bluuebunny/crossref_metadata_2025 huggingface dataset:
Folic Acid Fortification Prevents Morphological and Behavioral Consequences of X-Ray Exposure During Neurulation
Authors: Craenen Kai , Verslegers Mieke , Callaerts-Vegh Zsuzsanna , Craeghs Livine , Buset Jasmine , Govaerts Kristof , Neefs Mieke , Gsell Willy , Baatout Sarah , D'Hooge Rudi , Himmelreich Uwe , Moons Lieve , Benotmane Mohammed Abderrafi
Published: January 2021

Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.
Macrophages Respond Rapidly to Ototoxic Injury of Lateral Line Hair Cells but Are Not Required for Hair Cell Regeneration
Authors: Warchol Mark E. , Schrader Angela , Sheets Lavinia
Published: January 2021

The sensory organs of the inner ear contain resident populations of macrophages, which are recruited to sites of cellular injury. Such macrophages are known to phagocytose the debris of dying cells but the full role of macrophages in otic pathology is not understood. Lateral line neuromasts of zebrafish contain hair cells that are nearly identical to those in the inner ear, and the optical clarity of larval zebrafish permits direct imaging of cellular interactions. In this study, we used larval zebrafish to characterize the response of macrophages to ototoxic injury of lateral line hair cells. Macrophages migrated into neuromasts within 20 min of exposure to the ototoxic antibiotic neomycin. The number of macrophages in the near vicinity of injured neuromasts was similar to that observed near uninjured neuromasts, suggesting that this early inflammatory response was mediated by “local” macrophages. Upon entering injured neuromasts, macrophages actively phagocytosed hair cell debris. The injury-evoked migration of macrophages was significantly reduced by inhibition of Src-family kinases. Using chemical-genetic ablation of macrophages before the ototoxic injury, we also examined whether macrophages were essential for the initiation of hair cell regeneration. Results revealed only minor differences in hair cell recovery in macrophage-depleted vs. control fish, suggesting that macrophages are not essential for the regeneration of lateral line hair cells.
Computerized Cognitive Training by Healthy Older and Younger Adults: Age Comparisons of Overall Efficacy and Selective Effects on Cognition
Authors: Ng Nicole F. , Osman Allen M. , Kerlan Kelsey R. , Doraiswamy P. Murali , Schafer Robert J.
Published: January 2021

Among the non-pharmacological methods under development for maintaining cognitive function across the lifespan is computerized cognitive training (CCT). There has been considerable interest in using CCT to slow or remediate age-related cognitive decline, both normal and pathological. Toward these ends, it would be useful to know how the effects of CCT on cognitive function vary over the course of normal cognitive aging. Are there changes in either 1) the overall efficacy of CCT or 2) which cognitive faculties are affected? To address these two questions, we reanalyzed results from a large online study by Hardy et al. (1) of 4,715 adults between 18 and 80 that examined effects of CCT on both a neuropsychological test battery and self-reported ratings of cognition and affect in daily living. Combined across all participants, Hardy et al. found greater improvement on both types of assessment following 10 weeks of CCT with the commercial program Lumosity, as compared to practice with a control activity involving computerized crossword puzzles. The present study compared the size of these effects on the older (50–80) and younger (18–49) participants. To address the question of overall efficacy, we examined CCT effects (treatment minus control) on overall performance of the test battery and mean rating. No significant difference on either measure was found between the two age cohorts. To address the question of whether the same magnitude of overall effects on both age cohorts was due to equivalent effects on the same set of underlying cognitive functions, we examined the patterns of CCT effects across individual subtests and rated items. These patterns did not differ significantly between the two age cohorts. Our findings suggest that benefits from CCT can occur to a similar degree and in a similar way across an extended part of the adult lifespan. Moreover, the overall effects of CCT delivered over the internet were of the same small to medium size as those typically found in the lab or clinic. Besides improving access and reducing the cost of CCT for older adults, delivery over the internet makes long-term training more practicable, which could potentially yield larger benefits.
Recovery From Repeat Mild Traumatic Brain Injury in Adolescent Rats Is Dependent on Pre-injury Activity State
Authors: Ferguson Lindsay , Giza Christopher C. , Serpa Rebecka O. , Greco Tiffany , Folkerts Michael , Prins Mayumi L.
Published: January 2021

