bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult medial habenula neurons require GDNF receptor GFRα1 for synaptic stability and function
Authors: Fernández-Suárez Diana , Krapacher Favio A. , Pietrajtis Katarzyna , Andersson Annika , Kisiswa Lilian , Carrier-Ruiz Alvaro , Diana Marco A. , Ibáñez Carlos F.
Published: November 2021

The medial habenula (mHb) is an understudied small brain nucleus linking forebrain and midbrain structures controlling anxiety and fear behaviors. The mechanisms that maintain the structural and functional integrity of mHb neurons and their synapses remain unknown. Using spatiotemporally controlled Cre-mediated recombination in adult mice, we found that the glial cell–derived neurotrophic factor receptor alpha 1 (GFRα1) is required in adult mHb neurons for synaptic stability and function. mHb neurons express some of the highest levels of GFRα1 in the mouse brain, and acute ablation of GFRα1 results in loss of septohabenular and habenulointerpeduncular glutamatergic synapses, with the remaining synapses displaying reduced numbers of presynaptic vesicles. Chemo- and optogenetic studies in mice lacking GFRα1 revealed impaired circuit connectivity, reduced AMPA receptor postsynaptic currents, and abnormally low rectification index (R.I.) of AMPARs, suggesting reduced Ca2+ permeability. Further biochemical and proximity ligation assay (PLA) studies defined the presence of GluA1/GluA2 (Ca2+ impermeable) as well as GluA1/GluA4 (Ca2+ permeable) AMPAR complexes in mHb neurons, as well as clear differences in the levels and association of AMPAR subunits with mHb neurons lacking GFRα1. Finally, acute loss of GFRα1 in adult mHb neurons reduced anxiety-like behavior and potentiated context-based fear responses, phenocopying the effects of lesions to septal projections to the mHb. These results uncover an unexpected function for GFRα1 in the maintenance and function of adult glutamatergic synapses and reveal a potential new mechanism for regulating synaptic plasticity in the septohabenulointerpeduncular pathway and attuning of anxiety and fear behaviors.
NAMPT-derived NAD+ fuels PARP1 to promote skin inflammation through parthanatos cell death
Authors: Martínez-Morcillo Francisco J. , Cantón-Sandoval Joaquín , Martínez-Navarro Francisco J. , Cabas Isabel , Martínez-Vicente Idoya , Armistead Joy , Hatzold Julia , López-Muñoz Azucena , Martínez-Menchón Teresa , Corbalán-Vélez Raúl , Lacal Jesús , Hammerschmidt Matthias , García-Borrón José C. , García-Ayala Alfonsa , Cayuela María L. , Pérez-Oliva Ana B. , García-Moreno Diana , Mulero Victoriano
Published: November 2021

Several studies have revealed a correlation between chronic inflammation and nicotinamide adenine dinucleotide (NAD+) metabolism, but the precise mechanism involved is unknown. Here, we report that the genetic and pharmacological inhibition of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the salvage pathway of NAD+ biosynthesis, reduced oxidative stress, inflammation, and keratinocyte DNA damage, hyperproliferation, and cell death in zebrafish models of chronic skin inflammation, while all these effects were reversed by NAD+ supplementation. Similarly, genetic and pharmacological inhibition of poly(ADP-ribose) (PAR) polymerase 1 (Parp1), overexpression of PAR glycohydrolase, inhibition of apoptosis-inducing factor 1, inhibition of NADPH oxidases, and reactive oxygen species (ROS) scavenging all phenocopied the effects of Nampt inhibition. Pharmacological inhibition of NADPH oxidases/NAMPT/PARP/AIFM1 axis decreased the expression of pathology-associated genes in human organotypic 3D skin models of psoriasis. Consistently, an aberrant induction of NAMPT and PARP activity, together with AIFM1 nuclear translocation, was observed in lesional skin from psoriasis patients. In conclusion, hyperactivation of PARP1 in response to ROS-induced DNA damage, fueled by NAMPT-derived NAD+, mediates skin inflammation through parthanatos cell death.
Atypically larger variability of resource allocation accounts for visual working memory deficits in schizophrenia
Authors: Zhao Yi-Jie , Ma Tianye , Zhang Li , Ran Xuemei , Zhang Ru-Yuan , Ku Yixuan
Published: November 2021

Working memory (WM) deficits have been widely documented in schizophrenia (SZ), and almost all existing studies attributed the deficits to decreased capacity as compared to healthy control (HC) subjects. Recent developments in WM research suggest that other components, such as precision, also mediate behavioral performance. It remains unclear how different WM components jointly contribute to deficits in schizophrenia. We measured the performance of 60 SZ (31 females) and 61 HC (29 females) in a classical delay-estimation visual working memory (VWM) task and evaluated several influential computational models proposed in basic science of VWM to disentangle the effect of various memory components. We show that the model assuming variable precision (VP) across items and trials is the best model to explain the performance of both groups. According to the VP model, SZ exhibited abnormally larger variability of allocating memory resources rather than resources or capacity per se. Finally, individual differences in the resource allocation variability predicted variation of symptom severity in SZ, highlighting its functional relevance to schizophrenic pathology. This finding was further verified using distinct visual features and subject cohorts. These results provide an alternative view instead of the widely accepted decreased-capacity theory and highlight the key role of elevated resource allocation variability in generating atypical VWM behavior in schizophrenia. Our findings also shed new light on the utility of Bayesian observer models to characterize mechanisms of mental deficits in clinical neuroscience.
Programming cell growth into different cluster shapes using diffusible signals
Authors: Guo Yipei , Nitzan Mor , Brenner Michael P.
Published: November 2021

