bluuebunny/crossref_metadata_2025 huggingface dataset:
A REVIEW ON DENDRIMERS: A NOVEL APPROACH
Authors: Rathod Hemant
Published: February 2025

Dendrimers are novel class of approach in polymers. They are monodisperse macromolecules having extensively branched 3D structure which provides a high degree of surface functionality and versatility. They are used for biological and drug-delivery applications because of their unique properties like uniform size, high degree of branching, water solubility, multivalency, well-defined molecular weight and available internal cavities. The aim of this review to describe about dendrimer synthesis strategies, types of dendrimers with different functionalities, properties which having crucial importance and their potential applications.
Floating Drug Delivery System And its Applications: An Overview
Authors: Sharma Narendra
Published: February 2025

The purpose of writing this review on floating drug delivery systems (FDDS) was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multipleunit floating systems, and their classification and formulation aspects are covered in detail. This review also summarizes the in vitro techniques, in vivo studies to evaluate the performance and application of floating systems,and applications of these systems. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form.
Herbal Medicines and Their Neuroprotective Effects in Alzheimer's Disease and Associated Symptoms
Authors: Dobhal T
Published: February 2025

Alzheimer's disease(AD), a progressive neurodegenerative disorder, is the most common form of dementia which affects an estimated 10 million people worldwide. AD is characterized by a gradual decline in memory associated with shrinkage of brain tissue, localized loss of neurons mainly in the hippocampus and basal forebrain, and diminished level of central cholinergic neurotransmitter acetylcholine thereby causing trouble with memory, thinking, behaviour and social life. Many of the current drugs taken to treat the disease, such as donepezil, have unpleasant side effects and doctors are keen to find alternatives. Herbs and various naturally occurring compounds may play a promising role in the early treatment of AD and other conditions involving poor memory and dementia. One of the chief benefits is that they have low toxicity compared to pharmaceutical agents. This review will indicate the neuroprotective effect of various medicinal herbs in the treatment of Alzheimer's disease.
PREPARATION AND EVALUATION OF IBUPROFENTRANSDERMAL PATCH
Authors: Thakkallpally Swathi Rao
Published: February 2025

Ibuprofen is a NSAID used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea acts mainly by inhibition of COX-1and COX-2.The main aim of this work is to prepare and characterize the transdermal patch of Ibuprofen and to increase the therapeutic effectiveness of ibuprofen by increasing its transdermal permeation. Three formulations of ibuprofen were prepared using different drug: polymer ratio i.e. 1:1, 2:3 and 3:2 for PVP and ethyl cellulose using solvent casting method. Prepared patches were evaluated for weight, thickness, swelling index, drug content uniformity, folding endurance and in vitro release. Patches exhibited controlled release over more than 5 h in vitro release studies. It was concluded that the patches containing 250 g of ibuprofen in PVP and ethyl cellulose (2:3 ratio) showed good swelling and a promising controlled drug release, thus can be selected for a development of transdermal patches for effective therapeutic uses.
Stability Indicating RP–HPLC Method for The Estimation of Etravirine in Pure and Tablet Dosage Form
Authors: Gollapudi Chaitanya
Published: February 2025

A simple, fast and precise stability indicating RP – HPLC method was developed for the separation and quantification of Etravirine in pharmaceutical dosage form. The quantification was carried out using Universal C18 4.6X150mm, 5μm enhanced polar selectivity column and mobile phase comprised of 0.02M potassium dihydrogen phosphate & 0.003M di potassium hydrogen phosphate buffer pH adjusted to 3.5 with 0.1% orthophosphoric acid and acetonitrile in proportion of ratio 45:55 and degassed under ultrasonication. The flow rate was 1mL/min and the effluent was monitored at 285nm. The retention time of Etravirine was 4.547min. The method was validated in terms of linearity, precision, accuracy, specificity, limit of detection and limit of quantitation in accordance with ICH guidelines. Linearity of Etravirine was in the range of 10 – 60 μg/mL. The average percentage recovery of Etravirine was 99.02% from the tablet formulation. The stability – indicating capability was established by forced degradation experiments. The proposed method is suitable for determination of Etravirine in pharmaceutical dosage form.
Validate the sensitivity of detector of HPLC by linearity study on Desloratadine drug
Authors: Patel Hemant
Published: February 2025

Validation study generally to ensure the process, that detector is validate for the further process. Validation its named as specification or verification process for to confirm the process or design preactical. Desloratadine drug act as anti- histaminic, its use for the allergic condition, rhinitis, pluritis etc. Its metabolite of loratadine. By the validation study, I would like to confirm the sensitivity of the detector used in HPLC for the force degradation process. By the force degradation process, to confirm the stability of Desloratadine drug at various stress. To demonstrate the linearity of detector response for Desloratadine, prepare solutions of Desloratadine sample to achieve concentrations ranging from 80% to 120% of working test concentration. Injected all concentration solutions in duplicate into the liquid chromatograph & recorded the chromatograms. Calculated the Y-intercept, slope of regression line, correlation coefficient and R2 value.
Blockchain Technology for Supply Chain Efficiency in a Selected Business in Guangdong, China
Authors: Li Zhengchun , Li Changlu , Lorenzo Lorenzo C.
Published: February 2025

