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The size of the initial primordial follicle pool in the ovary depends on primordial follicle formation, which determines the female reproductive lifespan. However, the molecular regulation of primordial follicle formation in chickens remains unclear. In this study, the left ovaries of chickens were collected at 2 d posthatch (dph), 5.5 dph, and 10.5 dph to examine the formation of primordial follicles. Single-cell mRNA sequencing (scRNA-seq) and spatial transcriptomic analysis were performed to explore the ovarian microenvironment and identify regulatory pathways involved in the formation of primordial follicles in chickens. Histomorphological analysis of chicken ovary tissues revealed the presence of germ cell cysts at 1 dph, which began to disintegrate at 2 dph. Primordial follicles appeared at 5.5 dph and continued to develop into larger-diameter follicles. scRNA-seq and spatial transcriptomic analysis revealed 24 cellular clusters involved in chicken primordial follicle formation. The metabolic pathway of steroid hormone synthesis was found in pregranulosa and pretheca cells. Histological analysis showed that chicken ovaries did not form primordial follicles after the inhibition of the steroid hormone synthesis pathway by simvastatin or tamoxifen. In addition, mRNA transcriptomic and bioinformatics analyses revealed that GREB1 was a downstream gene of the steroid hormone synthesis pathway during the formation of chicken primordial follicles. This study provides a valuable foundation for investigating primordial follicle formation in avian species and optimizing their reproductive performance.
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Malignant peripheral nerve sheath tumor of the orbit is an exceedingly rare entity. These tumors exhibit locally aggressive behavior, recurrences, distant metastasis, and poor response to existing treatment protocols. Orbital nerve sheath tumors are often associated with neurofibromatosis 1, and malignant transformation of neurofibroma into malignant nerve sheath tumor has also been seen. The recommended treatment for localized disease is radical or wide surgical excision to achieve negative margins followed by chemoradiation. For extensive disease, chemotherapy and radiotherapy can be utilized to stabilize the disease. Due to poor response and outcomes with current regimens, the focus has been shifted to approaches utilizing molecular targets and immunological agents. Despite all the advancements, the outcomes still remain discouraging for moderate- to high-grade lesions and thus necessitate studies to design promising treatment modalities.
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The emergence of antimicrobial resistance within bacterial communities poses formidable challenges to existing therapeutic strategies aimed at mitigating biofilm-mediated infections. Recent advancements in this domain have spurred the development of targeted antimicrobial agents, designed to selectively eradicate the primary etiological agents while preserving the beneficial microbial diversity of the oral cavity. Targeting glucosyltransferases (GTFs), which play crucial roles in dental biofilm formation, offers a precise strategy to inhibit extracellular polysaccharide synthesis without compromising oral microbiota. This review article delves into the intricate mechanisms underlying dental caries, with a specific focus on the role of GTFs, enzymes produced by S. mutans. It further provides an overview of current research on GTF inhibitors, exploring their mechanisms of action, efficacy, and potential applications in clinical practice. Furthermore, it discusses the challenges and opportunities in the development of novel GTF inhibitors, emphasizing the need for innovative approaches to combat biofilm-mediated oral diseases effectively.
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Plant extract-mediated fabrication of metal nanocomposites is used in cell proliferation inhibition and topical wound treatment, demonstrating significant effectiveness. Salvia hispanica L. (chia) seed extract (CE) is used as the reaction medium for the green fabrication of ecofriendly ZnO(CE) nanoparticles (NPs) and Ag/Ag2O(CE) and ZnO/Ag/Ag2O(CE) nanocomposites. The resultant nanoparticles and nanocomposite materials were characterized using UV-visible, Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray (EDX) techniques. In the context of antioxidant studies, ZnO/Ag/Ag2O(CE) exhibited 57% reducing power and 86% 2,2, diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. All three materials showed strong antibacterial activity against Staphylococcus aureus (S. aureus), Escherichia coli (E.coli), and Bacillus subtilis (B. subtilis) bacterial strains. Additionally, ZnO(CE), Ag/Ag2O(CE), and ZnO/Ag/Ag2O(CE) also revealed 64.47%, 42.56%, and 75.27% in vitro Michigan Cancer Foundation-7 (MCF7) cancer cell line inhibition, respectively, at a concentration of 100 µg/mL. Selectively, the most effective composite material, ZnO/Ag/Ag2O(CE), was used to evaluate in vivo wound healing potential in rat models. The study revealed 96% wound closure in 10 days, which was quite rapid healing compared to wound healing using clinically available ointment. Therefore, in conclusion, the ZnO/Ag/Ag2O(CE) nanocomposite material could be considered for further testing and formulation as a good anticancer and wound healing agent.
