bluuebunny/crossref_metadata_2025 huggingface dataset:
Short- and long-term prognosis of glycemic control in COVID-19 patients with type 2 diabetes
Authors: Zhan K , Zhang X , Wang B , Jiang Z , Fang X , Yang S , Jia H , Li L , Cao G , Zhang K , Ma X
Published: January 2022

Background and aim

To systematically evaluate the associations between glycemic control and short- to long-term outcomes in coronavirus disease 2019 (COVID-19) patients with type 2 diabetes (T2D).

Design and methods

A multi-center prospective cohort study including 574 COVID-19 patients with T2D was conducted in Wuhan, China. All patients were followed-up 1 year after hospital discharge using a uniformed questionnaire including self-reported symptoms, and the chronic obstructive pulmonary disease assessment test items.

Results

Of the 574 patients, 443 (77.2%) had well-controlled blood glucose. Glycemic control was significantly associated with decreased risk of death [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.10–0.57], intensive care unit admission (OR 0.22, 95% CI 0.10–0.49), invasive mechanical ventilation (OR 0.25, 95% CI 0.08–0.72), disease progression (OR 0.25, 95% CI 0.11–0.55), and composite outcome (OR 0.26, 95% CI 0.14–0.49). The top five long-term sequelae include fatigue (31.5%), sweating (21.2%), chest tightness (15.1%), anxiety (12.2%), myalgia (10.6%) and short breath (6.4%). Glycemic control was associated with decreased risk of respiratory sequelae (OR 0.42, 95% CI 0.18–0.99; P = 0.048).

Conclusions

Glycemic control was significantly associated with short-term outcomes in COVID-19 patients with T2D and showed a significant association with long-term respiratory sequelae. The management and control of blood glucose has a positive impact on prognosis of COVID-19.
Domains and outcome measures for the assessment of limited cutaneous systemic sclerosis: an international collaborative scoping review
Authors: Lescoat Alain , Sandler Robert D , Zimmermann François , Roofeh David , Hughes Michael , Pauling John D , Murphy Susan L , Chen Yen T , Townsend Whitney  , Buch Maya H , Khanna Dinesh
Published: January 2022

Objectives

The aim of this study was to comprehensively identify instruments within relevant domains employed to assess lcSSc since the endorsement of its consensus definition in 1988. The overall objective is to inform the creation of a Combined Response Index for Scleroderma Trials Assessing lcSSc (CRISTAL).

Methods

MEDLINE and Embase were searched using terms selected to comprehensively retrieve titles and abstracts mentioning both lcSSc and dcSSc, along with those only mentioning lcSSc, SSc sine scleroderma, limited SSc and/or CREST/CRST. Because our initial assessment of the literature revealed that very few studies included only lcSSc subjects, we also assessed literature that included both cutaneous subsets. A total of 3964 titles and abstracts were screened by two reviewers, and 270 articles were selected for data extraction.

Results

We identified 27 domains encompassing 459 instruments. Instruments from ‘Skin involvement’, ‘Pulmonary involvement’ and ‘Health-related quality of life and general functioning’ were the most frequently retrieved. Among the 15 most represented instruments announced as primary end points in efficacy or effectiveness studies, 7 were clinician-reported outcomes (ROs), 7 were patient ROs, and one was a performance outcome (6 min-walk test). The mean proportion of lcSSc patients in studies of lcSSc, including studies that mention both lcSSc and dcSSc, was 56.4%, demonstrating that this subset is underrepresented in the literature, given that the prevalence of lcSSc ranges from 60% to 80% in national registries and international cohorts.

Conclusion

This scoping literature review provides a comprehensive identification of domains and outcomes used to assess lcSSc. Our results also highlight that lcSSc is underrepresented in the literature.
Activity interference in patients with Sjögren’s syndrome: a cross-sectional study of 149 patients in the UK
Authors: Schoon Hannah , Slack Emma , Pearce Mark , Ng Wan-Fai , Hackett Katie L
Published: January 2022

Objectives

To investigate which five activity interference categories out of pain, fatigue, mood, dryness and brain fog/mental fatigue scored highest in patients with primary Sjögren’s syndrome (pSS) and to investigate the association between activity interference and mood and physical functioning in these patients.

Methods

The Comprehensive Pain Evaluation Questionnaire (CPEQ) assessed activity interference (actions performed in daily life that are hindered) in 149 UK pSS patients. This was modified to include four additional symptoms (fatigue, mood, dryness and brainfog/mental fatigue). Functional impairment was measured using the Hospital Anxiety and Depression Scale (HADS) and the Improved Health Assessment Questionnaire (Improved HAQ). Univariable linear regression models were estimated to investigate the association between CPEQ results and the outcome scores obtained from the HADS and Improved HAQ. Multivariable linear regression models were estimated adjusting for patient age and length of disease.

Results

Fatigue had the biggest impact on seven activity domains: physical exercise (mean score of 3.49 out of 5 [s.d. 1.26]), performing household chores (mean 3.14 [s.d. 1.18]), gardening or shopping (mean 3.18 [s.d. 1.20]), socializing with others (mean 2.62 [s.d. 1.24]), recreation/hobbies (mean 2.88 [s.d. 1.20]), sexual relations (mean 3.00 [s.d. 1.52]), and mental efficacy (mean 2.69 [s.d. 1.17]). Regression analysis showed a positive correlation in which every point increase in an activity interference category saw the overall mood and physical functioning scores increase.