This study investigates the influence of blockchain technology integration on supply chain efficiency, considering demographic factors and organizational perspectives. Through a comprehensive analysis of survey data collected from diverse respondents, including sex distribution, age demographics, and hierarchical positions within organizations, the study explores perceptions of blockchain's significance and its impact on various supply chain functions. Key findings reveal a predominant representation of females and a demographic skewed towards younger age groups, indicating openness to technological advancements like blockchain. While blockchain is recognized for its role in ensuring record immutability and enhancing transparency, skepticism remains regarding its contribution to material management efficiency. Despite moderate improvements observed in inventory and logistics operations, challenges such as errors and delays persist, highlighting opportunities for further enhancement. Interestingly, no significant differences are found in perceptions of blockchain integration across gender and age groups, suggesting a unified understanding of its role in supply chain efficiency. However, variations are observed among hierarchical positions, with executives expressing higher confidence in blockchain's impact. Overall, there is a consistent perception of blockchain's positive influence on supply chain efficiency among all employees, regardless of job roles. The study underscores the need for continued research and exploration to fully harness the potential of blockchain technology in supply chain management. Recommendations include targeted initiatives to address challenges, enhance transparency, and streamline logistics operations, ensuring organizations maximize the benefits of blockchain integration for improved supply chain efficiency and resilience.
Problemy unifikacji prawa międzynarodowego transportu lotniczego
Authors: Żylicz Marek
Published: February 2025

Artykuł wskazuje, że historyczny rozwój stosunków międzynarodowych w lotnictwie doprowadził
do wykształcenia złożonej struktury międzynarodowej regulacji ekonomicznej. Reżim ten składa
się z umów wielostronnych oraz tysięcy umów bilateralnych i nie gwarantuje globalnej jednolitości
prawa rządzącego rynkiem transportu lotniczego. Dotychczas światowe ujednolicenie międzynarodowego
prawa lotniczego objęło głównie sferę bezpieczeństwa żeglugi powietrznej, a jedynie
w bardzo niewielkim stopniu dotyczyło działalności gospodarczej i konkurencji. Istnieje wiele czynników
kształtujących politykę lotniczą poszczególnych państw. Dlatego, podobnie jak w innych
sferach międzynarodowych stosunków gospodarczych, podstawową trudnością w stworzeniu
systemu globalnej regulacji ekonomicznej w lotnictwie jest znalezienie wspólnego mianownika
między państwami bardziej i mniej rozwiniętymi.
Status prawny wybranych przedsiębiorstw kolejowych jako podmiotów o szczególnym znaczeniu gospodarczo-obronnym
Authors: Pawłuszko Wojciech
Published: February 2025

Przedmiotem artykułu jest charakterystyka praw i obowiązków przedsiębiorstw kolejowych, które mają status prawny podmiotów o szczególnym znaczeniu gospodarczo-obronnym. Wiąże się on z realizacją szeregu jawnych i niejawnych obowiązków ograniczających swobodę prowadzenia przez nie działalności gospodarczej. Jednocześnie w warunkach zagrożenia suwerenności kraju oraz w czasie wojny takie przedsiębiorstwa aktywnie współtworzą system bezpieczeństwa państwa. Powoduje to, że mają one kluczowe znaczenie dla sprawnej i efektywnej obrony terytorium kraju.
Sustentabilidade econômico-financeira dos serviços de manejo de resíduos sólidos urbanos (RSU): aspectos legais e desafios para consecução
Authors: Carvalho Yuri Mariano , Machado Rodrigo Loth , Castro Samuel Rodrigues , De Almeida Júlia Righi
Published: February 2025

O financiamento dos serviços de manejo de resíduos sólidos urbanos (RSU) por meio de cobranças é um desafio para as governanças municipais brasileiras. Mesmo com a instituição da Política Nacional de Resíduos Sólidos (PNRS) por meio da Lei nº 12.305, em 2010, e de normativas que regulam a cobrança pelo manejo de RSU, a tributação específica tende a não existir ou a ser insuficiente no Brasil. Nesse contexto, esse artigo realiza uma revisão bibliográfica da cobrança pelos serviços de manejo de RSU no Brasil, visando identificar formas de se garantir a sustentabilidade econômico-financeira desses serviços. Inicialmente, é abordado o histórico legislativo por trás da matéria, apresentando as evoluções normativas brasileiras até se chegar nas legislações sobre o saneamento básico e então na PNRS. Em sequência, discute-se a sustentabilidade econômico-financeira dos serviços de manejo de RSU, apresentando as atuais conjunturas de cobranças no país, suas validações legais e seus problemas. Por fim, para além das soluções que perpassam pelo ânimo do Poder Público, propõe-se a judicialização da pauta para os Municípios em que a cobrança é ausente ou insuficiente/ineficaz. Dessa forma, garantir-se-ia a sustentabilidade econômico-financeira do manejo de RSU e a perpetuação do serviço, posto inclusive que é dimensão do direito constitucional ao meio ambiente ecologicamente equilibrado.
Ispanijos garbės vicekonsulatas Kaune ir vicekonsulo Jono Pakalkos veikla
Authors: Sužiedėlis Gabrielius
Published: February 2025

