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1.
Pak J Pharm Sci ; 37(1): 43-52, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38741399

RESUMO

Drug-resistant malaria is a global risk to the modern world. Artremisinin (ART) is one of the drugs of choice against drug-resistant (malaria) which is practically insoluble in water. The objective of our study was to improve the solubility of artemisinin (ART) via development of binary complexes of ART with sulfobutylether ß-cyclodextrins (SBE7 ß-CD), sulfobutylether ß-cyclodextrins (SBE7 ß-CD) and oleic acid (ternary complexes). These are prepared in various drugs to excipients ratios by physical mixing (PM) and solvent evaporation (SE) methods. Characterizations were achieved by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and attenuated total reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy. The aqueous-solubility in binary complexes was 12-folds enhanced than ternary complexes. Dissolution of binary and ternary complexes of artemisinin in simulated gastric fluid (pH 1.6) was found highest and 35 times higher for ternary SECx. The crystallinity of artemisinin was decreased in physical mixtures (PMs) while SECx exhibited displaced angles. The attenuated-intensity of SECx showed least peak numbers with more displaced-angles. SEM images of PMs and SECx showed reduced particle size in binary and ternary systems as compared to pure drug-particles. ATR-FTIR spectra of binary and ternary complexes revealed bonding interactions among artemisinin, SBE7 ß-CD and oleic acid.


Assuntos
Artemisininas , Ácido Oleico , Solubilidade , Difração de Raios X , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Artemisininas/química , Ácido Oleico/química , Espectroscopia de Infravermelho com Transformada de Fourier , Microscopia Eletrônica de Varredura , Antimaláricos/química , Excipientes/química , Composição de Medicamentos
2.
Mol Genet Genomics ; 299(1): 55, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771357

RESUMO

Neurodevelopmental disorders (NDDs) are a clinically and genetically heterogeneous group of early-onset pediatric disorders that affect the structure and/or function of the central or peripheral nervous system. Achieving a precise molecular diagnosis for NDDs may be challenging due to the diverse genetic underpinnings and clinical variability. In the current study, we investigated the underlying genetic cause(s) of NDDs in four unrelated Pakistani families. Using exome sequencing (ES) as a diagnostic approach, we identified disease-causing variants in established NDD-associated genes in all families, including one hitherto unreported variant in RELN and three recurrent variants in VPS13B, DEGS1, and SPG11. Overall, our study highlights the potential of ES as a tool for clinical diagnosis.


Assuntos
Sequenciamento do Exoma , Estudos de Associação Genética , Transtornos do Neurodesenvolvimento , Linhagem , Proteínas de Transporte Vesicular , Humanos , Transtornos do Neurodesenvolvimento/genética , Masculino , Feminino , Proteínas de Transporte Vesicular/genética , Estudos de Associação Genética/métodos , Criança , Pré-Escolar , Exoma/genética , Paquistão , Predisposição Genética para Doença , Mutação , Moléculas de Adesão Celular Neuronais/genética
3.
Artigo em Inglês | MEDLINE | ID: mdl-38696538

RESUMO

CONTEXT: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined. OBJECTIVE: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities. METHODS: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023. RESULTS: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04). CONCLUSION: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes.

