bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Factors Predicting a Favorable Opinion of Research Applications Submitted for an Ethical Review Process
Authors: Mirpuri Eduardo , García-Álvarez Lara , Acín-Gericó María Teresa , Bartolomé Blanca , Delgado Bolton Roberto C. , San-Martín Montserrat , Vivanco Luis
Published: June 2022

Introduction

In Spain, biomedical research applications must receive a positive ethical opinion from Research Ethics Committees (RECs) before being executed. There is limited information on how to optimize the ethical review process to reduce delays. This study was performed to characterize variables predicting favorable opinions at the first ethical review performed by a REC.

Material and Methods

The study assessed all research applications revised by a REC in 2019–2020. Data was extracted from REC's database of La Rioja, Spain. Variables collected covered three areas: (i) principal investigator's profile; (ii) study design; and (iii) ethical review process. A model based on multiple logistic regression analysis was created to identify variables explaining favorable opinions in first rounds of ethical review processes.

Results

The sample included 125 applications (41 submitted in 2019, and 84 in 2020). At the first review, nine (7%) applications were rejected, 56 (45%) were approved, and the remaining 60 (48%) required at least two reviews prior to approval. When comparing both years, a 2-fold increase in the number of applications submitted, and a difference in the ratio of applications with a favorable vs. non-favorable opinion were observed. Furthermore, a model predicted 71% of probability of obtaining a favorable opinion in the first ethical review. Three variables appeared as being explanatory: if the principal investigator is either the group leader or the department's head (OR = 17.39; p < 0.001), and if the informed consent (OR = 11.79; p = 0.01), and methods and procedures (OR = 34.15; p < 0.001) are well done.

Conclusions

These findings confirm an increase in the number of submissions and a difference in the ratio of applications approved by year. Findings observed also confirm deficiencies in “informed consent” and in “methods and procedures” are the two main causes of delay for favorable ethical opinions. Additionally, findings highlight the need that group leaders and heads of departments should be more involved in guiding and supervising their research teams, especially when research applications are led by less experienced researchers. Based on these findings, it is suggested that an adequate mentoring and targeted training in research could derive in more robust research applications and in smoother ethical review processes.
Microbial Communities in Biocrusts Are Recruited From the Neighboring Sand at Coastal Dunes Along the Baltic Sea
Authors: Glaser Karin , Van Ahn Tu , Pushkareva Ekaterina , Barrantes Israel , Karsten Ulf
Published: June 2022

Biological soil crusts occur worldwide as pioneer communities stabilizing the soil surface. In coastal primary sand dunes, vascular plants cannot sustain due to scarce nutrients and the low-water-holding capacity of the sand sediment. Thus, besides planted dune grass, biocrusts are the only vegetation there. Although biocrusts can reach high coverage rates in coastal sand dunes, studies about their biodiversity are rare. Here, we present a comprehensive overview of the biodiversity of microorganisms in such biocrusts and the neighboring sand from sampling sites along the Baltic Sea coast. The biodiversity of Bacteria, Cyanobacteria, Fungi, and other microbial Eukaryota were assessed using high-throughput sequencing (HTS) with a mixture of universal and group-specific primers. The results showed that the biocrusts recruit their microorganisms mainly from the neighboring sand rather than supporting a universal biocrust microbiome. Although in biocrusts the taxa richness was lower than in sand, five times more co-occurrences were identified using network analysis. This study showed that by comparing neighboring bare surface substrates with biocrusts holds the potential to better understand biocrust development. In addition, the target sequencing approach helps outline potential biotic interactions between different microorganisms groups and identify key players during biocrust development.
Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced Sepsis
Authors: Liu Jun , Ding Hui , Zhao Mingjie , Tu Fan , He Tian , Zhang Lizhu , Jing Yanfei , Rui Xiaohong , Zhang Shiliang
Published: June 2022

Sepsis is a systemic inflammatory response syndrome caused by infection, with high incidence and mortality. Therefore, it is necessary to carry out an effective anti-infection treatment. In this work, we designed and synthesized red blood cell (RBC) membrane-coated PLGA nanoparticles named γ3-RBCNPs, which target the highly expressed intercellular adhesion molecule-1 (ICAM-1) at the site of infection through the γ3 peptide on its surface and kill the Klebsiella pneumoniae through ciprofloxacin encapsulated in its core. In addition, the homogenous RBC membrane coated on the surface of the nanoparticles helps them avoid immune surveillance and prolong the circulation time of the drug in the body. We found that the γ3-RBCNPs target human umbilical vein endothelial cells (HUVECs) activated by TNF-α in vitro and the infected lung of mice in the sepsis model very well. In vitro evaluation suggested that γ3-RBCNPs have a low risk of acute hemolysis and are less likely to be engulfed by macrophages. In vivo evaluation showed that γ3-RBCNPs has a long half-life and good bio-safety. More importantly, we confirmed that γ3-RBCNPs have the good antibacterial and anti-infection ability in vivo and in vitro. Our research provides a new strategy for the nano-drug treatment of Klebsiella pneumoniae-induced sepsis.
L-Proline Synthesis Mutants of Bacillus subtilis Overcome Osmotic Sensitivity by Genetically Adapting L-Arginine Metabolism
Authors: Stecker Daniela , Hoffmann Tamara , Link Hannes , Commichau Fabian M. , Bremer Erhard
Published: June 2022

