bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Epidemiological Characterization of Acute Chagas Disease in Casanare, Eastern Colombia, 2012–2020
Authors: Rincón-Acevedo Claudia Yaneth , Parada-García Andrea Stella , Olivera Mario Javier , Torres-Torres Fernando , Zuleta-Dueñas Liliana Patricia , Hernández Carolina , Ramírez Juan David
Published: July 2021

Background: Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is considered a public health problem in Latin America. In Colombia, it affects more than 437,000 inhabitants, mainly in Casanare, an endemic region with eco-epidemiological characteristics that favor its transmission. The objective of this study was to describe the clinical and epidemiological characteristics of the cases of acute CD in Casanare, eastern Colombia, in the period 2012–2020.

Methods: In the present study, 103 medical records of confirmed cases of acute CD were reviewed. The departmental/national incidence and fatality were compared by year; the climatological data of mean temperature, relative humidity, and precipitation per year were reviewed and plotted at IDEAM (Colombian Meteorology Institute) concerning the number of cases of acute CD per month, and it was compared with the frequency of triatomines collected in infested houses by community surveillance. Univariate, bivariate, and multivariate analyses were performed, comparing symptoms and signs according to transmission routes, complications, and age groups.

Results: The incidence was 3.16 cases per 100,000 inhabitants, and the fatality rate was 20% in the study period. The most frequent symptoms included: fever 98.1%, myalgia 62.1%, arthralgia 60.2%, and headache 49.5%. There were significant differences in the frequency of myalgia, abdominal pain, and periorbital edema in oral transmission. The main complications were pericardial effusion, myocarditis, and heart failure in the group over 18 years of age. In Casanare, TcI Discrete Typing Unit (DTU) has mainly been identified in humans, triatomines, and reservoirs such as opossums and dogs and TcBat in bats. An increase in the number of acute CD cases was evidenced in March, a period when precipitation increases due to the beginning of the rainy season.

Conclusions: The results corroborate the symptomatic heterogeneity of the acute phase of CD, which delays treatment, triggering possible clinical complications. In endemic regions, clinical suspicion, diagnostic capacity, detection, and surveillance programs should be strengthened, including intersectoral public health policies for their prevention and control.
DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients
Authors: Campisi Manuela , Liviero Filippo , Maestrelli Piero , Guarnieri Gabriella , Pavanello Sofia
Published: July 2021

Aging is the predominant risk factor for most degenerative diseases, including chronic obstructive pulmonary disease (COPD). This process is however very heterogeneous. Defining the biological aging of individual tissues may contribute to better assess this risky process. In this study, we examined the biological age of induced sputum (IS) cells, and peripheral blood leukocytes in the same subject, and compared these to assess whether biological aging of blood leukocytes mirrors that of IS cells. Biological aging was assessed in 18 COPD patients (72.4 ± 7.7 years; 50% males). We explored mitotic and non-mitotic aging pathways, using telomere length (TL) and DNA methylation-based age prediction (DNAmAge) and age acceleration (AgeAcc) (i.e., difference between DNAmAge and chronological age). Data on demographics, life style and occupational exposure, lung function, and clinical and blood parameters were collected. DNAmAge (67.4 ± 5.80 vs. 61.6 ± 5.40 years; p = 0.0003), AgeAcc (−4.5 ± 5.02 vs. −10.8 ± 3.50 years; p = 0.0003), and TL attrition (1.05 ± 0.35 vs. 1.48 ± 0.21 T/S; p = 0.0341) are higher in IS cells than in blood leukocytes in the same patients. Blood leukocytes DNAmAge (r = 0.927245; p = 0.0026) and AgeAcc (r = 0.916445; p = 0.0037), but not TL, highly correlate with that of IS cells. Multiple regression analysis shows that both blood leukocytes DNAmAge and AgeAcc decrease (i.e., younger) in patients with FEV1% enhancement (p = 0.0254 and p = 0.0296) and combined inhaled corticosteroid (ICS) therapy (p = 0.0494 and p = 0.0553). In conclusion, new findings from our work reveal a differential aging in the context of COPD, by a direct quantitative comparison of cell aging in the airway with that in the more accessible peripheral blood leukocytes, providing additional knowledge which could offer a potential translation into the disease management.
Effect of Osmotic Stress on the Growth, Development and Pathogenicity of Setosphaeria turcica
Authors: Liu Yuwei , Gong Xiaodong , Li Moxiao , Si Helong , Zhou Qihui , Liu Xingchen , Fan Yu , Zhang Xiaoyu , Han Jianmin , Gu Shouqin , Dong Jingao
Published: July 2021