Ganėtinai turtingoje 1919–1940 m. Kauno, diplomatinio Lietuvos valstybės centro, istorijoje kaip itin mažai žinomas ir tirtas išsiskiria Ispanijos garbės vicekonsulato atvejis. Tai kelia dar daugiau klausimų atsižvelgus į tai, jog jis veikė ir reikšmingo tarptautinio konflikto, Ispanijos pilietinio karo, laikotarpiu. Siekiant rekonstruoti vicekonsulato veiklos visumą, tyrime pirmiausia nustatomos ir apibūdinamos lokacijos, kuriose veikė jo kanceliarija (bendrovė „Parama“) bei gyveno vicekonsulas Jonas Pakalka (Jono ir Aleksandros Vailokaičių namas). Antrojoje dalyje apibrėžiamas tuometės Lietuvos Respublikos bei Kauno santykis su Ispanijos pilietiniu karu, pristatomi pagrindiniai J. Pakalkos biografiniai faktai, ypatingą dėmesį skiriant jo politinėms pažiūroms. Trečiojoje dalyje, žvelgiant į regioninį diplomatijos istorijos kontekstą, pateikiamos prielaidos dėl galimų vicekonsulo veiklų. Nepaisant šaltinių stygiaus, tyrimas leido apibūdinti esminius vicekonsulato aspektus – patvirtinti jo veiklos laikotarpį ir vietas, iškelti versijas dėl J. Pakalkos paskyrimo priežasčių, įvertinti jo, kaip vicekonsulo, įsitraukimo į diplomatines veiklas motyvaciją ir tikimybę.
Physical Activity in Multiple Sclerosis: Real-World Data From Saskatchewan, Canada
Authors: Knox Katherine B. , Islam Akhtarul , Le Thuy , Donkers Sarah J. , Evans Charity , Lim Hyun J.
Published: February 2025

BACKGROUND:

Physical activity guidelines for multiple sclerosis (MS) were first published in 2013. Physical activity is safe and beneficial in MS, yet it is unclear if physical activity levels are changing in real-world settings.

METHODS:

The primary objective of this study is to determine if the physical activity levels of people with MS are changing. Between September 1, 2014, and February 22, 2022, when people first accessed a provincial MS drugs program in Saskatchewan, Canada, they were invited to complete the Godin Leisure-Time Exercise Questionnaire by mail. Scatter plots of total physical activity (TPA) and health contribution (HC) scores were generated from each person's questionnaire. Multivariable linear regression explored associations and interactions between disease-modifying treatment (DMT), sex, age, age at MS onset, and disease duration on physical activity level.

RESULTS:

The response rate was 50.8% (505 responses from 993 requests). Of the respondents, 69.7% were female; the mean age was 42.8 (± 11.5) years; median MS disease duration was 6.0 years (IQR, 2.0-14.0); and 47.4% had prior DMT exposure. There was no significant change in physical activity levels of new registrants over 7 years (regression slopes TPA: 0.71, P = .26; HC: 0.61, P = .21). Men reported higher physical activity levels than women (TPA: β = 11.95; P < .001; HC: β = 6.65; P < .001). There were interactions between age and disease duration on activity scores (TPA: β = 0.03; P = .003; HC: β = 0.03; P < .001). DMT exposure was not associated with physical activity.

CONCLUSIONS:

Physical activity levels of people with MS remained suboptimal for health benefits over a 7-year period. Future research should include how to use physical activity guidelines to impact real-world activity levels.
ФАКТИЧКА ЕКСПРОПРИЈАЦИЈА
Authors: Шукало Игор
Published: February 2025

Експропријација је институт којим се право својине физичког или правног лица на непокретностима ограничава или одузима уз одговарајућу накнаду, а сам поступак, услови и висина накнаде одређени су законом. Овим инситутом законодавац је настојао да направи баланс између заштите субјективног права и општег интереса. Јасно је да се ниједна држава, од времена старог Рима па до данас, не може развијати без градње објеката од јавног значаја (болнице, школе, електране иитд.)и без извођења инфраструктурних радова и да у том смислу држава односно јавна власт мора реаговати захватајући у имовинска права физичких и правних лица али само у строго прописаном поступку. Све остало доводи до повреде права својине које је гарантовано уставом и законима модерних држава. Постоје случајеви изградње објеката од јавног интереса или извођења других радова од јавног интереса који за посљедицу имају потпуно или дјелимично одузимање права својине физичким или правним лицима, иако не постоји одлука о одузимању, тј. рјешење о утврђивању општег интереса и рјешење о експропријацији. Правна теорија и правна пракса такве случајеве подводе под концепт фактичке експропријације, односно тзв. фактичког депосједирања, која се од концепта формалне експропријације разликује по одсуству битних елемената законски утврђеног поступка експропријације.
ЕЛЕКТРОНСКИ ПОТПИС И ЗАШТО ГА (НЕ) ПРИМЈЕЊУЈЕМО
Authors: Ђурић Дејана
Published: February 2025

Дигитализација је једна од ријечи која се, данас, често чује у сваком сегменту модерног пословања. Многе процедуре и послови у свијету бизниса за које је требало много времена, људи и папира да се заврше, су сада сведени на један или неколико „кликова“. До прије само пар година нам је било незамисливо да из властите куће можемо да нпр. платимо рачуне да избјегнемо чекање у редовима и да тиме уштедимо своје вријеме којег данас у овом ужурбаном начину живота имамо све мање. Први Закон о електронском потпису Републике Српске донесен је још 2002. године, али до данас није званично омогућена примјена електорнског потписа у пракси иако се у посљедњих неколико година, нарочито након формирања Министарства за научнотехнолошки развој, високо образовање и информационо друштво, дешавају одређени помаци у имплементацији. Дакле, ускоро се навршава 20 година од усвајања закона који и даље није имплементиран и који и даље представља мртво слово на папиру. На државном нивоу овај закон је донесен 2006. године и његова имплементација је ђелимично омогућена. Циљ овог рада јесте преглед законског оквира електронског потписа, могућност његове имплементације, проблеми на које наилазимо у пракси као и бенефити електронског потписа.
ТАДИЈА БУБАЛОВИЋ И НЕЗИР ПИВИЋ: МЕЂУНАРОДНО КРИВИЧНО ПРОЦЕСНО ПРАВО (Правни факултет Универзитета у Зеници, Зеница, 2021, стр. 342)
Authors: Симовић Владимир М.
Published: February 2025