Conclusion

Fatigue has the largest impact on pSS patients’ daily activities in this cohort. Length of disease reduced the impact of activity interference on patients’ overall health score.
The prognostic value of sST2 in connective tissue disease patients with pulmonary hypertension
Authors: Ye Huangshu , Wu Qianwen , Zhang Ning , Shi Jing , Zhang Haifeng , Wang Qiang , Zhang Miaojia , Sun Xiaoxuan
Published: January 2022

Objectives

Pulmonary arterial hypertension (PAH) is a severe complication of CTD, being one of the leading causes of mortality for patients with this condition. Soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker associated with adverse clinical outcomes in cardiovascular patients. In this study, we investigated the role of sST2 as a predictor of poor clinical outcome in patients with CTD associated with pulmonary hypertension (CTD-PH).

Methods

This retrospective cohort study enrolled 71 CTD-PH patients diagnosed by echocardiography. Twenty-one CTD patients without PH were selected for a control group. A receiver operating characteristic (ROC) curve assessed the predictive value of sST2 in assessing 3-year clinical worsening. Hazard ratios associated with potential predictors of clinical worsening were estimated using Cox proportional hazard models. The primary end point was clinical worsening.

Results

The level of sST2 was significantly elevated in CTD-PH patients compared with the control group. After a mean follow-up of 25.29 (1.88) months, end point events occurred in 26 patients. sST2 was an independent predictor of clinical worsening and all-cause death in patients with CTD-PH. sST2 ≥ 39.99 ng/ml discriminated 3-year clinical worsening with a sensitivity and specificity of 100% and 84.9%, respectively. The patients with both higher levels of sST2 (≥39.99 ng/ml) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (≥300 ng/l) had the worst prognosis.

Conclusion

sST2 ≥ 39.99 ng/ml predicts higher incidence of clinical worsening events in CTD-PH patients. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP.
COMPARISON OF CBCT AND CT IN TERMS OF DOSE VALUE OF ORGANS AT RISK IN PARANASAL SINUS IMAGING
Authors: Pak Farideh , Hosseini Pooya Seyed Mahdi , Shabani Hamed , Baradaran Samaneh , Salim Sadeq Ula
Published: January 2022

Irradiated dose to the organs at risk surrounding the paranasal sinuses was compared in cone beam computed tomography (CBCT) and multi spiral computed tomography with respect to the organs’ relative positions to the imaging field. A head and neck Alderson-Rando phantom equipped with thermoluminescence dosemeters pellets was irradiated according to three routine CBCT protocols and one protocol in multi spiral computed tomography. Dose value of organs outside the imaging field as well as those measured dose of organs inside the field were assessed. The highest measured doses were obtained from CT scan for most of the organs investigated in this study, whereas the lowest one was associated with the low-resolution mode of CBCT. Also, statistical analysis showed no significant differences between the dose values of out-of-field organs in all CBCT modes, whereas significant differences were observed between the radiation doses of CT and CBCT modes for all organs at risk inside and outside of the imaging field. CBCT is recommended on the basis of having a lower dose; however, the image qualities were the same in the two employed modalities, so the approach of lower dose can be made.
Impact of Substance Use Disorder on Between-Network Brain Connectivity in Early Psychosis
Authors: Chan Shi Yu , Nickerson Lisa D , Pathak Roma , Öngür Dost , Hall Mei-Hua
Published: January 2022

The Triple Network Model of psychopathology identifies the salience network (SN), central executive network (CEN), and default mode network (DMN) as key networks underlying the pathophysiology of psychiatric disorders. In particular, abnormal SN-initiated network switching impacts the engagement and disengagement of the CEN and DMN, and is proposed to lead to the generation of psychosis symptoms. Between-network connectivity has been shown to be abnormal in both substance use disorders (SUD) and psychosis. However, none have studied how SUD affects connectivity between sub-networks of the DMN, SN, and CEN in early stage psychosis (ESP) patients. In this study, we collected data from 113 ESP patients and 50 healthy controls to investigate the effect of SUD on between-network connectivity. In addition, we performed sub-group analysis by exploring whether past SUD vs current SUD co-morbidity, or diagnosis (affective vs non-affective psychosis) had a modulatory effect. Connectivity between four network-pairs, consisting of sub-networks of the SN, CEN, and DMN, was significantly different between ESP patients and controls. Two patterns of connectivity were observed when patients were divided into sub-groups with current vs past SUD. In particular, connectivity between right CEN and the cingulo-opercular salience sub-network (rCEN-CON) showed a gradient effect where the severity of abnormalities increased from no history of SUD to past+ to current+. We also observed diagnosis-specific effects, suggesting non-affective psychosis patients were particularly vulnerable to effects of substance use on rCEN-CON connectivity. Our findings reveal insights into how comorbid SUD affects between-network connectivity and symptom severity in ESP.
Hematopoietic Stem Cell-Independent Differentiation of Mast Cells From Mouse Intraembryonic VE-Cadherin+ Cells
Authors: Tsuruda Mariko , Morino-Koga Saori , Ogawa Minetaro
Published: January 2022