The accumulation of the compatible solute L-proline by Bacillus subtilis via synthesis is a cornerstone in the cell’s defense against high salinity as the genetic disruption of this biosynthetic process causes osmotic sensitivity. To understand how B. subtilis could potentially cope with high osmolarity surroundings without the functioning of its natural osmostress adaptive L-proline biosynthetic route (ProJ-ProA-ProH), we isolated suppressor strains of proA mutants under high-salinity growth conditions. These osmostress-tolerant strains carried mutations affecting either the AhrC transcriptional regulator or its operator positioned in front of the argCJBD-carAB-argF L-ornithine/L-citrulline/L-arginine biosynthetic operon. Osmostress protection assays, molecular analysis and targeted metabolomics showed that these mutations, in conjunction with regulatory mutations affecting rocR-rocDEF expression, connect and re-purpose three different physiological processes: (i) the biosynthetic pathway for L-arginine, (ii) the RocD-dependent degradation route for L-ornithine, and (iii) the last step in L-proline biosynthesis. Hence, osmostress adaptation without a functional ProJ-ProA-ProH route is made possible through a naturally existing, but inefficient, metabolic shunt that allows to substitute the enzyme activity of ProA by feeding the RocD-formed metabolite γ-glutamate-semialdehyde/Δ1-pyrroline-5-carboxylate into the biosynthetic route for the compatible solute L-proline. Notably, in one class of mutants, not only substantial L-proline pools but also large pools of L-citrulline were accumulated, a rather uncommon compatible solute in microorganisms. Collectively, our data provide an example of the considerable genetic plasticity and metabolic resourcefulness of B. subtilis to cope with everchanging environmental conditions.
High Diversity of Novel Viruses in the Tree Pathogen Phytophthora castaneae Revealed by High-Throughput Sequencing of Total and Small RNA
Authors: Raco Milica , Vainio Eeva J. , Sutela Suvi , Eichmeier Aleš , Hakalová Eliška , Jung Thomas , Botella Leticia
Published: June 2022

Phytophthora castaneae, an oomycete pathogen causing root and trunk rot of different tree species in Asia, was shown to harbor a rich diversity of novel viruses from different families. Four P. castaneae isolates collected from Chamaecyparis hodginsii in a semi-natural montane forest site in Vietnam were investigated for viral presence by traditional and next-generation sequencing (NGS) techniques, i.e., double-stranded RNA (dsRNA) extraction and high-throughput sequencing (HTS) of small RNAs (sRNAs) and total RNA. Genome organization, sequence similarity, and phylogenetic analyses indicated that the viruses were related to members of the order Bunyavirales and families Endornaviridae, Megabirnaviridae, Narnaviridae, Totiviridae, and the proposed family “Fusagraviridae.” The study describes six novel viruses: Phytophthora castaneae RNA virus 1–5 (PcaRV1-5) and Phytophthora castaneae negative-stranded RNA virus 1 (PcaNSRV1). All six viruses were detected by sRNA sequencing, which demonstrates an active RNA interference (RNAi) system targeting viruses in P. castaneae. To our knowledge, this is the first report of viruses in P. castaneae and the whole Phytophthora major Clade 5, as well as of the activity of an RNAi mechanism targeting viral genomes among Clade 5 species. PcaRV1 is the first megabirnavirus described in oomycetes and the genus Phytophthora.
Chinese Baijiu: The Perfect Works of Microorganisms
Authors: Tu Wenying , Cao Xiaonian , Cheng Jie , Li Lijiao , Zhang Ting , Wu Qian , Xiang Peng , Shen Caihong , Li Qiang
Published: June 2022

Chinese Baijiu is one of the famous distilled liquor series with unique flavors in the world. Under the open environment, Chinese Baijiu was produced by two solid-state fermentation processes: jiuqu making and baijiu making. Chinese Baijiu can be divided into different types according to the production area, production process, starter type, and product flavor. Chinese Baijiu contains rich flavor components, such as esters and organic acids. The formation of these flavor substances is inseparable from the metabolism and interaction of different microorganisms, and thus, microorganisms play a leading role in the fermentation process of Chinese Baijiu. Bacteria, yeasts, and molds are the microorganisms involved in the brewing process of Chinese Baijiu, and they originate from various sources, such as the production environment, production workers, and jiuqu. This article reviews the typical flavor substances of different types of Chinese Baijiu, the types of microorganisms involved in the brewing process, and their functions. Methods that use microbial technology to enhance the flavor of baijiu, and for detecting flavor substances in baijiu were also introduced. This review systematically summarizes the role and application of Chinese Baijiu flavor components and microorganisms in baijiu brewing and provides data support for understanding Chinese Baijiu and further improving its quality.
Genomic Insight Into Lacticaseibacillus paracasei SP5, Reveals Genes and Gene Clusters of Probiotic Interest and Biotechnological Potential
Authors: Kiousi Despoina Eugenia , Efstathiou Christos , Tegopoulos Konstantinos , Mantzourani Ioanna , Alexopoulos Athanasios , Plessas Stavros , Kolovos Petros , Koffa Maria , Galanis Alex
Published: June 2022