Osmotic stress is a severe condition frequently encountered by microorganisms; however, there is limited knowledge on the influence of hyperosmotic stress on the growth, development and pathogenicity of phytopathogenic fungi. Here, three osmotic conditions (0.4 M NaCl, 0.4 M KCl, and 0.6 M sorbitol supplemented in potato dextrose agar medium) were used to identify the effect of osmotic stress on the growth, development and pathogenicity of Setosphaeria turcica which is a plant pathogenic fungus and causes northern corn leaf blight disease in maize, sorghum, and related grasses. In osmotic stress, the growth rate of mycelium was decreased, and the number of vesicular structures and flocculent secretion outside the hypha cell wall were significantly increased. The qRT-PCR results showed that the osmotic stress quickly activated the HOG-MAPK pathway, up-regulated the expression of the downstream genes, and these genes were most highly expressed within 30 min of exposure to osmotic stress. Furthermore, the germination rate and the yield of conidia were significantly higher under osmotic stress than in the control. A pathogenicity analysis confirmed that pathogenicity of the conidia which were cultured under osmotic stress was significantly enhanced. By analyzing the knock-out mutants of an osmotic stress responsed gene StFPS1, an aquaglyceroporin downstream of the HOG-MAPK pathway, we found that StFPS1 was involved in the formation of appressorium and penetration peg, which affected the penetration ability of S. turcica. In summary, our work explained the correlation between osmotic stress and growth, development, and pathogenicity in S. turcica.
Structural and Genomic Insights Into Pyrazinamide Resistance in Mycobacterium tuberculosis Underlie Differences Between Ancient and Modern Lineages
Authors: Tunstall Tanushree , Phelan Jody , Eccleston Charlotte , Clark Taane G. , Furnham Nicholas
Published: July 2021

Resistance to drugs used to treat tuberculosis disease (TB) continues to remain a public health burden, with missense point mutations in the underlyingMycobacterium tuberculosisbacteria described for nearly all anti-TB drugs. The post-genomics era along with advances in computational and structural biology provide opportunities to understand the interrelationships between the genetic basis and the structural consequences ofM. tuberculosismutations linked to drug resistance. Pyrazinamide (PZA) is a crucial first line antibiotic currently used in TB treatment regimens. The mutational promiscuity exhibited by thepncA gene(target for PZA) necessitates computational approaches to investigate the genetic and structural basis for PZA resistance development. We analysed 424 missense point mutations linked to PZA resistance derived from ∼35KM. tuberculosisclinical isolates sourced globally, which comprised the four mainM. tuberculosislineages (Lineage 1–4). Mutations were annotated to reflect their association with PZA resistance. Genomic measures (minor allele frequency and odds ratio), structural features (surface area, residue depth and hydrophobicity) and biophysical effects (change in stability and ligand affinity) of point mutations on pncA protein stability and ligand affinity were assessed. Missense point mutations withinpncAwere distributed throughout the gene, with the majority (>80%) of mutations with a destabilising effect on protomer stability and on ligand affinity. Active site residues involved in PZA binding were associated with multiple point mutations highlighting mutational diversity due to selection pressures at these functionally important sites. There were weak associations between genomic measures and biophysical effect of mutations. However, mutations associated with PZA resistance showed statistically significant differences between structural features (surface area and residue depth), but not hydrophobicity score for mutational sites. Most interestinglyM. tuberculosislineage 1 (ancient lineage) exhibited a distinct protein stability profile for mutations associated with PZA resistance, compared to modern lineages.
TIM-3 and CEACAM1 are Prognostic Factors in Head and Neck Squamous Cell Carcinoma
Authors: Yang Fan , Zeng Ziqing , Li Jing , Ren Xiubao , Wei Feng
Published: July 2021

Background: T-cell Immunoglobulin and Mucin domain-containing molecule-3 (TIM-3) is a new immune checkpoint molecule which plays important and complex roles in regulating immune responses and in inducing immune tolerance. TIM-3 is expressed on activated T cells and its signaling on cytotoxic T cells leads to T cell exhaustion which is mediated by carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on tumor tissues and/or tumor infiltrating lymphocytes (TILs).

Methods: In the present study, we investigated TIM-3 and CEACAM1 immunohistochemical expression in 80 head and neck squamous cell carcinoma (HNSCC) specimens, linked to detailed outcome, clinic-pathological parameters. Here we reported scores and absolute counts of TIM-3+/CEACAM1+ TILs, and evaluated the expression of CEACAM1 on tumor tissues.

Results: The results showed that more TIM-3+ TILs infiltration correlated with poorer overall survival (p < 0.001), as did the presence of CEACAM1 on cancer cells (p < 0.001) and CEACAM1+ TILs in tumor microenvironment (p = 0.015). Multivariate Cox regression analysis revealed that high TIM-3+ TILs may be considered as an independent prognostic factor of poor disease outcome (hazard ratio, 2.066; 95% confidence interval, 1.027–4.159; p = 0.042), as well as cancer cells expressed CEACAM1 level (hazard ratio, 5.885; 95% confidence interval, 2.832–12.230; p < 0.001).

Conclusion: Our results indicate that expression of TIM-3 and CEACAM1 may represent a highly dysfunctional population of T cells. Our current findings suggest both of them were valuable predicting markers that might provide help for clinicians to design effective immunotherapeutic regimen against head and neck carcinoma.
Track-Density Ratio Mapping With Fiber Types in the Cerebral Cortex Using Diffusion-Weighted MRI
Authors: Choi Sang-Han , Jeong Gangwon , Hwang Young-Eun , Kim Yong-Bo , Lee Haigun , Cho Zang-Hee
Published: July 2021

