bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model
Authors: Duan Yuanqin , Chen Zhiwei , Li Hu , Shen Wei , Zeng Yi , Peng Mingli , Hu Peng
Published: November 2021

Accumulating evidence suggests that tenofovir disoproxil fumarate (TDF) can attenuate liver fibrosis directly, the mechanism of which, however, has not been fully elucidated, and there is a paucity of data concerning whether TDF can also mitigate other chronic liver diseases (CLDs). We aimed to identify the molecular targets and potential mechanism of TDF itself in ameliorating CLDs. RNA-sequencing was performed on mouse liver tissues treated with TDF or normal saline. Then the differentially expressed genes (DEGs) were screened, and enrichment analyses of the function and signaling pathways of DEGs were performed with Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape. Next, protein-protein interaction (PPI) networks were constructed and module analyses were utilized to identify significant genes. Subsequently, the DisGeNET platform was used to identify the potential target genes of TDF in mitigating these diseases. Finally, prediction of the transcription factors (TFs) and microRNAs (miRNAs) of the target genes was done to conjecture the underlying mechanism by which TDF relieved CLDs. As a result, a total of 854 DEGs were identified, and the DEGs were involved mainly in “immunity,” “inflammation,” and “metabolism” processes. In addition, 50 significant genes were obtained via PPI construction and module analyses. Furthermore, by means of DisGeNET, 19 genes (Adra2a, Cxcl1, Itgam, Cxcl2, Ccr1, Ccl5, Cxcl5, Fabp5, Sell, Lilr4b, Ccr2, Tlr2, Lilrb4a, Tnf, Itgb2, Lgals3, Cxcr4, Sucnr1, and Mme) were identified to be associated with nine CLDs. Finally, 34 miRNAs (especially mmu-miR-155-5p) and 12 TFs (especially Nfkb1) were predicted to be upstream of the nine target genes (Cxcl1, Cxcl2, Ccl5, Ccr2, Sell, Tlr2, Tnf, Cxcr4, and Mme) of TDF in ameliorating CLDs. In conclusion, our study suggests that TDF have the potential to ameliorate CLDs independently of its antiviral activity by affecting the expression of genes involved in hepatic immune, inflammatory, and metabolic processes via mmu-miR-155-5p-NF-κB signaling. These findings provided prima facie evidence for using TDF in CHB patients with concurrent CLDs.
Noninvasive Optical Measurements of Dynamic Cerebral Autoregulation by Inducing Oscillatory Cerebral Hemodynamics
Authors: Pham Thao , Fernandez Cristianne , Blaney Giles , Tgavalekos Kristen , Sassaroli Angelo , Cai Xuemei , Bibu Steve , Kornbluth Joshua , Fantini Sergio
Published: November 2021

Objective: Cerebral autoregulation limits the variability of cerebral blood flow (CBF) in the presence of systemic arterial blood pressure (ABP) changes. Monitoring cerebral autoregulation is important in the Neurocritical Care Unit (NCCU) to assess cerebral health. Here, our goal is to identify optimal frequency-domain near-infrared spectroscopy (FD-NIRS) parameters and apply a hemodynamic model of coherent hemodynamics spectroscopy (CHS) to assess cerebral autoregulation in healthy adult subjects and NCCU patients.

Methods: In five healthy subjects and three NCCU patients, ABP oscillations at a frequency around 0.065 Hz were induced by cyclic inflation-deflation of pneumatic thigh cuffs. Transfer function analysis based on wavelet transform was performed to measure dynamic relationships between ABP and oscillations in oxy- (O), deoxy- (D), and total- (T) hemoglobin concentrations measured with different FD-NIRS methods. In healthy subjects, we also obtained the dynamic CBF-ABP relationship by using FD-NIRS measurements and the CHS model. In healthy subjects, an interval of hypercapnia was performed to induce cerebral autoregulation impairment. In NCCU patients, the optical measurements of autoregulation were linked to individual clinical diagnoses.

Results: In healthy subjects, hypercapnia leads to a more negative phase difference of both O and D oscillations vs. ABP oscillations, which are consistent across different FD-NIRS methods and are highly correlated with a more negative phase difference CBF vs. ABP. In the NCCU, a less negative phase difference of D vs. ABP was observed in one patient as compared to two others, indicating a better autoregulation in that patient.

Conclusions: Non-invasive optical measurements of induced phase difference between D and ABP show the strongest sensitivity to cerebral autoregulation. The results from healthy subjects also show that the CHS model, in combination with FD-NIRS, can be applied to measure the CBF-ABP dynamics for a better direct measurement of cerebral autoregulation.
Safety and Clinical Effects of Switching From Intravenous to Oral Nimodipine Administration in Aneurysmal Subarachnoid Hemorrhage
Authors: Göttsche Jennifer , Schweingruber Nils , Groth Julian Christopher , Gerloff Christian , Westphal Manfred , Czorlich Patrick
Published: November 2021

Objective: Several guidelines recommend oral administration of nimodipine as vasospasm prophylaxis after aneurysmal subarachnoid hemorrhage (SAH). However, in clinical practice, the drug is administered orally and intravenously (i.v.), depending on clinical conditions and local treatment regimens. We have therefore investigated the safety and clinical effects of switching from i.v. to oral nimodipine therapy.

