bluuebunny/crossref_metadata_2025 huggingface dataset:
First-trimester exposure to benzodiazepines and risk of congenital malformations in offspring: A population-based cohort study in South Korea
Authors: Noh Yunha , Lee Hyesung , Choi Ahhyung , Kwon Jun Soo , Choe Seung-Ah , Chae Jungmi , Kim Dong-Sook , Shin Ju-Young
Published: March 2022

Background

Benzodiazepines are frequently prescribed during pregnancy; however, evidence about possible teratogenicity is equivocal. We aimed to evaluate the association between first-trimester benzodiazepine use and the risk of major congenital malformations.

Methods and findings

Using Korea’s nationwide healthcare database, we conducted a population-based cohort study of women who gave birth during 2011 to 2018 and their live-born infants. The exposure was defined as one or more benzodiazepine prescriptions during the first trimester. We determined the relative risks (RRs) and confidence intervals (CIs) of overall congenital malformations and 12 types of organ-specific malformations. Infants were followed from birth to death or 31 December 2019, whichever came first (up to 8 years of age). Propensity score fine stratification was employed to control for 45 potential confounders. Among a total of 3,094,227 pregnancies, 40,846 (1.3%) were exposed to benzodiazepines during the first trimester (mean [SD] age, 32.4 [4.1] years). The absolute risk of overall malformations was 65.3 per 1,000 pregnancies exposed to benzodiazepines versus 51.4 per 1,000 unexposed pregnancies. The adjusted RR was 1.09 (95% CI 1.05 to 1.13,p< 0.001) for overall malformations and 1.15 (1.10 to 1.21,p< 0.001) for heart defects. Based on mean daily lorazepam-equivalent doses, the adjusted RRs for overall malformations and heart defects were 1.05 (0.99 to 1.12,p= 0.077) and 1.12 (1.04 to 1.21,p= 0.004) for <1 mg/day and 1.26 (1.17 to 1.36,p< 0.001) and 1.31 (1.19 to 1.45,p< 0.001) for >2.5 mg/day doses, respectively, suggesting a dose–response relationship. A small but significant increase in risk for overall and heart defects was detected with several specific agents (range of adjusted RRs: 1.08 to 2.43). The findings were robust across all sensitivity analyses, and negative control analyses revealed a null association. Study limitations include possible exposure misclassification, residual confounding, and restriction to live births.

Conclusions

In this large nationwide cohort study, we found that first-trimester benzodiazepine exposure was associated with a small increased risk of overall malformations and heart defects, particularly at the higher daily dose. The absolute risks and population attributable fractions were modest. The benefits of benzodiazepines for their major indications must be considered despite the potential risks; if their use is necessary, the lowest effective dosage should be prescribed to minimize the risk.

Trial registration

ClinicalTrials.govNCT04856436.
Efficacy and community-effectiveness of insecticide treated nets for the control of visceral leishmaniasis: A systematic review
Authors: Montenegro-Quiñonez Carlos Alberto , Buhler Claudia , Horstick Olaf , Runge-Ranzinger Silvia , Rahman Kazi Mizanur
Published: March 2022

Visceral leishmaniasis (VL) has been targeted for elimination from Southeast Asia (SEA). The disease has been endemic in SEA, and in other parts of the world involving both humans and animals. One of the key strategies for combating VL is controlling for the vector sandfly. There are a few vector control strategies that are currently in practice. We sought to assess the efficacy and community effectiveness of insecticide treated nets (ITNs) in controlling the burden of sandfly and the occurrence of VL among humans. We conducted a systematic review following a study protocol and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. 6331 initial hits were retrieved from Google Scholar, Lilacs, PubMed, Science Direct, WHOlis, WHOiris and PAHOiris. 25 met the full inclusion criteria. Findings show that the insecticide impregnated bednets and the commercially treated long lasting insecticidal nets (LLINs) are effective in controlling sandflies, with mortalities as high as 75% lasting over a year; although their role in controlling VL in the community was not extensively studied, since effectiveness was usually measured with sandflies densities. Findings also show that insecticide impregnated bednets are low cost and well accepted in the community, however, early erosion of insecticides from nets could occur. Some studies also showed that killing of sandflies may not translate into reduction of VL, therefore sandfly knock down and killing data needs to be interpreted with caution. Conclusions of this review are (1) combining insecticide impregnated bednets, as targeted interventions, with another vector control measure, particularly indoor residual spraying, and in conjunction with case detection, could be the way forward to controlling VL in resource limited settings. (2) Given the current low incidence of VL in SEA, it can be difficult to further research the community effectiveness of those control measures in reducing VL.
Public opinion concerning governments’ response to the COVID-19 pandemic
Authors: Chen Cathy W. S. , Fan Tsai-Hung
Published: March 2022

Objectives

Governments around the world have implemented numerous policies in response to the COVID-19 pandemic. This research examines the political issues resulting in public opinion concerning their responses to the pandemic via an international perspective. The objectives of this study are to: (1) measure the association and determine whether differences in political support can be attributed to the presence of approval ratings during the pandemic, and to (2) identify exceptional cases based on statistical predictions.

