bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating tumour DNA dynamics during alternating chemotherapy and hormonal therapy in metastatic breast cancer: the ALERT study
Authors: Allsopp Rebecca , Guo Qi , Page Karen , Bhagani Shradha , Kasim Anna , Badman Philip , Kenny Laura , Stebbing Justin , Shaw Jacqueline
Published: March 2024

Purpose
Although changes in circulating tumour DNA (ctDNA) in breast cancer are well described, the kinetics of their fluctuations has not been described over short timescales. We investigated ctDNA dynamics during alternating cycles of chemotherapy and hormonal treatment in pre-treated patients with estrogen receptor positive metastatic breast cancer.
Methods
Patients received alternating, 9-week cycles of eribulin and aromatase inhibitors (AIs). The clinical primary endpoint, progression free survival (PFS) was monitored at 3, 6 and 9 months; secondary endpoints clinical benefit rate (CBR), safety and tolerability profiles were also assessed. Importantly, ctDNA fluctuations were monitored using the Oncomine™ Breast cfDNA assay to test whether biomarkers may change rapidly between chemotherapy and aromatase inhibitor (AI) treatment in the setting of advanced breast cancer, potentially reflecting disease dynamics.
Results
The median PFS was 202 days (95% CI: 135-undefined) and 235 days (95% CI: 235-undefined) at 6 and 9 months respectively, with a 50% CBR at both 6 and 9 months. Dynamic changes in ctDNA were observed in short timescales between chemotherapy and AI treatment and support the clinical benefit (CB) seen in individual patients and critically, appear informative of acquired resistance in real-time.
Conclusion
Changes in ctDNA can occur rapidly and reflect changes in patients’ clinical tumour responses (NCT02681523).
Optical UV detection of the glucose content in solution for application in glucose monitoring
Authors: urbiola Iker Rodrigo chavez , Cruz-Zabalegui Alexis , Tirado-Cantú Pablo Alfonso , Willar-Rodriguez Francisco , Chávez-Urbiola Edgar Arturo , Vorobiev Pavel , Vorobiev Yurii
Published: March 2024

The present work describes an optical method for glucose determination from frontier equations and predictive mechanisms. A theoretical description of the electronic transitions in glucose molecule treated as a quantum dot and experimental validation were carried out. The calculation relies on the photon absorption between the ground and the first excited state. The results were 263, and 277 nm for experimental and theoretical estimation, respectively. The glucose quantification was done by optical transmittance in a glucose solution. Photonic glucose absorption was recorded in the 5–30 mM range. The method showed a 0.00876%Abs/mM sensibility with linear behavior.
Sensitivity analysis of hygrothermal effect in triangular rigid frame area of V-shaped pier rigid frame bridge
Authors: Chu Xurong , Li Rui , Ding Hao , Wang Yubian , Alexandrovich Erofeev Alexander
Published: March 2024

The V-shaped pier rigid frame bridge is a multiple statically indeterminate structure with the consolidation of the pier beam foundation, and the secondary internal force effect of the triangular rigid frame area rigidly connected by the V pier and the No.0 block is significant under the action of temperature and humidity. Therefore, taking the Gunnong Bridge in Myanmar as the engineering background, by establishing the finite element model of the whole bridge space bar system and the local solid model of the triangular rigid frame area to study the sensitivity of the three most important ambient factors of temperature, humidity, and wind speed to the hygrothermal effect of the triangular rigid frame area of the V-shaped pier rigid frame bridge. The results show that the hygrothermal stress of box girder and V pier is linearly correlated with temperature and relative humidity, and nonlinearly correlated with wind speed. Under the influence of temperature, wind speed and relative humidity, the hygrothermal stress at the junction of V pier river water and air is greater than that at the upper and lower roots of V pier. The sensitivity of structural hygrothermal stress to temperature and relative humidity is constant, and the sensitivity to wind speed is linear negative correlation. When the wind speed is less than 6m/s, the sensitivity of wind speed is much greater than that of temperature and relative humidity.
Single cell sequencing and multiple machine learning identified CD2 and ITGAV as novel biomarkers for NASH-related fibrosis
Authors: Yan Xuebing , Li Chunyang , Xi Deyang , Hu Junhan , Raun Yuhua , Wang Jialu
Published: March 2024

Background
Non-Alcoholic Steatohepatitis (NASH) is a prevalent form of liver inflammation that can progress to fibrosis and even hepatocellular carcinoma. The purpose of this research is to explore the biomarkers for NASH-related fibrosis based on single cell sequencing and machine learning.
Methods
We retrieved three datasets from the GEO database (GSE228232, GSE162694, GSE130970). Within GSE228232, we conducted cell annotation, pseudotime analysis, cell communication, and high-dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA). In GSE162694, differential analysis, immune cell infiltration, and enrichment analyses were performed to discern the gene differences between the NASH and NASH-F groups. Ultimately, multiple machine learning algorithms were employed to validate the biological markers of NASH-F.
Results
In the analysis of the GSE162694 dataset, immune infiltration studies revealed significant differences in various types of T cells between the NASH and NASH-F groups. Pseudotime analysis indicated a strong association between NASH-F and T cells with high expression of Cd8a/b, Cxcr6, and Pdcd-1. Through single-cell sequencing and transcriptome analysis, we have isolated a set of 15 genes conserved between mouse models and human cases of NASH. This conserved gene set includes BCL11B, CD2, CD3E, CD5, GLS, GZMK, ICOS, ITGAV, LEF1, NEURL3, NR4A3, PFKP, RGS1, THEMIS, and THY1. Subsequent machine learning models corroborated CD2 and ITGAV as biomarkers for NASH-F.
Conclusion
Leveraging single-cell sequencing and multiple machine learning, our study delves into the pathogenesis of T cells in NASH-associated fibrosis and identifies CD2 and ITGAV as biomarkers of NASH-F.
Hybrid model of the FEM method and the SAR algorithm to perform reliability-based design optimization of the solder joints in the BGA assembly
Authors: Reddad Hakima , Zemzami Maria , Hami Norelislam El , Hmina Nabil , Nguyen Nhan-Quy
Published: March 2024

