bluuebunny/crossref_metadata_2025 huggingface dataset:
How Gender Influenced the Experience of Using a mHealth Intervention in Rural Mozambique: Secondary Qualitative Analysis of Community Health Worker Survey Data
Authors: Kinshella Mai-Lei Woo , Boene Helena , Sevene Esperança , Valá Anifa , Sharma Sumedha , Vidler Marianne , Magee Laura A. , von Dadelszen Peter , Munguambe Khátia , Payne Beth A.
Published: February 2022

Background

The mixed-gender community health worker (CHW) program in Mozambique is a window into the different experiences that male and female CHWs may face in their work. The objective of this study is to investigate how gender influenced the experiences of community health workers using the PIERS on the Move (POM) mHealth app in Mozambique.

Methods

This is a secondary analysis by gender of health care workers involved in the Mozambique Community Level Intervention for Pre-eclampsia (CLIP) cluster randomized trial (NCT01911494). A structured survey with 10 open-ended questions was used to elicit CHW experiences using the POM app. Data collection took place in 2017 after completion of the CLIP trial. This analysis examined emergent themes to consider how experiences may have been shaped by health worker gender.

Results

Of the 43 CHWs who used the POM app, there were 31 (72%) women and 12 (28%) men. Gender differences emerged in descriptions of how using POM increased their value and respect by pregnant women and community members. Fifty-eight percent of female CHWs (18/31) said that POM positively influenced their status in the community in comparison to 33% of their male counterparts (4/12). While the small sample sizes, particularly of male CHWs who used POM, preclude conclusions, these findings were supported by qualitative results. Female CHWs tended to elaborate more about community perceptions of their increased value and status as health care providers than male CHWs.

Conclusion

CHWs work within existing gender norms. While gender norms are perceived to support the comfort of women to speak to another woman about their maternal and child health issues, gender norms also work against female CHWs as their professionalism may be questioned more than for their male counterparts. CHW's narratives suggested that the mHealth intervention was valued beyond the technology itself because it also added symbolic clinical value and demonstrated a tangible investment in their professional capacities, which may have been especially appreciated by the female CHWs.
Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome
Authors: Durrant Louise R. , Bucca Giselda , Hesketh Andrew , Möller-Levet Carla , Tripkovic Laura , Wu Huihai , Hart Kathryn H. , Mathers John C. , Elliott Ruan M. , Lanham-New Susan A. , Smith Colin P.
Published: February 2022

Vitamin D is best known for its role in maintaining bone health and calcium homeostasis. However, it also exerts a broad range of extra-skeletal effects on cellular physiology and on the immune system. Vitamins D2 and D3 share a high degree of structural similarity. Functional equivalence in their vitamin D-dependent effects on human physiology is usually assumed but has in fact not been well defined experimentally. In this study we seek to redress the gap in knowledge by undertaking an in-depth examination of changes in the human blood transcriptome following supplementation with physiological doses of vitamin D2 and D3. Our work extends a previously published randomized placebo-controlled trial that recruited healthy white European and South Asian women who were given 15 µg of vitamin D2 or D3 daily over 12 weeks in wintertime in the UK (Nov-Mar) by additionally determining changes in the blood transcriptome over the intervention period using microarrays. An integrated comparison of the results defines both the effect of vitamin D3 or D2 on gene expression, and any influence of ethnic background. An important aspect of this analysis was the focus on the changes in expression from baseline to the 12-week endpoint of treatment within each individual, harnessing the longitudinal design of the study. Whilst overlap in the repertoire of differentially expressed genes was present in the D2 or D3-dependent effects identified, most changes were specific to either one vitamin or the other. The data also pointed to the possibility of ethnic differences in the responses. Notably, following vitamin D3 supplementation, the majority of changes in gene expression reflected a down-regulation in the activity of genes, many encoding pathways of the innate and adaptive immune systems, potentially shifting the immune system to a more tolerogenic status. Surprisingly, gene expression associated with type I and type II interferon activity, critical to the innate response to bacterial and viral infections, differed following supplementation with either vitamin D2 or vitamin D3, with only vitamin D3 having a stimulatory effect. This study suggests that further investigation of the respective physiological roles of vitamin D2 and vitamin D3 is warranted.
Single-Domain Antibodies Efficiently Neutralize SARS-CoV-2 Variants of Concern
Authors: Favorskaya Irina A. , Shcheblyakov Dmitry V. , Esmagambetov Ilias B. , Dolzhikova Inna V. , Alekseeva Irina A. , Korobkova Anastasia I. , Voronina Daria V. , Ryabova Ekaterina I. , Derkaev Artem A. , Kovyrshina Anna V. , Iliukhina Anna A. , Botikov Andrey G. , Voronina Olga L. , Egorova Daria A. , Zubkova Olga V. , Ryzhova Natalia N. , Aksenova Ekaterina I. , Kunda Marina S. , Logunov Denis Y. , Naroditsky Boris S. , Gintsburg Alexandr L.
Published: February 2022

