bluuebunny/crossref_metadata_2025 huggingface dataset:
Metaproteomics Reveals Similar Vertical Distribution of Microbial Transport Proteins in Particulate Organic Matter Throughout the Water Column in the Northwest Pacific Ocean
Authors: Kong Ling-Fen , Yan Ke-Qiang , Xie Zhang-Xian , He Yan-Bin , Lin Lin , Xu Hong-Kai , Liu Si-Qi , Wang Da-Zhi
Published: March 2021

Solubilized particulate organic matter (POM) rather than dissolved organic matter (DOM) has been speculated to be the major carbon and energy sources for heterotrophic prokaryotes in the ocean. However, the direct evidence is still lack. Here we characterized microbial transport proteins of POM collected from both euphotic (75 m, deep chlorophyll maximum DCM, and 100 m) and upper-twilight (200 m and 500 m) zones in three contrasting environments in the northwest Pacific Ocean using a metaproteomic approach. The proportion of transport proteins was relatively high at the bottom of the euphotic zone (200 m), indicating that this layer was the most active area of microbe-driven POM remineralization in the water column. In the upper-twilight zone, the predicted substrates of the identified transporters indicated that amino acids, carbohydrates, taurine, inorganic nutrients, urea, biopolymers, and cobalamin were essential substrates for the microbial community. SAR11, Rhodobacterales, Alteromonadales, and Enterobacteriales were the key contributors with the highest expression of transporters. Interestingly, both the taxonomy and function of the microbial communities varied among water layers and sites with different environments; however, the distribution of transporter types and their relevant organic substrates were similar among samples, suggesting that microbial communities took up similar compounds and were functionally redundant in organic matter utilization throughout the water column. The similar vertical distribution of transport proteins from the euphotic zone to the upper twilight zone among the contrasting environments indicated that solubilized POM rather than DOM was the preferable carbon and energy sources for the microbial communities.
A Nanomule Peptide Carrier Delivers siRNA Across the Intact Blood-Brain Barrier to Attenuate Ischemic Stroke
Authors: Eyford Brett A. , Singh Chaahat S. B. , Abraham Thomas , Munro Lonna , Choi Kyung Bok , Hill Tracy , Hildebrandt Rhonda , Welch Ian , Vitalis Timothy Z. , Gabathuler Reinhard , Gordon Jacob A. , Adomat Hans , Guns Emma S.T. , Lu Chieh-Ju , Pfeifer Cheryl G. , Tian Mei Mei , Jefferies Wilfred A.
Published: March 2021

The blood-brain barrier (BBB) hinders the distribution of therapeutics intended for treatment of neuroinflammation (NI) of the central nervous system. A twelve-amino acid peptide that transcytoses the BBB, termed MTfp, was chemically conjugated to siRNA to create a novel peptide-oligonucleotide conjugate (POC), directed to downregulate NOX4, a gene thought responsible for oxidative stress in ischemic stroke. The MTfp-NOX4 POC has the ability to cross the intact BBB and knockdown NOX4 expression in the brain. Following induction of ischemic stroke, animals pretreated with the POC exhibited significantly smaller infarcts; accompanied by increased protection against neurological deterioration and improved recovery. The data demonstrates that the MTfp can act as a nanomule to facilitate BBB transcytosis of siRNAs; where the NOX-4 specific siRNA moiety can elicit effective therapeutic knockdown of a gene responsible for oxidative stress in the central nervous system. This study is the first to conclusively demonstrate both siRNA-carrier delivery and therapeutic efficacy in any CNS disease model where the BBB remains intact and thus offers new avenues for potential treatments of oxidative stress underlying neuroinflammation in a variety of neuropathologies that are currently refractory to existing therapies.
Impact of Sleep Duration on Depression and Anxiety After Acute Ischemic Stroke
Authors: Liu Fei , Yang Yang , Wang Shuo , Zhang Xiao-Li , Wang An-Xin , Liao Xiao-Ling , Fang Hong-Juan , Qu Yue , Ma Wei-Guo , Zhang Ning , Wang Chun-Xue , Wang Yong-Jun
Published: March 2021

Background: Abnormal sleep duration predicts depression and anxiety. We seek to evaluate the impact of sleep duration before stroke on the occurrence of depression and anxiety at 3 months after acute ischemic stroke (AIS).

Methods: Nationally representative samples from the Third China National Stroke Registry were used to examine cognition and sleep impairment after AIS (CNSR-III-ICONS). Based on baseline sleep duration before onset of stroke as measured by using the Pittsburgh Sleep Quality Index (PSQI), 1,446 patients were divided into four groups: >7, 6–7, 5–6, and <5 h of sleep. Patients were followed up with the General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) for 3 months. Poststroke anxiety (PSA) was defined as GAD-7 of ≥5 and poststroke depression (PSD) as PHQ-9 of ≥5. The association of sleep duration with PSA and PSD was evaluated using multivariable logistic regression.

Results: The incidences of PSA and PSD were 11.2 and 17.6% at 3 months, respectively. Compared to a sleep duration of >7 h, 5–6 h, and <5 h of sleep were identified as risk factors of PSA [odds ratio (OR), 1.95; 95% confidence interval (CI), 1.24–3.07; P < 0.01 and OR, 3.41; 95% CI, 1.94–6.04; P < 0.01) and PSD (OR, 1.47; 95% CI, 1.00–2.17; P = 0.04 and OR, 3.05; 95% CI, 1.85–5.02; P < 0.01), while 6–7 h of sleep was associated with neither PSA (OR, 1.09; 95% CI, 0.71–1.67; P = 0.68) nor PSD (OR, 0.92; 95% CI, 0.64–1.30; P = 0.64). In interaction analysis, the impact of sleep duration on PSA and PSD was not affected by gender (P = 0.68 and P = 0.29, respectively).