The Lacticaseibacillus paracasei species is comprised by nomadic bacteria inhabiting a wide variety of ecological niches, from fermented foodstuffs to host-associated microenvironments. Lc. paracasei SP5 is a novel strain, originally isolated from kefir grains that presents desirable probiotic and biotechnological attributes. In this study, we applied genomic tools to further characterize the probiotic and biotechnological potential of the strain. Firstly, whole genome sequencing and assembly, were performed to construct the chromosome map of the strain and determine its genomic stability. Lc. paracasei SP5 carriers several insertion sequences, however, no plasmids or mobile elements were detected. Furthermore, phylogenomic and comparative genomic analyses were utilized to study the nomadic attributes of the strain, and more specifically, its metabolic capacity and ability to withstand environmental stresses imposed during food processing and passage through the gastrointestinal (GI) tract. More specifically, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-active enzyme (CAZymes) analyses provided evidence for the ability of the stain to utilize an array of carbohydrates as growth substrates. Consequently, genes for heat, cold, osmotic shock, acidic pH, and bile salt tolerance were annotated. Importantly bioinformatic analysis showed that the novel strain does not harbor acquired antimicrobial resistance genes nor virulence factors, in agreement with previous experimental data. Putative bacteriocin biosynthesis clusters were identified using BAGEL4, suggesting its potential antimicrobial activity. Concerning microbe-host interactions, adhesins, moonlighting proteins, exopolysaccharide (EPS) biosynthesis genes and pilins mediating the adhesive phenotype were, also, pinpointed in the genome of Lc. paracasei SP5. Validation of this phenotype was performed by employing a microbiological method and confocal microscopy. Conclusively, Lc. paracasei SP5 harbors genes necessary for the manifestation of the probiotic character and application in the food industry. Upcoming studies will focus on the mechanisms of action of the novel strain at multiple levels.
Transgenic Soybeans Expressing Phosphatidylinositol-3-Phosphate-Binding Proteins Show Enhanced Resistance Against the Oomycete Pathogen Phytophthora sojae
Authors: Helliwell Emily E. , Lafayette Peter , Kronmiller Brent N. , Arredondo Felipe , Duquette Madeleine , Co Anna , Vega-Arreguin Julio , Porter Stephanie S. , Borrego Eli J. , Kolomiets Michael V. , Parrott Wayne A. , Tyler Brett M.
Published: June 2022

Oomycete and fungal pathogens cause billions of dollars of damage to crops worldwide annually. Therefore, there remains a need for broad-spectrum resistance genes, especially ones that target pathogens but do not interfere with colonization by beneficial microbes. Motivated by evidence suggesting that phosphatidylinositol-3-phosphate (PI3P) may be involved in the delivery of some oomycete and fungal virulence effector proteins, we created stable transgenic soybean plants that express and secrete two different PI3P-binding proteins, GmPH1 and VAM7, in an effort to interfere with effector delivery and confer resistance. Soybean plants expressing the two PI3P-binding proteins exhibited reduced infection by the oomycete pathogenPhytophthora sojaecompared to control lines. Measurements of nodulation by nitrogen-fixing mutualistic bacteriumBradyrhizobium japonicum, which does not produce PI3P, revealed that the two lines with the highest levels ofGmPH1transcripts exhibited reductions in nodulation and in benefits from nodulation. Transcriptome and plant hormone measurements were made of soybean lines with the highest transcript levels ofGmPH1andVAM7, as well as controls, followingP. sojae- or mock-inoculation. The results revealed increased levels of infection-associated transcripts in the transgenic lines, compared to controls, even prior toP. sojaeinfection, suggesting that the plants were primed for increased defense. The lines with reduced nodulation exhibited elevated levels of jasmonate-isoleucine and of transcripts of aJAR1ortholog encoding jasmonate-isoleucine synthetase. However, lines expressingVAM7transgenes exhibited normal nodulation and no increases in jasmonate-isoleucine. Overall, together with previously published data from cacao and fromP. sojaetransformants, the data suggest that secretion of PI3P-binding proteins may confer disease resistance through a variety of mechanisms.
Antifungal Mechanisms and Application of Lactic Acid Bacteria in Bakery Products: A Review
Authors: Liu Aiping , Xu Ruixia , Zhang Shun , Wang Yuting , Hu Bin , Ao Xiaolin , Li Qin , Li Jianlong , Hu Kaidi , Yang Yong , Liu Shuliang
Published: June 2022

Bakery products are nutritious, but they are susceptible to fungal contamination, which leads to a decline in quality and safety. Chemical preservatives are often used to extend the shelf-life of bakery products, but long-term consumption of these preservatives may increase the risk of chronic diseases. Consumers increasingly demand food with fewer chemical preservatives. The application of lactic acid bacteria (LAB) as a novel biological preservative not only prolongs the shelf-life of bakery products but also improves the baking properties of bakery products. This review summarizes different types and action mechanisms of antifungal compounds produced by LAB, factors affecting the production of antifungal compounds, and the effects of antifungal LAB on bakery products, providing a reference for future applications of antifungal LAB in bakery products.
Avoid or Embrace? Practice Effects in Alzheimer’s Disease Prevention Trials
Authors: Aschenbrenner Andrew J. , Hassenstab Jason , Wang Guoqiao , Li Yan , Xiong Chengjie , McDade Eric , Clifford David B. , Salloway Stephen , Farlow Martin , Yaari Roy , Cheng Eden Y. J. , Holdridge Karen C. , Mummery Catherine J. , Masters Colin L. , Hsiung Ging-Yuek , Surti Ghulam , Day Gregory S. , Weintraub Sandra , Honig Lawrence S. , Galvin James E. , Ringman John M. , Brooks William S. , Fox Nick C. , Snyder Peter J. , Suzuki Kazushi , Shimada Hiroyuki , Gräber Susanne , Bateman Randall J.
Published: June 2022