The nerve fibers are divided into three categories: projection, commissural, and association fibers. This study demonstrated a novel cortical mapping method based on these three fiber categories using MR tractography data. The MR fiber-track data were extracted using the diffusion-weighted 3T-MRI data from 19 individuals’ Human Connectome Project dataset. Anatomical MR images in each dataset were parcellated using FreeSurfer software and Brainnetome atlas. The 5 million extracted tracks per subject by MRtrix software were classified based on the basic cortical structure (cortical area in the left and right hemisphere, subcortical area), after the tracks validation procedure. The number of terminals for each categorized track per unit-sized cortical area (1 mm3) was defined as the track-density in that cortical area. Track-density ratio mapping with fiber types was achieved by mapping the density-dependent color intensity for each categorized tracks with a different primary color. The mapping results showed a highly localized, unique density ratio map determined by fiber types. Furthermore, the quantitative group data analysis based on the parcellation information revealed that the majority of nerve fibers in the brain are association fibers, particularly in temporal, inferior parietal, and occipital lobes, while the projection and commissural fibers were mainly located in the superior part of the brain. Hemispheric asymmetries in the fiber density were also observed, such as long association fiber in the Broca’s and Wernicke’s areas. We believe this new dimensional brain mapping information allows us to further understand brain anatomy, function.
A Characterization of the Electrophysiological and Morphological Properties of Vasoactive Intestinal Peptide (VIP) Interneurons in the Medial Entorhinal Cortex (MEC)
Authors: Badrinarayanan Saishree , Manseau Frédéric , Williams Sylvain , Brandon Mark P.
Published: July 2021

Circuit interactions within the medial entorhinal cortex (MEC) translate movement into a coherent code for spatial location. Entorhinal principal cells are subject to strong lateral inhibition, suggesting that a disinhibitory mechanism may drive their activation. Cortical Vasoactive Intestinal Peptide (VIP) expressing inhibitory neurons are known to contact other interneurons and excitatory cells and are thus capable of providing a local disinhibitory mechanism, yet little is known about this cell type in the MEC. To investigate the electrophysiological and morphological properties of VIP cells in the MEC, we use in vitro whole-cell patch-clamp recordings in VIPcre/tdTom mice. We report several gradients in electrophysiological properties of VIP cells that differ across laminae and along the dorsal-ventral MEC axis. We additionally show that VIP cells have distinct morphological features across laminae. Together, these results characterize the cellular and morphological properties of VIP cells in the MEC.
Corticofugal VIP Gabaergic Projection Neurons in the Mouse Auditory and Motor Cortex
Authors: Bertero Alice , Garcia Charles , Apicella Alfonso junior
Published: July 2021

Anatomical and physiological studies have described the cortex as a six-layer structure that receives, elaborates, and sends out information exclusively as excitatory output to cortical and subcortical regions. This concept has increasingly been challenged by several anatomical and functional studies that showed that direct inhibitory cortical outputs are also a common feature of the sensory and motor cortices. Similar to their excitatory counterparts, subsets of Somatostatin- and Parvalbumin-expressing neurons have been shown to innervate distal targets like the sensory and motor striatum and the contralateral cortex. However, no evidence of long-range VIP-expressing neurons, the third major class of GABAergic cortical inhibitory neurons, has been shown in such cortical regions. Here, using anatomical anterograde and retrograde viral tracing, we tested the hypothesis that VIP-expressing neurons of the mouse auditory and motor cortices can also send long-range projections to cortical and subcortical areas. We were able to demonstrate, for the first time, that VIP-expressing neurons of the auditory cortex can reach not only the contralateral auditory cortex and the ipsilateral striatum and amygdala, as shown for Somatostatin- and Parvalbumin-expressing long-range neurons, but also the medial geniculate body and both superior and inferior colliculus. We also demonstrate that VIP-expressing neurons of the motor cortex send long-range GABAergic projections to the dorsal striatum and contralateral cortex. Because of its presence in two such disparate cortical areas, this would suggest that the long-range VIP projection is likely a general feature of the cortex’s network.
Dementia Prevalence, Comorbidities, and Lifestyle Among Jatinangor Elders
Authors: Ong Paulus Anam , Annisafitrie Febby Rosa , Purnamasari Novita , Calista Chandra , Sagita Noveline , Sofiatin Yulia , Dikot Yustiani
Published: July 2021

Introduction: Research on dementia prevalence and the potentially related risk factors from Indonesia is scarce. We sought to identify the prevalence of dementia, health risk factors, and lifestyle in Jatinangor elders.

Methods: A total of 686 participants completed questionnaires on lifestyle, health risk factors, and cognitive and functional tests from September 2013 to December 2013. We determined the prevalence of dementia; and the associations between health, leisure activities, dietary pattern, and dementia were analyzed using logistic regression.

Results: The prevalence of dementia was 29.15%. The risk factors differed between age groups. Those aged 60–74 years and who have a lower education level, lower occupational attainment, and less active intellectual and recreational activities were associated with higher dementia risk. Those aged > 75 years living in a rural area and who take less fruit were associated with a higher risk of dementia.

Conclusions: The prevalence of dementia in Jatinangor is high. The identified modifiable risk factors are a potential target for intervention and valuable for designing public health policies.
Parent and Teacher-Reported Child Outcomes Seven Years After Mild Traumatic Brain Injury: A Nested Case Control Study
Authors: Jones Kelly M. , Starkey Nicola , Barker-Collo Suzanne , Ameratunga Shanthi , Theadom Alice , Pocock Katy , Borotkanics Robert , Feigin Valery L.
Published: July 2021

Background:Increasing evidence suggests potential lifetime effects following mild traumatic brain injury (TBI) in childhood. Few studies have examined medium-term outcomes among hospitalized and non-hospitalized samples. Study aims were to describe children's behavioral and emotional adjustment, executive function (EF), quality of life, and participation at 7-years following mild TBI using parents' and teachers' reports.

