bluuebunny/crossref_metadata_2025 huggingface dataset:
The mortality experience of disabled persons in the United States during the COVID-19 pandemic
Authors: Weaver David A
Published: December 2023

New data from the Social Security Administration suggest there were 260 000 excess deaths in the United States among current or former disability beneficiaries during the first 22 months of the COVID-19 pandemic. These beneficiaries accounted for 26% of all excess deaths in the United States during this period. The pattern of deaths among disabled beneficiaries corresponds closely to known milestones in the pandemic's history. Disabled beneficiaries in New York, particularly those residing in institutions, had extremely elevated mortality with the onset of the pandemic in the spring of 2020. Across all regions in the United States, mortality among disability beneficiaries increased sharply with the onset of the winter of 2020–2021 and with the emergence of the Delta and Omicron variants in 2021. Elevated mortality was observed for persons with intellectual, mental, and physical impairments. Future public information campaigns about vaccines and other measures may be more successful if they include specific efforts to directly target disability beneficiaries. In addition, clinical trials and other research should consider including disabled persons as specific study groups as the severity of their underlying health impairments is likely comparable to that of persons of advanced age.
Inducing a summer brood break increases the efficacy of oxalic acid vaporization for Varroa destructor (Mesostigmata: Varroidae) control in Apis mellifera (Hymenoptera: Apidae) colonies
Authors: Berry Jennifer A , Braman S Kris , Delaplane Keith S , Bartlett Lewis J
Published: December 2023

The ectoparasitic mite, Varroa destructor (Anderson and Trueman), is the leading cause of western honey bee colony, Apis mellifera (L.), mortality in the United States. Due to mounting evidence of resistance to certain approved miticides, beekeepers are struggling to keep their colonies alive. To date, there are varied but limited approved options for V. destructor control. Vaporized oxalic acid (OA) has proven to be an effective treatment against the dispersal phase of V. destructor but has its limitations since the vapor cannot penetrate the protective wax cap of honey bee pupal cells where V. destructor reproduces. In the Southeastern United States, honey bee colonies often maintain brood throughout the year, limiting the usefulness of OA. Prior studies have shown that even repeated applications of OA while brood is present are ineffective at decreasing mite populations. In the summer of 2021, we studied whether incorporating a forced brood break while vaporizing with OA would be an effective treatment against V. destructor. Ninety experimental colonies were divided into 2 blocks, one with a brood break and the other with no brood break. Within the blocks, each colony was randomly assigned 1 of 3 treatments: no OA, 2 g OA, or 3 g OA. The combination of vaporizing with OA and a forced brood break increased mite mortality by 5× and reduced mite populations significantly. These results give beekeepers in mild climates an additional integrated pest management method for controlling V. destructor during the summer season.
Review: the risks of spray adjuvants to honey bees
Authors: Shannon Brandon , Jeon Hongyoung , Johnson Reed M
Published: December 2023

Pesticide applications are often made as tank mixes containing multiple pesticide products and may include spray adjuvants to enhance pesticidal activities. The primary aim of adjuvant products is to increase the spreading and sticking of spray droplets and to increase the penetration of active ingredients through the cuticles of leaves or targeted pests, which can reduce the amount of active ingredient needed for effective pest control. Adjuvants are made up of compounds drawn from the “inert ingredient” list maintained by EPA but are identified as “principal functioning agents” when used in adjuvant products. These inert compounds do not undergo the same testing and risk assessment process that is required of pesticide active ingredients and generally have no mitigation measures that prevent application onto crops during bloom at times of day when bees are foraging. Honey bees (Apis mellifera;Hymenoptera:Apidae) are at an increased risk of exposure to adjuvant tank mixtures while providing agricultural pollination services. Colony losses attributed to pesticide applications thought to have low risk to honey bees have been reported, highlighting the need to better understand the toxicity of adjuvants included in pesticide tank mixtures. This review summarizes current literature on the risks posed to honey bees by agricultural adjuvants and tank mix combinations of adjuvants with pesticides. Based on the current state of knowledge, we make recommendations to pesticide applicators, product manufacturers, regulatory agencies, and researchers regarding adjuvant toxicity to honey bees with the goal of reducing risks that adjuvants pose to honey bees and other beneficial insects.
Immature stages of Phloeosinus tacubayae (Curculionidae: Scolytinae): morphology and chaetotaxy of larva and pupa, sexual dimorphism of adults, and developmental time
Authors: Cervantes-Espinoza Montserrat , Alejandro Ruiz Enrico , Cuellar-Rodríguez Gerardo , Castro-Valderrama Ulises , Armendáriz-Toledano Francisco
Published: December 2023

