bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental trajectories of sensitivity to threat in children and adolescents predict larger medial frontal theta differentiation during response inhibition
Authors: Heffer Taylor , van Noordt Stefon , Willoughby Teena
Published: March 2023

Sensitivity to threat (ST) is thought to be a hallmark of the onset and maintenance of anxiety, which often manifests behaviorally as withdrawal, increased arousal and hypervigilant monitoring of performance. The current study investigated whether longitudinal trajectories of ST were linked to medial frontal (MF) theta power dynamics, a robust marker of performance monitoring. Youth (N = 432, Mage = 11.96 years) completed self-report measures of threat sensitivity annually for 3 years. A latent class growth curve analysis was used to identify distinct profiles of threat sensitivity over time. Participants also completed a GO/NOGO task while electroencephalography was recorded. We identified three threat sensitivity profiles: (i) high (n = 83), (ii) moderate (n = 273) and (iii) low ( n= 76). Participants in the high threat sensitivity class had greater levels of MF theta power differentiation (NOGO-GO) compared to participants in the low threat sensitivity class, indicating that consistently high threat sensitivity is associated with neural indicators of performance monitoring. Of concern, both hypervigilant performance monitoring and threat sensitivity have been associated with anxiety; thus, youth with high threat sensitivity may be at risk for the development of anxiety.
Insular and Striatal Correlates of Uncertain Risky Reward Pursuit in Schizophrenia
Authors: Purcell John R , Brown Joshua W , Tullar Rachel L , Bloomer Bess F , Kim Dae-Jin , Moussa-Tooks Alexandra B , Dolan-Bennett Katherine , Bangert Brianna M , Wisner Krista M , Lundin Nancy B , O’Donnell Brian F , Hetrick William P
Published: March 2023

Background and Hypothesis

Risk-taking in specific contexts can be beneficial, leading to rewarding outcomes. Schizophrenia is associated with disadvantageous decision-making, as subjects pursue uncertain risky rewards less than controls. However, it is unclear whether this behavior is associated with more risk sensitivity or less reward incentivization. Matching on demographics and intelligence quotient (IQ), we determined whether risk-taking was more associated with brain activation in regions affiliated with risk evaluation or reward processing.

Study Design

Subjects (30 schizophrenia/schizoaffective disorder, 30 controls) completed a modified, fMRI Balloon Analogue Risk Task. Brain activation was modeled during decisions to pursue risky rewards and parametrically modeled according to risk level.

Study Results

The schizophrenia group exhibited less risky-reward pursuit despite previous adverse outcomes (Average Explosions; F(1,59) = 4.06, P = .048) but the comparable point at which risk-taking was volitionally discontinued (Adjusted Pumps; F(1,59) = 2.65, P = .11). Less activation was found in schizophrenia via whole brain and region of interest (ROI) analyses in the right (F(1,59) = 14.91, P < 0.001) and left (F(1,59) = 16.34, P < 0.001) nucleus accumbens (NAcc) during decisions to pursue rewards relative to riskiness. Risk-taking correlated with IQ in schizophrenia, but not controls. Path analyses of average ROI activation revealed less statistically determined influence of anterior insula upon dorsal anterior cingulate bilaterally (left: χ2 = 12.73, P < .001; right: χ2 = 9.54, P = .002) during risky reward pursuit in schizophrenia.

Conclusions

NAcc activation in schizophrenia varied less according to the relative riskiness of uncertain rewards compared to controls, suggesting aberrations in reward processing. The lack of activation differences in other regions suggests similar risk evaluation. Less insular influence on the anterior cingulate may relate to attenuated salience attribution or inability for risk-related brain region collaboration to sufficiently perceive situational risk.
A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia
Authors: de Witte Lot D , Munk Laursen Thomas , Corcoran Cheryl M , Kahn René S , Birnbaum Rebecca , Munk-Olsen Trine , Bergink Veerle
Published: March 2023

Background

Doxycycline and minocycline are brain-penetrant tetracycline antibiotics, which recently gained interest because of their immunomodulatory and neuroprotective properties. Observational studies have suggested that exposure to these drugs may decrease the risk to develop schizophrenia, but results are inconsistent. The aim of this study was to investigate the potential association between doxycycline use and later onset of schizophrenia.

Design

We used data from 1 647 298 individuals born between 1980 and 2006 available through Danish population registers. 79 078 of those individuals were exposed to doxycycline, defined as redemption of at least 1 prescription. Survival analysis models stratified for sex with time-varying covariates were constructed to assess incidence rate ratios (IRRs) for schizophrenia (ICD-10 code F20.xx), with adjustment for age, calendar year, parental psychiatric status, and educational level.

Results

In the non-stratified analysis, there was no association between doxycycline exposure and schizophrenia risk. However, men who redeemed doxycycline had a significantly lower incidence rate for schizophrenia onset compared to men that did not (IRR 0.70; 95% CI 0.57–0.86). By contrast, women had a significantly higher incidence rate for schizophrenia onset, compared to women that did not redeem doxycycline prescriptions (IRR 1.23; 95% CI 1.08, 1.40). The effects were not found for other tetracycline antibiotics (IRR 1.00; 95% CI 0.91, 1.09).