Virus-neutralizing antibodies are one of the few treatment options for COVID-19. The evolution of SARS-CoV-2 virus has led to the emergence of virus variants with reduced sensitivity to some antibody-based therapies. The development of potent antibodies with a broad spectrum of neutralizing activity is urgently needed. Here we isolated a panel of single-domain antibodies that specifically bind to the receptor-binding domain of SARS-CoV-2 S glycoprotein. Three of the selected antibodies exhibiting most robust neutralization potency were used to generate dimeric molecules. We observed that these modifications resulted in up to a 200-fold increase in neutralizing activity. The most potent heterodimeric molecule efficiently neutralized each of SARS-CoV-2 variant of concern, including Alpha, Beta, Gamma, Delta and Omicron variants. This heterodimeric molecule could be a promising drug candidate for a treatment for COVID-19 caused by virus variants of concern.
Clinical Characteristics of Patients With IgG4-Related Disease Complicated by Hypocomplementemia
Authors: Fujita Yuya , Fukui Shoichi , Umeda Masataka , Tsuji Sosuke , Iwamoto Naoki , Nakashima Yoshikazu , Horai Yoshiro , Suzuki Takahisa , Okada Akitomo , Aramaki Toshiyuki , Ueki Yukitaka , Mizokami Akinari , Origuchi Tomoki , Watanabe Hiroshi , Migita Kiyoshi , Kawakami Atsushi
Published: February 2022

Background

A proportion of patients with immunogloblin G (IgG) 4-related disease (IgG4-RD) have hypocomplementemia. We aimed to identify characteristics of such patients.

Methods

We analyzed the demographic and clinical data and complement levels of 85 patients with IgG4-RD. We defined hypocomplementemia as serum C3 and/or C4 levels below the lower limit of normal at diagnosis. We also compared the characteristics of patients with and without IgG4-RD.

Results

Thirty-two (38%) patients had hypocomplementemia at diagnosis. Patients with hypocomplementemia had more lymph node (p < 0.01), lung (p < 0.01), and kidney (p = 0.02) involvement and a higher IgG4-RD responder index than those without (p = 0.05). Additionally, patients with hypocomplementemia had significantly higher IgG (p < 0.01), IgG4 (p < 0.01), and soluble interleukin 2-receptor (sIL-2R) (p < 0.01) levels and total IgG minus IgG4 (p < 0.01). C3 and C4 levels negatively correlated with IgG, IgG4, and sIL-2R levels, total IgG minus IgG4, and number of IgG4-RD responder index: a measure of the disease activity in IgG4-RD. Patients with hypocomplementemia at diagnosis had a significantly higher frequency of relapse (p = 0.024), as determined using the log-rank test. A multivariate logistic regression analysis showed the presence of hypocomplementemia was independently associated with relapse (OR, 6.842; 95% confidence interval [95%CI], 1.684–27.79; p = 0.007).

Conclusions

Patients with IgG4-RD with hypocomplementemia have a more active clinical phenotype, suggesting contributions of the complement system in the pathophysiology of IgG4-RD.
Improving Cancer Immunotherapy: Exploring and Targeting Metabolism in Hypoxia Microenvironment
Authors: Wei Jinfen , Hu Meiling , Du Hongli
Published: February 2022

Although immunotherapy has achieved good results in various cancer types, a large proportion of patients are limited from the benefits. Hypoxia and metabolic reprogramming are the common and critical factors that impact immunotherapy response. Here, we present current research on the metabolism reprogramming induced by hypoxia on antitumor immunity and discuss the recent progression among preclinical and clinical trials exploring the therapeutic effects combining targeting hypoxia and metabolism with immunotherapy. By evaluating the little clinical translation of the combined therapy, we provide insight into “understanding and regulating cellular metabolic plasticity under the current tumor microenvironment (TME),” which is essential to explore the strategy for boosting immune responses by targeting the metabolism of tumor cells leading to harsh TMEs. Therefore, we highlight the potential value of advanced single-cell technology in revealing the metabolic heterogeneity and corresponding phenotype of each cell subtype in the current hypoxic lesion from the clinical patients, which can uncover potential metabolic targets and therapeutic windows to enhance immunotherapy.
The Role of Recovery Phases in Mitigating the Negative Impacts of Marine Heatwaves on the Sea Star Asterias rubens
Authors: Wolf Fabian , Seebass Katja , Pansch Christian
Published: February 2022

During recent years, experimental ecology started to focus on regional to local environmental fluctuations in the context of global climate change. Among these, marine heatwaves can pose significant threats to marine organisms. Yet, experimental studies that include fluctuating thermal stress are rare, and if available often fail to base experimental treatments on available long-term environmental data. We evaluated 22-year high-resolution sea surface temperature data on the occurrence of heatwaves and cold-spells in a temperate coastal marine environment. The absence of a general warming trend in the data may in parts be responsible for a lack of changes in heatwave occurrences (frequency) and their traits (intensity, duration, and rate of change) over time. Yet, the retrieved traits for present-day heatwaves ensured most-natural treatment scenarios, enabling an experimental examination of the impacts of marine heatwaves and phases of recovery on an important temperate predator, the common sea star Asterias rubens. In a 68-days long experiment, we compared a 37- and a 28-days long heatwave with a treatment that consisted of three consecutive 12-days long heatwaves with 4 days of recovery in between. The heatwaves had an intensity of 4.6°C above climatological records, resulting in a maximum temperature of 23.25°C. We demonstrate that heatwaves decrease feeding and activity of A. rubens, with longer heatwaves having a more severe and lasting impact on overall feeding pressure (up to 99.7% decrease in feeding rate) and growth (up to 87% reduction in growth rate). Furthermore, heatwaves of similar overall mean temperature, but interrupted, had a minor impact compared to continuous heatwaves, and the impact diminished with repeated heatwave events. We experimentally demonstrated that mild heatwaves of today’s strength decrease the performance of A. rubens. However, this echinoderm may use naturally occurring short interruptions of thermal stress as recovery to persist in a changing and variable ocean. Thus, our results emphasize the significance of thermal fluctuations and especially, the succession and timing of heat-stress events.
Restriction Site-Associated DNA Sequencing Reveals Local Adaptation Despite High Levels of Gene Flow in Sardinella lemuru (Bleeker, 1853) Along the Northern Coast of Mindanao, Philippines
Authors: Labrador Kevin , Palermo Joseph Dominic , Agmata Altair , Ravago-Gotanco Rachel , Pante Ma. Josefa
Published: February 2022