Adolescents and young adults have the highest incidence of mild traumatic brain injury (mTBI); sport-related activities are a major contributor. Roughly a third of these patients diagnosed with mTBI are estimated to have received a subsequent repeat mTBI (rTBI). Previously, animal studies have only modeled mTBI in sedentary animals. This study utilizes physical activity as a dependent variable prior to rTBI in adolescent rats by allowing voluntary exercise in males, establishing the rat athlete (rathlete). Rats were given access to locked or functional running wheels for 10 d prior to sham or rTBI injury. Following rTBI, rathletes were allowed voluntary access to running wheels beginning on different days post-injury: no run (rTBI+no run), immediate run (rTBI+Immed), or 3 day delay (rTBI+3dd). Rats were tested for motor and cognitive-behavioral (anxiety, social, memory) and mechanosensory (allodynia) dysfunction using a novel rat standardized concussion assessment tool on post-injury days 1,3,5,7, and 10. Protein expression of brain derived neurotrophic factor (BDNF) and proliferator-activated gamma coactivator 1-alpha (PGC1α) was measured in the parietal cortex, hippocampus, and gastrocnemius muscle. Sedentary shams displayed lower anxiety-like behaviors compared to rathlete shams on all testing days. BDNF and PGC1α levels increased in the parietal cortex and hippocampus with voluntary exercise. In rTBI rathletes, the rTBI+Immed group showed impaired social behavior, memory impairment in novel object recognition, and increased immobility compared to rathlete shams. All rats showed greater neuropathic mechanosensory sensitivity than previously published uninjured adults, with rTBI+3dd showing greatest sensitivity. These results demonstrate that voluntary exercise changes baseline functioning of the brain, and that among rTBI rathletes, delayed return to activity improved cognitive recovery.
Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration
Authors: McDonough Ashley , Elsen Gina E. , Daza Ray M. , Bachleda Amelia R. , Pizzo Donald , DelleTorri Olivia M. , Hevner Robert F.
Published: January 2021

Previous studies demonstrated specific expression of transcription factor Tbr2 in unipolar brush cells (UBCs) of the cerebellum during development and adulthood. To further study UBCs and the role of Tbr2 in their development we examined UBC morphology in transgenic mouse lines (reporter and lineage tracer) and also examined the effects of Tbr2 deficiency in Tbr2 (MGI: Eomes) conditional knock-out (cKO) mice. In Tbr2 reporter and lineage tracer cerebellum, UBCs exhibited more complex morphologies than previously reported including multiple dendrites, bifurcating dendrites, and up to four dendritic brushes. We propose that “dendritic brush cells” (DBCs) may be a more apt nomenclature. In Tbr2 cKO cerebellum, mature UBCs were completely absent. Migration of UBC precursors from rhombic lip to cerebellar cortex and other nuclei was impaired in Tbr2 cKO mice. Our results indicate that UBC migration and differentiation are sensitive to Tbr2 deficiency. To investigate whether UBCs develop similarly in humans as in rodents, we studied Tbr2 expression in mid-gestational human cerebellum. Remarkably, Tbr2+ UBC precursors migrate along the same pathways in humans as in rodent cerebellum and disperse to create the same “fountain-like” appearance characteristic of UBCs exiting the rhombic lip.
Defective Autophagy and Mitophagy in Aging and Alzheimer’s Disease
Authors: Tran Michael , Reddy P. Hemachandra
Published: January 2021

Aging is the time-dependent process that all living organisms go through characterized by declining physiological function due to alterations in metabolic and molecular pathways. Many decades of research have been devoted to uncovering the cellular changes and progression of aging and have revealed that not all organisms with the same chronological age exhibit the same age-related declines in physiological function. In assessing biological age, factors such as epigenetic changes, telomere length, oxidative damage, and mitochondrial dysfunction in rescue mechanisms such as autophagy all play major roles. Recent studies have focused on autophagy dysfunction in aging, particularly on mitophagy due to its major role in energy generation and reactive oxidative species generation of mitochondria. Mitophagy has been implicated in playing a role in the pathogenesis of many age-related diseases, including Alzheimer’s disease (AD), Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. The purpose of our article is to highlight the mechanisms of autophagy and mitophagy and how defects in these pathways contribute to the physiological markers of aging and AD. This article also discusses how mitochondrial dysfunction, abnormal mitochondrial dynamics, impaired biogenesis, and defective mitophagy are related to aging and AD progression. This article highlights recent studies of amyloid beta and phosphorylated tau in relation to autophagy and mitophagy in AD.
Iron- and Zinc-Fortified Lentil (Lens culinaris Medik.) Demonstrate Enhanced and Stable Iron Bioavailability After Storage
Authors: Podder Rajib , Glahn Raymond P. , Vandenberg Albert
Published: January 2021

Lentil (Lens culinaris Medik.) is a quick-cooking, rapidly expanding protein-rich crop with high iron (Fe) and zinc (Zn), but low bioavailability due to the presence of phytate, similar to other grains. Lentils dual fortified with Fe and Zn can significantly improve the bioavailable Fe and Zn content. Three milled lentil product types (LPTs) were fortified with Fe using NaFeEDTA [ethylenediaminetetraacetic acid iron (III) sodium salt] (Fe fortified) or Zn from ZnSO4·H2O (Zn fortified), or both (dual fortified). Fe, Zn, phytic acid (PA) concentration, and relative Fe bioavailability (RFeB%) were assessed for samples from two fortified batches (initial and for 1 year stored). Fe, Zn, and RFeB% increased significantly in two batches of samples from the three LPTs, and decreased by 5–15% after 1 year of storage. PA concentration decreased from 8 to 15% after fortification of all samples from two batches of the three LPTs but showed different patterns of influence after storage. Dual-fortified lentil fortified with 24 mg Fe and 12 mg Zn 100 g−1 lentil had the highest amount of Fe and Zn, and the lowest PA concentration, and RFeB% was increased from 91.3 to 519.5%. Significant (p ≤ 0.01) Pearson correlations were observed between Fe concentration vs. PA:Fe molar ratio (MR), Fe concentration vs. RFeB%, RFeB% vs. PA:Fe MR, and Zn concentration vs. PA:Zn MR in all samples from two batches of the three LPTs. In conclusion, dual-fortified lentil can contribute significant bioavailable Fe and Zn to populations at risk of Fe and Zn deficiency.
The Clinical Significance and Mechanisms of REG4 in Human Cancers
Authors: Zhang Junyan , Zhu Zhi , Miao Zhifeng , Huang Xuanzhang , Sun Zhe , Xu Huimian , Wang Zhenning
Published: January 2021

