bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of civil society organizations (CSOs) in the COVID-19 response across the Global South: A multinational, qualitative study
Authors: Levine Adam C. , Park Anna , Adhikari Anindita , Alejandria Maria Carinnes P. , Bradlow Benjamin H. , Lopez-Portillo Maria F. , Mutwafy Salma , Zumbyte Ieva , Heller Patrick
Published: September 2023

Despite receiving less attention than high-income countries, low- and middle-income countries (LMICs) experienced more than 85% of global excess deaths during the first two years of the COVID-19 pandemic. Due to the unprecedented speed and scale of the COVID-19 pandemic, which placed large demands on government capacity, many LMICs relied on civil society organizations (CSOs) to assist in implementing COVID-19 response programs. Yet few studies have examined the critical role CSOs played in mitigating the effects of the COVID-19 pandemic in low resource settings. This study explored the CSO response to COVID-19 in five of the most heavily impacted LMICs in the Global South. Interviews were conducted from May to August 2021 with a purposive sample of CSO key informants within each of the five countries. A total of 52 CSOs were selected from which 53 key informants were interviewed either via Zoom or by phone. Interviews were coded and analyzed using NVivo or MAXQDA2020. Out of the 52 CSOs selected, 24 were national organizations, 8 were regional, and 20 were local. CSOs fell into six categories: community-based organizations, non-governmental organizations, unions/professional organizations, campaigns/social movements, research organizations/think tanks, and networks/coalitions. CSOs across all five countries adapted their missions, stretched their resources, and performed a wide range of activities that fit into five programmatic areas: food security and livelihood support, public health and medical care, cash transfer programs, risk communication and community education, and needs assessment. This qualitative analysis demonstrates the critical role CSOs played in supplementing government emergency aid response by delivering necessary resources and supporting highly vulnerable populations during the COVID-19 pandemic, as well as the primary challenges they faced in doing so. Given the generally weak state of public capacity in the LMICs studied, this role was vital to responding to the pandemic.
Rural household income mobility in Ethiopia: Dimensions, drivers and policy
Authors: Tigabu Yalfal Temesgen , Aredo Mengistu Ketema , Ademe Alelign
Published: September 2023

Welfare dynamics studies are useful in understanding how individuals, families, society, and a country are organised. For the last two decades, Ethiopia’s economic reports on income disparity, poverty, and other welfare metrics have been hopeful and controversial. It is crucial to understand how rural households of various income levels perform over time and income mobility. Income mobility can be observed as a change in position over time between two income vectors, with some climbing and others sliding down and changing places at various rates. This study, therefore, explored the rural households’ income mobility in Ethiopia using three waves of the Living Standards Measurement Study-Integrated Survey on Agriculture (LSMS-ISA) collected from 2011 to 2016. The Shorrocks rigidity index, transition probability matrix, Fields, and Ok methods were employed to analyse the relative and absolute income mobility. The logit model with conditional fixed effect was used to assess the drivers of individual households’ income mobility and the multinomial logit model with conditional fixed effect as an alternative model. Based on the finding of this study, it is suggested to implement different policies targeting income growth to shorten mobility gaps and address factors contributing to downward income mobility in rural households in Ethiopia are necessary.
Biochar supported metallo-inorganic nanocomposite: A green approach for decontamination of heavy metals from water
Authors: Khalid Sana , Chaudhary Muhammad Nawaz , Nazir Rabia , Ahmad Sajid Rashid , Hussain Naqi , Ayub Yaseen , Ibrar Muhammad
Published: September 2023

Heavy metal contamination of water has become a global environmental burden, which has stirred up agitation worldwide. Fabrication of adsorbents utilizing either low cost, environment friendly materials or waste products can be helpful in remediating environmental pollution. The current study evolved around the synthesis of nanocomposites derived from such raw precursors like spent tea waste biochar, hydroxyapatite, and clays. In this context, two nanocomposites, namely manganese ferrite doped hydroxyapatite/kaolinite/biochar (TK-NC) and manganese ferrite doped hydroxyapatite/vermiculite/biochar (TV-NC), were synthesized followed by their employment for decontamination of heavy metals from aqueous media. TK-NC and TV-NC exhibited the crystallite sizes in the range of 2.55–5.94 nm as obtained by Debye Scherrer Equation and Williamsons–Hall equation The fabricated nanocomposites were characterized using FT-IR, SEM-EDX, and powder XRD. Batch adsorption studies were performed, and influence of different adsorption parameters (contact time, reaction temperature, solution pH, adsorbent dose, and initial adsorbate concentration) on metal adsorption was examined. Thermodynamic studies revealed that the adsorption of Cr(VI), Ni(II) and Cu(II) on TK-NC and TV-NC was endothermic (+ΔH°) and indicates disorderness (+ΔS°) at the solid-liquid interface owing to the strong affinity of metal ions with adsorbent. The heavy metal uptake selectivity followed the following decreasing order; Cr(VI) > Cu(II) > Ni(II) by both nanocomposites, with adsorption capacities falling in the range of 204.68–343.05 mg g-1. Several adsorption kinetic and isotherm models were applied to experimentally calculated data, which suggest favorable adsorption of Cr(VI), Ni(II) and Cu(II) by TK-NC and TV-NC from the system while obeying general-order kinetics and R-P adsorption model, conferring the transition in adsorption kinetics order and involvement of multiple adsorption process.
Care trajectory differences in women and men with end-stage renal disease after dialysis initiation
Authors: Piveteau Juliette , Raffray Maxime , Couchoud Cécile , Chatelet Valérie , Vigneau Cécile , Bayat Sahar
Published: September 2023