Stock identification and delineation are important in the management and conservation of marine resources. These were highlighted as priority research areas for Bali sardinella (Sardinella lemuru) which is among the most commercially important fishery resources in the Philippines. Previous studies have already assessed the stocks of S. lemuru between Northern Mindanao Region (NMR) and Northern Zamboanga Peninsula (NZP), yielding conflicting results. Phenotypic variation suggests distinct stocks between the two regions, while mitochondrial DNA did not detect evidence of genetic differentiation for this high gene flow species. This paper tested the hypothesis of regional structuring using genome-wide single nucleotide polymorphisms (SNPs) acquired through restriction site-associated DNA sequencing (RADseq). We examined patterns of population genomic structure using a full panel of 3,573 loci, which was then partitioned into a neutral panel of 3,348 loci and an outlier panel of 31 loci. Similar inferences were obtained from the full and neutral panels, which were contrary to the inferences from the outlier panel. While the full and neutral panels suggested a panmictic population (global FST ∼ 0, p > 0.05), the outlier panel revealed genetic differentiation between the two regions (global FST = 0.161, p = 0.001; FCT = 0.263, p < 0.05). This indicated that while gene flow is apparent, selective forces due to environmental heterogeneity between the two regions play a role in maintaining adaptive variation. Annotation of the outlier loci returned five genes that were mostly involved in organismal development. Meanwhile, three unannotated loci had allele frequencies that correlated with sea surface temperature. Overall, our results provided support for local adaptation despite high levels of gene flow in S. lemuru. Management therefore should not only focus on demographic parameters (e.g., stock size and catch volume), but also consider the preservation of adaptive variation.
Atmosphere-Ocean Coupled Variability in the Arabian/Persian Gulf
Authors: Al Senafi Fahad
Published: February 2022

The Arabian Gulf comprises one of the world's most unique and fragile marine ecosystems; it is susceptible to the adverse effects of climate change due to its shallow depth and its location within an arid region that witnesses frequent severe atmospheric events. To reproduce these effects in numerical models, it is important to obtain a better understanding of the region's sea surface temperature (SST) variability patterns, as SST is a major driver of circulation in shallow environments. To this end, here, empirical orthogonal function (EOF) decomposition analysis was conducted to investigate interannual to multi-decadal SST variability in the Gulf from 1982 to 2020, using daily Level 4 Group for High Resolution SST (GHRSST) data. In this way, three dominant EOF modes were identified to contribute the Gulf's SST variability. Significant spatial and temporal correlations were found suggesting that throughout the 39-year study period, SST variability could be attributed to atmospheric changes driven by the El Nio-Southern Oscillation (ENSO), Atlantic Multi-decadal Oscillation (AMO), and Indian Ocean Dipole (IOD) climate modes. Spatial and temporal analyses of the dataset revealed that the average SST was 26.7°C, and that the warming rate from 1982 to 2020 reached up to 0.59°C/decade. A detailed examination of SST changes associated with heat exchange at the air-sea interface was conducted using surface heat fluxes from fifth generation (ERA5) European Centre for Medium-Range Weather Forecasts (ECMWF). Despite the SST warming trend, the accumulation of heat during the study period is suggesting that there was an overall loss of heat (cooling). This cooling reverted into heating in 2003 and has since been increasing.
Integrated Analysis of Metabolomics and Transcriptomics for Assessing Effects of Fish Meal and Fish Oil Replacement on the Metabolism of Rainbow Trout (Oncorhynchus mykiss)
Authors: Cao Yiming , Gao Qinfeng , Li Xueqi , Zhou Yangen , Dong Shuanglin , Wang Yinbo , Dai Zhongyi
Published: February 2022