The current knowledge of morphology and chaetotaxy of the different developmental stages within the subfamily Scolytinae presents an information deficit that needs to be addressed. Thus, the objective of the present study was to describe, the chaetotaxy and morphology of larvae and pupae, and determine the number of larval instars, the sexual dimorphism in adults, and the development time in Phloeosinus tacubayae. The number of larval instars was determined using traditional morphometry of cephalic capsule and multivariate analysis; description of morphology and chaetotaxy of larvae and pupae, and sexual dimorphism in adults was based on light microscopy and scanning electron microscopy photographs; finally, we quantified development time by mean reviews of 10 gallery systems selected randomly in infested logs, in the laboratory. Morphometric analysis of the cephalic capsule allowed the recognition of 3 different instars. Our results showed that the larvae of P. tacubayae have unique attributes in the body that differentiate them from other genera of the subfamily for example the epicranial suture is not marked, and differentiated from Phloeosinus canadensis, such as a smaller number of setae in the maxillae and without a tergal plate. The pupa had a smaller number of setae on the whole body. The most useful morphological characters to identify a sexual dimorphism in adults were found in the shape and relative position of the seventh and eighth tergites; development time lasted 40 days in total, being the pupal stage the one that took the longest to complete.
Cosmic metallicity evolution of Active Galactic Nuclei: implications for optical diagnostic diagrams
Authors: Dors Oli L , Cardaci M V , Hägele G F , Ilha G S , Oliveira C B , Riffel R A , Riffel R , Krabbe A C
Published: December 2023

We analyse the validity of optical diagnostic diagrams relying on emission-lines ratios and in the context of classifying Active Galactic Nuclei (AGNs) according to the cosmic metallicity evolution in the redshift range $0 \le z \le 11.2$. In this regard, we fit the results of chemical evolution models (CEMs) to the radial gradients of the N/O abundances ratio derived through direct estimates of electron temperatures (Te-method) in a sample of four local spiral galaxies. This approach allows us to select representative CEMs and extrapolate the radial gradients to the nuclear regions of the galaxies in our sample, inferring in this way the central N/O and O/H abundances. The nuclear abundance predictions for theoretical galaxies from the selected CEMs, at distinct evolutionary stages, are used as input parameters in AGN photoionization models built with the Cloudy code. We found that standard BPT diagnostic diagrams are able to classify AGNs with oxygen abundances $\rm 12+\log (O/H) \gtrsim 8.0$ [$(Z/Z_{\odot }) \gtrsim 0.2$] at redshift $z \lesssim 4$. On the other hand, the He iiλ4685/Hβ versus [N ii]λ6584/Hα diagram produces a reliable AGN classification independent of the evolutionary stage of these objects.
Machine-learning applications for cataclysmic variable discovery in the ZTF alert stream
Authors: Mistry D , Copperwheat C M , Darnley M J , Olier I
Published: December 2023

Cataclysmic variables (CV) encompass a diverse array of accreting white dwarf binary systems. Each class of CV represents a snapshot along an evolutionary journey, one with the potential to trigger a type Ia supernova event. The study of CVs offers valuable insights into binary evolution and accretion physics, with the rarest examples potentially providing the deepest insights. However, the escalating number of detected transients, coupled with our limited capacity to investigate them all, poses challenges in identifying such rarities. Machine learning (ML) plays a pivotal role in addressing this issue by facilitating the categorization of each detected transient into its respective transient class. Leveraging these techniques, we have developed a two-stage pipeline tailored to the Zwicky Transient Facility transient alert stream. The first stage is alerts filter aimed at removing non-CVs, while the latter is an ML classifier produced using Extreme Gradient Boosting, achieving a macro average area under the curve score of 0.92 for distinguishing between CV classes. By utilizing the generative topographic mapping algorithm with classifier posterior probabilities as input, we obtain representations indicating that CV evolutionary factors play a role in classifier performance, while the associated feature maps present a potent tool for identifying the features deemed most relevant for distinguishing between classes. Implementation of the pipeline in 2023 June yielded 51 intriguing candidates that are yet to be reported as CVs or classified with further granularity. Our classifier represents a significant step in the discovery and classification of different CV classes, a domain of research still in its infancy.
Molecular mechanism of specific DNA sequence recognition by NRF1
Authors: Liu Ke , Li Weifang , Xiao Yuqing , Lei Ming , Zhang Ming , Min Jinrong
Published: December 2023

Nuclear respiratory factor 1 (NRF1) regulates the expression of genes that are vital for mitochondrial biogenesis, respiration, and various other cellular processes. While NRF1 has been reported to bind specifically to GC-rich promoters as a homodimer, the precise molecular mechanism governing its recognition of target gene promoters has remained elusive. To unravel the recognition mechanism, we have determined the crystal structure of the NRF1 homodimer bound to an ATGCGCATGCGCAT dsDNA. In this complex, NRF1 utilizes a flexible linker to connect its dimerization domain (DD) and DNA binding domain (DBD). This configuration allows one NRF1 monomer to adopt a U-turn conformation, facilitating the homodimer to specifically bind to the two TGCGC motifs in the GCGCATGCGC consensus sequence from opposite directions. Strikingly, while the NRF1 DBD alone could also bind to the half-site (TGCGC) DNA of the consensus sequence, the cooperativity between DD and DBD is essential for the binding of the intact GCGCATGCGC sequence and the transcriptional activity of NRF1. Taken together, our results elucidate the molecular mechanism by which NRF1 recognizes specific DNA sequences in the promoters to regulate gene expression.
Starch phosphorylation regulates starch granule morphological homogeneity in Arabidopsis thaliana
Authors: Li Xiaoping , Ahmad Abubakar Musa , Zhong Yuyue , Ding Li , Blennow Andreas , Fettke Joerg
Published: December 2023