ТАДИЈА БУБАЛОВИЋ И НЕЗИР ПИВИЋ: МЕЂУНАРОДНО КРИВИЧНО ПРОЦЕСНО ПРАВО (Правни факултет Универзитета у Зеници, Зеница, 2021, стр. 342)
Overcoming multifaceted challenges in cancer treatment: Targeting signal transduction pathways and tumor microenvironment for enhanced therapeutic efficacy
Authors: Ansari Abdul Majeed , Sharma Naresh Kumar , Tripathi Kashinath , Bhardwaj Gautam , Chauhan Ritu , Tonk Rajiv Kumar , Shahwan Moyad , Tuli Hardeep Singh , Chauhan Abhishek
Published: February 2025

Cancer, a leading global cause of mortality, persists despite extensive research. While progress, notably in protein kinase-modulating drugs, is evident, a definitive cure remains elusive due to multifaceted challenges. This article discusses diverse approaches in cancer treatment, recognizing its complexity. Key hurdles include cancer progression stages, the intricate tumor microenvironment, drug resistance, pharmacodynamics, tumor hypoxia, and compromised immunity. Signal transduction pathways are crucial in cancer progression and resistance, particularly in immune regulation, hypoxia response, and autophagy. Understanding and targeting these pathways are vital for developing novel therapies. By elucidating the interplay between immunity, signaling, and therapeutics, researchers seek to overcome treatment obstacles. A comprehensive approach offers hope for improved outcomes and breakthroughs in cancer management.
Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome
Authors: Cozzolino Kira A , Sanford Lynn , Hunter Samuel , Molison Kayla , Erickson Benjamin , Courvan Meaghan CS , Jones Taylor , Ajit Deepa , Galbraith Matthew D , Espinosa Joaquín M , Bentley David , Allen Mary Ann , Dowell Robin D , Taatjes Dylan J
Published: February 2025

Hyperactive interferon (IFN) signaling is a hallmark of Down syndrome (DS), a condition caused by Trisomy 21 (T21); strategies that normalize IFN signaling could benefit this population. Mediator-associated kinases CDK8 and CDK19 drive inflammatory responses through incompletely understood mechanisms. Using sibling-matched cell lines with/without T21, we investigated Mediator kinase function in the context of hyperactive IFN in DS over a 75 min to 24 hr timeframe. Activation of IFN-response genes was suppressed in cells treated with the CDK8/CDK19 inhibitor cortistatin A (CA), via rapid suppression of IFN-responsive transcription factor (TF) activity. We also discovered that CDK8/CDK19 affect splicing, a novel means by which Mediator kinases control gene expression. To further probe Mediator kinase function, we completed cytokine screens and metabolomics experiments. Cytokines are master regulators of inflammatory responses; by screening 105 different cytokine proteins, we show that Mediator kinases help drive IFN-dependent cytokine responses at least in part through transcriptional regulation of cytokine genes and receptors. Metabolomics revealed that Mediator kinase inhibition altered core metabolic pathways in cell type-specific ways, and broad upregulation of anti-inflammatory lipid mediators occurred specifically in kinase-inhibited cells during hyperactive IFNγ signaling. A subset of these lipids (e.g. oleamide, desmosterol) serve as ligands for nuclear receptors PPAR and LXR, and activation of these receptors occurred specifically during hyperactive IFN signaling in CA-treated cells, revealing mechanistic links between Mediator kinases, lipid metabolism, and nuclear receptor function. Collectively, our results establish CDK8/CDK19 as context-specific metabolic regulators, and reveal that these kinases control gene expression not only via TFs, but also through metabolic changes and splicing. Moreover, we establish that Mediator kinase inhibition antagonizes IFN signaling through transcriptional, metabolic, and cytokine responses, with implications for DS and other chronic inflammatory conditions.
R-Spondin Mimetic, SZN-043, Induced Proliferation and Wnt Activity, Two Features Deficient in Human Alcohol-Associated Liver Disease
Authors: Fisher Trevor , Patel Mehaben , Deshmukh Shalaka , Shah Darshini , Lu Chenggang , Newman Maureen , Ye Jay , Fletcher Russell , Vanhove Geertrui F , Tibbitts Jay , Li Yang , Skill Nicholas J , Yang Zhihong , Liangpunsakul Suthat , Baribault Helene
Published: February 2025

Liver regeneration is impaired in patients suffering from alcohol-associated liver (ALD) diseases. Wnt ligands and their FZD receptors are dysregulated in diseased livers. R-spondin and their receptors are known to regulate Wnt activity via the stabilization of FZD receptors. Here, we investigated the components of the Wnt and R-Spondin-signaling pathways and their activity in patients with ALD. We found that while hepatocytes retained high levels of differentiation markers such as
ASGR1
and
ASGR2
, the expression of two R-spondin co-receptors,
LGR4
and
LGR5
, and of
CYP1A2
and Wnt target genes were strongly reduced.SZN-043, a hepatocyte-targeted R-Spondin mimetic, is a new investigational drug that stimulates the physiological Wnt repair pathway and proliferation of hepatocytes. Here, we show that SZN-043 induced hepatocyte proliferation in all models tested, including humanized mouse livers, a chronic-binge alcohol-induced liver injury, and a CCl
4
-induced fibrosis mouse model. Altogether, SZN-043 could be beneficial for the treatment of ALD.
Genome-wide survey and expression analysis of the OMT gene family in Stephania japonica
Authors: Bi Zenghao , He Tianxing , Liang Yuting , Zhou Changqing , Yu Yuetong , Leng Liang
Published: February 2025

Background

O-methyltransferase (OMT) is an important rate-limiting enzyme that plays a vital role in synthesizing various key metabolites, such as benzylisoquinoline alkaloids (BIA). Nevertheless, there is a dearth of extensive research on the analysis of the OMT gene family in Stephania japonica, a main source of cepharanthine with an anti-coronavirus effect.

