bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity, A Risk Factor for Mortality in SARS CoV-2 Infection: A Narrative Systematic Review
Authors: Reddy Sekhar , Ganie Mohd Ashraf , Koul Parvaiz A. , Sahar Tajali , Showkat Shaista
Published: December 2021

SARS CoV-2 is a β-coronavirus responsible for the current COVID-19 pandemic. Although there is increase severity and mortality described in the elderly population and people with co-morbidities, all age groups are susceptible to COVID-19. Recent data showed that obesity has also emerged as a significant risk factor for COVID-19 mortality. As per the WHO, most of the world's population lives in countries where obesity is highly prevalent. In this context, we aimed to review various studies that showed obesity as an independent risk factor for mortality in SARS CoV-2 infection. We followed the PRISMA guidelines to search for two databases including PubMed and Google Scholar using the key terms “COVID-19, OBES* and MORTALITY,” SARS CoV-2, OBES* and MORTALITY” “COVID-19, OBESITY, and MORTALITY,” SARS Cov-2, OBESITY and MORTALITY,” respectively, up to August 3, 2020. Twelve studies were finally included in this review after applying inclusion and exclusion criteria. All 12 studies included in the review consistently showed that obesity is a risk factor for mortality in patients with SARS CoV-2 infection. These studies have also shown evidence that obesity leads to increased hospitalization, ICU admission, increased need for mechanical ventilation, and poor prognosis among patients with SARS CoV-2 infection. Obesity is an independent risk factor for mortality in patients infected with this novel coronavirus. Appropriate triage, monitoring, and vigilance are required while dealing with individuals with obesity with SARS CoV2 infection, especially in the young obese population. More epidemiological studies need to be done taking BMI also into consideration in COVID-19 patients to find the exact cause of increased severity and mortality and develop appropriate preventive and therapeutic strategies.
Metformin Treatment Among Men With Diabetes and the Risk of Prostate Cancer: A Population-Based Historical Cohort Study
Authors: Freedman Laurence S , Agay Nirit , Farmer Ruth , Murad Havi , Olmer Liraz , Dankner Rachel
Published: December 2021

There is conflicting evidence regarding the association between metformin treatment and prostate cancer risk in diabetic men. We investigated this association in a population-based Israeli cohort of 145,617 men aged 21–89 years with incident diabetes who were followed over the period 2002–2012. We implemented a time-dependent covariate Cox model, using weighted cumulative exposure to relate metformin history to prostate cancer risk, adjusting for use of other glucose-lowering medications, age, ethnicity, and socioeconomic status. To adjust for time-varying glucose control variables, we used inverse probability weighting of a marginal structural model. With 666,553 person-years of follow-up, 1,592 men were diagnosed with prostate cancer. Metformin exposure in the previous year was positively associated with prostate cancer risk (per defined daily dose; without adjustment for glucose control, hazard ratio (HR) = 1.53 (95% confidence interval (CI): 1.19, 1.96); with adjustment, HR = 1.42 (95% CI: 1.04, 1.94)). However, exposure during the previous 2–7 years was negatively associated with risk (without adjustment for glucose control, HR = 0.58 (95% CI: 0.37, 0.93); with adjustment, HR = 0.60 (95% CI: 0.33, 1.09)). These positive and negative associations with previous-year and earlier metformin exposure, respectively, need to be confirmed and better understood.
Correlations between leaf economics, mechanical resistance and drought tolerance across 41 cycad species
Authors: Meng Yi-Yi , Xiang Wei , Wen Yin , Huang Dong-Liu , Cao Kun-Fang , Zhu Shi-Dan
Published: December 2021

Background and Aims

We conducted a comprehensive analysis of the functional traits of leaves (leaflets) of cycads. The aim of this study was to clarify the functional divergence between the earlier origin Cycadaceae and the later differentiated Zamiaceae, and the differences in trait associations between cycads and angiosperms.

Methods

We selected 20 Cycadaceae species and 21 Zamiaceae species from the same cycad garden in South China, and measured their leaf structure, economic traits, mechanical resistance (Fp) and leaf water potential at the turgor loss point (πtlp). In addition, we compiled a dataset of geographical distribution along with climatic variables for these cycad species, and some leaf traits of tropical–sub-tropical angiosperm woody species from the literature for comparison.

Key Results

The results showed significantly contrasting leaf trait syndromes between the two families, with Zamiaceae species exhibiting thicker leaves, higher carbon investments and greater Fp than Cycadaceae species. Leaf thickness (LT) and πtlp were correlated with mean climatic variables in their native distribution ranges, indicating their evolutionary adaptation to environmental conditions. Compared with the leaves of angiosperms, the cycad leaves were thicker and tougher, and more tolerant to desiccation. Greater Fp was associated with a higher structural investment in both angiosperms and cycads; however, cycads showed lower Fp at a given leaf mass per area or LT than angiosperms. Enhancement of Fp led to more negative πtlp in angiosperms, but the opposite trend was observed in cycads.

