bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies on the ethnopharmacology, antimicrobial activity, and toxicity of Catha edulis (Vahl.) Endl., in Sprague Dawley rats
Authors: Githua Kevin Kariuki , Maitho Timothy Elias , Nguta Joseph Mwanzia , Okumu Mitchel Otieno 
Published: August 2022

Background: The Mbeere South community of Embu County consume leaves of Catha edulis for its stimulant and euphoretic actions. Other indigenous uses of the plant are undocumented. Information on the pharmacology and safety of this plant is also scanty. This study aimed to document the ethnopharmacology, antimicrobial properties, and toxicity of C. edulis leaves collected from the Mbeere South community in Kenya. Methods: Ethnopharmacological data was collected from 35 informants using semi-structured questionnaires. Leaf extracts of C. edulis were prepared using acetone, water, and methanol. The antimicrobial properties of these extracts were evaluated against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. The toxicity of the aqueous extract was determined using hematological, biochemical, and histopathological parameters in male and female Sprague Dawley rats at 250 mg/kg, 500 mg/kg, and 1000 mg/kg doses over 28 days. p<0.05 was considered significant. Results: All informants were male, most were married, >50 years old, with >10 years of experience. The sources, local names, preparation, storage conditions, indications, frequency of use, dosage, and side effects of C. edulis were documented. All extracts were ineffective against E. coli, P. aeruginosa, and C. albicans. They had limited efficacy against B. cereus and S. aureus. Significant differences were observed in the hematological and biochemical parameters of rats at the tested doses. Low, intermediate, and high doses of the aqueous extract of C. edulis produced local congestion of the cardiac and hepatic vessels. Localized interstitial connective tissue proliferation, multifocal kidney interstitial hemorrhage, and localized tubular epithelium necrosis were also observed in female rats. Conclusions: The ethnobotanical uses of C. edulis among the Mbeere South community were documented for the first time. Limited antimicrobial efficacy and toxicity at high doses limit the use of leaves of C. edulis.
Peccary, a metaprogramming open-source R platform to improve pharmacometrics efficiency
Authors: Derippe Thibaud , Declèves Xavier , Fouliard Sylvain 
Published: August 2022

Background:A pharmacometrics (PMx) workflow usually requires several software tools to cover all the steps from data analysis to model evaluation and simulations. However, these tools do not always communicate well together, compromising the efficiency of the whole process. Highly inspired by the markdown/pandoc system, we developed Peccary, an R package and its dedicated Shiny Application with the objective to accelerate the use of previously released R packages through various translation and metaprogramming processes. Methods:Peccary was developed with an agile method, progressively aggregating snippets of R code produced during real-life pharmacometrics works. Its first subpackage, PeccAnalysis, can be used to produce and evaluate various R code for population description (using table1 package), plot exploration (ggplot) and non-compartment analysis (pknca). The second subpackage, PeccaReverse, allows writing a structural model using a minimalist (simplified deSolve) syntax, before metaprogramming model simulations (using either deSolve or RxODE) and design evaluation (through PopED), along with performing various model syntax translations (e.g., into NONMEM, Monolix or nlmixr files). Finally, the third subpackage, PeccaResult, standardizes run outputs of several PMx software (NONMEM, Monolix, Adapt, nlmixr) to perform various diagnostic evaluation tasks. Results:The metaprogramming system used in PeccAnalysis and PeccaReverse has many advantages. First, it simplifies the use of previously mentioned packages (by reducing the required knowledge and the time needed to program the output creation). Second, it creates links between independent tools (for instance using the same inputs for several tasks). Third, the produced R code can be reviewed for eventual manual modification, verification (quality control) or traceable report integration. Conclusion:Overall, Peccary was successful in improving PMx efficiency by providing a Shiny R platform that can produce various outputs during live meetings while keeping the possibility to extract Peccary-independent R source code for further in-depth control.
Need for long term safety studies before recommending viral vector vaccines in kids
Authors: Omer Hakim Muhammad , Zain Azhar Muhammad , Patel Urvish , Chahar Satya , Gupta Ruby , Samala Venkata Vikramaditya , Kukreja Geetika , Patil Ashish 
Published: August 2022