Conclusions: Sleep duration of shorter than 6 h was predictive of anxiety and depression after ischemic stroke.
Amantadine ER (Gocovri®) Significantly Increases ON Time Without Any Dyskinesia: Pooled Analyses From Pivotal Trials in Parkinson's Disease
Authors: Hauser Robert A. , Walsh Ryan R. , Pahwa Rajesh , Chernick Dustin , Formella Andrea E.
Published: March 2021

Background: Clinical trials for antiparkinsonian drugs aimed at managing motor complications typically use patient diaries to divide levodopa-induced dyskinesias (LID) into “troublesome” and “non-troublesome” categories. Yet, given the choice, most patients would prefer to live without experiencing any dyskinesia. However, the concept of evaluating time spent ON without any dyskinesia as an outcome has never been tested. We conducted analyses of pooled Gocovri pivotal trial data in order to evaluate the extent to which Gocovri increased the time PD patients spent ON without dyskinesia (troublesome or non-troublesome), beyond its already identified improvement in reducing troublesome dyskinesia.

Methods: Patients enrolled in phase 3 trials (EASE LID [NCT02136914] or EASE LID 3 [NCT02274766]) recorded time spent in the following PD diary states at baseline and Week 12 (endpoint): asleep, OFF, ON with troublesome dyskinesia, ON with non-troublesome dyskinesia, and ON without dyskinesia. Mixed model repeated measures analyses with estimated Cohen D effect sizes were performed on the modified intent to treat population to evaluate changes in time spent in these states.

Results: Patients randomized to receive Gocovri showed an increase in ON time without dyskinesia and corresponding decreases in ON time with dyskinesia and OFF time vs. placebo. Treatment effects were statistically significant for Gocovri vs. placebo starting at Week 2 and were sustained until Week 12. On MMRM analysis at Week 12, patients in the Gocovri group showed an adjusted mean ± SE increase over placebo of 2.9 ± 0.6 h in ON time without dyskinesia (Cohen D effect size 0.79) and an adjusted mean ± SE decrease of −1.9 ± 0.6 h in ON time with dyskinesia (troublesome + non-troublesome) (Cohen D effect size 0.49), that included a −1.5 ± 0.4 h placebo-adjusted reduction in ON time with troublesome dyskinesia and a −0.6 ± 0.4 h reduction in ON time with non-troublesome dyskinesia. OFF time was reduced by −1.0 ± 0.3 h compared to placebo.

Conclusions: Gocovri treatment more than doubled the daily time patients spent ON without dyskinesia. These results suggest that the Gocovri treatment effect was driven by a reduction in overall motor complications including ON time with both troublesome and non-troublesome dyskinesia as well as time spent OFF.
C-Gait for Detecting Freezing of Gait in the Early to Middle Stages of Parkinson’s Disease: A Model Prediction Study
Authors: Chen Zi-Yan , Yan Hong-Jiao , Qi Lin , Zhen Qiao-Xia , Liu Cui , Wang Ping , Liu Yong-Hong , Wang Rui-Dan , Liu Yan-Jun , Fang Jin-Ping , Su Yuan , Yan Xiao-Yan , Liu Ai-Xian , Xi Jianing , Fang Boyan
Published: March 2021

Graphical Abstract

Patients with early- to middle-stage PD (Hoehn and Yahr stages 1–3) were enrolled for C-Gait assessment and traditional walking ability assessments. The correlation of C-Gait assessment and traditional walking tests were studied. Two models were established based on C-Gait assessment and traditional walking tests to explore the value of C-Gait assessment in predicting freezing of gait.
Phase–Amplitude Coupling, Mental Health and Cognition: Implications for Adolescence
Authors: Sacks Dashiell D. , Schwenn Paul E. , McLoughlin Larisa T. , Lagopoulos Jim , Hermens Daniel F.
Published: March 2021

Identifying biomarkers of developing mental disorder is crucial to improving early identification and treatment—a key strategy for reducing the burden of mental disorders. Cross-frequency coupling between two different frequencies of neural oscillations is one such promising measure, believed to reflect synchronization between local and global networks in the brain. Specifically, in adults phase–amplitude coupling (PAC) has been shown to be involved in a range of cognitive processes, including working and long-term memory, attention, language, and fluid intelligence. Evidence suggests that increased PAC mediates both temporary and lasting improvements in working memory elicited by transcranial direct-current stimulation and reductions in depressive symptoms after transcranial magnetic stimulation. Moreover, research has shown that abnormal patterns of PAC are associated with depression and schizophrenia in adults. PAC is believed to be closely related to cortico-cortico white matter (WM) microstructure, which is well established in the literature as a structural mechanism underlying mental health. Some cognitive findings have been replicated in adolescents and abnormal patterns of PAC have also been linked to ADHD in young people. However, currently most research has focused on cross-sectional adult samples. Whereas initial hypotheses suggested that PAC was a state-based measure due to an early focus on cognitive, task-based research, current evidence suggests that PAC has both state-based and stable components. Future longitudinal research focusing on PAC throughout adolescent development could further our understanding of the relationship between mental health and cognition and facilitate the development of new methods for the identification and treatment of youth mental health.
Integrated Multi-Omic Analyses of the Genomic Modifications by Gut Microbiome-Derived Metabolites of Epicatechin, 5-(4′-Hydroxyphenyl)-γ-Valerolactone, in TNFalpha-Stimulated Primary Human Brain Microvascular Endothelial Cells
Authors: Corral-Jara Karla Fabiola , Nuthikattu Saivageethi , Rutledge John , Villablanca Amparo , Morand Christine , Schroeter Hagen , Milenkovic Dragan
Published: March 2021