Methods

We collect information from several open-sourced surveys conducted between June and September 2020 of public sentiment concerning governments’ response toward COVID-19. The 11 countries in our sample account for over 50% of the world’s Gross Domestic Product (GDP). The study includes country-specific random effects to take into account the data’s clustered structure. We consider “political partisanship” and “pre-pandemic approval ratings in 2019” as two potential explanatory variables and employ a mix-effect regression for bounded responses via variable transformation and the wild bootstrap resampling method.

Results

According to the wild bootstrap method, the mixed-effect regression explains 98% of the variation in approval ratings during the pandemic in September 2020. The findings reveal partisan polarization on COVID-19 policies in the U.S., with opposing supporters most likely to express negative sentiments toward the governing party.

Conclusions

The evidence suggests that approval ratings during the pandemic correlate to differences in political support and pre-pandemic approval ratings, as measured by approval ratings from the views between governing coalition supporters and opponents.
Differences in the spatial landscape of urban mobility: Gender and socioeconomic perspectives
Authors: Macedo Mariana , Lotero Laura , Cardillo Alessio , Menezes Ronaldo , Barbosa Hugo
Published: March 2022

Many of our routines and activities are linked to our ability to move; be it commuting to work, shopping for groceries, or meeting friends. Yet, factors that limit the individuals’ ability to fully realise their mobility needs will ultimately affect the opportunities they can have access to (e.g. cultural activities, professional interactions). One important aspect frequently overlooked in human mobility studies is how gender-centred issues can amplify other sources of mobility disadvantages (e.g. socioeconomic inequalities), unevenly affecting the pool of opportunities men and women have access to. In this work, we leverage on a combination of computational, statistical, and information-theoretical approaches to investigate the existence of systematic discrepancies in the mobility diversity (i.e. the diversity of travel destinations) of (1) men and women from different socioeconomic backgrounds, and (2) work and non-work travels. Our analysis is based on datasets containing multiple instances of large-scale, official, travel surveys carried out in three major metropolitan areas in South America: Medellín and Bogotá in Colombia, and São Paulo in Brazil. Our results indicate the presence of general discrepancies in the urban mobility diversities related to the gender and socioeconomic characteristics of the individuals. Lastly, this paper sheds new light on the possible origins of gender-level human mobility inequalities, contributing to the general understanding of disaggregated patterns in human mobility.
Functional products fortified with probiotic LAB isolated from Egyptian dairy sources showed hypolipidemic effects in Albino rats
Authors: Darwish Amira M. G. , Allam Marwa G. , Shokery Enaam S. , Ayad Eman H. E.
Published: March 2022

Biological food industry has increased economic importance of new Lactic Acid Bacteria (LAB) with functional aspects such as health promoting and enhanced sensorial traits. The objectives of the present study were the isolation and genotypic characterization (16S rRNA) of new LAB isolates from Egyptian Laban Rayeb, Zabady and mothers’ breast milk as potential probiotics. Strains were in vitro and in vivo evaluated for their safety and probiotic health promoting traits in Albino rats then applied into two types of functional dairy products. Three strains Streptococcus thermophilus MH422542, Enterococcus faecium MH422543 and Lactococcus lactis subsp lactis MH422545, were selected from a pool of 82 strains. St. thermophilus showed proteolytic activity and production of Exopolysaccharides (EPS). When evaluated in animal models; the strains showed hypolipidemic effects especially E. faecium that reduced atherogenic indices up to 88%. The strains modulated the gut microbiota by reducing Staphylococcus sp. and coliforms with no adverse effects either on blood parameters, antioxidant enzymes, cancer markers or hepatocytes histological examination. Only E. faecium MH422543 showed an immune response by increased white blood cells (WBC) while lymph and platelets values were not affected. The probiotic strains approved their convenience as starter/ adjunct cultures and enhanced organoleptic properties of the fermented dairy products.
Compositional stability of peat in ecosystem-scale warming mesocosms
Authors: Baysinger Mackenzie R. , Wilson Rachel M. , Hanson Paul J. , Kostka Joel E. , Chanton Jeffrey P.
Published: March 2022

Peatlands historically have acted as a C sink because C-fixation rates exceeded the rate of heterotrophic decomposition. Under future warmer conditions predicted for higher latitudes, however, that balance may shift towards higher rates of heterotrophic respiration leading to the release of previously stored C as CO2 and CH4. The Spruce and Peatlands Response Under Changing Environments (SPRUCE) experiment is designed to test the response of peatlands to climate forcing using a series of warmed enclosures in combination with peat below-ground heating from 0 to +9°C above ambient conditions. This experimental design allowed a test of chemical changes occurring within peatland soils following five years of warming. We analyzed samples in the uppermost 2m of peat using Fourier Transform Infrared Spectroscopy (FT-IR) to quantify the relative abundance of carbohydrate and aromatic compounds in the peat. The peat soils were subjected to deep peat heating (DPH) beginning in June of 2014 followed by whole ecosystem warming (WEW) in August of 2015. We found that the relative amounts of labile and recalcitrant chemical compound groups across the full peat depth interval did not significantly change after five years of exposure to warming. This appears the case even though previous studies have shown that net C losses and loss of bulk peat mass to be instability over that time period. Results suggest that the current store of carbon in peatlands are largely compositionally stable leading to no changes the in the ratio of chemical moieties on the initial four-year timescale of this experiment.
On an optimal testing strategy for workplace settings operating during the COVID-19 pandemic
Authors: Hernandez X. , Valentinotti S.
Published: March 2022