Methods: Patients with aneurysmal SAH between January 2014 and April 2018 and initial i.v. nimodipine therapy, which was subsequently switched to oral administration, were included in this retrospective study. Transcranial Doppler sonography (TCD) of the vessels of the anterior circulation was performed daily. The occurrence of vasospasm and infarction during the overall course of the treatment was recorded. Statistical level of significance was set to p < 0.05.

Results: A total of 133 patients (mean age 55.8 years, 65% female) initially received nimodipine i.v. after aneurysmal SAH, which was subsequently switched to oral administration after a mean of 12 days. There were no significant increases in mean flow velocities on TCD after the switch from i.v. to oral nimodipine administration regarding the anterior cerebral artery. For the middle cerebral artery, an increase from 62.36 to 71.78 cm/sec could only be detected in the subgroup of patients with infarction. There was no clustering of complicating events such as new-onset vasospasm or infarction during or after the switch.

Conclusions: Our results do not point to any safety concerns when switching nimodipine from initial i.v. to oral administration. Switching was neither associated with clinically relevant increases in TCD velocities nor other relevant adverse events.
Neurophysiological Predictors of Response to Medication in Parkinson's Disease
Authors: Filipović Saša R. , Kačar Aleksandra , Milanović Sladjan , Ljubisavljević Miloš R.
Published: November 2021

Background: Although dopaminergic medication has been the foundation of Parkinson's disease (PD) therapy for decades, sensitive and specific therapeutic response biomarkers that allow for better treatment optimization are lacking.

Objective: We tested whether the features of Transcranial Magnetic Stimulation-based neurophysiological measures taken off-medication are associated with dopaminergic medication-induced clinical effects.

Method: Motor cortex excitability [short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), and input-output (IO) curve], and plasticity [paired associative stimulation (PAS) protocol] neurophysiological measures were examined in 23 PD patients off-medication. Clinical features were quantified by the motor section of the Unified Parkinson's Disease Scale (total score and lateralized total, bradykinesia, and rigidity sub-scores), and the differences between measures off-medication and on-medication (following the usual morning dose), were determined. Total daily dopaminergic medication dose (expressed as levodopa equivalent daily dose-LEDD), was also determined.

Results: SICI significantly correlated with changes in lateralized UPDRS motor and bradykinesia sub-scores, suggesting that patients with stronger basal intracortical inhibition benefit more from dopaminergic treatment than patients with weaker intracortical inhibition. Also, ICF significantly negatively correlated with LEDD, suggesting that patients with stronger intracortical facilitation require less dopaminergic medication to achieve optimal therapeutic benefit. Both associations were independent of disease severity and duration.

Conclusions: The results suggest variability of (patho) physiological phenotypes related to intracortical inhibitory and facilitatory mechanisms determining clinical response to dopaminergic medication in PD. Measures of intracortical excitability may help predict patients' response to dopaminergic therapy, thus potentially providing a background for developing personalized therapy in PD.
Detecting Cognitive Impairment in Idiopathic Intracranial Hypertension Using Ocular Motor and Neuropsychological Testing
Authors: Wang Wendy , Clough Meaghan , White Owen , Shuey Neil , Van Der Walt Anneke , Fielding Joanne
Published: November 2021

Objective: To determine whether cognitive impairments in patients with Idiopathic Intracranial Hypertension (IIH) are correlated with changes in visual processing, weight, waist circumference, mood or headache, and whether they change over time.

Methods: Twenty-two newly diagnosed IIH patients participated, with a subset assessed longitudinally at 3 and 6 months. Both conventional and novel ocular motor tests of cognition were included: Symbol Digit Modalities Test (SDMT), Stroop Colour and Word Test (SCWT), Digit Span, California Verbal Learning Test (CVLT), prosaccade (PS) task, antisaccade (AS) task, interleaved antisaccade-prosaccade (AS-PS) task. Patients also completed headache, mood, and visual functioning questionnaires.

Results: IIH patients performed more poorly than controls on the SDMT (p< 0.001), SCWT (p = 0.021), Digit Span test (p< 0.001) and CVLT (p = 0.004) at baseline, and generated a higher proportion of AS errors in both the AS (p< 0.001) and AS-PS tasks (p = 0.007). Further, IIH patients exhibited prolonged latencies on the cognitively complex AS-PS task (p = 0.034). While weight, waist circumference, headache and mood did not predict performance on any experimental measure, increased retinal nerve fibre layer (RNFL) was associated with AS error rate on both the block [F(3, 19)=3.22, B = 0.30, p = 0.022] and AS-PS task [F(3, 20) = 2.65, B = 0.363, p = 0.013]. Unlike ocular motor changes, impairments revealed on conventional tests of cognition persisted up to 6 months.