Cerebral blood vessels are lined with endothelial cells and form the blood-brain barrier. Their dysfunction constitutes a crucial event in the physiopathology of neurodegenerative disorders and cognitive impairment. Epicatechin can improve cognitive functions and lower the risk for Alzheimer’s disease or stroke. However, molecular mechanisms of epicatechin on brain vascular endothelium are still unexplored. The objective of this study was to investigate the biological effects of gut microbiome-derived metabolites of epicatechin, 5-(4′-Hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-Hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, in TNF-α-stimulated human brain microvascular endothelial cells at low (nM) concentrations by evaluating their multi-omic modification (expression of mRNA, microRNA, long non-coding RNAs, and proteins). We observed that metabolites are biologically active and can simultaneously modulate the expression of protein-coding and non-coding genes as well as proteins. Integrative bioinformatics analysis of obtained data revealed complex networks of genomics modifications by acting at different levels of regulation. Metabolites modulate cellular pathways including cell adhesion, cytoskeleton organization, focal adhesion, signaling pathways, pathways regulating endothelial permeability, and interaction with immune cells. This study demonstrates multimodal mechanisms of action by which epicatechin metabolites could preserve brain vascular endothelial cell integrity, presenting mechanisms of action underlying epicatechin neuroprotective properties.
Systemic Review on Transcranial Electrical Stimulation Parameters and EEG/fNIRS Features for Brain Diseases
Authors: Yang Dalin , Shin Yong-Il , Hong Keum-Shik
Published: March 2021

Background

Brain disorders are gradually becoming the leading cause of death worldwide. However, the lack of knowledge of brain disease’s underlying mechanisms and ineffective neuropharmacological therapy have led to further exploration of optimal treatments and brain monitoring techniques.

Objective

This study aims to review the current state of brain disorders, which utilize transcranial electrical stimulation (tES) and daily usable noninvasive neuroimaging techniques. Furthermore, the second goal of this study is to highlight available gaps and provide a comprehensive guideline for further investigation.

Method

A systematic search was conducted of the PubMed and Web of Science databases from January 2000 to October 2020 using relevant keywords. Electroencephalography (EEG) and functional near-infrared spectroscopy were selected as noninvasive neuroimaging modalities. Nine brain disorders were investigated in this study, including Alzheimer’s disease, depression, autism spectrum disorder, attention-deficit hyperactivity disorder, epilepsy, Parkinson’s disease, stroke, schizophrenia, and traumatic brain injury.

Results

Sixty-seven studies (1,385 participants) were included for quantitative analysis. Most of the articles (82.6%) employed transcranial direct current stimulation as an intervention method with modulation parameters of 1 mA intensity (47.2%) for 16–20 min (69.0%) duration of stimulation in a single session (36.8%). The frontal cortex (46.4%) and the cerebral cortex (47.8%) were used as a neuroimaging modality, with the power spectrum (45.7%) commonly extracted as a quantitative EEG feature.

Conclusion

An appropriate stimulation protocol applying tES as a therapy could be an effective treatment for cognitive and neurological brain disorders. However, the optimal tES criteria have not been defined; they vary across persons and disease types. Therefore, future work needs to investigate a closed-loop tES with monitoring by neuroimaging techniques to achieve personalized therapy for brain disorders.
Rationalizing the Role of Monosodium Glutamate in the Protein Aggregation Through Biophysical Approaches: Potential Impact on Neurodegeneration
Authors: Ahanger Ishfaq Ahmad , Bashir Sania , Parray Zahoor Ahmad , Alajmi Mohamed F. , Hussain Afzal , Ahmad Faizan , Hassan Md. Imtaiyaz , Islam Asimul , Sharma Anurag
Published: March 2021

GRAPHICAL ABSTRACT 1

Kinetic measurements indicating that monosodium glutamate causes significant enhancement of aggregation of protein through nucleation-dependent polymerization mechanism. Even low concentration of MSG is involved in the unfolding of secondary structure of protein with the disappearance of original peaks (208 and 222 nm) and formation of unique peak (226 nm) in the far-UV CD.
Case Report: B Lymphocyte Disorders Under COVID-19 Inflammatory Pressure
Authors: Taliani Gloria , Follini Elena , Guglielmetti Lorenzo , Bernuzzi Patrizia , Faggi Alberto , Ferrante Patrizia , Fronti Elisa , Gerna Laura , Leoni Maria Cristina , Paolillo Franco , Ratti Giovanna , Ruggieri Alessandro , Valdatta Caterina , Donisi Alessandra , Zangrandi Adriano , Pochintesta Lara , Moroni Carlo , Sacchini Daria , Vallisa Daniele , Codeluppi Mauro ,   the COVID-Piacenza Group
Published: March 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects humans through the angiotensin converting enzyme-2 (ACE-2) receptor expressed on many cells, including lymphocytes. In Covid-19 patients IL-6 is overexpressed, and hyperactivated plasmacytoid lymphocytes are detected in peripheral blood film. We hypothesize that, due to the unpredictable interaction between the new virus and the B cell lineage of infected patients, a cascade of out of control events can ensue, capable of determining unexpected pathologic disorders involving such lineage. Here we report two cases of autoimmune hemolytic anemia (AIHA) and two cases of B-cell hematological malignancies developed or reactivated during acute SARS-CoV-2 infection. The temporal relationship of the events may suggest a potential causal relationship between SARS-CoV-2 infection and the hematopoietic disorders. We suggest that special attention should be paid to COVID-19 patients with underlining B cell lineage disorders.
Nano-Neurotheranostics: Impact of Nanoparticles on Neural Dysfunctions and Strategies to Reduce Toxicity for Improved Efficacy
Authors: Vinod Chiluka , Jena Srikanta
Published: March 2021