Methods

Two OMT family genes, SjCCoAOMT and SjCOMT, were identified from the high-quality genome of S. japonica during this investigation. Further analysis of SjCCoAOMT and SjCOMT genes involved chromosome distribution, gene structure, phylogenetic relationship, conserved motif, expression profile, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) experiments an d cis-acting elements analysis.

Results

There are six SjCCoAOMT members and fifty-two SjCOMT members in the genome of S. japonica, which are unevenly distributed on 11 chromosomes. OMTs could be clustered into SjCCoAOMT and SjCOMT subfamilies through phylogenetic relationship, consistent with the conserved motif and gene structure analysis results. The expression profile revealed SjCOMT11 and SjCOMT13 showed specific expression levels mainly in root. SjCOMT21, SjCOMT33 and SjCOMT37 were significantly expressed in the root and slightly expressed in the stem, bud and leaf. SjCOMT15 and SjCOMT45 were not only significantly expressed in root, but also expressed highly in leaf. Significantly enhanced expression of SjCOMT11, SjCOMT13, SjCOMT15, SjCOMT21, SjCOMT33, SjCOMT37, and SjCOMT45 suggested these OMTs are essential for cepharanthine synthesis in the S. japonica roots. Cis-acting element analysis revealed the potential roles of OMTs in S. japonica in growth, development, and resistance to stress. These findings provide insight into understanding the functions and characterization of OMTs from S. japonica and lay a foundation for further revealing the role of the OMT genes in the biosynthesis of cepharanthine.
Microplastic effects on mouse colon in normal and colitis conditions: A literature review
Authors: Zolotova Natalia , Dzhalilova Dzhuliia , Tsvetkov Ivan , Silina Maria , Fokichev Nikolai , Makarova Olga
Published: February 2025

Background

Taking into account the global spread of microplastic (MP) pollution, the problem of the MP impact on human health is relevant. MP enters the organism predominantly with water and food, and is mostly detected in the large intestine. Therefore, the connection between MP pollution and the increase in colitis is an important question. In order to assess the toxic and pathogenetic effects of MP, experimental studies were actively conducted during recent years, mainly on laboratory mice.

Objectives

The aim of our review was to summarize and systematize the data on the MP effect on mice colon under normal conditions and during colitis in order to assess the role of MP in the development of intestinal diseases. This manuscript could be relevant for ecologists, experimental biologists, and physicians dealing with problems related to anthropogenic environmental changes and inflammatory bowel diseases.

Survey Methodology

The search was conducted based on PubMed data about original experimental studies of the MP effects on the colon of healthy mice and mice with colitis.

Results

In healthy mice colon, MP can cause oxidative stress, increased permeability, immune cell infiltration, production of proinflammatory factors, and decreased mucus production. MP affects proliferation, apoptosis, and differentiation of epithelial cells, expression of tight junction components and glycocalyx, membrane transport, signaling pathways, metabolome, and intestinal microflora composition. In mice with acute and chronic experimental colitis, MP consumption leads to a more pronounced pathological process course.

Conclusions

MP may be one of the factors contributing to the development of colitis in humans. However, further research is needed.
Lipid Profile Indices and Inflammatory Biomarkers as Predictors of Subclinical Muscle Loss in Young Obese Females
Authors: E. Onuyoh-Adaitire, , F.O. Agoreyo, , G. Tafamel , S. Osayande, , B. Onuyoh-Adaitire , E. Enobakhare,
Published: February 2025

Background: Obesity is increasing at an alarming rate in some developing countries and the developed world. Elevated LDL (bad) cholesterol levels and lower HDL (good) cholesterol levels, increase the risk of many debilitating diseases. Muscle atrophy, is a condition that causes muscles to lose mass and strength and appear smaller than normal. It can occur in young adults due obesity. This study was aimed at investigating the lipid profile indices and inflammatory biomarkers as predictors of subclinical muscle loss in young obese females.
Methodology: The study was carried out employing 120 participants with 60 obese subjects as test subjects and 60 slim subjects as control. Plasma samples were collected for lipid profile analysis. Castelli Risk Index 1 and 2, and Atherogenic Index of Plasma were determined by calculation.
Results: There was no significant difference in triglyceride, LDL, and total cholesterol concentration between the control and test subjects (p>0.05) however there was significant reduction in HDL concentration and a significantly elevated value of castelli risk index-1 , castelli risk index-2, artherogenic index. IL-2, IL-6 and IL-12 in the obese participants compared to the non obese participants (p<0.05).
Conclusion: obesity led to an unfavorable lipid pattern of elevated the values of CRP, AIP, CRI I-II ratios, IL6, and IL-12 which are markers of systemic inflammation, and takes into account that elevated AIP and CRI I-II ratios may contribute to subclinical or masked muscle protein breakdown and inhibit muscle repair.
A Review of Reinforcement Learning: Current Trends and Future Prospects in Autonomous Systems
Authors: Ali Chreesk Sabah M. , Yasin Hajar Maseeh
Published: February 2025