Advances in genetic engineering technologies have allowed the construction of artificial genetic circuits, which have been used to generate spatial patterns of differential gene expression. However, the question of how cells can be programmed, and how complex the rules need to be, to achieve a desired tissue morphology has received less attention. Here, we address these questions by developing a mathematical model to study how cells can collectively grow into clusters with different structural morphologies by secreting diffusible signals that can influence cellular growth rates. We formulate how growth regulators can be used to control the formation of cellular protrusions and how the range of achievable structures scales with the number of distinct signals. We show that a single growth inhibitor is insufficient for the formation of multiple protrusions but may be achieved with multiple growth inhibitors, and that other types of signals can regulate the shape of protrusion tips. These examples illustrate how our approach could potentially be used to guide the design of regulatory circuits for achieving a desired target structure.
High-efficiency CRISPR gene editing in C. elegans using Cas9 integrated into the genome
Authors: Schwartz Matthew L. , Davis M. Wayne , Rich Matthew S. , Jorgensen Erik M.
Published: November 2021

Gene editing in C. elegans using plasmid-based CRISPR reagents requires microinjection of many animals to produce a single edit. Germline silencing of plasmid-borne Cas9 is a major cause of inefficient editing. Here, we present a set of C. elegans strains that constitutively express Cas9 in the germline from an integrated transgene. These strains markedly improve the success rate for plasmid-based CRISPR edits. For simple, short homology arm GFP insertions, 50–100% of injected animals typically produce edited progeny, depending on the target locus. Template-guided editing from an extrachromosomal array is maintained over multiple generations. We have built strains with the Cas9 transgene on multiple chromosomes. Additionally, each Cas9 locus also contains a heatshock-driven Cre recombinase for selectable marker removal and a bright fluorescence marker for easy outcrossing. These integrated Cas9 strains greatly reduce the workload for producing individual genome edits.
The FASTK family proteins fine-tune mitochondrial RNA processing
Authors: Ohkubo Akira , Van Haute Lindsey , Rudler Danielle L. , Stentenbach Maike , Steiner Florian A. , Rackham Oliver , Minczuk Michal , Filipovska Aleksandra , Martinou Jean-Claude
Published: November 2021

Transcription of the human mitochondrial genome and correct processing of the two long polycistronic transcripts are crucial for oxidative phosphorylation. According to the tRNA punctuation model, nucleolytic processing of these large precursor transcripts occurs mainly through the excision of the tRNAs that flank most rRNAs and mRNAs. However, some mRNAs are not punctuated by tRNAs, and it remains largely unknown how these non-canonical junctions are resolved. The FASTK family proteins are emerging as key players in non-canonical RNA processing. Here, we have generated human cell lines carrying single or combined knockouts of several FASTK family members to investigate their roles in non-canonical RNA processing. The most striking phenotypes were obtained with loss of FASTKD4 and FASTKD5 and with their combined double knockout. Comprehensive mitochondrial transcriptome analyses of these cell lines revealed a defect in processing at several canonical and non-canonical RNA junctions, accompanied by an increase in specific antisense transcripts. Loss of FASTKD5 led to the most severe phenotype with marked defects in mitochondrial translation of key components of the electron transport chain complexes and in oxidative phosphorylation. We reveal that the FASTK protein family members are crucial regulators of non-canonical junction and non-coding mitochondrial RNA processing.
Effectiveness of Nifurtimox Eflornithine Combination Therapy (NECT) in T. b. gambiense second stage sleeping sickness patients in the Democratic Republic of Congo: Report from a field study
Authors: Kuemmerle Andrea , Schmid Caecilia , Bernhard Sonja , Kande Victor , Mutombo Wilfried , Ilunga Medard , Lumpungu Ismael , Mutanda Sylvain , Nganzobo Pathou , Tete Digas Ngolo , Kisala Mays , Burri Christian , Blesson Severine , Valverde Mordt Olaf
Published: November 2021

Background

Nifurtimox-eflornithine combination therapy (NECT) for the treatment of second stage gambiense human African trypanosomiasis (HAT) was added to the World Health Organization’s Essential Medicines List in 2009 after demonstration of its non-inferior efficacy compared to eflornithine therapy. A study of NECT use in the field showed acceptable safety and high efficacy until hospital discharge in a wide population, including children, pregnant and breastfeeding women, and patients with a HAT treatment history. We present here the effectiveness results after the 24-month follow-up visit.

Methodology/Principal findings

In a multicenter, open label, single arm phase IIIb study, second stage gambiense HAT patients were treated with NECT in the Democratic Republic of Congo. Clinical cure was defined 24 months after treatment as survival without clinical and/or parasitological signs of HAT. Of the 629 included patients, 619 (98.4%) were discharged alive after treatment and were examined for the presence of trypanosomes, white blood cell count in cerebro-spinal fluid, and disease symptoms. The clinical cure rate of 94.1% was comparable for all subpopulations analyzed at the 24-month follow-up visit. Self-reported adverse events during follow-up were few and concerned mainly nervous system disorders, infections, and gastro-intestinal disorders. Overall, 28 patients (4.3%) died during the course of the trial. The death of 16 of the 18 patients who died during the follow-up period was assessed as unlikely or not related to NECT. Within 24 months, eight patients (1.3%) relapsed and received rescue treatment. Sixteen patients were completely lost to follow-up.