High quality daily testing for the presence of the SARS-CoV-2 in workplace settings has become part of the standard and mandatory protection measures implemented widely in response to the current pandemic. Such tests are often limited to a small fraction of the attending personnel due to cost considerations, limited availability and processing capabilities and the often cumbersome requirements of the test itself. A maximally efficient use of such an important and frequently scarce resource is clearly required. We here present an optimal testing strategy which minimises the presence of pre-symptomatic and asymptomatic infected members of the population in a workplace setting, derived under a series of simplifying statistical assumptions. These assumptions however, retain many of the generalities of the problem and yield robust results, as verified through a number of numerical simulations. We show that reduction in overall infected-person-days, IPD, by significant percentages can be achieved, for fixed numbers of tests per day of 5% and 10% of the population, of 30% and 50% in the IPD numbers, respectively.
Effect of statins on risk and mortality of urologic malignancies: Protocol of an umbrella review
Authors: Zhai Xinyu , Yi Pengsheng , Wang Xitao , Wang Haifeng , Yang Xuejun , Mei Zubing , Ge Minyao
Published: March 2022

Introduction

Urologic malignancies are the major causes of morbidity and mortality in men over 40 years old, accounting for more than 20% of all malignant tumors. Several meta-analyses are shown that statin exposure can reduce the morbidity and mortality of various urologic cancers. The adjuvant roles of statin in tumor prevention and anti-tumor activity are now being gradually recognized and have gained attention. Nevertheless, to date, multiple clinical studies and meta-analyses found inconsistent results of their anti-cancer effects. This study aims to evaluate the credibility of the published systematic reviews and meta-analyses that assessed the effects of statin exposure for the incidence and mortality of urologic cancers through an umbrella review.

Methods and analysis

The guidance of overviews of systematic reviews reported in the Cochrane Handbook for Systematic Reviews of interventions will be followed while performing and reporting this umbrella review. This project was registered in PROSPERO with the registration number of CRD42020208854. PubMed, Embase and Cochrane Library will be searched for systematic reviews to identify and appraise systematic reviews or meta-analyses of interventional and observational studies examining statin use and the risks of urologic cancer incidence and mortality without language restriction. The search will be carried out on 10 February 2022. Systematic reviews based on qualitative, quantitative or mixed-methods studies will be involved and critically evaluated by two authors using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2, an updated version of AMSTAR) tool. We will determine the level of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) tool. The summary effect estimates will be calculated using random-effects models. Between- study heterogeneity will be assessed using the I2 statistic. Furthermore, we will also assess the evidence of excess significance bias and evidence of small study effects.

Ethics and dissemination

Ethics approval is not required as we will search and gather data based on the published systematic reviews and meta-analyses. We plan to publish the results of this umbrella review in a peer-reviewed journal and will be presented at a urological disease conference. All the relevant additional data will also be uploaded to the online open access databases.

PROSPERO registration number

CRD42020208854.
Revision of Meiodorvillea Jumars, 1974 (Annelida: Dorvilleidae) including descriptions of three new species from the Southwestern Atlantic Ocean
Authors: de Oliveira Bonaldo Rafael , Menchini Steiner Tatiana , Zacagnini Amaral Antônia Cecília
Published: March 2022

Meiodorvillea Jumars, 1974 is a little-known genus of Dorvilleidae Chamberlin, 1919, characterized by its small size and reduced appendages and jaw apparatus. A revision of the genus is presented, including analysis of the type material of M. minuta (Hartman, 1965) and M. apalpata Jumars, 1974, as well as specimens collected from shelf and slope continental areas in Brazil. A neotype was designated for M. minuta and its distribution was extended to Brazil. The identity of M. chilensis (Hartmann-Schröder, 1965) is questioned and three new species from 21 to 1,300.7 meters depth are also described. Meiodorvillea penhae sp. nov. has furcate chaeta only in the first anterior chaetigers. In contrast, Meiodorvillea hartmanae sp. nov. has very small palps and asymmetrical thin furcate chaeta and Meiodorvillea jumarsi sp. nov. has dorsal cirri and geniculate chaeta only in the first anterior chaetigers.
Symptom clusters in chronic kidney disease and their association with people’s ability to perform usual activities
Authors: Moore Currie , Santhakumaran Shalini , Martin Glen P. , Wilkinson Thomas J. , Caskey Fergus J. , Magadi Winnie , Gair Rachel , Smith Alice C. , Wellsted David , van der Veer Sabine N.
Published: March 2022

Background

People living with a long-term condition, such as chronic kidney disease (CKD), often suffer from multiple symptoms simultaneously, making symptom management challenging. This study aimed to identify symptom clusters in adults with CKD across treatment groups and investigate their association with people’s ability to perform their usual activities.