Few studies investigated sex-related differences in care consumption after dialysis initiation. Therefore, the aim of this study was to compare the care trajectory in the first year after dialysis start between men and women by taking into account the context of dialysis initiation. All patients who started dialysis in France in 2015 were included. Clinical data of patients and context of dialysis initiation were extracted from the Renal Epidemiology and Information Network (REIN) registry. Data on care consumption in the first year after dialysis start came from the French national health data system (SNDS): hospital stays <24h, hospital stays to prepare or maintain vascular access, hospital stays >24h for kidney problems and hospital stays >24h for other problems, and consultations with a general practitioner. Variables were compared between men and women with the χ2 test and Student’s or Welch t-test and logistic regression models were used to identify the factors associated with care consumption after dialysis start. The analysis concerned 8,856 patients (36% of women). Men were less likely to have a hospital stays >24h for kidney problems than women (OR = 0.8, 95% CI = [0.7–0.9]) and less general practitioner consultations (OR = 0.8, 95% CI = [0.8–0.9]), in the year after dialysis initiation, after adjustment on patient’s characteristics. Moreover, hospital stays for vascular access preparation or maintenance were longer in women than men (median duration: 2 days [0–2] vs. 1 day [0–2], p < 0.001). In conclusion, despite greater comorbidities in men, this study found few differences in post-dialysis care trajectory between men and women.
The paradox of closing mutual funds to new investors
Authors: Covachev Svetoslav
Published: September 2023

I provide an explanation for the well-established paradox that mutual funds that close to new investors fail to maintain their pre-closure positive abnormal performance after closing. Using a large sample of active US equity mutual funds, I find that the within-style performance ranks of closed funds revert to the mean as strongly as those of a control group of open funds. Furthermore, I show that funds that are closed do not drastically alter their investment allocations and hold portfolios that are indistinguishable from their portfolios prior to closing in terms of risk-adjusted performance. Therefore, mean reverting stock returns explain the deterioration in fund performance after closing to new investors. I also document that funds are not capable of better preserving their assets when anticipating a decline in performance by closing to new investors and thus adding exclusivity. Furthermore, the control group of open funds does not suffer from excessive flows. Closing to new investors is at best unnecessary from the stand-alone perspective of the fund.
Pre-vaccination monocyte-to-lymphocyte ratio as a biomarker for the efficacy of malaria candidate vaccines: A subgroup analysis of pooled clinical trial data
Authors: Nyandele Jane Paula , Kibondo Ummi Abdul , Issa Fatuma , Van Geertruyden Jean Pierre , Warimwe George , Jongo Said , Abdulla Salim , Olotu Ally
Published: September 2023

Background

Pre-vaccination monocyte-to-lymphocyte ratio was previously suggested as a marker for malaria vaccine effectiveness. We investigated the potential of this cell ratio as a marker for malaria vaccine efficacy and effectiveness. Effectiveness was investigated by using clinical malaria endpoint, and efficacy was investigated by using surrogate endpoints of Plasmodium falciparum prepatent period, parasite density, and multiplication rates in a controlled human malaria infection trial (CHMI).

Methods

We evaluated the correlation between monocyte-to-lymphocyte ratio and RTS,S vaccine effectiveness using Cox regression modeling with clinical malaria as the primary endpoint. Of the 1704 participants in the RTS,S field trial, data on monocyte-to-lymphocyte ratio was available for 842 participants, of whom our analyses were restricted. We further used Spearman Correlations and Cox regression modeling to evaluate the correlation between monocyte-to-lymphocyte ratio and Whole Sporozoite malaria vaccine efficacy using the surrogate endpoints. Of the 97 participants in the controlled human malaria infection vaccine trials, hematology and parasitology information were available for 82 participants, of whom our analyses were restricted.

Results

The unadjusted efficacy of RTS,S malaria vaccine was 54% (95% CI: 37%-66%, p <0.001). No correlation was observed between monocyte-to-lymphocyte ratio and RTS,S vaccine efficacy (Hazard Rate (HR):0.90, 95%CI:0.45–1.80; p = 0.77). The unadjusted efficacy of Whole Sporozoite malaria vaccine in the appended dataset was 17.6% (95%CI:10%-28.5%, p<0.001). No association between monocyte-to-lymphocyte ratio and the Whole Sporozoite malaria vaccine was found against either the prepatent period (HR = 1.16; 95%CI:0.51–2.62, p = 0.72), parasite density (rho = 0.004, p = 0.97) or multiplication rates (rho = 0.031, p = 0.80).

Conclusion

Monocyte-to-lymphocyte ratio alone may not be an adequate marker for malaria vaccine efficacy. Further investigations on immune correlates and underlying mechanisms of immune protection against malaria could provide a clearer explanation of the differences between those protected in comparison with those not protected against malaria by vaccination.
From short to long term: Dynamic analysis of FDI and net export in global regions
Authors: Lakshani Sanduni , Sandaruwan Chanuka , Fernando Chanaka , Vidyapathirana Gayan , Jayathilaka Ruwan , Munasinghe Sumudu
Published: September 2023