Conclusions

Doxycycline exposure is associated with a sex-dependent effect on schizophrenia risk. The next steps are replication of the results in independent well-characterized population cohorts, as well as preclinical studies to investigate sex-specific effects of doxycycline on biological mechanisms implicated in schizophrenia.
A Bayesian Network Approach to Social and Nonsocial Cognition in Schizophrenia: Are Some Domains More Fundamental than Others?
Authors: Abplanalp Samuel J , Lee Junghee , Horan William P , Kern Robert S , Penn David L , Green Michael F
Published: March 2023

Objectives

Social and nonsocial cognition are defined as distinct yet related constructs. However, the relative independence of individual variables—and whether specific tasks directly depend on performance in other tasks—is still unclear. The current study aimed to answer this question by using a Bayesian network approach to explore directional dependencies among social and nonsocial cognitive domains.

Study Design

The study sample comprised 173 participants with schizophrenia (71.7% male; 28.3% female). Participants completed 5 social cognitive tasks and the MATRICS Consensus Cognitive Battery. We estimated Bayesian networks using directed acyclic graph structures to examine directional dependencies among the variables.

Study Results

After accounting for negative symptoms and demographic variables, including age and sex, all nonsocial cognitive variables depended on processing speed. More specifically, attention, verbal memory, and reasoning and problem solving solely depended on processing speed, while a causal chain emerged between processing speed and visual memory (processing speed → attention → working memory → visual memory). Social processing variables within social cognition, including emotion in biological motion and empathic accuracy, depended on facial affect identification.

Conclusions

These results suggest that processing speed and facial affect identification are fundamental domains of nonsocial and social cognition, respectively. We outline how these findings could potentially help guide specific interventions that aim to improve social and nonsocial cognition in people with schizophrenia.
Case series: expanding diagnostic markers in postorgasmic illness syndrome
Authors: Rosetti Leah , Kanani Amin , Witherspoon Luke , Flannigan Ryan , Elliott Stacy
Published: March 2023

Introduction

Postorgasmic illness syndrome (POIS) is a rare condition in which individuals develop generalized and flu-like symptoms after ejaculation. Several mechanisms and treatments for this disorder have been proposed but many questions remain.

Aims

We sought to present a summary of literature to date and highlight common symptoms, associated features, comorbidities, and laboratory findings in a clinical sample of patients with POIS.

Methods

We conducted a retrospective chart review of 6 patients with POIS in our clinic and presented compiled results.

Results

We identified newly described non–flu-like presentations, onset of symptoms with high states of arousal without ejaculation, and presence of psychiatric comorbidity in a majority of patients. We did not identify a postorgasm allergic response with bloodwork available.

Conclusion

POIS remains a poorly understood condition that likely comprises a number of different clinical entities. Further research on a larger clinical sample is necessary to better characterize POIS and understand its biological and psychological basis.
Our Friends Keep Us Together: The Stability of Adolescents’ Cross-Race Friendships
Authors: Neray Balint , Copeland Molly , Moody James
Published: March 2023

Substantive racial integration depends on both access to cross-race friendship opportunities (demographic integration) and the development of stable and rewarding social relations (social integration). Yet, we know little about the relative stability of cross-race friendship nominations over time. Cross-race friendships are also experienced within social contexts, where other individual, dyadic, and contextual factors may simultaneously affect whether such ties persist. Based on longitudinal network data on over 2,000 students in multiple communities, we test whether cross-race friendships are more or less stable than same-race friendships. We find that cross-race friendships at first glance appear less likely to persist than same-race friendships, but cross-race ties become no less stable than same-race ties after accounting for other social factors, including reciprocity and shared friends. This pattern suggests a threshold process where strong, socially recognized ties embedded among peers face less threat to maintaining friendship stability.
Vaccine Hesitancy and the Accumulation of Distrust
Authors: Decoteau Claire Laurier , Sweet Paige L
Published: March 2023

Scholarship on vaccine hesitancy portrays racially marginalized populations as undervaccinated, undereducated, or under the influence of social movements. However, these explanations cannot account for vaccine hesitancy among the Somali diaspora in Minneapolis. Drawing on interviews with Somali parents and health, education, and government professionals in Minneapolis, we argue that vaccine hesitancy among marginalized populations stems from accumulated distrust. Somalis’ distrust is relationally produced through their interactions with the healthcare system, where they experience both epistemic and corporeal harm. When health experts ignore Somalis’ history, knowledge, and embodied experiences, distrust accumulates. Our account reveals different expressions of vaccine hesitancy, thus highlighting the contingent, relational, and cumulative nature of distrust.
Genome evolution of dengue virus serotype 1 under selection by Wolbachia pipientis in Aedes aegypti mosquitoes
Authors: Thi Hue Kien Duong , Edenborough Kathryn , da Silva Goncalves Daniela , Thuy Vi Tran , Casagrande Etiene , Thi Le Duyen Huynh , Thi Long Vo , Thi Dui Le , Thi Tuyet Nhu Vu , Thi Giang Nguyen , Thi Xuan Trang Huynh , Lee Elvina , Donovan-Banfield I’ah , Thi Thuy Van Huynh , Minh Nguyet Nguyen , Thanh Phong Nguyen , Van Vinh Chau Nguyen , Wills Bridget , Yacoub Sophie , Flores Heather , Simmons Cameron
Published: March 2023