Metaheuristic optimization algorithms are powerful for solving complex optimization problems, almost when we lack information about the nature of their objective function. Meanwhile, the Finite Element Method (FEM) is a very powerful method for predicting and simulating the behavior of systems subjected to various stresses, whether electrical, thermal, mechanical, vibratory or magnetic. In the current study, we have proposed an optimization methodology that couples a metaheuristic algorithm - the Search and Rescue Algorithm (SAR) - with the finite element method. We then investigated the proposed methodology for optimizing the reliability of solder balls with respect to their geometry in a Ball Grid Array (BGA) assembly subjected to thermal cycling load. First, we performed a sensitivity analysis to determine the parameters influencing solder ball reliability, then we optimized the plastic deformation of solder balls, hence increasing their reliability as a function of their geometry through the proposed methodology, which results in improving the reliability of the entire electronic component.
Developing a city-wide, community-engaged cancer disparities research agenda
Authors: Leader Amy E. , Song Yawei , González Evelyn T. , Fortune Thierry , Graciani Nilsa , Zeigler-Johnson Charnita , Glanz Karen
Published: March 2024

Introduction: In response to high levels of cancer disparities in Philadelphia, PA, three NCI-designated clincal cancer centers formed Philadelphia Communities Conquering Cancer (PC3) to bring stakeholders together and establish infrastructure for future cancer reducing initiatives. The PC3 coalition aimed to develop a prioritized cancer disparities research agenda in order to align cancer center resources and research interests with the concerns of the community about cancer, and to ensure that initiatives were patient- and community-centered.
Methods: Agenda development activities culminated in a city-wide cancer disparities conference. The conference, attended by 55 diverse stakeholders, was the venue for small group discussion sessions about cancer concerns related to prevention, early detection, treatment, survivorship and quality of life. Sessions were guided by a moderator guide and were audiorecorded, transcribed, and analyzed by the PC3 leadership team. Results were reviewed and consensus was achieved with the help of PC3’s Stakeholder Advisory Committee.
Results: Stakeholders identified four thematic areas as top priorities for cancer disparities research and action in Philadelphia: communication between patients, providers, and caregivers; education that reaches patients and community members with tailored and targeted information; navigation that assists people in finding and accessing the right cancer screening or treatment option for them; and representation that diversifies the workforce in clinics, cancer centers, and research offices.
Conclusion: A community-informed, prioritized research agenda provides a road map for the three cancer centers to collaborate on future initiatives that are important to patients and stakeholders, to ultimately reduce the burden of cancer for all Philadelphians.
Advancing Embryo Selection: A Comparative Study of State-of-the-Art Deep Learning Models for IVF Embryo Quality Assessment
Authors: Tran Duc M. , Pham Phat T. , Nguyen Anh H. , Vu Hieu H. , Do Cuong , Pham Lam D.
Published: March 2024

This paper presents a comprehensive analysis of the application of deep learning models for embryo quality assessment in the field of in vitro fertilization (IVF). As embryo selection plays a crucial role in the success rates of IVF treatments, it is important to adopt an automated and accurate system to evaluate embryo viability. Our study focuses on comparing the effectiveness of four state-of-the-art deep learning models: VGG-19, EfficientNet, MobileNet, and ResNet, in classifying embryos based on their Inner cell mass (ICM) and trophectoderm (TE) cell characteristics from microscopic images. Utilizing a dataset of 1,020 embryonic images from two significant developmental stages distributed through the World Championship in Data Science and Artificial Intelligence 2023 - ISODS, we systematically trained and evaluated each model to address the challenges posed by small and imbalanced datasets commonly encountered in medical imaging. Through a series of experiments, including the application of data augmentation techniques and advanced model training strategies, we aimed to optimize model performance and minimize overfitting. The results revealed that EfficientNet-B0 has a high accuracy and robustness in distinguishing between viable and non-viable embryos. Additionally, we explored the potential of explainable AI techniques, such as Grad-CAM visualizations, to provide insights into the decision-making processes of the models. This study not only contributes to the advancement of automated embryo assessment systems but also lays the groundwork for future research to enhance IVF success rates through improved embryo selection methodologies.
Effect of benzoic acid-based and cinnamic acid-based polyphenols on foaming properties of ovalbumin at acidic, neutral and alkaline pH conditions
Authors: Wen Hedi , Zhang Deju , Ning Zhenzhen , Li Zihao , Zhang Yan , Liu Jingbo , Yu Ting , Zhang Ting
Published: March 2024