Methods:Nested case control study of 86 children (68% male, mean age at assessment = 11.27 years; range 7–17 years) who sustained a mild TBI 7-years previously, identified from a prospective, population-based study. They were compared to 69 children free from TBI (61% male, mean age at assessment = 11.12 years; range 5–17 years). In addition to parent-reported socio-demographic details, parents (mild TBIn= 86, non-TBIn= 69) completed age-appropriate standardized questionnaires about children's health-related quality of life, behavioral and emotional adjustment, EF, and social participation. Parents own mood was assessed using the Hospital Anxiety and Depression Scale. Teachers (mild TBIn= 53, non-TBIn= 42) completed questionnaires about children's behavioral and emotional adjustment, and EF.

Results:Parent reports showed median group-level scores for cases were statistically significantly greater than controls for emotional symptoms, conduct problems, hyperactivity/inattention, total behavioral difficulties, inhibitory control, shifting, planning/organizing, and Global Executive Composite (total) EF difficulties (p-values 0.001–0.029). Parent reports of child quality of life and social participation were similar, as were teacher reports of child behavioral and emotional adjustment, and EF (p> 0.05). When examining clinical cut-offs, compared to controls, cases had a higher risk of parent-reported total EF difficulties (odds ratio = 3.00) and, to a lesser extent, total behavior problems (odds ratio = 2.51).

Conclusions:As a group, children with a history of mild TBI may be at elevated risk for clinically significant everyday EF difficulties in the medium-term compared to non-TBI controls, as judged by their parents. Further multi-informant longitudinal research is required, following larger samples. Aspects requiring particular attention include pre-injury characteristics, such as sleep disturbances and comorbidities (e.g., headaches), that may act as potential confounders influencing the association between mild TBI and child behavioral problems.
Multisequence Quantitative Magnetic Resonance Neurography of Brachial and Lumbosacral Plexus in Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Su Xiaoyun , Kong Xiangquan , Alwalid Osamah , Wang Jing , Zhang Huiting , Lu Zuneng , Zheng Chuansheng
Published: July 2021

Background and Purpose

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon demyelinating disorder. Although treatable, it is difficult to diagnose. The purpose of this study was to evaluate the diagnostic performance and abnormalities of plexus via quantitative multisequence magnetic resonance neurography (MRN) for CIDP.

Methods

Brachial and lumbosacral (LS) plexus of 37 CIDP patients and 37 age- and gender-matched controls were examined by using multisequence MRN. Nerve diameter, nerve-to-muscle T2 signal intensity ratio (nT2), contrast-enhanced ratio (CR), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were determined in both plexus, and tractographies were performed. The disease histories and the Inflammatory Rasch-built Overall Disability Scale (I-RODS) questionnaire scores were documented before MRI scans.

Results

The sizes of nerve roots were larger in CIDP (p < 0.01). CR, nT2, and ADC were significantly higher, while FA was lower in CIDP than in controls (p < 0.01). FA had the highest sensitivity (0.809) and area under the curve (AUC) (0.925), while the highest specificity was 0.961 for CR in single parameters. The combination of FA and CR has the highest sensitivity, specificity, accuracy, and AUC in the LS plexus. CR only had a weak correlation with nT2 (p < 0.05). ADC and diameter had a positive correlation with nT2, and the diameter and nT2 had a negative correlation with FA in CIDP (p < 0.05). FA had a negative correlation with the duration in the CIDP (r’s = −0.404, p < 0.05). There was no significant correlation between the I-RODS scores and MR multiparameters (p < 0.05).

Conclusion

Multisequence MRN possesses a high diagnostic performance in the LS plexus. Sampling perfection with application-optimized contrasts using different flip angle evolutions (SPACE) combined with DTI and contrast enhancement serves as a recommended composite protocol for CIDP.
A Novel Bacteriocin From Lactobacillus Pentosus ZFM94 and Its Antibacterial Mode of Action
Authors: Dai Mengdi , Li Yanran , Xu Luyao , Wu Danli , Zhou Qingqing , Li Ping , Gu Qing
Published: July 2021

Bacteriocins are bioactive antimicrobial peptides synthesized in the ribosome of numerous bacteria and released extracellularly. Pentocin ZFM94 produced by Lactobacillus pentosus (L. pentosus) ZFM94, isolated from infant feces with strong antibacterial activity, was purified by ammonium sulfate precipitation, dextran gel chromatography, and reverse-phase high-performance liquid chromatography (RP-HPLC). The molecular mass of the purified bacteriocin was 3,547.74 Da determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Pentocin ZFM94 exhibited broad-spectrum antimicrobial activity against tested Gram-positive and Gram-negative bacteria, and the minimal inhibitory concentrations (MICs) of Micrococcus luteus (M. luteus) 10,209, Staphylococcus aureus (S. aureus) D48, and Escherichia coli (E. coli) DH5α were 1.75, 2.00, and 2.50 μm, respectively. Pentocin ZFM94 was heat-stable (30 min at 80°C) and showed inhibitory activity over a wide pH range (5.00–7.00). It could be degraded by trypsin and pepsin, but not by amylase, lysozyme, lipase, and ribonuclease A. Fluorescence leakage assay showed that pentocin ZFM94 induced disruption of the cell membrane and caused leakage of cellular content. Furthermore, lipid II was not an antibacterial target of pentocin ZFM94. This study laid the foundation for further development and utilization of L. pentosus ZFM94 and its bacteriocin.
Analysis of Immune-Related Signatures Related to CD4+ T Cell Infiltration With Gene Co-Expression Network in Pancreatic Adenocarcinoma
Authors: Tan Zhen , Lei Yubin , Zhang Bo , Shi Si , Liu Jiang , Yu Xianjun , Xu Jin , Liang Chen
Published: July 2021

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most invasive solid malignancies. Immunotherapy and targeted therapy confirmed an existing certain curative effect in treating PDAC. The aim of this study was to develop an immune-related molecular marker to enhance the ability to predict Stages III and IV PDAC patients.

