion validation techniques. The set of criteria include: parallelism between affirmative responses to FI questions and wealth strata; dose-response relationship between FI and dietary intake; and also FI severity and household wealth status.

Results
This study revealed that the HFIAS had satisfactory performance in four repeated measurements. The likelihood of affirmative responses to questions about FI decreased with ascending wealth quintiles. We observed an inverse dose-response relationship between FI and wealth status, and between FI and household dietary diversity.

Conclusions
The HFIAS showed an acceptable potential for measuring seasonal variations in FI in the study area. Our findings complement efforts to evaluate the scale’s applicability in various settings, in order to promote cross-culture monitoring and comparisons. However, it required a careful adaption for contextual and cultural sensitivities.
STEM materials: a new frontier for an intelligent sustainable world
Authors: Moretti Pier F. , Grzybowski Bartosz A. , Basios Vasileios , Fortunato Elvira , Suarez Diez Maria , Speck Olga , Martins Rodrigo 
Published: November 2019

AbstractMaterials are addressed as possible enablers for solutions to many global societal challenges. A foresight exercise has been conducted to identify research paths to design, with a new approach, a generation of materials which can provide multi-functionalities. These material systems have been named “stem”, in analogy to living cells where a base of primitive units can be designed and assembled for self-reacting to external inputs. These materials will embed a concept of “internet in things”, where their processing capacity will enable the systems to interact with the environment and express diverse functionalities. Stem materials do not exist yet, but many clues from different theoretical and experimental results suggest they can be developed, and because living organisms exist. This article aims at launching this new approach and promoting the structuring of a multi-disciplinary community to fill the research gaps.
Prevalence and correlates of psychiatric morbidity in Egyptian sample of dementia patients’ caregivers: a comparative descriptive study
Authors: El Razek Yasser Abd , Sabry Walaa , Hendawy Heba , Hegazy Dalia , Soultan Marwa , El Banna Mohamed 
Published: November 2019

Abstract
Background
A strong relationship between dementia caregiving and negative consequences on psychological health of caregivers has been established in numerous studies. A meticulous evaluation of caregiver mental status function is of utmost importance to gain better insight into daily caregiver functioning and to alleviate their high levels of burden. This study evaluated the prevalence of psychiatric morbidities and their sociodemographic and clinical correlates among a sample of dementia caregivers in Egypt. Twenty-five caregivers of patients with dementia were collected and compared with regard to their psychiatric morbidity with 25 careers of patients with chronic physical diseases. Patients were subjected to Mini-Mental State Examination (MMSE) and Arabic versions of activities of daily living (ADL) and instrumental activities of daily living (IADL), and caregivers were interviewed using the Arabic version of the General Health Questionnaire (GHQ), Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and Zarit Burden Interview (ZBI).

Results
Caregiver’s burden was significantly higher among the dementia caregiver group than the non-dementia group. Moreover, dementia caregivers provided more aid with a higher total of ADLs and provided help for more IADLs than did the non-dementia caregivers. They also showed higher psychiatric morbidity. Such morbidity was found to be related to hours of caring, years of caring, GHQ, ZBI, ADL/IADL, BPSD, and MMSE. On the other hand, ADL, IADL, and GHQ scores had the highest predictive significance of caregiver’s burden in our study.

Conclusions
Caregivers of patients with dementia are subjected to more burden and vulnerability to psychiatric disorders than the other caregiver group. That should raise a flag to pay extra support and care for those people, which in turn will benefit both the patient and the health care authorities in terms of quality and cost of the care provided.
Correlation Between Telomere Attrition of Zona Fasciculata and Adrenal Weight Reduction in Older Men
Authors: Nonaka Keisuke , Aida Junko , Takubo Kaiyo , Yamazaki Yuto , Gao Xin , Komatsu Akiko , Takakuma Shoichiro , Kakizaki Mototsune , Inoshita Naoko , Gomi Fujiya , Ishiwata Toshiyuki , Chong Ja-Mun , Arai Tomio , Sasano Hironobu 
Published: November 2019

Abstract

Context
Although numerous theories are reported on sex differences in longevity, the underlying biological mechanisms remain unknown. We previously reported that telomere length in the zona reticularis cells of the human adrenal cortex was significantly longer in older than that in younger subjects. However, we could not evaluate sex differences in the telomere lengths.

Objective
To compare the telomere lengths of adrenocortical and adrenal medullar cells between men and women from infancy through older adulthood.

Methods
Adrenal glands of 30 male (aged 0 to 100 years) and 25 female (aged 0 to 104 years) autopsied subjects were retrieved from autopsy files. Using quantitative fluorescence in situ hybridization, relative telomere lengths were determined in the parenchymal cells of the 3 adrenocortical zones and medulla. Age-related changes in the weight of adrenal glands were also investigated.

Main results
Older male subjects (aged 65 years or older) had significantly shorter telomere lengths in zona fasciculata (ZF) cells compared to the corresponding female subjects. In men, older subjects exhibited a significant age-related reduction in adrenal weight; however, no age-related changes in adrenal weight were detected in women.

Conclusion
Telomere attrition of ZF cells was correlated with adrenal weight reduction in older men but not in older women, suggesting a decreased number of ZF cells in older men. This may help us understand the possible biological mechanisms of sex difference in longevity of humans.