Methods

We conducted a secondary analysis of both cross-sectional and longitudinal data collected as part of a national service improvement programme in 14 kidney centres in England, UK. This data included symptom severity (17 items, POS-S Renal) and the extent to which people had problems performing their usual activities (single item, EQ-5D-5L). We categorised data by treatment group: haemodialysis (n = 1,462), transplantation (n = 866), peritoneal dialysis (n = 127), or CKD without kidney replacement therapy (CKD non-KRT; n = 684). We used principal component analysis to identify symptom clusters per treatment group, and proportional odds models to assess the association between clusters and usual activities.

Results

Overall, clusters related to: lack of energy and mobility; gastrointestinal; skin; and mental health. Across groups, the ‘lack of energy and mobility’ clusters were associated with having problems with usual activities, with odds ratios (OR) ranging between 1.24 (95% confidence interval [CI], 1.21–1.57) for haemodialysis and 1.56 for peritoneal dialysis (95% CI, 1.28–1.90). This association was confirmed longitudinally in haemodialysis (n = 399) and transplant (n = 249) subgroups.

Implications

Our findings suggest that healthcare professionals should consider routinely assessing symptoms in the ‘lack of energy & mobility’ cluster in all people with CKD, regardless of whether they volunteer this information; not addressing these symptoms is likely to be related to them having problems with performing usual activities. Future studies should explore why symptoms within clusters commonly co-occur and how they interrelate. This will inform the development of cluster-level symptom management interventions with enhanced potential to improve outcomes for people with CKD.
Identification and functional characterization of multiple inositol polyphosphate phosphatase1 (Minpp1) isoform-2 in exosomes with potential to modulate tumor microenvironment
Authors: Zubair Mohd , Hamzah Rabab , Griffin Robert , Ali Nawab
Published: March 2022

Inositol polyphosphates (InsPs) play key signaling roles in diverse cellular functions, including calcium homeostasis, cell survival and death. Multiple inositol polyphosphate phosphatase 1 (Minpp1) affects the cellular levels of InsPs and cell functions. The Minpp1 is an endoplasmic reticulum (ER) resident but localizes away from its cytosolic InsPs substrates. The current study examines the heterogeneity of Minpp1 and the potential physiologic impact of Minpp1 isoforms, distinct motifs, subcellular distribution, and enzymatic potential. The NCBI database was used to analyze the proteome diversity of Minpp1 using bioinformatics tools. The analysis revealed that translation of three different Minpp1 variants resulted in three isoforms of Minpp1 of varying molecular weights. A link between the minpp1 variant-2 gene and ER-stress, using real-time PCR, suggests a functional similarity between minpp1 variant-1 and variant-2. A detailed study on motifs revealed Minpp1 isoform-2 is the only other isoform, besides isoform-1, that carries a phosphatase motif for InsPs hydrolysis but no ER-retention signal. The confocal microscopy revealed that the Minpp1 isoform-1 predominantly localized near the nucleus with a GRP-78 ER marker, while Minpp1 isoform-2 was scattered more towards the cell periphery where it co-localizes with the plasma membrane-destined multivesicular bodies biomarker CD63. MCF-7 cells were used to establish that Minpp1 isoform-2 is secreted into exosomes. Brefeldin A treatment resulted in overexpression of the exosome-associated Minpp1 isoform-2, suggesting its secretion via an unconventional route involving endocytic-generated vesicles and a link to ER stress. Results further demonstrated that the exosome-associated Minpp1 isoform-2 was enzymatically active. Overall, the data support the possibility that an extracellular form of enzymatically active Minpp1 isoform-2 mitigates any anti-proliferative actions of extracellular InsPs, thereby also impacting the makeup of the tumor microenvironment.
The impact of unemployment benefits on birth outcomes: Quasi-experimental evidence from European linked register data
Authors: Kessler Dorian , Hevenstone Debra
Published: March 2022

Cash transfers have been shown to improve birth outcomes by improving maternal nutrition, increasing healthcare use, and reducing stress. Most of the evidence focuses on programs targeting the poorest in the US—a context with non-universal access to healthcare and strong health inequalities. It is thus unclear whether these results would apply to cash transfers targeting a less disadvantaged population and whether they apply to other contexts. We provide evidence on the impact of unemployment benefits on birth outcomes in Switzerland, where access to healthcare is near-universal and social assistance is relatively generous. Our study taps into a policy reform that reduced unemployment benefits by 56%. We use linked parent-child register data and difference-in-differences estimates as well as within sibling comparisons. We find that the reform did not impact birth outcomes when fathers were unemployed but reduced the birthweight of children when mothers were unemployed by 80g and body length by 6mm. There are stronger effects for children whose mothers were the primary earner before job loss, but effects do not differ systematically by household income. These results suggest that in the Swiss context, unemployment benefits improve birth outcomes by reducing (job search) stress rather than by improving nutrition or healthcare use. As such, cash transfers likely play a role for newborn health in most other contexts.
Travel ban effects on SARS-CoV-2 transmission lineages in the UAE as inferred by genomic epidemiology
Authors: Henschel Andreas , Feng Samuel F. , Hamoudi Rifat A. , Elbait Gihan Daw , Damiani Ernesto , Waasia Fathimathuz , Tay Guan K. , Mahboub Bassam H. , Uddin Maimunah Hemayet , Acuna Juan , Alefishat Eman , Halwani Rabih , Jelinek Herbert F. , Mustafa Farah , Alkaabi Nawal , Alsafar Habiba S. ,   on behalf of the UAE COVID-19 Collaborative Partnership
Published: March 2022

Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to the later introductions of the G-variant associated with international travel, rather than higher local transmissibility. For clades spanning different emirates, the most recent common ancestors pre-date domestic travel bans. In conclusion, we observe a steep and sustained decline of international transmissions immediately following the introduction of international travel restrictions.
Health perceptions among victims in post-accord Colombia: Focus groups in a province affected by the armed conflict
Authors: González-Uribe Catalina , Olmos-Pinzón Antonio , León-Giraldo Sebastián , Bernal Oscar , Moreno-Serra Rodrigo
Published: March 2022

The peace agreement with the Colombian guerrilla group Fuerzas Armadas Revolucionarias de Colombia—Ejército del Pueblo represented an opportunity for peacebuilding and victims’ reparation, rather than the end of the internal armed conflict. In this context, this study aimed to uncover the consequences of conflict on victims’ health and on health service provision, and their perceived health status during the post-accord stage in the Meta region, located in the country’s eastern plains. Historically, this region has been one of the territories most affected by the presence of conflict-related groups and armed confrontations. Through focus groups, this research explored the health perceptions and experiences of victims of armed conflict. Ten focus groups were conducted with men and women, victims of the armed-conflict, in four municipalities with different degrees of armed conflict intensity. The focus group transcripts were coded using NVivo. The results show that the way women have experienced conflict and the effects of conflict on mental health in general for men, women, and children were recurrent themes in the dialogue of victims. Likewise, it highlights the need to understand the barriers that the current health model imposes on the right to health itself. From the victim’s perspective, they experience stigmatization, discrimination, and revictimization when accessing health services. These barriers co-occur along with structural limitations of the health system that affect the general population.
Associations between biological and behavioral factors in early life and food consumption in Brazilian adolescents: Results from the ERICA study
Authors: Andrade Maria Laura Siqueira de Souza , Oliveira Juliana de Souza , Cabral Poliana Coelho , Cureau Felipe Vogt , Sá Leal Vanessa , de Lira Pedro Israel Cabral
Published: March 2022

The aim of the present study was to determine associations between biological and behavioral factors in early life and food consumption in Brazilian adolescents. The sample was composed of 36,956 adolescents (12–17 years of age) who participated in the “Study of Cardiovascular Risk in Adolescents”. Sociodemographic, biological, and behavioral variables were collected using questionnaires self-administered by the adolescents. Early-life factors were assessed using a questionnaire administered to the parents/guardians of the adolescents. Dependent variables related to food consumption (total energy intake and percentages of macronutrient intake [carbohydrates, lipids and proteins]) were measured using the 24-hour recall method and compared to dietary reference intakes. Data analysis was performed with the aid of STATA 14.0, using multiple linear regression analysis with respective β coefficients. The level of significance was set at 5% (p ≤ 0.05). Adolescents born with low weight had lower energy intake (-94.8 kcal, 95%CI: -177.2; -12.3, p = 0.024) and 1.25% higher carbohydrate intake (95%CI: 0.15; 2.34, p = 0.025) compared to those born with adequate weight. Those who received exclusive breast breastfeeding for three to six months ingested 1.32% more lipids than those who received exclusive breast breastfeeding for less than three months (95%CI: 0.37; 2.26, p = 0.006). In conclusion, low birth weight was associated with lower energy intake and a higher percentage of carbohydrate intake, whereas breastfeeding three to six months was associated with a higher percentage of lipid intake.
An interRAI derived frailty index predicts acute hospitalizations in older adults residing in retirement villages: A prospective cohort study
Authors: Bloomfield Katherine , Wu Zhenqiang , Tatton Annie , Calvert Cheryl , Peel Nancye , Hubbard Ruth , Jamieson Hamish , Hikaka Joanna , Boyd Michal , Bramley Dale , Connolly Martin J.
Published: March 2022

Objectives

The development of frailty tools from electronically recorded healthcare data allows frailty assessments to be routinely generated, potentially beneficial for individuals and healthcare providers. We wished to assess the predictive validity of a frailty index (FI) derived from interRAI Community Health Assessment (CHA) for outcomes in older adults residing in retirement villages (RVs), elsewhere called continuing care retirement communities.

Design

Prospective cohort study.

Setting and participants

34 RVs across two district health boards in Auckland, Aotearoa New Zealand (NZ). 577 participants, mean age 81 years; 419 (73%) female; 410 (71%) NZ European, 147 (25%) other European, 8 Asian (1%), 7 Māori (1%), 1 Pasifika (<1%), 4 other (<1%).

Methods

interRAI-CHA FI tool was used to stratify participants into fit (0–0.12), mild (>0.12–0.24), moderate (>0.24–0.36) and severe (>0.36) frail groups at baseline (the latter two grouped due to low numbers of severely frail). Primary outcome was acute hospitalization; secondary outcomes included long-term care (LTC) entry and mortality. The relationship between frailty and outcomes were explored with multivariable Cox regression, estimating hazard ratios (HRs) and 95% confidence intervals (95%CIs).