Conclusions

Our results reveal that variations in leaf traits of cycads are mainly influenced by taxonomy and the environment of their native range. We also demonstrate similar leaf functional associations in terms of economics, but different relationships with regard to mechanics and drought tolerance between cycads and angiosperms. This study expands our understanding of the ecological strategies and likely responses of cycads to future climate change.
Viral Load Status Before Switching to Dolutegravir-Containing Antiretroviral Therapy and Associations With Human Immunodeficiency Virus Treatment Outcomes in Sub-Saharan Africa
Authors: Romo Matthew L , Edwards Jessie K , Semeere Aggrey S , Musick Beverly S , Urassa Mark , Odhiambo Francesca , Diero Lameck , Kasozi Charles , Murenzi Gad , Lelo Patricia , Wyka Katarzyna , Kelvin Elizabeth A , Sohn Annette H , Wools-Kaloustian Kara K , Nash Denis ,   International epidemiology Databases to Evaluate AIDS (IeDEA)
Published: December 2021

Background

Dolutegravir is being rolled out globally as part of preferred antiretroviral therapy (ART) regimens, including among treatment-experienced patients. The role of viral load (VL) testing before switching patients already on ART to a dolutegravir-containing regimen is less clear in real-world settings.

Methods

We included patients from the International epidemiology Databases to Evaluate AIDS consortium who switched from a nevirapine- or efavirenz-containing regimen to one with dolutegravir. We used multivariable cause-specific hazards regression to estimate the association of the most recent VL test in the 12 months before switching with subsequent outcomes.

Results

We included 36 393 patients at 37 sites in 5 countries (Democratic Republic of the Congo, Kenya, Rwanda, Tanzania, Uganda) who switched to dolutegravir from July 2017 through February 2020, with a median follow-up of approximately 11 months. Compared with those who switched with a VL <200 copies/mL, patients without a recent VL test or with a preswitch VL ≥1000 copies/mL had significantly increased hazards of an incident VL ≥1000 copies/mL (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.99–4.19 and aHR, 6.60; 95% CI, 4.36–9.99, respectively) and pulmonary tuberculosis or a World Health Organization clinical stage 4 event (aHR, 4.78; 95% CI, 2.77–8.24 and aHR, 13.97; 95% CI, 6.62–29.50, respectively).

Conclusions

A VL test before switching to dolutegravir may help identify patients who need additional clinical monitoring and/or adherence support. Further surveillance of patients who switched to dolutegravir with an unknown or unsuppressed VL is needed.
Does Your Class Give More than a Hint of Your Lifetime Earnings?: Assessing Indicators for Lifetime Earnings Over the Life Course for Sweden
Authors: Shahbazian Roujman , Bihagen Erik
Published: December 2021

From a sociological stratification perspective, we would expect occupationally based measures to be valid proxies for lifetime earnings, but recent research suggests that annual earnings outperform occupational measures. In this article, we examine how class, occupation, education, and annual earnings are associated with lifetime earnings across almost complete working lives, at ages of around 20–65 years for Swedish cohorts born in the 1940s. Our results indicate that while annual earnings are considerably more accurate proxies for the lion’s share of working life, occupational measures are as expected more stable and somewhat better at the start and end of working lives. Our results also support the idea that micro-classes are better proxies of lifetime earnings than big classes. Contrary to some previous research, occupational measures perform better for women than for men in this respect, and occupational measures are better than education. Our main conclusions are that proxies for lifetime earnings have life-cycle biases that should be considered in, for instance, analyses of intergenerational mobility, and that occupationally based measures are more stable than annual earnings but, overall, are not very valid as indicators of lifetime earnings compared to annual earnings.
Presence of bacteria capable of PCB biotransformation in stormwater bioretention cells
Authors: Cao Siqi , Davis Allen , Kjellerup Birthe V
Published: December 2021

Core samples from bioretention cell media as well as surface stormwater sediment samples from seven urban areas were collected to assess the potential for biotransformation activity of polychlorinated biphenyls (PCBs). The presence of putative organohalide-respiring bacteria in these samples was studied. Based on extracted DNA, Dehalobacter, Dehalogenimonas and Dehalococcoides were detected. Other organohalide-respiring bacteria like Desulfitobacterium and Sulfurospirillum were not studied. Bacteria containing the genes encoding for biphenyl 2,3-dioxygenase (bphA) or 2,3-dihydroxybiphenyl 1,2-dioxygenase (bphC) were detected in 29 of the 32 samples. These genes are key factors in PCB aerobic degradation. Transcribed bacterial genes from putative organohalide-respiring bacteria as well as genes encoding for bphA and bphC were obtained from the microbial community, thus showing the potential of organohalide respiration of PCBs and aerobic PCB degradation under both aerobic and anaerobic conditions in the surface samples collected at the bioretention site. Presence and concentrations of 209 PCB congeners in the bioretention media were also assessed. The total PCB concentration ranged from 38.4 ± 2.3 ng/g at the top layer of the inlet to 11.6 ± 1.2 ng/g at 20–30 cm at 3 m from the inlet. These results provide documentation that bacteria capable of PCB transformation, including both anaerobic dechlorination and aerobic degradation, were present and active in the bioretention.
The Paid and Unpaid Working Life Expectancy at 50 in Europe
Authors: Ophir Ariane
Published: December 2021

Objectives

Amid growing concerns about the economic implications of population aging and the sustainability of older adults’ working life, unpaid family care work receives less attention despite its direct relevance to population aging. This article systematically compares the paid and unpaid working life expectancy at age 50 to understand the overlap and trade-off between paid and unpaid work among older European adults.