Hematopoietic stem cell (HSC)-independent hematopoiesis from hemogenic endothelial cells (HECs) in the mouse embryo has been recognized as a source of tissue-resident hematopoietic cells in adult mice. Connective tissue mast cells (MCs) have been reported to originate from VE-cadherin (VE-cad)-expressing HECs in the yolk sac and embryo proper (EP) by a VE-cad-Cre-mediated lineage-tracing analysis. However, it remains unclear whether MCs are generated via a conventional HSC-dependent hematopoietic differentiation pathway, or whether through a fast-track pathway bypassing the emergence of HSCs. Here, we investigated whether EP-derived VE-cad+ cells differentiate into MCs independently of HSCs. VE-cad+ cells isolated from the embryonic day (E) 9.5-10.5 EP robustly formed connective tissue-type MCs in a newly established co-culture system using PA6 stromal cells. In contrast, bone marrow (BM) reconstitution assays of cultured cells indicated that E9.5 VE-cad+ cells did not differentiate into transplantable HSCs in this culture condition. Lymphoid-biased HSCs with a limited self-renewal capacity were occasionally detected in some cultures of E10.5 VE-cad+ cells, while MC growth was constantly observed in all cultures examined. HSCs purified from adult BM required a more extended culture period to form MCs in the PA6 co-culture than the embryonic VE-cad+ cells. Furthermore, E9.5-E10.5 VE-cad+ cells contributed to tissue-resident MCs in postnatal mice when transplanted into the peritoneal cavity of newborn mice. These results suggest that EP-derived VE-cad+ cells generate MCs independently of HSC development in vitro and possess the potential of generating connective tissue MCs in vivo, although the exact differentiation program remains unsolved.
On the Need for New Measures of Phylogenomic Support
Authors: Thomson Robert C , Brown Jeremy M
Published: January 2022

The scale of data sets used to infer phylogenies has grown dramatically in the last decades, providing researchers with an enormous amount of information with which to draw inferences about evolutionary history. However, standard approaches to assessing confidence in those inferences (e.g., nonparametric bootstrap proportions [BP] and Bayesian posterior probabilities [PPs]) are still deeply influenced by statistical procedures and frameworks that were developed when information was much more limited. These approaches largely quantify uncertainty caused by limited amounts of data, which is often vanishingly small with modern, genome-scale sequence data sets. As a consequence, today’s phylogenomic studies routinely report near-complete confidence in their inferences, even when different studies reach strongly conflicting conclusions and the sites and loci in a single data set contain much more heterogeneity than our methods assume or can accommodate. Therefore, we argue that BPs and marginal PPs of bipartitions have outlived their utility as the primary means of measuring phylogenetic support for modern phylogenomic data sets with large numbers of sites relative to the number of taxa. Continuing to rely on these measures will hinder progress towards understanding remaining sources of uncertainty in the most challenging portions of the Tree of Life. Instead, we encourage researchers to examine the ideas and methods presented in this special issue of Systematic Biology and to explore the area further in their own work. The papers in this special issue outline strategies for assessing confidence and uncertainty in phylogenomic data sets that move beyond stochastic error due to limited data and offer promise for more productive dialogue about the challenges that we face in reaching our shared goal of understanding the history of life on Earth.[Big data; gene tree variation; genomic era; statistical bias.]
Electro-analytical sensing of anti-hypotensive agents: application to dosage forms and human urine
Authors: Alharthi Sarah , Batakoushy Hany A , Alharthy Saif A , Abd El-Magied Mahmoud O , Salem Waheed M
Published: January 2022

A new and valid method was developed for the quantitative voltammetric analysis of midodrine hydrochloride (MID) in pharmaceutical tablets (Midodrine) and biological samples. The method is based on electro-oxidation of MID supported by both disposable pencil electrode (PE) and glassy carbon electrode (GCE). The analysis was carried out using cyclic voltammetry, differential pulse voltammetry (DPV), and square wave voltammetry (SWV) techniques. The proposed analytical method was validated according to ICH guidelines. MID was successively assayed at concentration ranges of 1.15–6.55 and 0.58–3.05 μg mL−1 at PE. Also, MID was successively assayed at concentration ranges of 1.15–5.28 and 2.86–27.6 μg mL−1 at GCE for DPV and SWV methods, respectively. The proposed method was successfully used for the analysis of MID in its dosage form and human urine with good recoveries of 99.66 ± 0.33, 99.8 ± 0.45 at PE and 99.8 ± 0.25, 98.7 ± 1.27 at GCE for the DPV and SWV methods, respectively. The suggested method could be applied to the studied drug in the quality control lab as well as in its pharmacokinetic studies.
Hepatoprotective effect of diallyl trisulfide against lipopolysaccharide and D-galactosamine induced acute liver failure in mice via suppressing inflammation and apoptosis
Authors: Yu Ziqiang , Ding Yun , Zeng Tao , Zhao Xiulan , Zhang Cuili
Published: January 2022