Conclusion: We found multi-domain cognitive impairments in IIH patients that were unrelated to clinical characteristics. Marked ocular motor inhibitory control deficits were predicted by RNFL thickness but remained distinct from other cognitive changes, underscoring the significance of visual processing changes in IIH.
Higher Visual Function Deficits in Children With Cerebral Visual Impairment and Good Visual Acuity
Authors: Chandna Arvind , Ghahghaei Saeideh , Foster Susan , Kumar Ram
Published: November 2021

In clinical practice Cerebral Visual Impairment (CVI) is typically diagnosed by observation of abnormal visually guided behaviors which indicate higher visual function deficits (HVFDs) suggesting abnormal brain development or brain damage in a child with a suitable clinical history. HVFDs can occur even in the presence of good visual acuity and may remain undiagnosed because the good visual acuity does not prompt further investigation. This leads to a lack of understanding of the child’s visual perceptual difficulties. In a prospective study, we determined the spectrum of HVFDs in a group of children with history suggestive of brain damage or disruption of brain development and an independent diagnosis of CVI in comparison with typically developing children with a structured 51 question inventory, the Higher Visual Function Question Inventory (HVFQI-51) adapted from the Cerebral Vision Impairment Inventory, CVI-I. Here, we show that the HVFQI-51 can detect a range of HVFDs in children with CVI with good visual acuity and clearly distinguishes these children from typically developing children. HVFDs in our study group could mostly be attributed to dorsal stream visual processing dysfunction though the spectrum varied between children. We report on the inclusion of the “not applicable” response option in analysis providing a picture of HVFDs more in tune with the overall disability of each child. We also propose a subset of 11 questions (Top-11) which discriminate between children with CVI vs. behaviors seen in typical children: this provides both a potential screening tool for initial assessment of HVFDs and a measure of CVI-related impairment, and needs further validation in a secondary independent sample.
Voltage Imaging in Drosophila Using a Hybrid Chemical-Genetic Rhodamine Voltage Reporter
Authors: Kirk Molly J. , Benlian Brittany R. , Han Yifu , Gold Arya , Ravi Ashvin , Deal Parker E. , Molina Rosana S. , Drobizhev Mikhail , Dickman Dion , Scott Kristin , Miller Evan W.
Published: November 2021

We combine a chemically-synthesized, voltage-sensitive fluorophore with a genetically encoded, self-labeling enzyme to enable voltage imaging in Drosophila melanogaster. Previously, we showed that a rhodamine voltage reporter (RhoVR) combined with the HaloTag self-labeling enzyme could be used to monitor membrane potential changes from mammalian neurons in culture and brain slice. Here, we apply this hybrid RhoVR-Halo approach in vivo to achieve selective neuron labeling in intact fly brains. We generate a Drosophila UAS-HaloTag reporter line in which the HaloTag enzyme is expressed on the surface of cells. We validate the voltage sensitivity of this new construct in cell culture before driving expression of HaloTag in specific brain neurons in flies. We show that selective labeling of synapses, cells, and brain regions can be achieved with RhoVR-Halo in either larval neuromuscular junction (NMJ) or in whole adult brains. Finally, we validate the voltage sensitivity of RhoVR-Halo in fly tissue via dual-electrode/imaging at the NMJ, show the efficacy of this approach for measuring synaptic excitatory post-synaptic potentials (EPSPs) in muscle cells, and perform voltage imaging of carbachol-evoked depolarization and osmolarity-evoked hyperpolarization in projection neurons and in interoceptive subesophageal zone neurons in fly brain explants following in vivo labeling. We envision the turn-on response to depolarizations, fast response kinetics, and two-photon compatibility of chemical indicators, coupled with the cellular and synaptic specificity of genetically-encoded enzymes, will make RhoVR-Halo a powerful complement to neurobiological imaging in Drosophila.
Effects of Post-natal Dietary Milk Fat Globule Membrane Polar Lipid Supplementation on Motor Skills, Anxiety, and Long-Term Memory in Adulthood
Authors: Sultan Sébastien , Hauser Jonas , Oliveira Manuel , Rytz Andreas , Preitner Nicolas , Schneider Nora
Published: November 2021

Early life nutrition critically impacts post-natal brain maturation and cognitive development. Post-natal dietary deficits in specific nutrients, such as lipids, minerals or vitamins are associated with brain maturation and cognitive impairments. Specifically, polar lipids (PL), such as sphingolipids and phospholipids, are important cellular membrane building blocks and are critical for brain connectivity due to their role in neurite outgrowth, synaptic formation, and myelination. In this preclinical study, we assessed the effects of a chronic supplementation with a source of PL extracted from an alpha-lactalbumin enriched whey protein containing 10% lipids from early life (post-natal day (PND) 7) to adulthood (PND 72) on adult motor skills, anxiety, and long-term memory. The motor skills were assessed using open field and rotarod test. Anxiety was assessed using elevated plus maze (EPM). Long-term object and spatial memory were assessed using novel object recognition (NOR) and Morris water maze (MWM). Our results suggest that chronic PL supplementation improved measures of spatial long-term memory accuracy and cognitive flexibility in the MWM in adulthood, with no change in general mobility, anxiety and exploratory behavior. Our results indicate memory specific functional benefits of long-term dietary PL during post-natal brain development.
Fatty Acid Composition, Antioxidant, and in vitro Anti-inflammatory Activity of Five Cold-Pressed Prunus Seed Oils, and Their Anti-biofilm Effect Against Pathogenic Bacteria
Authors: Fratianni Florinda , d'Acierno Antonio , Ombra Maria Neve , Amato Giuseppe , De Feo Vincenzo , Ayala-Zavala Juan Fernando , Coppola Raffaele , Nazzaro Filomena
Published: November 2021