Vaccines have played a central role in dealing with COVID-19 pandemic. Now regulatory agencies in USA and around the world have begun approving vaccination for kids. Long term safety profile of live attenuated viral vaccines, inactivated viral vaccines and peptide-based vaccines are well studied in children, are safe and can play a central role in controlling the spread of COVID19 in children. But the long-term safety profile of viral vector-based vaccines is not studied. In the present correspondence we highlight the possibility of random insertional mutagenesis and potential side effects, which might be evident after long-term. Regulators must take into consideration the possibility of insertional mutagenesis and conduct long term studies before approving the viral vector vaccines in children, so that the public have trust in the regulatory agencies and are compliant towards vaccinating their children with safe and effective vaccines.
Bioelectrical impedance vector analysis as an indicator of malnutrition in children under five years with and without pneumonia in Mchinji District, Malawi: An exploratory mixed-methods analysis
Authors: Dunning Hanna , Zadutsa Beatiwel , Kainja Esther , Colbourn Tim , McCollum Eric D. , Makwenda Charles , Wells Jonathan , Grijalva-Eternod Carlos S. , King Carina 
Published: August 2022

Background: Bioelectrical impedance vector analysis (BIVA) is a non-invasive assessment of body composition and cellular health, which may improve the assessment of nutritional status in sick children. We explored the reliability, clinical utility, and acceptability of BIVA, as an indicator of nutritional status for children under five years with and without pneumonia, in Malawi. Methods: We conducted a parallel convergent mixed-methods exploratory study in Mchinji District Hospital, Malawi, in 2017. We planned to recruit a convenience sample of children aged 0-59 months with clinical pneumonia, and without an acute illness. Children had duplicate anthropometric and BIVA measurements taken. BIVA measurements of phase angle (PA) were taken of the whole body, and trunk and arm segments. Reliability was assessed by comparing the variability in the two measures, and clinical utility by estimating the association between anthropometry and PA using linear regression. Focus group discussions with healthcare workers who had not previously used BIVA instrumentation were conducted to explore acceptability. Results: A total of 52 children (24 with pneumonia and 28 healthy) were analysed. The reliability of sequential PA measurements was lower than anthropometric measurements, but trunk and arm segments performed better. The largest associations with PA were a negative relationship with weight-for-age z-score (WAZ) and PA in children with pneumonia in the trunk segment, and a positive association with WAZ in the full body measurement in healthy children. Healthcare workers in focus group discussions expressed trust in BIVA technology and that it would enable more accurate diagnosis of malnutrition; however, they raised concerns about the sustainability and necessary resources to implement BIVA. Conclusions: While healthcare workers were positive towards BIVA as a novel technology, implementation challenges should be expected. The differential direction of association between anthropometry and PA for children with pneumonia warrants further investigation.
SARS-CoV-2 seroprevalence in three Kenyan health and demographic surveillance sites, December 2020-May 2021
Authors: Etyang Anthony O. , Adetifa Ifedayo , Omore Richard , Misore Thomas , Ziraba Abdhalah K. , Ng’oda Maurine A. , Gitau Evelyn , Gitonga John , Mugo Daisy , Kutima Bernadette , Karanja Henry , Toroitich Monica , Nyagwange James , Tuju James , Wanjiku Perpetual , Aman Rashid , Amoth Patrick , Mwangangi Mercy , Kasera Kadondi , Ng’ang’a Wangari , Akech Donald , Sigilai Antipa , Karia Boniface , Karani Angela , Voller Shirine , Agoti Charles N. , Ochola-Oyier Lynette I. , Otiende Mark , Bottomley Christian , Nyaguara Amek , Uyoga Sophie , Gallagher Katherine , Kagucia Eunice W. , Onyango Dickens , Tsofa Benjamin , Mwangangi Joseph , Maitha Eric , Barasa Edwine , Bejon Philip , Warimwe George M. , Scott J. Anthony G. , Agweyu Ambrose 
Published: August 2022

Background
Most of the studies that have informed the public health response to the COVID-19 pandemic in Kenya have relied on samples that are not representative of the general population. We conducted population-based serosurveys at three Health and Demographic Surveillance Systems (HDSSs) to determine the cumulative incidence of infection with SARS-CoV-2.