Regenerating islet-derived type 4 (REG4), a member of the calcium-dependent lectin gene superfamily, is abnormally expressed in various cancers, such as colorectal, gastric, gallbladder, pancreatic, ovarian, prostate, and lung cancer. REG4 is associated with a relatively unfavorable prognosis and clinicopathologic features in cancers, including advanced tumor and nodal stage, histological differentiation, and liver and peritoneal metastasis. Moreover, REG4-positive cancer cells show more frequent resistance to chemoradiotherapy, especially 5-FU-based chemotherapy. REG4 participates in many aspects of carcinogenesis, including cell proliferation, apoptosis, cell cycle, invasion, metastasis, and drug resistance. The underlying mechanisms are complex and involve a series of signaling mediators and multiple pathways. Thus, REG4 may be a potential diagnostic and prognostic biomarker as well as a candidate therapeutic target in cancer patients. In this review, we systematically summarize the advances about the clinical significance, biological functions, and mechanisms underlying REG4 in cancer to provide new directions for future cancer research.
Patients With Chronic Hepatitis C Virus Infection Are at an Increased Risk of Colorectal Cancer: A Nationwide Population-Based Case-Control Study in Taiwan
Authors: Su Fu-Hsiung , Bai Chyi-Huey , Le Thi Nga , Muo Chih-Hsin , Chang Shih-Ni , Te Arlene , Sung Fung-Chang , Yeh Chih-Ching
Published: January 2021

Aim

Studies evaluating colorectal cancer (CRC) risk associated with chronic hepatitis C virus (HCV) infection are limited.

Methods

In this case-control study, we identify 67,670 CRC cases newly diagnosed from 2005 to 2011 and randomly selected 67,670 controls without HCV and CRC from the same database, frequency matched by age and sex of cases.

Results

Results of logistic regression analysis revealed that the adjusted odds ratio (aOR) of CRC was 1.16 (95% confidence interval [CI] = 1.08–1.24, p < 0.001) in association with chronic HCV. The CRC risk was slightly greater for women than for men. The risk decreased with age, with the aOR decreased from 2.26 (95% CI = 1.32–3.87, p = 0.003) in patients under 45 years old to 1.31 (95% CI = 1.10–1.55, p = 0.03) in patients aged 50–59, and 1.10 (95% CI = 1.00–1.22, p = 0.061) in patients aged over 70.

Conclusions

Our findings suggested that patients with chronic HCV infection are at an elevated risk of developing CRC. Our data also imply that the CRC prevention programs are needed to target younger HCV patients.
Research Progress of Sirtuin4 in Cancer
Authors: Bai Yibing , Yang Jiani , Cui Ying , Yao Yuanfei , Wu Feng , Liu Caiqi , Fan Xiaona , Zhang Yanqiao
Published: January 2021

Sirtuins (SIRTs) are members of the silent information regulator-2 family. They are a conserved family of nicotinamide adenine dinucleotide-dependent protein lysine deacylases. SIRTS are involved in intricate cellular processes. There are seven subtypes of SIRTs (1–7) in mammals. SIRT4 is located mainly in mitochondria and has various catalytic activities. These enzyme activities give it a diverse range of important biologic functions, such as energy metabolism, oxidative stress, and aging. Cancer is characterized as reprogramming of energy metabolism and redox imbalance, and SIRT4 can affect tumorigenesis. Here, we review the structure, localization, and enzyme activity of SIRT4 and its role in various neoplasms.
Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients
Authors: Yang Yang , Ahn Jaeil , Raghunathan Rekha , Kallakury Bhaskar V. , Davidson Bruce , Kennedy Zuzana Brnakova , Zaia Joseph , Goldman Radoslav
Published: January 2021

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.
Effect of Induction Chemotherapy in Nasopharyngeal Carcinoma: An Updated Meta-Analysis
Authors: Yang Shan-Shan , Guo Jian-Gui , Liu Jia-Ni , Liu Zhi-Qiao , Chen En-Ni , Chen Chun-Yan , OuYang Pu-Yun , Han Fei , Xie Fang-Yun
Published: January 2021

Background

Previous meta-analysis had evaluated the effect of induction chemotherapy in nasopharyngeal carcinoma. But two trials with opposite findings were not included and the long-term result of another trial significantly differed from the preliminary report. This updated meta-analysis was thus warranted.