To broaden the application of ovalbumin (OVA) in food formulations, it is meaningful to improve its foaming characteristics. This study aimed to investigate the effect of benzoic acid-based (3,4-dihydroxybenzoic acid, DA) and cinnamic acid-based polyphenols (trans-2-hydroxycinnamic acid, T2A) on the foaming properties of OVA at acidic (pH 3.0), neutral (pH 7.4) and alkaline (pH 9.0) pH conditions. Both the addition of polyphenols and acid treatment enhanced the foaming properties of OVA. Surface hydrophobicity, circular dichroism, free sulfhydryl groups, and Fourier transform infrared spectroscopy results indicated that after acidic workup, the presence of stronger hydrophobic interactions in OVA-polyphenol aggregates induced more disordered protein conformation and conversion or breakage of disulfide bonds. Particle size and zeta potential indicated that acidic treatment neutralized protein surface charges, further inducing self-aggregation and swelling of OVA, ultimately enhancing foaming properties. Comparatively, T2A exhibited better foam-inducing capacity due to its stronger interaction with OVA, leading to the unfolding of the OVA structure and the exposure of more hydrophobic groups. The intrinsic and 3-D fluorescence spectra experiments also confirmed that OVA-T2A aggregates at pH 3.0 had greater altered non-covalent interaction forces and protein secondary and tertiary structures compared to other complexes. This study provides a theoretical basis for designing protein formulations with excellent foaming properties.
Kooperationskonflikte in inklusiven Settings
Authors: Urbanek Claudia , Quante Alina , Rank Astrid
Published: March 2024

Schulische Inklusion funktioniert nicht ohne Kooperation. Diese bringt einerseits Potentiale mit sich, kann aber auch zu Konflikten führen. Konflikte können auf verschiedenen Ebenen verortet und in verschiedene Typen unterschieden werden. Im Text werden zunächst die sozialwissenschaftliche Konzeptionalisierung von Konflikten und der Forschungsstand zu Konflikten in der inklusiven Kooperation dargestellt. Anschließend werden anhand der Interviewdaten des BMBF-Projekts „P-ink“ Beispiele für typische Kooperationskonflikte zwischen grundschul- und sonderpädagogischen Lehrkräften analysiert. Im Fazit werden Möglichkeiten herausgearbeitet, wie Qualifizierung für Inklusion dem Thema „Kooperationskonflikte“ begegnen kann.
Abstract
Inclusion in schools is not possible without collaboration. It entails potential as well as conflicts. Conflicts take place on different levels and can be divided into different types. Following a socioscientific conception of conflicts and empirical research findings, the article analyses examples of typical collaboration conflicts between primary school teachers and special education teachers based on interview data from the BMBF-Projekts “P-ink“. At last we carve out possibilities how qualification for inclusion can deal with the topic of “Collaboration conflicts”.
Tunnelling to holographic traversable wormholes
Authors: Bintanja Suzanne , Freivogel Ben , Rolph Andrew
Published: March 2024

We study nonperturbative effects of quantum gravity in a system consisting of a coupled pair of holographic CFTs. The AdS_44/CFT_33 system has three possible ground states: two copies of empty AdS, a pair of extremal AdS black holes, and an eternal AdS traversable wormhole. We give a recipe for calculating transition rates via gravitational instantons and test it by calculating the emission rate of radiation shells from a black hole. We calculate the nucleation rate of a traversable wormhole between a pair of AdS-RN black holes in the canonical and microcanonical ensembles. Our results give predictions of nonpertubative quantum gravity that can be tested in a holographic simulation.
Occurrence and concentrations of traditional and emerging contaminants in onsite wastewater systems and water supply wells in eastern North Carolina, USA
Authors: Humphrey Charles P. , Iverson Guy , Hvastkovs Eli , Pradhan Sushama
Published: March 2024

Onsite wastewater treatment systems (OWTSs) and private wells are commonly used in Eastern North Carolina, USA. Water from private wells is not required to be tested after the initial startup, and thus persons using these wells may experience negative health outcomes if their water is contaminated with waste-related pollutants including bacteria, nitrate or synthetic chemicals such as hexafluoropropylne oxide dimer acid and its ammonium salt (GenX). Water samples from 18 sites with OWTSs and groundwater wells were collected for nitrate, Escherichia coli (E. coli), total coliform, and GenX concentration analyses. Results showed that none of the 18 water supplies were positive for E. coli, nitrate concentrations were all below the maximum contaminant level of 10 mg L−1, and one well had 1 MPN 100 mL−1 of total coliform. However, GenX was detected in wastewater collected from all 18 septic tanks and 22% of the water supplies tested had concentrations that exceeded the health advisory levels for GenX. Water supplies with low concentrations of traditionally tested for pollutants (nitrate, E. coli) may still pose health risks due to elevated concentrations of emerging contaminants like GenX and thus more comprehensive and routine water testing is suggested for this and similar persistent compounds.
Facile removal of rhodamine B and metronidazole with mesoporous biochar prepared from palm tree biomass: adsorption studies, reusability, and mechanisms
Authors: Azeez Luqmon , Adefunke Oyinlola , Oyedeji Abdulrasaq O. , Agbaogun Babatunde K. , Busari Hassan K. , Adejumo Ayoade L. , Agbaje Wasiu B. , Adeleke Adebayo E. , Samuel Awolola O.
Published: March 2024