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer’s disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed “practice effects”). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials are similar to those from observational studies and how these potential differences impact trials is unknown. In the current study, we analyzed data from the recently completed DIAN-TU-001 clinical trial (TU) and the associated DIAN-Observational (OBS) study. Results indicated that asymptomatic mutation carriers in the TU exhibited persistent practice effects on several key outcomes spanning the entire trial duration. Critically, these practice related improvements were larger on certain tests in the TU relative to matched participants from the OBS study. Our results suggest that the magnitude of practice effects may not be captured by modeling potential endpoints in observational studies where assessments are typically less frequent and drug expectancy effects are absent. Using alternate instrument forms (represented in our study by computerized tasks) may partly mitigate practice effects in clinical trials but incorporating practice effects as outcomes may also be viable. Thus, investigators must carefully consider practice effects (either by minimizing them or modeling them directly) when designing cognitive endpoint AD prevention trials by utilizing trial data with similar assessment frequencies.
Accuracy of Step Count Estimations in Parkinson’s Disease Can Be Predicted Using Ambulatory Monitoring
Authors: Shokouhi Navid , Khodakarami Hamid , Fernando Chathurini , Osborn Sarah , Horne Malcolm
Published: June 2022

Objectives

There are concerns regarding the accuracy of step count in Parkinson’s disease (PD) when wearable sensors are used. In this study, it was predicted that providing the normal rhythmicity of walking was maintained, the autocorrelation function used to measure step count would provide relatively low errors in step count.

Materials and Methods

A total of 21 normal walkers (10 without PD) and 27 abnormal walkers were videoed while wearing a sensor [Parkinson’s KinetiGraph (PKG)]. Median step count error rates were observed to be <3% in normal walkers but ≥3% in abnormal walkers. The simultaneous accelerometry data and data from a 6-day PKG were examined and revealed that the 5th percentile of the spectral entropy distribution, among 10-s walking epochs (obtained separately), predicted whether subjects had low error rate on step count with reference to the manual step count from the video recording. Subjects with low error rates had lower Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS III) scores and UPDRS III Q10–14 scores than the high error rate counterparts who also had high freezing of gait scores (i.e., freezing of gait questionnaire).

Results

Periods when walking occurred were identified in a 6-day PKG from 190 non-PD subjects aged over 60, and 155 people with PD were examined and the 5th percentile of the spectral entropy distribution, among 10-s walking epochs, was extracted. A total of 84% of controls and 72% of people with PD had low predicted error rates. People with PD with low bradykinesia scores (measured by the PKG) had step counts similar to controls, whereas those with high bradykinesia scores had step counts similar to those with high error rates. On subsequent PKGs, step counts increased when bradykinesia was reduced by treatment and decreased when bradykinesia increased. Among both control and people with PD, low error rates were associated with those who spent considerable time making walks of more than 1-min duration.

Conclusion

Using a measure of the loss of rhythmicity in walking appears to be a useful method for detecting the likelihood of error in step count. Bradykinesia in subjects with low predicted error in their step count is related to overall step count but when the predicted error is high, the step count should be assessed with caution.
Association Between Mitochondrial Function and Rehabilitation of Parkinson's Disease: Revealed by Exosomal mRNA and lncRNA Expression Profiles
Authors: Wang Yixuan , Liu Yonghong , Jin Zhaohui , Liu Cui , Yu Xin , Chen Keke , Meng Detao , Liu Aixian , Fang Boyan
Published: June 2022