Methods

Literature search was conducted to identify randomized controlled trials focusing on the additional efficacy of induction chemotherapy in nasopharyngeal carcinoma. Trial-level pooled analysis of hazard ratio (HR) for progression free survival and overall survival and risk ratio (RR) for locoregional control rate and distant control rate were performed.

Results

Twelve trials were eligible. The addition of induction chemotherapy significantly prolonged both progression free survival (HR=0.68, 95% confidence interval [CI] 0.60–0.76, p<0.001) and overall survival (HR=0.67, 95% CI 0.54–0.80, p<0.001), with 5-year absolute benefit of 11.31% and 8.95%, respectively. Locoregional (RR=0.80, 95% CI 0.70–0.92, p=0.002) and distant control (RR=0.70, 95% CI 0.62–0.80) rates were significantly improved as well. The incidence of grade 3–4 adverse events during the concurrent chemoradiotherapy was higher in leukopenia (p=0.028), thrombocytopenia (p<0.001), and fatigue (p=0.038) in the induction chemotherapy group.

Conclusions

This meta-analysis supported that induction chemotherapy could benefit patients with nasopharyngeal carcinoma in progression free survival, overall survival, locoregional, and distant control rate.
COVID-19: High-JAKing of the Inflammatory “Flight” by Ruxolitinib to Avoid the Cytokine Storm
Authors: Botta Cirino , Indrieri Alessia , Garofalo Eugenio , Biamonte Flavia , Bruni Andrea , Pasqua Pino , Cesario Francesco , Costanzo Francesco Saverio , Longhini Federico , Mendicino Francesco
Published: January 2021

Since SARS-CoV-2 outbreak in December 2019, world health-system has been severely impacted with increased hospitalization, Intensive-Care-Unit (ICU) access and high mortality rates, mostly due to severe acute respiratory failure and multi-organ failure. Excessive and uncontrolled release of proinflammatory cytokines (cytokine release/storm syndrome, CRS) have been linked to the development of these events. The recent advancements of immunotherapy for the treatment of hematologic and solid tumors shed light on many of the molecular mechanisms underlying this phenomenon, thus rendering desirable a multidisciplinary approach to improve COVID-19 patients’ outcome. Indeed, currently available therapeutic-strategies to overcome CRS, should be urgently evaluated for their capability of reducing COVID-19 mortality. Notably, COVID-19 shares different pathogenic aspects with acute graft-versus-host-disease (aGVHD), hemophagocytic-lymphohistiocytosis (HLH), myelofibrosis, and CAR-T-associated CRS. Specifically, similarly to aGVHD, an induced tissue damage (caused by the virus) leads to increased cytokine release (TNFα and IL-6) which in turn leads to exaggerated dendritic cells, macrophages (like in HLH) and lymphocytes (as in CAR-T) activation, immune-cells migration, and tissue-damage (including late-stage fibrosis, similar to myelofibrosis). Janus Kinase (JAK) signaling represents a molecular hub linking all these events, rendering JAK-inhibitors suitable to limit deleterious effects of an overwhelming inflammatory-response. Accordingly, ruxolitinib is the only selective JAK1 and JAK2-inhibitor approved for the treatment of myelofibrosis and aGVHD. Here, we discuss, from a molecular and hematological point of view, the rationale for targeting JAK signaling in the management of COVID-19 patients and report the clinical results of a patient admitted to ICU among the firsts to be treated with ruxolitinib in Italy.
Salivary Gland Pleomorphic Adenomas Presenting With Extremely Varied Clinical Courses. A Single Institution Case-Control Study†
Authors: Piwowarczyk Krzysztof , Bartkowiak Ewelina , Kosikowski Paweł , Chou Jadzia Tin-Tsen , Wierzbicka Małgorzata
Published: January 2021

Objective

Pleomorphic adenomas (PAs) with divergent clinical behavior, differing from the vast majority of PAs, were distinguished. “Fast” PAs are characterized by an unexpectedly short medical history and relatively rapid growth. The reference group consisted of “slow” PAs with very stable biology and long-term progression. We divide the PA group as a whole into three subsets: “fast,” “normal,” and “slow” tumors. Our goal is a multifactorial analysis of the “fast” and “slow” PA subgroups.

Methods

Consecutive surgeries in a tertiary referral center, the Department of Otolaryngology and Laryngological Surgery, Poznan University of Medical Sciences, Poland, were carried out between 2002 and 2011. Out of 1,154 parotid tumors, 636 (55.1%) were PAs. The data were collected prospectively in collaboration with the Polish National Registry of Benign Salivary Gland Tumors. The main outcome measure was the recurrence rate in “fast” and “slow” PA subgroups. All surgical qualifications and surgeries were performed by two experienced surgeons.