Acute liver failure (ALF), characterized by the quick occurrence of disorder in liver, is a serious liver injury with extremely high mortality. Therefore, we investigated whether diallyl trisulfide (DATS), a natural product from garlic, protected against ALF in mice and studied underlying mechanisms. In the present study, lipopolysaccharide (LPS) (10 μg·kg−1)/D-galactosamine (D-gal) (500 mg·kg−1) was intraperitoneally injected to ICR mice to induce ALF. The mice were orally administered 20-, 40-, or 80-mg·kg−1 DATS) 1 h before LPS/D-gal exposure. Serum biochemical analyses and pathological study found that DATS pretreatment effectively prevented the ALF in LPS/D-gal-treated mice. Mechanistically, pretreatment of DATS inhibited the increase of the numbers of CD11b+ Kupffer cells and other macrophages in the liver, the release of tumor necrosis factor-α into the blood, and Caspase-1 activation induced by LPS/D-gal treatment in mice. Furthermore, DATS inhibited the activation of Caspase-3, downregulation of Bcl-2/Bax ratio, and increase of TUNEL positive staining. Altogether, our findings suggest that DATS exhibits hepatoprotective effects against ALF elicited by LPS/D-gal challenge, which probably associated with anti-inflammation and anti-apoptosis.
Blood Pressure Variation with Altitudes in Children: A Cross-Sectional Observational Study from Himalayan Hills
Authors: Rajashekar Bhukya , Sarkar Uttam Kumar , Datta Debadyuti , Mondal Tanushree , Sarkar Mihir , Sengupta Tapti , Hazra Avijit , Mondal Rakesh
Published: January 2022

Objectives

We aimed to evaluate blood pressure (BP) in Indian children who had similar demographic characteristics but hailed from different altitudes.

Methods

BP of school going children, aged 5 to 12 years, at five different locations varying in altitude (near sea level: n = 425; 2000 feet: n = 244; 4000 feet: n = 248; 6000 feet: n = 242 and 8000 feet: n = 250) was measured in a mountainous district in Himalaya. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded by aneroid sphygmomanometer in the sitting posture using a calibrated instrument and four trained resident doctors. The average of three readings was taken.

Results

Of the 1229 children whose data were analyzed, 50.4% were boys. SBP showed a progressive rise from 99.5 (4.00) mmHg [mean (standard deviation)] at near sea level to 106.7 (4.17) mmHg at 8000 feet. Similarly, DBP showed a rise from 60.1 (3.67) mmHg to 66.8 (4.58) mmHg over the same altitude range. Analysis of covariance for BP variation with altitude, with age as covariate, indicated a modest but statistically significant rise in both SBP and DBP with altitude. Higher BP values was noted among children residing at higher than at lower altitude (0.8% at sea level to 18.8% at 8000 feet). Correlations between SBP and DBP values and height and weight, though positive and significant at p < 0.01 level, were weak.

Conclusions

These data will help in correct interpretation of BP readings in children residing at high altitude.
Development and Molecular Cytogenetic Characterization of Novel Primary Wheat-Rye 1RS.1BL Translocation Lines from Multiple Rye Sources with Resistance to Stripe Rust
Authors: Ren Tianheng , Jiang Qing , Sun Zixin , Zhao Liqi , Peng Wanhua , Ren Zhenglong , Tan Feiquan , Luo Peigao , Li Zhi
Published: January 2022

Stripe rust (caused by Puccinia striiformis f. sp. tritici) is one of the most severe diseases for wheat production. An important method to improve the stripe rust resistance of wheat is to introduce resistance genes from related species into the wheat genome. The 1RS.1BL wheat–rye translocation from Petkus rye has contributed substantially to wheat resistance breeding worldwide. However, given the breakdown of the stripe rust resistance gene Yr9 in 1RS, its importance for wheat improvement has decreased. In this study, we developed 166 new primary 1RS.1BL translocation lines by crossing rye varieties Weining, Baili, and Aigan with several wheat cultivars. Cytogenetic and molecular analyses indicated that all of these lines contained a pair of intact 1RS.1BL translocation chromosomes. The stripe rust resistance of these translocation lines and their wheat parents was evaluated in southwestern China during the severe stripe rust epidemics in 2015 and 2021. The results showed diverse effects of the 1RS.1BL translocations from different rye cultivars on resistance to stripe rust. The highest genetic diversity was observed in 1RS.1BL translocations derived from diverse rye varieties but in the same wheat background. The development of diverse 1RS.1BL translocation lines offers ample opportunities to introduce new variations into wheat for improving stripe rust resistance. Finally, 71 new translocation lines, including nine developed from the cross of MY11 × Aigan, four from MY11 × Baili, 40 from MY11 × Weining, 14 from A42912 × Baili, and four from A42912 × Weining. These lines showed consistent resistance to stripe rust in fields under frequent changes of the pathogen races and could be useful genetic stocks for breeding wheat cultivars with resistance to stripe rust.
Treating hypertension in Black patients
Authors: Gardner Nathan J.
Published: January 2022

For the first time in its history, the Eighth Joint National Committee (JNC-8) published hypertension guidelines that varied depending on patient race, with different treatment recommendation for Black and non-Black patients. Although initial therapy in non-Black patients is to be carried out with one of four agents—thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs)—the recommendation for Black patients removed ACE inhibitors and ARBs from the algorithm. This article reviews some of the physiologic theories for the difference in recommendations and discusses potential complications with race-based treatment algorithms.
Validation of the Vulvovaginal Symptom Questionnaire in Turkish women with genitourinary syndrome of menopause
Authors: Tekin Arzu Bilge , Yassa Murat , Kalkan Uzeyir , Sargin Mehmet Akif , Keskin Ilkhan , Usta Serhat , Budak Dogus , Buran Ayca Miray , Tug Niyazi
Published: January 2022

Objective:

This study aims to psychometrically validate the Turkish version of the Vulvovaginal Symptom Questionnaire (VSQ).