Reducing dependency on dietary fish meal (FM) and fish oil (FO) is extremely important for the sustainable development of the aquaculture industry. However, the metabolic consequences and mechanisms underlying the replacement of dietary FM and FO by terrestrial proteins (TPs) and lipids remain unclear. To reveal the effects of replacing dietary FM and/or FO on the metabolic changes, the integrated analysis of metabolomics and transcriptomics were employed to evaluate the changes in metabolites and genes of rainbow trout (Oncorhynchus mykiss) feeding different experimental diets. Four diets were formulated for the 84-day duration of the experiment: control group (FMFO), FM and vegetable oil (FMVO), terrestrial protein and FO (TPFO), and terrestrial protein and vegetable oil (TPVO). Integrated metabolomic and transcriptomic analyses revealed the significant difference in the metabolic pathways of O. mykiss among the three replacement schemes, i.e., single replacement of dietary FM by TP, single replacement of dietary FO by VO, and combined replacement of FM by TP and FO by VO. The combined replacement of FM and FO by TP and VO, respectively, disturbed immune function, energy metabolism, cellular protein biosynthesis capacity, and lipid metabolism of O. mykiss. The reduction of antioxidant capacity was only observed in individuals feeding diets with replacement of FM by TP. Furthermore, as soon as the dietary FM and/or FO were reduced, cellular protein biosynthesis ability was suppressed and accompanied by higher energy consumption in response to fluctuations of dietary quality, resulting in reduced growth performance. Interestingly, adenylosuccinate and adenosine monophosphate involved in purine metabolism were induced by both individual and combined replacement of FM and FO by TPs and lipids, respectively. It suggested that these two metabolites might be potential biomarkers for O. mykiss fed diets with reduction of FM and/or FO. This study constitutes a new understanding of the molecular and metabolic mechanisms of O. mykiss in response to the replacement of dietary FM and/or FO by TP and/or VO, respectively, and built a theoretical basis for further improvement of aquafeed formulation and sustainable development of aquaculture.
Challenges in Multimorbidity Research: Lessons Learned From the Most Recent Randomized Controlled Trials in Primary Care
Authors: Fortin Martin , Stewart Moira , Almirall José , Beaupré Priscilla
Published: February 2022

Multimorbidity has received much attention and there is a growing number of original studies. However, randomized controlled trials (RCTs) have failed to demonstrate effectiveness of interventions aimed at improving outcomes for patient with multimorbidity in primary care. The purpose of this article is to synthesize and analyze the most recent RCTs to identify the factors that may have contribute to the success or lack of success in order to draw lessons to inform further development in intervention research. A scoping review was conducted to include current up-to-date state-of-the-art studies in primary care published from 2019. Nine articles reporting on six RCTs studies were included in the review. The findings were mixed, with primary outcomes showing no differences between intervention and control groups in four of the six but differences in secondary outcomes in all six. All studies involved family practice patients but interventions took place at different sites, and the time between the beginning of the intervention and the time of evaluation of outcomes varied across studies. Authors reported issues regarding the need for training of care teams, the roles and composition of the teams, the selection of patients and implementation barriers of the complex interventions in trying contexts with not enough time for the changes required. The randomized controlled design may not be the best evaluation design given the complexity of the interventions, and alternative designs should be considered in which qualitative components are included. Further attention to outcome measures and to equity issues is recommended.
Speech Perception and Dichotic Listening Are Associated With Hearing Thresholds and Cognition, Respectively, in Unaided Presbycusis
Authors: Torrente Mariela C. , Vergara Rodrigo , Moreno-Gómez Felipe N. , Leiva Alexis , San Martin Simón , Belkhiria Chama , Marcenaro Bruno , Delgado Carolina , Delano Paul H.
Published: February 2022

Presbycusis or age-related hearing loss is a prevalent condition in the elderly population, which affects oral communication, especially in background noise, and has been associated with social isolation, depression, and cognitive decline. However, the mechanisms that relate hearing loss with cognition are complex and still elusive. Importantly, recent studies show that the use of hearing aids in presbycusis, which is its standard management, can induce neuroplasticity and modify performance in cognitive tests. As the majority of the previous studies on audition and cognition obtained their results from a mixed sample of subjects, including presbycusis individuals fitted and not fitted with hearing aids, here, we revisited the associations between hearing loss and cognition in a controlled sample of unaided presbycusis. We performed a cross-sectional study in 116 non-demented Chilean volunteers aged ≥65 years from the Auditory and Dementia study cohort. Specifically, we explored associations between bilateral sensorineural hearing loss, suprathreshold auditory brain stem responses, auditory processing (AP), and cognition with a comprehensive neuropsychological examination. The AP assessment included speech perception in noise (SIN), dichotic listening (dichotic digits and staggered spondaic words), and temporal processing [frequency pattern (FP) and gap-in-noise detection]. The neuropsychological evaluations included attention, memory, language, processing speed, executive function, and visuospatial abilities. We performed an exploratory factor analysis that yielded four composite factors, namely, hearing loss, auditory nerve, midbrain, and cognition. These four factors were used for generalized multiple linear regression models. We found significant models showing that hearing loss is associated with bilateral SIN performance, while dichotic listening was associated with cognition. We concluded that the comprehension of the auditory message in unaided presbycusis is a complex process that relies on audition and cognition. In unaided presbycusis with mild hearing loss (<40 dB HL), speech perception of monosyllabic words in background noise is associated with hearing levels, while cognition is associated with dichotic listening and FP.
Differences in the Alcohol Preference Assessment of Shy and Bold Zebrafish
Authors: Bellot Marina Sanson , Guermandi Isabela Inforzato , Camargo-dos-Santos Bruno , Giaquinto Percília Cardoso
Published: February 2022