Background/Aim: Sweet almond (Prunus amygdalus dulcis) oil is one of the most famous cold-pressed seed oils. However, other species of Prunus can provide oils with healthy properties. We analyzed the fatty acid (FA) composition, as well as the antioxidant, the in vitro anti-inflammatory properties, and the antibiofilm activity of five commercial vegetable cold-pressed seed oils of apricot, peach, plum, cherry, and black cherry.

Methods: Gas Chromatography-Mass Spectrometry was performed for the analysis of FAs The antioxidant property of the oils was carried using different tests [2, 2-diphenyl-1-picrylhydrazyl (DPPH assay)], Ferric Reducing Antioxidant Power (FRAP), and the 2, 20 -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS·+). The denaturation assay performed on bovine serum albumin (BSA) was used to evaluate the in vitro anti-inflammatory activity. The anti-biofilm activity was assessed using five pathogenic strains, namely, Acinetobacter baumannii, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus, through the crystal violet test and the 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide (MTT), used to evaluate the metabolism of the microbial cells present within the biofilm.

Results: Oleic acid and linoleic acids were the most abundant FAs. Black cherry seed oil exhibited the best antioxidant activity, but in general, the amount of oil needed to inhibit the activity of 1 ml of DPPH assay at 50% did not exceed 10 μg. The extract concentration for the 50% inhibition of the denaturation of the protein (IC50) did not exceed 4.4 μg. Linoleic and stearic acids affected the antioxidant activity of the oils; oleic acid, linolenic, and palmitoleic acids exhibited beneficial effects in preserving the BSA denaturation, as shown by the correlation data. The oils were able to inhibit the biofilm formation of the pathogens (up to 71.40% of inhibition) as well as act against their mature biofilm, although with different strengths, with values up to 61.54%. Concurrently, they also acted on the pathogen metabolism.

Conclusion: The oils represent a valuable source of some healthy FAs. They showed potential antioxidant and anti-inflammatory in vitro activity, in addition, their potential effect on the biofilm can offer important ideas for research and reflection on their use as functional foods and/or ingredients.
Computed Tomography–Based Body Composition in Patients With Ovarian Cancer: Association With Chemotoxicity and Prognosis
Authors: Del Grande Maria , Rizzo Stefania , Nicolino Gabriele Maria , Colombo Ilaria , Rossi Lorenzo , Manganaro Lucia , Del Grande Filippo
Published: November 2021

Purpose

To assess the association between computed tomography (CT)-derived quantitative measures of body composition profiling and chemotherapy-related complications, in terms of dose reduction, premature discontinuation of chemotherapy, and cycle delays in patients with ovarian cancer. Secondary purposes were to evaluate associations between sarcopenia and survival, and to evaluate differences in body composition profiling at baseline and after neoadjuvant chemotherapy.

Materials and Methods

The study population was retrospectively selected from a database of patients with newly diagnosed ovarian cancer (any stage) referred to our Institution between Feb 2011 and Mar 2020. Clinical data were recorded, and CT images at the level of the 3rd lumbar vertebra were stored. By using specific software, skeletal muscle area (SMA), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle density (SMD) were extracted. Skeletal muscle index (SMI) was then calculated. Statistical analysis was performed by logistic regression models to identify body composition features predictive of dose reduction, premature end of chemotherapy, and cycle delays. Kaplan-Meier analyses were performed to assess overall survival (OS) and progression-free survival (PFS). The log-rank test was used to determine differences in OS and PFS between sarcopenic and non-sarcopenic patients. Wilcoxon test was performed to compare body composition features before and after neoadjuvant chemotherapy (NACT).

Results

Sixty-nine patients were included. A significant association was found between VAT and cycle delays (OR = 1.01, z = 2.01, 95% CI: 1.00–1.02, p < 0.05), between SMA and early discontinuation of chemotherapy (OR = 1.03, z = 2.10, 95% CI: 1.00–1.05, p < 0.05), and between mean SMD and cycle delays (OR = 0.92, z = −2.70, 95%CI: 0.87–0.98, p < 0.01). No significant difference emerged for OS in sarcopenic and non-sarcopenic patients, nor in CT body composition features before and after NACT.