Nanotheranostics is one of the emerging research areas in the field of nanobiotechnology offering exciting promises for diagnosis, bio-separation, imaging mechanisms, hyperthermia, phototherapy, chemotherapy, drug delivery, gene delivery, among other uses. The major criteria for any nanotheranostic-materials is 1) to interact with proteins and cells without meddling with their basic activities, 2) to maintain their physical properties after surface modifications and 3) must be nontoxic. One of the challenging targets for nanotheranostics is the nervous system with major hindrances from the neurovascular units, the functional units of blood-brain barrier. As blood-brain barrier is crucial for protecting the CNS from toxins and metabolic fluctuations, most of the synthetic nanomaterials cannot pass through this barrier making it difficult for diagnosing or targeting the cells. Biodegradable nanoparticles show a promising role in this aspect. Certain neural pathologies have compromised barrier creating a path for most of the nanoparticles to enter into the cells. However, such carriers may pose a risk of side effects to non-neural tissues and their toxicity needs to be elucidated at preclinical levels. This article reviews about the different types of nanotheranostic strategies applied in nervous dysfunctions. Further, the side effects of these carriers are reviewed and appropriate methods to test the toxicity of such nano-carriers are suggested to improve the effectiveness of nano-carrier based diagnosis and treatments.
Cytocompatibility Properties of an Herbal Compound Solution Support In vitro Wound Healing
Authors: Zhou Peng , Chrepa Vanessa , Karoussis Ioannis , Pikos Michael A. , Kotsakis Georgios A.
Published: March 2021

The aim of this study was to evaluate the cytocompatibility of an herbal extract compound oral rinse [StellaLife VEGA (SLife)] against relevant human cellular models of oral surgical wound healing. SL was compared to the gold standard for peri-/post-operative oral surgical use, i.e., Chlorhexidine (CHX) and to a commonly utilized essential-oil (EO) based antiseptic rinse. Fibroblasts and primary oral stem cells of the apical papilla (SCAPs) were employed to assess its comparative cytotoxicity to the active comparator antiseptic rinses and its effects on wound healing in vitro. In cytotoxicity assays, multiple timepoints were tested ranging from clinically relevant of 60-s rinsing to protracted challenge of up to 5 min, to determine dose-dependent toxicity. The SLife group consistently demonstrated minimal cytotoxicity as compared to active comparators across experimental timepoints and different cells lines. At concentrations up to 20% v/v SLife-challenged fibroblasts and SCAPs demonstrated no significant toxicity as compared to unstimulated controls (p > 0.05). When assessing wound healing, a scratch wound assay revealed significantly accelerated cell migration for SLife as compared to CHX (p < 0.05). Notably, all active comparator antiseptic rinses affected wound healing responses by significantly reducing total collagen deposition after intermittent “rinsing” intervals that simulated post-surgical oral rinsing. Nonetheless, intermittent as well as continuous challenge of cells with SLife had a positive effect in functional collagen assays. An herbal extract compound-based oral rinse was found to be cytocompatible to cells critical to oral wound healing and to promote fibroblast migration and differentiation, contrary to existing antiseptic rinses that lack selective cytotoxicity.
It Takes a Team to Make It Through: The Role of Social Support for Survival and Self-Care After Allogeneic Hematopoietic Stem Cell Transplant
Authors: Song Yaena , Chen Stephanie , Roseman Julia , Scigliano Eileen , Redd William H. , Stadler Gertraud
Published: March 2021

Background

Social support plays an important role for health outcomes. Support for those living with chronic conditions may be particularly important for their health, and even for their survival. The role of support for the survival of cancer patients after receiving an allogeneic hematopoietic cell transplant (alloHCT) is understudied. To better understand the link between survival and support, as well as different sources and functions of support, we conducted two studies in alloHCT patients. First, we examined whether social support is related to survival (Study 1). Second, we examined who provides which support and which specific support-related functions and tasks are fulfilled by lay caregivers and healthcare professionals (Study 2).

Methods

In Study 1, we conducted a retrospective chart review of alloHCT patients (N = 173, 42.8% female, age: M = 49.88) and registered availability of a dedicated lay caregiver and survival. In Study 2, we prospectively followed patients after alloHCT (N = 28, 46.4% female, age: M = 53.97, 46.4% ethnic minority) from the same hospital, partly overlapping from Study 1, who shared their experiences of support from lay caregivers and healthcare providers in semi-structured in-depth interviews 3 to 6 months after their first hospital discharge.

Results

Patients with a dedicated caregiver had a higher probability of surviving to 100 days (86.7%) than patients without a caregiver (69.6%), OR = 2.84, p = 0.042. Study 2 demonstrated the importance of post-transplant support due to patients’ emotional needs and complex self-care regimen. The role of lay caregivers extended to many areas of patients’ daily lives, including support for attending doctor’s appointments, managing medications and financial tasks, physical distancing, and maintaining strict dietary requirements. Healthcare providers mainly fulfilled medical needs and provided informational support, while lay caregivers were the main source of emotional and practical support.