4.
Heliyon ; 10(9): e30494, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38756585

RESUMO

The glioblastoma brain tumour (GBM) stands out as the most aggressive and resistant-to-treatment malignancy. Nevertheless, the gut-brain connection plays a pivotal role in influencing the growth and activation of the central nervous system. In this particular investigation, we aimed to assess and characterize the gut microbial ecosystem in GBM patients, both quantitatively and qualitatively. We collected faecal samples from 15 healthy volunteers and 25 GBM patients. To delve into the microbial content, we employed PCR-DGGE, targeting the V3 region of the 16S rRNA gene, and conducted qPCR to measure the levels of crucial intestinal bacteria. For a more in-depth analysis, high-throughput sequencing was performed on a selection of 20 random faecal samples (10 from healthy individuals and 10 from GBM patients), targeting the V3+V4 region of the 16S rRNA gene. Our findings from examining the richness and diversity of the gut microbiota unveiled that GBM patients exhibited significantly higher microbial diversity compared to healthy individuals. At the phylum level, Proteobacteria saw a significant increase, while Firmicutes experienced a noteworthy decrease in the GBM group. Moving down to the family level, we observed significantly elevated levels of Enterobacteriaceae, Bacteroidaceae, and Lachnospiraceae in GBM patients, while levels of Veillonellaceae, Rikenellaceae, and Prevotellaceae were notably lower. Delving into genera statistics, we noted a substantial increase in the abundance of Parasutterella, Escherichia-Shigella, and Bacteroides, alongside significantly lower levels of Ruminococcus 2, Faecalibacterium, and Prevotella_9 in the GBM group compared to the control group. Furthermore, when examining specific species, we found a significant increase in Bacteroides vulgatus and Escherichia coli in the GBM group. These observations collectively indicate a marked dysbiosis in the gut microbial composition of GBM patients. Additionally, the GBM group exhibited notably higher levels of alpha diversity when compared to the control group. This increase in diversity suggests a significant bacterial overgrowth in the gut of GBM patients in contrast to the controls. As a result, this research opens up potential avenues to gain a better understanding of the underlying mechanisms, pathways, and potential treatments for GBM, stemming from the significant implications of gut microbial dysbiosis in these patients.

5.
Saudi Pharm J ; 32(6): 102091, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38757070

RESUMO

Introduction: Saudi Arabia has begun reforming its government-run health care system to increase efficiency and reduce costs. One effort is the adoption of an electronic prescribing system (Wasfaty) and outsourcing pharmaceutical services from government-run clinics to community pharmacies (CP). This study aims to compare satisfaction with pharmaceutical services offered in the two systems. Materials and methods: This cross-sectional observational study used existing survey data collected from patients (≥15 years of age) visiting government primary health care centers from January 2022 to June 2022. Satisfaction with three pharmaceutical services (availability of medications, pharmacist's explanation of the prescription, and waiting time to get medications) were the main outcomes. Results: The study comprised 91,317 participants, 74.06 % of them were CP/Wasfaty users. CP/Wasfaty patients had lower odds of satisfaction with the three pharmaceutical services: availability of medications (OR = 0.49, 95 % CI = 0.47-0.51), pharmacists' explanation of prescription (OR = 0.55, 95 % CI = 0.53-0.58), and waiting time to get medications (OR = 0.81, 95 % CI = 0.75-0.88). Additional findings showed variations in satisfaction levels based on demographic factors and clinic types. Conclusions: The significant differences observed in satisfaction levels based on demographic characteristics and type of clinics visited emphasize the importance of tailoring pharmaceutical services to meet the specific needs and expectations of different patient populations.

6.
Int J Mol Sci ; 25(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732033

RESUMO

Extreme temperature during summer may lead to heat stress in cattle and compromise their productivity. It also poses detrimental impacts on the developmental capacity of bovine budding oocytes, which halt their fertility. To mitigate the adverse effects of heat stress, it is necessary to investigate the mechanisms through which it affects the developmental capacity of oocytes. The primary goal of this study was to investigate the impact of heat stress on the epigenetic modifications in bovine oocytes and embryos, as well as on oocyte developmental capacity, reactive oxygen species, mitochondrial membrane potential, apoptosis, transzonal projections, and gene expression levels. Our results showed that heat stress significantly reduced the expression levels of the epigenetic modifications from histone H1, histone H2A, histone H2B, histone H4, DNA methylation, and DNA hydroxymethylation at all stages of the oocyte and embryo. Similarly, heat stress significantly reduced cleavage rate, blastocyst rate, oocyte mitochondrial-membrane potential level, adenosine-triphosphate (ATP) level, mitochondrial DNA copy number, and transzonal projection level. It was also found that heat stress affected mitochondrial distribution in oocytes and significantly increased reactive oxygen species, apoptosis levels and mitochondrial autophagy levels. Our findings suggest that heat stress significantly impacts the expression levels of genes related to oocyte developmental ability, the cytoskeleton, mitochondrial function, and epigenetic modification, lowering their competence during the summer season.