Individuals differ in their preference for alcohol and propensity to develop alcoholism, where the behavioral profile, such as the bold-shy axis, plays an important role for such a difference. However, literature is limited and conflicting on the causes and consequences of this relationship. Translational studies using animal models, such as zebrafish, can help identify behavioral traits that predispose individuals to drink alcohol compulsively. Here, the preference for alcohol was investigated in two distinct traits in zebrafish: shy and bold. For this purpose, fish were separated into shy and bold traits and then a conditioned place preference paradigm was used, a strategy that allows the rewarding effects from alcohol to be assessed by the ability to enhance the animal’s preference for an environment that initially was not preferred. It was found that bold zebrafish actively searched for the environment that was paired to alcohol after one acute exposure, whereas, shy fish changed their place preference even without alcohol administration, showing that the conditioned place preference protocol, given the short amount time to assess place preference, is not ample enough for shy fish to choose. Our results show that behavioral profiles must be considered in further studies since differences between shy and bold individuals on preference behavior can strongly interfere in the assessment of drug preference, mainly when using the conditioned place preference paradigm.
Own Pain Distress Mediates the Link Between the Lifestyle Facet of Psychopathy and Estimates of Pain Distress in Others
Authors: Brazil Inti A. , Atanassova Dimana V. , Oosterman Joukje M.
Published: February 2022

Psychopathy is a multifaceted personality construct entailing interpersonal-affective disturbances, antisocial traits, and a tendency to lead an erratic lifestyle. Elevated levels of psychopathic traits have been linked to having an altered experience of pain, reduced responsivity to distress in others, and making poor moral choices that bring harm to others. In the context of moral decision-making, it is possible that the capacity to estimate the distress felt by others is linked to a limitation in the first-hand experience of distress, as the presence of psychopathic traits increases. We employed a model-based approach in a non-offender sample (n = 174) to investigate whether pain-related distress mediated the links between facets of psychopathy and estimates of the pain distress potentially experienced by others. Participants judged the permissibility of moral dilemmas and rated how much pain distress they would experience while making such judgements, as well as how much pain distress they believed the “victims” would feel as a result of the moral choice made by the participant. We found that ratings of own pain distress predicted beliefs about the distress others may experience, and elevated scores on the lifestyle facet of psychopathy uniquely predicted lower estimates of own pain distress. Furthermore, own pain distress mediated the relationship between the lifestyle facet and beliefs about others’ distress. Finally, exploratory zero-order correlation analyses revealed that ratings of own pain distress decreased as the scores on multiple psychopathic traits increased. Only the lifestyle facet correlated in the negative direction with beliefs about others’ distress. Taken together, our findings suggest that beliefs about how much pain distress others may experience is indeed mediated by own pain distress, and that the tendency to lead an erratic lifestyle is linked to alterations in this mechanism.
Linking Multi-Layer Dynamical GCN With Style-Based Recalibration CNN for EEG-Based Emotion Recognition
Authors: Bao Guangcheng , Yang Kai , Tong Li , Shu Jun , Zhang Rongkai , Wang Linyuan , Yan Bin , Zeng Ying
Published: February 2022

Electroencephalography (EEG)-based emotion computing has become one of the research hotspots of human-computer interaction (HCI). However, it is difficult to effectively learn the interactions between brain regions in emotional states by using traditional convolutional neural networks because there is information transmission between neurons, which constitutes the brain network structure. In this paper, we proposed a novel model combining graph convolutional network and convolutional neural network, namely MDGCN-SRCNN, aiming to fully extract features of channel connectivity in different receptive fields and deep layer abstract features to distinguish different emotions. Particularly, we add style-based recalibration module to CNN to extract deep layer features, which can better select features that are highly related to emotion. We conducted two individual experiments on SEED data set and SEED-IV data set, respectively, and the experiments proved the effectiveness of MDGCN-SRCNN model. The recognition accuracy on SEED and SEED-IV is 95.08 and 85.52%, respectively. Our model has better performance than other state-of-art methods. In addition, by visualizing the distribution of different layers features, we prove that the combination of shallow layer and deep layer features can effectively improve the recognition performance. Finally, we verified the important brain regions and the connection relationships between channels for emotion generation by analyzing the connection weights between channels after model learning.
Beyond the Motor Cortex: Thalamic Iron Deposition Accounts for Disease Severity in Amyotrophic Lateral Sclerosis
Authors: Li Qianwen , Zhu Wenjia , Wen Xinmei , Zang Zhenxiang , Da Yuwei , Lu Jie
Published: February 2022

Objective

Previous studies have reliably identified iron deposition in the motor cortex as potential pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we intended to investigate iron deposition, gray matter (GM) atrophy, and their associations with disease severity in the motor cortex and the thalamus in patients with ALS.

Methods

A total of 34 patients with ALS (age 51.31 ± 8.24 years, 23 males) and 34 nonneurological controls (age 50.96 ± 9.35 years, 19 males) were enrolled between 2018 and 2020. The Revised ALS Functional Rating Scale (ALSFRS-R) and the Penn upper motor neuron (UMN) score were measured. MRI data included quantitative susceptibility mapping (QSM) for iron deposition and three-dimensional (3D) T1 for gray matter volume. After a between-group comparison, Pearson's correlation coefficient was used for identifying correlations of iron deposition, GM volume, and clinical measurements.