Starch granule morphological homogeneity presents a gap in starch research. Transitory starch granules in wild-type plants are discoid, regardless of species. Notably, while the shape of starch granules can differ among mutants, it typically remains homogeneous within a genotype. We found an Arabidopsis thaliana mutant, dpe2sex4, lacking both the cytosolic disproportionating enzyme 2 (DPE2) and glucan phosphatase SEX4, showing an unprecedented bimodal starch granule diameter distribution when grown under a light/dark rhythm. dpe2sex4 contained 2 types of starch granules: large granules and small granules. In contrast to the double starch initiation in wheat (Triticum aestivum) endosperm, where A-type granules are initiated first and B-type granules are initiated later, dpe2sex4 small and large granules developed simultaneously in the same chloroplast. Compared with the large granules, the small granules had more branched amylopectin and less surface starch-phosphate, thus having a more compact structure that may hinder starch synthesis. During plant aging, the small granules barely grew. In in vitro experiments, fewer glucosyl residues were incorporated in small granules. Under continuous light, dpe2sex4 starch granules were morphologically homogeneous. Omitting the dark phase after a 2-wk light/dark cycle by moving plants into continuous light also reduced morphological variance between these 2 types of granules. These data shed light on the impact of starch phosphorylation on starch granule morphology homogeneity.
Assessing Admiration for Women Who Do “Men’s Work”
Authors: Pike Isabel , Pierotti Rachael S , Mbaye Mame Soukeye
Published: December 2023

Drawing on interviews and focus groups from Conakry, the capital city of the Republic of Guinea in West Africa, this article examines how people talk about women working in male-dominated skilled trades alongside women’s accounts of their work experiences in those sectors. We find that the idea of women doing gender atypical work, whom we call “crossovers,” evokes widespread admiration. They are unanimously described as brave and virtuous, contrasted with women who rely on money from relationships with men. However, this celebration falters in the workplace, where crossovers often experience paternalism and harassment. Building on theories of both gender beliefs and femininities, we attribute this discrepancy to the differential threats to the gender order that are posed by accommodating crossovers at work versus speaking positively about them. Working together requires men to confront actual women’s unexpected capabilities, while rhetorically celebrating crossovers may in fact reify stereotypes about most women and fail to fundamentally undermine men’s authority. Crossovers can serve as sources of inspiration for an alternative gender order, but we find that professed admiration for “exceptional” groups of women has both limitations and risks. We conclude by suggesting that the subversive potential of admiration for gender atypical behavior must be empirically examined, rather than assumed, with attention to why such women are seen as admirable as well as how this admiration is borne out in social interactions.
Gas Humidification During Helmet Continuous Positive Airway Pressure
Authors: Ambrosetti Lorenzo , Giani Marco , Rezoagli Emanuele , Fiorillo Chiara , Vitale Daniela , Giacchè Damiano , Ravasio Giambattista , Fumagalli Roberto , Foti Giuseppe , Lucchini Alberto
Published: December 2023

Background

In the last decades, the use of the helmet interface to deliver noninvasive respiratory support has steadily increased. When delivering oxygen therapy, conditioning of inspired gas is mandatory, as the water content of medical gas is neglectable. To minimize the risk of airway damage, it is recommended to achieve an absolute humidity greater than 10 mg H2O/L. The primary aim of the study was to assess the performance of 3 different heated humidifiers to condition gas during helmet continuous positive airway pressure and to compare them with a setting without active humidification.

Methods

We performed a crossover randomized physiological study in healthy volunteers. Absolute humidity, relative humidity, and temperature were measured during 4 steps (no humidification and the 3 heated humidifiers, performed in a randomized order) and at 3 time points (after 1, 5, and 10 minutes).

Results

Eight subjects participated to the study. Without active humidification, absolute humidity was constantly below the recommended level. All humidifiers conditioned the inspired gases to an average absolute humidity greater than 10 mg H2O/L. Overall, the best performance, in terms of absolute humidity, was obtained with H900 (19.74 ± 0.50 mg H2O/L), followed by TurbH2O (−6.82 mg H2O/L vs H900; 95% confidence interval, −8.49 to −5.14; P < .05) and F&P 810 (−9.03 mg H2O/L vs H900; 95% confidence interval, −10.70 to −7.35; P < .05).

Conclusions

Active humidification is required to achieve adequate conditioning of inspired gas during helmet continuous positive airway pressure. The choice between different humidifiers available on the market should be made according to the local needs and expertise.
HCC is associated with diabetes and longitudinal blood glucose control in a national cohort with cirrhosis
Authors: Mezzacappa Catherine , Mahmud Nadim , Serper Marina , John Binu V. , Taddei Tamar H. , Kaplan David E.
Published: December 2023

Background:

Diabetes is associated with HCC; however, the impact of longitudinal blood glucose (BG) control on HCC risk in cirrhosis is not well known. We investigated this knowledge gap in a cohort of United States Veterans with cirrhosis from 2015 to 2021.

Methods:

We used repeated hemoglobin A1c measurements to categorize follow-up time according to BG control (defined as hemoglobin A1c < 7%) state over time: uncontrolled, nonsustained control (≤2 y), or sustained control (>2 y). We performed a sensitivity analysis using hemoglobin A1c < 8% to define BG control. We used Fine and Gray Cox proportional hazards regression with death and transplant as competing events to compare rates of incident HCC.