Rehabilitation has been proposed as a valid measure complementary to the management of Parkinson's disease (PD). However, the mechanism underlying is not clear yet. The differential expressions of exosomal messenger RNA (mRNA) and long noncoding RNAs (lncRNAs) may play a critical role in PD progression and rehabilitation. To compare the differential expressions of exosomal mRNAs and lncRNAs, patients with PD (PWPs, Hoehn and Yahr stages 1.5-2.5, n = 6) and age- and sex-matched healthy controls (HCs, n = 6) were included in this study. All PWPs received a 2-week rehabilitation treatment in the hospital, which seemingly led to improvement in both the motor and non-motor functions. A set of differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) extracted from exosomes in blood samples via next-generation sequencing (NGS) was screened out. Compared to HCs, 2,337 vs. 701 mRNAs and 1,278 vs. 445 lncRNAs were significantly upregulated and significantly downregulated, respectively, in pre-rehabilitation (pre-rehab) PWPs; 2,490 vs. 629 mRNAs and 1,561 vs. 370 lncRNAs were significantly upregulated and significantly downregulated, respectively, in post-rehabilitation (post-rehab) PWPs. Compared to pre-rehab PWPs, 606 vs. 1,056 mRNAs and 593 vs. 1,136 lncRNAs were significantly upregulated and significantly downregulated, respectively, in post-rehab PWPs. Overall, 14 differentially expressed mRNAs (DEmRNAs) and 73 differentially expressed lncRNAs (DElncRNAs) were expressed in the blood exosomes of HCs, pre- and post-rehab PWPs, simultaneously. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified 243 significantly co-expressed lncRNA-mRNA pairs. One DEmRNA of interest (ENSG00000099795, NDUFB7) and three corresponding DElncRNAs (ENST00000564683, ENST00000570408, and ENST00000628340) were positively related. Quantitative real-time polymerase chain reaction (qRT-PCR) validated that the expression levels of NDUFB7 mRNA and the 3 DElncRNAs increased significantly in pre-rehab PWPs, but decreased significantly in post-rehab PWPs compared to HCs. NDUFB7 mRNA is a marker related to mitochondrial respiration. It is reasonably believed that mitochondrial function is associated with PD rehabilitation, and the mitochondrial pathway may involve in the pathogenesis of PD.
Development and Validation of a Nomogram for Predicting Postoperative Delirium in Patients With Elderly Hip Fracture Based on Data Collected on Admission
Authors: Yang Yin , Wang Tianpei , Guo Hua , Sun Ye , Cao Junjun , Xu Peng , Cai Yongsong
Published: June 2022

Delirium is a common postoperative complication in elderly hip fracture patients that seriously affects patients’ lives and health, and early delirium risk prediction, and targeted measures can significantly reduce the incidence of delirium. The purpose of this study was to develop and validate a nomogram for the prediction of postoperative delirium (POD) in elderly hip fracture patients. A total of 328 elderly patients with hip fractures enrolled retrospectively in department 1 of our hospital were randomly divided into the training set (n = 230) and the internal validation set (n = 98). The least absolute shrinkage and selection operator (LASSO) regression analysis was used for feature variable selection, and multivariate logistic regression with a backward stepwise method was used to construct a nomogram in the training set. The discrimination efficacy and calibration efficacy of the nomogram were evaluated through the receiver operating characteristic (ROC) curve and calibration curve, respectively. The clinical usefulness was estimated through decision curve analysis (DCA) and clinical impact curve (CIC) analysis. Another validation set from department 2 of our hospital, containing 76 elderly patients with hip fractures, was used for external validation of the nomogram. A total of 43 (13.1%) and 12 (15.8%) patients had POD in department 1 and department 2, respectively. The nomogram was constructed by three predictors, including dementia, chronic obstructive pulmonary disease (COPD), and albumin level. The nomogram showed good discrimination efficacy and calibration efficacy, with the AUC of 0.791 (95% CI, 0.708–0.873), 0.820 (95% CI, 0.676–0.964), and 0.841 (95% CI, 0.717–0.966) in the training set, the internal validation set, and the external validation set, respectively. Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. The nomogram constructed by dementia, COPD, and albumin level can be conveniently used to predict POD in patients with elderly hip fractures.
Prenatal Low-Protein and Low-Calorie Diets Differentially Alter Arcuate Nucleus Morphology in Newborn Male Rats
Authors: Blanco Noemí , Fernández-García Jose Manuel , Carrillo Beatriz , Ballesta Antonio , García-Úbeda Rocío , Collado Paloma , Pinos Helena
Published: June 2022

Background

Malnutrition during the early stages of development produces alterations that can compromise the functioning of the hypothalamic circuits that regulate food intake. The purpose of this study is to analyze the effects that a low-protein and low-calorie diet has on the morphology of the arcuate nucleus (ARC) of the hypothalamus in newborn male and female rats.

Methods

On gestational day 6 (G6), six pregnant rats were divided into two groups. One group was made up of three pregnant rats, which were fed ad libitum with a control diet (20% casein), and the other one was made up of three pregnant rats, which were fed ad libitum with a low-protein diet (8% casein) and 30% of a calorie-restricted diet. On the day of birth, pups were sacrificed, resulting in four experimental groups: control male, control female, low-protein and low-calorie diet male, and low-protein and low-calorie diet female (n = 5 in each group). The volume and number of neurons, together with the neuronal density and number of apoptotic cells, were measured.

Results

Males on a low-protein and low-calorie diet showed a significant increase in the number of neurons and in the neuronal density of the ARC with regard to the rest of the groups studied. These increases were also reflected in the posterior part of the nucleus. Although the existence of sexual dimorphism was not detected in any of the parameters studied in the control groups, the number of neurons and neuronal density showed differences between males and females fed with a low-protein and low-calorie diets due to the increase in the number of neurons shown by the male. No significant differences were found in the number of apoptotic cells.