Conclusions/Significance

NECT treatment administered under field conditions was effective and sufficiently well tolerated, no major concern arose for children or pregnant or breastfeeding women. Patients with a previous HAT treatment history had the same response as those who were naïve. In conclusion, NECT was confirmed as effective and appropriate for use in a broad population, including vulnerable subpopulations.

Trial registration

The trial is registered at ClinicalTrials.gov, number NCT00906880.
Evaluation of photography using head-mounted display technology (ICAPS) for district Trachoma surveys
Authors: Naufal Fahd , Brady Christopher J. , Wolle Meraf A. , Saheb Kashaf Michael , Mkocha Harran , Bradley Christopher , Kabona George , Ngondi Jeremiah , Massof Robert W. , West Sheila K.
Published: November 2021

Background

As the prevalence of trachoma declines worldwide, it is becoming increasingly expensive and challenging to standardize graders in the field for surveys to document elimination. Photography of the tarsal conjunctiva and remote interpretation may help alleviate these challenges. The purpose of this study was to develop, and field test an Image Capture and Processing System (ICAPS) to acquire hands-free images of the tarsal conjunctiva for upload to a virtual reading center for remote grading.

Methodology/Principal findings

This observational study was conducted during a district-level prevalence survey for trachomatous inflammation—follicular (TF) in Chamwino, Tanzania. The ICAPS was developed using a Samsung Galaxy S8 smartphone, a Samsung Gear VR headset, a foot pedal trigger and customized software allowing for hands-free photography. After a one-day training course, three trachoma graders used the ICAPS to collect images from 1305 children ages 1–9 years, which were expert-graded remotely for comparison with field grades. In our experience, the ICAPS was successful at scanning and assigning barcodes to images, focusing on the everted eyelid with adequate examiner hand visualization, and capturing images with sufficient detail to grade TF. The percentage of children with TF by photos and by field grade was 5%. Agreement between grading of the images compared to the field grades at the child level was kappa = 0.53 (95%CI = 0.40–0.66). There were ungradable images for at least one eye in 199 children (9.1%), with more occurring in children ages 1–3 (18.5%) than older children ages 4–9 (4.2%) (χ2 = 145.3, p<0.001).

Conclusions/Significance

The prototype ICAPS device was robust, able to image 1305 children in a district level survey and transmit images from rural Tanzania to an online grading platform. More work is needed to improve the percentage of ungradable images and to better understand the causes of disagreement between field and photo grading.
Transmission dynamics, clinical characteristics and sero-surveillance in the COVID-19 outbreak in a population dense area of Colombo, Sri Lanka April- May 2020
Authors: Jeewandara Chandima , Guruge Dinuka , Jayathilaka Deshni , Deshan Madhusanka Panambara Arachchige , Pushpakumara Pradeep Darshana , Tanussiya Ramu Shyrar , Sepali Aberathna Inoka , Saubhagya Rasikangani Danasekara Danasekara Rallage , Pathmanathan Thilagaraj , Gunatilaka Buddhini , Malavige Sauni , Dias Yowan , Wijayamuni Ruwan , Ogg Graham S. , Malavige Gathsaurie Neelika
Published: November 2021

Background

The transmission dynamics of SARS-CoV-2 varies depending on social distancing measures, circulating SARS-CoV-2 variants, host factors and other environmental factors. We sought to investigate the clinical and epidemiological characteristics of a SARS-CoV-2 outbreak that occurred in a highly dense population area in Colombo, Sri Lanka from April to May 2020.

Methodology/principal findings

We carried out RT-qPCR for SARS-CoV2, assessed the SARS-CoV-2 specific total and neutralizing antibodies (Nabs) in a densely packed, underserved settlement (n = 2722) after identification of the index case on 15th April 2020. 89/2722 individuals were detected as infected by RT-qPCR with a secondary attack rate among close contacts being 0.077 (95% CI 0.063–0.095). Another 30 asymptomatic individuals were found to have had COVID-19 based on the presence of SARS-CoV-2 specific antibodies. However, only 61.5% of those who were initially seropositive for SARS-CoV-2 had detectable total antibodies at 120 to 160 days, while only 40.6% had detectable Nabs. 74/89 (83.1%) of RT-qPCR positive individuals were completely asymptomatic and all 15 (16.9%) who experienced symptoms were classified as having a mild illness. 18 (20.2%) were between the ages of 61 to 80. 11/89 (12.4%) had diabetes, 8/89 (9%) had cardiovascular disease and 4 (4.5%) had asthma. Of the two viruses that were sequenced and were of the B.1 and B.4 lineages with one carrying the D614G mutation.