The introgression of antiviral strains of Wolbachia into Aedes aegypti mosquito populations is a public health intervention for the control of dengue. Plausibly, dengue virus (DENV) could evolve to bypass the antiviral effects of Wolbachia and undermine this approach. Here, we established a serial-passage system to investigate the evolution of DENV in Ae. aegypti mosquitoes infected with the wMel strain of Wolbachia. Using this system, we report on virus genetic outcomes after twenty passages of serotype 1 of DENV (DENV-1). An amino acid substitution, E203K, in the DENV-1 envelope protein was more frequently detected in the consensus sequence of virus populations passaged in wMel-infected Ae. aegypti than wild-type counterparts. Positive selection at residue 203 was reproducible; it occurred in passaged virus populations from independent DENV-1-infected patients and also in a second, independent experimental system. In wild-type mosquitoes and human cells, the 203K variant was rapidly replaced by the progenitor sequence. These findings provide proof of concept that wMel-associated selection of virus populations can occur in experimental conditions. Field-based studies are needed to explore whether wMel imparts selective pressure on DENV evolution in locations where wMel is established.
The Economic Impact of Deepening Trade Agreements
Authors: Fontagné Lionel , Rocha Nadia , Ruta Michele , Santoni Gianluca
Published: March 2023

This paper explores the economic impacts of preferential trade agreements, conditional on their level of ambition. It clusters 278 agreements, encompassing 910 provisions over 18 policy areas and estimates the trade elasticity for the different clusters. These elasticities are used in a series of general-equilibrium counterfactual situations for endowment economies, revealing that deepening existing agreements (the intensive margin of regional integration) could boost world trade by 3.9 percent and world GDP by 0.9 percent. The expected gains from deepening agreements within or across regions vary depending on the initial depth of agreements and the size of regional markets.
Pathogenicity of Rice Blast (Pyricularia oryzae) Isolates from the Ryukyu Archipelago, Okinawa, in Southern Japan
Authors: Ajitomi Atsushi , Khan Mohanmad Ashik Iqbal , Nguyen Thi Nhai , Nguyen Thi Oanh , Fukuta Yoshimichi
Published: March 2023

Rice ( Oryza sativa L.) is a major crop, and blast ( Pyricularia oryzae Cavara) has been the most serious disease in Japan. Ninety-seven rice blast isolates were collected from the Ryukyu Archipelago, including Okinawa Main Island (OK) and Yaeyama Islands (YA), in Japan's southern region. The pathogenicities of blast isolates were clarified by an inoculation test based on the resistance reaction patterns to differential varieties (DVs) and a susceptible control, Lijiangxintuanheigu (LTH). Virulent isolates occurred with high frequencies to LTH and DVs for Pish, Pia, Pii, Pi3, Pik-s, and Pi19(t). The DVs for Pib, Pik-m, Pi1, Pik-h, Pik, Pik-p, Pi7(t), Pi9(t), Piz, Piz-5, Piz-t, Pita-2 (two lines), Pil2(t), and Pi20(t) had low frequencies, and those for Pit, Pi5(t), and Pita (two lines) had intermediate frequencies. These isolates were classified into two groups (I and II) based on the reaction patterns to DVs by cluster analysis. The virulence of the blast isolates from cluster II against DVs for Pit, Pi5(t), Pita (two lines), and Pi20(t) was much greater than that of those in cluster I. Cluster I blast isolates were distributed dominantly in OK, and those of cluster II were in YA. This is the first report on the distribution of blast races in the Ryukyu Archipelago in Japan. This information will be useful for developing sustainable protection systems and rice breeding against blast disease.
Environmental Conditions Modulate Plant Virus Vertical Transmission and Survival of Infected Seeds
Authors: Gutiérrez-Sánchez Álvaro , Cobos Alberto , López-Herranz Marisa , Canto Tomás , Pagán Israel
Published: March 2023

Seed transmission is a major mode for plant virus persistence and dispersal, as it allows for virus survival within the seed in unfavorable conditions and facilitates spread when they become more favorable. To access these benefits, viruses require infected seeds to remain viable and germinate in altered environmental conditions, which may also be advantageous for the plant. However, how environmental conditions and virus infection affect seed viability, and whether these effects modulate seed transmission rate and plant fitness, is unknown. To address these questions, we utilized turnip mosaic virus, cucumber mosaic virus, and Arabidopsis thaliana as model systems. Using seeds from plants infected by these viruses, we analyzed seed germination rates, as a proxy of seed viability, and virus seed transmission rate under standard and altered temperature, CO2, and light intensity. With these data, we developed and parameterized a mathematical epidemiological model to explore the consequences of the observed alterations on virus prevalence and persistence. Altered conditions generally reduced overall seed viability and increased virus transmission rate compared with standard conditions, which indicated that under environmental stress, infected seeds are more viable. Hence, virus presence may be beneficial for the host. Subsequent simulations predicted that enhanced viability of infected seeds and higher virus transmission rate may increase virus prevalence and persistence in the host population under altered conditions. This work provides novel information on the influence of the environment in plant virus epidemics.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Reduced Use of Invasive Procedures Leads to a Change of Frequencies of Prenatally Detected Chromosomal Aberrations: Population Data From the Years 2012–2016
Authors: Sipek Antonin , Gregor Vladimir , Sipek Antonin , Klaschka Jan , Maly Marek , Calda Pavel
Published: March 2023

Prenatal chromosomal aberration screening mainly focuses on the identification of the autosomal trisomy of chromosomes 21, 18, and 13 (Down syndrome, Edwards syndrome, and Patau syndrome, respectively). This screening may be often combined with other first-semester screenings to promote earlier detection of other pregnancy complications, including chromosomal aberrations. In the Czech Republic, there is no unified policy for prenatal screening. The main prenatal diagnostic centers provide combined prenatal screening in the first semester, whereas some conduct biochemical screening in the second trimester. Those with positive screening results or abnormal ultrasound are offered invasive diagnostic procedures, such as chorionic villus sampling (CVS) or amniocentesis, along with additional genetic testing. Whereas the number of amniocenteses has declined, the number of CVS is increasing. The aim of this study was to examine the results of chromosomal aberrations screening in a population with a high rate of first-trimester screening and low rate of noninvasive prenatal testing.