Results

Over mean follow-up of 2.5 years, 33% (69/209) of fit, 58% (152/260) mildly frail and 79% (85/108) moderate-severely frail participants at baseline had at least one acute hospitalization. Compared to the fit group, significantly increased risk of acute hospitalization were identified in mildly frail (adjusted HR = 1.88, 95%CI = 1.41–2.51, p<0.001) and moderate-severely frail (adjusted HR = 3.52, 95%CI = 2.53–4.90, p<0.001) groups. Similar increased risk in moderate-severely frail participants was seen in LTC entry (adjusted HR = 5.60 95%CI = 2.47–12.72, p<0.001) and mortality (adjusted HR = 5.06, 95%CI = 1.71–15.02, p = 0.003).

Conclusions and implications

The FI derived from interRAI-CHA has robust predictive validity for acute hospitalization, LTC entry and mortality. This adds to the growing literature of use of interRAI tools in this way and may assist healthcare providers with rapid identification of frailty.
Cell-penetrating peptides containing the progesterone receptor polyproline domain inhibits EGF signaling and cell proliferation in lung cancer cells
Authors: Kaewjanthong Panthita , Sooksai Sarintip , Sasano Hironobu , Hutvagner Gyorgy , Bajan Sarah , McGowan Eileen , Boonyaratanakornkit Viroj
Published: March 2022

Non-small cell lung cancer (NSCLC) accounts for the majority (80–85%) of all lung cancers. All current available treatments have limited efficacy. The epidermal growth factor receptor (EGFR) plays a critical role in the development and progression of NSCLC, with high EGFR expression associated with increased cell proliferation and poor prognosis. Thus, interfering with EGFR signaling has been shown to effectively reduce cell proliferation and help in the treatment of NSCLC. We previously demonstrated that the progesterone receptor (PR) contains a polyproline domain (PPD) that directly interacts with Src homology 3 (SH3) domain-containing molecules and expression of PR-PPD peptides inhibits NSCLC cell proliferation. In this study, we investigated whether the introduction of PR-PPD by cell-penetrating peptides (CPPs) could inhibit EGF-induced cell proliferation in NSCLC cells. PR-PPD was attached to a cancer-specific CPP, Buforin2 (BR2), to help deliver the PR-PPD into NSCLC cells. Interestingly, addition of BR2-2xPPD peptides containing two PR-PPD repeats was more effective in inhibiting NSCLC proliferation and significantly reduced EGF-induced phosphorylation of Erk1/2. BR2-2xPPD treatment induced cell cycle arrest by inhibiting the expression of cyclin D1 and CDK2 genes in EGFR-wild type A549 cells. Furthermore, the combination treatment of EGFR-tyrosine kinase inhibitors (TKIs), including Gefitinib or Erlotinib, with BR2-2xPPD peptides further suppressed the growth of NSCLC PC9 cells harboring EGFR mutations as compared to EGFR-TKIs treatment alone. Importantly, BR2-2xPPD peptides mediated growth inhibition in acquired Gefitinib- and Erlotinib- resistant lung adenocarcinoma cells. Our data suggests that PR-PPD is the minimal protein domain sufficient to inhibit NSCLC cell growth and has the potential to be developed as a novel NSCLC therapeutic agent.
Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. Against rheumatoid arthritis using network pharmacology and experimental validation
Authors: Hu Jing , Zhao Lintao , Li Ning , Yang Yuanyuan , Qu Tong , Ren Hui , Cui Xiaomin , Tao Hongxun , Chen Zhiyong , Peng Yu
Published: March 2022

Background

Porana sinensis Hemsl. has been widely used as a substitute for Erycibes Caulis to treat rheumatoid arthritis (RA) in traditional Chinese medicine (TCM). However, little is known about the active ingredients and pharmacological mechanisms that mediate the action of P. sinensis against RA.

Methods

The compounds contained in P. sinensis were analyzed by Q Exactive Focus mass spectrometer. The active constituents and pharmacological mechanism of P. sinensis against RA were clarified using a network pharmacology-based investigation. LPS-induced RAW 264.7 cells was used to verify anti-inflammatory effects of the active compounds screened by network pharmacology. Collagen-induced arthritis model was used to further investigate the mechanism of P. sinensis against RA.

Results

The potential components and targets of P. sinensis against RA were analyzed using network pharmacology, and five compounds, twenty-five targets, and eight pathways were identified. Experimental validation suggested that P. sinensis extract and five compounds (esculetin, umbelliferone, trans-N-feruloyltyramine, caffeic acid and scopolin) could inhibit the release of inflammatory mediators (NO, TNF-α, IL-1β and IL-6) in LPS-induced RAW 264.7 cell. P. sinensis extract attenuated the severity, pathological changes, and release of cytokines (IL-6 and HIF-1α) during RA progression by regulating the PI3K/AKT and HIF-1 pathways.