Methods:

Postmenopausal women with and without genitourinary syndrome of menopause (GSM) were included as the target population and the control group. Psychometric properties were validated both for sexually active (21 items) and passive women (16 items). Several a priori hypotheses were formulated to assess construct validity. Scores of GSM-Assessment Tool, Female Sexual Function Index, Michigan Incontinence Severity Index, Female Genital Self-Image Scale, and Menopause Rating Scale and their correlation with VSQ scores were compared.

Results:

A total of 242 postmenopausal women were included. The VSQ showed good internal consistency with a Cronbach alpha coefficient of 0.822 (0.800-0.821) and 0.873 (0.853-0.870) in sexually active and passive women, respectively. Originally proposed model (4-factor model, n = 162) showed adequate fit in women with active sexuality and the 3-factor model (n = 242) showed moderate fit. The test-retest reliability was good for symptoms, emotions, and life impact subscales (intraclass correlation coefficient [ICC]: 0.846, 0.835, and 0.755, respectively) and moderate for sexual impact subscale (ICC: 0.643). More than 75% of hypotheses were confirmed.

Conclusions:

Our study shows successful cross-cultural adaptation and validation with sufficient psychometric properties for VSQ to be used in Turkish postmenopausal women with GSM.
Association of adiposity evaluated by anthropometric, BIA, and DXA measures with cardiometabolic risk factors in nonobese postmenopausal women: the CoLaus/OsteoLaus cohort
Authors: Stamm Elisabeth , Marques-Vidal Pedro , Rodriguez Elena Gonzalez , Vollenweider Peter , Hans Didier , Lamy Olivier
Published: January 2022

Objective:

After menopause, body composition changes with body fat accumulation, and an increase in cardiometabolic risk factors. Total fat mass, regional fat mass, and visceral adipose tissue (VAT) may be estimated with anthropometric measures, bioelectrical impedance analysis (BIA), and dual-energy X-ray absorptiometry (DXA). The aim of our study was to assess which measurement correlated best with cardiometabolic risk factors in healthy nonobese postmenopausal women.

Methods:

The CoLaus/OsteoLaus cohort included 1,500 postmenopausal women (age range 50-80). We analyzed correlations between: 1) measurements of body composition assessed by anthropometric measures, BIA, and DXA and 2) these measurements and different selected cardiometabolic risk factors, such as blood pressure, lipid markers (cholesterol subtypes and triglycerides), and metabolic markers (glucose, insulin, adiponectin, and leptin). Spearman correlation coefficient, stepwise forward regression, and linear regression analyses were used to determine association between anthropometric measurements and cardiometabolic risk factors.

Results:

In the 803 included participants (mean age 62.0 ± 7.1 y, mean body mass index 25.6 kg/m2 ± 4.4), correlations between total fat mass measured by BIA and total fat mass, android fat, gynoid fat, or VAT measured by DXA are very strong (from r = 0.531, [99% confidence interval (CI), 0.443-0.610] to r = 0.704, [99% CI, 0.640-0.758]). Body mass index and waist circumference have a higher correlation with VAT (r = 0.815, [99% CI, 0.772-0.851] and r = 0.823 [99% CI, 0.782-0.858], respectively) than BIA (r = 0.672 [99% CI, 0.603-0.731]). Among the anthropometric measurement and the measurements derived from DXA and BIA, VAT is the parameter most strongly associated with cardiometabolic risk factors. VAT better explains the variation of most of the cardiometabolic risk factors than age and treatment. For example, nearly 5% of the variability of the diastolic blood pressure (9.9 vs 4.9), nearly 15% of the variability of high-density lipoprotein cholesterol (20.3 vs 3.8) and triglyceride (21.1 vs 6.5), 25.3% of the variability of insulin (33.3 vs 8.1), and 37.5% of the variability of leptin (37.7 vs 1.1) were explained by VAT.

Conclusions:

BIA seems not to be a good tool to assess VAT. At the population level, waist circumference and body mass index seem to be good tools to estimate VAT. VAT measured by DXA is the parameter most correlated with cardiometabolic risk factors and could become a component of the cardiometabolic marker on its own.
A report on pharmacists with the NCMP credential
Authors: Rafie Sally , Sandoval Audra M. , Vernon Veronica P. , Cook Elizabeth A.
Published: January 2022

Objective:

To characterize the demographics and practices of pharmacists with The North American Menopause Society Certified Menopause Practitioner (NCMP) credential.

Methods:

A cross-sectional electronic survey was disseminated to pharmacists with the NCMP credential in June 2018. Twenty-four items were posed to respondents regarding demographics, educational background, and employment, in addition to perspectives regarding the utility of the credential in practice. The questions consisted of multiple choice, as well as open-ended responses.

Results:

Of the 40 pharmacists who were invited to participate, 26 (65%) responded. The majority of respondents were women (84%), practicing for at least 10 years (range 5-47 y), based in Canada (70%), and practicing in the community (43%) or compounding (39%) pharmacies. Most pharmacists reported pursuing the credential for credibility with patients (81%), to increase their knowledge about menopause (77%), and for credibility with other healthcare providers (73%). Almost all (88%) plan to renew their credential. Among these pharmacists, many are presently counseling about treatment options (78%) and educating about selected treatment (78%). Pharmacists are most interested in initiating systemic hormonal therapy (61%) and modifying or continuing systemic hormonal therapy (57%).

