bluuebunny/crossref_metadata_2025 huggingface dataset:
Planning for a Crisis, but Preparing for Every Day: What Predicts Schools' Preparedness to Respond to a School Safety Crisis?
Authors: Bradshaw Catherine P. , Debnam Katrina J. , Kush Joseph M. , Lindstrom Johnson Sarah
Published: February 2022

This study aimed to identify potential gaps related to crisis preparedness at 98 public secondary schools. We focused on crises that may occur following a substantiated eminent threat of school violence. Crisis preparedness data collected by trained external assessors captured knowledge of the procedure for responding in a safety-related crisis and process for notifying school staff, as well as the posting of the crisis plan in school locations. Data were analyzed in conjunction with data on student- and staff-reported school climate, school demographics, and external observations of the school. Analyses indicated that the staff were least aware of the process for notifying staff that a crisis was occurring. Middle schools, schools with higher levels of school disorder, and those with poorer reading and math scores were less likely to know the procedure, know the notification process, and have the plans posted in all locations. Schools also need to improve posting of school crisis procedures in shared and open spaces, such as the cafeteria and gymnasium; this is especially critical given that many school shootings occur in these large open spaces. Multilevel analyses indicated that staff perceptions of safety were significantly higher in schools in which the procedure was posted in all locations. Together, these findings provide evidence of a link among crisis planning, school context, and school climate, and complement the need for additional training on what to do following the substantiation of a credible and eminent threat.
The Beneficial Effects of Beta Blockers on the Long-Term Prognosis of Patients With Premature Atrial Complexes
Authors: Huang Ting-Chun , Lee Po-Tseng , Huang Mu-Shiang , Chiu Pin-Hsuan , Su Pei-Fang , Liu Ping-Yen
Published: February 2022

Aims

Premature atrial complexes (PACs) have been reported to increase the risk of adverse cardiovascular outcomes. Beta blockers at low dosages may help to reduce PAC symptoms, but it is unclear whether they can improve long-term outcomes.

Methods

Patients enrolled from a Holter cohort in a medical referral center were stratified into high-burden (≥100 beats/24 h) and low-burden (<100 beats/24 h) sub-cohorts, and propensity score matching between treatment groups and non-treatment groups was conducted for each sub-cohort.

Results

In the high-burden sub-cohort, after propensity score matching, the treatment group and non-treatment group respectively had 208 and 832 patients. The treatment group had significantly lower mortality rates than the non-treatment group [hazard ratio (HR) = 0.521, 95% confidence interval (CI) = 0.294–0.923, p = 0.025], but there was no difference in new stroke (HR = 0.830, 95% CI = 0.341–2.020, p = 0.681), and new atrial fibrillation (HR = 1.410, 95% CI = 0.867–2.292, p = 0.167) events. In the low-burden sub-cohort, after propensity score matching, there were 614 patients in the treatment group and 1,228 patients in the non-treatment group. Compared to the non-treatment group, up to 40% risk reduction in mortality was found in the treatment group (HR = 0.601, 95% CI = 0.396–0.913, p = 0.017), but no differences in new stroke (HR =0.969, 95% CI = 0.562–1.670, p = 0.910) or atrial fibrillation (HR = 1.074, 95% CI = 0.619–1.863, p = 0.800) were found.

Conclusions

Beta blockers consistently decreased long-term mortality in high-burden and low-burden patients. Interestingly, this effect was not achieved through reduction of new-onset stroke or AF, and further research is warranted.
Cardiovascular Risk According to Body Mass Index in Women of Reproductive Age With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
Authors: Zhuang Chenchen , Luo Xufei , Wang Wenjuan , Sun Runmin , Qi Miaomiao , Yu Jing
Published: February 2022

Background

Polycystic ovary syndrome (PCOS) is a heterogeneous condition that affects women of reproductive age. The association between PCOS and cardiovascular risk according to body mass index (BMI) categories is unclear.

Objective

We evaluated the association between cardiovascular risk according to BMI categories and PCOS in women of reproductive age.

Methods

A literature search was conducted in the EMBASE, MEDLINE, Cochrane Library, and PubMed databases from their inception to 9 September, 2021. Observational cross-sectional, retrospective, and prospective controlled studies were included. The main analyses examined the relationship between cardiovascular risks (i.e., blood pressure and lipid levels) and BMI in women of reproductive age with PCOS.

Results

Thirty-eight studies, with a total of 6,078 subjects, were included in this metaanalysis. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in women of reproductive age with PCOS. Lower high-density lipoprotein (HDL)-cholesterol [SMD (95% CI): −0.21 (−0.35, −0.08), p = 0.002], higher triglycerides [SMD (95% CI): 0.38 (0.29, 0.48), p < 0.001], higher low-density lipoprotein (LDL)-cholesterol [SMD (95% CI): 0.29 (0.20, 0.39), p < 0.001], higher nonHDL-cholesterol [SMD (95% CI): 0.42 (0.31, 0.52), p < 0.001] and waist-to-hip ratio (WHR) [MD (95% CI): 0.03 (0.02, 0.04), p < 0.001] were seen in women of reproductive age with PCOS. In addition, the subgroup analysis revealed that systolic BP and HDL-cholesterol increased at BMI < 25 kg/m2 and BMI 25–30 kg/m2. Diastolic BP increased at BMI 25–30 kg/m2. Triglycerides, LDL-cholesterol, nonHDL-cholesterol, and WHR increased in all BMI categories.