Conclusions

In ovarian cancer patients, CT-derived body composition profiling might predict the risk of chemotoxicity. In particular, VAT and SMD are associated with chemotherapy cycle delays, and SMA with early discontinuation of chemotherapy.
Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer
Authors: Wiest Nathaniel , Majeed Umair , Seegobin Karan , Zhao Yujie , Lou Yanyan , Manochakian Rami
Published: November 2021

Over the last decade, the treatment of advanced non-small cell lung cancer (NSCLC) has undergone rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. In patients with epidermal growth factor receptor (EGFR) gene mutant (EGFRm) NSCLC, newer-generation tyrosine kinase inhibitors (TKIs) are providing unparalleled survival benefit and tolerability. Unfortunately, most patients will experience disease progression and thus an urgent need exists for improved subsequent lines of therapies. The concurrent revolution in immune checkpoint inhibitor (ICI) therapy is providing novel treatment options with improved clinical outcomes in wild-type EGFR (EGFRwt) NSCLC; however, the application of ICI therapy to advanced EGFRm NSCLC patients is controversial. Early studies demonstrated the inferiority of ICI monotherapy to EGFR TKI therapy in the first line setting and inferiority to chemotherapy in the second line setting. Additionally, combination ICI and EGFR TKI therapies have demonstrated increased toxicities, and EGFR TKI therapy given after first-line ICI therapy has been correlated with severe adverse events. Nonetheless, combination therapies including dual-ICI blockade and ICI, chemotherapy, and angiogenesis inhibitor combinations are areas of active study with some intriguing signals in preliminary studies. Here, we review previous and ongoing clinical studies of ICI therapy in advanced EGFRm NSCLC. We discuss advances in understanding the differences in the tumor biology and tumor microenvironment (TME) of EGFRm NSCLC tumors that may lead to novel approaches to enhance ICI efficacy. It is our goal to equip the reader with a knowledge of current therapies, past and current clinical trials, and active avenues of research that provide the promise of novel approaches and improved outcomes for patients with advanced EGFRm NSCLC.
Hybrid or Mixed Myelodysplastic/Myeloproliferative Disorders – Epidemiological Features and Overview
Authors: Kuendgen Andrea , Kasprzak Annika , Germing Ulrich
Published: November 2021

The WHO-category Myelodysplastic/Myeloproliferative neoplasms (MDS/MPNs) recognizes a unique group of clonal myeloid malignancies exhibiting overlapping features of myelodysplastic as well as myeloproliferative neoplasms. The group consists of chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, BCR-ABL1-negative (aCML), juvenile myelomonocytic leukemia (JMML), myelodysplastic/myeloproliferative neoplasm with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U). The most frequent entity in this category is CMML, while all other diseases are extremely rare. Thus, only very limited data on the epidemiology of these subgroups exists. An appropriate diagnosis and classification can be challenging since the diagnosis is still largely based on morphologic criteria and myelodysplastic as well as myeloproliferative features can be found in various occurrences. The diseases in this category share several features that are common in this specific WHO-category, but also exhibit specific traits for each disease. This review summarizes published data on epidemiological features and offers a brief overview of the main diagnostic criteria and clinical characteristics of the five MDS/MPN subgroups.
Pain and Other Neurological Symptoms Are Present at 3 Months After Hospitalization in COVID-19 Patients
Authors: Savarraj Jude P. J. , Burkett Angela B. , Hinds Sarah N. , Paz Atzhiry S. , Assing Andres , Juneja Shivanki , Colpo Gabriela D. , Torres Luis F. , Cho Sung-Min , Gusdon Aaron M. , McCullough Louise D. , Choi H. Alex
Published: November 2021

COVID-19 is an ongoing pandemic with a devastating impact on public health. Acute neurological symptoms have been reported after a COVID-19 diagnosis, however, the long-term neurological symptoms including pain is not well established. Using a prospective registry of hospitalized COVID-19 patients, we assessed pain and neurological function (including functional, cognitive and psychiatric assessments) of several hospitalized patients at 3 months. Our main finding is that 60% of the patients report pain symptoms. 71% of the patients still experienced neurological symptoms at 3 months and the most common symptoms being fatigue (42%) and PTSD (25%). Cognitive symptoms were found in 12%. Our preliminary findings suggests the importance of investigating long-term outcomes and rationalizes the need for further studies investigating the neurologic outcomes and symptoms of pain after COVID-19.
Efficacies and Toxicities of Seven Chemotherapy Regimens for Advanced Hodgkin Lymphoma
Authors: Pei Fajun , Yu Yang , Dong Bin , Guan Hui , Dong Xinzhe , Zhao Fen
Published: November 2021

Background/Aims: Hodgkin Lymphoma (HL) has become one of the most treatable cancers, with more than 80% patients in the advanced stage being cured through improvement of therapeutic regimens. Nevertheless, some treatments were accompanied with toxicities.

Methods: In the current study, a network meta-analysis (NMA) was conducted to compare the efficacies and toxicities of different chemotherapy regimens for advanced Hodgkin lymphoma (HL). We reviewed PubMed and EMBASE databases from inception to May 2018, and identified randomized controlled trials (RCTs) in which advanced HL patients received chemotherapy. Fourteen eligible RCTs published between 1992 and 2017 were enrolled in this NMA. These studies included a total of 5,964 HL patients, and assessed at least one of seven different chemotherapy regimens. Direct and indirect evidence was combined to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), and to establish a surface under the cumulative ranking (SUCRA) curve.