Conclusion

The findings highlight the importance of studying support from lay caregivers as well as healthcare providers, to better understand how they work together to support patients’ adherence to recommended self-care and survival.
Pivoting to Childbirth at Home or in Freestanding Birth Centers1 in the US During COVID-19: Safety, Economics and Logistics
Authors: Daviss Betty-Anne , Anderson David A. , Johnson Kenneth C.
Published: March 2021

Birth-related decisions principally center on safety; giving birth during a pandemic brings safety challenges to a new level, especially when choosing the birth setting. Amid the COVID-19 crisis, the concurrent work furloughs, business failures, and mounting public and private debt have made prudent expenditures an inescapable second concern. This article examines the intersections of safety, economic efficiency, insurance, liability and birthing persons’ needs that have become critical as the pandemic has ravaged bodies and economies around the world. Those interests, and the challenges and solutions discussed in this article, remain important even in less troubled times. Our economic analysis suggests that having an additional 10% of deliveries take place in private homes or freestanding birth centers could save almost $11 billion per year in the United States without compromising safety.
Penile Rehabilitation and Treatment Options for Erectile Dysfunction Following Radical Prostatectomy and Radiotherapy: A Systematic Review
Authors: Nicolai Melianthe , Urkmez Ahmet , Sarikaya Selcuk , Fode Mikkel , Falcone Marco , Albersen Maarten , Gul Murat , Hatzichristodoulou Georgios , Capogrosso Paolo , Russo Giorgio Ivan
Published: March 2021

After radical prostatectomy (RP) or radiotherapy (RT) for prostate cancer, erectile dysfunction (ED) is the main complication next to urinary incontinence, affecting quality of life. The pathophysiology of ED after these treatments is believed to include neuropraxia causing reduced oxygenation and structural changes of the tissue in the corpora cavernosa. Next to the option of sparing the nerves during RP, research has been focusing on methods for penile rehabilitation after RP and RT, since it occurs often, even after nerve-sparing techniques were used. In animal studies, the use of phosphodiesterase type 5 inhibitors (PDE5i) after cavernous nerve damage is supported, but results in human studies are contradictory. Non-medical treatment options such as vacuum device therapy, hyperbaric oxygen therapy, yoga, aerobic, or pelvic floor training may be helpful, but evidence is scarce. Clear guidelines for penile rehabilitation are not yet available. However, care and support for ED after RP and RT is highly demanded by a large group of patients, so measures have to be taken even though the evidence is not strong yet. In this systematic review, an overview of the literature for penile rehabilitation and treatment options for ED after RP and RT is provided, using only randomized controlled trials (RCT).
Ameliorative Effects of Calcium Sprays on Yield and Grain Nutritional Composition of Maize (Zea mays L.) Cultivars under Drought Stress
Authors: Abbas Mohamed , Abdel-Lattif Hashim , Shahba Mohamed
Published: March 2021

Drought stress is seriously affecting maize production. To investigate the influence of calcium (Ca) foliar application on maize production and chemical composition of grains under drought stress, two experiments were carried out at Cairo University Research Station, Giza, Egypt, during the summer seasons of 2018 and 2019. The experimental design was split-split plot design with a completely randomized blocks arrangement with three replications. Water regimes were assigned to the main plots [100 (control), 75, and 50% of estimated evapotranspiration]. Calcium levels (zero and 50 mg/L) were assigned to the sub plots. Maize cultivars (SC-P3444, Sammaz-35 and EVDT) were assigned to the sub-sub plots. Three maize cultivars were sprayed with Ca solution concentration (50 mg/L) under normal and drought conditions. The control treatment (0 mg/L) was sprayed with an equal amount of distilled water for comparison. Results indicated a significant decrease in total yield and grain characteristics [protein, ash, total sugars, nitrogen (N), phosphorus (P), potassium (K), and iron (Fe) contents] as a response of drought. Calcium foliar application significantly increased maize yield, protein, ash, carbohydrates, starch, total sugars, and ionic contents of grains, except for manganese (Mn), under all irrigation levels. Based on the drought tolerance index (DTI), only cultivar SC-P3444 showed drought tolerance while cultivars Sammaz-35 and EVDT were sensitive to drought stress. Foliar application of Ca on SC-P3444 cultivar achieved the highest grain yield per hectare (8061 kg) under the water regime of 100% of the total evapotranspiration, followed by Sammaz-35 (7570 kg), and EVDT (7191 kg) cultivars. At the water regime of 75% of estimated evapotranspiration (75% irrigation), Ca foliar application increased grain yield by 16, 13 and 14% in SC-P3444, Sammaz-35, and EVDT, respectively. At the water regime of 50% of the estimated evapotranspiration (50% irrigation), Ca foliar application increased grain yield by 17, 16, and 13% in SC-P3444, Sammaz-35, and EVDT, respectively. In brief, Ca had a clear impact on productivity and grain quality with important implications for maize yield under normal and water stress conditions. Our findings demonstrate that foliar application of Ca enabled drought stressed maize plants to survive better under stress. The most water stress tolerant cultivar was SC-P3444 followed by Sammaz-35 and EVDT under drought stress.
Sodium Fluoride In Vitro Treatment Affects the Expression of Gonadotropin and Steroid Hormone Receptors in Chicken Embryonic Gonads
Authors: Grzegorzewska Agnieszka Karolina , Grot Ewa , Sechman Andrzej
Published: March 2021