Conclusions

PCOS is associated with cardiovascular risk. Lipid levels and BP increased in women of reproductive age with PCOS, regardless of BMI.

Systematic Review Registration

Open Science Framework (10.17605/OSF.IO/92NBY).
Pressure-Natriuresis Response Is Diminished in Old Age
Authors: Kim Yang Gyun , Moon Ju-Young , Oh Bermseok , Chin Ho Jun , Kim Dong Ki , Park Jung Hwan , Shin Sung Joon , Choi Bum Soon , Lim Chun Soo , Lee Sang Ho
Published: February 2022

Background

Age-related alterations in renal sodium handling affect blood pressure (BP). We aimed to clarify whether the pressure-natriuresis response changes with age, leading to BP elevation.

Methods

A total of 4,859 participants with normal renal function from the Korean Genome and Epidemiology Study (KoGES) and 235 patients with non-diabetic chronic kidney disease (CKD) from the ESPECIAL trial were included and divided into the younger and older groups. In ESPECIAL, participants took olmesartan from weeks 0 to 16 and were educated about a low-salt diet (LSD) from weeks 8 to 16.

Results

In both studies, older participants showed lower estimated glomerular filtration rate (eGFR) and urine concentration index and higher albuminuria. In KoGES, BP was higher and urine sodium was lower in older participants. In ESPECIAL, diastolic BP at 0 week was lower in older participants. Olmesartan reduced BP in both groups, whereas LSD decreased systolic BP only in older participants. Urine sodium increased in younger participants but decreased in older participants after olmesartan use. In KoGES, urine sodium was correlated with BP in both groups after adjusting for age, sex, and eGFR; however, the correlation coefficient was lower in older participants. In ESPECIAL, only younger participants showed a significant positive association between systolic BP and urine sodium in multiple regression analysis.

Conclusions

The pressure-natriuresis response was diminished in older participants with or without CKD.
Permafrost Base Degradation: Characteristics and Unknown Thread With Specific Example From Hornsund, Svalbard
Authors: Dobiński Wojciech , Kasprzak Marek
Published: February 2022

Permafrost degradation is one of the most pressing issues in the modern cryosphere related to climate change. Most attention is paid to the degradation of the top of the active permafrost associated with contemporary climate. This is the most popular issue because in the subsurface part of it there is usually the greatest accumulation of ground ice in direct relation to the changes taking place. The melting of ground ice is the cause of the greatest changes related to subsidence and other mass-wasting processes. The degradation of the subsurface permafrost layer is also responsible for the increased emission of CO2 and methane. However, this is not a fully comprehensive look at the issue of permafrost degradation, because depending on its thickness, changes in its thermal properties may occur more or less intensively throughout its entire profile, also reaching the base of permafrost. These changes can degrade permafrost throughout its profile. The article presents the basic principles of permafrost degradation in its overall approach. Both the melting of the ground ice and the thermal degradation of permafrost, as manifested in an increase in its temperature in part or all of the permafrost profile, are discussed. However, special attention is paid to the degradation characteristics from the permafrost base. In the case of moderately thick and warm permafrost in the zone of its sporadic and discontinuous occurrence, this type of degradation may particularly contribute to its disappearance, and surficial consequences of such degradation may be more serious than we expect on the basis of available research and data now. A special case of such degradation is the permafrost located in the coastal zone in the vicinity of the Hornsund Spitsbergen, where a multidirectional thermal impact is noted, also causing similar degradation of permafrost: from the top, side and bottom. Especially the degradation of permafrost from the permafrost base upwards is an entirely new issue in considering the evolution of permafrost due to climate change. Due to the difficulties in its detection, this process may contribute to the threats that are difficult to estimate in the areas of discontinuous and sporadic permafrost.
A Novel Method for Determining Geophone Orientations From Zero-Offset VSP Data Constrained by Scalar Field
Authors: Yang Yuyong , Qi Qiaomu , Zhou Huailai , Wang Zhengyang
Published: February 2022

In vertical seismic profile (VSP) acquisition, the orientation of the three-component geophones in a borehole is often not aligned due to random rotation of the wireline receiver array. Knowing the geophone orientation is crucial for rotating the waveforms back to the position where the geophones are assumed to be aligned. This procedure is critical in three-component VSP data processing as it provides the correct wavefields for subsequent VSP data imaging and inversion. For zero-offset or near zero-offset VSP measurements, the direct P-wave propagates nearly vertically, and the horizontal geophones receive only a small fraction of the direct P-wave energy. The first-arrival in the horizontal component data is often of low signal-to-noise ratio (SNR). As a result, it is difficult to apply conventional first-arrival–based methods for obtaining accurate geophone orientations. On the other hand, a seismic event comprising individual waveform would achieve maximum correlation if all corresponding geophones are aligned. The geometric characteristics, that is, the slope and continuity of a seismic event in the vector wavefield are the same with those of the modules of the vector wavefield. The latter, also known as the scalar wavefield, can be used for scanning geophone orientations based on waveform correlation. In this study, we propose to use the scalar field to extract the slope of seismic events. The orientation of the individual geophone was calculated with the constraint of the slope. We use both synthetic and field data to demonstrate the effectiveness and applicability of the proposed method. The results show that the new method can provide wavefields of horizontal component VSP data with much higher accuracy and resolution.
Assessment of Osteoporosis in Lumbar Spine: In Vivo Quantitative MR Imaging of Collagen Bound Water in Trabecular Bone
Authors: Liu Jin , Liao Jian-Wei , Li Wei , Chen Xiao-Jun , Feng Jia-Xin , Yao Lin , Huang Pan-Hui , Su Zhi-Hai , Lu Hai , Liao Yu-Ting , Li Shao-Lin , Ma Ya-Jun
Published: February 2022

Aim

Bone collagen matrix makes a crucial contribution to the mechanical properties of bone by imparting tensile strength and elasticity. The collagen content of bone is accessible via quantification of collagen bound water (CBW) indirectly. We prospectively study the performance of the CBW proton density (CBWPD) measured by a 3D short repetition time adiabatic inversion recovery prepared ultrashort echo time (STAIR-UTE) magnetic resonance imaging (MRI) sequence in the diagnosis of osteoporosis in human lumbar spine.