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Baeyer-Villiger oxidation is a well-known reaction utilized for the synthesis of lactones and ester functionalities from ketones. Chiral lactones can be synthesized from chiral or racemic ketones by employing asymmetric Baeyer-Villiger oxidation. These lactones act as key intermediates in the synthesis of most of the biologically active natural products, their analogues, and derivatives. Various monooxygenases and oxidizing agents facilitate BV oxidation, providing a broad range of synthetic applications in organic chemistry. The variety of enzymatic and chemoselective Baeyer-Villiger oxidations and their substantial role in the synthesis of natural products i.e., alkaloids, polyketides, fatty acids, terpenoids, etc. (reported since 2018) have been summarized in this review article.
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INTRODUCTION: To estimate the direct and indirect costs of bladder cancer prior to and following cystectomy in a U.S. sample of patients. METHODS: This retrospective, observational analysis of de-identified patients with bladder cancer utilized the MarketScan Commercial Claims & Encounters and Health & Productivity Management databases. Adult patients with bladder cancer plus ≥ 1 claim for partial or radical cystectomy between 1 October 2015 and 31 December 2020 (date of the cystectomy = index date) and who were continuously enrolled for 6 months pre- (baseline) and post-index (follow-up) were included in the sample. All-cause total healthcare costs and indirect costs associated with short-term and long-term disability (STD and LTD) employer claims were assessed during each of the 6-month baseline and follow-up periods. RESULTS: The study included N = 142 patients; mean age 56 ± 6 years, 76% (male), and 42% had a baseline Deyo-Charlson Comorbidity Index ≥ 2. Baseline mean total all-cause direct healthcare costs were $51,473 ± $48,560 (median: $36,202), and $99,524 ± 86,839 (median: $75,444) during follow-up. At baseline, 32% of patients had ≥ 1 STD claim, equating to a mean 134 ± 303 h lost and $2,353 ± $6,445 in total payments per patient. Follow up STD claims increased 23.4% equating to a mean 218 ± 324 h lost and $3,679 ± $7,795 per patient. Patient LTD claims increased from baseline to follow-up (1-3%), with post-cystectomy LTD claims resulting in 574 ± 490 h lost, and $1,636 ± $1,429 in total payments. Over 85% of the population had a cystectomy related complication, the most common were genitourinary-related (47.9%) and infection/sepsis (33.1%). CONCLUSIONS: Cystectomy was associated with complications and decreased work productivity post-surgery. Findings may aid to inform decisions regarding cystectomy vs. bladder preservation approaches, and underscores an ongoing need to further develop bladder preservation therapies within the bladder cancer treatment landscape.
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Cistectomia , Gastos em Saúde , Revisão da Utilização de Seguros , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/economia , Cistectomia/economia , Cistectomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Gastos em Saúde/estatística & dados numéricos , Estados Unidos , Efeitos Psicossociais da Doença , Comorbidade , Idoso , Custos de Cuidados de Saúde/estatística & dados numéricos , AdultoRESUMO
The development of ecofriendly fabrication phenomenon is essential requirement for commercialization of non-fullerene acceptors. Recently, end-capped modeling is employed for computational design of five non-fullerene acceptors to elevate various photovoltaic properties. All new molecules are formulated by altering the peripheral acceptors of CH3-2F and DFT methodology is employed to explore the opto-electronic, morphological and charge transfer analysis. From the computational investigation, all reported molecules manifested red shifted absorption with remarkable reduced band gap. Among investigated molecules, FA1-FA3 evinced effectively decreased value of band gaps and designed molecules have low excitation energy justifying proficient charge transference. The lower values of binding energy of FA1 and FA2 suggest their facile exciton dissociation leading to improved charge mobility. By blending with J61 donor, FA4 have sufficiently enhanced value of VOC (1.72 eV) and fill factor (0.9228). Energy loss of the model (R) is 0.57 eV and statistical calculation demonstrate that all our modified molecules except FA3 has profoundly reduced energy loss compelling in its pivotal utilization. From accessible supportive outcomes of recent investigation, it is recommended that our modified chromophore exhibit remarkable noteworthy applications in solar cells for forthcoming innovations.