Results

Slow PAs, compared to fast PAs, presented in older patients (53.25 ± 15.29 versus 47.92 ± 13.44 years). Multifactor logistic regression analysis with recurrence (yes/no) as the outcome variable, fast/slow as the predictor variable and age, gender, margin, FN status as covariates showed that fast PAs were significantly predicting recurrence vs. slow PAs (p = 0.035). Fast PAs were increasing the risk of PAs 10-fold vs. slow PAs, exp β = 10.20, CI95 [1.66; 197.87]. The variables impacting relapse were recent accelerated growth of the tumor OR = 3.35 (SE = 0.56), p = 0.030, positive margins OR = 7.18 (SE = 0.57), p < 0.001, incomplete or bare capsule OR = 9.91 (SE = 0.53), p = 0.001 and location III OR = 3.12 (SE = 0.53), p = 0.033. In the multivariate model only positive margin was selected as the best predictor of relapse, OR = 5.01 (SE = 0.60), p = 0.007.

Conclusions

The simple clinical aspect of slow or fast PA progression is of great practical importance and can constitute a surrogate of the final histopathological information that is derived from the surgical specimen. The slow or fast nature of the PA to some extent indicates prognostic features such as recurrence risk. This finding requires correlation with histological and molecular features in further stages of research.
The Role of Multiparametric Magnetic Resonance in Volumetric Modulated Arc Radiation Therapy Planning for Prostate Cancer Recurrence After Radical Prostatectomy: A Pilot Study
Authors: Sardaro Angela , Turi Barbara , Bardoscia Lilia , Ferrari Cristina , Rubini Giuseppe , Calabrese Angela , Ammirati Federica , Grillo Antonietta , Leo Annamaria , Lorusso Filomenamila , Santorsola Antonio , Stabile Ianora Antonio Amato , Scardapane Arnaldo
Published: January 2021

Background and Purpose

Volumetric modulated arc radiotherapy (RT) has become pivotal in the treatment of prostate cancer recurrence (RPC) to optimize dose distribution and minimize toxicity, thanks to the high-precision delineation of prostate bed contours and organs at risk (OARs) under multiparametric magnetic resonance (mpMRI) guidance. We aimed to assess the role of pre-treatment mpMRI in ensuring target volume coverage and normal tissue sparing.

Material and Methods

Patients with post-prostatectomy RPC eligible for salvage RT were prospectively recruited to this pilot study. Image registration between planning CT scan and T2w pre-treatment mpMRI was performed. Two sets of volumes were outlined, and DWI images/ADC maps were used to facilitate precise gross tumor volume (GTV) delineation on morphological MRI scans. Two rival plans (mpMRI-based or not) were drawn up.

Results

Ten patients with evidence of RPC after prostatectomy were eligible. Preliminary data showed lower mpMRI-based clinical target volumes than CT-based RT planning (p = 0.0003): median volume difference 17.5 cm3. There were no differences in the boost volume coverage nor the dose delivered to the femoral heads and penile bulb, but median rectal and bladder V70Gy was 4% less (p = 0.005 and p = 0.210, respectively) for mpMRI-based segmentation.

Conclusions

mpMRI provides high-precision target delineation and improves the accuracy of RT planning for post-prostatectomy RPC, ensures better volume coverage with better OARs sparing and allows non-homogeneous dose distribution, with an aggressive dose escalation to the GTV. Randomized phase III trials and wider datasets are needed to fully assess the role of mpMRI in optimizing therapeutic strategies.
Genome-Wide Identification and Analysis of the Methylation of lncRNAs and Prognostic Implications in the Glioma
Authors: He Yijie , Wang Lidan , Tang Jing , Han Zhijie
Published: January 2021

Glioma is characterized by rapid cell proliferation and extensive infiltration among brain tissues, but the molecular pathology has been still poorly understood. Previous studies found that DNA methylation modifications play a key role in contributing to the pathogenesis of glioma. On the other hand, long noncoding RNAs (lncRNAs) has been discovered to be associated with some key tumorigenic processes of glioma. Moreover, genomic methylation can influence expression and functions of lncRNAs, which contributes to the pathogenesis of many complex diseases. However, to date, no systematic study has been performed to detect the methylation of lncRNAs and its influences in glioma on a genome-wide scale. Here, we selected the methylation data, clinical information, expression of lncRNAs, and DNA methylation regulatory proteins of 537 glioma patients from TCGA and TANRIC databases. Then, we performed a differential analysis of lncRNA expression and methylated regions between low-grade glioma (LGG) and glioblastoma multiform (GBM) subjects, respectively. Next, we further identified and verified potential key lncRNAs contributing the pathogenesis of glioma involved in methylation modifications by an annotation and correlation analysis, respectively. In total, 18 such lncRNAs were identified, and 7 of them have been demonstrated to be functionally linked to the pathogenesis of glioma by previous studies. Finally, by the univariate Cox regression, LASSO regression, clinical correlation, and survival analysis, we found that all these 18 lncRNAs are high-risk factors for clinical prognosis of glioma. In summary, this study provided a strategy to explore the influence of lncRNA methylation on glioma, and our findings will be benefit to improve understanding of its pathogenesis.
Clinical Aspects of Neonatal Hypoglycemia: A Mini Review
Authors: Edwards Taygen , Harding Jane E.
Published: January 2021

Introduction: Neonatal hypoglycemia is common and a preventable cause of brain damage. The goal of management is to prevent or minimize brain injury. The purpose of this mini review is to summarize recent advances and current thinking around clinical aspects of transient neonatal hypoglycemia.