Methods

A total of 189 participants with a mean age of 56 (ranged from 50 to 86) years old were underwent MRI, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DXA) in lumbar spine. Major fracture risk was also evaluated for all participants using Fracture Risk Assessment Tool (FRAX). Lumbar CBWPD, bone marrow fat fraction (BMFF), bone mineral density (BMD) and T score values were calculated in three vertebrae (L2–L4) for each subject. Both the CBWPD and BMFF were correlated with BMD, T score, and FRAX score for comparison. The abilities of the CBWPD and BMFF to discriminate between three different cohorts, which included normal subjects, patients with osteopenia, and patients with osteoporosis, were also evaluated and compared using receiver operator characteristic (ROC) analysis.

Results

The CBWPD showed strong correlation with standard BMD (R2 = 0.75, P < 0.001) and T score (R2 = 0.59, P < 0.001), as well as a moderate correlation with FRAX score (R2 = 0.48, P < 0.001). High area under the curve (AUC) values (≥ 0.84 using QCT as reference; ≥ 0.76 using DXA as reference) obtained from ROC analysis demonstrated that the CBWPD was capable of well differentiating between the three different subject cohorts. Moreover, the CBWPD had better correlations with BMD, T score, and FRAX score than BMFF, and also performed better in cohort discrimination.

Conclusion

The STAIR-UTE-measured CBWPD is a promising biomarker in the assessment of bone quality and fracture risk.
Dulung Proglacial Lake, Suru Sub-Basin, Western Himalaya: Evolution, Controls and Impacts on Glacier Stability
Authors: Garg Siddhi , Garg Purushottam Kumar , Yousuf Bisma , Shukla Aparna , Shukla Uma Kant
Published: February 2022

Proglacial lakes are continually developing and expanding across the Himalayan glaciered terrain in response to climate change. These lakes are known to destabilize the glaciers by enhancing their frontal ablation, causing higher than average glacier area and mass losses. Thus, to comprehend the dynamics of proglacial lakes and their influence on the overall glacier health, we study the lake-terminating Dulung Glacier located in the Suru sub-basin, Ladakh, western Himalaya and compare it with the adjacent land-terminating Chilung Glacier. The pronounced melting of the Dulung Glacier, supported by glacier topography (surface gradient between accumulation and ablation zone) and valley morphology (wider near the snout and narrower downwards), seems to be the prime reason for the formation, accommodation and sustenance of the proglacial lake. The expansion in proglacial lake (.008 km2a−1) during 1977–2018 is accompanied by an enhanced degeneration of the Dulung Glacier (mass balance: −.47 ± .06 m w.e.a−1, shrinkage rate: .3 ± .001% a−1; retreat rate: 32 ± .7 ma−1, surface ice velocity reduction: 16%), which has accelerated post-1993. In comparison, land-terminating Chilung Glacier shows lower degeneration rates (mass balance: −.28 ± .02 m w.e.a−1; shrinkage rate: .2 ± .001% a−1; retreat rate: 17 ± 0.7 ma−1, surface ice velocity reduction: 8%) during 1971–2018. This suggests a substantial impact of the proglacial lake in enhancing the Dulung Glacier’s sensitivity towards climate change compared to the Chilung Glacier. If the current rate of lake expansion continues, it would further enhance the Dulung Glaciers’ degeneration rates, thus impacting its stability.
Early Brain microRNA/mRNA Expression is Region-Specific After Neonatal Hypoxic-Ischemic Injury in a Mouse Model
Authors: Peeples Eric S. , Sahar Namood-e , Snyder William , Mirnics Karoly
Published: February 2022

Background: MicroRNAs (miRNAs) may be promising therapeutic targets for neonatal hypoxic-ischemic brain injury (HIBI) but targeting miRNA-based therapy will require more precise understanding of endogenous brain miRNA expression.

Methods: Postnatal day 9 mouse pups underwent HIBI by unilateral carotid ligation + hypoxia or sham surgery. Next-generation miRNA sequencing and mRNA Neuroinflammation panels were performed on ipsilateral cortex, striatum/thalamus, and cerebellum of each group at 30 min after injury. Targeted canonical pathways were predicted by KEGG analysis.

Results: Sixty-one unique miRNAs showed differential expression (DE) in at least one region; nine in more than one region, including miR-410-5p, -1264-3p, 1298-5p, -5,126, and -34b-3p. Forty-four mRNAs showed DE in at least one region; 16 in more than one region. MiRNAs showing DE primarily targeted metabolic pathways, while mRNAs targeted inflammatory and cell death pathways. Minimal miRNA-mRNA interactions were seen at 30 min after HIBI.