Conclusions:

Pharmacists find the NCMP credential to be valuable. Although pharmacists are engaged in counseling and recommendations, they desire prescriptive authority related to menopause care. Future studies should explore the various pharmacist care models and evaluate the impact of pharmacist care on organizational operations and patient outcomes.
Disorder-and cognitive demand-specific neurofunctional alterations during social emotional working memory in generalized anxiety disorder and major depressive disorder
Authors: Xu Xiaolei , Xin Fei , Liu Congcong , Chen Yuanshu , Yao Shuxia , Zhou Xinqi , Zhou Feng , Huang Yulan , Dai Jing , Wang Jinyu , Zou Zhili , Kendrick Keith M , Zhou Bo , Becker Benjamin
Published: January 2022

Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) are both characterized by cognitive and social impairments. Determining disorder-specific neurobiological alterations in GAD and MDD by means of functional magnetic resonance imaging (fMRI) may promote determination of precise diagnostic markers. This study aimed to examine disorder-specific behavioral and neural alterations at the intersection of social and cognitive processing in treatment-naïve first-episode GAD (n=35) and MDD (n=37) patients compared to healthy controls (n=35) by employing a social-emotional n-back fMRI paradigm. No behavioral differences between patients and healthy controls were observed. However, GAD patients exhibited decreased bilateral dorsomedial prefrontal cortex (dmPFC) engagement during the 0-back condition yet increased dmPFC engagement during the 1-back condition compared to MDD and healthy participants. In contrast, MDD patients exhibited increased dmPFC-insula coupling during 0-back, yet decreased coupling during 1-back, compared to GAD and healthy participants. Dimensional symptom-load analysis confirmed that increased dmPFC-insula connectivity during 0-back was positively associated with depressive symptom load. These findings suggest that the dmPFC engaged in integrating of affective and cognitive components and self-other processing exhibits GAD-specific neurofunctional dysregulations whereas functional dmPF communication with insula, a region involved in salience processing, may represent an MDD-specific neurofunctional deficit.
CAR Density Influences Antitumoral Efficacy of BCMA CAR T cells and Correlates with Clinical Outcome
Authors: Rodriguez-Marquez Paula , Calleja-Cervantes Maria E. , Serrano Guillermo , Oliver-Caldes Aina , Palacios-Berraquero Maria L. , Martin-Mallo Angel , Calviño Cristina , Español-Rego Marta , Ceballos Candela , Lozano Teresa , Martin-Uriz Patxi San , Vilas-Zornoza Amaia , Rodriguez-Diaz Saray , Martinez-Turrillas Rebeca , Jauregui Patricia , Alignani Diego , Viguria Maria C. , Redondo Margarita , Pascal Mariona , Juan Manel , Urbano-Ispizua Alvaro , Rodriguez-Otero Paula , Alfonso-Pierola Ana , Paiva Bruno , Lasarte Juan Jose , Inoges Susana , de Cerio Ascension Lopez-Diaz , San-Miguel Jesus , de Larrea Carlos Fernandez , Hernaez Mikel , Rodriguez-Madoz Juan R. , Prosper Felipe
Published: January 2022

Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study we address the impact of CAR density on the functionality of BCMA-CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with upregulation of exhaustion markers, increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of Gene Regulatory Networks using scRNA-seq identified regulons associated to activation and exhaustion upregulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Finally, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with significant impact on clinical response.

Teaser

High CAR molecule density affects CAR T cell activity and associates with impaired clinical response.
Gaseous micro-embolism (GME) is associated with systemic inflammatory response syndrome (SIRS) after open heart surgery. A missing piece of a complex puzzle?
Authors: Demertzis Stefanos , Puthettu Mira , Nafi Matteo , Bagnato Pietro , Cassina Tiziano , Vandenberghe Stijn
Published: January 2022

Background

Gaseous micro-embolism (GME) occurring during contemporary open heart surgery is poorly studied. Current understanding of the biological impact of cardiac surgery focuses on the surgical aggression itself together with contact activation of inflammatory cascades by the extracorporeal circulation (ECC), both promoting various degrees of a systemic inflammatory response syndrome (SIRS).

Methods and Findings

We prospectively collected data on GME in the ECC circuit according to a quality control protocol during a 12-month period at our institution. Bubbles were measured means of a last generation multi-channel ultrasound measuring unit (BCC300, Gampt GmbH, Meerseburg, Germany) upstream of the arterial line filter. For analysis, bubbles were separated in three size categories: small (S) (10-40 µm), medium (M) (41-200 µm) and large (L) (201-2000 µm). Small bubbles were considered as noise and excluded. A total of 58 out of 70 open heart procedures were included in the final evaluation performed on 58 patients (45 males, 13 females, mean age 66 ± 9 years). Patient baseline data, type of procedure and perfusion data were retrieved. Preoperative treatment with beta-blockers, ACE-inhibitors, calcium-antagonists and statins was considered. Postoperative SIRS was identified according to modified SIRS and qSOFA criteria.

A variably high amount of GME was detected (mean count 847 ± 2560), we focused on M-sized GME (mean count 820 ± 2546, mean volume 233 ± 730 nL). A total of 22 patients (38%) developed SIRS. To account for differences between patient groups (SIRS-/ SIRS+) propensity score (PS) matching was performed on the presence of M-bubbles at or above the 75thpercentile (count and volume). The impact of such GME on the development of SIRS was statistically highly significant, as shown by the corresponding average treatment effects (ATE).