Results: The groups of babies at highest risk of hypoglycemia are well defined. However, the optimal frequency and duration of screening for hypoglycemia, as well as the threshold at which treatment would prevent brain injury, remains uncertain. Continuous interstitial glucose monitoring in a research setting provides useful information about glycemic control, including the duration, frequency, and severity of hypoglycemia. However, it remains unknown whether continuous monitoring is associated with clinical benefits or harms. Oral dextrose gel is increasingly being recommended as a first-line treatment for neonatal hypoglycemia. There is some evidence that even transient and clinically undetected episodes of neonatal hypoglycemia are associated with adverse sequelae, suggesting that prophylaxis should also be considered. Mild transient hypoglycemia is not associated with neurodevelopmental impairment at preschool ages, but is associated with low visual motor and executive function, and with neurodevelopmental impairment and poor literacy and mathematics achievement in later childhood.

Conclusion: Our current management of neonatal hypoglycemia lacks a reliable evidence base. Randomized trials are required to assess the effects of different prophylactic and treatment strategies, but need to be adequately powered to assess outcomes at least to school age.
Improvement of Prediction Performance With Conjoint Molecular Fingerprint in Deep Learning
Authors: Xie Liangxu , Xu Lei , Kong Ren , Chang Shan , Xu Xiaojun
Published: January 2021

The accurate predicting of physical properties and bioactivity of drug molecules in deep learning depends on how molecules are represented. Many types of molecular descriptors have been developed for quantitative structure-activity/property relationships quantitative structure-activity relationships (QSPR). However, each molecular descriptor is optimized for a specific application with encoding preference. Considering that standalone featurization methods may only cover parts of information of the chemical molecules, we proposed to build the conjoint fingerprint by combining two supplementary fingerprints. The impact of conjoint fingerprint and each standalone fingerprint on predicting performance was systematically evaluated in predicting the logarithm of the partition coefficient (logP) and binding affinity of protein-ligand by using machine learning/deep learning (ML/DL) methods, including random forest (RF), support vector regression (SVR), extreme gradient boosting (XGBoost), long short-term memory network (LSTM), and deep neural network (DNN). The results demonstrated that the conjoint fingerprint yielded improved predictive performance, even outperforming the consensus model using two standalone fingerprints among four out of five examined methods. Given that the conjoint fingerprint scheme shows easy extensibility and high applicability, we expect that the proposed conjoint scheme would create new opportunities for continuously improving predictive performance of deep learning by harnessing the complementarity of various types of fingerprints.
Acute Treatment With Fingolimod Does Not Confer Long-Term Benefit in a Mouse Model of Intracerebral Haemorrhage
Authors: Diaz Diaz Andrea C. , Shearer Jennifer A. , Malone Kyle , Waeber Christian
Published: January 2021

Intracerebral haemorrhage (ICH) has no specific treatment, but accounts for up to 15% of all strokes and has the highest mortality. Fingolimod (FTY720) is an immunomodulator approved for the management of multiple sclerosis, with abundant evidence of efficacy in experimental ischemic stroke, and more limited evidence in experimental ICH. The goal of this study was to confirm the efficacy of fingolimod in experimental ICH using rigorous and statistically well-powered studies. ICH was induced in C57BL/6JOlaHsd male and female mice by intrastriatal bacterial collagenase injection. Fingolimod (0.5 mg/kg) or saline was administered intraperitoneally after 0.5, 24 and 72 h, in a randomized and blinded manner. Functional improvement with cylinder, wire hanging, and foot fault tests was evaluated one and two weeks later. Lesion volume and hemispheric atrophy were quantified at the 14-day endpoint. There was a higher mortality in saline-treated females compared to fingolimod-treated females and saline-treated males. There was no treatment- or gender-related difference in the behavioural tests. Histological outcome measures did not differ between any of the groups. These results, contrasting with those of previous studies of fingolimod in experimental ICH, emphasize the importance of rigorous testing of this agent in models more representative of the clinical situation.
Alcohol Induced Brain and Liver Damage: Advantages of a Porcine Alcohol Use Disorder Model
Authors: Shin Soo K. , Kaiser Erin E. , West Franklin D.
Published: January 2021

Alcohol is one of the most commonly abused intoxicants with 1 in 6 adults at risk for alcohol use disorder (AUD) in the United States. As such, animal models have been extensively investigated with rodent AUD models being the most widely studied. However, inherent anatomical and physiological differences between rodents and humans pose a number of limitations in studying the complex nature of human AUD. For example, rodents differ from humans in that rodents metabolize alcohol rapidly and do not innately demonstrate voluntary alcohol consumption. Comparatively, pigs exhibit similar patterns observed in human AUD including voluntary alcohol consumption and intoxication behaviors, which are instrumental in establishing a more representative AUD model that could in turn delineate the risk factors involved in the development of this disorder. Pigs and humans also share anatomical similarities in the two major target organs of alcohol- the brain and liver. Pigs possess gyrencephalic brains with comparable cerebral white matter volumes to humans, thus enabling more representative evaluations of susceptibility and neural tissue damage in response to AUD. Furthermore, similarities in the liver result in a comparable rate of alcohol elimination as humans, thus enabling a more accurate extrapolation of dosage and intoxication level to humans. A porcine model of AUD possesses great translational potential that can significantly advance our current understanding of the complex development and continuance of AUD in humans.
Ex vivo Methods for Measuring Cardiac Muscle Mechanical Properties
Authors: Knight Walter E. , Ali Hadi R. , Nakano Stephanie J. , Wilson Cortney E. , Walker Lori A. , Woulfe Kathleen C.
Published: January 2021