Method

Using data from the Survey of Health and Retirement in Europe with the Sullivan method, the article presents gender differences across 17 countries in life expectancy at age 50 at various paid (employment) and unpaid (caregiving) role configurations.

Results

When work is defined to include unpaid family caregiving, women and men have similar working life expectancies at age 50, in contrast to prior research. However, its paid and unpaid components are gendered. The results also show that at age 50, women are expected to spend a similar number of years providing grandchild care and activities of daily living/instrumental activities of daily living care and that most of these years take place after retirement.

Discussion

The results highlight that the gendered tension between paid and unpaid work persists into older adulthood and needs to be accounted for in working life expectancy measures. The results also underscore the gendered implications of population aging and unpaid work in older adulthood for retirement age policies and strategies for promoting gender equality in later life.
Measuring Sex and Gender in Aging and Alzheimer’s Research: Results of a National Survey
Authors: Stites Shana D , Cao Hannah , Harkins Kristin , Flatt Jason D
Published: December 2021

Objectives

Differences between men and women are common in published research on aging and Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). What do these differences mean? To answer this, rigorous measurement is needed. We investigated current methods for measuring sex/gender in aging and AD/ADRD cohort studies.

Methods

An online survey was sent to National Institute on Aging-funded Alzheimer’s Disease Research Centers (n = 38) and investigator-initiated cohort studies (n = 38) to assess practices around enrollment of men and women and measurement of sex and gender.

Results

The response rate was 65.8% (n = 50). All enrolled men and all but two investigator-initiated studies enrolled women. Most cohorts (43/50) had no documented definitions for categories of “men” or “women.” Over 85% of cohorts relied solely on self-report questions to capture sex/gender data (n = 43/50). Issues with administration were also identified (n = 7).

Discussion

Our findings identify gaps in current approaches used to measure sex and gender in aging and AD/ADRD research. We discuss opportunities to bridge these gaps and advance measurement of sex and gender in aging and AD/ADRD research. Changes are needed to ensure inclusion and representation of sociocultural diversity in research samples, and consistency in data collection in aging and AD/ADRD research.
Prenatal Poly I:C Challenge Affects Behaviors and Neurotransmission via Elevated Neuroinflammation Responses in Female Juvenile Rats
Authors: Su Yueqing , Lian Jiamei , Hodgson James , Zhang Wenchang , Deng Chao
Published: December 2021

Background

Exposure to polyriboinosinic-polyribocytidylic acid (Poly I:C) in pregnant rats has been reported to cause schizophrenia-like behaviors and abnormal neurotransmissions in adult, particularly male, offspring. However, what is less well understood are the effects of maternal Poly I:C exposure on adolescent behaviors and neurotransmission in female juvenile rats.

Methods

Female adolescent Poly I:C offspring were constructed by treating with 5 mg/kg Poly I:C on timed pregnant rats (gestation day 15). A battery of behavioral tests was conducted during postnatal day 35–60. Neurotransmitter receptors and inflammation markers in brain regions were evaluated by RT-qPCR on postnatal day 60.

Results

Open field, elevated plus maze, and forced swimming tests revealed that prenatal Poly I:C exposure led to elevated anxiety-like and depression-like behaviors in female adolescent offspring. Deficits in pre-pulse inhibition and social interaction were also observed. However, the Poly I:C rats had better performance than the controls in the novel object recognition memory test, which demonstrated a behavioral phenotype with improved cognitive function. Prenatal Poly I:C exposure caused brain region–specific elevation of the P2X7 receptor- and NF-κB-NLRP3-IL-1β inflammatory signaling in female juvenile rats. Prenatal Poly I:C exposure decreased expression of GABAA receptor subunits Gabrb3 in the prefrontal cortex and Gabrb1 and dopamine D2 receptor in the hippocampus, but increased NMDA receptor subunit Grin2a in the prefrontal cortex, 5-HT2A in the hippocampus, and Gabrb3 and D2 receptor in the nucleus accumben.

Conclusions

Prenatal Poly I:C challenge causes behavioral deficits and brain-specific neurotransmission changes via elevated neuroinflammation responses in female adolescent offspring rats.
An EjbHLH14-EjHB1-EjPRX12 module is involved in methyl jasmonate alleviation of chilling-induced lignin deposition in loquat fruit
Authors: Zhang Mengxue , Shi Yanna , Liu Zimeng , Zhang Yijin , Yin Xueren , Liang Zihao , Huang Yiqing , Grierson Donald , Chen Kunsong
Published: December 2021