Method

In this study, weighted gene co-expression network (WGCNA) analysis and a deconvolution algorithm (CIBERSORT) that evaluated the cellular constituent of immune cells were used to evaluate PDAC expression data from the GEO (Gene Expression Omnibus) datasets, and identify modules related to CD4+ T cells. LASSO Cox regression analysis and Kaplan–Meier curve were applied to select and build prognostic multi-gene signature in TCGA Stages III and IV PDAC patients (N = 126). This was followed by independent Stages III and IV validation of the gene signature in the International Cancer Genome Consortium (ICGC, N = 62) and the Fudan University Shanghai Cancer Center (FUSCC, N = 42) cohort. Inherited germline mutations and tumor immunity exploration were applied to elucidate the molecular mechanisms in PDAC. Univariate and Multivariate Cox regression analyses were applied to verify the independent prognostic factors. Finally, a prognostic nomogram was created according to the TCGA-PDAC dataset.

Results

A four-gene signature comprising NAPSB, ZNF831, CXCL9 and PYHIN1 was established to predict overall survival of PDAC. This signature also robustly predicted survival in two independent validation cohorts. The four-gene signature could divide patients into high and low-risk groups with disparity overall survival verified by a Log-rank test. Expression of four genes positively correlated with immunosuppression activity (PD-L1 and PD1). Immune-related genes nomogram and corresponding calibration curves showed significant performance for predicting 3-year survival in TCGA-PDAC dataset.

Conclusion

We constructed a novel four-gene signature to predict the prognosis of Stages III and IV PDAC patients by applying WGCNA and CIBERSORT algorithm scoring to transcriptome data different from traditional methods of filtrating for differential genes in cancer and healthy tissues. The findings may provide reference to predict survival and was beneficial to individualized management for advanced PDAC patients.
The Relationship Between Late Morbidity and Dose–Volume Parameter of Rectum in Combined Intracavitary/Interstitial Cervix Cancer Brachytherapy: A Mono-Institutional Experience
Authors: Zhang Ning , Liu Ying , Han Dongmei , Guo Xin , Mao Zhuang , Yang Wei , Cheng Guanghui
Published: July 2021

Purpose

To establish a dose volume–effect relationship for predicting late rectal complication (LRC) in locally advanced cervical cancer patients treated with external beam radiotherapy (EBRT) followed by combined intracavitary/interstitial brachytherapy (IC/IS-BT).

Materials and Methods

A retrospective analysis was performed in 110 patients with locally advanced cervical cancer who underwent definitive radiotherapy combined with IC/IS-BT from July 2010 to September 2018. We report the 90% of the target volume receiving the minimum dose for high risk clinical target volume (HR-CTV D90) and intermediate risk clinical target volume (IR-CTV D90), and the minimum doses to the most exposed 0.1, 1, and 2 cm³ D0.1cm3,D1cm3,D2cm3 doses at the International Commission on Radiation Units and Measurements (DICRU) for organs at risk (OARs). The total dose of EBRT plus brachytherapy was transformed to the biologically equivalent dose in 2 Gy fractions (EQD2) with α/β value of 10 Gy for target, 3 Gy for organs at risk using the linear quadratic model. The morbidity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria. The Probit model was used to establish a prediction model on rectum between the organs at risk for dose and LRC. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of dose volume parameters for LRC.

Results

The median follow-up time was 72.3 months. The mean ( ± standard deviation) D2cm3,D1cm3,D0.1cm3, and DICRU values of rectum were 64.72 ± 7.47 GyEQD2, 70.18 ± 5.92 GyEQD2, 79.32 ± 7.86 GyEQD2, and 67.22 ± 7.87 GyEQD2, respectively. The Probit model showed significant relationships between D1cm3 or D0.1cm3, and the probability of grade1–4, grade 2–4 rectal events at 1 year, and between D1cm3and the probability of grade2–4 rectal events at 3 and 5 years. The dose values for 10% complication rates (ED10) of D1cm3were 74.18 (70.42–76.71) GyEQD2, 67.80 (59.91, 71.08) GyEQD2, 66.37 (52.00, 70.27) GyEQD2 for grade 2–4 with rectal morbidity at 1, 3, and 5 years, respectively.

Conclusion

Our study proved that D1cm3 andD0.1cm3were considered as useful dosimetric parameters for predicting the risk of grade1–4 and grade2–4 LRC at 1-year, and D1cm3might be an indicator for predicting grade2-4 LRC at 3/5years. The patients with rectal D1cm3>66.37–74.18 GyEQD2 should be closely observed for grade2–4 LRC.
Blood Circulating miRNA Pairs as a Robust Signature for Early Detection of Esophageal Cancer
Authors: Song Yang , Zhu Suzhu , Zhang Ning , Cheng Lixin
Published: July 2021