Conclusion: This study identified miRNAs that deserve future study to assess their potential as therapeutic targets in neonatal HIBI. Additionally, the differences in miRNA expression between regions suggest that future studies assessing brain miRNA expression to guide therapy development should consider evaluating individual brain regions rather than whole brain to ensure the sensitivity needed for the development of targeted therapies.
The Risk of Adverse Effects of TNF-α Inhibitors in Patients With Rheumatoid Arthritis: A Network Meta-Analysis
Authors: He Bei , Li Yun , Luo Wen-wen , Cheng Xuan , Xiang Huai-rong , Zhang Qi-zhi , He Jie , Peng Wen-xing
Published: February 2022

Objectives

To evaluate the safety of each anti-TNF therapy for patients with rheumatoid arthritis (RA) and then make the best choice in clinical practice.

Methods

We searched PUBMED, EMBASE, and the Cochrane Library. The deadline for retrieval is August 2021. The ORs, Confidence Intervals (CIs), and p values were calculated by STATA.16.0 software for assessment.

Result

72 RCTs involving 28332 subjects were included. AEs were more common with adalimumab combined disease-modifying anti-rheumatic drugs (DMARDs) compared with placebo (OR = 1.60, 95% CI: 1.06, 2.42), DMARDs (1.28, 95% CI: 1.08, 1.52), etanercept combined DMARDs (1.32, 95% CI: 1.03, 1.67); certolizumab combined DMARDs compared with placebo (1.63, 95% CI: 1.07, 2.46), DMARDs (1.30, 95% CI: 1.10, 1.54), etanercept combined DMARDs (1.34, 95% CI: 1.05, 1.70). In SAEs, comparisons between treatments showed adalimumab (0.20, 95% CI: 0.07, 0.59), etanercept combined DMARDs (0.39, 95% CI: 0.15, 0.96), golimumab (0.19, 95% CI: 0.05, 0.77), infliximab (0.15, 95% CI: 0.03,0.71) decreased the risk of SAEs compared with golimumab combined DMARDs. In infections, comparisons between treatments showed adalimumab combined DMARDs (0.59, 95% CI: 0.37, 0.95), etanercept (0.49, 95% CI: 0.28, 0.88), etanercept combined DMARDs (0.56, 95% CI: 0.35, 0.91), golimumab combined DMARDs (0.51, 95% CI: 0.31, 0.83) decreased the risk of infections compared with infliximab combined DMARDs. No evidence indicated that the use of TNF-α inhibitors influenced the risk of serious infections, malignant tumors.

Conclusion

In conclusion, we regard etanercept monotherapy as the optimal choice for RA patients in clinical practice when the efficacy is similar. Conversely, certolizumab + DMARDs therapy is not recommended.

Systematic Review Registration

identifier PROSPERO CRD42021276176.
Bacterial Communities in Coral Offspring Vary Between in situ and ex situ Spawning Environments
Authors: Shiu Jia-Ho , Lin Che-Hung , Mulla Aziz Jabir , Dang Viet Do Hung , Fong Chia-Ling , Nozawa Yoko
Published: February 2022

Examining the bacterial communities of offspring is key to understanding the establishment of coral-bacteria associations. Although high sensitivity to the environment is expected, previous studies have only examined bacterial communities of coral offspring in ex situ (laboratory) environments, not in in situ (field) environments. Here, we examined and compared the effect of ex situ and in situ environments on bacterial communities of newly released offspring (eggs and larvae) and their maternal colonies in two phylogenetically distant coral species with different reproductive modes: Dipsastraea speciosa (Scleractinia; spawner) and Heliopora coerulea (Octocorallia; brooder). Our results demonstrated that the spawning environments do not affect the bacterial composition in maternal colonies, but influence that of the offspring (eggs of D. speciosa and larvae of H. coerulea). Dominant bacterial operational taxonomic units (OTUs) varied between in situ and ex situ environments in the eggs of D. speciosa. The composition of bacterial communities among larvae of H. coerulea samples was more diverse in in situ environments than in ex situ environments. This study provides the first information on in situ bacterial communities in coral eggs and larvae and highlights their sensitivities to the local environment. Future studies must take into consideration the influence of ex situ environments on bacterial communities in coral offspring.
Measuring the Efficiency of Alternative Biodiversity Monitoring Sampling Strategies
Authors: Hernan Gema , Dubel Alexandra K. , Caselle Jennifer E. , Kushner David J. , Miller Robert J. , Reed D. C. , Sprague Joshua L. , Rassweiler Andrew
Published: February 2022

Monitoring is a crucial tool for measuring the progress and success of environmental policies and management programs. While many studies have evaluated the effectiveness of biodiversity sampling methods, few have compared their efficiency, which is crucial given the funding constraints present in all conservation efforts. In this study we demonstrate how existing analytical tools can be applied to (i) assess the relationship between sampling effort and resulting confidence in biodiversity metrics, and (ii) compare the efficiency of different methods for monitoring biodiversity. We tested this methodology on data from marine fish surveys, including: roving surveys within permanent areas, randomly placed belt transects, and randomly placed transects conducted by citizen scientists using a reduced species list. We constructed efficiency curves describing how increasing effort spent on each method reduced uncertainty in biodiversity estimates and the associated ability to detect change in diversity. All programs produced comparable measurements of species diversity for all metrics despite substantial differences in the species being surveyed by each method. The uncertainty of diversity estimations fell faster and reached a lower level for the roving diver method. Strikingly, the transect method conducted by citizen scientists performed almost identically to the more taxonomically resolved transect method conducted by professional scientists, suggesting that sampling strategies that recorded only a subset of species could still be effective, as long as the excluded species were chosen strategically. The methodology described here can guide decisions about how to measure biodiversity and optimize the resources available for monitoring, ultimately improving management outcomes.
Sleep-Disordered Breathing Is Associated With Reduced Left Atrial Strain Measured by Cardiac Magnetic Resonance Imaging in Patients After Acute Myocardial Infarction
Authors: Wester Michael , Pec Jan , Lebek Simon , Fisser Christoph , Debl Kurt , Hamer Okka , Poschenrieder Florian , Buchner Stefan , Maier Lars S. , Arzt Michael , Wagner Stefan
Published: February 2022