Loquat fruit are susceptible to chilling injuries induced by postharvest storage at low temperature. The major symptoms are increased lignin content and flesh firmness, which cause a leathery texture. Pretreatment with methyl jasmonate (MeJA) can alleviate this low-temperature-induced lignification, but the mechanism is not understood. In this study, we characterized a novel class III peroxidase, EjPRX12, and studied its relationship to lignification. Transcript levels of EjPRX12 were attenuated following MeJA pretreatment, consistent with the reduced lignin content in fruit. In vitro enzyme activity assay indicated that EjPRX12 polymerized sinapyl alcohol, and overexpression of EjPRX12 in Arabidopsis promoted lignin accumulation, indicating that it plays a functional role in lignin polymerization. We also identified an HD-ZIP transcription factor, EjHB1, repressed by MeJA pretreatment, which directly bound to and significantly activated the EjPRX12 promoter. Overexpression of EjHB1 in Arabidopsis promoted lignin accumulation with induced expression of lignin-related genes, especially AtPRX64. Furthermore, a JAZ-interacting repressor, EjbHLH14, was characterized, and it is proposed that MeJA pretreatment caused EjbHLH14 to be released to repress the expression of EjHB1. These results identified a novel regulatory pathway involving EjbHLH14-EjHB1-EjPRX12 and revealed the molecular mechanism whereby MeJA alleviated lignification of loquat fruit at low temperature.
Halo concentration strengthens dark matter constraints in galaxy–galaxy strong lensing analyses
Authors: Amorisco Nicola C , Nightingale James , He Qiuhan , Amvrosiadis Aristeidis , Cao Xiaoyue , Cole Shaun , Etherington Amy , Frenk Carlos S , Li Ran , Massey Richard , Robertson Andrew
Published: December 2021

A defining prediction of the cold dark matter cosmological model is the existence of a very large population of low-mass haloes. This population is absent in models in which the dark matter particle is warm (WDM). These alternatives can, in principle, be distinguished observationally because haloes along the line of sight can perturb galaxy–galaxy strong gravitational lenses. Furthermore, the WDM particle mass could be deduced because the cut-off in their halo mass function depends on the mass of the particle. We systematically explore the detectability of low-mass haloes in WDM models by simulating and fitting mock lensed images. Contrary to previous studies, we find that haloes are harder to detect when they are either behind or in front of the lens. Furthermore, we find that the perturbing effect of haloes increases with their concentration: Detectable haloes are systematically high-concentration haloes, and accounting for the scatter in the mass–concentration relation boosts the expected number of detections by as much as an order of magnitude. Haloes have lower concentration for lower particle masses and this further suppresses the number of detectable haloes beyond the reduction arising from the lower halo abundances alone. Taking these effects into account can make lensing constraints on the value of the mass function cut-off at least an order of magnitude more stringent than previously appreciated.
Intermolecular Interactions Drive Protein Adaptive and Coadaptive Evolution at Both Species and Population Levels
Authors: Peng Junhui , Svetec Nicolas , Zhao Li
Published: December 2021

Proteins are the building blocks for almost all the functions in cells. Understanding the molecular evolution of proteins and the forces that shape protein evolution is essential in understanding the basis of function and evolution. Previous studies have shown that adaptation frequently occurs at the protein surface, such as in genes involved in host–pathogen interactions. However, it remains unclear whether adaptive sites are distributed randomly or at regions associated with particular structural or functional characteristics across the genome, since many proteins lack structural or functional annotations. Here, we seek to tackle this question by combining large-scale bioinformatic prediction, structural analysis, phylogenetic inference, and population genomic analysis of Drosophila protein-coding genes. We found that protein sequence adaptation is more relevant to function-related rather than structure-related properties. Interestingly, intermolecular interactions contribute significantly to protein adaptation. We further showed that intermolecular interactions, such as physical interactions, may play a role in the coadaptation of fast-adaptive proteins. We found that strongly differentiated amino acids across geographic regions in protein-coding genes are mostly adaptive, which may contribute to the long-term adaptive evolution. This strongly indicates that a number of adaptive sites tend to be repeatedly mutated and selected throughout evolution in the past, present, and maybe future. Our results highlight the important roles of intermolecular interactions and coadaptation in the adaptive evolution of proteins both at the species and population levels.
Deviation from baseline mutation burden provides powerful and robust rare-variants association test for complex diseases
Authors: Jiang Lin , Jiang Hui , Dai Sheng , Chen Ying , Song Youqiang , Tang Clara Sze-Man , Pang Shirley Yin-Yu , Ho Shu-Leong , Wang Binbin , Garcia-Barcelo Maria-Mercedes , Tam Paul Kwong-Hang , Cherny Stacey S , Li Mulin Jun , Sham Pak Chung , Li Miaoxin
Published: December 2021

Identifying rare variants that contribute to complex diseases is challenging because of the low statistical power in current tests comparing cases with controls. Here, we propose a novel and powerful rare variants association test based on the deviation of the observed mutation burden of a gene in cases from a baseline predicted by a weighted recursive truncated negative-binomial regression (RUNNER) on genomic features available from public data. Simulation studies show that RUNNER is substantially more powerful than state-of-the-art rare variant association tests and has reasonable type 1 error rates even for stratified populations or in small samples. Applied to real case-control data, RUNNER recapitulates known genes of Hirschsprung disease and Alzheimer's disease missed by current methods and detects promising new candidate genes for both disorders. In a case-only study, RUNNER successfully detected a known causal gene of amyotrophic lateral sclerosis. The present study provides a powerful and robust method to identify susceptibility genes with rare risk variants for complex diseases.
HiCRes: a computational method to estimate and predict the genomic resolution of Hi-C libraries
Authors: Marchal Claire , Singh Nivedita , Corso-Díaz Ximena , Swaroop Anand
Published: December 2021