Conclusion

Our results show that a low-protein and low-calorie diet during the prenatal stage produces alterations in the ARC of the hypothalamus in newborn animals and, more importantly, that the effects of malnutrition are evident in males but not in females. Therefore, it is essential to follow a balanced diet during the early stages of life to ensure optimal development of the neural circuits that regulate eating.
DNA-like Helices as Nanosized Polarizers of Electromagnetic Waves
Authors: Semchenko Igor V. , Mikhalka Ivan S. , Khakhomov Sergei A. , Samofalov Andrey L. , Balmakou Aliaksei P.
Published: June 2022

The possibility of using a conducting double DNA-like helix as the basis of an electromagnetic wave polarizer, which converts an incident linearly polarized wave into a reflected wave with circular polarization, has been shown. A high-frequency resonance is studied, at which the wavelength of the incident radiation is approximately equal to the length of a helical turn. The simulation of a double DNA-like helix has been carried out. The electric currents arising in the helical strands under waves with circular polarization at high-frequency resonance have been analyzed. Fundamentally different behavior of the double DNA-like helix concerning waves with right-hand or left-hand circular polarization has been established, which can be called the effect of polarization selectivity. This effect is manifested in the fact that a double DNA-like helix at high-frequency resonance can create a reflected wave having only one sign of circular polarization. The electric vector of the reflected wave produces a turn in space with the opposite winding direction compared to the double helix. These studies also highlight the electromagnetic forces of interaction between helical strands. The equilibrium of the double DNA-like helix has been studied, including as an element of metamaterials and as an object with a high potential for use in nanotechnology.
Neural Circuitry for Stress Information of Environmental and Internal Odor Worlds
Authors: Mori Kensaku , Sakano Hitoshi
Published: June 2022

In mammals, odor information detected in the olfactory epithelium is converted to a topographic map of activated glomeruli in the olfactory bulb. Odor signals are then conveyed by projection neurons to the olfactory cortex for decision making. Odor information is processed by two distinct pathways, one is innate and the other is learned, which are separately activated during exhalation and inhalation, respectively. There are two types of odor signals, exteroceptive and interoceptive, which are also processed in different phases of respiration. Exteroceptive sensory information whether attractive/pleasant or aversive/stressful, is evaluated by the valence regions in the amygdala. Stress is an alert signal telling the body to take an action so that the normal condition can be recovered. When the odor quality is negative, the brain sets up a behavioral strategy to avoid the danger or to improve the situation. In this review article, we will describe the recent progress in the study of olfactory perception focusing on stress responses to external and internal odors.
R-loop Mediated DNA Damage and Impaired DNA Repair in Spinal Muscular Atrophy
Authors: Cuartas Juliana , Gangwani Laxman
Published: June 2022

Defects in DNA repair pathways are a major cause of DNA damage accumulation leading to genomic instability and neurodegeneration. Efficient DNA damage repair is critical to maintain genomicstability and support cell function and viability. DNA damage results in the activation of cell death pathways, causing neuronal death in an expanding spectrum of neurological disorders, such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), Alzheimer’s disease (AD), and spinal muscular atrophy (SMA). SMA is a neurodegenerative disorder caused by mutations in the Survival Motor Neuron 1 (SMN1) gene. SMA is characterized by the degeneration of spinal cord motor neurons due to low levels of the SMN protein. The molecular mechanism of selective motor neuron degeneration in SMA was unclear for about 20 years. However, several studies have identified biochemical and molecular mechanisms that may contribute to the predominant degeneration of motor neurons in SMA, including the RhoA/ROCK, the c-Jun NH2-terminal kinase (JNK), and p53-mediated pathways, which are involved in mediating DNA damage-dependent cell death. Recent studies provided insight into selective degeneration of motor neurons, which might be caused by accumulation of R-loop-mediated DNA damage and impaired non-homologous end joining (NHEJ) DNA repair pathway leading to genomic instability. Here, we review the latest findings involving R-loop-mediated DNA damage and defects in neuron-specific DNA repair mechanisms in SMA and discuss these findings in the context of other neurodegenerative disorders linked to DNA damage.
The Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review
Authors: Hulshof Lianne A. , van Nuijs Danny , Hol Elly M. , Middeldorp Jinte
Published: June 2022

Alzheimer's disease (AD) is the most common cause of dementia, affecting 35 million people worldwide. One pathological feature of progressing AD is the loss of synapses. This is the strongest correlate of cognitive decline. Astrocytes, as an essential part of the tripartite synapse, play a role in synapse formation, maintenance, and elimination. During AD, astrocytes get a reactive phenotype with an altered gene expression profile and changed function compared to healthy astrocytes. This process likely affects their interaction with synapses. This systematic review aims to provide an overview of the scientific literature including information on how astrocytes affect synapse formation and elimination in the brain of AD patients and in animal models of the disease. We review molecular and cellular changes in AD astrocytes and conclude that these predominantly result in lower synapse numbers, indicative of decreased synapse support or even synaptotoxicity, or increased elimination, resulting in synapse loss, and consequential cognitive decline, as associated with AD. Preventing AD induced changes in astrocytes might therefore be a potential therapeutic target for dementia.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=148278, identifier [CRD148278].
Regional Variability in the Care and Outcomes of Subarachnoid Hemorrhage Patients in the United States
Authors: Shah Vishank A. , Kazmi Syed Omar , Damani Rahul , Harris Alyssa Hartsell , Hohmann Samuel F. , Calvillo Eusebia , Suarez Jose I.
Published: June 2022

Background and Objectives

Regional variability in subarachnoid hemorrhage (SAH) care is reported in physician surveys. We aimed to describe variability in SAH care using patient-level data and identify factors impacting hospital outcomes and regional variability in outcomes.