Aims

Sleep disordered breathing (SDB) is known to cause left atrial (LA) remodeling. However, the relationship between SDB severity and LA dysfunction is insufficiently understood and may be elucidated by detailed feature tracking (FT) strain analysis of cardiac magnetic resonance images (CMR). After myocardial infarction (MI), both the left ventricle and atrium are subjected to increased stress which may be substantially worsened by concomitant SDB that could impair consequential healing. We therefore analyzed atrial strain in patients at the time of acute MI and 3 months after.

Methods and Results

40 patients with acute MI underwent CMR and polysomnography (PSG) within 3–5 days after MI. Follow-up was performed 3 months after acute MI. CMR cine data were analyzed using a dedicated FT software. Atrial strain (ε) and strain rate (SR) for atrial reservoir ([εs]; [SRs]), conduit ([εe]; [SRe]) and booster function ([εa]; [SRa]) were measured in two long-axis views. SDB was defined by an apnea-hypopnea-index (AHI) ≥15/h. Interestingly, LA εs and εe were significantly reduced in patients with SDB and correlated negative with AHI as a measure of SDB severity at both baseline and follow-up. Intriguingly, patients that exhibited a reduced AHI at follow-up were more likely to have developed improved atrial reservoir and conduit strain (linear regression, p=0.08 for εs and εe). Patients with improved SDB (ΔAHI < −5/h) exhibited a mean improvement of LA reservoir strain of +7.2 ± 8.4% whereas patients with SDB deterioration (ΔAHI> + 5/h) showed a mean decrease of −5.3 ± 11.0% (p = 0.0131). Similarly, the difference for LA conduit function was +4.8 ± 5.9% (ΔAHI < −5/h) vs −3.6 ± 8.8% (ΔAHI> +5/h). Importantly, conventional volumetric parameters for atrial function (LA area, LA volume index) did not correlate with AHI at baseline or follow-up.

Conclusion

Our results show that LA function measured by CMR strain but not by volumetry is impaired in patients with SDB during acute cardiac injury. Consistent with a mechanistic association, improvement of SBD at follow-up resulted in improved LA strain. LA strain measurement might thus provide insight into atrial function in patients with SDB.
Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine–A Study Protocol
Authors: Chopra Arvind , Chavan-Gautam Preeti , Tillu Girish , Saluja Manjit , Borse Swapnil , Sarmukaddam Sanjeev , Chaudhuri Susmita , Rao BCS , Yadav Babita , Srikanth Narayanam , Patwardhan Bhushan
Published: February 2022

Introduction

Vaccines have emerged as the most effective tool in the fight against COVID-19. Governments all over the world have rolled out the COVID-19 vaccine program for their populations. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD™) is widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Withania somnifera (Ashwagandha) and its potential as a vaccine adjuvant. We propose to study the safety, immunogenicity and clinical protection offered by a 6-month regimen of Ashwagandha in participants who volunteer to be vaccinated against COVID-19 (COVISHIELDTM) in the ongoing national program of vaccination.

Methods and Analysis

We designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. The administration of Ashwagandha will begin within 7 days of the first or second dose of COVISHIELDTM. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. All adverse events will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user-friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks.

Ethics and Dissemination

Ethics approval was obtained through the Central and Institutional Ethics Committees. Participant recruitment commenced in December 2021. Results will be presented in conferences and published in preprints followed by peer-reviewed medical journals.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [CTRI/2021/06/034496].
Immune Cells Profiles in the Different Sites of COVID-19-Affected Lung Lobes in a Single Patient
Authors: Iwabuchi Sadahiro , Miyamoto Kyohei , Hatai Mayuko , Mikasa Yurina , Katsuda Masahiro , Murata Shin-ichi , Kondo Toshikazu , Yamaue Hiroki , Hashimoto Shinichi
Published: February 2022

Whereas the COVID-19 disease pathophysiology is under investigation, it is important to identify the pathways of viral transmission and inflammation from the pre-illness to the disease-onset stages. We analyzed five lung lobes from a patient with COVID-19 who finally died after prolonged lung protective ventilation. Pathological examination revealed moderate inflammation in upper lung lobes and uneven yet severe inflammation and diffuse alveolar damage in lower lung lobes. SARS-CoV-2 was detected at higher levels not in severely, but rather moderately inflamed middle lung lobes, and immunohistochemistry and bulk RNA-sequencing results showed that immune cells were detected at higher levels in lower lung lobes. The mRNA expression of cytokine families varied. We found an increase in keratin 5- or aquaporin 3-expressing basal cells in the severely inflamed lower lung lobes, and the alveolar stromal tissues were filled with them. Thus, this analysis of lung samples from a patient helps to determine the COVID-19 pathophysiology at a specific time point, and the virus localization and inflammatory responses at each site of the lungs provide various important indications.
How Healthcare Utilization Due to Dizziness and Vertigo Differs Between Older and Younger Adults
Authors: Prell Tino , Finn Sigrid , Axer Hubertus
Published: February 2022

Background

Vertigo and dizziness are common in older adults. We describe self-reported healthcare utilization because of dizziness and vertigo in older adults attending a tertiary care specialized vertigo center.