Discussion/conclusion

Almost all infected individuals developed mild or asymptomatic illness despite the presence of comorbid illnesses. Since the majority of those who were in this underserved settlement were not infected despite circulation of the D614G variant, it would be important to further study environmental and host factors that lead to disease severity and transmission.
Where to draw the line?
Authors: Sheng Heping , Wilder John , Walther Dirk B.
Published: November 2021

We often take people’s ability to understand and produce line drawings for granted. But where should we draw lines, and why? We address psychological principles that underlie efficient representations of complex information in line drawings. First, 58 participants with varying degree of artistic experience produced multiple drawings of a small set of scenes by tracing contours on a digital tablet. Second, 37 independent observers ranked the drawings by how representative they are of the original photograph. Matching contours between drawings of the same scene revealed that the most consistently drawn contours tend to be drawn earlier. We generated half-images with the most- versus least-consistently drawn contours and asked 25 observers categorize the quickly presented scenes. Observers performed significantly better for the most compared to the least consistent half-images. The most consistently drawn contours were more likely to depict occlusion boundaries, whereas the least consistently drawn contours frequently depicted surface normals.
The added value of cognition-targeted exercise versus symptom-targeted exercise for multiple sclerosis fatigue: A randomized controlled pilot trial
Authors: Alketbi Azza , Basit Salah , Hamza Nouran , Walton Lori M. , Moustafa Ibrahim M.
Published: November 2021

Background

Fatigue is considered one of the most common symptoms of multiple sclerosis (MS) and lacks a current standardized treatment. Therefore, the aim of this study was to examine the feasibility and effectiveness of a cognition-targeted exercise versus symptom-targeted exercise for MS fatigue.

Methods

In this Pilot, parallel-group, randomized controlled trial, sixty participants with multiple sclerosis, were randomly assigned to either a Cognition-Targeted Exercise (CTE) (N = 30, mean age 41) or a Symptom-Targeted Exercise (STE) (N = 30, mean age 42). The participants in the experimental group received eight, 50-minute sessions of weekly Cognitive Behavior Therapy (CBT) in addition to a CTE Program; whereas, participants in the control group received eight, 50-minute sessions of weekly CBT in addition to the standardized physiotherapy program (STE Program). Feasibility was assessed through recruitment rate, participant retention, adherence and safety, in addition to clinical outcome measures, including: (1) Modified Fatigue Impact Scale (MFIS), (2) Work and Social Adjustment Scale (WSAS), (3) Hospital Anxiety and Depression Scale (HADS), and Perceived Stress Scale (PSS). All outcome measures were assessed at baseline (pretreatment), following completion of the eight visit intervention protocol, and at 3-months follow-up.

Results

The recruitment rate was 60% and 93% of participants completed the entire study. The recruited participants complied with 98% of the required visits. No adverse events were recorded. A Generalized Estimation Equation Model revealed a significant difference over time as an interaction term during the post and follow up visit for all clinical outcome measures (p < .001).

Conclusion

The addition of CTE to CBT exhibited positive and more lasting influence on MS fatigue outcomes compared to Symptom-Targeted Exercise (STE). Feasibility and efficacy data from this pilot study provide support for a full-scale RCT of CTE as an integral component of Multiple Sclerosis fatigue management.
Safety and efficacy of esaxerenone in Japanese hypertensive patients with heart failure with reduced ejection fraction: A retrospective study
Authors: Iwahana Togo , Saito Yuichi , Okada Sho , Kato Hirotoshi , Ono Ryohei , Kobayashi Yoshio
Published: November 2021

Esaxerenone, a mineralocorticoid receptor blocker (MRB), is a new antihypertensive agent. However, esaxerenone-related data with respect to hypertension with heart failure are limited. We investigated the safety and efficacy of esaxerenone in hypertensive patients with heart failure with reduced ejection fraction (HFrEF). Hypertensive patients with HFrEF treated with esaxerenone were retrospectively analyzed at two timepoints (short-term: 35±15 days; mid-term: 167±45 days). Adverse events including hyperkalemia (K+ >5.5 mEq/L), worsening renal function (WRF; estimated glomerular filtration rate (eGFR) reduction by ≥20%), and hypotension (systolic blood pressure <90 mmHg) were evaluated. eGFR and K+, serum creatinine, and brain natriuretic peptide (BNP) levels at baseline, short-term, and mid-term assessments were compared. Patients administered esaxerenone as their first MRB (first-MRB cohort) and those who converted from another MRB (conversion cohort) were separately analyzed. There were 50 (56±10 years old, 26% female) patients. At the short-term assessment, hyperkalemia or hypotension was not observed at a dose of 2.0±0.9 mg/day. Seven patients (14%) showed WRF. K+ was slightly elevated (4.12±0.41 to 4.25±0.39 mmol/L, p = 0.07) and eGFR was significantly reduced (66.9±19.6 mL/min/1.73 m2 to 62.4±19.7 mL/min/1.73 m2, p = 0.006). In the conversion cohort, significant changes in K+ and eGFR from baseline were not observed at the short-term assessment. BNP levels were consistently improved regardless of the cohorts (first-MRB cohort, 310 [110–370] pg/mL to 137 [47–152] pg/mL, p = 0.001; conversion cohort, 181 [30–203] pg/mL to 108 [26–146] pg/mL, p = 0.028). At the mid-term assessment, there were no significant changes in K+ and eGFR compared with the short-term assessment. In conclusion, esaxerenone was safe for hypertensive patients with HFrEF. Hyperkalemia and hypotension were rarely noted, while eGFR was marginally reduced. Moreover, esaxerenone might be beneficial for HFrEF in terms of BNP level reduction.
Electroacupuncture could balance the gut microbiota and improve the learning and memory abilities of Alzheimer’s disease animal model
Authors: Jiang Jing , Liu Hao , Wang Zidong , Tian Huiling , Wang Shun , Yang Jiayi , Ren Jingyu
Published: November 2021