This was a population-based study, using data from the National Registry of Congenital Anomalies of the Czech Republic from 2012 to 2016. Included were all cases of prenatally diagnosed chromosomal aberrations. The proportions of the autosomal trisomies and other chromosomal aberrations were calculated and compared. The denominator was the number of live births per year.

A total of 3009 prenatally diagnosed cases of chromosomal aberrations were identified during the study period. The most common aberrations were the major autosomal trisomies (1885 cases [62.6%]). The number of invasive prenatal diagnostic procedures decreased from 11,517 cases (1099.54 per 10,000) to 7042 cases (622.73 per 10,000) during the study period. From 2012 to 2016, the number of prenatally diagnosed major autosomal trisomies increased (329 cases [30.86 per 10,000] vs 423 cases [37.41 per 10,000], respectively; Poisson regression: P = 0.014), and the number of other aberrations decreased (246 cases [23.07 per 10,000] vs 217 cases [19.19 per 10,000], respectively; Poisson regression: P = 0.017). There was a highly statistically significant increase of 57.22% in 2012 to 66.09% in 2016 in the rate of the major autosomal trisomies group (logistic regression: P < 0.001).

The study found that, during a 5-year period, when invasive prenatal diagnostic procedures declined, there was also a decrease in the number of nonmajor chromosomal aberrations. Noninvasive prenatal testing was not shown to impact these data.
Endocervical Sampling in Women With Suspected Cervical Neoplasia: A Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies
Authors: Damkjær Mathias , Laursen Jacob Brink , Petersen Lone Kjeld , Schledermann Doris , Booth Berit Bargum , Dolleris Britta Blume , Laursen Henrik Sehested , Schroll Jeppe Bennekou
Published: March 2023

HPV-induced cervical neoplasia progresses through a predictable natural course of disease, starting with mild cervical intraepithelial neoplasia (CIN1) and developing into severe degrees (CIN3) and eventually to invasive cervical cancer. A positive finding on initial screening for cervical neoplasia results in further diagnostics involving sampling with an endocervical brush (EB) or endocervical curettage (ECC). There exists a considerable variation in the choice of test method for obtaining these endocervical or cervical canal samples.

This meta-analysis aimed to retrospectively determine the diagnostic test accuracy (DTA) and patient discomfort of the EB and ECC for the detection of cervical neoplasia in women with any indication for colposcopy, biopsies, and endocervical sampling. All diagnostic studies and randomized clinical trials that included women with abnormal cytology results in cervical cancer screening or women with red flag symptoms undergoing colposcopy, biopsy, EB, or ECC were included. The target condition was cervical neoplasia, and the reference standard was the final histological result. A bivariate random-effects model was used to determine summary estimates of sensitivity and specificity with 95% confidence intervals (CIs). A meta-analysis assessing summary relative risk for inadequate samples was also conducted.

A total of 7 studies were included in the meta-analysis with a total sample size of 1097 women. Three studies were randomized clinical trials, and 4 were cohort studies, and they took place between 1988 and 2013. A DTA meta-analysis for summary sensitivity and specificity found an overall pooled sensitivity of 81% (95% CI, 48–95) for EB and 70% (95% CI, 42–89) for ECC. The overall pooled specificity was 73% (95% CI, 36–93) for EB and 81% (95% CI, 56–94). The overall relative risk was found to be 2.53 (95% CI, 0.58–11.0; P = 0.215) for ECC compared with EB for inadequate samples. Two studies reported patient discomfort as an outcome, and only a single study reported a significant difference between ECC and EB in favor of ECC (visual analog scale score 2.55 vs 1.99).

The results of this meta-analysis comparing the DTA of EB and ECC found no significant difference between EB and ECC in DTA, inadequate sampling rate, or adverse effects. The overall sensitivity was found to be slightly higher for EB than for ECC and the specificity to be slightly higher for ECC than EB, although these results were not statistically significant.
The Proportion of Patients With Rheumatoid Arthritis Achieving ACR20/50/70; Consistent Patterns of a 60/40/20 as Demonstrated by a Systematic Review and Meta-analysis
Authors: Mokbel Abir , Movahedi Mohammad , Philippopoulos Eleni , Ojani Pantea , Keystone Edward C.
Published: March 2023

Objectives

We aimed to demonstrate that the proportion of rheumatoid arthritis patients achieving 20%/50%/70% improvement in American College of Rheumatology (ACR20/50/70) responses to Food and Drug Administration–approved biologic disease-modifying antirheumatic drugs (bDMARDs) after an inadequate response to methotrexate (MTX) and after failure of the first bDMARDs followed a consistent pattern.

Methods

This systematic review and meta-analysis was performed in accordance with MECIR (Methodological Expectations for Cochrane Intervention Reviews) standards. Two separate groups of randomized controlled trials were included: the first group included studies with biologic-naive patients who added bDMARD to MTX as intervention arm compared with the placebo plus MTX group. The second group included biologic-irresponsive (IR) patients who used a second bDMARD plus MTX after the first bDMARD failure compared with placebo plus MTX group. Primary outcome was defined as the proportion of rheumatoid arthritis patients achieving ACR20/50/70 responses at 24 ± 6 weeks.