It is crucial to examine the impact between foreign direct investment (FDI) and net exports (NE) for unveiling international trade dynamics, and the economic development of different geographical regions. It yields sharp insights into how FDI inflows, driven by theories such as backward linkage, export platform, and knowledge transfer, enhance a host country’s export capacity and contribute to economic growth. Moreover, studying the reciprocal linkages between FDI and NE helps recognise the aspects of domestic factors, such as productivity and the product life cycle, in attracting FDI and increasing export performance. Based on those theories, the study aims to ascertain the dynamic causality or correlation between FDI and NE across all regions with the utilisation of panel data gathered from 110 countries, considering the period from 2002 to 2020. The Wavelet coherence method is used to investigate the relationship between these variables across different frequencies and periods, followed by a Granger causality test. The findings demonstrated that FDI and NE have a significant relationship in most regions, with a bidirectional relationship between FDI and NE across all continents. The results could assist respective governments and policymakers in formulating policies related to FDI flows and offer insights into how a host country can attract more FDI and boost NE.
RSV infection in children hospitalised with severe lower respiratory tract infection in a low-middle-income setting: A cross-sectional observational study
Authors: Morgan Nicole , Buys Heloise , Muloiwa Rudzani
Published: September 2023

Introduction

Low- and middle-income countries carry the largest burden of Respiratory syncytial virus (RSV) disease, with most deaths occurring in these settings. This study aimed to investigate the burden of RSV disease in South African children hospitalised with lower respiratory tract infection (LRTI), with specific reference to incidence, risk factors, and co-infections.

Methods

A database from a previous prospective study containing demographic, laboratory and clinical data on children hospitalised with LRTIs in Cape Town, South Africa, was used. A nasopharyngeal swab (NP) and induced sputum (IS) were tested for RSV PCR. Descriptive statistics were used to characterise the study population, and a multivariable analysis of risk factors and co-infections was done.

Results

RSV was detected in 142 (30.9%; 95% CI 26.7–35.3) of the included 460 study children with LRTI. The median age of RSV-positive children was 4.6 (IQR 2.4–9.7) months compared to RSV-negative children of 10.5 (IQR 4.4–21.3) months, P = <0.001. Most cases occurred in autumn and winter with 126 (89%) cases over this period. IS demonstrated greater sensitivity for RSV diagnosis with 135 cases (95.1%) detected on IS and 57 cases (40.1%) identified on NP; P<0.001. The median length of hospital stay was 3.3 (SD 4.2) days in the RSV positive group and 2.7 (SD 3.3) days in the RSV negative group; P<0.001. The median number of detected viral pathogens was 1 (IQR 0–2) in RSV-positive children (when RSV was excluded from the count) compared to 2 (IQR 2–3) in RSV negative children; P<0.001. The presence of RSV was independently associated with a reduction in the frequency of most viruses tested for on PCR.

Conclusions

RSV is common in children hospitalised with LRTI and mainly affects younger children. There is an urgent need to find an effective vaccine to prevent RSV pneumonia in children worldwide, especially in LMICs that carry the greatest burden of disease.
An enhanced three-stage design with trend analysis for allergen immunotherapy trials
Authors: Tang Xinyu , Rabin Ronald L. , Yan Lihan K.
Published: September 2023

We previously introduced a three-stage design and associated end-of-stage analyses for allergen immunotherapy (AIT) trials. End-of-stage differences alone may not provide a fuller picture of Stages 2 and 3 effects because they may depend upon stage-specific durations. Therefore, we introduce an additional trend analysis to evaluate the difference in progression curves of two groups over the entire stage. Results from such analysis are used to inform persistence of end-of-stage benefit and thus provide evidence for stagewise effects beyond the study periods. We jointly apply end-of-stage and trend analyses to support the enhanced three-stage design to determine treatment response over time and sustained response to AIT. A simulation study was performed to illustrate the statistical properties (bias and power) of trend analyses under varying statistical missing mechanisms and effect sizes. The extent of bias depended on the missing mechanism and magnitude. Powers were largely driven by effect and sample sizes as well as pre-specified success margins, particularly of relative trend. As an illustration, assuming relative treatment differences of 25–30%, stagewise dropout rate of 15%, and parallel outcome progressions, a sample size of 200 per group may achieve 97% power to demonstrate a treatment effect and 53% power to demonstrate a sustained effect post-treatment. Trend analysis supplements the end-of-stage analysis to enhance the statistical claims of stagewise effects. Inferential statistics support our proposed trend analysis for evaluating benefits of AIT over time and inform clinical understanding and decisions.
Mortality risk after the first occurrence of osteoporotic vertebral compression fractures in the general population: A nationwide cohort study
Authors: Son Hee Jung , Park Se-Jun , Kim Jeong-Keun , Park Jin-Sung
Published: September 2023

Osteoporotic vertebral compression fractures (OVCF) can cause severe pain, changes in balance, gait velocity, muscle fatigue, risk of falls, and subsequent fractures. Thus, OVCF significantly lowers the individual’s health-related quality of life. Additionally, OVCF may increase patient mortality rates. However, studies on post-OVCF mortality are limited. This study aimed to evaluate mortality risk after the first occurrence of OVCF in the general population using a nationwide dataset from the Korean National Health Insurance System. We identified 291,203 newly diagnosed patients with OVCF and 873,609 patients without OVCF at a ratio of 1:3 matched by sex and age between 2010 and 2012. We investigated the latent characteristics of patients’ demographic information and chronic comorbidities that could affect mortality when diagnosed with OVCF. By comparing the cohort data, the hazard ratio for subsequent mortality in patients with OVCF was calculated and adjusted based on several risk factors. Despite adjusting for demographic characteristics and chronic comorbidities, the risk of mortality was 1.22 times higher in the OVCF cohort than in the control group. Multivariate analysis showed that male sex, old age, low-income status, and high Charlson Comorbidity Index were associated with a higher risk of mortality. In addition, the presence of chronic comorbidities, including diabetes mellitus, ischemic heart disease, stroke, chronic obstructive pulmonary disease, cancer, and end-stage renal disease, was shown to increase the risk of mortality. This population-based cohort study showed that newly diagnosed OVCF significantly increased the subsequent risk of mortality. Moreover, post-OVCF mortality is influenced by demographic characteristics and chronic comorbidities.
Investigating the Distributional Effect of the UK Carbon Price Floor
Authors: Nguyen William
Published: September 2023