Results

The two-sample t-tests revealed increased iron deposition in the left precentral gyrus (peak voxel T = 4.78, PSVC = 0.03) and the thalamus (peak voxel: right: T = 6.38, PSVC < 0.001; left: T = 4.64, PSVC = 0.02) in patients with ALS. GM volume of the precentral gyrus (T = −2.42, P = 0.02) and the bilateral thalamus (T = −4.10, P < 0.001) were reduced. Negative correlations were found between the increased QSM values and the decreased GM volume (P < 0.04, one-tailed) in patients with ALS. Iron deposition in the left precentral gyrus was positively correlated with the UMN score (R = 0.40, P = 0.02) and the GM volume was negatively correlated with the UMN score (R = −0.48, P = 0.004). Negative correlation between thalamic iron deposition and the ALSFRS-R (R = −0.36, P = 0.04) score was observed.

Discussion

Iron deposition in the thalamus, in addition to the motor cortex, is accompanied by GM atrophy and is associated with disease severity in patients with ALS, indicating that the thalamus is also a pathological region in patients with ALS.
A Single-Health System Case Series of New-Onset CNS Inflammatory Disorders Temporally Associated With mRNA-Based SARS-CoV-2 Vaccines
Authors: Ballout Ahmad A. , Babaie Anna , Kolesnik Michael , Li Jian Yi , Hameed Natasha , Waldman Glenn , Chaudhry Frasat , Saba Sami , Harel Asaff , Najjar Souhel
Published: February 2022

Background

Since 2020, over 250 million doses of mRNA-based SARS-CoV-2 vaccines have been administered in the United States and hundreds of millions worldwide between the Pfizer-BioNTech and Moderna SARS-CoV-2 vaccines. To date, there have been rare reports associating mRNA-based SARS-CoV-2 vaccines with episodes of inflammatory and autoimmune CNS disorders. We report a case series of five patients with new-onset neurological disorders of inflammatory or immunological origin temporally associated with these vaccines.

Methods

A case-series of five patients within a single 23-hospital health system who developed new-onset CNS inflammatory disease within 2 weeks of receiving a dose of an mRNA-based SARS-CoV-2 vaccine.

Results

Five cases of post-vaccination CNS disorders of immune origin (fatal ADEM; n = 1, new-onset NMOSD; n = 2, new-clinical onset MS-like syndrome but with preexisting clinically silent mild demyelination; n = 1, meningoencephalitis; n = 1) observed within 2 weeks of inoculation with either the first or second dose of mRNA-based SARS-CoV-2 vaccines (Moderna = 3, Pfizer = 2).

Discussion

To our knowledge, these are among the emerging cases of CNS adverse events of immunological or inflammatory origin. These findings should be interpreted with great caution as they neither prove a mechanistic link nor imply a potential long-term increased risk in post-vaccination CNS autoimmunity. Larger prospective studies assessing the potential association between mRNA-based vaccination and the development of neurological adverse events of suspected immune origin, particularly among those with underlying CNS or systemic autoimmune disorders, are needed. The use of mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high efficacy in overcoming this pandemic.
Longitudinal Assessment of Behaviour and Associated Bio-Markers Following Chronic Consumption of β-Sitosterol β-D-Glucoside in Rats: A Putative Model of Parkinson’s Disease
Authors: Bigelow Logan J. , Perry Melissa A. , Ogilvie Sarah L. , Tasker R. Andrew
Published: February 2022

The consumption of cycad (Cycas circinalis) seeds has been linked to the development of Amyotrophic Lateral Sclerosis-Parkinsonism Dementia Complex (ALS-PDC) in humans. ALS-PDC is a clinically variable disease presenting as a combination of symptoms typical of PD and/or ALS. Chronic consumption of β-sitosterol β-D-glucoside (BSSG), a component of the cycad seed, by rats (Rattus norvegicus) has been previously reported to initiate a progressive pathology that develops over several months and manifests as behavioural and histopathological changes that resemble characteristic features of Parkinson’s disease. As part of an independent multi-site validation study, we have tried to replicate and further characterize the BSSG model with a focus on motor function, and associated immunohistochemical markers. Beginning at 3 months of age, male CD® (Sprague Dawley) rats (N = 80) were dosed orally with either a flour pellet or a flour pellet containing BSSG (3 mg) daily (5×/week) for 16 weeks consistent with previous reports of the model. Following BSSG intoxication, separate cohorts of animals (n = 10/treatment) were exposed to a behavioural test battery at 16, 24, 32, or 40 weeks post-initial BSSG feeding. The test battery consisted of the open field test, cylinder test, and ultrasonic vocalization (USV) assessment. No changes in behaviour were observed at any time point. Following behavioural testing, animals were processed for immunohistochemical markers of substantia nigra integrity. Immunohistochemistry of brain tissue revealed no differences in the microglial marker, Iba1, or the dopaminergic integrity marker, tyrosine hydroxylase (TH), in the substantia nigra at any assessment point. The absence of any group differences in behaviour and immunhistochemistry indicates an inability to replicate previous reports. Further investigation into the sources of variability in the model is necessary prior to further utilization of the BSSG model in preclinical studies.
Comparative Analysis of Nutritional Components and Phytochemical Attributes of Selected Thai Rice Bran
Authors: Wisetkomolmat Jiratchaya , Arjin Chaiwat , Satsook Apinya , Seel-audom Mintra , Ruksiriwanich Warintorn , Prom-u-Thai Chanakan , Sringarm Korawan
Published: February 2022