Results

Twenty-one studies initiated between 1999 and 2017 were included: 15 studies for the biologic-naive group and 6 studies for the biologic-IR group. For the biologic-naive group, the proportions of patients achieving ACR20/50/70 were 61.4% (95% confidence interval [CI], 58.7%–64.1%), 37.8% (95% CI, 34.8%–40.8%), and 18.8% (95% CI, 16.1%–21.4%), respectively. For the biologic-IR group, proportions of patients achieving ACR20/50/70 were 48.5% (95% CI, 42.2%–54.8%), 27.3% (95% CI, 21.6%–33.0%), and 12.9% (95% CI, 11.3%–14.8%), respectively.

Conclusion

We were able to systematically demonstrate that ACR20/50/70 responses to biologic-naive follow a consistent pattern of 60%, 40%, and 20%, respectively. We also demonstrated that the ACR20/50/70 responses to a biologic IR follow a certain pattern of 50%, 25%, and 12.5%, respectively.
GENDER-RELATED VARIATIONS IN PATHOPHYSIOLOGICAL RESPONSES TO METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS PNEUMONIA AND SEPSIS
Authors: Homma Kento , Liu Keibun , Niimi Yosuke , Fukuda Satoshi , Hirasawa Yasutaka , Baljinnyam Tuvshintugs , Bazhanov Nikolay , Nawgiri Ranjana , Muthukumarana Palawinnage , Lucas Rudolf , Prough Donald , Enkhbaatar Perenlei
Published: March 2023

In preclinical studies, the protective effects of female sex hormones and the immunosuppressive effects of male sex hormones were demonstrated. However, gender-related differences in multiorgan failure and mortality in clinical trials have not been consistently explained. This study aims to investigate gender-related differences in the development and progression of sepsis using a clinically relevant ovine model of sepsis. Adult Merino male (n=7) and female (n=7) sheep were surgically prepared with multiple catheters before the study. To induce sepsis, bronchoscopy instilled methicillin-resistant Staphylococcus aureus into sheep's lungs. The time from the bacterial inoculation until the modified Quick Sequential Organ Failure Assessment (q-SOFA) score became positive was measured and analyzed primarily. We also compared the SOFA score between these male and female sheep over time. Survival, hemodynamic changes, the severity of pulmonary dysfunction, and microvascular hyperpermeability were also compared. The time from the onset of bacterial inoculation to the positive q-SOFA in male sheep was significantly shorter than in female sheep. Mortality was not different between these sheep (14% vs. 14%). There were no significant differences in hemodynamic changes and pulmonary function between the two groups at any time point. Similar changes in hematocrit, urine output, and fluid balance were observed between females and males. The present data indicate that the onset of multiple organ failure and progression of sepsis is faster in male sheep than in female sheep, even though the severity of cardiopulmonary function is comparable over time. Further studies are warranted to validate the above results.
EVALUATION OF HYDROCORTISONE, VITAMIN C, AND THIAMINE FOR THE TREATMENT OF SEPTIC SHOCK: A RANDOMIZED CONTROLLED TRIAL (THE HYVITS TRIAL)
Authors: Mohamed Adham , Abdelaty Mohamed , Saad Mohamed O. , Shible Ahmed , Mitwally Hassan , Akkari Abdel-Rauof , Elbuzidi Abdurrahmaan , Bintaher Awadh , Hashim Ahmed , Abdelrahim Magid , Afzal Mohammad , El-Enany Rasha , El-Hamid Maha , Bakdach Dana , Karic Edin , Shehatta Ahmed , Ibrahim Abdul-Salam , Lance Marcus , Hssain Ali Ait , Hassan Ibrahim
Published: March 2023

Purpose: The aim of the study is to evaluate the effect of combined hydrocortisone, vitamin C, and thiamine (triple therapy) on the mortality of patients with septic shock. Methods: This multicenter, open-label, two-arm parallel-group, randomized controlled trial was conducted in four intensive care units in Qatar. Adult patients diagnosed with septic shock requiring norepinephrine at a rate of ≥0.1 μg/kg/min for ≥6 h were randomized to a triple therapy group or a control group. The primary outcome was in-hospital mortality at 60 days or at discharge, whichever occurred first. Secondary outcomes included time to death, change in Sequential Organ Failure Assessment (SOFA) score at 72 h of randomization, intensive care unit length of stay, hospital length of stay, and vasopressor duration. Results: A total of 106 patients (53 in each group) were enrolled in this study. The study was terminated early because of a lack of funding. The median baseline SOFA score was 10 (interquartile range, 8–12). The primary outcomes were similar between the two groups (triple therapy, 28.3% vs. control, 35.8%; P = 0.41). Vasopressor duration among the survivors was similar between the two groups (triple therapy, 50 h vs. control, 58 h; P = 0.44). Other secondary and safety endpoints were similar between the two groups. Conclusion: Triple therapy did not improve in-hospital mortality at 60 days in critically ill patients with septic shock or reduce the vasopressor duration or SOFA score at 72 h. Trial Registration:
ClinicalTrials.gov identifier: NCT03380507. Registered on December 21, 2017.
THE IL-33/ST2 AXIS PROMOTES ACUTE RESPIRATORY DISTRESS SYNDROME BY NATURAL KILLER T CELLS
Authors: Zou Lijuan , Dang Wenpei , Tao Yiming , Zhao Hui , Yang Bin , Xu Xinxin , Li Yongsheng
Published: March 2023

Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled inflammation, which manifests as leukocyte infiltration and lung injury. However, the molecules that initiate this infiltration remain incompletely understood. We evaluated the effect of the nuclear alarmin IL-33 on lung damage and the immune response in LPS-induced lung injury. We established a LPS-induced lung injury mouse model. We used genetically engineered mice to investigate the relationship among the IL-33/ST2 axis, NKT cells, and ARDS. We found that IL-33 was localized to the nucleus in alveolar epithelial cells, from which it was released 1 h after ARDS induction in wild-type (WT) mice. Mice lacking IL-33 (IL-33−/−) or ST2 (ST2−/−) exhibited reduced neutrophil infiltration, alveolar capillary leakage, and lung injury in ARDS compared with WT mice. This protection was associated with decreased lung recruitment and activation of invariant nature killer (iNKT) cells and activation of traditional T cells. Then, we validated that iNKT cells were deleterious in ARDS in CD1d−/− and Vα14Τg mice. Compared with WT mice, Vα14Τg mice exhibited increased lung injury in ARDS, and the CD1d−/− mice showed outcomes opposite those of the Vα14Τg mice. Furthermore, we administered a neutralizing anti-ST2 antibody to LPS-treated WT and Vα14Τg mice 1 h before LPS administration. We found that IL-33 promoted inflammation through NKT cells in ARDS. In summary, our results demonstrated that the IL-33/ST2 axis promotes the early uncontrolled inflammatory response in ARDS by activating and recruiting iNKT cells. Therefore, IL-33 and NKT cells may be therapeutic target molecules and immune cells, respectively, in early ARDS cytokine storms.
Comments on Case Report: A fatal case of Aspergillus felis infection in an immunocompetent host.
Authors: Barrs Vanessa R.
Published: March 2023

Not applicable
Prevention of liver fibrosis and steatosis progression among heavy drinkers with and without HIV after 30-day drinking-reduction program
Authors: Ahn Seungjun , Richards Veronica , Thomas Emmanuel , Jayaweera Dushyantha , Govind Varan , Li Zhigang , Cohen Ronald A. , Cook Robert L.
Published: March 2023

Background

This is the first attempt to assess changes in liver abnormalities before and after contingency management (CM) to reduce heavy drinking beyond 30-days of follow-up.

Objective

The main objective was to determine whether liver fibrosis and steatosis, measured using FibroScan, change significantly between baseline, 30-days, and 90-days among older adults who drink heavily at baseline, enrolled in the CM intervention for alcohol reduction. The secondary aim of the study was to assess whether the changes in liver outcome measures differ across alcohol consumption categories.

Methods

A prospective study (ClinicalTrials.govregistry:NCT03353701) of 46 older adults (63% male, 76.1% Black, mean age = 56.4) with heavy drinking at the baseline, living with or without HIV infection was evaluated. A linear mixed-effects model was used to analyze the FibroScan Transient Elastography (TE for fibrosis) and Controlled Attenuation Parameter (CAP for steatosis).

Results

There were no significant changes in liver fibrosis and steatosis measures after 90-days of drinking abstinence among heavy drinkers with or without stratified TE or CAP values at baseline.

Conclusions

CM for drinking reduction may not be effective at least short-term prospective in preventing liver fibrosis and steatosis progression for subjects without severe liver disease at baseline.
High-sensitivity C-reactive protein modifies the prognostic value of platelet count for clinical outcomes after ischemic stroke
Authors: Liu Fanghua , Yang Pinni , Wang Yinan , Shi Mengyao , Wang Ruirui , Xu Qingyun , Peng Yanbo , Chen Jing , Zhang Jintao , Wang Aili , Xu Tan , Zhang Yong-hong , He Jiang
Published: March 2023

Background

Platelets play a critical role in the formation of thrombosis and embolism, and high-sensitivity C-reactive protein (HS-CRP) is an important indicator of inflammation, which contribute to the development of ischemic stroke development. This study aimed to examine whether the relationship between baseline platelet count and adverse clinical outcomes is modulated by HS-CRP in patients with ischemic stroke.

Methods

A total of 3267 patients with ischemic stroke were included in the analysis. The primary outcome was a combination of death and major disability (modified Rankin Scale [mRS] score ≥3) at 1 year after ischemic stroke. Secondary outcomes included major disability, death, vascular events, composite outcome of vascular events or death, and an ordered 7-level categorical score of the mRS at 1 year. Multivariate logistic regression and Cox proportional hazards regression models were used to assess the association between the baseline platelet count and clinical outcomes stratified by HS-CRP levels when appropriate, odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI) were calculated for the highest quartiles of platelet counts compared with the lowest quartile.

Results

The elevated platelet count was associated with the primary outcome (OR, 3.14;95% CI, 1.77-5.58), major disability (OR, 2.07;95%CI, 1.15-3.71), death (HR, 2.75;95%CI, 1.31-5.79), composite outcome of vascular events or death (HR, 2.57;95%CI, 1.38-4.87), and the ordered 7-level categorical score of the mRS at 1 year (OR, 2.01 [95%CI, 1.33-3.04]) among patients with high HS-CRP levels (allPtrend<0.05). However, platelet count was not associated with the primary outcome (OR, 1.13; 95%CI, 0.75-1.71), major disability (OR, 1.34; 95%CI, 0.87-2.08), death (HR, 0.48; 95%CI, 0.19-1.24), composite outcome of vascular events or death (HR, 0.79; 95%CI, 0.45-1.37), and the ordered 7-level categorical score of the mRS at 1 year (OR, 1.17; 95%CI, 0.91-1.49) (allPtrend>0.05) in those with low HS-CRP levels. There was an interaction effect of platelet count and HS-CRP on the primary outcome, death, composite outcome of vascular events or death, and the ordered 7-level categorical score of the mRS at 1 year after ischemic stroke (allPinteraction<0.05).

