bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractLegumes 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

SummaryBrain 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

ABSTRACTBackgroundThe 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.MethodsThis 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.ResultsOf 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.ConclusionThe 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

AbstractBackgroundAfter 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.MethodsIndividual 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.ResultsMedian 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.ConclusionsThe 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 IdentifierNCT03419325
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

ABSTRACTBackgroundPatients 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.MethodsThe 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.ResultsThe 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.ConclusionsThe 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

AbstractBACKGROUNDNormobaric 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).METHODSPatients 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.RESULTSA 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.CONCLUSIONSThe 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.REGISTRATIONURL: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

ABSTRACTBackgroundBlood 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.MethodsWe 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. RResultsWe 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.ConclusionThere 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

AbstractGut 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.
Investigating risk of public–private partnerships (PPPs) for smart transportation infrastructure project development
Authors: Nguyen Tiep , Hallo Leonie , Gunawan Indra 
Published: December 2023

PurposeThe 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/approachThe 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.FindingsThe 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/valueThis 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.
Mayor re-election and earnings management: evidence from Portuguese municipalities
Authors: Ferreira Augusta 
Published: December 2023

PurposeThe aim of this paper is to investigate whether Mayors in Portugal engage in earnings management close to zero with the motivation of re-election.Design/methodology/approachThe data used in this study were annual financial information from Portuguese municipalities from 2005 to 2016, as well as data on elections and Mayor re-elections involving three political cycles. The methodologies employed were quantitative, including graphical and panel data regressions.FindingsThe results indicate that municipalities used discretionary accruals to engage in earnings management to report net earnings close to zero, and re-election seems to be a motivation for earnings management behaviour. Furthermore, the results suggest that municipalities in which the Mayor is re-elected are less likely to report positive net earnings close to zero.Originality/valueThis paper makes a valuable contribution to the literature on earnings management in municipalities. At the theoretical level, it makes it possible to identify whether re-election is a motivation for earnings management and, in this sense, to identify patterns of behaviour by managers. On a practical level, the knowledge of a manager's behaviour patterns will help to anticipate his or her future behaviour and, consequently, may prevent inefficiencies.