Methods

A retrospective multi-center cross-sectional cohort study of consecutive non-traumatic SAH patients in the Vizient Clinical Data Base, between January 1st, 2009 and December 30th, 2018 was performed. Participating hospitals were divided into US regions: Northeast, Midwest, South, West. Regional demographics, co-morbidities, severity-of-illness, complications, interventions and discharge outcomes were compared. Multivariable logistic regression was performed to identify factors independently associated with primary outcomes: hospital mortality and poor discharge outcome. Poor discharge outcome was defined by the Nationwide Inpatient Sample-SAH Outcome Measure, an externally-validated outcome measure combining death, discharge disposition, tracheostomy and/or gastrostomy. Regional variability in the associations between care and outcomes were assessed by introducing an interaction term for US region into the models.

Results

Of 109,034 patients included, 24.3% were from Northeast, 24.9% Midwest, 34.9% South, 15.9% West. Mean (SD) age was 58.6 (15.6) years and 64,245 (58.9%) were female. In-hospital mortality occurred in 21,991 (20.2%) and 44,159 (40.5%) had poor discharge outcome. There was significant variability in severity-of-illness, co-morbidities, complications and interventions across US regions. Notable findings were higher prevalence of surgical clipping (18.8 vs. 11.6%), delayed cerebral ischemia (4.3 vs. 3.1%), seizures (16.5 vs. 14.8%), infections (18 vs. 14.7%), length of stay (mean [SD] days; 15.7 [19.2] vs. 14.1 [16.7]) and health-care direct costs (mean [SD] USD; 80,379 [98,999]. vs. 58,264 [74,430]) in the West when compared to other regions (all p < 0.0001). Variability in care was also associated with modest variability in hospital mortality and discharge outcome. Aneurysm repair, nimodipine use, later admission-year, endovascular rescue therapies reduced the odds for poor outcome. Age, severity-of-illness, co-morbidities, hospital complications, and vasopressor use increased those odds (c-statistic; mortality: 0.77; discharge outcome: 0.81). Regional interaction effect was significant for admission severity-of-illness, aneurysm-repair and nimodipine-use.

Discussion

Multiple hospital-care factors impact SAH outcomes and significant variability in hospital-care and modest variability in discharge-outcomes exists across the US. Variability in SAH-severity, nimodipine-use and aneurysm-repair may drive variability in outcomes.
Feasibility, Safety, and Effectiveness of Telerehabilitation in Mild-to-Moderate Parkinson's Disease
Authors: Bianchini Edoardo , Onelli Camilla , Morabito Carmen , Alborghetti Marika , Rinaldi Domiziana , Anibaldi Paolo , Marcolongo Adriano , Salvetti Marco , Pontieri Francesco E.
Published: June 2022

Introduction

Parkinson's disease (PD) patients frequently engage in rehabilitation to ameliorate symptoms. During the Coronavirus disease 2019 (COVID-19) pandemic, access to rehabilitation programs has been markedly limited, consequently, telerehabilitation gained popularity. In this prospective, open-label, and pilot study, we aimed to investigate feasibility, safety, and efficacy of telerehabilitation in mild-to-moderate PD patients.

Materials and Methods

Twenty-three PD patients, with Hoehn and Yahr stage <3, without gait disturbances or dementia and capable of using the televisit platform, were recruited for a 5-week telerehabilitation program, consisting of 1 remote visit with a therapist and a minimum of two sessions of >30-min of self-conducted exercises per week. Patients received video tutorials of exercises and were asked to keep a diary of sessions. At baseline (T0), at the end of the intervention (T1), and 1 month after the end of treatment (T2), patients were remotely assessed with MDS-UPDRS part I-III, PDQ-39, Functional Independence Measure (FIM), and Frontal Assessment Battery scales, respectively. Acceptable compliance to the program was defined as >60% matching of frequency and duration of sessions, whereas optimal compliance was set at >80% matching.

Results

The dropout rate was 0%. Over 85% of patients reached acceptable adherence cut-off and around 70% reached optimal one. No adverse events were reported during sessions. The repeated measure analysis of variance (rANOVA) showed a significant effect of factor “time” for MDS-UPDRS-III (p < 0.0001) with a mean reduction of 4.217 points between T0 and T1 and return to baseline at T2. No significant effect was found for other outcome measures.

Conclusion

Our findings demonstrate that telerehabilitation is safe, feasible, and effective on motor symptoms in mild-to-moderate PD patients.
Multisensory Integration Dominates Hypnotisability and Expectations in the Rubber Hand Illusion
Authors: Slater Mel , Ehrsson H. Henrik
Published: June 2022