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Introduction: The Macrophage Migration Inhibitory Factor (MIF), a key pro-inflammatory mediator, is responsible for modulating immune responses. An array of inflammatory and autoimmune diseases has been linked to the dysregulated activity of MIF. The significance in physiological as well as pathophysiological phenomena underscores the potential of MIF as an attractive target with pharmacological relevance. Extensive research in past has uncovered a number of inhibitors, while the ISO-1, or (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester being recognized as a benchmark standard so far. Recent work by Yang and coworkers identified five promising dietary flavonoids, with superior activity compared to the standard ISO-1. Nevertheless, the exact atomic-level inhibitory mechanism is still elusive. Methods: To improve the dynamic research, and rigorously characterize, and compare molecular signatures of MIF complexes with ISO-1 and flavonoids, principal component analysis (PCA) was linked with molecular dynamics (MD) simulations and binding free energy calculations. Results: The results suggest that by blocking the tautomerase site these small molecule inhibitors could modify the MIF activity by disrupting the intrinsic dynamics in particular functional areas. The stability matrices revealed the average deviation values ranging from 0.27-0.32 nm while the residue level fluctuations indicated that binding of the selected flavonoids confer enhanced stability relative to the ISO-1. Furthermore, the gyration values extracted from the simulated trajectories were found in the range of 1.80-1.83 nm. Discussion: Although all the tested flavonoids demonstrated remarkable results, the one obtained for the potent inhibitors, particularly Morin and Amentoflavone exhibited a good correlation with biological activity. The PCA results featured relatively less variance and constricted conformational landscape than others. The stable ensembles and reduced variation in turns might be the possible reasons for their outstanding performance documented previously. The results from the present exploration provide a comprehensive understanding of the molecular complexes formed by flavonoids and MIF, shedding light on their potential roles and impacts. Future studies on MIF inhibitors may benefit from the knowledge gathered from this investigation.
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BACKGROUND: We conducted this study to assess the compliance with secondary rheumatic prophylaxis among preoperative patients with rheumatic mitral valve disease undergoing valvular heart surgery at a tertiary care cardiac hospital in a developing country. METHODS: This is a descriptive cross-sectional study conducted at a tertiary care cardiac hospital in Karachi, Pakistan. The inclusion criteria encompassed patients of any sex, aged between 18 and 80 years, who had been diagnosed with rheumatic mitral valve disease through transthoracic echocardiography and had undergone valvular heart surgery. The level of compliance with secondary rheumatic prophylaxis and barriers toward noncompliance was assessed during routine preoperative interview session. This preventive measure plays a crucial role in reducing the progression of the disease and improving patient outcomes. RESULTS: Out of the 239 patients included in the study, 125 (52.3%) were females, with a mean age of 38.8 ± 11.8 years. The majority of patients (88.7%) came from rural areas. Among the patients, 79 (33.1%) received rheumatic prophylaxis, while 160 (66.9%) did not adhere to it regularly. The common barriers for receiving rheumatic prophylaxis were non availability (41.0%) and nonaffordability (40.6%). Additionally, 28.0% of patients had lacked awareness of the importance of rheumatic prophylaxis, and 2.5% expressed fear of injection site pain and subsequent symptoms. CONCLUSIONS: A concerning level of noncompliance with secondary rheumatic prophylaxis was observed. The barriers identified in patients who did not receive rheumatic prophylaxis were primarily related to affordability, availability, lack of awareness, and fear of injection site pain and subsequent symptoms.