Alzheimer’s disease (AD), as one of most common dementia, mainly affects older people from the worldwide. In this study, we intended to explore the possible mechanism of improving cognitive function and protecting the neuron effect by electroacupuncture. Method: We applied senescence-accelerated mouse prone 8 (SAMP8) mice as AD animal model, used Morris water maze, HE staining, 16S rDNA amplicon sequencing of gut microbiota and ELISA to demonstrate our hypothesis. Results: electroacupuncture improved the learning and memory abilities in SAMP8 mice (P<0.05) and could protect the frontal lobe cortex and hippocampus of SAMP8 mice; electroacupuncture significantly decreased the expression of IL-1β (P<0.01), IL-6 (P<0.01) and TNF-α (P<0.01 in hippocampus, P<0.05 in serum) in serum and hippocampus; electroacupuncture balanced the quantity and composition of gut microbiome, especially of the relative abundance in Delta-proteobacteria (P<0.05) and Epsilon-proteobacteria (P<0.05). Conclusion: electroacupuncture treatment could inhibit the peripheral and central nerve system inflammatory response by balancing the gut microbiota.
A new mathematical approach to improve the original dietary inflammatory index (DII) calculation
Authors: Pawlow Xenia , Ott Raffael , Winkler Christiane , Ziegler Anette-G. , Hummel Sandra
Published: November 2021

Accumulating evidence links dietary intake to inflammatory processes involved in non-communicable disease (NCD) development. The dietary inflammatory index (DII) designed by Shivappa et al. has been shown to capture the inflammatory potential of dietary behavior in a large number of epidemiological studies. Thus, the DII may serve as future tool to assess someone’s nutritional inflammatory capacities and hence, the individual risks for NCD development later in life. The calculation method of the DII, however, can benefit from alternative mathematical steps, particularly regarding the transformation from standardized daily food consumption to percentile scores. Here, we provide novel approaches, the scaling-formula (SF) and scaling-formula with outlier detection (SFOD) methods, with the aim to optimize the DII calculation method proposed by Shivappa and colleagues. We illustrate on simulated data specific limitations of the original DII calculation and show the benefits of the SF/SFOD by using simulated data and data from the prospective TEENDIAB study cohort, which supports the application of SF/SFOD in future epidemiological and clinical studies.
Aceptación tecnológica y adicción a las redes sociales en contextos obligatorios virtuales
Authors: VILLALBA-COMDORI KLINGE ORLANDO , Maldonado-Mahauad Jorge , Berroa-Garate Hania Carola , Lavalle-Gonzales Angela Katiusca , Rodriguez-Quispe Jorge Louis , Becerra-Castillo Socrates Gustavo , Flores-Tapia John Alexander , Arias-Chávez Dennis
Published: November 2021

El acceso a las nuevas Tecnologías de la Información y Comunicación por parte de la población se han incrementado en los últimos años, lo que ha llevado a que estas se integren de manera natural a la vida diaria de las personas. El ámbito educativo y empresarial sin duda son los sectores que mayores beneficios han obtenido con estos avances, tanto en lo positivo como de lo negativo. El presente estudio tiene por finalidad analizar la relación entre la aceptación tecnológica y la adicción a las redes sociales en estudiantes universitarios de la ciudad de Arequipa, Perú. La población estuvo conformada por estudiantes del segundo ciclo de 46 escuelas profesionales de la Universidad Nacional de San Agustín de Arequipa. Para la selección de la muestra se recurrió a un procedimiento no probabilístico incidental, seleccionando en total n=2470 estudiantes. Los instrumentos aplicados fueron el modelo de aceptación tecnológica (TAM), diseñada por Yong y el Cuestionario de Adicción a las Redes Sociales (ARS) de Escurra y Salas. Los resultados muestran que existe relación directa y baja entre la aceptación tecnológica y la adicción a las redes sociales dado que la correlación de Pearson es de .211, el tamaño del efecto es de 0.4593 y la potencia estadística es de 0.997. Se concluye que existe correlación de tipo muy débil; sin embargo, el tamaño del efecto es grande y la potencia estadística, muy alta. Estos resultados permiten abrir nuevos espacios de estudio de estos fenómenos
EU/US/CTAD TASK FORCE: LESSONS LEARNED FROM RECENT AND CURRENT ALZHEIMER’S PREVENTION TRIALS
Authors: Aisen P. , Touchon J. , Amariglio R. , Andrieu S. , Bateman R. , Breitner J. , Donohue M. , Dunn B. , Doody R. , Fox N. , Gauthier S. , Grundman M. , Hendrix S. , Ho C. , Isaac M. , Raman R. , Rosenberg P. , Schindler R. , Schneider L. , Sperling R.A. , Tariot P. , Welsh-Bohmer K. , Weiner M. , Vellas B.
Published: November 2021