This paper empirically investigates the distributional effects of the UK carbon price floor (CPF) on households’ electricity expenditure. I employ the difference-in-differences model to analyse the impact of the carbon price floor on vertical inequality. The main result finds that households in the poorest quintile are most impacted by the electricity price increase. I further explore the heterogenous effect on households within the bottom quintile by considering various household characteristics. This paper contributes to the existing literature on carbon pricing policies, in particular their impact on inequality both across income groups and within households in the poorest quintile.
Perspektif Tasawuf terhadap Kematian
Authors: Sofyan Nurul Hikmah , Anindya Aryu Inayati
Published: September 2023

Abstract
This article raises the issue of human fear of death. Fear of death will be a problem if it is excessive and does not encourage someone to prepare for death. Therefore, there is a need for study of death from sufism perspective to look again at the essence of death so that the unnatural fear of death can at least be reduced. This study uses a qualitative method with an irfani analysis technique that is adjusted to meet the need of sufism approach in this study. The result of this paper is that death is the separation of humans from what has been entrusted to humans in the world because of a moving from the world to a completely different realm. As for the destruction of body through death, it is not followed by the death of spirit. It causes spirit is created from God’s spirit, the human spirit by nature always yearns and always wants to return to where it came from. In order for the nature of spirit's longing for God to be maintained, a servant is required to always control or at least reduce worldly desires that can prevent a servant from having an inclination towards God.
Keywords: Death, Body, Human Longing, Human Spirit
Jaime Balmes sobre la frenología
Authors: Aonso Diego Juan Carlos
Published: September 2023

En el año 1843 se establece un debate entre el teólogo Jaime Balmes y el frenólogo Mariano Cubí. El primero cuestiona los fundamentos científicos de la naciente ciencia de la medición de cráneos y sus incursiones ilegítimas en otros ámbitos del saber. El debate constituye un ejemplo temprano del diálogo entre la ciencia y la teología en la España del siglo XIX.
Soft sensor method for endpoint carbon content and temperature of BOF based on multi-cluster dynamic adaptive selection ensemble learning
Authors: Shao Bin , Liu Hui , Chen Fu-gang
Published: September 2023

The accurate control of the endpoint in converter steelmaking is of great significance and value for energy saving, emission reduction, and steel quality improvement. The key to endpoint control lies in accurately predicting the carbon content and temperature. Converter steelmaking is a dynamic process with a large fluctuation of samples, and traditional ensemble learning methods ignore the differences among the query samples and use all the sub-models to predict. The different performances of each sub-model lead to the performance degradation of ensemble learning. To address this issue, we propose a soft sensor method based on multi-cluster dynamic adaptive selection (MC-DAS) ensemble learning for converter steelmaking endpoint carbon content and temperature prediction. First, to ensure the diversity of the ensemble learning base model, we propose a clustering algorithm with different data partition characteristics to construct a pool of diverse base models. Second, a model adaptive selection strategy is proposed, which involves constructing diverse similarity regions for individual query samples and assessing the model’s performance in these regions to identify the most suitable model and weight combination for each respective query sample. Compared with the traditional ensemble learning method, the simulation results of actual converter steelmaking process data show that the prediction accuracy of carbon content within ±0.02% error range reaches 92.8%, and temperature within ±10°C error range reaches 91.6%.
Künstliche Intelligenz in der umweltorientierten Logistik
Authors: Bergmann Leopold , Janetzky Mathias , Ritter Milena
Published: September 2023

Der Trend zur intelligenten Logistik ist allgegenwärtig. Bereits heute lässt sich dies anhand der gestiegenen Anzahl hochkomplexer Optimierungen entlang der Supply Chain erkennen, die eine höhere Transparenz, beschleunigte Prozesse und schlussendlich die Erfüllung der Kundenbedürfnisse sicherstellen. Mehrheitlich rechtfertigen ökonomische Verbesserungspotenziale den Einsatz von KI-Technologien in der Logistik. Welche ökologischen Potenziale darüber hinaus ausgeschöpft werden können, analysiert der vorliegende Beitrag.
Effizient digitalisieren mit Shopfloor Services
Authors: Sapel Patrick , Bega Maximilian , Ercan Furkan , Schmitz Mauritius , Hopmann Christian , Kuhlenkötter Bernd
Published: September 2023

Digitalisierte Geschäftsprozesse versprechen den Unternehmen Mehrwerte, wie z. B. kürzere Durchlaufzeiten. Diese Prozesse sind jedoch selten standardisiert, sodass insbesondere kleine und mittlere Unternehmen (KMU) aufgrund finanzieller und personeller Hürden kaum von den Mehrwerten profitieren. Dieser Beitrag stellt eine für KMU entwickelte Hard- und Softwareinfrastruktur sowie vordefinierte Shopfloor Services vor, die KMU dabei helfen können, digitalisierte Geschäftsprozesse aufwandsarm zu implementieren.
Resilienz aus der Wertstromperspektive
Authors: Steinmeyer Maximilian , Metternich Joachim
Published: September 2023