Biochar was produced by pyrolysing palm tree bark biomass at 500 °C for the removal of rhodamine B (RhB) and metronidazole (MET). Fourier-transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller, X-ray diffraction (XRD), scanning electron microscopy, and energy-dispersive X-ray analyses were used to characterize the biochar. The biochar obtained was crystalline, mesoporous (SBET: 189.157 m2 g−1; pore diameter: 2.207 nm), clustered with prominent O–H and C = O functional groups. The pHpzc of the biochar was 7.98, and it adsorbed RhB and MET maximally at pH 3.4 and 7.2, respectively. The Langmuir and Freundlich isotherms described RhB and MET adsorption, respectively, with maximum adsorption capacities (qmax) of 31.81–224.30 mg/g for RhB and 95.44–26.76 mg/g for MET from 303 to 313 K. Both adsorbates exhibit favourable physisorption processes with pseudo-second-order kinetics, as the most appropriate. The thermodynamic parameter (−ΔG°) demonstrates spontaneous adsorption processes for RhB and MET, with spontaneity increasing with temperature for RhB and decreasing with increasing temperature for MET. The adsorption process was endothermic (+ΔH°) for RhB and exothermic (−ΔH°) for MET. Given its reusability of 96 and 95% for RhB and MET, respectively, mesoporous biochar derived from palm trees is a more promising adsorbent.
Ascertainment of the most suitable water harvesting sites in a data-scarce region via an integrated PROMETHEE-II–AHP method in GIS environment
Authors: Ashraf Muhammad Usman , Masood Muhammad , Iqbal Mudassar , Ahsan Muhammad Farhan , Mustafa Anees ul
Published: March 2024

People residing in arid and semi-arid regions face significant challenges because of water scarcity and floods. These challenges become more severe in downstream areas of hill torrents that experience highly unpredictable periods of droughts and floods due to highly variable rainfall. Constructing small dams in hill torrents to capture rainwater from watersheds, mitigate flash floods, and recharge artificial groundwater is one of the solutions to address these issues in South Punjab. However, the success of rainwater harvesting (RWH) systems depends on their technical design and suitable site selection. To identify appropriate sites for small dams for rainwater harvesting, a combination of Geographical Information Systems (GIS), Remote Sensing (RS), and Multi-Criteria Decision Analysis (MCDA) has been utilized in the catchment of the Vidore Hill Torrent, Punjab, Pakistan. The primary goal of this study was to evaluate the use of RS and MCDA in developing a suitability map, in a data-scarce region that can be useful for hydrologists, decision-makers, and planners in quickly identifying areas with the highest potential for RWH. The model incorporated several factors, including slope, runoff depth, land use, soil texture, drainage density, and lineament density. Implementing this method could also support policy changes toward widespread adoption of RWH.
Multi-criteria decision-making methods for optimal design of intermittent water distribution network
Authors: Ramani Katineni , Umamahesh Nanduri V.
Published: March 2024

Multi-objective optimization of water distribution networks (WDNs) is crucial for achieving a balance between cost, equity, and reliability. The present study conducts a comparative analysis, evaluating the effectiveness of four multi-objective optimization algorithms implemented within the EPANET framework for the optimal design of three distinct WDNs taken from the literature. The networks were optimized considering three objectives: maximizing network resilience, and uniformity coefficient (CU, a measure of uniformity), alongside minimizing the cost of the network. Further, multi-criteria decision-making (MCDM) analysis is carried out, encompassing various MCDM techniques and weighting methods, to explore the sensitivity of solution rankings. In Network 1, non-dominated sorting genetic algorithm 2 (NSGA-II) produced suboptimal solutions with CU and In values below 0.4, while caRamel, multi-objective particle swarm optimization based on crowding distance (MOPSO-CD), and multi-objective evolutionary algorithm with decomposition (MOEA/D) showcased increasing CU and In values towards 1, paralleled by a rise in network cost. The performance of NSGA-II in Network 3 was unsatisfactory (CU < 0.32), while the other algorithms demonstrated satisfactory values (>0.98) for reliability and (>0.5) for CU. The findings offer valuable insights into cost-effective strategies for achieving equity in water supply without substantial impact on overall network cost. The findings of the study also underscore the sensitivity of ranking outcomes in MCDM analysis to the choice of technique and weighting method.
An improved transfer coefficient method considering the combined effect of reservoir level variation and rainfall and its application in the stability evaluation of multistage sliding ancient landslides
Authors: Gou Xiaofeng , Xu Mo , Li Xiao , Li Anrun , Deng Hui
Published: March 2024

In this paper, by considering the dynamic water pressure and particle migration effect caused by reservoir level variation, the weakening effect of slip zone soil influenced by rainfall infiltration, and the interaction force between multistage sliding bodies, an improved transfer coefficient method for multistage sliding ancient landslide is proposed under the combined action of reservoir level variation and rainfall. The results show that (1) the combined action of reservoir level variation and rainfall has a significant influence on the stability of multistage sliding ancient landslides. (2) The sliding force calculated by the improved transfer coefficient method is smaller than the calculation result by the traditional transfer coefficient method, and the residual sliding force is larger. The different sliding body stability coefficient is reduced by about 28.84, 18.13, 19.26, and 21.01%, respectively. (3) The stability results calculated by the traditional transfer coefficient are higher than the improved transfer coefficient method, which may lead to deviation in the multistage sliding ancient landslide stable state judgment. (4) This improved transfer coefficient method can provide a reference for the multistage sliding ancient landslides stability accurate evaluation in hydropower station reservoir area.
Optimizing start-up strategies for the two-inflow nitritation/anammox process: Influence on biofilm microbial community composition
Authors: Zulkarnaini Zulkarnaini , Matsuura Norihisa , Kanazawa Sui , Honda Ryo , Yamamoto-Ikemoto Ryoko
Published: March 2024