At a meeting of the EU/US/Clinical Trials in Alzheimer’s Disease (CTAD) Task Force in December 2016, an international group of investigators from industry, academia, and regulatory agencies reviewed lessons learned from ongoing and planned prevention trials, which will help guide future clinical trials of AD treatments, particularly in the pre-clinical space. The Task Force discussed challenges that need to be addressed across all aspects of clinical trials, calling for innovation in recruitment and retention, infrastructure development, and the selection of outcome measures. While cognitive change provides a marker of disease progression across the disease continuum, there remains a need to identify the optimal assessment tools that provide clinically meaningful endpoints. Patient- and informant-reported assessments of cognition and function may be useful but present additional challenges. Imaging and other biomarkers are also essential to maximize the efficiency of and the information learned from clinical trials.
Virtual and Augmented Reality Changing Horizons in Dentistry
Authors: Bhandari Amit , Jain Vanshika , Bhandari Rashi
Published: November 2021

Augmented and virtual reality (AR-VR) is a fast developing technology that has been used in the field of medicine for a long time. It has also found its way in dentistry and the preliminary assessments so far have shown promising results. Aim: The presented scoping review was conducted with an aim of identifying the current applications of AR-VR in the field of dental training and education. The paper also highlights the presently available dental simulators, their features and areas of use. Result: It was found that AR-VR is not restricted to teaching of upcoming dentists but also helps practicing physicians to return to basics and refine their skills. Inclusion of haptics provides a realistic experience by simulating the tactile sensations. Instant feedback feature act as a source of motivation to cover the missed bases. Conclusion: AR-VR technology has numerous advantages in dental education and training. However, the currently available systems require imports and are bulky to be transported in difficult terrains. Thereby it is important that indigenous systems be developed that have enhanced feasibility to be used for training of Armed Forces for managing trauma cases encountered in the field.
Predictive Thin Plate Spline Model for Estimation of Load Carriage at Varying Gradient and Speed
Authors: Elias Susan , Naganandhini L.
Published: November 2021

Laboratory-based experimental studies are being carried out for Indian soldiers to estimate optimal load carriage at different gradients and walking speeds. These experiments involve the recording of Cardio-respiratory responses such as Heart Rate (HR), Oxygen Consumption (VO2), Energy Expenditure (EE), Respiratory Frequency (RF), Minute Ventilation (VE), and Maximal Aerobic capacity (%VO2max). Due to limitations in the data sample size that can be obtained in laboratory-based experiments, there is a need for mathematical interpolation to obtain intermediate values in the study. Load carriage can be affected by factors that can be controlled, such as the speed of marching, and also by external factors that cannot be controlled like ambient temperature. Real-time interactions of all the factors also have an impact on the load-carrying capacity. Planning of the mission operations requires the specification of well-defined work-rest schedules and indication of total load limits, to ensure the operational effectiveness of the military personnel. In this paper, we present a Predictive 3-Dimensional Thin Plate Spline Model for efficient estimation of load. We developed a Multiple Linear Regression Model for predicting %VO2max for combinations of load and gradient. The accuracy of the model was 85 per cent and the maximum permissible loads were derived from the prediction model for the physiological limits of 50 per cent, 60 per cent, and 75 per cent of VO2max. A Thin Plate Spline based interpolation technique was used on this Multiple Linear Regression Model to generate optimal load at intermediate values for the experimental study. A similar predictive Interpolation Model was also developed for estimating load for varying walking speeds at level ground.
Effect of Job Satisfaction on Psychological Well Being and Perceived Stress among Government and Private Employee
Authors: Bansal Dr Dolly , Gulati Prachi , Pathak Dr Vijendra Nath
Published: November 2021

The wellbeing and health of people are influenced by satisfaction about their job. The essence of job satisfaction is explained as mental gratification derived from one’s job. To know how the job satisfaction of an individual affects the other domains of an individual’s life like, psychological well-being and perceived stress in making an individual over-all healthy being. The study aims to investigate the Job satisfaction levels on psychological well-being and Perceived stress among government and private employees. Convenient sampling method was used in this study. In this study the sample consisted of 100 employees; 48 employees from the government sector and 52 employees from the private sector of the Delhi/ NCR region. For this study the behaviour tools used were job satisfaction scale, psychological well-being, and Perceived stress scale were taken for the study. These tools are used to measure government and private employee psycho social health issues. SPSS-18 software was used for data management. The results revealed significant negative correlation between Job satisfaction and Purpose in Life (r= -0.21) at p<0.05 level of significance. Perceived stress had a negative correlation between Autonomy (r= -.23) and Positive relation with others (r= -0.20) at p<0.05 level of significance. There was a significant difference between Government and Private sectors on Positive relations with others (p=0.003) at p<0.05 and Perceived stress (p=0.000) at p<0.05.
Heart function assessment during aging in apolipoprotein E knock-out mice
Authors:   Human Genetic Laboratory, University of Medicine and Pharmacy of Craiova, Craiova, Romania, Liehn Elisa A. ,   Department of Cardiology, Angiology and Intensive Care, Medical Faculty, University Hospital Aachen, Aachen, Germany,   Victor Babes National Institute of Pathology, Bucharest, Romania, Lupan Ana-Mihaela ,   Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest, Romania, Diaconu Rodica ,   Human Genetic Laboratory, University of Medicine and Pharmacy of Craiova, Craiova, Romania,   Department of Cardiology, Angiology and Intensive Care, Medical Faculty, University Hospital Aachen, Aachen, Germany, Ioana Mihaela ,   Human Genetic Laboratory, University of Medicine and Pharmacy of Craiova, Craiova, Romania, Streata Ioana ,   Human Genetic Laboratory, University of Medicine and Pharmacy of Craiova, Craiova, Romania, Manole Catalin ,   Victor Babes National Institute of Pathology, Bucharest, Romania, Burlacu Alexandrina ,   Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest, Romania
Published: November 2021