Conclusion

The study provides a basis for the application of P. sinensis against RA. Our findings may provide suggestions for developing P. sinensis into a substitute for Erycibes Caulis.
Association between integrase strand transfer inhibitor (INSTIs) use with insulin resistance and incident diabetes mellitus in persons living with HIV: A systematic review and meta-analysis protocol
Authors: Mulindwa Frank , Kamal Habiba , Castelnuovo Barbara , Bollinger Robert C. , Schwarz Jean-Marc , Brussealers Nele
Published: March 2022

Introduction

Poeple living with HIV have higher prevalence of diabetes mellitus and metabolic perturbations compared to non-HIV populations. Diabetes and metabolic syndrome co-morbidities add significant burden to HIV care. Currently, WHO recommends integrase strand transfer inhibitors (INSTIs) as the first or second line therapy in people with HIV due to overall good tolerability and safety profile. However, whether INSTI use increases the risk of incident diabetes (with or without metabolic syndrome) compared to other anti-retroviral therapies (ART) is controversial. In this systematic review and meta-analysis, we aim to examine this risk in HIV-positive populations receiving INSTIs compared to other ART regimens (not containing INSTIs).

Methods and analysis

The study will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. This protocol adheres to the Standard Protocol Items for reporting systematic reviews and meta-analyses checklist. Eligibility criteria will be original peer-reviewed published articles and conference abstracts with no language or geographical restriction; that report the ocurrence of diabetes mellitus as a discrete outcome or part of metabolic syndrome, in adult PLWHIV receiving INSTIs compared to other ART regimens. PubMed/ Medline, Web of Science, Embase and Cochrane Database of Systematic Reviews will be searched from 1st- January-2000 to 31st—January-2022. Per our a priori, screening, inclusion and data extraction will be conducted separately by two investigators, and a senior researcher will be consulted in case of disagreement. The quality of included studies will be assessed by the Newcastle-Ottawa Scale (NOS) for cohort and case-control studies and the revised Cochrane risk-of-bias tool (ROB2) for randomized controlled trials. The quantitative synthesis of the study outcomes will be explored in different subgroups and sensitivity analyses. Meta regression will also be performed to further test the predictors of the outcome.

Ethics and dissemination

Ethical approval is waived as the study is a review of published litterature. The analyses will be presented in conferences and published as a scientific article.

Trial registrartion

PROSPERO registration number is; CRD42021273040.
Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/ IRF3-mediated IFN-β production
Authors: Zhao Jin , Chen Jiaoshan , Wang Congcong , Liu Yajie , Li Minchao , Li Yanjun , Li Ruiting , Han Zirong , Wang Junjian , Chen Ling , Shu Yuelong , Cheng Genhong , Sun Caijun
Published: March 2022

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.
To Study the Pattern of Histopathological Findings in Cases of Medicolegal Autopsies
Authors: Sarngal Shiffali , Arora Swati , Sharma Shveta , Gandhi Shivani
Published: March 2022

BACKGROUND Medicolegal autopsy is an important procedure to ascertain the causes of sudden and unexplained deaths. It provides direct access to organ and tissues which otherwise is not possible with other diagnostic modalities. In addition to the morphological examination of tissues and organs we can also take representative samples from these tissues and organs. These samples may be subjected to histopathological examination and biochemical examination. These types of examinations prove quite helpful in cases of poisoning and sudden unexplained deaths where simple morphological examination may be inconclusive. It provides us an opportunity to study the natural course of evolution of many diseases. Incidental histopathological findings in autopsy also prove useful to account for many clinically undiagnosed diseases in the community like clinically undiagnosed neoplasms, infections and inflammatory diseases. We wanted to study the pattern of histopathological findings in medicolegal autopsy specimens and also age and sex distribution of cases of medicolegal autopsies. METHODS This prospective and descriptive study was conducted on three hundred and twenty specimens received randomly from one hundred and four cases of medicolegal autopsies irrespective of cause of death in Department of Pathology, Government medical college, Jammu. The specimens were processed and then stained with haematoxylin and eosin stain. RESULTS Maximum patients were seen in the age group of 31-40 yrs. (37.5%) followed by 21- 30 yrs. (25.9%). Males constituted (70.1%), females constituted about (29.8 %). Most common organ received was heart (31.8%), lung (30.6%) and liver (30.3%). Most common cause of death was sudden death 31(29.8%), myocardial infarction 21(20.1%), poisoning 20 (19.2%), assault 7 (6.7%), drowning 7 (6.7%), hanging 6(5.7%), road traffic accidents 5 (4.8%), firearm injuries 4 (3.8%) and electrocution 3 (2.8%). The lungs constituted 44.1% of all the histopathological findings, heart (20.5%), liver (10.2 %) kidney (7.3 %), spleen (5.8%), brain (4.4%), skin and neck structures (4.4%) and uterus (2.9%). CONCLUSIONS Atherosclerosis has become quite frequent cause of sudden and unexplained death in younger age group. So, we need to educate this age group about healthy lifestyle and importance of prophylactic screening to those having risk factors for cardiovascular diseases. KEY WORDS Medicolegal Autopsy, Sudden Death, Atherosclerosis
What does it mean to decolonise the school music curriculum?
Authors: Philpott Chris
Published: March 2022