It is important to raise awareness regarding rice's nutritional quality and health benefits in terms of enhancing rice consumption in people's daily diets. This study evaluated the proximate components and phytochemical profiles of 11 Thai rice bran varieties, 4 non-colored rice brans and 7 colored rice brans, collected from the same agricultural fields. The chemical composition (ash, fat, proteins, fiber, and gross energy) was determined using proximate analysis methods. High-performance liquid chromatography was used to analyze the γ-oryzanol, tocopherols, and anthocyanins, while gas chromatography mass spectrometry determined the free fatty compounds. The phenolic profile was determined using liquid chromatography-mass spectrometry. The results showed great variations in each parameter of the nutritional and bioactive components among different rice bran varieties. Statistical analysis was also performed correlating the results obtained from PCA to categorize the samples by their nutritional characteristics into three main groups: group A with a high content of protein and fiber, group B with a high content of fat and gross energy, and group C with low fat and energy values but high amounts of functional, active components, particularly γ-oryzanol. Anthocyanins were detected in only one sample of colored rice bran. The major free fatty acids found in rice bran samples were oleic, linoleic, and palmitic acids. Systematic assessment of the concentration of these compounds gained from this study would be helpful to the industrial sector for selecting phytochemical-rich varieties as a value-added component in nutritional products.
Comparison of the Characteristics and Prognosis Between Very Young Women and Older Women With Breast Cancer: A Multi-Institutional Report From China
Authors: Yang Yaping , Wei Weidong , Jin Liang , He Haiyan , Wei Mengna , Shen Shiyu , Pi Hao , Liu Zhiqin , Li Hengyu , Liu Jieqiong
Published: February 2022

Purpose

Our understanding of breast cancer in very young women (≤35 years old) remains limited. We aimed to assess the clinicopathological characteristics, molecular subtype, and treatment distribution and prognosis of these young patients compared with patients over 35 years.

Methods

We retrospectively analyzed non-metastatic female breast cancer cases treated at three Chinese academic hospitals between January 1, 2008, and December 31, 2018. Local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were compared between different age groups and stratified with distinct molecular subtypes.

Results

A total of 11,671 women were eligible for the final analyses, and 1,207 women (10.3%) were ≤35 years at disease onset. Very young breast cancer women were more likely to be single or childless, have higher-grade disease, have more probability of lymphovascular invasion (LVI) in tumor and triple-negative subtype, and be treated by lumpectomy, chemotherapy especially more anthracycline- and paclitaxel-based chemotherapy, endocrine therapy plus ovarian function suppression (OFS), anti-HER2 therapy, and/or radiotherapy than older women (P < 0.05 for all). Very young women had the lowest 5-year LRFS and DFS among all age groups (P < 0.001 for all). When stratified by molecular subtype, very young women had the worst outcomes vs. women from the 35~50-year-old group or those from >50-year-old group for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) subtype, including LRFS, DFS, and OS (P < 0.05 for all). In terms of LRFS and DFS, multivariate analyses showed similar results among the different age groups.

Conclusion

Our study demonstrated that very young women with breast cancer had higher-grade tumors, more probability of LVI in tumor, and more triple-negative subtype, when compared with older patients. They had less favorable survival outcomes, especially for patients with the HR+/HER2− subtype.
Case Report: Hematologic Recovery Following Stereotactic Ablative Radiotherapy in a Patient With Early-Stage Non-Small Cell Lung Cancer and Paraneoplastic Myelofibrosis
Authors: Sloan Lindsey , Naik Rakhi P. , Umrau Kavita , Xian Rena Ruiyu , Marrone Kristen A. , Voong Khinh Ranh
Published: February 2022

Herein, we report the first case presentation of paraneoplastic myelofibrosis associated with cancer. Paraneoplastic syndromes occur in some patients with thoracic malignancies; however, myelofibrosis is not commonly seen in non-small cell lung cancer (NSCLC). We report a case of myelofibrosis in a patient with a new diagnosis of NSCLC that resolved after stereotactic ablative radiotherapy (SABR). In conclusion, NSCLC may evoke unexpected systemic effects that resolve with treatment.
All-Trans-Retinoic Acid Combined With Valproic Acid Can Promote Differentiation in Myeloid Leukemia Cells by an Autophagy Dependent Mechanism
Authors: Benjamin Dalyia N. , O’Donovan Tracey R. , Laursen Kristian B. , Orfali Nina , Cahill Mary R. , Mongan Nigel P. , Gudas Lorraine J. , McKenna Sharon L.
Published: February 2022

Acute myeloid leukemia (AML) is an aggressive blood cancer with an overall survival of 30%. One form of AML, acute promyelocytic leukemia (APL) has become more than 90% curable with differentiation therapy, consisting of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Application of differentiation therapy to other AML subtypes would be a major treatment advance. Recent studies have indicated that autophagy plays a key role in the differentiation of ATRA-responsive APL cells. In this study, we have investigated whether differentiation could be enhanced in ATRA resistant cells by promoting autophagy induction with valproic acid (VPA). ATRA sensitive (NB4) and resistant leukemia cells (NB4R and THP-1) were co-treated with ATRA and valproic acid, followed by assessment of autophagy and differentiation. The combination of VPA and ATRA induced autophagic flux and promoted differentiation in ATRA-sensitive and -resistant cell lines. shRNA knockdown of ATG7 and TFEB autophagy regulators impaired both autophagy and differentiation, demonstrating the importance of autophagy in the combination treatment. These data suggest that ATRA combined with valproic acid can promote differentiation in myeloid leukemia cells by mechanism involving autophagy.
Trajectories of Pain in Very Old Age: The Role of Eudaimonic Wellbeing and Personality
Authors: Wettstein Markus , Schilling Oliver Karl , Wahl Hans-Werner
Published: February 2022