Methods
We selected random age-stratified population-based samples at HDSSs in Kisumu, Nairobi and Kilifi, in Kenya. Blood samples were collected from participants between 01 Dec 2020 and 27 May 2021. No participant had received a COVID-19 vaccine. We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Locally-validated assay sensitivity and specificity were 93% (95% CI 88–96%) and 99% (95% CI 98–99.5%), respectively. We adjusted prevalence estimates using classical methods and Bayesian modelling to account for the sampling scheme and assay performance.

Results
We recruited 2,559 individuals from the three HDSS sites, median age (IQR) 27 (10–78) years and 52% were female. Seroprevalence at all three sites rose steadily during the study period. In Kisumu, Nairobi and Kilifi, seroprevalences (95% CI) at the beginning of the study were 36.0% (28.2–44.4%), 32.4% (23.1–42.4%), and 14.5% (9.1–21%), and respectively; at the end they were 42.0% (34.7–50.0%), 50.2% (39.7–61.1%), and 24.7% (17.5–32.6%), respectively. Seroprevalence was substantially lower among children (<16 years) than among adults at all three sites (p≤0.001).

Conclusion
By May 2021 in three broadly representative populations of unvaccinated individuals in Kenya, seroprevalence of anti-SARS-CoV-2 IgG was 25–50%. There was wide variation in cumulative incidence by location and age.
Initiating gender-affirming hormones for transgender and non-binary people: A qualitative study of providers’ perspectives on requiring mental health evaluations
Authors: Stroumsa Daphna , Minadeo Leah A. , Maksutova Mariam , Moravek Molly B. , Stephenson Rob , Pfeiffer Paul N. , Wu Justine P. 
Published: August 2022

Objective
Gender-affirming hormones (GAH)—the use of sex hormones to induce desired secondary sex characteristics in transgender individuals—is vital healthcare for many transgender people. Among prescribers of GAH, there is debate regarding the value of a universal requirement for an evaluation by a mental health provider prior to GAH initiation. The purpose of this qualitative study was to describe the range of attitudes and approaches to mental health evaluation among GAH providers in the United States. We analyzed the providers’ attitudes and base our recommendations on this analysis.

Methods
We conducted semi-structured interviews with 18 healthcare providers who prescribe GAH across the United States. Participants were purposefully recruited using professional networks and snowball sampling to include those who require mental health evaluation and those who do not. We adapted domains from the Theoretical Domains Framework—a framework for understanding influences on health professional behavior—to inform the interviews and analysis. Guided by these domains, we iteratively coded text and identified theoretical relationships among the categories.

Results
While some felt a universal requirement for mental health “clearance” was necessary for the identification of appropriate candidates for GAH, others described this requirement as a form of “gatekeeping” that limits access to care. Themes we identified included providers’ ability to ascertain gender identity; concern about mental illness; GAH provider and mental health provider expertise; and provider roles. All providers appreciated the potential advantages of mental health support during GAH treatment.

Conclusion
Providers in our study practice on a continuum of care rather than adhering to strict rules about the requirement for mental health evaluation prior to GAH treatment. Where they fall on this continuum is influenced primarily by their perceptions of transgender identity and transition, and their interpretation of risk for significant mental illness and its association with transness. Providers who required universal evaluation by a mental health professional tended to hold essentialist, medicalized, and binary ideas of gender and transness.
Effect of timing of coronary revascularization in patients with post-infectious myocardial infarction
Authors: Tsai Chuan-Tsai , Lu Ya-Wen , Chou Ruey-Hsing , Kuo Chin-Sung , Huang Po-Hsun , Wu Cheng-Hsueh , Huang Shao-Sung 
Published: August 2022

Objectives
Acute infection is a well-known provocative factor of acute myocardial infarction (AMI). Prognosis is worse when it is associated with sepsis. Coronary revascularization is reported to provide benefit in these patients; however, the optimal timing remains uncertain.

Methods
This retrospective study was performed at a tertiary center in Taipei from January 2010 to December 2017. 1931 patients received coronary revascularization indicated for AMI. Among these, 239 patients were hospitalized for acute infection but later developed AMI. Patients with either an ST-elevation myocardial infarct or the absence of obstructive coronary artery disease were excluded. Revascularization was performed via either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). We defined early and delayed revascularization groups if it was performed within or after 24 hours of the diagnosis of AMI, respectively. We evaluated whether the timing of revascularization altered 30-day and one-year all-cause mortality.