Results: A cluster analysis was performed to evaluate efficacies and toxicities of different regimens. The COPP + ABVD (cyclophosphamide + vincristine + procarbazine + prednisone + doxorubicin + bleomycin + vinblastine + dacarbazine) regimen had the highest SUCRA partial response and overall remission rate values, while the ABVD regimen resulted in the lowest incidences of anemia, thrombocytopenia, neutropenia, and leucopenia.

Conclusion: Cluster analysis revealed that COPP + ABVD had the best efficacy against advanced HL among the seven regimens, and ABVD had the lowest toxicity.
Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature
Authors: Lenoir Camille , Rollason Victoria , Desmeules Jules A. , Samer Caroline F.
Published: November 2021

Background:Available in-vitro and animal studies indicate that inflammation impacts cytochromes P450 (CYP) activityviamultiple and complex transcriptional and post-transcriptional mechanisms, depending on the specific CYP isoforms and the nature of inflammation mediators. It is essential to review the current published data on the impact of inflammation on CYP activities in adults to support drug individualization based on comorbidities and diseases in clinical practice.

Methods:This systematic review was conducted in PubMed through 7th January 2021 looking for articles that investigated the consequences of inflammation on CYP activities in adults. Information on the source of inflammation, victim drugs (and CYPs involved), effect of disease-drug interaction, number of subjects, and study design were extracted.

Results:The search strategy identified 218 studies and case reports that met our inclusion criteria. These articles were divided into fourteen different sources of inflammation (such as infection, autoimmune diseases, cancer, therapies with immunomodulator…). The impact of inflammation on CYP activities appeared to be isoform-specific and dependent on the nature and severity of the underlying disease causing the inflammation. Some of these drug-disease interactions had a significant influence on drug pharmacokinetic parameters and on clinical management. For example, clozapine levels doubled with signs of toxicity during infections and the concentration ratio between clopidogrel’s active metabolite and clopidogrel is 48-fold lower in critically ill patients. Infection and CYP3A were the most cited perpetrator of inflammation and the most studied CYP, respectively. Moreover, some data suggest that resolution of inflammation results in a return to baseline CYP activities.

Conclusion:Convincing evidence shows that inflammation is a major factor to be taken into account in drug development and in clinical practice to avoid any efficacy or safety issues because inflammation modulates CYP activities and thus drug pharmacokinetics. The impact is different depending on the CYP isoform and the inflammatory disease considered. Moreover, resolution of inflammation appears to result in a normalization of CYP activity. However, some results are still equivocal and further investigations are thus needed.
Young Children’s Eating in the Absence of Hunger: Links With Child Inhibitory Control, Child BMI, and Maternal Controlling Feeding Practices
Authors: Philippe Kaat , Chabanet Claire , Issanchou Sylvie , Monnery-Patris Sandrine
Published: November 2021

This study aimed to gain a better understanding of the associations between young children’s eating in the absence of hunger (EAH), inhibitory control, body mass index (BMI) and several maternal controlling feeding practices (food as reward, restriction for health, restriction for weight control). In addition, to more properly assess the relationship between children’s and maternal variables, the link between EAH and restriction was explored separately in two directionalities: “child to parent” or “parent to child.” To do this, mothers of 621 children aged 2.00–6.97years (51% boys,M=4.11years,SD=1.34) filled in a questionnaire with items from validated questionnaires. Structural equation modeling (SEM) was used to analyze the data. The results showed, whatever the directionality considered, a positive association between children’s eating in the absence of hunger and their BMI z-scores. Restriction for health and restriction for weight control were differently linked to EAH and to children’s BMI z-scores. Namely, low child inhibitory control, food as reward and restriction for health were identified as risk factors for EAH. Restriction for weight control was not linked to EAH, but was predicted by child BMI z-scores. Interventions aiming to improve children’s abilities to self-regulate food intake could consider training children’s general self-regulation, their self-regulation of intake, and/or promoting adaptive parental feeding practices.
Digital Narratives During the Pandemic: TV Series, Social Media, and Conversations on the Internet
Authors: Martínez-Borda Rut , de-la-Fuente Julián , Lacasa Pilar
Published: November 2021

The situation of lockdown experienced during the months from March to June 2020 changed the daily lives of people in Spain and their leisure circumstances. This study analyses the narrative representations that people construct when they watched streaming TV series, during the covid-19 pandemic. To access these representations, the Spanish texts that appear on the Internet are analysed, including social networks and other social media. The paper adopts quantitative approaches that use big data analysis complemented with other qualitative approaches and inspired by content and discourse analysis. Findings show that these narrative representations constructed through conversations are on three levels in which context is revealed: first, institutional and community; second, online or offline interpersonal relationships which mention people as facts or as aspirations of their daily lives; and third, personal lives in the reconstruction of the series, projected on the plot reconstruction and the identity of the actors.
Developmental Trajectories of Letter and Speech Sound Integration During Reading Acquisition
Authors: Karipidis Iliana I. , Pleisch Georgette , Di Pietro Sarah V. , Fraga-González Gorka , Brem Silvia
Published: November 2021