Three-dimensional (3D) conformation of the chromatin is crucial to stringently regulate gene expression patterns and DNA replication in a cell-type specific manner. Hi-C is a key technique for measuring 3D chromatin interactions genome wide. Estimating and predicting the resolution of a library is an essential step in any Hi-C experimental design. Here, we present the mathematical concepts to estimate the resolution of a dataset and predict whether deeper sequencing would enhance the resolution. We have developed HiCRes, a docker pipeline, by applying these concepts to several Hi-C libraries.
Regulation of AR mRNA translation in response to acute AR pathway inhibition
Authors: Somasekharan Syam Prakash , Saxena Neetu , Zhang Fan , Beraldi Eliana , Huang Jia Ni , Gentle Christina , Fazli Ladan , Thi Marisa , Sorensen Poul H , Gleave Martin
Published: December 2021

We report a new mechanism of androgen receptor (AR) mRNA regulation and cytoprotection in response to AR pathway inhibition (ARPI) stress in prostate cancer (PCA). AR mRNA translation is coordinately regulated by RNA binding proteins, YTHDF3 and G3BP1. Under ambient conditions m6A-modified AR mRNA is bound by YTHDF3 and translationally stimulated, while m6A-unmodified AR mRNA is bound by G3BP1 and translationally repressed. When AR-regulated PCA cell lines are subjected to ARPI stress, m6A-modified AR mRNA is recruited from actively translating polysomes (PSs) to RNA-protein stress granules (SGs), leading to reduced AR mRNA translation. After ARPI stress, m6A-modified AR mRNA liquid–liquid phase separated with YTHDF3, while m6A-unmodified AR mRNA phase separated with G3BP1. Accordingly, these AR mRNA messages form two distinct YTHDF3-enriched or G3BP1-enriched clusters in SGs. ARPI-induced SG formation is cell-protective, which when blocked by YTHDF3 or G3BP1 silencing increases PCA cell death in response to ARPI stress. Interestingly, AR mRNA silencing also delays ARPI stress-induced SG formation, highlighting its supportive role in triggering this stress response. Our results define a new mechanism for stress adaptive cell survival after ARPI stress involving SG-regulated translation of AR mRNA, mediated by m6A RNA modification and their respective regulatory proteins.
Interim analysis of the COSA (COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter) registry
Authors: Schmidt Julius J , Borchina Dan Nicolae , van't Klooster Mariet , Bulhan-Soki Khalida , Okioma Reuben , Herbst Larissa , Rodríguez Diego Sandoval , Premužić Vedran , Büttner Stefan , Bader Birgit , Serednicki Wojciech , Zasada Ewa , Schmitz Michael , Quabach Ralf A , Hrincheva Maria , Fühner Thomas , Kielstein Jan T
Published: December 2021

Background

The Seraph® 100 Microbind® Affinity Blood Filter is a haemoperfusion device that is licensed for the reduction of pathogens, including several viruses, in the blood. It received Emergency Use Authorization for the treatment of severe coronavirus disease 2019 (COVID-19) by the Food and Drug Administration (FDA). Several studies have shown that the blood viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlates with adverse outcomes and removal of the nucleocapsid of the SARS-CoV-2 virus by the Seraph® 100 has been recently demonstrated. The aim of this registry was to evaluate the safety and efficacy of Seraph® 100 treatment for COVID-19 patients.

Methods

Twelve hospitals from six countries representing two continents documented patient and treatment characteristics as well as outcome parameters without reimbursement. Additionally, mortality and safety results of the device were reported. A total of 102 treatment sessions in 82 patients were documented in the registry. Four patients were excluded from mortality analysis due to incomplete outcome data, which were available in the other 78 patients.

Results

Overall, a 30-day mortality rate of 46.2% in the 78 patients with complete follow-up was reported. The median treatment time was 5.00 h (4.00–13.42) and 43.1% of the treatments were performed as haemoperfusion only. Adverse events of the Seraph® 100 treatment were reported in 8.8% of the 102 treatments and represented the premature end of treatment due to circuit failure. Patients who died were treated later in their intensive care unit (ICU) stay and onset of COVID symptoms. They also had higher ferritin levels. Multivariate Cox regression revealed that delayed Seraph® 100 treatment after ICU admission (>60 h), as well as bacterial superinfection, were associated with mortality. While average predicted mortality rate according to Sequential Organ Failure Assessment (SOFA) score in ICU patients was 56.7%, the observed mortality was 50.7%. In non-ICU patients, Coronavirus Clinical Characterisation Consortium (4C) score average predicted a mortality rate of 38.0%, while the observed mortality rate was 11.1%.