Low-energy nitrogen removal from ammonium-rich wastewater is crucial in preserving the water environment. A one-stage nitritation/anammox process with two inflows treating ammonium-containing wastewater, supplied from inside and outside the wound filter, is expected to stably remove nitrogen. Laboratory-scale reactors were operated using different start-up strategies; the first involved adding nitritation inoculum after anammox biomass formation in the filter, which presented a relatively low nitrogen removal rate (0.171 kg N/m3 · d), at a nitrogen loading rate of 1.0 kg N/m3 · d. Conversely, the second involved the gradual cultivation of anammox and nitritation microorganisms, which increased the nitrogen removal rate (0.276 kg N/m3 · d). Furthermore, anammox (Candidatus Brocadia) and nitritation bacteria (Nitrosomonadaceae) coexisted in the biofilm formed on the filter surface. The abundance of nitritation bacteria (10.5%) in the reactor biofilm using the second start-up strategy was higher than that using the first (3.7%). Thus, the two-inflow nitritation/anammox process effectively induced habitat segregation using a suitable start-up strategy.
Profiling wastewater characteristics in intra-urban catchments using online monitoring stations
Authors: Corominas Lluís , Zammit Ian , Badia Sergi , Pueyo-Ros Josep , Bosch Lluís Maria , Calle Eusebi , Martínez David , Chesa Maria José , Chincolla Cristian , Martínez Ariadna , Llopart-Mascaró Anna , Varela Francisco Javier , Domene Elena , Garcia-Sierra Marta , Garcia-Acosta Xavier , Satorras Mar , Raich-Montiu Jordi , Peris Roger , Horno Raül , Rubión Edgar , Simón Sergi , Ribalta Marc , Palacín Ian
Published: March 2024

This study aims to investigate the differences in intra-urban catchments with different characteristics through real-time wastewater monitoring. Monitoring stations were installed in three neighbourhoods of Barcelona to measure flow, total chemical oxygen demand (COD), pH, conductivity, temperature, and bisulfide (HS-) for 1 year. Typical wastewater profiles were obtained for weekdays, weekends, and holidays in the summer and winter seasons. The results reveal differences in waking up times and evening routines, commuting behaviour during weekends and holidays, and water consumption. The pollutant profiles contribute to a better understanding of pollution generation in households and catchment activities. Flows and COD correlate well at all stations, but there are differences in conductivity and HS- at the station level. The article concludes by discussing the operational experience of the monitoring stations.
Unraveling Amentoflavone's Therapeutic Potential in Alzheimer's Disease:
A Preclinical Assessment
Authors: Singh Sushma , Agrawal Neetu , Goyal Ahsas
Published: March 2024

Alzheimer’s disease is one of the neurodegenerative diseases which causes cognition
deficit. There are currently few medications available to treat Alzheimer's disease, even
though researchers have devoted a great deal of time studying the condition and offering many
benefits. Thus, only a few drugs are available for the treatment of Alzheimer’s disease. Amentoflavone
is a dietary component found in many plants and herbs that has several health advantages.
Amentoflavone has demonstrated strong protective benefits against a range of brain
illnesses in preclinical trials, most frequently in Alzheimer's disease. Amentoflavone, a biflavonoid,
can be identified in a variety of herbs upon isolation. Considering the beneficial properties
of this compound, this review emphasizes the pharmacological effects and botanical sources of
amentoflavone, as well as the compound's benefits and possible applications in the treatment of
Alzheimer's disorders.
The Role of CYPs and Transporters in the Biotransformation and Transport of
the Anti-hepatitis C Antiviral Agents Asunaprevir, Daclatasvir, and
Beclabuvir: Impact of Liver Disease, Race and Drug-drug Interactions on
Safety and Efficacy
Authors: Murray Michael
Published: March 2024

Asunaprevir, daclatasvir, and beclabuvir are direct-acting antiviral agents used in the treatment of
patients infected with hepatitis C genotype 1b. This article reviews the biotransformation and disposition of these
drugs in relation to the safety and efficacy of therapy. CYP3A4 and 3A5 catalyze the oxidative biotransformation
of the drugs, while P-glycoprotein mediates their efflux from tissues. Asunaprevir is also a substrate
for the influx transporters OATP1B1 and OATP2B1 and the efflux transporter MRP2, while beclabuvir is also
a substrate for the efflux transporter BCRP. Liver disease decreases the expression of CYPs and transporters
that mediate drug metabolism and disposition. Serum asunaprevir concentrations, but not those of daclatasvir
or beclabuvir, are increased in patients with severe liver disease, which may produce toxicity. Pharmacogenomic
variation in CYPs and transporters also has the potential to disrupt therapy with asunaprevir, daclatasvir and
beclabuvir; some variants are more prevalent in certain racial groups. Pharmacokinetic drug-drug interactions,
especially where asunaprevir, daclatasvir, and beclabuvir are victim drugs, are mediated by coadministered rifampicin,
ketoconazole and ritonavir, and are attributable to inhibition and/or induction of CYPs and transporters.
Conversely, there is also evidence that asunaprevir, daclatasvir and beclabuvir are perpetrators of drug
interactions with coadministered rosuvastatin and dextromethorphan. Together, liver disease, pharmacogenomic
variation and drug-drug interactions may disrupt therapy with asunaprevir, daclatasvir and beclabuvir due to
the impaired function of important CYPs and transporters.
Identification and Synthesis of Oxidative-Degradation and Starting
Materials-Attributed Impurities in Lisdexamfetamine Dimesylate
Authors: Chaugule Suryabhan B. , Gole Pradeep L. , Haldankar Siddhesh , Kishore DVP , Bonde Nilesh L. , Kotharkar Sandeep A.
Published: March 2024