BACKGROUND: Apolipoprotein (apo) E isoforms have strong correlations with metabolic and cardiovascular diseases. However, it is not clear if apoE has a role in development of non-ischemic cardiomyopathy. Our study aims to analyze the involvement of apoE in non-ischemic cardiomyopathy. METHODS AND RESULTS: Serial echo-cardiographic measurements were performed in old wildtype and apoE deficient (apoE-/-) mice. Morphological and functional cardiac parameters were in normal range in both groups at the age of 12 month. At the age of 18 months, both groups had shown ventricular dilation and increased heart rates. However, the apoE-/- mice presented signs of diastolic dysfunction by hypertrophic changes in left ventricle, due probably to arterial hypertension. The right ventricle was not affected by age or genotype. CONCLUSION: Even in the absence of high fat diet, apoE deficiency in mice induces mild changes in the cardiac function of the left ventricle during aging, by developing diastolic dysfunction, which leads to heart failure with preserved ejection fraction. However, further studies are necessary to conclude over the role of apoE in cardiac physiology and its involvement in development of heart failure.
Rapid Extraction of the Spatial Distribution of Physical Saliency and Semantic Informativeness from Natural Scenes in the Human Brain
Authors: Kiat John E. , Hayes Taylor R. , Henderson John M. , Luck Steven J.
Published: November 2021

Physically salient objects are thought to attract attention in natural scenes. However, research has shown that meaning maps, which capture the spatial distribution of semantically informative scene features, trump physical saliency in predicting the pattern of eye moments in natural scene viewing. Meaning maps even predict the fastest eye movements, suggesting that the brain extracts the spatial distribution of potentially meaningful scene regions very rapidly. To test this hypothesis, we applied representational similarity analysis to ERP data. The ERPs were obtained from human participants (N= 32, male and female) who viewed a series of 50 different natural scenes while performing a modified 1-back task. For each scene, we obtained a physical saliency map from a computational model and a meaning map from crowd-sourced ratings. We then used representational similarity analysis to assess the extent to which the representational geometry of physical saliency maps and meaning maps can predict the representational geometry of the neural response (the ERP scalp distribution) at each moment in time following scene onset. We found that a link between physical saliency and the ERPs emerged first (∼78 ms after stimulus onset), with a link to semantic informativeness emerging soon afterward (∼87 ms after stimulus onset). These findings are in line with previous evidence indicating that saliency is computed rapidly, while also indicating that information related to the spatial distribution of semantically informative scene elements is computed shortly thereafter, early enough to potentially exert an influence on eye movements.

SIGNIFICANCE STATEMENTAttention may be attracted by physically salient objects, such as flashing lights, but humans must also be able to direct their attention to meaningful parts of scenes. Understanding how we direct attention to meaningful scene regions will be important for developing treatments for disorders of attention and for designing roadways, cockpits, and computer user interfaces. Information about saliency appears to be extracted rapidly by the brain, but little is known about the mechanisms that determine the locations of meaningful information. To address this gap, we showed people photographs of real-world scenes and measured brain activity. We found that information related to the locations of meaningful scene elements was extracted rapidly, shortly after the emergence of saliency-related information.
Acoustic Context Modulates Natural Sound Discrimination in Auditory Cortex through Frequency-Specific Adaptation
Authors: López-Jury Luciana , García-Rosales Francisco , González-Palomares Eugenia , Kössl Manfred , Hechavarria Julio C.
Published: November 2021

Sound discrimination is essential in many species for communicating and foraging. Bats, for example, use sounds for echolocation and communication. In the bat auditory cortex there are neurons that process both sound categories, but how these neurons respond to acoustic transitions, that is, echolocation streams followed by a communication sound, remains unknown. Here, we show that the acoustic context, a leading sound sequence followed by a target sound, changes neuronal discriminability of echolocation versus communication calls in the cortex of awake bats of both sexes. Nonselective neurons that fire equally well to both echolocation and communication calls in the absence of context become category selective when leading context is present. On the contrary, neurons that prefer communication sounds in the absence of context turn into nonselective ones when context is added. The presence of context leads to an overall response suppression, but the strength of this suppression is stimulus specific. Suppression is strongest when context and target sounds belong to the same category, e.g.,echolocation followed by echolocation. A neuron model of stimulus-specific adaptation replicated our resultsin silico. The model predicts selectivity to communication and echolocation sounds in the inputs arriving to the auditory cortex, as well as two forms of adaptation, presynaptic frequency-specific adaptation acting in cortical inputs and stimulus-unspecific postsynaptic adaptation. In addition, the model predicted that context effects can last up to 1.5 s after context offset and that synaptic inputs tuned to low-frequency sounds (communication signals) have the shortest decay constant of presynaptic adaptation.