In many ways the school music curriculum has become increasingly diverse since the 1970s. For example, ‘pop’ and ‘world’ musics have been listed in UK curricula and syllabuses with an aim of becoming more inclusive. However, this article argues that such approaches to curriculum as content have confounded social justice in school music, and in particular when perpetuating a prejudicial discourse. To understand this discourse, three ‘distortions’ of the material nature of musical knowledge are explored as potential sources of ongoing student alienation from school music: reification, hegemonic appropriation and the loss of meaning. These distortions are also exemplified through a case study critique of social realism and the UK government’s Model Music Curriculum. By way of conclusion, and as a possible resolution to the distortions, some characteristics of a curriculum as process are proposed that have implications for decolonisation and wider issues of social justice, such as class and gender.
MAKNA GURU DALAM TRADISI ISLAM SASAK: REPRESENTASI LOMBOK DALAM NOVEL SANGGARGURI
Authors: Satrya HD Dharma
Published: March 2022

This article discusses the meaning of Lombok in contemporary Indonesian novels with a focus on the novel Sanggarguri. The novel discusses the concept of heterodox teachers in Islam. The novel is presented in the context of opposing orthodox Islamic discourse on the concept of ‘guru’. To discover the concept of ‘guru’ in Sanggarguri, this article applies representation theory with a constructionist approach. With that approach, the novel is assumed not to be a presentation about Lombok, but a representation of Lombok. Data were language, both word and paragraph, both in narrative and metaphorical form. Data analysis was performed using semiotic and discourse methods. The results of the analysis show that the novel Sanggarguri conceptualizes Lombok into a traditional discourse by using the names of flowers (kembang) as stages that exist in Sasak Islamic spirituality. The stages from gadung flower to ‘Sanggar Guri teacher’, a wisdom expert teacher, reveal that the concept of a teacher in heterodox Sasak Islam is open to anyone. It belongs to anyone and anywhere. The concept is different from the concept of ‘guru’ in orthodox Islam promoted by ‘tuan guru’, whose knowledge is connected to Haramain. Therefore, only a few people can become ‘tuan guru’. The discourse of ‘guru’ in Sanggarguri is against the discourse of ‘tuan guru’ on the meaning of ‘guru’.
Site-specific nanobody-oligonucleotide conjugation for super-resolution imaging
Authors: Teodori Laura , Omer Marjan , Märcher Anders , K. Skaanning Mads , L. Andersen Veronica , S. Nielsen Jesper , Oldenburg Emil , Lin Yuchen , V. Gothelf Kurt , Kjems Jørgen
Published: March 2022

Camelid single-domain antibody fragments, also called nanobodies, constitute a class of binders that are small in size (~15 kDa) and possess antigen-binding properties similar to their antibody counterparts. Facile production of recombinant nanobodies in several microorganisms has made this class of binders attractive within the field of molecular imaging. Particularly, their use in super-resolution microscopy has improved the spatial resolution of molecular targets due to a smaller linkage error. In single-molecule localization microscopy techniques, the effective spatial resolution can be further enhanced by site-specific fluorescent labeling of nanobodies owing to a more homogeneous protein-to-fluorophore stoichiometry, reduced background staining and a known distance between dye and epitope. Here, we present a protocol for site-specific bioconjugation of DNA oligonucleotides to three distinct nanobodies expressed with an N- or C-terminal unnatural amino acid, 4-azido-L-phenylalanine (pAzF). Using copper-free click chemistry, the nanobody-oligonucleotide conjugation reactions were efficient and yielded highly pure bioconjugates. Target binding was retained in the bioconjugates, as demonstrated by bio-layer interferometry binding assays and the super-resolution microscopy technique, DNA points accumulation for imaging in nanoscale topography (PAINT). This method for site-specific protein-oligonucleotide conjugation can be further extended for applications within drug delivery and molecular targeting where site-specificity and stoichiometric control are required.
Notes from the Editors, March 2022
Authors: Editors -
Published: March 2022

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The struggle over schools today requires battles over both the privatization of education and the current attempts to limit its social content and meaning. Those fighting against this changing totality must align themselves with the embattled radical teachers in the trenches. In the famous words of Grace Lee Boggs, more than a half-century ago, it is necessary to create "a new system of education that will have as its means and its end the development of the great masses of people to govern over themselves and administer over things."
A Commune Called 'Che'
Authors: Gilbert Chris
Published: March 2022

The Che Guevara Commune is far removed from the bustle of Venezuela's huge coastal cities. You reach it by following a steep winding road from the shores of Lake Maracaibo into La Culata National Park. Lush vegetation and tall bucare trees provide good shade for coffee and cacao, which has only begun to be farmed in recent decades in this region, due to the migration triggered by the construction of the Pan-American Highway along the lake's perimeter in the 1950s.
What 1930s Radicals Totally Knew
Authors: Borchert Scott , Day Susie
Published: March 2022

The Great Depression is almost one century old. Today in the United States we remember this international economic collapse, and the suffering it engendered, by reading novels and essays about it, watching plays, viewing paintings—often forgetting that the U.S. government of that time encouraged and financially supported much of this art. Not only art: the Depression was one of the few times that the federal government ever stepped in to help ordinary people get on their feet.