Esophageal cancer (EC) is a common malignant tumor in the digestive system which is often diagnosed at the middle and late stages. Noninvasive diagnosis using circulating miRNA as biomarkers enables accurate detection of early-stage EC to reduce mortality. We built a diagnostic signature consisting of four miRNA pairs for the early detection of EC using individualized Pairwise Analysis of Gene Expression (iPAGE). Profiling of miRNA expression identified 496 miRNA pairs with significant relative expression change. Four miRNA pairs consistently selected from LASSO were used to construct the final diagnostic model. The performance of the signature was validated using two independent datasets, yielding both AUCs and PRCs over 0.99. Furthermore, precision, recall, and F-score were also evaluated for clinical application, when a fixed threshold is given, resulting in all the scores are larger than 0.92 in the training set, test set, and two validation sets. Our results suggested that the 4-miRNA signature is a new biomarker for the early diagnosis of patients with EC. The clinical use of this signature would have improved the detection of EC for earlier therapy and more favorite prognosis.
Restoration of Proresolution Pathway with Exogenous Resolvin D1 Prevents Sevoflurane-Induced Cognitive Decline by Attenuating Neuroinflammation in the Hippocampus in Rats with Type 2 Diabetes Mellitus
Authors: Sun Qingmei , Yan Hongdan , Chen Falong , Jiang Fen , Chen Wenjuan , Li Dongliang , Guo Yongmin
Published: July 2021

Sevoflurane (SEV), a commonly used volatile anesthetic, has been shown to cause cognitive decline in diabetic rats by aggregating neuroinflammation in the hippocampus, but the underlying mechanisms are unknown. Recent evidence suggests that neuroinflammation could be a consequence of failure to resolve inflammation by specialized pro-resolving lipid mediators including resolvin D1 (RvD1). Here we first examined whether type 2 diabetes mellitus (DM) alters RvD1 proresolution pathway. Diabetic Goto-Kakizaki (GK) rats and non-diabetic Wistar rats received control or 2.6% SEV exposure for 4 h. Seven days after exposure, GK control rats, compared with Wistar control rats, had significantly lower RvD1 levels in plasma and CSF and decreased RvD1 receptor FPR2 expression in the hippocampus. SEV increased RvD1 levels in plasma and CSF and FPR2 expression in the hippocampus in Wistar rats but not in GK rats. We next examined whether RvD1 treatment of GK rats can prevent SEV-induced neuroinflammation and cognitive decline. GK rats received control, SEV or SEV and once-daily treatment with exogenous RvD1 (0.2 ug/kg, ip) for 7 days. RvD1 administration markedly increased RvD1 levels in plasma and CSF and FPR2 expression in the hippocampus in GK rats received SEV. Compared with GK control rats, GK rats received SEV exhibited shorter freezing times in trace fear conditioning task, which was accompanied by increased microglia activity and pro-inflammatory cytokine expression in the hippocampus. RvD1 administration attenuated SEV-induced increases in microglia activity and pro-inflammatory cytokine expression in the hippocampus, preventing cognitive decline in GK rats. Notably, neither SEV nor RvD1 altered metabolic parameters in GK rats. The results suggest that RvD1 proresolution pathway is impaired in the brain of diabetic GK rats. which may enhance the susceptibility to SEV, contributing to neuroinflammation and cognitive decline. Restoration of RvD1 proresolution pathway in diabetic GK rats with exogenous RvD1 can prevent SEV-induced cognitive decline by attenuating neuroinflammation in the hippocampus.
The Use of Genotoxicity Endpoints as Biomarkers of Low Dose Radiation Exposure in Interventional Cardiology
Authors: Habibi Martha , Karyofyllis Panagiotis K. , Nikolakopoulou Aggeliki , Papagiannis Panagiotis , Karaiskos Pantelis , Georgakilas Alexandros G. , Hatzi Vasiliki I. , Malakos Ioannis , Kollaros Nikolaos , Mastorakou Irene , Voudris Vassilis , Terzoudi Georgia I.
Published: July 2021

The effect of the reportedly low ionizing radiation doses, such as those very often delivered to patients in interventional cardiology, remains ambiguous. As interventional cardiac procedures may have a significant impact on total collective effective dose, there are radiation protection concerns for patients and physicians regarding potential late health effects. Given that very low doses (<100 mSv) are expected to be delivered during these procedures, the purpose of this study was to assess the potency and suitability of current genotoxicity biomarkers to detect and quantitate biological effects essential for risk estimation in interventional cardiology. Specifically, the biomarkers γ-H2AX foci, dicentric chromosomes, and micronuclei, which underpin radiation-induced DNA damage, were studied in blood lymphocytes of 25 adult patients before and after interventional cardiac procedures. Even though the mean values of all patients as a group for all three endpoints tested show increased yields relative to baseline following medical exposure, our results demonstrate that only the γ-H2AX biomarker enables detection of statistically significant differences at the individual level (p< 0.001) for almost all patients (91%). Furthermore, 24 h after exposure, residual γ-H2AX foci were still detectable in irradiated lymphocytes. Their decline was found to vary significantly among the individuals and the repair kinetics of γ-H2AX foci was found to range from 25 to 95.6% of their maximum values obtained.
The Relevance of Genomic Epidemiology for Control of Tuberculosis in West Africa
Authors: Asare Prince , Asante-Poku Adwoa , Osei-Wusu Stephen , Otchere Isaac Darko , Yeboah-Manu Dorothy
Published: July 2021