Results
At one month, 24 (26%) patients died in early revascularization group and 32 (22%) patients in delayed revascularization group. At one year, 40 (43%) and 59 (40%) patients died on early and delayed revascularization groups respectively. Early revascularization did not result in lower 30-day all-cause mortality (P = 0.424), and one-year all-cause mortality (Hazard ratio (HR): 0.935; 95% confidence interval (CI): 0.626–1.397, P = 0.742) than delay revascularization.

Conclusions
Timing of coronary revascularization of post infectious acute coronary syndrome may be arranged according to individual risk category as those without sepsis.
Immune hyporeactivity to bacteria and multiple TLR-ligands, yet no response to checkpoint inhibition in patients just after meeting Sepsis-3 criteria
Authors: Bick Alexandra , Buys Willem , Engler Andrea , Madel Rabea , Atia Mazen , Faro Francesca , Westendorf Astrid M. , Limmer Andreas , Buer Jan , Herbstreit Frank , Kirschning Carsten J. , Peters Jürgen 
Published: August 2022

Rationale
The immune profile of sepsis patients is incompletely understood and hyperinflammation and hypoinflammation may occur concurrently or sequentially. Immune checkpoint inhibition (ICI) may counter hypoinflammation but effects are uncertain. We tested the reactivity of septic whole blood to bacteria, Toll-like receptor (TLR) ligands and to ICI.

Methods
Whole blood assays of 61 patients’ samples within 24h of meeting sepsis-3 criteria and 12 age and sex-matched healthy volunteers. Measurements included pattern/danger-associated molecular pattern (P/DAMP), cytokine concentrations at baseline and in response to TLR 2, 4, and 7/8 ligands, heat-inactivated Staphylococcus aureus or Escherichia coli, E.coli lipopolysaccharide (LPS), concentration of soluble and cellular immune checkpoint molecules, and cytokine concentrations in response to ICI directed against programmed-death receptor 1 (PD1), PD1-ligand 1, or cytotoxic T-lymphocyte antigen 4, both in the absence and presence of LPS.

Main results
In sepsis, concentrations of P/DAMPs and inflammatory cytokines were increased and the latter increased further upon incubation ex vivo. However, cytokine responses to TLR 2, 4, and 7/8 ligands, heat-inactivated S. aureus or E. coli, and E. coli LPS were all depressed. Depression of the response to LPS was associated with increased in-hospital mortality. Despite increased PD-1 expression on monocytes and T-cells, and monocyte CTLA-4 expression, however, addition of corresponding checkpoint inhibitors to assays failed to increase inflammatory cytokine concentrations in the absence and presence of LPS.

Conclusion
Patients first meeting Sepsis-3 criteria reveal 1) depressed responses to multiple TLR-ligands, bacteria, and bacterial LPS, despite concomitant inflammation, but 2) no response to immune checkpoint inhibition.
Dynamics and Potential Significance of Spontaneous Activity in the Habenula
Authors: Suryadi  , Cheng Ruey-Kuang , Birkett Elliot , Jesuthasan Suresh , Chew Lock Yue 
Published: August 2022

AbstractThe habenula is an evolutionarily conserved structure of the vertebrate brain that is essential for behavioral flexibility and mood control. It is spontaneously active and is able to access diverse states when the animal is exposed to sensory stimuli. Here we investigate the dynamics of habenula spontaneous activity, to gain insight into how sensitivity is optimized. Two-photon calcium imaging was performed in resting zebrafish larvae at single-cell resolution. An analysis of avalanches of inferred spikes suggests that the habenula is subcritical. Activity had low covariance and a small mean, arguing against dynamic criticality. A multiple regression estimator of autocorrelation time suggests that the habenula is neither fully asynchronous nor perfectly critical, but is reverberating. This pattern of dynamics may enable integration of information and high flexibility in the tuning of network properties, thus providing a potential mechanism for the optimal responses to a changing environment.
KEARIFAN KETATANEGARAAN DAN GENDER MELAYU ISLAM PAHANG DI ACEH: SATU ANALISA
Authors: Ahmad Farid Abd Jalal  , Rahimin Affandi Abdul Rahim  , Mohamad Hilmi Mad Said  , Muhammad Jumaidy Abdul Manap  
Published: August 2022