Results:

Our study included 81,907 individuals, 56.2% of whom had diabetes at baseline. There were 8,002 incident HCCs. The rate of HCC was 18% higher in diabetes (95% CI: 13% – 24%), and the relative increase in the rate of HCC varied by etiology of cirrhosis from nonsignificant (HCV) to an increase of 120% (HBV). Uncontrolled and nonsustained BG control was associated with 1.80 (95% CI: 1.70–1.91) and 2.34 (95% CI: 2.21–2.48) times the rate of HCC compared to sustained BG control, respectively. Using Hgb A1c < 8% to define BG control, HCC rates in uncontrolled and nonsustained BG control were 2.43 (2.28–2.58) and 2.23 (2.11–2.36) times that observed in sustained BG control.

Conclusions:

Associations between diabetes and HCC in cirrhosis vary according to the longitudinal BG control state. Inadequate BG control is consistently associated with a higher risk of HCC, and long-term BG control should be considered in comprehensive cirrhosis care.
Platelet-inspired synthetic nanoparticles improve hemostasis and hemodynamics in a rabbit model of abdominal hemorrhage
Authors: Srinivasan Amudan J. , Secunda Zachary A. , Mota-Alvidrez Roberto I. , Luc Norman F. , Disharoon Dante , Traylor Baylee , Pawlowski Christa L. , Brown Joshua B. , Bruckman Michael A. , Gupta Anirban Sen , Neal Matthew D.
Published: December 2023

BACKGROUND

Early platelet transfusion is associated with reduced mortality in traumatic hemorrhage. However, platelet usage is severely limited because of the challenges of donor availability, platelet portability, and storage. Here, we report on a bioinspired synthetic platelet (SP) nanoconstruct that utilizes liposome surface-decoration with peptides that mimic injury site-specific platelet adhesion to von Willebrand Factor and collagen, and fibrinogen-mediated platelet aggregation. Synthetic platelet has previously shown promising hemostatic outcomes in vitro and in vivo. Here, we evaluated hemostasis and hemodynamic effects of SP in a rabbit model of abdominal hemorrhage.

METHODS

Twenty-three adult male New Zealand white rabbits (2.5–3.5 kg) were treated with either buffer, control particles (CPs), or SP. Under general anesthesia with invasive monitoring, rabbits underwent laparotomy with combined splenic and hepatic injury. Hemodynamics were monitored for 30 minutes and blood loss was quantified. Blood counts, aggregometry, catecholamine and platelet factor 4 (PF4) assays were performed at multiple timepoints. Analysis used analysis of variance and post hoc Tukey testing with α = 0.05.

RESULTS

Rabbits in the SP (n = 7) group had significantly lower weight-normalized blood loss compared with both buffer (n = 8) and CP (n = 8) animals (21.1 vs. 33.2 vs. 40.4 g/kg, p < 0.001). Synthetic platelet–treated animals had higher systolic blood pressure area under curve compared with buffer- and CP-treated animals (1567 vs. 1281 vs. 1109 mm Hg*min, p = 0.006), although post hoc differences were only significant for the SP/CP comparison (p = 0.005). Platelet counts, catecholamine levels, PF4, and aggregometry were similar between groups.

CONCLUSION

Synthetic platelet treatment significantly reduced blood loss and improved hemodynamics in a rabbit abdominal hemorrhage model. Synthetic platelet has potential as an intravenous hemostatic platelet surrogate with donor-independent availability and scalable manufacture.
SAN: mitigating spatial covariance heterogeneity in cortical thickness data collected from multiple scanners or sites
Authors: Zhang Rongqian , Chen Linxi , Oliver Lindsay D. , Voineskos Aristotle N. , Park Jun Young
Published: December 2023

In neuroimaging studies, combining data collected from multiple study sites or scanners is becoming common to increase the reproducibility of scientific discoveries. At the same time, unwanted variations arise by using different scanners (inter-scanner biases), which need to be corrected before downstream analyses to facilitate replicable research and prevent spurious findings. While statistical harmonization methods such as ComBat have become popular in mitigating inter-scanner biases in neuroimaging, recent methodological advances have shown that harmonizing heterogeneous covariances results in higher data quality. In vertex-level cortical thickness data, heterogeneity in spatial autocorrelation is a critical factor that affects covariance heterogeneity. Our work proposes a new statistical harmonization method called SAN (Spatial Autocorrelation Normalization) that preserves homogeneous covariance vertex-level cortical thickness data across different scanners. We use an explicit Gaussian process to characterize scanner-invariant and scanner-specific variations to reconstruct spatially homogeneous data across scanners. SAN is computationally feasible, and it easily allows the integration of existing harmonization methods. We demonstrate the utility of the proposed method using cortical thickness data from the Social Processes Initiative in the Neurobiology of the Schizophrenia(s) (SPINS) study. SAN is publicly available as an R package.
Diversity of Insecticidal PA1b Homologs among Legume Seeds from Middle Eastern Region
Authors: Diya F. , Charles H. , Vallier A. , Karaki L. , Kfoury L. , Da Silva P. , Rizk F.
Published: December 2023