Assuntos
Metilação de DNA , Epigênese Genética , Resposta ao Choque Térmico , Potencial da Membrana Mitocondrial , Oócitos , Estresse Oxidativo , Espécies Reativas de Oxigênio , Animais , Bovinos , Oócitos/metabolismo , Resposta ao Choque Térmico/genética , Espécies Reativas de Oxigênio/metabolismo , Feminino , Histonas/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/genética , Apoptose/genética , Desenvolvimento Embrionário/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo
7.
J Saudi Heart Assoc ; 36(1): 8-13, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566900

RESUMO

Objective: To assess the risk factors associated with neurological complications and poor short-term outcomes following pediatric heart surgery. Methodology: A cross-sectional study was conducted in a cardiac intensive care unit between June 2019 and June 2022. The data of all children less than 15 years old who underwent open-heart surgery and had CT brain were extracted from hospital records. The primary outcome was the incidence of CNS insult, and secondary outcomes included death after surgery, length of stay in ICU and hospital. Data analysis was performed using SPSS version 23, and a p-value less than or equal to 0.05 was considered statistically significant. Results: Total 1850 surgeries were performed in the specified period of time. The study included 208 children who had CT Brain, with a median age of 5 months. 2.81 % children had neurological complications, with 25 % of patients who had CT brain. The most common neurological complication was seizure (7.2 %). There were no significant differences observed between CNS insult and age, gender, syndrome, or prematurity (p > 0.05), except for a significant association between previous CNS insult and CNS insult after surgery (p = 0.001). Children with CNS insult had significantly higher ICU and hospital length of stay, mortality after surgery, and mortality within 2 weeks of surgery (p ≤ 0.05). Conclusion: Seizure was most common neurological manifestation after cardiac surgeries in children. CNS insult after surgery was associated with worse outcomes, including longer hospital stays and increased mortality.

8.
Heliyon ; 10(7): e28635, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586366

RESUMO

Cedrus deodara is the central conifer plant affected by ozone and nitrogen pollutants among forest species worldwide. The growth of C. deodara depends upon the ectomycorrhizal (ECM) association, which is usually disturbed by these factors. This study aims to understand how these factors affect plants at physiological and biochemical levels. Three fungal strain consortiums were inoculated with two-year-old C. deodara seedlings. The stresses of 100 kg N h-1and 100 ppb O3 were applied for six months to study their impact on chlorophyll and antioxidant enzymes (SOD, CAT, and APX). The results showed that C2 (Consortium of Cedrus deodara) positively impacted the growth of selected plant species. The high photosynthesis rate was determined by enhanced chlorophyll content, and C2-treated plants showed high chlorophyll content. Relatively, chlorophyll a and b contents increased significantly in the seedlings treated with Ethylenediurea (EDU) alone and with ozone stress. In addition, a significant difference was observed between EDU and O3-treated plants (14% EDU400-O3 and 23% EDU600-O3) and the control. Overall, antioxidant activities were higher in the treated samples than in the control. The order of SOD activity was C2 (448 U/gFW) and lowest (354.7 U/gFW) in control. APX also showed higher activity in treated plants in C1 ≥ C2 ≥ C3+O3, whereas CAT activity was the highest in C2 treatments. Ozone and nitrogen-stressed plants showed higher activities than EDU-treated plants compared to non-treated ones. Our findings highlight the importance of understanding the signaling effects of numerous precursors. Moreover, an extended investigation of seedlings developing into trees must be conducted to verify the potential of ectomycorrhizal strains associated with C. deodara and comprehend EDU's role as a direct molecular scavenger of reactive toxicants.