Pain is common in very old age and in the last years prior to death. However, little is known regarding longitudinal trajectories of pain in very old age and at the end of life. Moreover, whereas medical and morbidity-related factors contributing to pain are established, the role of psychosocial factors, such as eudaimonic wellbeing or personality as potential determinants of late-life pain trajectories has so far not been sufficiently investigated. We used data from the LateLine project. The sample consisted ofn= 118 very old adults (M= 90.5 years,SD= 2.8 years) who were living alone at baseline and who had died between 2009 and 2021. They took part in up to 16 measurement occasions (M= 5.2,SD= 4.7, range 1–16) within an observational interval of 7 years. Assessment of pain was based on the SF-36 bodily pain subscale. Key indicators of eudaimonic wellbeing (autonomy, environmental mastery, and purpose in life) as well two of the Big Five personality traits (neuroticism and extraversion) were included as predictors. We controlled in all analyses for gender, education, subjective health, and depressive symptoms. Contrasting pain trajectories over chronological age (time since birth) vs. time to death, a time-to-death-related model resulted in a better model fit and accounted for a larger amount of pain variability than the age-related model. Mean-level change in pain, both over age and time to death, was not significant, but there was substantial interindividual variability in intraindividual trajectories. Age-related change in pain was significantly predicted by autonomy and neuroticism, with increasing pain among those who had lower initial autonomy scores and higher initial neuroticism scores. With regard to time-to-death-related trajectories of pain, higher purpose in life as well as lower extraversion at baseline predicted less increase or even steeper decrease in pain with approaching death. Our findings suggest that, despite overall mean-level stability in pain both over age and time to death, there is a substantial proportion of individuals who reveal deterioration in pain over time. Regarding the role of psychosocial predictors, personality traits and eudaimonic wellbeing are related with late-life pain trajectories both over age and time-to-death.
Engineered Bacteria EcN-MT Alleviate Liver Injury in Cadmium-Exposed Mice via its Probiotics Characteristics and Expressing of Metallothionein
Authors: Zou Changwei , Chen Ying , Li Hongyu , Li Wenyu , Wei Jin , Li Ziyan , Wang Xinliang , Chen Tingtao , Huang Hong
Published: February 2022

Cadmium (Cd) exposure is a widespread problem in many parts of the world, but effective means to treat Cd exposure is still lacking. Hence, an engineered strain expressing metallothionein (MT) named Escherichia coli Nissle 1917 (EcN)-MT was constructed, and its potential in the treatment of Cd exposure was evaluated. The in vitro studies showed that metallothionein expressed by EcN-MT could significantly bind Cd. Further, the in vivo results indicated that EcN-MT strain could reduce 26.3% Cd in the liver and increase 24.7% Cd in the feces, which greatly decreased malondialdehyde (MDA) levels and increased catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) levels in liver, and reduced the expression of toll-like receptor4 (TLR4), nuclear factor-κB (NF-κB), the myeloid differentiation factor 88 (Myd88) andincreased B-cell lymphoma 2 (Bcl-2)/Bcl-2-Associated X (Bax). Moreover, high throughput sequencing results indicated that EcN-MT strain greatly enhanced the beneficial bacteria of Ruminococcaceae, Lactobacillaceae, Akkermansia, Muribaculaceae, Lachnospiraceae, Dubosiella and restored the disturbed microbial ecology to the normal level. Therefore, the high Cd binding capacity of the expressed metallothionein, together with the beneficial characteristics of the host bacteria EcN, makes EcN-MT a sound reagent for the treatment of subchronic Cd exposure-induced liver injury.
Enhanced Microwave Electric Field Measurement With Cavity-Assisted Rydberg Electromagnetically Induced Transparency
Authors: Li Shaohua , Yuan Jinpeng , Wang Lirong , Xiao Liantuan , Jia Suotang
Published: February 2022

We report a scheme for enhancing microwave electric field measurement by cavity-assisted Rydberg electromagnetically induced transparency in the 87Rb coherent atomic system. The vacuum Rabi splitting appears when the probe field is strongly coupled with intracavity atoms. The cavity-assisted electromagnetically induced transparency with dual-peak profile is observed as a strong coupling laser is further introduced into the optical ring cavity. The optimal atomic density, resulting in an appropriate vacuum Rabi splitting interval and cavity-assisted electromagnetically induced transparency amplitude, is determined for the coupling effect criterion of the probe field and intracavity atoms. Finally, the cavity-assisted electromagnetically induced transparency is employed to accurately measure the microwave electric field strength, and a measurement sensitivity factor of about 2 is improved owing to an enhanced photon–atom interaction. This study is beneficial for the development of compact, broadband, and self-calibrating microwave receivers.