Legumes play a central role in various food systems, with significant socio-economic and environmental impacts. Their high protein content, composed mainly of globulins and albumins, makes them valuable for human food and animal feed. Among the albumins, is Pea Albumin 1 b (PA1b), a 37 amino acid peptide, extracted from the seeds of the peaPisum sativum. The protein displays the knottin scaffold and exhibits potent insecticidal activity against certain insects including cereal weevils and mosquitoes. This toxicity is attributed to the coexistence of several isoforms in peas. The natural diversity of PA1b-like molecules within the legume species of the Fabaceae family has been studied using various molecular, biochemical, and bioinformatic tools. SeveralA1genes coding for this peptide have been characterized in soybeans, bean, barrel medick and other legume species. The aim of is study is to precisely characterize partial A1 genes in legumes of the Faboideae subfamily from the Middle East region using PCR homology. Specifically, the research focuses on the sequence structure of Pea Albumin 1 b (PA1b) variants and establishes phylogenetic relationships between these sequences and publicly available A1b homologs. The toxic effects of seed flour containing PA1b-like molecules are assessed, demonstrating that the newly characterized PA1b homologs retain structural conservation. The study observes both conservation and diversification among A1b homologs, consistent with the divergence of lineages within the Fabaceae family. The toxic effects associated with putative A1b molecules are found across different species and within the same species from different geographical origins. In particular, novel candidates such asVicia sativaandMedicago minimashow promising insecticidal A1b activity. Further analysis of isoforms from these species, including an examination of their expression in different tissues and organs should be undertaken to facilitate the potential use of A1b molecules in agricultural practice.
A therapeutic small molecule lead enhances γ-oscillations and improves cognition/memory in Alzheimer’s disease model mice
Authors: Wei Xiaofei , Campagna Jesus J. , Jagodzinska Barbara , Wi Dongwook , Cohn Whitaker , Lee Jessica , Zhu Chunni , Huang Christine S. , Molnár László , Houser Carolyn R. , John Varghese , Mody Istvan
Published: December 2023

Brain rhythms provide the timing and concurrence of brain activity required for linking together neuronal ensembles engaged in specific tasks. In particular, the γ-oscillations (30-120 Hz) orchestrate neuronal circuits underlying cognitive processes and working memory. These oscillations are reduced in numerous neurological and psychiatric disorders, including early cognitive decline in Alzheimer’s disease (AD). Here we report on a potent brain permeable small molecule, DDL-920 that increases γ-oscillations and improves cognition/memory in a mouse model of AD, thus showing promise as a new class of therapeutics for AD. As a first in CNS pharmacotherapy, our lead candidate acts as a potent, efficacious, and selective negative allosteric modulator (NAM) of the γ-aminobutyric acid type A receptors (GABAARs) assembled from α1β2δ subunits. We identified these receptors through anatomical and pharmacological means to mediate the tonic inhibition of parvalbumin (PV) expressing interneurons (PV+INs) critically involved in the generation of γ-oscillations. Our approach is unique as it is meant to enhance cognitive performance and working memory in a state-dependent manner by engaging and amplifying the brain’s endogenous γ-oscillations through enhancing the function of PV+INs.
Dolutegravir-related hyperglycemia among children and adolescents <18 years in Northern and Eastern Uganda: A cross-sectional study
Authors: Akello Fridah , Nalwanga Damalie , Musiime Victor , Kiguli Sarah
Published: December 2023

Background

The World Health Organization (WHO) recommended Dolutegravir (DTG) as the preferred anchor drug for first and second line Anti-Retroviral Treatment (ART) regimen. Case reports and studies have demonstrated new onset hyperglycemia among adults initiated or transitioned to DTG. There is paucity of data on DTG-related hyperglycemia among children and adolescents and subsequently, glycemic screening is not routinely conducted for those using DTG. We determined the prevalence and factors associated with DTG-related hyperglycemia in this age category.

Methods

This cross-sectional study was conducted from 28thOctober 2022 to 11thSeptember 2023 at Soroti and Lira Regional Referral Hospitals. 251 children and adolescents under 18 years, on a DTG based ART regimen, were consecutively enrolled and data analyzed for 240 participants. Socio-demographic, anthropometric measurements, clinical, and laboratory variables were collected using a questionnaire. Random blood glucose testing, urine dipstick and HbA1c analyses were conducted. Data was entered into epiData version 4.6, cleaned, and analyzed using STATA version 17.0. Logistic regression was used to determine the relationship between outcome and predictor variables. A p-value < 0.05 was considered statistically significant at multivariate analysis.

Results

Of the 240 study participants, 55.4 %(n=133) were female and 71.7 %(n =172) were over 10 years. The prevalence of DTG-related-hyperglycemia was 20% (n=49) and 95.9% (n=47) met the criteria for pre-diabetes. Health education talks on Adverse events related to Dolutegravir was protective for hyperglycemia(aOR 0.4, 95% CI 0.2-0.9), p = 0.035.

Conclusion

The prevalence of DTG-related-hyperglycemia was high, occurring in every 2 in 10 children and adolescents. Health education talks on adverse events associated with DTG use were found to be protective against hyperglycemia. Routine glycemic screening and monitoring therefore should be emphasized. Additionally, a strategy for health education talks focusing on lifestyle modifications to reduce the occurrence of hyperglycemia should be developed.
Implementing a Pharmacogenomic-driven Algorithm to Guide Antiplatelet Therapy among Caribbean Hispanics: A non-randomized prospective cohort study
Authors: Nuñez-Medina Héctor , Monero Mariangeli , Torres Lorna M , Leal Enrique , Sepúlveda Lorena González- , Mayor Ángel M , Renta Jessicca Y , González-García Edgardo R , González Ariel , Melin Kyle , Scott Stuart A , Ruaño Gualberto , Hernandez-Suarez Dagmar F , Duconge Jorge
Published: December 2023

Background

After percutaneous coronary intervention (PCI), clopidogrel resistant patients are at an increased risk of major adverse cardiovascular and cerebrovascular events (MACCEs). We aimed to assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the occurrence of these ischemic events and improves outcomes among Caribbean Hispanic patients from Puerto Rico, who are underrepresented in clinical pharmacogenomic (PGx)-guided implementation studies.