9.
Cureus ; 16(3): e56287, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38623112

RESUMO

We present a compelling case of a patient initially diagnosed with a simple sliding hiatus hernia (HH), which was managed conservatively through optimised medical therapy. Over the span of a few years, she developed new symptoms which included epigastric discomfort and pain, prompting further clinical review and imaging investigation. These revealed the progression of her HH from a simple form to a more complex rolling or para-oesophageal type. This outcome highlights the importance of recognising a potential for progression during the clinical assessment of patients with a history of reflux symptoms and the onset of new epigastric discomfort or pain. Understanding this continuum of HHs is essential for physicians as management plans may need to switch from a conservative to a more invasive approach.

10.
Heliyon ; 10(7): e29143, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38623241

RESUMO

The human body is affected by ultraviolet radiation because it can penetrate and harm bodily cells. Although skin cancer and early aging are consequences of prolonged exposure to ultraviolet (UV) rays, sun rays signify immediate excessive exposure. In this context, some structural, optical, electrical, and mechanical properties of the beryllium-based cubic fluoro-perovskite RBeF3 (R[bond, double bond]K and Li) compounds are examined through the use of density functional theory (DFT) within generalized gradient approximation (GGA) using the Perdew-Burke-Ernzerhof (PBE) approximations (GGA-PBE). The compounds KBeF3 and LiBeF3 have space group 221-pm3m, and their lattice constants and volumes are (3.765, 3.566) Å and (53.380, 45.379) Å3, respectively, based on their structural properties. Computed results indicate that the compounds' bandgaps are 7.35 eV and 7.12 eV, respectively, with an indirect nature for KBeF3 and LiBeF3. The properties of the band structure indicate that both compounds are insulators. The bonding properties of these compounds, RBeF3, are a combination of covalent and ionic. Optical properties of the compounds are examined which reflect the light-matter interaction like reflectivity, conductivity, and absorption. These materials were likely very hard but brittle, based on a higher bulk modulus B from elastic features, the B/G ratio, Pugh's ratio, and Vickers hardness. The compound RBeF3, as determined by the findings, is used as a UV protection and reflection layer for car and room windows.

11.
Ann Thorac Surg ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621650

RESUMO

Neoadjuvant immunotherapy has gone from an idea to an indication in locally advanced lung cancer. Several phase III trials have demonstrated the superiority of neoadjuvant chemoimmunotherapy compared with chemotherapy in this setting. Although such progress has revolutionized the treatment of locally advanced disease, the unmet needs of stage I and stage II patients without lymph node disease have largely been underrepresented in existing trials. Up-front resection with few patients going on to complete adjuvant therapy remains the norm for most stage I and II patients. Emerging evidence now supports the exploration of supplemental checkpoint blockade in well-selected early-stage, node-negative patients with large tumors and no actionable driver mutations. Although concerns surrounding safety and risk exist, patient selection could be substantially improved using novel biomarker approaches that leverage our understanding of the tumor immune microenvironment of lung cancer. This review provides a comprehensive overview of the opportunities and controversies of perioperative immunotherapy in node-negative lung cancer.

12.
Eval Rev ; : 193841X241246826, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38665096

RESUMO

Maternal mortality, largely stemming from complications during pregnancy and childbirth, impacts poor expecting women with limited healthcare access in rural Pakistan. Conditional Cash Transfers (CCTs), commonly implemented in developing nations, are designed to improve the well-being of vulnerable populations by focusing on health and education. A CCT initiative named Chief Minister's Special Initiative for Mother and Child Health (CM-SIMCH) was launched in Khyber Pakhtunkhwa (KP), one of the less-developed provinces of Pakistan, to empower expecting women to access quality healthcare. This study investigates the factors influencing CM-SIMCH program participation and assesses its impact on the health of expecting women by analyzing health-seeking hospital visits in KP, Pakistan. The study utilizes the Propensity Score Matching (PSM) technique to analyze cross-sectional data obtained from 303 expecting women residing in the Nowshera district of KP. The PSM allows for a balanced comparison of participants who received the CM-SIMCH transfers with those who did not, assessing its impact on maternal healthcare access and outcomes. Empirical results show that factors such as education and family system positively influence the participation of expecting women in the CM-SIMCH program, whereas travel costs exert a negative effect. The intervention leads to a notable increase in hospital visits among these women, contributing to improved health outcomes in KP. This underscores the program's potential effectiveness in addressing maternal healthcare challenges and enhancing healthcare access for vulnerable women in less-developed areas. Therefore, empirical evidence supports the CM-SIMCH program's potential to promote maternal health and improve healthcare access in KP. The study recommends government intervention in health sector as a strategic imperative to empower women and enhance infant health.