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Conhecimentos, Atitudes e Prática em Saúde , Valva Mitral , Cardiopatia Reumática , Prevenção Secundária , Humanos , Feminino , Masculino , Cardiopatia Reumática/cirurgia , Cardiopatia Reumática/diagnóstico por imagem , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Paquistão , Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem , Adulto Jovem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Adolescente , Cooperação do Paciente , Idoso , Fatores de Risco , Doenças das Valvas Cardíacas/cirurgia , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/complicações , Conscientização , Resultado do Tratamento , Fidelidade a Diretrizes , Idoso de 80 Anos ou mais , Países em Desenvolvimento , Centros de Atenção Terciária , Cuidados Pré-Operatórios , Educação de Pacientes como AssuntoRESUMO
In the current quantum chemical study, indacenodithiophene donor core-based the end-capped alterations of the reference chromophore BTR drafted eight A2-A1-D-A1-A2 type small non-fullerene acceptors. All the computational simulations were executed under MPW1PW91/6-31G (d, p) level of DFT. The UV-Vis absorption, open circuit voltage, electron affinity, ionization potential, the density of states, reorganization energy, orbital analysis, and non-covalent interactions were studied and compared with BTR. Several molecules of our modeled series BT1-BT8 have shown distinctive features that are better than those of the BTR. The open circuit voltage (VOC) of BT5 has a favorable impact, allowing it to replace BTR in the field of organic solar cells. The charge carrier motilities for proposed molecules generated extraordinary findings when matched to the reference one (BTR). Further charge transmission was confirmed by creating the complex with a PM6 donor molecule. The remarkable dipole moment contributes to the formation of non-covalent bond interactions with chloroform, resulting in superior charge mobility. Based on these findings, it can be said that every tailored molecule has the potential to surpass chromophore molecule (BTR) in OSCs. So, all tailored molecules may enhance the efficiency of photovoltaic cells due to the involvement of potent terminal electron-capturing acceptor2 moieties. Considering these obtained results, these newly presented molecules can be regarded for developing efficient solar devices in the future.
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Elétrons , Fulerenos , Energia Solar , Fulerenos/química , Modelos Moleculares , Teoria Quântica , Tiofenos/química , Estrutura MolecularRESUMO
BACKGROUND: COVID-19 epidemiology changed with the emergence of SARS-CoV-2 variants of concern (VOC). Pakistan administered mostly inactivated vaccines. We investigated the association between VOC and breakthrough infections in a mixed-vaccination-status population of Karachi. METHODS: We investigated SARS-CoV-2 VOC tested in 392 respiratory specimens collected between May and December 2021. Data for age, sex, hospital admission, vaccinations, together with CT values of the diagnostic PCR test were analyzed. RESULTS: The median age of COVID-19 cases tested was 40 (27-57) years and 43.4% were female. Delta variants were most common (56.4%) followed by Alpha (15.9%), Omicron (12.2%), Beta/Gamma (11.3%), and others (4.3%). Eighteen percent of cases were hospitalized whereby, predominant VOC were Beta/Gamma (40.8%), Alpha (35.2%) and Delta (22.5%). Overall, 55.4% of individuals were fully vaccinated, 7.4% were partially vaccinated and 37.2% were unvaccinated. Most (74.6%) inpatients were unvaccinated. Vaccines comprised inactivated (85.34%), single-shot vector (8.62%), two-shot vector (3.02%) and mRNA (3.02%) types. Omicron variants showed lower viral loads as compared to Alpha, Beta/Gamma, and Delta (p = 0.017). The risk of infection with Delta and Omicron variants was higher, 8 weeks after vaccination. The majority of those with breakthrough infections after receiving inactivated vaccines acquired COVID-19 within 4 months of vaccination. CONCLUSION: Our data highlights the shifting of VOC from Delta to Omicron during 2021 and that COVID-19 vaccinations reduced both hospitalizations and viral transmission. It informs on the increased risk of breakthrough infection within 8 weeks of vaccination, indicating the need for booster vaccinations.