Conclusions

Significant GME was associated with postoperative SIRS after cardiac surgery in our setting. This novel finding warrants further confirmation.
Comparison between mid-nasal swabs and buccal swabs for SARS-CoV-2 detection in mild COVID-19 patients
Authors: Blanco Ignacio , Violán Concepción , Suñer Clara , Garcia-Prieto Julio , Argerich Maria José , Rodriguez-Illana Meritxell , Moreno Nemesio , Cardona Pere-Joan , Blanco Anna , Torán-Monserrat Pere , Clotet Bonaventura , Bonet Josep Ma , Prat Nuria
Published: January 2022

Background

The use of rapid antigen diagnostics tests (Ag-RDT) has gained widespread acceptance as an alternative method for diagnosis of COVID-19 outside of health care settings. Various authors have reported that saliva is a reliable specimen, alternative to nasopharyngeal and mid-nasal swabs, to detect SARS-CoV-2 infections by RT-PCR. We assessed the performance of buccal swabs containing saliva for SARS-CoV-2 detection by Ag-RDT, using mid-nasal specimens as a reference in the northern area of Barcelona (Catalonia, Spain)

Methods

In the context of routine clinical diagnosis of mild COVID-19 patients, we enrolled 300 adults in a study to directly compare mid-nasal swabs and saliva specimens for SARS-CoV-2 detection by Ag-RDT.. When mid-nasal and buccal Ag-RDTs showed discordant results, a third mid-nasal swab was collected and analysed by RT-PCR.

Results

Paired samples were successfully obtained in 300 suspected cases of SARS-CoV-2 infection. Of the 300 paired samples, Ag-RDT with the mid-nasal swab detected 139 (46.3%) positive COVID-19 cases. In comparison, buccal swabs showed a sensitivity and specificity of 31.7% (44/139) and 98.8% (159/161), respectively. 65 discordant results with positive mid-nasal swabs and negative buccal swabs were tested by RT-qPCR. All samples tested by Rt-PCR resulted positive, with a mean cycle threshold (Ct) of 28.3 (SD 7.3).

Conclusion

Our findings show that mid-nasal swabs have better performance than buccal swabs for detecting SARS-CoV-2 with Ag-RDT tests. Of note, the sensitivity of buccal samples was affected in samples with high viral loads (Ct<33), suggesting that buccal swabs might not be sensitive enough to detect individuals at risk of transmission. Taken together, the existing literature and the results provided in our analysis we advise against the use of buccal specimens for SARS-CoV-2 diagnostics with Ag-RDT.
Broad Spectrum Antimicrobial Potential of Crassula ovata
Authors: Puga Troy , Schafer Josh , Buffalo Alexander , Agbedanu Prince N.
Published: January 2022

This study investigates the antimicrobial properties of Crassula ovata (C. ovata) against both gram-positive and gram-negative bacteria. About 1-3g samples of C. Ovata leaf samples were extracted with 95 % ethanol and the extract infused into paper discs by soaking and drying. The dried discs were screened against various strains of bacteria and the antimicrobial effects of the infused agents determined by measuring zones of inhibition due to the agents infused into the discs. By the zones of inhibition, C. ovata showed antimicrobial activity against the following gram-negative bacteria: E. coli (14 mm mean zone of clearing), P. vulgaris (13 mm mean zone of clearing), E. cloacae (16 mm mean zone of clearing), and K. pneumoniae (13 mm mean zone of clearing). C. ovata showed antimicrobial activity against the following gram-positive bacteria: S. aureus (22 mm mean zone of clearing) and S. agalactiae (8 mm mean zone of clearing). C. ovata did not show antimicrobial activity against S. pyogenes. By its antimicrobial activity against gram-positive and gram-negative bacteria, C. ovata displayed broad spectrum antimicrobial activity against E. coli, S. aureus, S. agalactiae, P. vulgaris, E. cloacae, and K. pneumoniae. C. ovata may have the potential to serve as a broad-spectrum antimicrobial in the future. Further testing should be done to investigate the toxicities and side effects of C. ovata. Further testing must also be done with C. ovata against drug-resistant strains of bacteria.
Assessing responsiveness to direct verbal suggestions in depersonalization-derealization disorder
Authors: Millman L. S. Merritt , Hunter Elaine C. M. , David Anthony S. , Orgs Guido , Terhune Devin B.
Published: January 2022

The dissociative disorders and germane conditions are reliably characterized by elevated responsiveness to direct verbal suggestions. However, it remains unclear whether atypical responsiveness to suggestion is similarly present in depersonalization-derealization disorder (DDD). 55 DDD patients and 36 healthy controls completed a standardised behavioural measure of direct verbal suggestibility that includes a correction for compliant responding (BSS-C), and psychometric measures of depersonalization-derealization (CDS), mindfulness (FFMQ), imagery vividness (VVIQ), and anxiety (GAD-7). Patients displayed nonsignificantly lower suggestibility than controls, (g= 0.26) but significantly lower mindfulness (g= 1.38), and imagery vividness (g= 0.63), and significantly greater anxiety (g= 1.39). Although suggestibility did not correlate with severity of depersonalization-derealization symptoms in controls,r=-.03 [95% CI: -.36, .30], there was a weak tendency for a positive association in patients,r=.25, [95% CI: -.03, .48]. Exploratory analyses revealed that patients with more severe anomalous bodily experiences were also more responsive to suggestion, an effect not seen in controls. This study demonstrates that DDD is not characterized by elevated responsiveness to direct verbal suggestions. These results have implications for the aetiology and treatment of this condition, as well as its classification as a dissociative disorder in psychiatric nosology.
Genetic control of neuronal activity enhances axonal growth only on permissive substrates
Authors: Mesquida-Veny Francina , Martinez-Torres Sara , Del Río José Antonio , Hervera Arnau
Published: January 2022