13.
Heliyon ; 10(8): e29523, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38665566

RESUMO

The advancement of artificial intelligence (AI) and the ubiquity of social media have become transformative agents in contemporary educational ecosystems. The spotlight of this inquiry focuses on the nexus between AI and social media usage in relation to academic performance and mental well-being, and the role of smart learning in facilitating these relationships. Using partial least squares-structural equation modeling (PLS-SEM) on a sample of 401 Chinese university students. The study results reveal that both AI and social media have a positive impact on academic performance and mental well-being among university students. Furthermore, smart learning serves as a positive mediating variable, amplifying the beneficial effects of AI and social media on both academic performance and mental well-being. These revelations contribute to the discourse on technology-enhanced education, showing that embracing AI and social media can have a positive impact on student performance and well-being.

14.
Front Biosci (Landmark Ed) ; 29(4): 165, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38682212

RESUMO

The Editors-in-Chief have retracted the article titled "[Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by Leucophyllum frutescens (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays]" ([1]) due to significant concerns regarding the reliability and integrity of the data presented. After the publication of the article, several issues were brought to our attention regarding the originality and authenticity of the visual data within the manuscript. Specifically, Figure 4 of the article contains images that are identical to those in the previously published papers [2, 3]. This duplication of images raises serious questions about the validity of the results and the adherence to ethical standards of research. Despite multiple attempts to contact the authors for an explanation and an opportunity to address these concerns, no satisfactory response was provided. Given the lack of accountability and the serious nature of the academic misconduct implied, the Editor-in-Chief, after careful consideration and in accordance with the publication's ethical guidelines, has decided to retract the article.

15.
Front Public Health ; 12: 1324858, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665242

RESUMO

In this article, we present a mathematical model for human immunodeficiency virus (HIV)/Acquired immune deficiency syndrome (AIDS), taking into account the number of CD4+T cells and antiretroviral treatment. This model is developed based on the susceptible, infected, treated, AIDS (SITA) framework, wherein the infected and treated compartments are divided based on the number of CD4+T cells. Additionally, we consider the possibility of treatment failure, which can exacerbate the condition of the treated individual. Initially, we analyze a simplified HIV/AIDS model without differentiation between the infected and treated classes. Our findings reveal that the global stability of the HIV/AIDS-free equilibrium point is contingent upon the basic reproduction number being less than one. Furthermore, a bifurcation analysis demonstrates that our simplified model consistently exhibits a transcritical bifurcation at a reproduction number equal to one. In the complete model, we elucidate how the control reproduction number determines the stability of the HIV/AIDS-free equilibrium point. To align our model with the empirical data, we estimate its parameters using prevalence data from the top four countries affected by HIV/AIDS, namely, Eswatini, Lesotho, Botswana, and South Africa. We employ numerical simulations and conduct elasticity and sensitivity analyses to examine how our model parameters influence the control reproduction number and the dynamics of each model compartment. Our findings reveal that each country displays distinct sensitivities to the model parameters, implying the need for tailored strategies depending on the target country. Autonomous simulations highlight the potential of case detection and condom use in reducing HIV/AIDS prevalence. Furthermore, we identify that the quality of condoms plays a crucial role: with higher quality condoms, a smaller proportion of infected individuals need to use them for the potential eradication of HIV/AIDS from the population. In our optimal control simulations, we assess population behavior when control interventions are treated as time-dependent variables. Our analysis demonstrates that a combination of condom use and case detection, as time-dependent variables, can significantly curtail the spread of HIV while maintaining an optimal cost of intervention. Moreover, our cost-effectiveness analysis indicates that the condom use intervention alone emerges as the most cost-effective strategy, followed by a combination of case detection and condom use, and finally, case detection as a standalone strategy.