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Vacinas contra COVID-19 , COVID-19 , Hospitalização , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , Feminino , Masculino , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Adulto , Pessoa de Meia-Idade , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Hospitalização/estatística & dados numéricos , Paquistão/epidemiologia , Índice de Gravidade de Doença , Vacinação/estatística & dados numéricos , Infecções IrruptivasRESUMO
BACKGROUND: Advances in molecular imaging strategies have had an effect on precise diagnosis and treatment. Research has been intensified to develop more effective and versatile radiopharmaceuticals to uplift diagnostic efficiency and, consequently, the treatment. PURPOSE: To label the flutamide (FLUT) coupled with diethylenetriamine pentaacetate (DTPA) with technetium-99â m (99mTc) and to evaluate its binding efficiency with rhabdomyosarcoma (RMS) cancer cells. MATERIAL AND METHODS: Radiolabeling of FLUT with 185â MBq freshly eluted 99mTcO4-1 was carried out via DTPA bifunctional chelating agent using stannous chloride reducing agent at pH 5. The labeled compound was assessed for its purity using chromatography analysis, stability in saline and blood serum, AND charge using paper electrophoresis. Normal biodistribution was studied using a mouse model, while binding affinity with RMS cancer cells was studied using an internalization assay. The in vivo accumulation of RMS cancer cells in a rabbit model was monitored using a SPECT gamma camera. RESULTS: Radiolabeling reaction displayed a pharmaceutical yield of 97% and a stability assay showed >95% intact radiopharmaceutical up to 6â h in saline and blood serum. In vitro internalization studies showed the potential of [99mTc]DTPA-FLUT to enter into cancer cells. This biodistribution study showed rapid blood clearance and minimum uptake by body organs, and scintigraphy displayed the [99mTc]DTPA-FLUT uptake by lesion, induced by RMS cancer cell lines in rabbit. CONCLUSION: Stable, newly developed [99mTc]DTPA-FLUT seeks its way to internalize into RMS cancer cells, indicating it could be a potential candidate for the diagnosis of RMS cancer.
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BACKGROUND AND OBJECTIVES: Acute appendicitis is one of the most commonly encountered surgical emergencies on a global level. Due to the requirement of an immediate clinical diagnosis and the presence of limited resources, clinicians and diagnosticians refer to scoring systems to diagnose this condition, among which Alvarado and Tzanakis scoring systems are widely used. This meta-analysis aims to compare the diagnostic accuracy of these two systems. METHODS: We searched PubMed, Google Scholar, and SCOPUS databases. All studies that reported diagnostic parameters of Alvarado and Tzanakis scores in patients with suspected acute appendicitis were selected. Diagnostic values such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were extracted from the selected studies and statistical analysis was performed with Meta Disc 1.4 software. Quality assessment of the selected studies was performed using the QUADAS-2 and QUADAS-C tools. Fourteen studies were included in our meta-analysis which enrolled 2235 patients. RESULTS: The overall sensitivity of the Tzanakis score was calculated as 0.86 (95% CI; 0.84-00.87) while the specificity was 0.73 (95% CI; 0.69-0.78). In addition, the area under the curve (AUC) was 0.9261 (SE; 0.0169) and the diagnostic Odds Ratio (OR) was 22.52 (95% CI; 9.47-53.56). The pooled sensitivity of Alvarado score was 0.67 (95% CI; 0.65-0.69) and the specificity was 0.74 (95% CI; 0.69-0.79). Moreover, the area under the curve (AUC) of the Alvarado score was 0.7389 (SE; 0.0489) and the diagnostic Odds Ratio was 4.92 (95% CI; 2.48-9.75). INTERPRETATION AND CONCLUSION: The Tzanakis scoring system has a higher sensitivity, area under the curve, and diagnostic odds ratio when compared to the Alvarado score. However, the Alvarado score has a marginally better specificity making it more reliable in excluding acute appendicitis.
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PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617. METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1-4.9 h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates. RESULTS: 56 patients (means age 76.2 ± 8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS. CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.
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Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Lutécio , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Idoso , Lutécio/uso terapêutico , Dipeptídeos/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Imagem Corporal Total , Idoso de 80 Anos ou mais , Radioisótopos , Antígeno Prostático EspecíficoRESUMO
Background: In this study, we aim to discuss the long-term clinical outcomes of intravascular ultrasound imaging-guided percutaneous intervention (IVUS-PCI) versus angiography-guided percutaneous coronary intervention (PCI) in complex coronary lesions over a mean period of 2 years. Methods: A systematic search and meta-analysis were conducted to assess the efficacy of using intravascular ultrasound or optical coherence tomography guidance in coronary artery stenting compared to angiography. Results: A total of 11 randomized controlled trials with 6740 patients were included. For the primary outcome, a pooled analysis (3.2 vs 5.6%). For secondary outcomes, the risk was significantly low in image-guided percutaneous intervention compared with angiography. Conclusion: Intravascular imaging-guided PCI is significantly more effective than angiography-guided PCI in reducing the risk of target lesion revascularization, target vessel revascularization, cardiac death, major adverse cardiovascular events and stent thrombosis.