Conclusions

The treatment of COVID-19 patients with Seraph® 100 is well tolerated and the circuit failure rate was lower than previously reported for kidney replacement therapy (KRT) in COVID-19 patients. Mortality correlated with late initiation of Seraph treatment after ICU admission and bacterial superinfection. Compared with predicted mortality according to 4C and SOFA scores, mortality of Seraph® 100-treated patients reported in the registry was lower.
Species-specific partial gene duplication in Arabidopsis thaliana evolved novel phenotypic effects on morphological traits under strong positive selection
Authors: Huang Yuan , Chen Jiahui , Dong Chuan , Sosa Dylan , Xia Shengqian , Ouyang Yidan , Fan Chuanzhu , Li Dezhu , Mortola Emily , Long Manyuan , Bergelson Joy
Published: December 2021

Gene duplication is increasingly recognized as an important mechanism for the origination of new genes, as revealed by comparative genomic analysis. However, how new duplicate genes contribute to phenotypic evolution remains largely unknown, especially in plants. Here, we identified the new gene EXOV, derived from a partial gene duplication of its parental gene EXOVL in Arabidopsis thaliana. EXOV is a species-specific gene that originated within the last 3.5 million years and shows strong signals of positive selection. Unexpectedly, RNA-sequencing analyses revealed that, despite its young age, EXOV has acquired many novel direct and indirect interactions in which the parental gene does not engage. This observation is consistent with the high, selection-driven substitution rate of its encoded protein, in contrast to the slowly evolving EXOVL, suggesting an important role for EXOV in phenotypic evolution. We observed significant differentiation of morphological changes for all phenotypes assessed in genome-edited and T-DNA insertional single mutants and in double T-DNA insertion mutants in EXOV and EXOVL. We discovered a substantial divergence of phenotypic effects by principal component analyses, suggesting neofunctionalization of the new gene. These results reveal a young gene that plays critical roles in biological processes that underlie morphological evolution in A. thaliana.
Distinct neuroanatomic subtypes in antipsychotic-treated patients with schizophrenia classified by the predefined classification in a never-treated sample
Authors: Zhao Qiannan , Li Jiao , Xiao Yuan , Cao Hengyi , Wang Xiao , Zhang Wenjing , Li Siyi , Liao Wei , Gong Qiyong , Lui Su
Published: December 2021

Background

Distinct neuroanatomic subtypes have been identified in never-treated patients with schizophrenia based on cerebral structural abnormalities, but whether antipsychotic-treated patients would be stratified under the guidance of such previously formed classification remains unclear.

Objective

The present study aimed to investigate alterations of brain structures in antipsychotic-treated patients with schizophrenia based on a predefined morphological classification and their relationships with cognitive performance.

Methods

Cortical thickness, surface area, and subcortical volume were extracted from 147 antipsychotic-treated patients with schizophrenia using structural magnetic resonance imaging for classification. The Brief Assessment of Cognition in Schizophrenia (BACS) and Positive and Negative Syndrome Scale (PANSS) were used to assess cognition and symptoms.

Results

Antipsychotic-treated patients were categorized into three subtypes with distinct patterns of brain morphological alterations. Subtypes 1 and 2 were characterized by widespread deficits in cortical thickness but relatively limited deficits in surface area. In contrast, subtype 3 demonstrated cortical thickening mainly in parietal-occipital regions and widespread deficits in surface area. All three subgroups demonstrated cognitive deficits compared with healthy controls. Significant associations between neuroanatomic and cognitive abnormalities were only observed in subtype 1, where cortical thinning in the left lingual gyrus was conversely related to symbol coding performance.

Conclusions

Similar to drug-naïve patients, neuroanatomic heterogeneity exists in antipsychotic-treated patients, with disparate associations with cognition. These findings promote our understanding of relationships between neuroanatomic abnormalities and cognitive performance in the context of heterogeneity. Moreover, these results suggest that neurobiological heterogeneity needs to be considered in cognitive research in schizophrenia.
Correlation between salivary gland ultrasonography and scintigraphy in primary Sjögren’s syndrome
Authors: Min Hong Ki , Kim Se Hee , Lee Kyung-Ann , Jo Joon-Hyung , So Young , Chung Hyun Woo , Lee Sang-Heon , Kim Hae-Rim
Published: December 2021

Objective

To compare findings on salivary gland ultrasonography (SGUS) and salivary gland scintigraphy (SGS) in patients with primary SS (pSS).

Methods

The study cohort included patients newly diagnosed with pSS who underwent SGUS and SGS at the same time at our tertiary care hospital. Baseline demographics, laboratory data, clinical data and SGUS and SGS findings were collected. An SGUS cut-off score ≥14 defined positive SGUS findings and was used to classify patients in SGUS+ and SGUS− groups. SGS findings were quantified by the parotid:submandibular uptake ratio (PU:SU) and percentage parotid/submandibular excretion (%PE/%SE). The correlation between SGUS and SGS findings was evaluated.