In kurzer Abfolge auftretende Krisen stellen die Wertströme produzierender Unternehmen auf unterschiedliche Weise vor große Herausforderungen: Lieferketten brechen plötzlich zusammen, Preissteigerungen werden unkalkulierbar oder Mitarbeitende fallen unerwartet aus. Um diese Herausforderungen mit einer möglichst niedrigen Beeinträchtigung in den Zieldimensionen Flexibilität, Qualität, Produktivität und Durchlaufzeit zu bewältigen, müssen Wertströme resilienter werden. In der bisherigen Analyse und Gestaltung von Wertströmen wird Resilienz jedoch kaum berücksichtigt. Daher zeigt dieser Beitrag, wie Wertströme aus der Resilienzperspektive betrachtet werden können, und schlägt erste Maßnahmen zur Steigerung der Wertstromresilienz vor.
Apresentação
Authors: Trotte Alyssa , Henrique da Mota Ferreira Daniel , Silva Reghim Mariane , Nunes Raul
Published: September 2023

No caso da pandemia de Covid-19, a América Latina presenciou as mais diversas formas de mobilização social. Num primeiro momento, muitos atores fizeram uma conversão abrupta de atividades presenciais para atividades digitais, a exemplo dos eventos transmitidos ao vivo e da criação de hashtags. Contudo, logo os conflitos sociais foram também para as ruas, com marchas, greves e enfrentamentos, que aglutinaram pautas trabalhistas, questões de raça e gênero, aspectos territoriais e também tópicos próprios dA pandemia, como a demanda por auxílios financeiros e insumos para a proteção contra a contaminação pelo vírus. Além disso, destacaram-se também ações solidárias, como a distribuição de alimentos, as cozinhas comunitárias e as doações de itens como máscaras e balões de oxigênio. Nesse sentido, parte do esforço deste dossiê acompanha reflexões e problematizações que tiveram início na construção do Observatório de Movimentos Sociais da América Latina, enquanto parte do Núcleo de Estudos de Teoria Social e América Latina (NETSAL). O Observatório foi construído com o objetivo de produzir um monitoramento dos movimentos sociais e demais formas de ativismo que vicejavam na América Latina durante o período pandêmico. Foi realizado acompanhamento dos países por meio da cobertura da imprensa, análises de páginas dos movimentos em redes sociais e interlocuções com ativistas a fim de entender a conjuntura dos países. Esse monitoramento foi publicado trimestralmente em um relatório com a situação de cada país que ganhou o nome de Comunica América Latina
Capital cultural e educação
Authors: Henrique Voos Charles , Rautenberg Pereira Amanda
Published: September 2023

Considerando os impactos do contexto familiar e social na Educação Básica e seus resultados

na vida dos alunos, objetiva

-

se compreender de que forma a trajetória escolar interfere na

vida acadêmica no ensino superior

tendo em conta

o capital cultural e dem

ais conceitos do

sociólogo Pierre Bourdieu. Para tanto, procede-se ao estudo de caso com alunos dos cursos

de graduação de Pedagogia e de Direito de uma instituição de ensino superior de Joinville,

utilizando-se de questionários como instrumento de coleta

de dados. Desse modo, observou-se que as realidades sociais presentes nos diferentes contextos impactam diretamente o

desempenho acadêmico dos estudantes e relacionam-se com demais valores culturais de seu

meio familiar.
Embedding R inside the PhysPK Bio-simulation Software for Pharmacokinetics Population Analysis
Authors: Sánchez-Herrero Sergio , Martínez Fernando Carbonero , Serna Jenifer , Cuquerella-Gilabert Marina , Rueda-Ferreiro Almudena , Juan Angel A. , Calvet Laura
Published: September 2023

Background: PhysPK stands as a flexible and robust bio-simulation and modeling software designed for analysis of population pharmacokinetics (PK) and pharmacodynamics (PD) systems. PhysPK equips users with standard diagnostic plots for pre- and post-analysis to delineate PK and PD within population-based frameworks. Furthermore, PhysPK facilitates the establishment of mathematical models that elucidate the intricate interplay between exposure, safety, and efficacy.

Methods: Enhancing simulation modeling capabilities necessitates seamless integration between commercial discrete-event PK and PD simulation tools and external software. This synergy can be amplified by incorporating open-source solutions, like R, which boasts a rich array of comprehensive packages tailored for diverse tasks, including data analysis (ggplot2), scientific computation (stats), application development (shiny), back-end web development (dplyr), and machine learning (CARAT). The integration of R within PhysPK holds the potential to efficiently interpret and analyze PK/PD output and routines using R packages.

Results: This article presents a tutorial that highlights the incorporation of R code within PhysPK and the rendering of R scripts within the PhysPK monitor. The tutorial utilizes a two-compartment model for comparison against the analysis developed by Hosseini et al. in 2018 within the context of the gPKPDSim application and WinNonlin® software. The illustrative example that is provided and discussed demonstrate estimated and simulated plots, revealing negligible differences in the significance for CL and CLd (6.89 ± 0.2 and 45.5 ± 17.4 [reference], and 7.06 ± 0.32 and 49.04 ± 9.2 [PhysPK], respectively), as well as volumes V1 and V2 (49.15 ± 3.8 and 34.61 ± 5.2 [reference], and 48.8 ± 3.66, and 33.2 ± 3.95 [PhysPK], respectively).