Reading acquisition in alphabetic languages starts with learning the associations between speech sounds and letters. This learning process is related to crucial developmental changes of brain regions that serve visual, auditory, multisensory integration, and higher cognitive processes. Here, we studied the development of audiovisual processing and integration of letter-speech sound pairs with an audiovisual target detection functional MRI paradigm. Using a longitudinal approach, we tested children with varying reading outcomes before the start of reading acquisition (T1, 6.5 yo), in first grade (T2, 7.5 yo), and in second grade (T3, 8.5 yo). Early audiovisual integration effects were characterized by higher activation for incongruent than congruent letter-speech sound pairs in the inferior frontal gyrus and ventral occipitotemporal cortex. Audiovisual processing in the left superior temporal gyrus significantly increased from the prereading (T1) to early reading stages (T2, T3). Region of interest analyses revealed that activation in left superior temporal gyrus (STG), inferior frontal gyrus and ventral occipitotemporal cortex increased in children with typical reading fluency skills, while poor readers did not show the same development in these regions. The incongruency effect bilaterally in parts of the STG and insular cortex at T1 was significantly associated with reading fluency skills at T3. These findings provide new insights into the development of the brain circuitry involved in audiovisual processing of letters, the building blocks of words, and reveal early markers of audiovisual integration that may be predictive of reading outcomes.
Exploring Protective Factors in Wellbeing: How Sensory Processing Sensitivity and Attention Awareness Interact With Resilience
Authors: Gulla Bożena , Golonka Krystyna
Published: November 2021

The aim of the study is to analyze the relationship between sensory processing sensitivity (SPS), attention awareness, and resilience and to determine whether attention awareness may moderate the relation between sensitivity and resilience. The sample consisted of 273 adults (239 women; Mage=24.12, SD=6.59years). The highly sensitive person scale, the resiliency assessment scale, and the mindful attention awareness scale were used in the study. The results indicate significant relationships between SPS and resilience; emotional reactivity is especially associated with lower resilience, whereas sensing the subtle is associated with higher resilience. The regression analyses revealed that SPS is a significant predictor of resilience, but diverse aspects of sensitivity explain resilience differently. Attentional awareness was found to be a significant moderator that strengthens the positive relationship between sensing the subtle and tolerance of negative emotions. The consequences of high sensitivity include high levels of distress, anxiety, and a sense of overload; therefore, searching for protective factors is important to maintain the wellbeing of highly sensitive people. As one of the characteristics of highly sensitive persons, sensing the subtle may be an important resource that allows to them to deal effectively with difficult situations. Training on attention awareness and conscious presence may be an important way to deal with negative emotions and develop personal competences. The results indicate that these strategies may be of high significance for improving wellbeing and protecting highly sensitive persons against various stress factors.
A Unifying Theory for Autism: The Pathogenetic Triad as a Theoretical Framework
Authors: Sarovic Darko
Published: November 2021

This paper presents a unifying theory for autism by applying the framework of a pathogenetic triad to the scientific literature. It proposes a deconstruction of autism into three contributing features (an autistic personality dimension, cognitive compensation, and neuropathological risk factors), and delineates how they interact to cause a maladaptive behavioral phenotype that may require a clinical diagnosis. The autistic personality represents a common core condition, which induces a set of behavioral issues when pronounced. These issues are compensated for by cognitive mechanisms, allowing the individual to remain adaptive and functional. Risk factors, both exogenous and endogenous ones, show pathophysiological convergence through their negative effects on neurodevelopment. This secondarily affects cognitive compensation, which disinhibits a maladaptive behavioral phenotype. The triad is operationalized and methods for quantification are presented. With respect to the breadth of findings in the literature that it can incorporate, it is the most comprehensive model yet for autism. Its main implications are that (1) it presents the broader autism phenotype as a non-pathological core personality domain, which is shared across the population and uncoupled from associated features such as low cognitive ability and immune dysfunction, (2) it proposes that common genetic variants underly the personality domain, and that rare variants act as risk factors through negative effects on neurodevelopment, (3) it outlines a common pathophysiological mechanism, through inhibition of neurodevelopment and cognitive dysfunction, by which a wide range of endogenous and exogenous risk factors lead to autism, and (4) it suggests that contributing risk factors, and findings of immune and autonomic dysfunction are clinically ascertained rather than part of the core autism construct.
Do Old Age and Comorbidity via Non-Communicable Diseases Matter for COVID-19 Mortality? A Path Analysis
Authors: Goswami Gour Gobinda , Mahapatro Mausumi , Ali A. R. M. Mehrab , Rahman Raisa
Published: November 2021