Abstract - This study examines the constitutional wisdom and gender of Malay Muslims in Pahang which was detected in Aceh. The influence of these two aspects of wisdom existed in the historical tradition of Acheh. This study will utilize historical facts from primary and secondary sources in the areas that it touched on. To demonstrate, there are some prominent key factors that are worth mentioning. Firstly, the relationship between Aceh and Pahang began with familial ties which later led to intellectual ties based on religion. Secondly, there was the influence of Aceh scholars, namely Nurudin Al-Raniri and Hamzah Al-Fansuri in Pahang. The said influence involved the field of Malay Islamic Constitution. Thirdly, the wisdom of the Malay Muslim gender grew from the prominence of Puteri Kamelia in Aceh. The impact of this wisdom can be seen until now, in Acehnese culture.
Abstrak - Kajian ini akan melihat kearifan ketatanegaraan dan gender Melayu Islam Pahang yang dikesan penggunaannya di Aceh. Apa yang dibanggakan, pengaruh pemikiran Melayu Pahang dapat dikesan penggunaannya dalam kearifan ketatanegaraan dan gender di Aceh. Lebih bermakna lagi, kerana Aceh adalah kuasa besar di Alam Melayu suatu masa dahulu. Dalam sejarah mencatatkan bagaimana bahawa kitab ilmu Islam milik sarjana Aceh telah disebarkan ke seluruh jajahan empayar Aceh. Jadi, sedikit sebanyak idealism Melayu milik Pahang turut tersebar sama.
Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension
Authors: Fleseriu Maria , Newell-Price John , Pivonello Rosario , Shimatsu Akira , Auchus Richard J , Scaroni Carla , Belaya Zhanna , Feelders Richard A , Vila Greisa , Houde Ghislaine , Walia Rama , Izquierdo Miguel , Roughton Michael , Pedroncelli Alberto M , Biller Beverly M K 
Published: August 2022

Abstract

Objective
To investigate the long-term efficacy and tolerability of osilodrostat, a potent oral 11β-hydroxylase inhibitor, for treating Cushing's disease (CD).

Design/methods
A total of 137 adults with CD and mean 24-h urinary free cortisol (mUFC) &gt; 1.5 × upper limit of normal (ULN) received osilodrostat (starting dose 2 mg bid; maximum 30 mg bid) during the prospective, Phase III, 48-week LINC 3 (NCT02180217) core study. Patients benefiting from osilodrostat at week 48 could enter the optional extension (ending when all patients had received ≥ 72 weeks of treatment or discontinued). Efficacy and safety were assessed for all enrolled patients from the core study baseline.

Results
Median osilodrostat exposure from the core study baseline to study end was 130 weeks (range 1–245) and median average dose was 7.4 mg/day (range 0.8–46.6). The reduction in mean mUFC achieved during the core was maintained during the extension and remained ≤ ULN. Of 106 patients, 86 (81%) patients who entered the extension had mUFC ≤ ULN at week 72. Improvements in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism (fat pads, central obesity, rubor, striae, and hirsutism in females), and quality of life in the core study were also maintained or improved further during the extension. No new safety signals were reported; 15/137 (10.9%) and 12/106 (11.3%) patients discontinued for adverse events during the core and extension, respectively. Mean testosterone in females decreased towards baseline levels during the extension.

Conclusions
Data from this large, multicentre trial show that long-term treatment with osilodrostat sustains cortisol normalisation alongside clinical benefits in most patients with CD and is well tolerated.
Solving the Terminology Problem of Accounting Manipulations (Earnings Management and Creative Accounting)
Authors: Bachtijeva Diana 
Published: August 2022

The work presents a variety of terms that name accounting manipulations. After analyzing scientific sources and conducting an analysis of the bibliographic data of the publications presented on the Web of Science website, the terminology problems prevailing in foreign and Lithuanian literature are revealed. This terminology brings a lot of confusion when dealing with the problem of accounting manipulations. The article examines the reasons for the use of different terms, presents the results of the conducted expert assessment. Experts appreciated the phenomenon – accounting manipulations that affect the amount of profit. They named associations derived from the terms "earnings management" and "creative accounting" used in Lithuanian literature. According to experts, the Lithuanian term that best reflects the phenomenon is manipulative accounting. The article presents the definition of manipulative accounting, which is constructed on the basis of the literature analysis.