Sodium fluoride (NaF), in addition to preventing dental decay may negatively affect the body. The aim of this study was to examine the effect of a 6 h in vitro treatment of gonads isolated from 14-day-old chicken embryos with NaF at doses of 1.7 (D1), 3.5 (D2), 7.1 (D3), and 14.2 mM (D4). The mRNA expression of luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), estrogen receptors (ESR1 and ESR2), progesterone receptor (PGR), and the immunolocalization of progesterone receptors were examined in the tissue. In the ovary, the expression of FSHR and LHR increased following the NaF treatment. In the case of FSHR the highest stimulatory effect was noticed in the D2 group, while the expression of LHR increased in a dose-dependent manner. A gradual increase in ESR1 and PGR mRNA levels was also observed in the ovary following the NaF treatment, but only up to the D3 dose of NaF. The highest ESR2 level was also found in the D3 group. In the testes, the lowest dose of NaF significantly decreased the expression of FSHR, ESR1, ESR2, and PGR. On the other hand, an increase in PGR expression was observed in the D3 group. The expression of LHR in the testes was not affected by the NaF treatment. Immunohistochemical analysis showed that NaF exposure increased progesterone receptor expression in the ovarian cortex, while it decreased its expression in the testes. These results reveal that NaF may disturb the chicken embryonic development and different mechanisms of this toxicant action exist within the females and males.
Generating Airborne Ultrasonic Amplitude Patterns Using an Open Hardware Phased Array
Authors: Morales Rafael , Ezcurdia Iñigo , Irisarri Josu , Andrade Marco A. B. , Marzo Asier
Published: March 2021

Holographic methods from optics can be adapted to acoustics for enabling novel applications in particle manipulation or patterning by generating dynamic custom-tailored acoustic fields. Here, we present three contributions towards making the field of acoustic holography more widespread. Firstly, we introduce an iterative algorithm that accurately calculates the amplitudes and phases of an array of ultrasound emitters in order to create a target amplitude field in mid-air. Secondly, we use the algorithm to analyse the impact of spatial, amplitude and phase emission resolution on the resulting acoustic field, thus providing engineering insights towards array design. For example, we show an onset of diminishing returns for smaller than a quarter-wavelength sized emitters and a phase and amplitude resolution of eight and four divisions per period, respectively. Lastly, we present a hardware platform for the generation of acoustic holograms. The array is integrated in a single board composed of 256 emitters operating at 40 kHz. We hope that the results and procedures described within this paper enable researchers to build their own ultrasonic arrays and explore novel applications of ultrasonic holograms.
Enhancement of Optical Chirality Using Metasurfaces for Enantiomer-Selective Molecular Sensing
Authors: Jeon Sangtae , Kim Soo Jin
Published: March 2021

Circular dichroism (CD) is a physical property observed in chiral molecules by inducing the difference of absorption between left- and right-handed circularly polarized light (CPL). Circular dichroism spectroscopy is widely used in the field of chemistry and biology to distinguish the enantiomers, which typically show either positive or severe side effects in biological applications depending on the molecular structures’ chirality. To effectively detect the chirality of molecules, diverse designs of nanostructured platforms are proposed based on optical resonances that can enhance the optical chirality and amplify the signal of circular dichroism. However, the underlying physics between the optical chirality and the resonance in a nanostructure is largely unexplored, and thus designing rules for optimal chiral detection is still elusive. Here, we carry out an in-depth analysis of chiral enhancement (C enhancement) in nanostructured surfaces to find the relationship between optical resonances and chirality. Based on the relations, we optimize the nanostructured metasurface to induce effective chiral detection of enantiomers for diverse conditions of molecule distribution. We believe that the proposed designing rules and physics pave the important pathway to enhance the optical chirality for effective circular dichroism spectroscopy.
Radiation Effects on Pure-Silica Multimode Optical Fibers in the Visible and Near-Infrared Domains: Influence of OH Groups
Authors: Campanella Cosimo , De Michele Vincenzo , Morana Adriana , Mélin Gilles , Robin Thierry , Marin Emmanuel , Ouerdane Youcef , Boukenter Aziz , Girard Sylvain
Published: March 2021

Signal transmission over optical fibers in the ultraviolet to near-infrared domains remains very challenging due to their high intrinsic losses. In radiation-rich environments, this is made even more difficult due to the radiation-induced attenuation (RIA) phenomenon. We investigated here how the number of hydroxyl groups (OH) present in multi-mode (MM) pure-silica core (PSC) optical fibers influences the RIA levels and kinetics. For this, we tested three different fiber samples: one “wet”, one “dry” and one with an intermediate “medium” OH content. The RIA of the three samples was measured in the 400–900 nm (~3 eV to ~1.4 eV) spectral range during and after an X-ray irradiation at a dose rate of 6 Gy(SiO2) s−1 up to a total accumulated dose of 300 kGy(SiO2). Furthermore, we evaluated the H2-pre-loading efficiency in the medium OH sample to permanently improve both its intrinsic losses and radiation response in the visible domain. Finally, the spectral decomposition of the various RIA responses allows us to better understand the basic mechanisms related to the point defects causing the excess of optical losses. Particularly, it reveals the relationship between the initial OH groups content and the generation of non-bridging oxygen hole centers (NBOHCs). Moreover, the presence of hydroxyl groups also affects the contribution from other intrinsic defects such as the self-trapped holes (STHs) to the RIA in this spectral domain.
3D Printing for Soft Tissue Regeneration and Applications in Medicine
Authors: Pantermehl Sven , Emmert Steffen , Foth Aenne , Grabow Niels , Alkildani Said , Bader Rainer , Barbeck Mike , Jung Ole
Published: March 2021