Methods

Data from 765 patients (45% were ≥60 years old) with chronic dizziness and vertigo who attended a daycare multimodal treatment program were recorded. Data included sociodemographic parameters, dizziness-related characteristics, the Body Sensations Questionnaire (BSQ), the Agoraphobic Cognitions Questionnaire (ACQ), and the Hospital Anxiety and Depression Scale (HADS). Also, healthcare utilization, including (1) physician and clinical services, (2) hospitalizations in the year before consulting the vertigo center, (3) prescription of drugs and other professional services were included. Descriptive statistics, exploratory data analysis, and regression models were used.

Results

Intensity of dizziness was similar in both age groups, however, distress due to dizziness was more severe in younger persons. Dizziness symptoms lasted longer in older adults than in younger persons. Older adults had a somatic diagnosis (74.6 vs. 35.0%) more frequently and reported more falls (37.2 vs. 28.5%) than younger individuals. Anxiety about bodily sensations was higher in younger patients (mean BSQ1 = 9.33 ± 5.6) than in older patients (mean BSQ1 = 6.72 ± 5.4). Older persons had fewer depressive symptoms (mean HADS depression = 5.8 ± 3.6 vs. 6.5 ± 4.1) and less anxiety (mean HADS anxiety = 5.7 ± 3.7 vs. 7.8 ± 4.1) than younger individuals. Younger people were more frequently hospitalized (24.4%) than older adults (16.3%) in the year before consulting the vertigo center. Also, younger patients and patients with non-somatic etiologies had considerably more consultations with healthcare providers than older patients. Older adults received less medication (50.3%), less physiotherapy (41%), and less psychological therapy (11.6%) for vertigo than younger people (59.7, 52.2, 20.4%, respectively).

Conclusion

Age-associated differences in healthcare utilization were defined in selected patients attending a specialized vertigo center. Since dizziness is frequently a heterogeneous disorder requiring interdisciplinary care, its diagnostic and therapeutic work-up must be improved for older patients with dizziness.
Development of 1,5-Diaryl-Pyrazole-3-Formate Analogs as Antifungal Pesticides and Their Application in Controlling Peanut Stem Rot Disease
Authors: Ma Yihui , Yang Jun , Yang Dangwei , Qin Guangyu , Zu Junhuai
Published: February 2022

Graphical Abstract

3-Chloropyridinyl moiety grants compound 6 with comparable antifungal effect to tebuconazole and thifluzamide against Sclerotium rolfsii in a dose-dependent manner.
Rapid Detection of Mycobacterium tuberculosis in Pleural Fluid Using Resuscitation-Promoting Factor-Based Thin Layer Agar Culture Method
Authors: Du Fengjiao , Xing Aiying , Li Zihui , Pan Liping , Jia Hongyan , Du Boping , Sun Qi , Wei Rongrong , Liu Zhongquan , Zhang Zongde
Published: February 2022

Background

Pleural tuberculous is difficult to diagnose. Culture is still considered the gold standard, especially in resource-limited settings where quick, cheap, and easy techniques are needed. The aim of the study was to evaluate resuscitation-promoting factors (Rpfs)-based thin layer agar (TLA) culture method for quick detection of Mycobacterium tuberculosis in pleural fluid.

Methods

Patients with suspected pleural TB were enrolled prospectively in our hospital, pleural fluid of all patients were collected, stained with Ziehl–Neelsen for acid-fast bacilli (AFB), cultured on Rpfs-TLA, TLA, and Löwenstein–Jensen (LJ) medium, and identified according to recommended procedures.

Results

A total of 137 suspected pleural TB were enrolled and categorized, including 103 pleural TB (49 confirmed and 54 probable pleural TB) and 34 non-TBP patients. The sensitivity of Rpfs-TLA for total pleural TB was 43.7% (34.5∼53.3%), higher than that of TLA 29.1% (21.2∼38.5%) and LJ 26.2% (18.7∼35.5%) (p < 0.01), and all specificity was 100% in the diagnosis of pleural TB. Median time to detection of a positive culture was 11.8 days (95% CI 10.4∼13.4) for Rpfs-TLA, 21.0 days (95% CI 19.1∼22.9) for TLA, and 30.5 days (95% CI 28.5∼32.5) for LJ (p < 0.001).