Conclusions: Our study underscores the potential of integrating open-source software, replete with an array of innovative packages, to elevate predictive capabilities and streamline analyses in PK methods. This integration ushers in new avenues for an advanced intelligent simulation modeling within the realm of PK, thus holding significant promise for the advancement of drug research and development.
High-Resolution Tractography Protocol to Investigate the Pathways between Human Mediodorsal Thalamic Nucleus and Prefrontal Cortex
Authors: Mengxing Liu , Lerma-Usabiaga Garikoitz , Clascá Francisco , Paz-Alonso Pedro M.
Published: September 2023

Animal studies have established that the mediodorsal nucleus (MD) of the thalamus is heavily and reciprocally connected with all areas of the prefrontal cortex (PFC). In humans, however, these connections are difficult to investigate. High-resolution imaging protocols capable of reliably tracing the axonal tracts linking the human MD with each of the PFC areas may thus be key to advance our understanding of the variation, development, and plastic changes of these important circuits, in health and disease. Here, we tested in adult female and male humans the reliability of a new reconstruction protocol based onin vivodiffusion MRI to trace, measure, and characterize the fiber tracts interconnecting the MD with 39 human PFC areas per hemisphere. Our protocol comprised the following three components: (1) defining regions of interest; (2) preprocessing diffusion data; and, (3) modeling white matter tracts and tractometry. This analysis revealed largely separate PFC territories of reciprocal MD–PFC tracts bearing striking resemblance with the topographic layout observed in macaque connection-tracing studies. We then examined whether our protocol could reliably reconstruct each of these MD–PFC tracts and their profiles across test and retest sessions. Results revealed that this protocol was able to trace and measure, in both left and right hemispheres, the trajectories of these 39 area-specific axon bundles with good-to-excellent test-retest reproducibility. This protocol, which has been made publicly available, may be relevant for cognitive neuroscience and clinical studies of normal and abnormal PFC function, development, and plasticity.

SIGNIFICANCE STATEMENTReciprocal MD–PFC interactions are critical for complex human cognition and learning. Reliably tracing, measuring and characterizing MD–PFC white matter tracts using high-resolution noninvasive methods is key to assess individual variation of these systems in humans. Here, we propose a high-resolution tractography protocol that reliably reconstructs 39 area-specific MD–PFC white matter tracts per hemisphere and quantifies structural information from diffusion MRI data. This protocol revealed a detailed mapping of thalamocortical and corticothalamic MD–PFC tracts in four different PFC territories (dorsal, medial, orbital/frontal pole, inferior frontal) showing structural connections resembling those observed in tracing studies with macaques. Furthermore, our automated protocol revealed high test-retest reproducibility and is made publicly available, constituting a step forward in mapping human MD–PFC circuits in clinical and academic research.
Presynaptic Kainate Receptors onto Somatostatin Interneurons Are Recruited by Activity throughout Development and Contribute to Cortical Sensory Adaptation
Authors: Stachniak Tevye J. , Argunsah Ali Ö. , Yang Jenq-Wei , Cai Linbi , Karayannis Theofanis
Published: September 2023

Somatostatin (SST) interneurons produce delayed inhibition because of the short-term facilitation of their excitatory inputs created by the expression of metabotropic glutamate receptor 7 (mGluR7) and presynaptic GluK2-containing kainate receptors (GluK2-KARs). Using mice of both sexes, we find that as synaptic facilitation at layer (L)2/3 SST cell inputs increases during the first few postnatal weeks, so does GluK2-KAR expression. Removal of sensory input by whisker trimming does not affect mGluR7 but prevents the emergence of presynaptic GluK2-KARs, which can be restored by allowing whisker regrowth or by acute calmodulin activation. Conversely, late trimming or acute inhibition of Ca2+/calmodulin-dependent protein kinase II is sufficient to reduce GluK2-KAR activity. This developmental and activity-dependent regulation also produces a specific reduction of L4 GluK2-KARs that advances in parallel with the maturation of sensory processing in L2/3. Finally, we find that removal of both GluK2-KARs and mGluR7 from the synapse eliminates short-term facilitation and reduces sensory adaptation to repetitive stimuli, first in L4 of somatosensory cortex, then later in development in L2/3. The dynamic regulation of presynaptic GluK2-KARs potentially allows for flexible scaling of late inhibition and sensory adaptation.

SIGNIFICANCE STATEMENTExcitatory synapses onto somatostatin (SST) interneurons express presynaptic, calcium-permeable kainate receptors containing the GluK2 subunit (GluK2-KARs), activated by high-frequency activity. In this study we find that their presence on L2/3 SST synapses in the barrel cortex is not based on a hardwired genetic program but instead is regulated by sensory activity, in contrast to that of mGluR7. Thus, in addition to standard synaptic potentiation and depression mechanisms, excitatory synapses onto SST neurons undergo an activity-dependent presynaptic modulation that uses GluK2-KARs. Further, we present evidence that loss of the frequency-dependent synaptic components (both GluK2-KARs and mGluR7 via Elfn1 deletion) contributes to a decrease in the sensory adaptation commonly seen on repetitive stimulus presentation.
Effectiveness of a Teaching Material: News-Based Teaching of Mount Ungaran
Authors: Nuryani Sri , Rahayuningsih Margareta , Irsadi Andin , Fibriana Fidia
Published: September 2023