Impurities are an integral part of drug substances, even though they have not been studied
in the pharmacological evaluation of the Benefit-Risk (BR) profiles. Hence, understanding their
origin and controlling them have prime importance during drug substance development. The structures
of some of the impurities in lisdexamfetamine dimesylate, a central nervous system stimulant
drug, have been confirmed based on literature and analytical data. The study has been undertaken to
evaluate impurities arising from oxidative degradation and impurities due to material attributes. All
the listed impurities have been identified, synthesized, and characterized by spectral tools. We have,
herein, reported the synthesis of two oxidative degradant impurities, 2-hydroxylisdexamfetamine
dimesylate and 4-hydroxylisdexafetamine dimesylate. In addition, chiral isomeric impurities of
lisdexamfetamine dimesylate as (S,R), (R,S) and (R,R)-lisdexamfetamine dimesylate have also been
reported. These impurities have been identified, synthesized and a control strategy for mitigating risk
in lisdexamfetamine dimesylate is provided.
Additional Non-contrast CT to Portal Venous Phase is not Relevant for Patients
referred for Colonic Diverticulitis or Sigmoiditis Suspicion
Authors: Dray Bertille , Aubé Christophe , Boishardy Thomas , Besnier Louis , Darii Carolina , Bougard Marie , Paisant Anita
Published: March 2024

Objective::

To evaluate the usefulness of unenhanced CT added to the portal venous phase in the diagnostic accuracy of acute colonic
diverticulitis/sigmoiditis.

Methods::

Between January 1st and December 31st, 2020, all consecutive adult patients referred to the radiology department for clinical suspicion of acute
colonic diverticulitis/sigmoiditis were retrospectively screened. To be included, patients must have undergone a CT with both unenhanced (UCT)
and contrast-enhanced portal venous phase CT (CECT). CT examinations were assessed for features of diverticulitis, complications, differential
diagnosis and incidental findings using UCT + CECT association, medical management, and follow-up as the reference. Radiation doses were
recorded on our image archiving system and assessed.

Results::

Of the 114 patients included (mean age was 67±18 years; 60% were female), 46 had acute colonic diverticulitis/sigmoiditis. No diagnosis of
sigmoiditis/diverticulitis, complication or differential diagnosis was missed with the CECT alone. Apart from diverticulitis, only one 2 mm meatal
urinary microlithiasis was missed with no impact on patient management. The confidence level in diagnosis was not increased by UCT. The
average DLP of CECT was 450 mGy.cm, and 382 mGy.cm for UCT. The use of a single-phase CECT acquisition allowed a reduction of 45.9% of
the irradiation.

Conclusion::

Unenhanced CT is not necessary for patients addressed with clinical suspicion of acute colonic diverticulitis/sigmoiditis, and CECT alone protocol
must be used.
Bioinspired Catalysis with Biomimetic Clusters
Authors: Banerjee Abhishek , Paul Bishwajit , Marakatti Vijaykumar S.
Published: March 2024

Biomimetic clusters dubbed inorganic complexes are the foci of many
enzymes that are frequently earmarked for biochemical pathways. Specifically, the
biomimetic clusters are made up of transition metal(s) chelated with organic ligands.
This book chapter details redox active enzymes for the most fundamental biochemical
processes. Bio-inorganic chemists have been synthesizing numerous biomimetic
clusters that have the ability not only to mimic the active site structural features but
also to mimic their functions. In a similar vein, the fixation of nitrogen into ammonia is
akin to the fundamental biological process and thus can be considered a biomimetic
biological process. Therefore, novel materials, including electrides, nitrides, hydrides,
and basic oxides, have created a niche in facilitating biochemical reaction products.
Insights into biomimetic clusters, especially inorganic catalysts’ mimics, new materials
facilitating biological chemistries, and their mechanisms will uncover new avenues for
small molecule activation, with different catalytic mechanisms yet to be elucidated.
Psychostimulant Medications for Physical Function and Spasticity in Children With Cerebral Palsy: Protocol for a Randomized Controlled Trial
Authors: Alotaibi Mansour , Almutairi Anwar B , Alhirsan Saleh , Alkazemi Afrah , Alharbi Maha , Alrashdi Naif , Taqi Ahmad , Alamiri Bibi , Vogtle Laura , Alqahtani Mohammed M
Published: March 2024

Background

Cerebral palsy (CP) is a prevalent nonprogressive disorder that leads to impaired movement (ie, spasticity), posture, and balance, which affects functions such as walking and upper extremity tasks. Current medical treatments show efficacy in improving motor performance but have considerable side effects. Emerging off-label use of central nervous system (CNS) medications for improving motor performance has shown promising results in children with CP and other populations.

Objective

The aim of this study is to describe a protocol for a pilot randomized controlled trial (RCT) to examine the safety, tolerability, and efficacy of methylphenidate (MPH) and modafinil on spasticity and motor performance in children with CP.

Methods

This will be a protocol study for a pilot, triple-masked, placebo-controlled RCT (a class I trial following the American Academy of Neurology criteria) with blinded patients, outcome assessors, and intervention delivery team. Eligible children should be diagnosed with CP levels I or II based on the Gross Motor Function Classification System and be aged between 7 and 12 years. Thirty-six children with CP will be randomized into 3 groups to receive (1) MPH (2.5 mg of MPH + 100 mg placebo), (2) modafinil (100 mg modafinil + 2.5 mg placebo), or (3) a placebo (2.5 mg placebo + 100 mg placebo), in addition to physical therapy for 12 weeks. Primary outcomes include the Gross Motor Function Measure–66 and the Modified Ashworth Scale. Secondary outcomes include the Timed Up and Go test, 5 Time Sit to Stand test, Modified Clinical Test for Sensory Interaction of Balance, and 10-Meter Walk Test.

Results

The protocol has been accepted by Kuwait University (VDR/EC-225) and the Ministry of Health of Kuwait (2022/2157). The inclusion of participants will start in June 2024.