Conclusion

Rpfs-TLA is an accurate, rapid, cheap, and easy culture method, which makes it promising for use in clinical laboratories.
Microglia Polarization From M1 to M2 in Neurodegenerative Diseases
Authors: Guo Shenrui , Wang Hui , Yin Yafu
Published: February 2022

Microglia-mediated neuroinflammation is a common feature of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Microglia can be categorized into two opposite types: classical (M1) or alternative (M2), though there’s a continuum of different intermediate phenotypes between M1 and M2, and microglia can transit from one phenotype to another. M1 microglia release inflammatory mediators and induce inflammation and neurotoxicity, while M2 microglia release anti-inflammatory mediators and induce anti-inflammatory and neuroprotectivity. Microglia-mediated neuroinflammation is considered as a double-edged sword, performing both harmful and helpful effects in neurodegenerative diseases. Previous studies showed that balancing microglia M1/M2 polarization had a promising therapeutic prospect in neurodegenerative diseases. We suggest that shifting microglia from M1 to M2 may be significant and we focus on the modulation of microglia polarization from M1 to M2, especially by important signal pathways, in neurodegenerative diseases.
Brain Neural Activity Patterns in an Animal Model of Antidepressant-Induced Manic Episodes
Authors: Chen Min , Chen Guangdong , Tian Hongjun , Dou Guangqian , Fang Tao , Cai Ziyao , Cheng Langlang , Chen Suling , Chen Ce , Ping Jing , Lin Xiaodong , Chen Chunmian , Zhu Jingjing , Zhao Feifei , Liu Chuanxin , Yue Weihua , Song Xueqin , Zhuo Chuanjun
Published: February 2022

Background: In the treatment of patients with bipolar disorder (BP), antidepressant-induced mania is usually observed. The rate of phase switching (from depressive to manic) in these patients exceeds 22%. The exploration of brain activity patterns during an antidepressant-induced manic phase may aid the development of strategies to reduce the phase-switching rate. The use of a murine model to explore brain activity patterns in depressive and manic phases can help us to understandthe pathological features of BP. The novel object recognition preference ratio is used to assess cognitive ability in such models.

Objective: To investigate brain Ca2+activity and behavioral expression in the depressive and manic phases in the same murine model, to aid understanding of brain activity patterns in phase switching in BP.

Methods:In vivotwo-photon imaging was used to observe brain activity alterations in a murine model in which induce depressive-like and manic-like behaviors were induced sequentially. The immobility time was used to assess depressive-like symptoms and the total distance traveled was used to assess manic-like symptoms.

Results:In vivotwo-photon imaging revealed significantly reduced brain Ca2+activity in temporal cortex pyramidal neurons in the depressive phase in mice exposed to chronic unpredictable mild stress compared with naïve controls. The brain Ca2+activity correlated negatively with the novel object recognition preference ratio within the immobility time. Significantly increased brain Ca2+activity was observed in the ketamine-induced manic phase. However, this activity did not correlate with the total distance traveled. The novel object recognition preference ratio correlated negatively with the total distance traveled in the manic phase.
Case Report: Event-Related Desynchronization Observed During Volitional Swallow by Electroencephalography Recordings in ALS Patients With Dysphagia
Authors: Ogawa Akari , Koganemaru Satoko , Takahashi Toshimitsu , Takemura Yuu , Irisawa Hiroshi , Matsuhashi Masao , Mima Tatsuya , Mizushima Takashi , Kansaku Kenji
Published: February 2022

Dysphagia is a severe disability affecting daily life in patients with amyotrophic lateral sclerosis (ALS). It is caused by degeneration of both the bulbar motor neurons and cortical motoneurons projecting to the oropharyngeal areas. A previous report showed decreased event-related desynchronization (ERD) in the medial sensorimotor areas in ALS dysphagic patients. In the process of degeneration, brain reorganization may also be induced in other areas than the sensorimotor cortices. Furthermore, ALS patients with dysphagia often show a longer duration of swallowing. However, there have been no reports on brain activity in other cortical areas and the time course of brain activity during prolonged swallowing in these patients. In this case report, we investigated the distribution and the time course of ERD and corticomuscular coherence (CMC) in the beta (15–25 Hz) frequency band during volitional swallow using electroencephalography (EEG) in two patients with ALS. Case 1 (a 71-year-old man) was diagnosed 2 years before the evaluation. His first symptom was muscle weakness in the right hand; 5 months later, dysphagia developed and exacerbated. Since his dietary intake decreased, he was given an implantable venous access port. Case 2 (a 64-year-old woman) was diagnosed 1 year before the evaluation. Her first symptom was open-nasal voice and dysarthria; 3 months later, dysphagia developed and exacerbated. She was given a percutaneous endoscopic gastrostomy. EEG recordings were performed during volitional swallowing, and the ERD was calculated. The average swallow durations were 7.6 ± 3.0 s in Case 1 and 8.3 ± 2.9 s in Case 2. The significant ERD was localized in the prefrontal and premotor areas and lasted from a few seconds after the initiation of swallowing to the end in Case 1. The ERD was localized in the lateral sensorimotor areas only at the initiation of swallowing in Case 2. CMC was not observed in either case. These results suggest that compensatory processes for cortical motor outputs might depend on individual patients and that a new therapeutic approach using ERD should be developed according to the individuality of ALS patients with dysphagia.
Optical Sensors and Actuators for Probing Proximity-Dependent Biotinylation in Living Cells
Authors: Chen Rui , Zhang Ningxia , Zhou Yubin , Jing Ji
Published: February 2022

Proximity-dependent biotinylation techniques have been gaining wide applications in the systematic analysis of protein-protein interactions (PPIs) on a proteome-wide scale in living cells. The engineered biotin ligase TurboID is among the most widely adopted given its enhanced biotinylation efficiency, but it faces the background biotinylation complication that might confound proteomic data interpretation. To address this issue, we report herein a set of split TurboID variants that can be reversibly assembled by using light (designated “OptoID”), which enable optogenetic control of biotinylation based proximity labeling in living cells. OptoID could be further coupled with an engineered monomeric streptavidin that permits real-time monitoring of biotinylation with high temporal precision. These optical actuators and sensors will likely find broad applications in precise proximity proteomics and rapid detection of biotinylation in living cells.
Visual Mismatch Negativity: A Mini-Review of Non-pathological Studies With Special Populations and Stimuli
Authors: Czigler István , Kojouharova Petia
Published: February 2022