The use of additive manufacturing (AM) technologies is a relatively young research area in modern medicine. This technology offers a fast and effective way of producing implants, tissues, or entire organs individually adapted to the needs of a patient. Today, a large number of different 3D printing technologies with individual application areas are available. This review is intended to provide a general overview of these various printing technologies and their function for medical use. For this purpose, the design and functionality of the different applications are presented and their individual strengths and weaknesses are explained. Where possible, previous studies using the respective technologies in the field of tissue engineering are briefly summarized.
Evidence of Neurovascular Un-Coupling in Mild Alzheimer’s Disease through Multimodal EEG-fNIRS and Multivariate Analysis of Resting-State Data
Authors: Chiarelli Antonio M. , Perpetuini David , Croce Pierpaolo , Filippini Chiara , Cardone Daniela , Rotunno Ludovica , Anzoletti Nelson , Zito Michele , Zappasodi Filippo , Merla Arcangelo
Published: March 2021

Alzheimer’s disease (AD) is associated with modifications in cerebral blood perfusion and autoregulation. Hence, neurovascular coupling (NC) alteration could become a biomarker of the disease. NC might be assessed in clinical settings through multimodal electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Multimodal EEG-fNIRS was recorded at rest in an ambulatory setting to assess NC and to evaluate the sensitivity and specificity of the methodology to AD. Global NC was evaluated with a general linear model (GLM) framework by regressing whole-head EEG power envelopes in three frequency bands (theta, alpha and beta) with average fNIRS oxy- and deoxy-hemoglobin concentration changes in the frontal and prefrontal cortices. NC was lower in AD compared to healthy controls (HC) with significant differences in the linkage of theta and alpha bands with oxy- and deoxy-hemoglobin, respectively (p = 0.028 and p = 0.020). Importantly, standalone EEG and fNIRS metrics did not highlight differences between AD and HC. Furthermore, a multivariate data-driven analysis of NC between the three frequency bands and the two hemoglobin species delivered a cross-validated classification performance of AD and HC with an Area Under the Curve, AUC = 0.905 (p = 2.17 × 10−5). The findings demonstrate that EEG-fNIRS may indeed represent a powerful ecological tool for clinical evaluation of NC and early identification of AD.
Identification of Gait-Cycle Phases for Prosthesis Control
Authors: Di Gregorio Raffaele , Vocenas Lucas
Published: March 2021

The major problem with transfemoral prostheses is their capacity to compensate for the loss of the knee joint. The identification of gait-cycle phases plays an important role in the control of these prostheses. Such control is completely up to the patient in passive prostheses or partly facilitated by the prosthesis in semiactive prostheses. In both cases, the patient recovers his/her walking ability through a suitable rehabilitation procedure that aims at recreating proprioception in the patient. Understanding proprioception passes through the identification of conditions and parameters that make the patient aware of lower-limb body segments’ postures, and the recognition of the current gait-cycle phase/period is the first step of this awareness. Here, a proposal is presented for the identification of the gait-cycle phases/periods under different walking conditions together with a control logic for a possible active/semiactive prosthesis. The proposal is based on the detection of different gait-cycle events as well as on different walking conditions through a load sensor, which is implemented by analyzing the variations in some gait parameters. The validation of the proposed method is done by using gait-cycle data present in the literature. The proposal assumes the prosthesis is equipped with an energy-storing foot without mobility.
Predictors of Pharmaco-Resistance in Patients with Post-Stroke Epilepsy
Authors: Lattanzi Simona , Rinaldi Claudia , Cagnetti Claudia , Foschi Nicoletta , Norata Davide , Broggi Serena , Rocchi Chiara , Silvestrini Mauro
Published: March 2021

Objectives: The study aimed to explore the clinical predictors of pharmaco-resistance in patients with post-stroke epilepsy (PSE). Methods: Patients with epilepsy secondary to cerebral infarct or spontaneous intracerebral hemorrhage were included. The study outcome was the occurrence of pharmaco-resistance defined as the failure of adequate trials of two tolerated and appropriately chosen and used antiseizure medication schedules, whether as monotherapies or in combination, to achieve sustained seizure freedom. Results: One-hundred and fifty-nine patients with PSE and a median follow-up of 5 (3–9) years were included. The mean age of the patients at stroke onset was 56.7 (14.9) years, and 104 (65.4%) were males. In the study cohort, 29 participants were pharmaco-resistant. Age at stroke onset [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.93–0.99; p = 0.044], history of intracerebral hemorrhage (OR 2.95, 95% CI 1.06–8.24; p = 0.039), severe stroke (OR 5.43, 95% CI 1.82–16.16; p = 0.002), status epilepticus as initial presentation of PSE (OR 7.90, 1.66–37.55; p = 0.009), and focal to bilateral tonic-clonic seizures (OR 3.19, 95% CI 1.16–8.79; p = 0.025) were independent predictors of treatment refractoriness. Conclusions: Pharmaco-resistance developed in approximately 20% of patients with PSE and was associated with younger age at stroke onset, stroke type and severity, status epilepticus occurrence, and seizure types.
Neuroendocrine Assessment of Dopaminergic Function during Antidepressant Treatment in Major Depressed Patients
Authors: Duval Fabrice , Mokrani Marie-Claude , Erb Alexis , Gonzalez Lopera Felix , Danila Vlad , Tomsa Mihaela
Published: March 2021