Conclusions

The combination of CNS stimulant medications and controlling for rehabilitation has not been studied yet. The findings of this study may determine if using CNS stimulant medications is beneficial for the reduction of spasticity and improvement of physical function in children with spastic CP.

Trial Registration

ClinicalTrials.gov NCT05675098; https://clinicaltrials.gov/study/NCT05675098

International Registered Report Identifier (IRRID)

PRR1-10.2196/53728
Efektivitas Program Latihan Aerobik pada Penurunan Nyeri Dismenore Primer: Meta-analysis
Authors: Fadli Arif , Rustanti Marti , Windiastoni Yoga Handita
Published: March 2024

Latar   Belakang: Wanita dengan Dismenore Primer (DP) dapat merasakan nyeri hebat akibat hiperkontraktilitas saat menstruasi, hipoksia, dan iskemia otot rahim. Wanita dengan DP akan mengalami hambatan aktivitas belajar dan keseharian. Obat analgetik efektif menurunkan nyeri dismenore primer dengan efek samping mual dan muntah. Program latihan aerobik bisa menjadi solusi pengobatan nyeri  DP tanpa efek samping.Tujuan: Penelitian ini bertujuan untuk mengevaluasi efektivitas program latihan aerobik untuk pengurangan nyeri akibat dismenore primer.Metode: Systematic review dan meta-analisis artikel publikasi  tahun 2013 s/d 2023 pada desain Randomized Control Trial di data based PubMed, GoogleScholar, OVID, ResearchGate, ScienceDirect. Program Revman 5.3 digunakan dalam analisis data dengan ukuran efek terapi pada penurunan nyeri DP.Hasil: 5 artikel dengan 312 wanita DP dimasukan sintesis meta-analisis. Hasilnya menunjukan bahwa latihan aerobik efektif menurunkaan nyeri akibat dismenore primer dibandingkan dengan kelompok kontrol tanpa intervensi dengan ukuran efek terapi adalah besar (d= -2,03; CI= -3,37 – 0,69; P <0,00001).Kesimpulan: Program latihan aerobik efektif menurunkan nyeri akibat dismenore primer. Latihan aerobik dapat menurunkan nyeri melalui peningkatan sirkulasi darah sistemik yang disertai penurunan sensitifitas gerak akibat dismenore primer.
Research on Blockchain-driven Agricultural Products E-commerce Supply Chain Innovation under Game Perspective
Authors: Wu Feng , Tang Qiuxia , Zhou Jun , Xu Yu
Published: March 2024

With the arrival of the big data era, digital technology has achieved an unprecedented development speed, and blockchain, as a representative of digital technology, solves the problem of mutual trust between multiple transaction subjects in different scenarios with the technological advantages of decentralisation, timestamping and non-tampering. Currently, in the agricultural products e-commerce supply chain scenario, there is the problem of credit risk of agricultural products producers and sellers. Aiming at the pain points of agricultural products e-commerce supply chain, this paper analyses from the perspective of game, through blockchain incentive mechanism, and puts forward blockchain-driven agricultural products e-commerce supply chain innovation suggestions.
The Neocolonial Structural Model Re-Foundation and The Pragmatic Inference of Organizational Culture in Ngugi Wa Thiongo’s Devil on The Cross (1980)
Authors: Diallo Souleymane
Published: March 2024

Through the frame frequency of the imported state and the westernization of the African political order, the social construction of the African bureaucracy appears as a structural device of abstraction, exploitation, and brutality. Then, through the frame of reference with the importation of conceptual juridical coordination and perceptual representative consensus, the African public administration enhances a frameshift transformation and a succession of causality. Therefore, in combinatorial and transactional analysis, the framework of Devil On The Cross progresses in a method of empirical processing decomposition. Within this respect, the elemental and pure imaginary of the African administration proceeds as a functional derivative governmentality and a colonial functional inception power. Subsequently, with its interaction design, processing system, and volume technique, the realm of Devil On The Cross inserts a paradigmatic analysis and a value engineering within which this African administration happens as an characteristic structural formula and an inefficient relational frame theory. Moreover, within the space-time continuum, the configuration management and the linear configuration programming of the African management apparatus, Devil On The Cross becomes a holomorphic function and an analytic continuation that reveal the anachronism nature and the asynchronous system of the African post-colonial administration.
Alianzas por la educación de la diáspora mexicana: el papel de las universidades mexicanas
Authors: Orozco Aguirre Sofía
Published: March 2024

Este artículo subraya la dimensión e importancia de la diáspora mexicana y la necesidad de apoyar su educación media y superior. Detalla los servicios que el Instituto de los Mexicanos en el Exterior y la red consular aportan hacia este fin, incluyendo las Ventanillas de Orientación Educativa y la Semana Binacional de Educación. Destaca la importancia de generar y consolidar alianzas para la oferta de la educación abierta y en línea a estas poblaciones.
Preservación Digital y Derechos de Autor, una visión analógica en un mundo digital: problemas de regulación en la Ley de Derechos de Autor en España
Authors: Corado Guerrero Miguel Ángel
Published: March 2024