Methods

Individual platelet function testing (PRU) measures,CYP2C19*2 andPON1rs662 genotypes, clinical and demographic data from 8 medical facilities were included. Patients were separated into standard of care (SoC) and genotype-guided groups (150 each). Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Alternative therapy with ticagrelor was recommended for patients with a high risk score ≥2. Statistical associations between patient time free of MACCEs and predictor variables (i.e., treatment groups, risk scores) were tested in this population using Kaplan-Meier survival analyses and Cox proportional-hazards regression models.

Results

Median age of participants is 67 years; BMI: 27.8; 48% women; 14% smokers; 59% with type-2 diabetes mellitus (T2DM). Among patients with high-risk scores who were free from MACCE events 6 months after coronary stenting, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in terms of reducing the incidence rate of atherothrombotic events.

Conclusions

The clinical utility of our PGx-driven CDS algorithm to reduce the incidence rate of MACCEs among post-PCI Caribbean Hispanic patients on clopidogrel was externally demonstrated.

Clinical Trial Registration Unique Identifier

NCT03419325
Predicting prolonged mechanical ventilation after endovascular treatment for acute vertebrobasilar artery occlusion
Authors: Cai Qiankun , Hong Minying , Xu Yingjie , Zhang Shuai , Huang Zhixin , Xu Pengfei , Huang Xianjun , Liu Shufen , Huang Zhengping , Ye Lichao , Chen Jixing , Huang Hongyu , Zheng Feng , Sun Wen
Published: December 2023

Background

Patients with acute vertebrobasilar artery occlusion (VBAO) after endovascular treatment (EVT) frequently require mechanical ventilation (MV). This study aims to develop and validate a predictive score for prolonged mechanical ventilation (PMV) in patients with VBAO after EVT.

Methods

The derivation cohort prospectively recruited acute VBAO patients undergoing EVT from four comprehensive stroke centers (CSCs) in China. PMV was defined as continuous MV for ≥96 hours. Two multivariable logistic regressions were performed to predict predictive models based on whether adding radiographic results at follow-up. The performance of two models was evaluated for discrimination, calibration, and clinical utility. A validation cohort of 444 patients from acute Posterior circulation ischemic Stroke registry was enrolled to validate two models.

Results

The derivation cohort consisted of 498 patients from four CSCs, among whom 204 (41.0%) required PMV. Reperfusion status, National Institutes of Health Stroke Scale scores, collateral circulation status, history of atrial fibrillation, fasting blood glucose, circulation insufficiency, the presence of malignant cerebellar edema, and symptomatic intracranial hemorrhage at follow-up imaging were found to be independent predictors of PMV in multivariable logistic regression. These variables were combined to create the basic and radiographic PAIRS scores. The basic PAIRS and radiographic PAIRS scores demonstrated adequate discrimination in derivation cohort (C-index, 0.77 [95%CI 0.73 to 0.81] and 0.80 [95%CI 0.77 to 0.84]), as well as the validation cohort (C-index, 0.70 [95%CI 0.65 to 0.75] and 0.75 [95%CI 0.70 to 0.80]), and had well-fitted calibration plot for both cohorts. Decision curve analysis showed that both PAIRS scores had satisfied net benefit in predicting PMV across various thresholds.

Conclusions

The PAIRS scores provide adequate accurate predictions of PMV in VBAO patients after EVT. These findings can assist patient families and caregivers in better understanding the treatment trajectory.
Normobaric Hyperoxia Combined with Endovascular Treatment Based on Temporal Gradient: A dose-escalation study
Authors: Li Weili , Wang Sifei , Liu Lan , Chen Jiahao , Lan Jing , Ding Jiayue , Chen Zhiying , Yuan Shuhua , Qi Zhifeng , Wei Ming , Ji Xunming
Published: December 2023

BACKGROUND

Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke (AIS). Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment (EVT).

METHODS

Patients with acute stroke who had an indication for EVT at Tianjin Huanhu Hospital were included and randomly assigned to four groups (1:1 ratio) based on NBO therapy duration: 1) Sham-NBO group (oxygen 1 L/min continuously for 4 h); 2) NBO-2h group (10 L/min continuously for 2 h); 3) NBO-4h group (10 L/min continuously for 4 h); and 4) NBO-6h group (10 L/min continuously for 6 h). The primary outcome was cerebral infarction volume at 72 h after randomization. The primary safety outcome was the 90-d mortality rate.