Cardiovascular disease continues to be the leading cause of morbidity and mortality in the United States and thousands of manuscripts each year are aimed at elucidating mechanisms underlying cardiac disease. The methods for quantifying cardiac performance are quite varied, with each technique assessing unique features of cardiac muscle mechanical properties. Accordingly, in this review, we discuss current ex vivo methods for quantifying cardiac muscle performance, highlighting what can be learned from each method, and how each technique can be used in conjunction to complement others for a more comprehensive understanding of cardiac function. Importantly, cardiac function can be assessed at several different levels, from the whole organ down to individual protein-protein interactions. Here, we take a reductionist view of methods that are commonly used to measure the distinct aspects of cardiac mechanical function, beginning with whole heart preparations and finishing with the in vitro motility assay. While each of the techniques are individually well-documented in the literature, there is a significant need for a comparison of the techniques, delineating the mechanical parameters that can are best measured with each technique, as well as the strengths and weaknesses inherent to each method. Additionally, we will consider complementary techniques and how these methods can be used in combination to improve our understanding of cardiac mechanical function. By presenting each of these methods, with their strengths and limitations, in a single manuscript, this review will assist cardiovascular biologists in understanding the existing literature on cardiac mechanical function, as well as designing future experiments.
Predicting Temporal Gait Kinematics: Anthropometric Characteristics and Global Running Pattern Matter
Authors: Patoz Aurélien , Lussiana Thibault , Gindre Cyrille , Mourot Laurent
Published: January 2021

Equations predicting stride frequency (SF) and duty factor (DF) solely based on running speed have been proposed. However, for a given speed, kinematics vary depending on the global running pattern (GRP), i.e., the overall individual movement while running, which depends on the vertical oscillation of the head, antero-posterior motion of the elbows, vertical pelvis position at ground contact, antero-posterior foot position at ground contact, and strike pattern. Hence, we first verified the validity of the aforementioned equations while accounting for GRP. Kinematics during three 50-m runs on a track (n= 20) were used with curve fitting and linear mixed effects models. The percentage of explained variance was increased by ≥133% for DF when taking into account GRP. GRP was negatively related to DF (p= 0.004) but not to SF (p= 0.08), invalidating DF equation. Second, we assessed which parameters among anthropometric characteristics, sex, training volume, and GRP could relate to SF and DF in addition to speed, using kinematic data during five 30-s runs on a treadmill (n= 54). SF and DF linearly increased and quadratically decreased with speed (p< 0.001), respectively. However, on an individual level, SF was best described using a second-order polynomial equation. SF and DF showed a non-negligible percentage of variance explained by random effects (≥28%). Age and height were positively and negatively related to SF (p≤ 0.05), respectively, while GRP was negatively related to DF (p< 0.001), making them key parameters to estimate SF and DF, respectively, in addition to speed.
Genome-Wide Association Study Reveals Candidate Genes Involved in Fruit Trait Variation in Persian Walnut (Juglans regia L.)
Authors: Bernard Anthony , Crabier Julie , Donkpegan Armel S. L. , Marrano Annarita , Lheureux Fabrice , Dirlewanger Elisabeth
Published: January 2021

Elucidating the genetic determinants of fruit quality traits in walnut is essential to breed new cultivars meeting the producers and consumers’ needs. We conducted a genome-wide association study (GWAS) using multi-locus models in a panel of 170 accessions of Juglans regia from the INRAE walnut germplasm collection, previously genotyped using the AxiomTMJ. regia 700K SNP array. We phenotyped the panel for 25 fruit traits related to morphometrics, shape, volume, weight, ease of cracking, and nutritional composition. We found more than 60 marker-trait associations (MTAs), including a highly significant SNP associated with nut face diameter, nut volume and kernel volume on chromosome 14, and 5 additional associations were detected for walnut weight. We proposed several candidate genes involved in nut characteristics, such as a gene coding for a beta-galactosidase linked to several size-related traits and known to be involved in fruit development in other species. We also confirmed associations on chromosomes 5 and 11 with nut suture strength, recently reported by the University of California, Davis. Our results enhance knowledge of the genetic control of important agronomic traits related to fruit quality in walnut, and pave the way for the development of molecular markers for future assisted selection.
A Comprehensive in vitro and in silico Analysis of Nematicidal Action of Essential Oils
Authors: Kundu Aditi , Dutta Anirban , Mandal Abhishek , Negi Lalit , Malik Monika , Puramchatwad Rajshekhar , Antil Jyoti , Singh Anupama , Rao Uma , Saha Supradip , Kumar Rajesh , Patanjali Neeraj , Manna Suman , Kumar Anil , Dash Sukanta , Singh P. K.
Published: January 2021