Results

For analysis, 18 patients with SGUS+ findings and 18 with SGUS− findings were recruited, for a total study cohort of 36 patients. There were no between-group differences in baseline demographics and clinical and laboratory data. The PU, %PE, SU and %SE were significantly lower in the SGUS+vs SGUS− group. The SGUS score for the parotid gland was negatively correlated to the PU (r = −0.36, P = 0.03) and %PE (r = −0.35, P = 0.04). The SGUS score of the submandibular gland was negatively correlated to the SU (r = −0.42, P = 0.01) and %SE (r = −0.39, P = 0.02).

Conclusions

Patients with a higher SGUS score had lower salivary gland function. The SGUS score showed a significant correlation with PU, %PE, SU and %SE. These findings are indicative of a possible predictive role of SGUS to diagnose salivary gland dysfunction.
Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
Authors: Dahlqvist Johanna , Ekman Diana , Sennblad Bengt , Kozyrev Sergey V , Nordin Jessika , Karlsson Åsa , Meadows Jennifer R S , Hellbacher Erik , Rantapää-Dahlqvist Solbritt , Berglin Ewa , Stegmayr Bernd , Baslund Bo , Palm Øyvind , Haukeland Hilde , Gunnarsson Iva , Bruchfeld Annette , Segelmark Mårten , Ohlsson Sophie , Mohammad Aladdin J , Svärd Anna , Pullerits Rille , Herlitz Hans , Söderbergh Annika , Rosengren Pielberg Gerli , Hultin Rosenberg Lina , Bianchi Matteo , Murén Eva , Omdal Roald , Jonsson Roland , Eloranta Maija-Leena , Rönnblom Lars , Söderkvist Peter , Knight Ann , Eriksson Per , Lindblad-Toh Kerstin
Published: December 2021

Objective

To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV).

Methods

Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay.

Results

PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 × 10−61, odds ratio (OR) 0.10; rs9277341, P = 1.5 × 10−44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 × 10−10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 × 10−25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 × 10−7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele.

Conclusion

We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
Search-Based Peer Groups and Commonality in Liquidity
Authors: Brockman Paul , Chung Dennis Y , Snow Neal M
Published: December 2021

We examine search-based peer (SBP) groups proposed by Lee, Ma, and Wang (2015) and their relationship with commonality in liquidity. Our results confirm that SBP affiliation is a significant determinant of commonality in liquidity and, unlike market- and industry-commonality, SBP-commonality has been increasing over the past 15 years. We separate retail from institutional investor queries by tracing the IP locations of Electronic Data Gathering, Analysis, and Retrieval (EDGAR) searches. Our results show that retail investors are responsible for roughly 85% of the EDGAR searches that generate SBP groups. Overall, our study provides new evidence of a significant demand-side commonality associated with SBP affiliations.
Longitudinal Comparison of Continuing Medical Education Learning Objectives and Intent-to-Change Statements of Participants
Authors: Dunson Blake , Park Yoon Soo , Richards Boyd , Hirshfield Laura E. , Jensen Randy L.
Published: December 2021

Introduction:

Successful completion of continuing medical education (CME) activities is often required for ongoing physician board certification, licensure, and hospital privileges. CME activities are designed to address professional knowledge or practice gaps. The authors examined participants' “intent to change” after CME activities to evaluate whether CME activity content was suitably linked with the stated learning objectives.

Methods:

The authors performed a retrospective mixed-methods thematic content analysis of written and electronic records from American Association of Neurological Surgeons–sponsored CME activities. Data from 2011 through 2016 were analyzed using a quantitative, deductive content analysis approach. Data were examined for each year separately as well as longitudinally over the six consecutive years. Intent-to-change data that did not align with meeting objectives were analyzed inductively using a qualitative content analysis approach to explore potential unintended learning themes.

Results:

The authors examined 85 American Association of Neurological Surgeons CME activities (424 CME objectives). The objectives were compared with 1950 intent-to-change statements. Thematic patterns of recurrent intent-to-change statements that matched with CME objectives included topics of resident education, complication avoidance, clinical best practices and evidence, new innovations, and novel surgical techniques. Just over a third of intent-to-change statements (37.3%) were not related to any meeting objective. Approximately a quarter of these unmatched statements led to new learning objectives in subsequent years.

Conclusions:

An examination of CME learning objectives and participant intent-to-change statements provides information for examination of both meeting planner and learner attitudes for future CME activity planning.
Effectiveness and Dissemination of the Interprofessional Pediatric Pain PRN Curriculum
Authors: Manworren Renee C. B. , Basco Megan
Published: December 2021

Introduction:

Cultural transformation is needed for health care to be sensitive to children's pain. The Pediatric Pain Practice Registered Nurses (PRN) Curriculum is the first free, open access, downloadable, interprofessional pain continuing education (IPPCE) curriculum developed to empower health care professionals to translate evidence-based pain care into clinical practice. To evaluate the curriculum and its experiential flipped-learning strategies, we used a mixed methods approach.

Methods:

Interprofessional pediatric teams from eight health care systems evaluated the curriculum after attending Pediatric Pain PRN Courses in the Fall of 2017 (N = 90). Qualitative methods were used to evaluate the acceptability, feasibility, and utility of the curriculum and IPPCE strategies. Pain knowledge and attitudes were measured pre-IPPCE/post-IPPCE with the Pediatric Healthcare Provider's Knowledge & Attitude Survey Regarding Pain (PHPKAS). Web analytics were used to describe dissemination for the first year after the curriculum's webpage launch.