SIGNIFICANCE STATEMENTWe studied cortical responses to isolated calls and call mixtures in awake bats and show that (1) two neuronal populations coexist in the bat cortex, including neurons that discriminate social from echolocation sounds well and neurons that are equally driven by these two ethologically different sound types; (2) acoustic context (i.e., other natural sounds preceding the target sound) affects natural sound selectivity in a manner that could not be predicted based on responses to isolated sounds; and (3) a computational model similar to those used for explaining stimulus-specific adaptation in rodents can account for the responses observed in the bat cortex to natural sounds. This model depends on segregated feedforward inputs, synaptic depression, and postsynaptic neuronal adaptation.
Teaching of Marxism-Leninism in Czechoslovakia 1948–1989
Authors: Devátá Markéta
Published: November 2021

The article deals with one of the key tools of forming a socialist-minded intelligentsia at universities, the teaching of Marxism-Leninism. The author summarizes results of her research in which she focused, apart from a factual account, also on constituent actors and their mutual interactions. On the Communist Party of Czechoslovakia and the objectives it had in the beginning of the project and which it was pursuing and adjusting for decades afterwards. On teachers of Marxism-Leninism, who kept the project going and were also looking for some space for their own concepts in it, and naturally also on students’ attitudes and approaches to the teaching of Marxism-Leninism.
Physical Education for Italian School Children during the Totalitarian Fascist Regime
Authors: Alfieri Paolo
Published: November 2021

Recent general and educational historiography suggests that, under Mussolini, physical training was viewed as a key instrument for disciplining children’s ideas and values as well as their bodies, and thus for inoculating them with fascist ideology. In this essay, I trace the evolution of the regime’s totalitarian educational project in relation to the teaching of physical education in primary schools, a novel topic and heuristic perspective that has been typically overlooked by historiographers. To this end, I analyse national legislation, school curricula, ministerial circulars, and teachers’ manuals and journals, examining developments in physical education for school-age children in terms of both its pedagogical or ideological meanings and the teaching methods adopted.
Social–environmental analysis of estuary water quality in a populous urban area
Authors: Tseng Hsiao-Chun , Newton Alice , Gong Gwo-Ching , Lin Chia-Chia
Published: November 2021

Asia has been experiencing rapid industrialization, urbanization, and economic growth in recent decades. Taiwan was one of the 4 Asian dragons, regions that experienced rapid industrialization and exceptionally high growth rates between the early 1960s and 1990s, but at a high cost to the environment, and thus, it was heavily polluted. Estuaries are highly dynamic and diverse ecosystems that provide multiple ecosystem services that maintain marine ecosystem health and benefit humankind. However, estuaries and the ecosystem services they provide are rapidly degrading due to increasing pressures and changes, especially those in populous, urban areas. Social–environmental analysis integrates scientific information and social activities and thereby provides a comprehensive understanding for the multiparty, joint decision-making processes necessary for successful, sustainable management. In this study, 60 years of economic data and 26 years of water quality data are examined using social–environmental frameworks, the driver-pressure-state-impact-response framework, and the systems approach framework to analyze the management of water quality for an estuary in a populous urban area, the Tamsui River estuary, in Taiwan. Potential societal responses and management measures are identified that can be implemented to reduce human activities, diminish pressure, ameliorate water quality, and enhance the state of the estuarine systems in the Tamsui River and its estuary. The recommended societal responses are increased education, the establishment of community-based river rangers, wetland and mangrove conservation, the development of a circular economy, the implementation of governance measures, and improvements in monitoring and assessments. Improvement of the water quality in the Tamsui River estuary increases the hedonic value of property for people who live near the riverside. Currently, the number of tourists and tourism-based businesses have increased. Nevertheless, improvements in water quality in the Tamsui River estuary bring well-being and benefits that could be further enhanced to increase the cost/benefit relation of the management measures.
Co-creation of knowledge in agroecology
Authors: Utter Alisha , White Alissa , Méndez V. Ernesto , Morris Katlyn
Published: November 2021

The co-creation of knowledge is gaining recognition and use within the science, practice, and movement of agroecology. Knowledge co-creation fosters participatory learning and development, which differs from passive knowledge sharing. This approach can bridge the real and perceived gaps across diverse forms of knowledge, including what is often distinguished as farmers’ traditional, Indigenous, tacit, or local knowledge and experts’ scientific, western, or generalizable knowledge. Formal academic documentation of processes and outcomes related to knowledge co-creation is limited; therefore, we bring in examples of published research, drawing from fields of agroecology, participatory action research, and science and technology studies, along with a firsthand farmer perspective on co-creation. Combined, these frameworks offer insight into the potential benefits of knowledge co-creation in agroecology. Many of these challenges, such as navigating power dynamics, may be addressed through mindful research and community practices, including strong communication and transparent expectations and goals. Co-creation processes have traditionally and continually taken place between farmers and throughout communities without academic acknowledgment and/or interpretation of such. We reinstate the invaluable role of farmer-centered inquiry, understanding, and application, which offer benefits to individual farmers and their extended communities of practice and research, in addition to holding spiritual and cultural significance. The co-creation of knowledge in agroecology presents a compelling, adaptive approach and outcome for the increasingly complex challenges facing farmers and the agrifood system.