Neural tissue has limited regenerative ability, to cope with that, in the recent years a diverse set of novel tools have been used to tailor neurostimulation therapies and promote functional regeneration after axonal injuries. In this report, we explore cell-specific methods to modulate neuronal activity, including opto- and chemogenetics to assess the effect of specific neuronal stimulation in the promotion of axonal regeneration after injury. We found that opto- or chemogenetic modulations of neuronal activity on both dorsal root ganglia and corticospinal motor neurons increase their axonal growth capacity only on permissive substrates.
Multivalent binding proteins can drive collapse and reswelling of chromatin in confinement
Authors: Guha Sougata , Mitra Mithun K.
Published: January 2022

Collapsed conformations of chromatin have been long suspected of being mediated by interactions with multivalent binding proteins, such as CTCF, which can bring together distant sections of the chromatin fiber. In this study, we use Langevin dynamics simulation of coarse grained chromatin polymer to show that the role of binding proteins can be more nuanced than previously suspected. In particular, for chromatin polymer in confinement, entropic forces can drive reswelling of collapsed chromatin with increasing binder concentrations. The reswelling transition happens at physiologically relevant binder concentrations and the extent of reswelling is mediated both by the concentration of binding proteins as well as the strength of confinement. We also study the kinetics of collapse and reswelling and show that both processes occur in similar timescales. We characterise this reswelling of chromatin in biologically relevant regimes and discuss implications for the spatial organisation of the genome.
Trichomes on female reproductive tract: rapid diversification and underlying gene regulatory network in Drosophila suzukii and its related species
Authors: Tanaka Kentaro M. , Takahashi Kanoko , Rice Gavin , Rebeiz Mark , Kamimura Yoshitaka , Takahashi Aya
Published: January 2022

Background

The ovipositors of some insects are external female genitalia, which have their primary function to deliver eggs. Drosophila suzukii and its sibling species D. subpulchrella are known to have acquired highly sclerotized and enlarged ovipositors upon their shifts in oviposition sites from rotting to ripening fruits. Inside the ovipositor plates, there are scale-like polarized protrusions termed “oviprovector scales” that are likely to aid the mechanical movement of the eggs. The size and spatial distribution of the scales need to be rearranged following the divergence of the ovipositors. In this study, we examined the features of the oviprovector scales in D. suzukii and its closely related species. We also investigated whether the scales are single-cell protrusions comprised of F-actin under the same conserved gene regulatory network as the well-characterized trichomes on the larval cuticular surface.

Results

The oviprovector scales of D. suzukii and D. subpulchrella were distinct in size and spatial arrangement compared to those of a closely related species D. biarmipes and D. melanogaster. The comparisons of the size of the scales suggested that the apical cell area of the oviprovector has expanded upon the elongation of the ovipositor plates in these species. Our transcriptome analysis revealed that 43 out of the 46 genes known to be involved in the trichome gene regulatory network are expressed in the developing female genitalia of D. suzukii and D. subpulchrella. An antibody staining depicted the presence of Shavenbaby (Svb) in the inner cavity of the developing ovipositors of D. melanogaster at 44–48 h after puparium formation (APF). Also, shavenoid (sha) was expressed in the corresponding patterns in the developing ovipositors and showed differential expression levels between D. suzukii and D. subpulchrella at 48 h APF.

Conclusions

The oviprovector scales have divergent size and spatial arrangements among species. Therefore, these scales may represent a rapidly diversifying morphological trait of the female reproductive tract reflecting ecological contexts. Furthermore, our results showed that the gene regulatory network underlying trichome formation is adopted to develop the rapidly evolving trichomes on the oviprovectors of these flies.
Neuro-toxicogenomic mapping of TMT induced neurotoxicity using human minibrain reveals associated adverse outcome events
Authors: Subashika Govindan , Daniel Alpern , Stoppini Luc , Deplancke Bart , Adrien Roux
Published: January 2022

Genome-wide transcriptomic interrogation of organoids and 3D tissue models are increasingly used for characterizing drug, toxicity responses and neurodevelopmental disorders. We established here a neuro-toxicogenomic assay by utilizing “minibrain”, a humanin vitro3D brain model system and a low-cost, highly multiplexable RNA-seq methodology (BRB-seq) for screening the effect of trimethyltin chloride (TMT) induced neurotoxicity. We demonstrate that transcriptomic profiling is insightful to the cellular composition and regional identity of the minibrain. Further, we characterize the transcriptomic changes associated with the dose-time neurotoxic response of minibrain upon exposure to TMT. The distinct gene expression changes and molecular candidates identified with our pipeline provides insight to map the key events involved in the adverse outcome pathway of TMT associated neurotoxicity. We identify processes such as endoplasmic reticulum stress, dysregulation of synaptic genes and downregulation of neuron-morphology associated genes upon exposure to TMT. In response to TMT, we identify activation of an early response homeostatic mechanism in minibrain and an interplay of STAT pathways correlating with the dose severity. In this study, we present a neuro-toxicogenomic assay that demonstrates the power of a low-cost transcriptomic screening to study chemical induced neurotoxicity.