Assuntos
Linfócitos T CD4-Positivos , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Modelos Teóricos , Prevalência , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Antirretrovirais/uso terapêutico , Número Básico de Reprodução
17.
Int J Mol Sci ; 25(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38612721

RESUMO

The improvement of in vitro embryo development is a gateway to enhance the output of assisted reproductive technologies. The Wnt and Hippo signaling pathways are crucial for the early development of bovine embryos. This study investigated the development of bovine embryos under the influence of a Hippo signaling agonist (LPA) and a Wnt signaling inhibitor (DKK1). In this current study, embryos produced in vitro were cultured in media supplemented with LPA and DKK1. We comprehensively analyzed the impact of LPA and DKK1 on various developmental parameters of the bovine embryo, such as blastocyst formation, differential cell counts, YAP fluorescence intensity and apoptosis rate. Furthermore, single-cell RNA sequencing (scRNA-seq) was employed to elucidate the in vitro embryonic development. Our results revealed that LPA and DKK1 improved the blastocyst developmental potential, total cells, trophectoderm (TE) cells and YAP fluorescence intensity and decreased the apoptosis rate of bovine embryos. A total of 1203 genes exhibited differential expression between the control and LPA/DKK1-treated (LD) groups, with 577 genes upregulated and 626 genes downregulated. KEGG pathway analysis revealed significant enrichment of differentially expressed genes (DEGs) associated with TGF-beta signaling, Wnt signaling, apoptosis, Hippo signaling and other critical developmental pathways. Our study shows the role of LPA and DKK1 in embryonic differentiation and embryo establishment of pregnancy. These findings should be helpful for further unraveling the precise contributions of the Hippo and Wnt pathways in bovine trophoblast formation, thus advancing our comprehension of early bovine embryo development.


Assuntos
Apoptose , Embrião de Mamíferos , Feminino , Gravidez , Bovinos , Animais , Diferenciação Celular , Contagem de Células , Procedimentos Clínicos
18.
JAMA Oncol ; 10(5): 621-633, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38512301

RESUMO

Importance: To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%. Objective: To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials. Data Sources: MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of neoadjuvant chemoimmunotherapy and chemotherapy that included at least 10 patients. Study Selection: Observational studies and trials reporting the use of neoadjuvant radiotherapy, including chemoradiotherapy, molecular targeted therapy, or immunotherapy monotherapy, were excluded. Main Outcomes and Measures: Surgical, pathological, and efficacy end points and adverse events were pooled using a random-effects meta-analysis. Results: Among 43 eligible trials comprising 5431 patients (4020 males [74.0%]; median age range, 55-70 years), there were 8 randomized clinical trials with 3387 patients. For randomized clinical trials, pooled overall survival (hazard ratio, 0.65; 95% CI, 0.54-0.79; I2 = 0%), event-free survival (hazard ratio, 0.59; 95% CI, 0.52-0.67; I2 = 14.9%), major pathological response (risk ratio, 3.42; 95% CI, 2.83-4.15; I2 = 31.2%), and complete pathological response (risk ratio, 5.52; 95% CI, 4.25-7.15; I2 = 27.4%) favored neoadjuvant chemoimmunotherapy over neoadjuvant chemotherapy. For patients with baseline tumor PD-L1 levels less than 1%, there was a significant benefit in event-free survival for neoadjuvant chemoimmunotherapy compared with chemotherapy (hazard ratio, 0.74; 95% CI, 0.62-0.89; I2 = 0%). Conclusion and Relevance: This study found that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across surgical, pathological, and efficacy outcomes. These findings suggest that patients with resectable NSCLC with tumor PD-L1 levels less than 1% may have an event-free survival benefit with neoadjuvant chemoimmunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Terapia Neoadjuvante , Idoso , Humanos , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Terapia Neoadjuvante/efeitos adversos , Resultado do Tratamento
19.
PeerJ Comput Sci ; 10: e1813, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435563