A meta-analysis was conducted to compare intravascular ultrasound guidance/optical coherence tomography percutaneous coronary intervention with angiography percutaneous coronary intervention with target lesion revascularization as the primary outcome and target vessel revascularization, stent thrombosis, myocardial infarction, major adverse cardiovascular events, all cause death and cardiac death as the secondary outcomes.
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Angiografia Coronária , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Ultrassonografia de Intervenção , Humanos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/diagnóstico , Intervenção Coronária Percutânea/métodos , Cirurgia Assistida por Computador/métodos , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Ultrassonografia de Intervenção/métodosRESUMO
INTRODUCTION AND IMPORTANCE: Epidermoid cysts also known as epidermal inclusion cysts are the most common type of cutaneous cysts. These are derived from ectoderm with a lining of stratified squamous epithelium. Penile epidermoid cysts however are very rare. We report a case of Fifteen years old male with complain of slow growing mass at ventral aspect of shaft of penis along with urethrocutaneous fistula following hypospadias surgery. Surgical excision was done of the cyst. Histopathology of the sample revealed an epidermoid cyst. CASE PRESENTATION: We report a case of a Fifteen years boy who underwent midshaft hypospadias repair at the age of five years. During postoperative period stent was removed and one week after that he developed a urethrocutaneous fisula. At seven years of age patient reported a small swelling on the penile shaft which gradually increased in size over the years, however, he seeks no medical care for it. CLINICAL DISCUSSION: At time of presentation swelling was separately appreciable from urehtrocuataneous fistula and extending from subcoroanal to midshaft of penis. We did excision of epidermal cyst and repair of urethrocutaneous fistula. CONCLUSIONS: Epidermal inclusion cyst as a complication of hypospadias surgery is a very rare situation. The diagnosis is made histologically and surgical excision is sufficient for treatment.
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Free Fatty Acid Receptor 4 (FFAR4), a G-protein-coupled receptor, is responsible for triggering intracellular signaling pathways that regulate various physiological processes. FFAR4 agonists are associated with enhancing insulin release and mitigating the atherogenic, obesogenic, pro-carcinogenic, and pro-diabetogenic effects, normally associated with the free fatty acids bound to FFAR4. In this research, molecular structure-based machine-learning techniques were employed to evaluate compounds as potential agonists for FFAR4. Molecular structures were encoded into bit arrays, serving as molecular fingerprints, which were subsequently analyzed using the Bayesian network algorithm to identify patterns for screening the data. The shortlisted hits obtained via machine learning protocols were further validated by Molecular Docking and via ADME and Toxicity predictions. The shortlisted compounds were then subjected to MD Simulations of the membrane-bound FFAR4-ligand complexes for 100 ns each. Molecular analyses, encompassing binding interactions, RMSD, RMSF, RoG, PCA, and FEL, were conducted to scrutinize the protein-ligand complexes at the inter-atomic level. The analyses revealed significant interactions of the shortlisted compounds with the crucial residues of FFAR4 previously documented. FFAR4 as part of the complexes demonstrated consistent RMSDs, ranging from 3.57 to 3.64, with minimal residue fluctuations 5.27 to 6.03 nm, suggesting stable complexes. The gyration values fluctuated between 22.8 to 23.5 nm, indicating structural compactness and orderliness across the studied systems. Additionally, distinct conformational motions were observed in each complex, with energy contours shifting to broader energy basins throughout the simulation, suggesting thermodynamically stable protein-ligand complexes. The two compounds CHEMBL2012662 and CHEMBL64616 are presented as potential FFAR4 agonists, based on these insights and in-depth analyses. Collectively, these findings advance our comprehension of FFAR4's functions and mechanisms, highlighting these compounds as potential FFAR4 agonists worthy of further exploration as innovative treatments for metabolic and immune-related conditions.