The effects of antidepressants on dopamine (DA) receptor sensitivity in the mesolimbic–hypothalamic system have yielded contradictory results. The postsynaptic DA receptor function was evaluated by the cortisol response to apomorphine (APO; 0.75 mg SC) in 16 drug-free DSM-5 major depressed inpatients and 18 healthy hospitalized control (HC) subjects. Cortisol response to the dexamethasone suppression test (DST) was also measured. After two and four weeks of antidepressant treatment (ADT), the DST and APO test were repeated in all patients. Cortisol response to APO (∆COR) was not influenced by the hypothalamic–pituitary–adrenal (HPA) axis activity, as assessed by the DST. Pre-treatment ∆COR values did not differ significantly between patients and HCs. During ADT, ∆COR values were lower than in HCs at week 2 and 4. After four weeks of treatment, among the eight patients who had blunted ∆COR values, seven were subsequent remitters, while among the eight patients who had normal ∆COR values, seven were non-remitters. Considering the limitations of our study, the results suggest that following chronic ADT, the desensitization of postsynaptic DA receptors connected with the regulation of the HPA axis at the hypothalamic level is associated with clinical remission. These results could reflect increased DA levels in the mesolimbic pathway.
Preparation of Pt/CNT Thin-Film Electrodes by Electrochemical Potential Pulse Deposition for Methanol Oxidation
Authors: Quintero-Ruiz Jose , Ruiz-Rosas Ramiro , Quílez-Bermejo Javier , Salinas-Torres David , Cazorla-Amorós Diego , Morallón Emilia
Published: March 2021

High-quality performance of catalysts is increasingly required to meet industry exigencies. However, chemical synthesis is often insufficient to maximize the potential properties of the catalysts. On the other hand, electrochemical synthesis has arisen as a promising alternative to overcome these limitations and provide precise control in the preparation of catalysts. In this sense, this work involved the well-controlled electrochemical synthesis of a catalyst based on platinum nanoparticle deposition on carbon nanotubes using only electrochemical treatments. Thin films of functionalized carbon nanotubes were cast onto the surface of a glassy carbon electrode using potential pulsed electrodeposition, resulting in a better distribution of the carbon nanotubes on the electrode when comparing with traditional methods. Then, platinum nanoparticles were electrodeposited on the carbon nanotube-modified electrode. To check the performance of the catalyst and the relevance of the electrochemical synthesis treatments, the samples were analyzed as electrocatalysts towards methanol electrooxidation, showing an important improvement in the catalytic activity in comparison with electrodes that were prepared by traditional methodologies.
microRNAs as Novel Therapeutics in Cancer
Authors: Romano Giulia , Acunzo Mario , Nana-Sinkam Patrick
Published: March 2021

In the last 20 years, the functional roles for miRNAs in gene regulation have been well established. MiRNAs act as regulators in virtually all biological pathways and thus have been implicated in numerous diseases, including cancer. They are particularly relevant in regulating the basic hallmarks of cancer, including apoptosis, proliferation, migration, and invasion. Despite the substantial progress made in identifying the molecular mechanisms driving the deregulation of miRNAs in cancer, the clinical translation of these important molecules to therapy remains in its infancy. The paucity of vehicles available for the safe and efficient delivery of miRNAs and ongoing concerns for toxicity remain major obstacles to clinical application. Novel formulations and the development of new vectors have significantly improved the stability of oligonucleotides, increasing the effectiveness of therapy. Furthermore, the use of specific moieties for delivery in target tissues or cells has increased the specificity of treatment. The use of new technologies has allowed small but important steps toward more specific therapeutic delivery in tumor tissues and cells. Although a long road remains, the path ahead holds great potential. Currently, a few miRNA drugs are under investigation in human clinical trials with promising results ahead.
Aminopeptidase Expression in Multiple Myeloma Associates with Disease Progression and Sensitivity to Melflufen
Authors: Miettinen Juho J. , Kumari Romika , Traustadottir Gunnhildur Asta , Huppunen Maiju-Emilia , Sergeev Philipp , Majumder Muntasir M. , Schepsky Alexander , Gudjonsson Thorarinn , Lievonen Juha , Bazou Despina , Dowling Paul , O`Gorman Peter , Slipicevic Ana , Anttila Pekka , Silvennoinen Raija , Nupponen Nina N. , Lehmann Fredrik , Heckman Caroline A.
Published: March 2021

Multiple myeloma (MM) is characterized by extensive immunoglobulin production leading to an excessive load on protein homeostasis in tumor cells. Aminopeptidases contribute to proteolysis by catalyzing the hydrolysis of amino acids from proteins or peptides and function downstream of the ubiquitin–proteasome pathway. Notably, aminopeptidases can be utilized in the delivery of antibody and peptide-conjugated drugs, such as melflufen, currently in clinical trials. We analyzed the expression of 39 aminopeptidase genes in MM samples from 122 patients treated at Finnish cancer centers and 892 patients from the CoMMpass database. Based on ranked abundance, LAP3, ERAP2, METAP2, TTP2, and DPP7 were highly expressed in MM. ERAP2, XPNPEP1, DPP3, RNPEP, and CTSV were differentially expressed between relapsed/refractory and newly diagnosed MM samples (p < 0.05). Sensitivity to melflufen was detected ex vivo in 11/15 MM patient samples, and high sensitivity was observed, especially in relapsed/refractory samples. Survival analysis revealed that high expression of XPNPEP1, RNPEP, DPP3, and BLMH (p < 0.05) was associated with shorter overall survival. Hydrolysis analysis demonstrated that melflufen is a substrate for aminopeptidases LAP3, LTA4H, RNPEP, and ANPEP. The sensitivity of MM cell lines to melflufen was reduced by aminopeptidase inhibitors. These results indicate critical roles of aminopeptidases in disease progression and the activity of melflufen in MM.