Conclusions

An elevated platelet count was associated with adverse clinical outcomes in ischemic stroke patients with high HS-CRP levels but not in those with low HS-CRP levels, the HS-CRP level had a modifying effect on the association between platelet count and clinical outcomes in patients with ischemic stroke, suggesting that strategies for anti-inflammatory and antiplatelet therapy should be developed according to the results of both platelet and HS-CRP testing.
Prevalence and Factors Associated with Cryptosporidiosis Among Livestock and Dogs in Kasese District, Uganda: A Cross-Sectional Study
Authors: Kankya Clovice , Okello Justine , Natweta Baguma James , Wambi Rogers , Rose Ninsiima Lesley , Tubihemukama Methodius , Tricia Kulabako Christine , Munyeme Musso , Hartnack Sonja , Okello Walter , Bugeza James , Muleme James
Published: March 2023

Background

Cryptosporidiosis is a common cause of diarrheal disease in livestock and dogs, and it can result in significant economic losses due to decreased productivity and higher treatment costs. The cryptosporidiosis burden in livestock and dogs is largely unknown and underexploited. We designed a cross-sectional research study to determine the prevalence and factors associated with cryptosporidiosis in livestock and dogs.

Methods

The questionnaire data was downloaded from the Kobotoolbox server in excel format for cleaning and analysis. Laboratory results were matched with the questionnaire data and statistical analysis was performed using STATA version 14 and R version 4.2.2. Descriptive statistics were conducted to determine the frequencies, percentages, and proportions of the different study variables. For the categorical variables, 95% binomial and multinomial confidence intervals were obtained using the commands BinomCI(), with Jeffreys approach, and MultinomCI() available in the DescTools package. To adjust for potential clustering within household, a logistic mixed model approach with household as random effect was chosen and performed using the package glmmTMB. The outcome was a positive or negative test result of each dog. A likelihood ratio test using the lmtest package was used to determine if a predictor was significantly associated with the outcome. To adjust for multiple comparisons, the multcomp package with Tukeys approach was used. First all variables were included in a univariable approach. Second all variables with p-values <0.2 were included in a multivariable model..

Results

Dogs were over 50times more likely to have the cryptosporidium infection compared to goat. With aOR 56.07, 95%CI= [10.2569,306.5307] and p-value <0.001. Furthermore, being of Mukonjo tribe was over 20times more likely to have cryptosporidiosis compared to being Musongora. At aOR 24.92, 95%CI= [3.6971,168.0655], p-value 0.0010. Additionally, persons who drunk water from the river ponds were 76.93 times more likely to have cryptosporidium infection compared to the counterparts whose source of drinking water were from protected sources with aOR 76.93, 95% CI= [3.71,1595.324] p-value= 0.0050.

Conclusion

Cryptosporidiosis still remains a big public health problem in Kasese District. Dogs are more at risk of having cryptosporidiosis whereas drinking from river ponds was highly attributed to acquiring cryptosporidiosis.
Manipulation in grazing, viral pressure and resource availability leads to success in the isolation of abundant marine bacteria
Authors: Rey-Velasco Xavier , Deulofeu Ona , Sanz-Sáez Isabel , Cardelús Clara , Ferrera Isabel , Gasol Josep M. , Sánchez Olga
Published: March 2023

Isolation of microorganisms is a useful approach to gather knowledge about their genomic properties, physiology, and ecology, in addition to allowing characterization of novel taxa. We performed an extensive isolation effort on samples from seawater manipulation experiments that were carried out during the four astronomical seasons in a coastal site in the NW Mediterranean to evaluate the impact of grazing, viral mortality, resource competition and light on bacterioplankton growth. Isolates were retrieved using two growth media and their full 16S rRNA gene was sequenced to assess their identity and compute their culturability across seasons and experimental conditions. A total of 1643 isolates were obtained, which mainly affiliated to classesGammaproteobacteria(44%),Alphaproteobacteria(26%) andBacteroidia(17%). The most commonly isolated genera wereAlteromonasandLimimaricola. While isolates varied across culture media, seasons and treatments, those pertaining to classGammaproteobacteriawere the most abundant in all experiments, whileBacteroidiawas preferentially enriched in the treatments with reduced grazing. Sixty-one isolates had a similarity below 97% to cultured taxa and are thus putatively novel. Comparison of isolate sequences with 16S rRNA gene amplicon sequences from the same samples showed that the percentage of reads corresponding to isolates was 21.4% within the whole dataset, with dramatical increases in summer virus-reduced (71%) and diluted (47%) treatments. In fact, we were able to isolate the top-10 abundant taxa in several experiments and from the whole dataset.