Tuberculosis (TB), an airborne infectious disease caused by Mycobacterium tuberculosis complex (MTBC), remains a global health problem. West Africa has a unique epidemiology of TB that is characterized by medium- to high-prevalence. Moreover, the geographical restriction of M. africanum to the sub-region makes West Africa have an extra burden to deal with a two-in-one pathogen. The region is also burdened with low case detection, late reporting, poor treatment adherence leading to development of drug resistance and relapse. Sporadic studies conducted within the subregion report higher burden of drug resistant TB (DRTB) than previously thought. The need for more sensitive and robust tools for routine surveillance as well as to understand the mechanisms of DRTB and transmission dynamics for the design of effective control tools, cannot be overemphasized. The advancement in molecular biology tools including traditional fingerprinting and next generation sequencing (NGS) technologies offer reliable tools for genomic epidemiology. Genomic epidemiology provides in-depth insight of the nature of pathogens, circulating strains and their spread as well as prompt detection of the emergence of new strains. It also offers the opportunity to monitor treatment and evaluate interventions. Furthermore, genomic epidemiology can be used to understand potential emergence and spread of drug resistant strains and resistance mechanisms allowing the design of simple but rapid tools. In this review, we will describe the local epidemiology of MTBC, highlight past and current investigations toward understanding their biology and spread as well as discuss the relevance of genomic epidemiology studies to TB control in West Africa.
Backreaction in Cosmology
Authors: Schander S. , Thiemann T.
Published: July 2021

In this review, we investigate the question of backreaction in different approaches to cosmological perturbation theory, and with a special focus on quantum theoretical aspects. By backreaction we refer here to the effects of matter field or cosmological inhomogeneities on the homogeneous dynamical background degrees of freedom of cosmology. We begin with an overview of classical cosmological backreaction which is ideally suited for physical situations in the late time Universe. We then proceed backwards in time, considering semiclassical approaches such as semiclassical or stochastic (semiclassical) gravity which take quantum effects of the perturbations into account. Finally, we review approaches to backreaction in quantum cosmology that should apply to the very early Universe where classical and semiclassical approximations break down. The main focus is on a recently proposed implementation of backreaction in quantum cosmology using a Born–Oppenheimer inspired method.
Isolation of Endophytic Salt-Tolerant Plant Growth-Promoting Rhizobacteria From Oryza sativa and Evaluation of Their Plant Growth-Promoting Traits Under Salinity Stress Condition
Authors: Jhuma Tania Akter , Rafeya Jannatul , Sultana Shahnaz , Rahman Mohammad Tariqur , Karim Muhammad Manjurul
Published: July 2021

The application of plant growth-promoting rhizobacteria (PGPR) as vital components for plant growth promotion against biotic and abiotic stresses could be a promising strategy to improve crop production in areas vulnerable to increasing salinity. Here, we isolated Seventy-five endophytic bacteria from roots of healthy Oryza sativa grown in a saline environment of the southern coastal region of Bangladesh. The endophytes in a culture of ~108 CFU/ml showed arrays of plant growth-promoting (PGP) activities: phytohormone (Indole acetic acid) production (1.20–60.13 μg/ ml), nutrient (phosphate) solubilization (0.02–1.81 μg/ml) and nitrogen fixation (70.24–198.70 μg/ml). Four genomically diverse groups were identified namely, Enterobacter, Achromobacter, Bacillus, and Stenotrophomonas using amplified ribosomal DNA restriction analysis followed by their respective 16S rDNA sequence analyses with that of the data available in NCBI GenBank. These four specific isolates showed tolerance to NaCl ranging from 1.37 to 2.57 mol/L in the nutrient agar medium. Under a 200 mmol/L salt stress in vitro, the bacteria in a culture of 108 CFU/ml exhibited competitive exopolysaccharide (EPS) production: Stenotrophomonas (65 μg/ml) and Bacillus (28 μg/ml), when compared to the positive control, Pseudomonas spp. (23.65 μg/ml), a phenomenon ably supported by their strong biofilm-producing abilities both in a microtiter plate assay, and in soil condition; and demonstrated by images of the scanning electron microscope (SEM). Overall, the isolated endophytic microorganisms revealed potential PGP activities that could be supported by their biofilm-forming ability under salinity stress, thereby building up a sustainable solution for ensuring food security in coastal agriculture under changing climate conditions.
Applications of Machine Learning for the Classification of Porcine Reproductive and Respiratory Syndrome Virus Sublineages Using Amino Acid Scores of ORF5 Gene
Authors: Kim Jeonghoon , Lee Kyuyoung , Rupasinghe Ruwini , Rezaei Shahbaz , Martínez-López Beatriz , Liu Xin
Published: July 2021

Porcine reproductive and respiratory syndrome is an infectious disease of pigs caused by PRRS virus (PRRSV). A modified live-attenuated vaccine has been widely used to control the spread of PRRSV and the classification of field strains is a key for a successful control and prevention. Restriction fragment length polymorphism targeting the Open reading frame 5 (ORF5) genes is widely used to classify PRRSV strains but showed unstable accuracy. Phylogenetic analysis is a powerful tool for PRRSV classification with consistent accuracy but it demands large computational power as the number of sequences gets increased. Our study aimed to apply four machine learning (ML) algorithms, random forest, k-nearest neighbor, support vector machine and multilayer perceptron, to classify field PRRSV strains into four clades using amino acid scores based on ORF5 gene sequence. Our study used amino acid sequences of ORF5 gene in 1931 field PRRSV strains collected in the US from 2012 to 2020. Phylogenetic analysis was used to labels field PRRSV strains into one of four clades: Lineage 5 or three clades in Linage 1. We measured accuracy and time consumption of classification using four ML approaches by different size of gene sequences. We found that all four ML algorithms classify a large number of field strains in a very short time (<2.5 s) with very high accuracy (>0.99 Area under curve of the Receiver of operating characteristics curve). Furthermore, the random forest approach detects a total of 4 key amino acid positions for the classification of field PRRSV strains into four clades. Our finding will provide an insightful idea to develop a rapid and accurate classification model using genetic information, which also enables us to handle large genome datasets in real time or semi-real time for data-driven decision-making and more timely surveillance.
Copper/Carbon Core/Shell Nanoparticles: A Potential Material to Control the Fish Pathogen Saprolegnia parasitica
Authors: Zhang Jv , Chen Juncai , Huang Qianjun , MacKinnon Brett , Nekouei Omid , Liu Hong , Jia Peng , Wang Jinjin , Li Na , Huang Liqing , Yang Ying , Ng Pok , St-Hilaire Sophie
Published: July 2021