En el presente artículo se tratarán los principales conflictos y frenos que tiene la legislación española en Derechos de Autor respecto a la Preservación Digital y sus estrategias. El primer freno consiste en la escasa actualización legislativa, que implica que la velocidad de avance tecnológico es mucho mayor que la adaptación y producción normativa del poder legislativo. Además de contemplar una redacción legal generalista, con limitaciones y escasas interpretaciones. En segundo lugar, se encuentra la presión de las grandes empresas que quieren superponer su visión al legislador, esta coyuntura afecta al articulado (art. 37 del TRLPI) y por ende al uso de estrategias de preservación. En tercer lugar, trataremos la protección tecnológica (DRM), la cual establece usos permitidos en los objetos digitales, restringiendo así toda estrategia que parta desde la copia del objeto digital, además de no contemplar las limitaciones establecidas en el art. 37 de la TRLPI. Finalmente, se tratarán los contratos que son formas de acceder a grandes colecciones y fondos, no obstante, su uso implica una aceptación de determinadas limitaciones y usos que imposibilitan, a los entes, el preservar esos objetos digitales.
Los nuevos desafíos del control parlamentario en México. Análisis y reflexiones
Authors: Mora-Donatto Cecilia
Published: March 2024

Este artículo analiza los instrumentos de control parlamentario en el derecho mexicano, tema que nuevamente se vuelve relevante, porque en 2018 habrá dos nuevos instrumentos de esta naturaleza, que son: la aprobación por la Cámara de Diputados del Plan Nacional de Desarrollo y la aprobación por el Senado de la Estrategia Nacional de Seguridad Pública. Si a lo anterior le agregamos la reforma constitucional de 2014, que permitirá la reelección legislativa consecutiva, estas circunstancias darán, sin duda, una mayor importancia a estas facultades de control que ejercerán cada una de las Cámaras.
Selection of Either (Fly Ash, Rubber And Rice Husk) Material for Rigid Pavement: Review
Authors: Hemlata  , Kumar Er Rohit , Singh Dr Gurvinder
Published: March 2024

Abstract: Road transportation plays a crucial role in India's economic development, providing cost-effective, accessible, and adaptable means of transportation for both passengers and freight. Pavement, as a key component of highway design, must withstand vehicular loads and foot traffic while ensuring safe and efficient movement. This paper reviews existing literature on pavement materials, focusing on sustainable alternatives such as fly ash-based geopolymers, basalt fiber-reinforced concrete, and asphalt mixtures incorporating recycled aggregates and rubber. Additionally, it proposes the combination of rice husk and crumb rubber in concrete as a sustainable approach for pavement construction. The study aims to evaluate the mechanical properties of concrete with partial material replacements through experimental investigation. By addressing gaps in durability studies, comparative analysis, and non-destructive testing, this research seeks to provide valuable insights into the feasibility and sustainability of utilizing waste materials in concrete production. Ultimately, it aims to contribute to advancing sustainable practices in the construction industry and addressing the challenge of waste accumulation.
An Assessment of Accurate Range Estimator for Electric Vehicle Applications
Authors: Godara Dinesh , Bhaskar Dr. M.K. , Parihar Manish
Published: March 2024

Abstract: The world’s primary modes of transportation are facing two major problems: rising oil costs and increasing carbon emissions. As a result, electric vehicles (EVs) are gaining popularity as they are independent of oil and do not produce greenhouse gases. However, despite their benefits, several operational issues still need to be addressed for EV adoption to become widespread. One of the main obstacles for the acceptance of EV’s is the driver’s fear of being stranded by a depleted battery. In other words, accurate estimation of the remaining SOC is required to provide positive edge towards adoption of EV. In this work, an EV is tested for a drive line cycle of 10 Km for a trip, and key parameters such as elevation, speed, body dynamics, vehicle dimensions, on track speed have been collected. A model of EV power train is developed in MATLAB Simulink from the data logged and a static app is being developed which estimates the vehicle dynamic forces, power consumption, energy utilized for the trip, State of Charge (SOC) and remaining mileage of the vehicle.
Expert consensus on evidence-based recommendations for the diagnosis, treatment, and follow-up of X-linked hypophosphatemic rickets (XLH)
Authors: Cárdenas Aguilera Juan Guillermo , Medina-Orjuela Adriana , Meza-Martínez Adriana Isabel , Prieto Juan Carlos , Zarante-Bahamón Ana María , Cáceres-Mosquera Jimena Adriana , Mejía-Gaviria Natalia , Serrano-Gayubo Ana Katherina , Baquero-Rodríguez Richard , Chacón-Acevedo Kelly , Guerrero-Tinoco Gustavo Adolfo , Uribe-Ríos Alejandro , García-Rueda María Fernanda , Abad-Londoño Verónica , Nossa-Almanza Sergio Alejandro , Aroca-Martínez Gustavo , Román-González Alejandro , Endo-Cáceres Jorge Alberto , Llano-Linares Juan Pablo , Florenzano Pablo , Díaz-Curiel Manuel , Vaisbich María Helena , Zanchetta María Belen , Guerra-Hernández Norma Elizabeth , Stefano Eduardo Enrique , Brunetto Oscar
Published: March 2024

Introduction: X-linked hypophosphatemic rickets is a hereditary condition causing disruptions in bone mineral homeostasis. The morbidity associated with this condition has exhibited variability in previous decades, possibly stemming from variations in case definitions and diagnostic confirmation procedures.
Objective: Our aim was to generate evidence-informed recommendations for the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLH.
Methodology: Integration of a literature review with a modified Delphi method, guided by expert consensus.
Results: Following the screening and selection of 1041 documents, 41 were chosen to address the queries posed by the developer group. Experts, consulted through a modified Delphi consensus, endorsed 97 recommendations on the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLH. Notably, the quality of the evidence was deemed to be low.
Conclusions: The recommendations proposed here will allow early and timely diagnosis of X-linked hypophosphatemic rickets, while optimizing resources for its treatment and follow-up. In addition, it will help clarify the burden of the disease and improve health outcomes for this population.