RESULTS

A total of 100 patients were included (Sham-NBO group, n=25; NBO-2h group, n=25; NBO-4h group, n=25; and NBO-6h group, n=25). The 72-h cerebral infarct volumes were 39.4 ± 34.3 ml, 30.6 ± 30.1ml, 19.7 ± 15.4 ml, and 22.6 ± 22.4 ml, respectively (P=0.013). The NBO-4h and NBO-6h groups exhibited significant differences compared to the Sham-NBO group (adjusted P values: 0.011 and 0.027, respectively). No significant differences were found between the NBO-4h and NBO-6h groups. The National Institute of Health Stroke Scale (NIHSS) scores at 24 h, 72 h, and 7 d, and the changes in NIHSS scores from baseline to 24 h were significantly different in the NBO-4h and NBO-6h groups compared with the Sham-NBO group (P<0.05). No significant differences were observed between the NBO-4h and NBO-6h groups in the NIHSS assessments. No significant differences were noted among groups in the 90-d mortality rate, symptomatic intracranial haemorrhage, early neurological deterioration, and severe adverse events.

CONCLUSIONS

The effectiveness of NBO therapy was associated with oxygen administration duration. In patients with AIS who undergone EVT, NBO treatment for 4-6 h may yield better outcomes than other oxygen therapy regimens or low flow oxygen therapy.

REGISTRATION

URL:https://www.clinicaltrials.gov; Unique identifier:NCT05404373.
VARIANCE: Variability of Assessed BP Readings In Acute Neuro-intervention Cases and its Effect on outcomes
Authors: Van Orden Kimberlee , Staniszewski Thomas , Jajo Maryo , Torres Dolores , Poynor Briana , Alwood Benjamin , Agrawal Kunal , Meyer Brett , Meyer Dawn
Published: December 2023

Background

Blood pressure variability (BPV) following endovascular thrombectomy (EVT) in AIS has been associated with poor outcome. Variables that predict high BPV must be examined to improve outcome. The purpose of this study is to analyze predictors and effect of BPV on outcome in patients with good recanalization after EVT.

Methods

We conducted a retrospective analysis of prospectively collected data from an IRB approved registry of two academic Comprehensive Stroke Centers between 2017-2022. Patients were included if they had 1) anterior circulation large vessel occlusions (LVO) and 2) EVT with TICI 2b-3. All BPs were recorded as immediate pre-op SBP/DBP (one minute prior to procedure), immediate post-op SBP/DBP (at time of recanalization), and 24 hours post revascularization. Demographic variables, stroke time metrics, and symptomatic ICH (sICH) were assessed. Outcome included discharge disposition and 90 day modified Rankin Scale. Good short-term outcome was disposition to home/acute rehabilitation and good long-term outcome was mRS 0-2. BPV was the average of the differences between measurements divided by the number of measurements. R

Results

We identified 253 patients (mean age 70±14, 51.4% female, 49% white, 30.4% Hispanic). Median NIHSS was 17±8 and mean onset to groin puncture was 478±326 mins. Mean door to groin puncture was 86±110 mins. Good discharge occurred in 58.9% of patients. Mean BPV was 30.6±25.6mmHg and was significantly correlated with female sex, home antihypertensive use, and immediate pre and post-op SBP. BPV was not associated with age, initial NIHSS, Hispanic ethnicity, HTN, sICH, discharge disposition or 90 day mRS.

Conclusion

There was a significant correlation of high BPV with female sex and home antihypertensives use. BPV was not correlated with short or long term outcome in this population, however, BPV was lower than prior populations. Assessment of BPV in various stroke centers and populations is necessary to understand the effect of BPV on stroke outcome.
Modulation of Alzheimer’s Disease Brain Pathology in Mice by Gut Bacterial Deletion: The Role of Il-17a and Microglial MyD88
Authors: Hao Wenlin , Luo Qinghua , Tomic Inge , Quan Wenqiang , Hartmann Tobias , Menger Michael D. , Fassbender Klaus , Liu Yang
Published: December 2023

Gut bacteria regulate brain pathology of Alzheimer’s disease (AD) patients and animal models; however, the underlying mechanism remains unclear. In this study, 3-month-old APP-transgenic female mice with and without knock-out ofIl-17agene, or haploinsufficiency of MyD88 in microglia were treated with antibiotics-supplemented or normal drinking water for 2 months. Antibiotic treatment eradicated gut bacteria, particularly in the phylaBacteroidetesandFirmicutes, and reduced Il-17a-expressing CD4-positive T lymphocytes. Deletion of gut bacteria inhibited inflammatory activation in the brain and microglia, and reduced cerebral Aβ levels in APP-transgenic mice, which was abolished by deficiency of Il-17a or haploinsufficiency of MyD88 in microglia. As possible mechanisms regulating Aβ pathology, deletion of gut bacteria inhibited β-secretase activity and increased the expression of Abcb1 and Lrp1 in the brain or at the blood-brain barrier, which were also reversed by the absence of Il-17a. Interestingly, a crossbreeding experiment between APP-transgenic mice andIl-17aknockout mice further showed that deficiency of Il-17a had already increased Abcb1 and Lrp1 expression at the blood-brain barrier. Thus, deletion of gut bacteria attenuates inflammatory activation and amyloid pathology in APP-transgenic mice via Il-17a and microglial MyD88-involved signalling pathways. Our study contributes to a better understanding of the gut-brain axis in AD pathophysiology.
Evidence for selfing in a vertebrate from whole-genome sequencing
Authors: Böhne Astrid , Oğuzhan Zeynep , Chrysostomakis Ioannis , Vitt Simon , Meuthen Denis , Martin Sebastian , Kukowka Sandra , Thünken Timo
Published: December 2023