Copper-based fungicides have a long history of usage in agriculture and aquaculture. With the rapid development of metal-based nanoparticles, copper-based nanoparticles have attracted attention as a potential material for prevention and control ofSaprolegnia parasitica. The present study investigated the effectiveness of copper/carbon core/shell nanoparticles (CCCSNs) and a commercial CCCSNs filter product (COPPERWARE®) againstS. parasiticain a recirculating system. Results showed that the growth of agar plugs with mycelium was significantly suppressed after exposure to both CCCSNs powder and COPPERWARE®filters. Even the lowest concentration of CCCSNs used in our study (i.e., 100 mg/mL) exhibited significant inhibitory effects onS. parasitica. The smallest quantity of the filter product COPPERWARE®(3.75 × 3.7 × 1.2 cm, 2.58 g) used in our aquarium study also demonstrated significant inhibition compared with the control group. However, we observed leaching of copper into the water especially when larger quantities of COPPERWARE®were used. Water turbidity issues were also observed in tanks with the filter material. Besides these issues, which should be further investigated if the product is to be used on aquatic species sensitive to copper, CCCSNs has promising potential for water disinfection.
Constrained Eigenvalue Minimization of Incomplete Pairwise Comparison Matrices by Nelder-Mead Algorithm
Authors: Tekile Hailemariam Abebe , Fedrizzi Michele , Brunelli Matteo
Published: July 2021

Pairwise comparison matrices play a prominent role in multiple-criteria decision-making, particularly in the analytic hierarchy process (AHP). Another form of preference modeling, called an incomplete pairwise comparison matrix, is considered when one or more elements are missing. In this paper, an algorithm is proposed for the optimal completion of an incomplete matrix. Our intention is to numerically minimize a maximum eigenvalue function, which is difficult to write explicitly in terms of variables, subject to interval constraints. Numerical simulations are carried out in order to examine the performance of the algorithm. The results of our simulations show that the proposed algorithm has the ability to solve the minimization of the constrained eigenvalue problem. We provided illustrative examples to show the simplex procedures obtained by the proposed algorithm, and how well it fills in the given incomplete matrices.
Mortality of Dairy Sheep during the Peri-Parturient Period: Results of a Field Investigation in Greece
Authors: Politis Antonis P. , Vasileiou Natalia G. C. , Cripps Peter J. , Liagka Dimitra V. , Boufis Petros T. , Valasi Irene , Mavrogianni Vasia S. , Fthenakis George C.
Published: July 2021

Objectives of the study were (a) to investigate the incidence risk of peri-parturient mortality in dairy flocks in Greece, (b) to study when such mortality occurs in relation to lambing, (c) to identify clinical problems associated with the deaths, and (d) to evaluate potentially associated factors. The deaths of ewes during the peri-parturient period (10 days before to 7 days after lambing) were monitored in 60 flocks over two years. In the ewes that died, detailed post-mortems were performed. The incidence risk of peri-parturient deaths was 0.7%. The daily incidence rate of deaths before, at, and after lambing was 0.05, 0.04, and 0.03%, respectively. Clinical problems most frequently associated with peri-parturient deaths were pregnancy toxaemia, ruminal acidosis and post-partum genital problems. For the occurrence of peri-parturient deaths in flocks, the average lambing rate in the flocks was the only significant factor. Regarding deaths before or after lambing, the season during which lambing took place and the number of animals in the flock, respectively, were found to be significant. Most ewes (54.5%) that died at lambing (dystocia) were primigravidae.
Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases
Authors: Tsai Kai-Fan , Chen Yung-Lung , Chiou Terry Ting-Yu , Chu Tian-Huei , Li Lung-Chih , Ng Hwee-Yeong , Lee Wen-Chin , Lee Chien-Te
Published: July 2021

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral glucose-lowering agents. Apart from their glucose-lowering effects, large clinical trials assessing certain SGLT2 inhibitors have revealed cardiac and renal protective effects in non-diabetic patients. These excellent outcomes motivated scientists and clinical professionals to revisit their underlying mechanisms. In addition to the heart and kidney, redox homeostasis is crucial in several human diseases, including liver diseases, neural disorders, and cancers, with accumulating preclinical studies demonstrating the therapeutic benefits of SGLT2 inhibitors. In the present review, we aimed to update recent advances in the antioxidant roles of SGLT2 inhibitors in common but debilitating human diseases. We anticipate that this review will guide new research directions and novel therapeutic strategies for diabetes, cardiovascular diseases, nephropathies, liver diseases, neural disorders, and cancers in the era of SGLT2 inhibitors.