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Aprendizado de Máquina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Receptores Acoplados a Proteínas G , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/química , Humanos , Ligantes , Ligação Proteica , Teorema de Bayes , Sítios de LigaçãoRESUMO
BACKGROUND: Hexaploid bread wheat underwent a series of polyploidization events through interspecific hybridizations that conferred adaptive plasticity and resulted in duplication and neofunctionalization of major agronomic genes. The genetic architecture of polyploid wheat not only confers adaptive plasticity but also offers huge genetic diversity. However, the contribution of different gene copies (homeologs) encoded from different subgenomes (A, B, D) at different growth stages remained unexplored. METHODS: In this study, hybrid of elite cultivars of wheat were developed via reciprocal crosses (cytoplasm swapping) and phenotypically evaluated. We assessed differential expression profiles of yield-related negative regulators in these cultivars and their F1 hybrids and identified various cis-regulatory signatures by employing bioinformatics tools. Furthermore, the preferential expression patterns of the syntenic triads encoded from A, B, and D subgenomes were assessed to decipher their functional redundancy at six different growth stages. RESULTS: Hybrid progenies showed better heterosis such as up to 17% increase in the average number of grains and up to 50% increase in average thousand grains weight as compared to mid-parents. Based on the expression profiling, our results indicated significant dynamic transcriptional expression patterns, portraying the different homeolog-dominance at the same stage in the different cultivars and their hybrids. Albeit belonging to same syntenic triads, a dynamic trend was observed in the regulatory signatures of these genes that might be influencing their expression profiles. CONCLUSION: These findings can substantially contribute and provide insights for the selective introduction of better cultivars into traditional and hybrid breeding programs which can be harnessed for the improvement of future wheat.
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Melhoramento Vegetal , Triticum , Triticum/genética , Hibridização Genética , Vigor Híbrido/genéticaRESUMO
The two-dimensional (2D) semiconducting family of XSi2N4 (X = Mo and W), an emergent class of air-stable monolayers, has recently gained attention due to its distinctive structural, mechanical, transport, and optical properties. However, the electrical contact between XSi2N4 and metals remains a mystery. In this study, we inspect the electronic and transport properties, specifically the Schottky barrier height (SBH) and tunneling probability, of XSi2N4-based van der Waals contacts by means of first-principles calculations. Our findings reveal that the electrical contacts of XSi2N4 with metals can serve as the foundation for nanoelectronic devices with ultralow SBHs. We further analyzed the tunneling probability of different metal contacts with XSi2N4. We found that the H-phase XSi2N4/metal contact shows superior tunneling probability compared to that of HÌ-based metal contacts. Our results suggest that heterostructures at interfaces can potentially enable efficient tunneling barrier modulation in metal contacts, particularly in the case of MoSi2N4/borophene compared to MoSi2N4/graphene and WSi2N4/graphene in transport-efficient electronic devices. Among the studied heterostructures, tunneling efficiency is highest at the H and HÌ-MoSi2N4/borophene interfaces, with barrier heights of 2.1 and 1.52 eV, respectively, and barrier widths of 1.04 and 0.8 Å. Furthermore, the tunneling probability for these interfaces was identified to be 21.3 and 36.4%, indicating a good efficiency of carrier injection. Thus, our study highlights the potential of MoSi2N4/borophene contact in designing power-efficient Ohmic devices.
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OBJECTIVE: The aim of this study was to examine the short-term patency rates and associated factors of open lower limb, iliofemoral to tibial bypass using cryopreserved saphenous vein (CSV) in a minority population at an acute care hospital in New York City. METHODS: A retrospective analysis of patients undergoing infra-inguinal bypass from iliofemoral vessels to tibial arteries with CSV between March 2020-April 2022 at an acute care facility (Harlem Hospital Center, Harlem, New York) was performed. Data including patient demographics, comorbidities, type of operation, follow-up surveillance, and salvage procedures were collected. Results were presented in patency line graphs and a life table. Target limb revascularization (TLR) and amputation free survival (AFS) were also calculated. RESULTS: Eleven bypass procedures were included in the analysis. Patients were followed for a mean of 10.8 months. Cumulative primary patency rates at 1, 6, and 12 months were 72.7%, 54.5%, and 40.9%, respectively. TLR was 36.4% and the AFS was 66.67% at the mean 10.8-month follow-up. CONCLUSIONS: The patency rates of minority patients undergoing bypass with CSV were analyzed with creation of a life table and calculation of patency rates, TLR and AFS. The short-term primary patency rates and post-operative outcomes were found to be comparable to larger studies in non-minority cohorts. These results suggest that larger studies as well as prospective analyses and randomized controlled trials in this patient cohort and demographic are needed, as well as optimal selection of patients to determine true clinical implications.