Nematicidal potential of essential oils (EOs) has been widely reported. Terpenoids present in most of the essential oils have been reported responsible for their bioactivity though very less is known about their modes of action. In the present study, anin vitroscreening of nine Eos, namely,Citrus sinensis(OEO),Myrtus communis(MTEO),Eucalyptus citriodora(CEO),Melaleuca alternifolia(TEO),Acorus calamus(AEO),Commiphora myrrha(MREO),Cymbopogon nardus(CNEO),Artemisia absinthium(WEO), andPogostemon cablin(PEO) againstMeloidogyne incognitarevealed OEO, CNEO, and TEO as most effective with LC5039.37, 43.22, and 76.28 μg ml–1respectively. EOs had varying compositions of mono- and sesquiterpenes determined by gas chromatography-mass spectrometry (GC-MS) analysis. Thein silicomolecular interactions screening of major EO constituents and the seven selected target proteins of the nematode indicated highest binding affinity of geraniol-ODR1 (odorant response gene 1) complex (ΔG = -36.9 kcal mol–1), due to extensive H-bonding, hydrophobic and π-alkyl interactions. The relative binding affinity followed the order: geraniol-ODR1 > β-terpineol-ODR1 > citronellal-ODR1 >l-limonene-ODR1 > γ-terpinene-ODR1. Taken together, the cumulativein vitroand computational bioefficacy analysis related to the chemoprofiles of EOs provides useful leads on harnessing the potential of EOs as bionematicides. The insight on biochemical ligand–target protein interactions described in the present work will be helpful in logical selection of biomolecules and essential oils for development of practically viable bionematicidal products.
Resistance to ‘Candidatus Liberibacter asiaticus,’ the Huanglongbing Associated Bacterium, in Sexually and/or Graft-Compatible Citrus Relatives
Authors: Alves Mônica N. , Lopes Silvio A. , Raiol-Junior Laudecir L. , Wulff Nelson A. , Girardi Eduardo A. , Ollitrault Patrick , Peña Leandro
Published: January 2021

Huanglongbing (HLB) is the most destructive, yet incurable disease of citrus. Finding sources of genetic resistance to HLB-associated ‘CandidatusLiberibacter asiaticus’ (Las) becomes strategic to warrant crop sustainability, but no resistantCitrusgenotypes exist. SomeCitrusrelatives of the family Rutaceae, subfamily Aurantioideae, were described as full-resistant to Las, but they are phylogenetically far, thus incompatible withCitrus. Partial resistance was indicated for certain cross-compatible types. Moreover, other genotypes from subtribe Citrinae, sexually incompatible but graft-compatible withCitrus, may provide new rootstocks able to restrict bacterial titer in the canopy. Use of seedlings from monoembryonic species and inconsistencies in previous reports likely due to Las recalcitrance encouraged us to evaluate more accurately theseCitrusrelatives. We tested for Las resistance a diverse collection of graft-compatible Citrinae species using an aggressive and consistent challenge-inoculation and evaluation procedure. Most Citrinae species examined were either susceptible or partially resistant to Las. However,Eremocitrus glaucaand Papua/New GuineaMicrocitrusspecies as well as their hybrids and those withCitrusarose here for the first time as full-resistant, opening the way for using these underutilized genotypes as Las resistance sources in breeding programs or attempting using them directly as possible new Las-resistantCitrusrootstocks or interstocks.
Self-Esteem, Self-Monitoring, and Temperamental Traits in Action: Who Is Involved in Humanitarian, Political, and Religious Non-profit Organizations?
Authors: Kanafa-Chmielewska Dorota
Published: January 2021

Self-esteem, self-monitoring, and temperamental traits are important factors that influence human behavior. The purpose of the present study was to compare groups involved in humanitarian (n= 61), political (n= 68), and religious (n= 54) activities in terms of intergroup differences in self-esteem, self-monitoring, and temperamental traits. There are two research questions that we sought to address: “What are the relationships between self-esteem, self-monitoring, and temperamental traits among those involved in social, religious, and humanitarian aid activities?” and “Do temperamental traits affect self-esteem and self-monitoring among volunteers?” The study was conducted in Poland among adults aged 18 years and older, during meetings of six selected non-profit organizations, consisting of two organizations each in the humanitarian, political, and religious areas. The study used the Polish versions of the Rosenberg Self-esteem Scale, Snyders’ Self-Monitoring Scale, and the EAS Temperament Questionnaire. Volunteers of humanitarian organizations had the lowest self-esteem among all the examined groups. Politicians turned out to be more pragmatic than those involved in religious activities and humanitarian aid. Between the three examined groups, there were statistically significant differences in temperamental activity; the most active are those politically involved, followed by participants involved in humanitarian aid and religious activities. Moreover, volunteers involved in humanitarian aid reported a higher level of temperamental fear than those involved in political and religious activities. Furthermore, there were group differences in their reasons for social involvement. We discuss the potential sources of differences and consequences of outcomes for human resource practice in non-profit organizations.