The news-based teaching is a teaching material that contains news integrated with the results of exploring the biodiversity on Mount Ungaran for high school students in  Biology subject. Teaching materials were prepared based on the results of the needs analysis. Early observation of High School 12 Semarang students showed that Biology learning sources were still insufficient to achieve basic competence. This study aimed to develop valid news-based teaching material of Mount Ungaran Biodiversity using the research and development (RD) method for effective cognitive, psychomotor, and affective learning outcomes. The research method subjected the students of High School 12 Semarang to explore the biodiversity news of Mount Ungaran on the websites. Also, the students searched the information from Research Development (RD). The results showed that (1) news-based teaching material on Mount Ungaran biodiversity was valid and appropriate as a learning source (96%), (2) and it was effective to improve the students’ cognitive, psychomotor, and affective learning outcomes of biodiversity topic.
Molecular Docking of the Cannabis sativa L. Bioactive Compound Against Inflammation Induced by Cigarette Smoke Exposure
Authors: Lisdiana Lisdiana , Mustikaningtyas Dewi
Published: September 2023

Cigarette smoke can modulate and increase chronic inflammation of the respiratory tract. The constituents of cigarette smoke-induced inflammation can activate several cell signaling pathways, including mitogen-activated protein kinases (MAPK), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription (STAT), and activatory protein-1 (AP-1). Cannabis plant (Cannabis sativa L.) contains many phytochemical compounds including cannabinoids, terpenes and phenolic compounds, which have potential in medicine, one of them is as an anti-inflammatory. This study aims to determine the interactions formed between bioactive compounds from cannabis plants in anti-inflammatory activity caused by cigarette smoke induction in the JAK/STAT and MAPK pathways through a study in silico. This research method was carried out in a descriptive exploratory manner using   online databases such as PubChem, PASS online, SEA (Similarity Ensemble Approach) and Swiss Target Prediction, STRING. Docking simulation was carried out using PyRx 0.8. Data from software and web devices were analyzed descriptively and compared with control compounds. The docking results show that the compounds from Cannabis sativa L. can act as an anti-inflammatory in the context of cigarette smoke-induced inflammation. This is indicated by the similarity of amino acid residues resulting from the interaction of the aspirin drug (control) with the anti-inflammatory receptor protein in the compound cannabidihydrophenanthrene with PDGFRA and KDR receptors and compounds cannabicyclol with AKT1 and KDR receptors. This is indicated by the presence of value affinity is low indicating a stable and strong bond.
In Vitro Antiinflammatory Activity of Bajakah (Spatholobus littoralis) Stem Extract
Authors: Rousdy Diah Wulandari , Wardoyo Elvi Rusmiyanto
Published: September 2023

The plant of Bajakah tampala (Spatholobus littoralis Hassk) has been utilized in traditional medication. Previous studies have proven the existence of in vivo anti-inflammatory activities of Bajakah plant (S. littoralis) in lowering the degree of carrageenan-induced paw oedema in mice. This study aims to determine the anti-inflammatory mechanism of S. littoralis extract in vitro through an approach of enzyme inhibition involved in the inflammatory reaction. The concentration of ethanol extract of Bajakah used was 0.1; 0.2; 0.4; 0.8; 1.6 mg/ml. The parameters measured were lipoxygenase enzyme inhibition, protein denaturation inhibition, protease enzyme inhibition, as well as plasma membrane stabilization. The results of the study showed the potential of the ethanol extract of Bajakah stems in inhibiting the inflammatory process viewed from the ability to inhibit inflammation-related enzymes. S. littoralis extract concentration of 1.6 mg/ml showed the best inhibition of the protein denaturation process (75.9%), the inhibition of trypsin protease enzyme (26.1%) and the stability of erythrocyte membrane (93.7%). However, the extracts of S. littoralis did not provide inhibition for the lipoxygenase enzyme in the range of 0.2-3.8%. This study proves the role of S. littoralis extract in the anti-inflammatory mechanism. It has the potential to be developed into standardized herbs.
Visceral Organ Weight of Pengging Duck after the Addition of Nanochitosan as Feed Additive
Authors: Kwardoyo Khevalin , Sunarno Sunarno , Mardiati Siti Muflichatun
Published: September 2023

The productivity of pengging ducks is determined by optimizing the function of the body's organs. The feed consumed greatly determines the growth and development of the internal organs in the pengging duck. Nanochitosan is a polysaccharide that has potential as a feed additive which functions to increase feed digestibility, nutrient absorption, promote growth to help optimize the function of visceral organs. This study aims to analyze the effect of nanochitosan as a feed additive on the function of the visceral organs of pengging ducks in terms of the weight of the visceral organs. The visceral organs studied included the ventriculus, intestines, liver, pancreas, spleen, and heart. This study was designed in a completely randomized design (CRD) consisting of 5 treatments (0; 2.5; 5; 7.5; 10 g nanochitosan/kg feed) with 5 replications. Nanochitosan feed additive treatment was given for 8 week. Variables that were measured in this study included weight of ventriculus, intestinal, liver, pancreas, spleen, and heart of pengging ducks. The research data showed that nanochitosan as a feed additive had no significant effect on visceral weight of pengging ducks (P0.05). The conclusion of this study is that nanochitosan as a feed additive does not cause changes in the function of the visceral organs based on the indication of the weight of the visceral organs measured, namely the ventricles, intestines, liver, pancreas, spleen, and heart. The novelty of this research is the use of nanochitosan as a feed additive to improve the performance of penging ducks by maintaining the size of the visceral organs. It is hoped that the results of this research on nanochitosan feed additive can be used by local laying duck farms in Indonesia because it is safe and as an effort to improve the performance and productivity of ducks.
Phylogenetic Relationship of Cymbidium Mosaic Virus from the Native Orchids of South Kalimantan, Indonesia
Authors: Mursyidin Dindin Hidayatul , Saputra Ahmad Winarto
Published: September 2023