This paper used Our World data for coronavirus disease-2019 (COVID-19) death count, test data, stringency, and transmission count and prepared a path model for COVID-19 deaths. We augmented the model with age structure-related variables and comorbidity via non-communicable diseases for 117 countries of the world for September 23, 2021, on a cross-section basis. A broad-based global quantitative study incorporating these two prominent channels with regional variation was unavailable in the existing literature. Old age and comorbidity were identified as two prime determinants of COVID-19 mortality. The path model showed that after controlling for these factors, one SD increase in the proportion of persons above 65, above 70, or of median age raised COVID-19 mortality by more than 0.12 SDs for 117 countries. The regional intensity of death is alarmingly high in South America, Europe, and North America compared with Oceania. After controlling for regions, the figure was raised to 0.213, which was even higher. For old age, the incremental coefficient was the highest for South America (0.564), and Europe (0.314), which were substantially higher than in Oceania. The comorbidity channel via non-communicable diseases illustrated that one SD increase in non-communicable disease intensity increased COVID-19 mortality by 0.132 for the whole sample. The regional figure for the non-communicable disease was 0.594 for South America and 0.358 for Europe compared with the benchmark region Oceania. The results were statistically significant at a 10% level of significance or above. This suggested that we should prioritize vaccinations for the elderly and people with comorbidity via non-communicable diseases like heart disease, cancer, chronic respiratory disease, and diabetes. Further attention should be given to South America and Europe, which are the worst affected regions of the world.
Impacts of Landscape Evolution on Heterotrophic Carbon Loss in Intensively Managed Landscapes
Authors: Yan Qina , Kumar Praveen
Published: November 2021

Soil respiration that releases CO2 into the atmosphere roughly balances the net primary productivity and varies widely in space and time. However, predicting its spatial variability, particularly in intensively managed landscapes, is challenging due to a lack of understanding of the roles of soil organic carbon (SOC) redistribution resulting from accelerated soil erosion. Here we simulate the heterotrophic carbon loss (HCL)—defined as microbial decomposition of SOC—with soil transport, SOC surface redistribution, and biogeochemical transformation in an agricultural field. The results show that accelerated soil erosion extends the spatial variation of the HCL, and the mechanical-mixing due to tillage further accentuates the contrast. The peak values of HCL occur in areas where soil transport rates are relatively small. Moreover, HCL has a strong correlation with the SOC redistribution rate rather than the soil transport rate. This work characterizes the roles of soil and SOC transport in restructuring the spatial variability of HCL at high spatio-temporal resolution.
The Dilemmas of Water Quality and Food Security Interactions in Low- and Middle-Income Countries
Authors: Linderhof Vincent , de Lange Thijs , Reinhard Stijn
Published: November 2021

Water is a factor input for many food system activities such as agriculture, food processing and consumption. However, food system activities also affect water resources. Moreover, the shift in focus of food security in Low- and Middle-Income Countries (LMICs) from producing enough staple foods toward healthy diets stimulates local production of fresh food such as fruit, vegetables and fish even in water scarce regions. To secure local production, polluted water is used for food production, processing and consumption, which might jeopardize human health. However, scientific evidence is still scattered and fragmented. The aim of this study is to systematically investigate the empirical tested impacts of water quality on the food system activities and vice versa. Using a comprehensive framework, we sketch the inter-relationships between water quality and food systems based on a literature study. Food system activities included food production (crop production, livestock and aquaculture), food processing, and food consumption. Multiple contaminants were incorporated such as nitrogen, phosphorus, pesticides, pathogens, cyanotoxins, and heavy metals. Moreover, we considered different water sources such as groundwater, surface water, wastewater and coastal water. We found that food system activities contaminate water in several ways, and these differ between food system activity and type of food produced. The impact of water quality on the food system depends on the food produced, the type of contaminant and techniques of food preparation. In addition, food is contaminated in multiple ways along the food system. Irrigation with polluted water may sound familiar, but polluted water is sometimes also used in food processing (cleaning of equipment or food products), and in food preparation (at home or by street vendors). Hygiene in food consumption is crucial to prevent fecal-oral transmission. However, water, sanitation and hygiene (WASH) received little attention in relation to food consumption. If local production of fresh food is encouraged to improve food security, all aspects of water quality should be analyzed to avoid undesirable consequences.
Higher Dimensional Bianchi Type-I Cosmological Models With Massive String in General Relativity
Authors: Singh Kangujam Priyokumar , Baro Jiten , Meitei Asem Jotin
Published: November 2021

Here we studied Bianchi type-I cosmological models with massive strings in general relativity in five dimensional space time. Out of the two different cases obtained here, one case leads to a five dimensional Bianchi type-I string cosmological model in general relativity while the other yields the vacuum Universe in general relativity in five dimensional space time. The physical and geometrical properties of the model Universe are studied and compared with the present day’s observational findings. It is observed that our model is anisotropic, expanding, shearing, and decelerates at an early stage and then accelerates at a later time. The model expands along x, y, and z axes and the extra dimension contracts and becomes unobservable at t → ∞. We also observed that the sum of the energy density (ρ) and the string tension density (λ) vanishes (ρ + λ = 0).