A growing number of recent genomic studies report asexual parthenogenetic reproduction in a wide range of taxa, including vertebrate species from the reptile, bird, and fish lineages. Yet, self-fertilization (selfing) has been recorded only in a single vertebrate, the mangrove killifishKryptolebias marmoratus. In cichlid fishes, sex determination is notably diverse and can be influenced by the environment, and sequential hermaphroditism has been reported for some species. Here, we present evidence for a case of facultative selfing in the cichlid fishBenitochromis nigrodorsalis, which is otherwise known as biparentally reproducing ovophilic mouthbrooder from Western Africa. Our laboratory observations revealed that a wild-caught individual produced repeatedly viable offspring in absence of a mating partner. By analyzing genome-wide single-nucleotide polymorphism (SNP) data, we compare that individual and two of its offspring to shed light on its reproductive mode. First, our results confirm uniparental reproduction. Second, overall heterozygosity is reduced in the offspring compared with outbred individuals. Retained maternal heterozygosity in the offspring is ∼51%, which is close to the theoretically expected value of a heterozygosity reduction of 50% by selfing. Heterozygosity patterns along individual chromosomes do not point to alternative parthenogenetic reproductive mechanisms like automixis by terminal or central fusion. Facultative selfing may represent an adaptive strategy ensuring reproduction when mating partners are absent and, hence, contribute to the cichlids’ enormous evolutionary success.
Investigating risk of public–private partnerships (PPPs) for smart transportation infrastructure project development
Authors: Nguyen Tiep , Hallo Leonie , Gunawan Indra
Published: December 2023

Purpose

The purpose of this paper is to rank critical risks and determine major categories of risks to be considered by public–private partnerships (PPPs) investors when investing in “smart” transportation infrastructure. Such investment is sorely needed in many mega cities around the world currently suffering from serious impacts of traffic congestion, pollution and lack of usability of transport systems.

Design/methodology/approach

The study used literature review focused upon smart transportation infrastructure projects financed by PPP arrangements to create a questionnaire which was refined by subject matter experts and then completed by 126 experienced respondents. Exploratory factor analysis was used to create major categories emerging from the collected data. Interviews with ten experts were used to validate the findings.

Findings

The most highly major ranked risks shared by these participants were lack of expertise in complex project implementation, political interference, lack of PPP project data and lack of a collaboration mechanism between government and private sectors. Factor analysis showed that in terms of risk likelihood, stakeholder engagement, implementation process issues, the natural environment, data-sharing and technology complexity emerged. In terms of risk impact, major factors were stakeholder engagement, trust versus resistance issues, the natural environment and factors concerning uncertainty.

Originality/value

This paper addresses a somewhat unexplored area, the risks involved in investing in PPP smart transportation infrastructure. Such infrastructure projects are embedded in their environments, and approaches using a complexity lens can emerge overriding risk concerns for investors when undertaking such projects.
Sailing through silence: exploring how negative gossip leaves breeding grounds for quiet quitting in the workplace
Authors: Srivastava Shalini , Saxena Anubhuti , Kapoor Vartika , Qadir Abdul
Published: December 2023

Purpose

Gossip spreads like wildfire, damaging relationships, decaying trust and creating a negative work environment. This study aims to investigate the relationship between negative workplace gossip (NWG) and quiet quitting (QQ), while considering the mediating effects of workplace stress and emotional exhaustion (EE).

Design/methodology/approach

Drawing upon the conservation of resource theory, the study aimed to comprehend this association in the context of 267 employees from diverse sectors in India, including health care, IT, banking and education. Through a three-wave time lagged survey design, using partial least squares structural equation modeling, significant findings were uncovered.

Findings

The results revealed a positive link between NWG and QQ. There was also a positive correlation between NWG and workplace stress. In addition, workplace stress and EE were found to mediate the relationship between NWG and QQ.

Practical implications

The findings have implications for both theory and practice. Organizations should consider implementing strategies to mitigate the prevalence of negative gossip and foster a healthier work environment, promoting employee well-being and retention.

Originality/value

The study reveals the “black box” between NWG and QQ, adding to the body of knowledge on the novel concept of QQ. Second, the study expands the literature on NWG, by examining impact path of how it leads to stress and EE, leading to QQ.
How do economic policy uncertainty and leverage impact firm-level cash holding distribution of housing companies in an emerging economy? A quantile regression approach
Authors: Rajhans Rajni Kant
Published: December 2023

Purpose

High economic policy uncertainty forces firms to accumulate a higher level of cash than during normal business periods. However, it is not evident that economic policy uncertainty has a homogeneous impact across cash-holding distributions. This paper aims to study the impact of economic policy uncertainty, leverage and their interaction on cash-holding distributions.

Design/methodology/approach

This study adopted a quantile regression approach to examine the influence of economic policy uncertainty and firm leverage on firm-level cash-holding distributions. To investigate the influence across quantiles, the author estimated 19 quantiles between 0.05 and 0.95.

Findings

This study finds that both economic policy uncertainty and firm leverage significantly affect firm-level cash-holding distributions heterogeneously. But, the impact of the interaction of these two variables is significant only for firms placed in the 60th to 85th quantiles of cash holding distribution.

Originality/value

The study adds to the existing knowledge of determinants of firm-level cash holdings but takes exogenous variables as economic policy uncertainty. The paper builds on a unique sample setting wherein, the cash holdings of all nonfinancial firms have increased many folds, including housing companies in an emerging economy.