This review focuses on the use of reinforcement learning (RL) for autonomous systems and current trends and future prospects. It is therefore the intended goal to critically evaluate the concept of RL for improving autonomous decision making with focus on current and emerging issues including; sample efficiency, scalability, and safety. This review methodology is a synthesis of 10 studies which has been conducted between the years 2021 and 2024. However, these are some of the challenges that seem to plague RL even as it has potential to be used in realistic applications such as robots, self-driving cars and smart grid. The review also opines that due to developments of algorithms, computer intrinsics and safety mechanism, RL perhaps holds the key to the future for autonomous systems.
Antiplasmodial Properties of Medicinal Plants from East Singhbhum District of Jharkhand in India
Authors: Jahan Nuzhat , Shrivastava Pragya , Rahman Shakeel Ur
Published: February 2025

It has been reported that malaria is one of the most important vector-borne diseases in Jharkhand with significant morbidity and mortality. The National Vector Borne Disease Control Programme has prepared new treatment guidelines for malaria that recommend phytochemical constituents-based therapy as the first-line drug for malaria. It is being observed in the treatment of malaria that the cases of drug resistance are increasing day by day. Finding new antiplasmodial or antimalarial plant species to develop effective malarial drugs is the necessity of time to avoid the problem of drug resistance. The tribal people have been using traditional medicinal plants since ancient times. They are using the medicinal plants found in their area for the treatment of fever, loss of appetite, digestive disorders, diabetes, jaundice, joint pain, skin and various other diseases. A community-level study was conducted to document the traditional knowledge and identify the antimalarial plant species with the help of traditional healers (vaidya/Hakeem) as well as by involving Sabar, Santal, Ho tribes and other communities of the area. The present study is focused on the exploration of antiplasmodial and antimalarial medicinal plants which are traditionally used by the ethnic or tribal people of East Singhbhum district in Jharkhand. Further, the review of scientific literature was conducted to validate the documented knowledge and related antimalarial plant species. A total of 28 medicinal plants of East Singhbhum have been identified and reviewed which have good antiplasmodial properties. These medicinal plants are rich in bioactive compounds such as flavonoids, alkaloids, terpenoids, tannins, essential oils, anthraquinones pyrroles etc. The present study deals with the details of those active compounds and concludes the best drug for control of Plasmodium vivax and P. falciparum. However, more advanced research is needed to establish the effectiveness of bioactive compounds in vitro and in vivo, understand their basic mechanisms of action and begin the process of clinical research.
Rate of Coccidiosis in Chicken Farms in Uyo Metropolis, Akwa Ibom State, Nigeria
Authors: T. E. Olajide, , L. O. Oriaku, , I. F. Merenini, , K. Yogesh, , J. Gupta,
Published: February 2025

Despite large number of chickens in Nigeria, contribution to national economy or benefit from this sector of activity is very limited due to diseases and management, out of which chicken coccidiosis is a leading problem. Coccidiosis is a major problem in the farm with inadequate hygienic measures and factors such as age, sex and biosecurity which are the most common factors that contribute for the occurrence of coccidiosis. This study was conducted to investigate the prevalence and incidence of coccidiosis in chicken farms in Uyo metropolis, Akwa Ibom State, Nigeria. Selected numbers of chicken farms within Uyo metropolis were used for this study. A total of 100 faecal samples from live birds comprising 62 young and 38 adult birds were randomly collected as bird’s fresh droppings from both young and adult sections of the farm. Samples were analyzed using standard parasitological methods and techniques. An overall prevalence rate of 46%% was obtained. Higher prevalence rates were recorded in young bird as 48.38% while adult had 42.10%. Then five species of Eimeria that were identified include E. tennela, E. maxima, E. necatrix, E. alervuhina and E. brunette at 28%, 25%, 15.6%, 18.8% and 12.5% respectively. . . Therefore, appropriate control strategies should be designed considering important risk factors and focus should be given to biosecurity practices in the prevention and control of coccidiosis. In addition, further studies are needed to be conducted to identify the prevalent Eimeria species for strategic control.
Assessment of Enablers and Barriers to Childhood Immunisation in Gassol Local Government Area of Taraba State, Nigeria
Authors: Babylon Philemon , Aliyu Abubakar Salim , Aiyagbonrhule Phillips , Sadiq Abubakar , Solomon Musa Enyibi , Yamusa Christiana Adamu
Published: February 2025

Childhood immunization remains a critical public health strategy to reduce morbidity and mortality associated with vaccine-preventable diseases. This study assesses the enablers and barriers to childhood immunization in Gassol Local Government Area (LGA) of Taraba State, Nigeria, using a qualitative research approach. Data were collected through Key Informant Interviews (KII) and Focus Group Discussions (FGD) with caregivers, healthcare workers, and community leaders. Key enablers identified include community awareness campaigns, support from local leaders, accessible healthcare infrastructure, trust in healthcare professionals, and government and NGO-supported initiatives. Conversely, barriers to immunization encompass cultural beliefs, misinformation about vaccines, logistical challenges such as vaccine stockouts and inconvenient scheduling, limited engagement by healthcare workers, and financial constraints faced by caregivers. The findings show the importance of targeted strategies to strengthen community engagement, improve healthcare accessibility, and address sociocultural and economic barriers.
Characters Association and Selection Criteria for Irrigated Ecosystem in Rice (Oryza sativa L.) Genotypes
Authors: Tiwari Rishita , Sharma Bhawana , Parikh Mangla , Gauraha Deepak
Published: February 2025