RESUMO

Background: Blood diseases such as leukemia, anemia, lymphoma, and thalassemia are hematological disorders that relate to abnormalities in the morphology and concentration of blood elements, specifically white blood cells (WBC) and red blood cells (RBC). Accurate and efficient diagnosis of these conditions significantly depends on the expertise of hematologists and pathologists. To assist the pathologist in the diagnostic process, there has been growing interest in utilizing computer-aided diagnostic (CAD) techniques, particularly those using medical image processing and machine learning algorithms. Previous surveys in this domain have been narrowly focused, often only addressing specific areas like segmentation or classification but lacking a holistic view like segmentation, classification, feature extraction, dataset utilization, evaluation matrices, etc. Methodology: This survey aims to provide a comprehensive and systematic review of existing literature and research work in the field of blood image analysis using deep learning techniques. It particularly focuses on medical image processing techniques and deep learning algorithms that excel in the morphological characterization of WBCs and RBCs. The review is structured to cover four main areas: segmentation techniques, classification methodologies, descriptive feature selection, evaluation parameters, and dataset selection for the analysis of WBCs and RBCs. Results: Our analysis reveals several interesting trends and preferences among researchers. Regarding dataset selection, approximately 50% of research related to WBC segmentation and 60% for RBC segmentation opted for manually obtaining images rather than using a predefined dataset. When it comes to classification, 45% of the previous work on WBCs chose the ALL-IDB dataset, while a significant 73% of researchers focused on RBC classification decided to manually obtain images from medical institutions instead of utilizing predefined datasets. In terms of feature selection for classification, morphological features were the most popular, being chosen in 55% and 80% of studies related to WBC and RBC classification, respectively. Conclusion: The diagnostic accuracy for blood-related diseases like leukemia, anemia, lymphoma, and thalassemia can be significantly enhanced through the effective use of CAD techniques, which have evolved considerably in recent years. This survey provides a broad and in-depth review of the techniques being employed, from image segmentation to classification, feature selection, utilization of evaluation matrices, and dataset selection. The inconsistency in dataset selection suggests a need for standardized, high-quality datasets to strengthen the diagnostic capabilities of these techniques further. Additionally, the popularity of morphological features indicates that future research could further explore and innovate in this direction.

20.
Genes (Basel) ; 15(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38540338

RESUMO

DNA analysis of traces from commonly found objects like knives, smartphones, tapes and garbage bags related to crime in aquatic environments is challenging for forensic DNA laboratories. The amount of recovered DNA may be affected by the water environment, time in the water, method for recovery, transport and storage routines of the objects before the objects arrive in the laboratory. The present study evaluated the effect of four storage conditions on the DNA retrieved from bloodstains, touch DNA, fingerprints and hairs, initially deposited on knives, smartphones, packing tapes, duct tapes and garbage bags, and submerged in lake water for three time periods. After retrieval, the objects were stored either through air-drying at room temperature, freezing at -30 °C, in nitrogen gas or in lake water. The results showed that the submersion time strongly influenced the amount and degradation of DNA, especially after the longest submersion time (21 days). A significant variation was observed in success for STR profiling, while mtDNA profiling was less affected by the submersion time interval and storage conditions. This study illustrates that retrieval from water as soon as possible and immediate storage through air-drying or freezing before DNA analysis is beneficial for the outcome of DNA profiling in crime scene investigations.


Assuntos
Lagos , Impressões Digitais de DNA , DNA Mitocondrial , Água , Humanos
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