Some recent papers by P. Lush and colleagues have argued that the rubber hand illusion (RHI), where participants can feel a rubber hand as their own under appropriate multisensory stimulation, may be caused mainly by hypnotic suggestibility and expectations (demand characteristics). These papers rely primarily on a study with 353 participants who took part in a RHI experiment carried out in a classical way with brush stroking. Participants experienced a synchronous condition where the rubber hand was seen to be touched in synchrony with touch felt on their corresponding hidden real hand, or the touches were applied asynchronously as a control. Each participant had a related measure of their hypnotisability on a scale known as the Sussex-Waterloo Scale of Hypnotisability (SWASH). The authors found a correlation between the questionnaire ratings of the RHI in the synchronous condition and the SWASH score. From this, they concluded that the RHI is largely driven by suggestibility and further proposed that suggestibility and expectations may even entirely explain the RHI. Here we examine their claims in a series of extensive new analyses of their data. We find that at every level of SWASH, the synchronous stimulation results in greater levels of the illusion than the asynchronous condition; moreover, proprioceptive drift is greater in the synchronous case at every level of SWASH. Thus, while the level of hypnotisability does modestly influence the subjective reports (higher SWASH is associated with somewhat higher illusion ratings), the major difference between the synchronous and asynchronous stimulation is always present. Furthermore, by including in the model the participants’ expectancy ratings of how strongly they initially believed they would experience the RHI in the two conditions, we show that expectations had a very small effect on the illusion ratings; model comparisons further demonstrate that the multisensory condition is two-to-three-times as dominant as the other factors, with hypnotisability contributing modestly and expectations negligibly. Thus, although the results indicate that trait suggestibility may modulate the RHI, presumably through intersubject variations in top-down factors, the findings also suggest that the primary explanation for the RHI is as a multisensory bodily illusion.
Understanding the Neural Basis of Prospective Memory Using Functional Near-Infrared Spectroscopy
Authors: Koo Yu Wen , Neumann David L. , Ownsworth Tamara , Yeung Michael K. , Shum David H. K.
Published: June 2022

Prospective memory (PM) is the ability to perform a planned action at an intended future time. This study examined the neural correlates of PM using functional near-infrared spectroscopy (fNIRS). This study employed a within-participants design. A laboratory PM task was adapted for use with fNIRS to investigate regions of interest and levels of brain activation during task performance in 32 participants (63% female, Mage = 21.31 years, SDage = 4.62 years). Participants first completed a working memory (WM) task (N-back ongoing task) followed by a WM plus PM task while neural activity was measured using fNIRS. Behavioral results revealed an interference effect for reaction time on the WM task, whereby participants were significantly slower to respond in the WM plus PM task compared to the WM task. Ongoing task accuracies did not differ between the two conditions. fNIRS results revealed a higher level of neural activity in the fronto-polar prefrontal cortex and dorsolateral prefrontal cortex in the WM plus PM task compared to the WM Condition. These findings highlight that fNIRS is a suitable tool for studying and understanding the neural basis of PM.
Guidelines for Burr Hole Surgery in Combination With Tumor Treating Fields for Glioblastoma: A Computational Study on Dose Optimization and Array Layout Planning
Authors: Cao Fang , Mikic Nikola , Wong Eric T. , Thielscher Axel , Korshoej Anders Rosendal
Published: June 2022

Tumor treating fields (TTFields) is an anti-cancer technology increasingly used for the treatment of glioblastoma. Recently, cranial burr holes have been used experimentally to enhance the intensity (dose) of TTFields in the underlying tumor region. In the present study, we used computational finite element methods to systematically characterize the impact of the burr hole position and the TTFields transducer array layout on the TTFields distribution calculated in a realistic human head model. We investigated a multitude of burr hole positions and layouts to illustrate the basic principles of optimal treatment planning. The goal of the paper was to provide simple rules of thumb for physicians to use when planning the TTFields in combination with skull remodeling surgery. Our study suggests a number of key findings, namely that (1) burr holes should be placed directly above the region of interest, (2) field enhancement occurs mainly underneath the holes, (3) the ipsilateral array should directly overlap the holes and the contralateral array should be placed directly opposite, (4) arrays in a pair should be placed at far distance and not close to each other to avoid current shunting, and finally (5) rotation arrays around their central normal axis can be done without diminishing the enhancing effect of the burr holes. Minor deviations and adjustments (<3 cm) of arrays reduces the enhancement to some extent although the procedure is still effective in these settings. In conclusion, our study provides simple guiding principles for implementation of dose-enhanced TTFields in combination with burr-holes. Future studies are required to validate our findings in additional models at the patient specific level.
Gesture Recognition by Ensemble Extreme Learning Machine Based on Surface Electromyography Signals
Authors: Peng Fulai , Chen Cai , Lv Danyang , Zhang Ningling , Wang Xingwei , Zhang Xikun , Wang Zhiyong
Published: June 2022

In the recent years, gesture recognition based on the surface electromyography (sEMG) signals has been extensively studied. However, the accuracy and stability of gesture recognition through traditional machine learning algorithms are still insufficient to some actual application scenarios. To enhance this situation, this paper proposed a method combining feature selection and ensemble extreme learning machine (EELM) to improve the recognition performance based on sEMG signals. First, the input sEMG signals are preprocessed and 16 features are then extracted from each channel. Next, features that mostly contribute to the gesture recognition are selected from the extracted features using the recursive feature elimination (RFE) algorithm. Then, several independent ELM base classifiers are established using the selected features. Finally, the recognition results are determined by integrating the results obtained by ELM base classifiers using the majority voting method. The Ninapro DB5 dataset containing 52 different hand movements captured from 10 able-bodied subjects was used to evaluate the performance of the proposed method. The results showed that the proposed method could perform the best (overall average accuracy 77.9%) compared with decision tree (DT), ELM, and random forest (RF) methods.