In this mini-review, we summarized the results of 12 visual mismatch negativity (vMMN) studies that attempted to use this component as a tool for investigating differences between non-clinical samples of participants as well as the possibility of automatic discrimination in the case of specific categories of visual stimuli. These studies investigated the effects of gender, the effects of long-term differences between the groups of participants (fitness, experience in different sports, and Internet addiction), and the effects of short-term states (mental fatigue and hypoxia), as well as the vMMN effect elicited by artworks as a special stimulus category.
Preliminary Evidence That Circadian Alignment Predicts Neural Response to Monetary Reward in Late Adolescent Drinkers
Authors: Hasler Brant P. , Graves Jessica L. , Soehner Adriane M. , Wallace Meredith L. , Clark Duncan B.
Published: February 2022

Background

Robust evidence links sleep and circadian rhythm disturbances to alcohol use and alcohol-related problems, with a growing literature implicating reward-related mechanisms. However, the extant literature has been limited by cross-sectional designs, self-report or behavioral proxies for circadian timing, and samples without substantive alcohol use. Here, we employed objective measures of sleep and circadian rhythms, and an intensive prospective design, to assess whether circadian alignment predicts the neural response to reward in a sample of late adolescents reporting regular alcohol use.

Methods

Participants included 31 late adolescents (18–22 y/o; 19 female participants) reporting weekly alcohol use. Participants completed a 14-day protocol including pre- and post-weekend (Thursday and Sunday) circadian phase assessmentsviathe dim light melatonin onset (DLMO), in counterbalanced order. Sleep-wake timing was assessedviaactigraphy. Circadian alignment was operationalized as the DLMO-midsleep interval; secondary analyses considered social jet lag based on weekday-weekend differences in midsleep or DLMO. Neural response to reward (anticipation and outcome) was assessedviaa monetary reward fMRI task (Friday and Monday scans). Alcohol use was assessed at baseline andviaecological momentary assessment. Mean BOLD signal was extracted from two regions-of-interest (striatum and medial prefrontal cortex, mPFC) for analyses in regression models, accounting for age, sex, racial identity, and scan order.

Results

In primary analyses, shorter DLMO-midsleep intervals (i.e., greater misalignment) on Thursday predicted lower striatal and mPFC responses to anticipated reward, but not reward outcome, on Friday. Lower neural (striatum and mPFC) responses to anticipated reward on Friday correlated with more binge-drinking episodes at baseline, but were not associated with alcohol use in the post-scan weekend. In secondary analyses, greater social jet lag (particularly larger weekend delays in midsleep or DLMO) was associated with lower neural responses to reward anticipation on Monday.

Conclusion

Findings provide preliminary evidence of proximal associations between objectively determined circadian alignment and the neural response to anticipated monetary reward, which is linked in turn to patterns of problematic drinking. Replication in a larger sample and experimental designs will be important next steps to determining the extent to which circadian misalignment influences risk for alcohol involvementviaalterations in reward function.
Microglia and Astrocyte Function and Communication: What Do We Know in Humans?
Authors: Garland Emma F. , Hartnell Iain J. , Boche Delphine
Published: February 2022

Microglia and astrocytes play essential roles in the central nervous system contributing to many functions including homeostasis, immune response, blood–brain barrier maintenance and synaptic support. Evidence has emerged from experimental models of glial communication that microglia and astrocytes influence and coordinate each other and their effects on the brain environment. However, due to the difference in glial cells between humans and rodents, it is essential to confirm the relevance of these findings in human brains. Here, we aim to review the current knowledge on microglia-astrocyte crosstalk in humans, exploring novel methodological techniques used in health and disease conditions. This will include an in-depth look at cell culture and iPSCs, post-mortem studies, imaging and fluid biomarkers, genetics and transcriptomic data. In this review, we will discuss the advantages and limitations of these methods, highlighting the understanding these methods have brought the field on these cells communicative abilities, and the knowledge gaps that remain.
Basolateral Amygdala Mediates Central Mechanosensory Feedback of Musculoskeletal System
Authors: Liu Nian , Li Botai , Zhang Lu , Yang Dazhi , Yang Fan
Published: February 2022

Musculoskeletal diseases, such as osteoporosis and sarcopenia, are tremendous and growing public health concerns. Considering the intimate functional relationship between muscle and bone throughout development, growth, and aging, muscle provides the primary source of skeletal loading through contraction force. However, significant gaps exist in our knowledge regarding the role of muscle in bone homeostasis and little is known regarding the mechanism through which the central nervous system responds and regulates unloading-induced bone loss. Here, we showed that the basolateral amygdala (BLA) and medial part of the central nucleus (CeM) are anatomically connected with the musculoskeletal system. Unloading-induced bone loss is accompanied by a decrease in serum semaphorin 3A (Sema3A) levels as well as sensory denervation. In vivo fiber photometry recordings indicated that the mechanical signal is integrated by the BLA and CeM within 24 h and subsequently regulates bone remodeling. Moreover, chemogenetic activation of BLACaMKII neurons mitigates severe bone loss caused by mechanical unloading via increased serum levels of Sema3A and sensory innervation. These results indicate that the BLA integrates the mechanosensory signals rapidly and mediates the systemic hormonal secretion of Sema3A to maintain bone homeostasis.