Information on viral genetics, including their phylogenetic relationship, is valuable in controlling viral infection and screening for the development of virus-resistant cultivars in the future. The objectives of this study were to detect and characterize the Cymbidium mosaic virus (CymMV) from the native orchids of South Kalimantan, Indonesia, by the RT-PCR method. Also, to determine their phylogenetic relationship based on a partial genome of RdRp by the ML and PCA methods. Following RT-PCR analysis, one of 10 samples of native orchids used was positively infected by CymMV. In early detection, the RdRp region of CymMV has approximately 530 bp in size. After being sequenced and aligned with other isolates, this region has 121 polymorphic or mutation sites, a GC content of 45.21%, a transition/transversion bias value of 3.52, and nucleotide diversity (0.0415). The phylogenetic analysis revealed that CymMV from South Kalimantan, Indonesia, has closest related to similar isolates from Korea Type 2 (AF016914.1), Niigata, Japan (AB197937.1), Hawaii (EF125180.1), and Taiwan M2 (EU314803.1), with the coefficient divergence of 0.025. But, it has very distantly related to Hawaii 18-1 (EF125178.1) with a coefficient of 0.142. The results provide urgent information in supporting the native orchid's conservation and breeding efforts, locally and globally, including mitigating or controlling the viral infection and screening for the development of virus-free or resistant cultivars in the future.
Polyketide Synthase Gene Domain Exploration of Marine Sponge Symbiont Bacteria Collected From Weh Island
Authors: Santosa Sukmawan Fajar , Nazaruddin Nazaruddin , Sari Wahyu Eka , Febriani Febriani
Published: September 2023

Sponges have long been known as a source for isolating secondary metabolites. These natural compounds are biosynthetic products of symbiont bacteria from various phyla colonizing sponge tissue. Some symbiont bacteria are known to produce bioactive compounds that would have antibacterial activity, such as polyketide, due to competition in colonizing and obtaining nutrients from their hosts. In general, this study aims to explore the biosynthetic potential of seven sponge-symbiont bacteria by detecting the gene domain involved in the production of polyketide compounds. Sponge-symbiont bacteria isolation was carried out on one species of sponge collected from a depth of ±15 m in the Iboih area, Weh Island, Aceh Province, Indonesia. The bacteria was allowed to grow in Sea Water Complete agar medium and incubated at 280C for 10-14 days. The production of polyketide compounds involves the enzyme polyketide synthase (PKS). Polyketide synthase was detected by detecting the encoding gene domain involved in the production of polyketide compounds using PCR method. Five of the seven isolates of sponge symbiont bacteria were detected to contain the PKS gene domain. Furthermore, molecular identification confirm by 16S rRNA sequencing showed that the isolates belonged to the phylum Firmicutes and Actinobacteria. The result indicated that the sponge symbiont bacteria collected from Weh Island had the biosynthetic potential to produce polyketide compounds. These compounds would have antimicrobial activities that will play a major role in the medical field. Research related to screening PKS genes in marine sponge symbionts bacteria from Weh Island has never been reported before, thus adding to the novelty of this research.
Chemical Analysis of Sea urchin Diademasetosum Gonads
Authors: Djafar Mohamad Haikal K. , Solang Margaretha , Hamidun Marini Susanti , Abdul Aryati , Kumaji Syam S. , Nane La
Published: September 2023

Sea urchins Diademasetosum can be found in shallow waters. Sea urchin gonads are nutritionally valuable and capable of accumulating heavy metals. This study aims to determine the moisture content, ash, protein, fat, carbohydrate, Pb, Cd metal content and determine the Maximum Tolerable Intake (MTI) of sea urchin D. setosum gonads. Gonad samples were obtained from three coasts of Huangobotu, Botubarani and Kurenai, Kabila Bone Sub-district, Bone Bolango Regency, using a purposive sampling technique. Gonads were analyzed proximate, including moisture, ash, protein, fat and carbohydrate content. Analysis of Pb and Cd levels using an atomic absorption spectrophotometer. The results were analyzed statistically using One-Way ANOVA Test. The results showed that the average moisture, ash, protein, fat, and carbohydrate content of gonads on the coast of Huangobotu, Botubarani, and Kurenai were significantly different (p0.005); moisture content 71.91%, 75.04%, 78.51%; ash content 1.88%, 1.15%, 2.76%; protein content 9.90%, 12.81%, 15.53%; fat content 7.33%, 3.05%, 4.84%; carbohydrate content 2.35%, 7.92%, 4.93%. Pb levels were significantly different (p0.005) 0.063 mg/kg, 0.039 mg/kg, and 0.018 mg/kg, respectively; Cd levels were not significantly different (p0.005) 0.020 mg/kg, 0.012 mg/kg, 0.014 mg/kg respectively. MTI Pb adults 23.8kg, 38.4kg, 83.3kg, children 5.9kg, 9.6kg, 20.8kg. MTI Cd adults 21kg, 35kg, 30kg, children 5.25kg, 8.75kg, 7.5kg. D. setosumhas potential as a source of protein and can be utilized as food by considering the MTI value.