Grain yield in rice is a complex quantitative trait influenced by various yield determining traits besides environmental factors. Understanding the association of different characters is essential to determine their contribution towards yield. Evaluating both the direction and strength of correlation helps assess how improvement in one trait may lead to enhancements or simultaneous changes in other traits. The current study aimed to determine correlation and path coefficients among the Sixty-five rice accessions for eight traits to establish selection criteria that may aid in developing high yielding genotypes. The correlation analysis revealed that traits such as number of filled grains per plant, spikelet fertility (%), 100 seed weight (g), biological yield per plant (g) and harvest index had positive significant association with the grain yield per plant. Path coefficient analysis unveils that panicle length, panicle number per plant, number of filled grains per panicle, spikelet fertility, 100 seed weight, biological yield per plant and harvest index had maximum positive direct effect on grain yield per plant. Based on the results of this study, selection for higher biological yield, spikelet fertility and harvest index will be beneficial for obtaining higher grain yield in rice crop. These characters play a major role in shaping the single plant yield in rice on which selection pressure has to be applied for enhancing the seed yield.
A First Case Report of Mannheimia haemolytica in Caprine Mastitis in Theni District of Tamil Nadu, India
Authors: Rajasekaran Ranjani , Padmanath K. , Suresh P. , Rathnapraba S.
Published: February 2025

Aim: To identify and assess the etiological agent responsible for caprine mastitis in a doe, analyse the antibiotic sensitivity and provide suitable treatment.
Study Design: Clinical examination and microbiological analysis, followed by antibiotic sensitivity testing.
Place and Duration of Study: Veterinary College and Research Institute, Theni. Case presented in the month of November, 2023.
Methodology: A 31 kg doe with a history of udder swelling and watery milk from the right quarter was examined. Clinical examination revealed a swollen, painful and indurated udder. The California Mastitis Test confirmed the mastitis, and the milk sample was collected aseptically for microbiological analysis. After initial inoculation in nutrient broth and after overnight incubation, the culture was streaked onto MacConkey agar. Bacterial identification was done by routine biochemical tests). Antibiotic sensitivity testing (ABST) was conducted using the Kirby-Bauer disc diffusion method.
Results: Gram staining revealed Gram-negative coccobacilli with bipolar staining resembling Mannheimia hemolytica. The tiny red pinpoint colonies on MacConkey agar and positive catalase, oxidase, and indole tests were suggestive of Mannheimia hemolytica. ABST showed resistance to Penicillin, Ampicillin, Methicillin, and Metronidazole, while sensitivity was observed to Amoxicillin Clavulanic acid, Ciprofloxacin, Gentamicin, Cefixime, Ceftriaxone, Enrofloxacin, Chloramphenicol, Streptomycin, Tetracycline, Oxytetracycline, Trimethoprim, and Sulfonamide. Treatment with Ceftriaxone (10 mg/kg) intra-venously and Meloxicam (0.5 mg/kg) intramuscularly, along with topical Mastilep for three days, alleviated udder pain and hardness.
Conclusion: Mastitis in goats is commonly caused by Staphylococcus spp.; however, Mannheimia hemolytica is a rare but possible etiological agent. This case represents the first report of Mannheimia hemolytica-induced mastitis in Tamil Nadu, indicating a need for further molecular study of this pathogen in caprine mastitis. Mannheimia hemolytica can impinge on the wellness of goats; therefore timely diagnosis and therapeutic interventions are highly essential to maintain the economic status of goat farms.
Addressing Systemic Racism and Racialized Violence to Reduce Firearm Injury and Mortality Inequities
Authors: Randolph Schenita D. , Gonzalez-Guarda Rosa M. , Pearson Jay
Published: April 2024

This JAMA Forum discusses systemic racism and racialized violence, promising approaches to address inequities in firearm violence, and ways to treat the trauma of gun violence.
Clinical Value of Molecular Targets and FDA-Approved Genome-Targeted Cancer Therapies
Authors: Tibau Ariadna , Hwang Thomas J. , Molto Consolacion , Avorn Jerry , Kesselheim Aaron S.
Published: April 2024

Importance

The number of new genome-targeted cancer drugs has increased, offering the possibility of personalized therapy, often at a very high cost.

Objective

To assess the validity of molecular targets and therapeutic benefits of US Food and Drug Administration–approved genome-targeted cancer drugs based on the outcomes of their corresponding pivotal clinical trials.

Design and Settings

In this cohort study, all genome-targeted cancer drugs that were FDA-approved between January 1, 2015, and December 31, 2022, were analyzed. From FDA drug labels and trial reports, key characteristics of pivotal trials were extracted, including the outcomes assessed.

Main Outcomes and Measures

The strength of evidence supporting molecular targetability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit for their approved indications was evaluated using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS). Substantial clinical benefit was defined as a grade of A or B for curative intent and 4 or 5 for noncurative intent. Molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-MCBS were rated as high-benefit genomic-based cancer treatments.

Results

A total of 50 molecular-targeted drugs covering 84 indications were analyzed. Forty-five indications (54%) were approved based on phase 1 or phase 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials, and 48 (57%) were approved on the basis of subgroup analyses. By each indication, 46 of 84 primary end points (55%) were overall response rate (median [IQR] overall response rate, 57% [40%-69%]; median [IQR] duration of response, 11.1 [9.2-19.8] months). Among the 84 pivotal trials supporting these 84 indications, 38 trials (45%) had I-A ESCAT targetability, and 32 (38%) had I-B targetability. Overall, 24 of 84 trials (29%) demonstrated substantial clinical benefit via ESMO-MCBS. Combining these ratings, 24 of 84 indications (29%) were associated with high-benefit genomic-based cancer treatments.