Results:

Learners rated their achievement of course objectives as moderate–great. PHPKAS scores significantly increased (P < .0005); but significant differences in physician and nurse PHPKAS question responses pre-IPPCE/post-IPPCE were found. Within 2 years of the IPPCE, three health care systems were certified as Childkind Hospitals, five Pediatric Pain PRN Programs were established, and various practice changes and improved patient outcomes, such as decreased hospital lengths of stay and emergency department returns for pain, were realized. Curriculum dissemination was global.

Discussion:

Results support the acceptability, effectiveness, feasibility, utility, and global dissemination of the curriculum and IPPCE strategies. More rigorous patient outcome data are needed; however, this study demonstrated the benefit of a free, open-access, downloadable, interprofessional health care provider continuing education curriculum.
Rho kinase inhibition ameliorates vascular remodeling and blood pressure elevations in a rat model of apatinib-induced hypertension
Authors: Li Caie , Ma Liping , Wang Qiongying , Shao Xuejiao , Guo Lu , Chen Jianshu , Wang Wenjuan , Yu Jing
Published: December 2021

Objectives:

Hypertension is one of the major adverse effects of tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factors. However, the mechanism underlying TKIs-induced hypertension remains unclear. Here, we explored the role of the RhoA/Rho kinase (ROCK) signaling pathway in elevation of blood pressure (BP) induced by apatinib, a selective TKI approved in China for treatment of advanced or metastatic gastric cancer. A nonspecific ROCK inhibitor, Y27632, was then combined with apatinib and its efficacy in alleviating apatinib-induced hypertension was evaluated.

Methods:

Normotensive female Wistar–Kyoto rats were exposed to two different doses of apatinib, or apatinib combined with Y27632, or vehicle for 2 weeks. BP was monitored by a tail-cuff plethysmography system. The mRNA levels and protein expression in the RhoA/ROCK pathway were determined, and vascular remodeling assessed.

Results:

Administration of either a high or low dose of apatinib was associated with a rapid rise in BP, reaching a plateau after 12 days. Apatinib treatment mediated upregulation of RhoA and ROCK II in the mid-aorta, more significant in the high-dose group. However, ROCK I expression showed no statistically significant differences. Furthermore, the mRNA level of GRAF3 decreased dose-dependently. Apatinib administration was also associated with decreased levels of MLCP, and elevated endothelin-1 (ET-1) and collagen I, which were accompanied with increased mid-aortic media. However, treatment with Y27632 attenuated the above changes.

Conclusion:

These findings suggest that activation of the RhoA/ROCK signaling pathway could be the underlying mechanism of apatinib-induced hypertension, while ROCK inhibitor have potential therapeutic value.
Rapid Viral Testing and Antibiotic Prescription in Febrile Children With Respiratory Symptoms Visiting Emergency Departments in Europe
Authors: Tan Chantal D. , Hagedoorn Nienke N. , Dewez Juan E. , Borensztajn Dorine M. , von Both Ulrich , Carrol Enitan D. , Emonts Marieke , van der Flier Michiel , de Groot Ronald , Herberg Jethro , Kohlmaier Benno , Levin Michael , Lim Emma , Maconochie Ian K. , Martinon-Torres Federico , Nijman Ruud G. , Pokorn Marko , Rivero-Calle Irene , Strle Franc , Tsolia Maria , Vermont Clementien L. , Yeung Shunmay , Zachariasse Joany M. , Zenz Werner , Zavadska Dace , Moll Henriette A.
Published: December 2021

Background.

Inappropriate antibiotic prescribing often occurs in children with self-limiting respiratory tract infections, contributing to antimicrobial resistance. It has been suggested that rapid viral testing can reduce inappropriate antibiotic prescribing. We aimed to assess the association between rapid viral testing at the Emergency Department (ED) and antibiotic prescription in febrile children.

Methods.

This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0–18 years) attending 12 European EDs. In children with respiratory symptoms visiting 6 EDs equipped with rapid viral testing, we performed multivariable logistic regression analysis regarding rapid viral testing and antibiotic prescription adjusted for patient characteristics, disease severity, diagnostic tests, focus of infection, admission, and ED.

Results.

A rapid viral test was performed in 1061 children (8%) and not performed in 11,463 children. Rapid viral test usage was not associated with antibiotic prescription (aOR 0.9, 95% CI: 0.8–1.1). A positive rapid viral test was associated with less antibiotic prescription compared with children without test performed (aOR 0.6, 95% CI: 0.5–0.8), which remained significant after adjustment for CRP and chest radiograph result. Twenty percent of the positively tested children received antibiotics. A negative rapid viral test was not associated with antibiotic prescription (aOR 1.2, 95% CI: 1.0–1.4).

Conclusions.

Rapid viral test usage did not reduce overall antibiotic prescription, whereas a positive rapid viral test did reduce antibiotic prescription at the ED. Implementation of rapid viral testing in routine emergency care and compliance to the rapid viral test outcome will reduce inappropriate antibiotic prescribing at the ED.