IMPORTANCE

The traditional observation that we can only culture 1% of bacteria for a given environment has recently been questioned on several grounds, among other reasons because it is importantly influenced by environmental conditions. We cultured a high amount of heterotrophic bacterial strains from experiments where seawater environmental conditions had been manipulated and found that decreasing grazing and viral pressure as well as rising nutrient availability are key factors increasing the success in isolating marine bacteria. Our data clearly suggests that the “1% culturability paradigm” needs to be revised and reinforces bacterial cultures as a powerful way to discover new taxa.
Systematic Identification of Post-Transcriptional Regulatory Modules
Authors: Khoroshkin Matvei , Buyan Andrey , Dodel Martin , Navickas Albertas , Yu Johnny , Trejo Fathima , Doty Anthony , Baratam Rithvik , Zhou Shaopu , Joshi Tanvi , Garcia Kristle , Choi Benedict , Miglani Sohit , Subramanyam Vishvak , Modi Hailey , Markett Daniel , Corces M. Ryan , Kulakovskiy Ivan V. , Mardakheh Faraz , Goodarzi Hani
Published: March 2023

In our cells, a limited number of RNA binding proteins (RBPs) are responsible for all aspects of RNA metabolism across the entire transcriptome. To accomplish this, RBPs form regulatory units that act on specific target regulons. However, the landscape of RBP combinatorial interactions remains poorly explored. Here, we performed a systematic annotation of RBP combinatorial interactions via multimodal data integration. We built a large-scale map of RBP protein neighborhoods by generatingin vivoproximity-dependent biotinylation datasets of 50 human RBPs. In parallel, we used CRISPR interference with single-cell readout to capture transcriptomic changes upon RBP knockdowns. By combining these physical and functional interaction readouts, along with the atlas of RBP mRNA targets from eCLIP assays, we generated an integrated map of functional RBP interactions. We then used this map to match RBPs to their context-specific functions and validated the predicted functions biochemically for four RBPs. This study highlights the previously underappreciated scale of the inter-RBP interactions, be it genetic or physical, and is a first step towards a more comprehensive understanding of post-transcriptional regulatory processes and their underlying molecular grammar.
Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study
Authors: Cousins Henry C. , Altman Russ B.
Published: March 2023

Background

Spironolactone has been proposed as a potential modulator of SARS-CoV-2 cellular entry. We aimed to measure the effect of spironolactone use on the risk of adverse outcomes following COVID-19 hospitalization.

Methods

We performed a retrospective cohort study of COVID-19 outcomes for patients with or without exposure to spironolactone, using population-scale claims data from the Komodo Healthcare Map. We identified all patients with a hospital admission for COVID-19 in the study window, defining treatment status based on spironolactone prescription orders. The primary outcomes were progression to respiratory ventilation or mortality during the hospitalization. Odds ratios (OR) were estimated following either 1:1 propensity score matching (PSM) or multivariable regression. Subgroup analysis was performed based on age, gender, body mass index (BMI), and dominant SARS-CoV-2 variant.

Findings

Among 898,303 eligible patients with a COVID-19-related hospitalization, 16,324 patients (1.8%) had a spironolactone prescription prior to hospitalization. 59,937 patients (6.7%) met the ventilation endpoint, and 26,515 patients (3.0%) met the mortality endpoint. Spironolactone use was associated with a significant reduction in odds of both ventilation (OR 0.82; 95% CI: 0.75-0.88; p < 0.001) and mortality (OR 0.88; 95% CI: 0.78-0.99; p = 0.033) in the PSM analysis, supported by the regression analysis. Spironolactone use was associated with significantly reduced odds of ventilation for all age groups, men, women, and non-obese patients, with the greatest protective effects in younger patients, men, and non-obese patients.

Interpretation

Spironolactone use was associated with a protective effect against ventilation and mortality following COVID-19 infection, amounting to up to 64% of the protective effect of vaccination against ventilation and consistent with an androgen-dependent mechanism. The findings warrant initiation of large-scale randomized controlled trials to establish a potential therapeutic role for spironolactone in COVID-19 patients.
The safety and efficacy of remimazolam tosylate combined with propofol in upper gastrointestinal endoscopy: a multicenter, randomized clinical trial
Authors: Wei Ai , Ma Shijin , Dou Yuzhe , Wang Xiaojun , Wu Jianxiong , Zhou Shuzhi , Deng Yanfang , Liu Xinquan , Li Dongming , Yang Mengchang
Published: March 2023

Introduction

Hypotension is the most common adverse event under propofol-mediated sedation and is possible to cause varying degrees of damage to patients. Whereas remimazolam has a poorer sedative effect than propofol.

Aim

The aim of this study was to explore the advantages of the combination of remimazolam tosylate and propofol.

Methods

304 patients were divided into the remimazolam tosylate group, the propofol group, and the remimazolam tosylate plus propofol group. The primary outcome was the incidence of hypotension. Secondary outcomes included the results of sedation and recovery.

Results

The incidence of hypotension was 56.7% in the P group, 12.6% in the RT group, and 31.3% in the R+P group, withP< 0.001. The incidence of body movement was significantly higher in the RT group (26.1%) than in the P group (10.3%) and the R+P group (12.5%),P=0.004. The endoscopist satisfaction was higher in the P (3.87±0.44) and R+P (3.95±0.22)groups than in the RT(3.53±0.84) group. The incidence of adverse events, in descending order, was P group, RT group, and R+P group (93.8%vs.61.3%vs.42.7%).

Conclusion

Co-administration had fewer adverse events than propofol monotherapy, also had a better sedative effect and higher endoscopist satisfaction than remimazolam monotherapy.

Clinical trial registration number

NCT05429086