Conclusions and Relevance

The results of this cohort study demonstrate that among recently approved molecular-targeted cancer therapies, fewer than one-third demonstrated substantial patient benefits at approval. Benefit frameworks such as ESMO-MCBS and ESCAT can help physicians, patients, and payers identify therapies with the greatest clinical potential.
Trends in Oral Tongue Cancer Incidence in the US
Authors: Burus Todd , Damgacioglu Haluk , Huang Bin , Christian W. Jay , Hull Pamela C. , Ellis Amanda R. , Arnold Susanne M. , Deshmukh Ashish A. , Lang Kuhs Krystle A.
Published: April 2024

Importance

Oral tongue cancer (OTC) incidence has increased rapidly among young (<50 years) non-Hispanic White individuals in the US during the past 2 decades; however, it is unknown if age-associated trajectories have persisted.

Objective

To examine US trends in OTC incidence and project future case burden.

Design, Setting, and Participants

This cross-sectional analysis of OTC incidence trends used the US Cancer Statistics Public Use Database, which covers approximately 98% of the US population, and included individuals with an OTC diagnosis reported to US cancer registries between January 1, 2001, and December 31, 2019.

Exposures

Sex, race and ethnicity, and age.

Main Outcomes and Measures

Estimated average annual percentage change in OTC incidence from 2001 to 2019. Given the substantial incidence rate increases among non-Hispanic White individuals compared with those of racial and ethnic minority groups, subsequent analyses were restricted to non-Hispanic White individuals. Forecasted OTC incidence trends and case burden among non-Hispanic White individuals to 2034.

Results

There were 58 661 new cases of OTC identified between 2001 and 2019. Male individuals (57.6%), non-Hispanic White individuals (83.7%), those aged 60 years or older (58.0%), and individuals with localized stage disease at diagnosis (62.7%) comprised most cases. OTC incidence increased across all age, sex, and racial and ethnic groups, with marked increases observed among non-Hispanic White individuals (2.9% per year; 95% CI, 2.2%-3.7%). Increases among female individuals aged 50 to 59 years were most notable and significantly outpaced increases among younger non-Hispanic White female individuals (4.8% per year [95% CI, 4.1%-5.4%] vs 3.3% per year [95% CI, 2.7%-3.8%]). While all non-Hispanic White birth cohorts from 1925 to 1980 saw sustained increases, rates stabilized among female individuals born after 1980. Should trends continue, the burden of new OTC cases among non-Hispanic White individuals in the US is projected to shift more toward older individuals (from 33.1% to 49.3% among individuals aged 70 years or older) and female individuals (86% case increase vs 62% among male individuals).

Conclusions and Relevance

The results of this cross-sectional study suggest that the period of rapidly increasing OTC incidence among younger non-Hispanic White female individuals in the US is tempering and giving way to greater increases among older female individuals, suggesting a birth cohort effect may have been associated with previously observed trends. Recent increases among non-Hispanic White individuals 50 years or older of both sexes have matched or outpaced younger age groups. Continuing increases among older individuals, particularly female individuals, may be associated with a shift in the OTC patient profile over time.
Deciphering the Drug Delivery Potential of Milk Exosome Nanovesicles for Aminobenzylpenicillin Therapeutic Efficacy against Contagious Staphylococcus Aureus in Bovine Mastitis
Authors: Kumar Jitendra , Onteru Suneel Kumar , Singh Dheer
Published: April 2024

The emergence of antimicrobial resistance and failure of antibiotic treatment are challenging tasks for managing bovine mastitis, which is mainly caused by the contagious Staphylococcus aureus (S. aureus).To overcome these difficulties, there is an urgent need for a novel drug system. In the present study, the aim is to develop next‐generation therapeutics against S. aureus by harnessing the drug delivery potential of milk nanovesicles called milk exosomes (mENs). In the present work, a drug system is developed by encapsulating aminobenzylpenicillin (AMP) in mENs (mENs‐AMP). Electron microscopy and zeta‐sizer results indicate that the size of mENs‐AMP ranged from 55.79 ± 2.8 to 85.53 ± 7.4 nm. The AMP loading efficiency in mENs is 88.61% with its sustained release. Fluorescence spectroscopy results indicated that mENs are biocompatible with mammary epithelial cells. In vitro studies show that the antibacterial activity and the minimum inhibitory concentrations of mENs‐AMP are eleven times greater and four times lower than that of unencapsulated AMP, respectively. The mENs‐AMP exhibit significantly higher therapeutic efficacy than AMP at the same dosage and treatment frequency. Validation of this approach is demonstrated in mastitis‐affected animals through an observation in the reduction of somatic cell counts and bacterial loads in the milk of treated animals.
Peptide Mimics of the Cysteine‐Rich Regions of HapX and SreA Bind a [2Fe‐2S] Cluster In Vitro
Authors: Rossetto Daniele , Sebastianelli Lorenzo , Oberegger Simon , Todorovic Smilja , Haas Hubertus , Mansy Sheref S.
Published: April 2024

HapX and SreA are transcription factors that regulate the response of the fungus Aspergillus fumigatus to the availability of iron. During iron starvation, HapX represses genes involved in iron consuming pathways and upon a shift to iron excess, HapX activates these same genes. SreA blocks the expression of genes needed for iron uptake during periods of iron availability. Both proteins possess cysteine‐rich regions (CRR) that are hypothesized to be necessary for the sensing of iron levels. However, the contribution of each of these domains to the function of the protein has remained unclear. Here, the ability of peptide analogs of each CRR is determined to bind an iron‐sulfur cluster in vitro. UV–vis and resonance Raman (RR) spectroscopies reveal that each CRR is capable of coordinating a [2Fe‐2S] cluster with comparable affinities. The iron–sulfur cluster coordinated to the CRR‐B domain of HapX displays particularly high stability. The data are consistent with HapX and SreA mediating responses to cellular iron levels through the direct coordination of [2Fe‐2S] clusters. The high stability of the CRR‐B peptide may also find use as a starting point for the development of new green catalysts.