Optoelectronic analysis of designed semi-circular shaped thiophene-based bridged Y-series NFAs for organic solar cell applications.

The highly adaptable optoelectronic and morphological properties of non-fullerene acceptors (NFAs) have made them a prominent research topic in the organic solar cell (OSC) field. This work describes the design of new molecules and investigates the potential optoelectronic aspects of remodified Y-series NFAs endowing with five new semi-circular shaped derivatives (BTPB1-BTPB5) based on the DFT-based quantum simulations. The designed molecules possess higher-lying LUMO energy levels with narrowed bandgaps and excellent coherence between the acceptor and core via inserted bridges. The molecules demonstrate a significant red shift and a wide-ranging absorption spectrum extending from 400 nm to 1500 nm, with the most extensive absorption occurring in the near-infrared (NIR) region. Effective π-π stacking and drastically lower binding energy certify facile charge dissociation and transmission rate. Thiophene-based bridge modification decreased reorganization energy by 47 % which results in facile charge transmission and high current density. Theoretically, simulated PCE is achieved as high as 31.49 % owing to the higher-lying LUMOs. The results demonstrate the value of designing systems and exploring new possibilities for developing effective Y-series NFAs-based high-performance organic solar cells.

Comparative efficacy of endoscopic ultrasound-guided biliary drainage versus endoscopic retrograde cholangiopancreatography as first-line palliation in malignant distal biliary obstruction: a systematic review and meta-analysis.

Background: Malignant distal biliary obstruction (MDBO) is a challenging clinical condition commonly managed with endoscopic retrograde cholangiopancreatography (ERCP). However, endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative, especially in complex cases where ERCP fails or is deemed risky. This study aimed to compare the efficacy, safety and cost-effectiveness of EUS-BD vs. ERCP in the palliation of MDBO. Methods: We conducted a systematic review and meta-analysis, following PRISMA guidelines. Three databases were searched up to December 2023, including MEDLINE/PubMed, OVID and the Cochrane Central Register of Controlled Trials, for studies comparing EUS-BD with ERCP. Primary outcomes were technical and clinical success rates, while secondary outcomes included procedural times, hospital stay duration, 30-day mortality, reintervention rates, and adverse events such as pancreatitis. Results: Seven studies involving 1245 patients met the inclusion criteria. The meta-analysis revealed that EUS-BD had a technical success rate of 92%, compared to 85% for ERCP. Clinical success rates were similar for both EUS-BD and ERCP, at approximately 89%. EUS-BD was associated with a significantly lower incidence of pancreatitis (2% vs. 10% for ERCP). Conclusions: EUS-BD offers a viable and potentially superior alternative to ERCP for the primary palliation of MDBO, particularly in terms of technical success and a lower risk of pancreatitis. These findings support the adoption of EUS-BD in clinical settings equipped to perform this technique, though future research should focus on long-term outcomes and further economic analysis to solidify these recommendations.

Linezolid-resistant Enterococcus faecium clinical isolates from Pakistan: a genomic analysis.

BACKGROUND: Linezolid-resistant Enterococcus faecium (LRE) is a global priority pathogen. Thirteen LRE were reported from clinical specimens between November 2021 and April 2023 at two laboratories in Karachi, Pakistan. We aimed to investigate the strain types and genes associated with linezolid resistance among these isolates. Whole genome sequencing (WGS) was performed and analyzed by multilocus sequence typing (MLST). The presence of linezolid resistance genes was identified using ResFinder v4.1.11 and the LRE-finder tool. RESULTS: Twelve isolates belonged to clonal complex 17 (CC17); ST80 (n = 10), ST612 (n = 1) and ST1380 (n = 1). Six isolates showed the presence of optrA gene and G2576T mutations in the 23S rRNA gene, while six showed poxtA and cfr(D) genes. One isolate showed the combination of optrA, cfr(D) and poxtA genes. CONCLUSION: Our findings show the circulation of CC17 sequence types with a known outbreak potential and we identified molecular mechanisms of resistance that were not previously reported from Pakistan.

Unlocking Plant Resilience: Advanced Epigenetic Strategies Against Heavy Metal and Metalloid Stress.

The escalating threat of heavy metal and metalloid stress on plant ecosystems requires innovative strategies to strengthen plant resilience and ensure agricultural sustainability. This review provides important insights into the advanced epigenetic pathways to improve plant tolerance to toxic heavy metals and metalloid stress. Epigenetic modifications, including deoxyribonucleic acid (DNA) methylation, histone modifications, and small ribonucleic acid (RNA) engineering, offer innovative avenues for tailoring plant responses to mitigate the impact of heavy metal and metalloid stress. Technological advancements in high-throughput genome sequencing and functional genomics have unraveled the complexities of epigenetic regulation in response to heavy metal and metalloid contamination. Recent strides in this field encompass identifying specific epigenetic markers associated with stress resilience, developing tools for editing the epigenome, and integrating epigenetic data into breeding programs for stress-resistant crops. Understanding the dynamic interaction between epigenetics and stress responses holds immense potential to engineer resilient crops that thrive in environments contaminated with heavy metals and metalloids. Eventually, harnessing epigenetic strategies presents a promising trajectory toward sustainable agriculture in the face of escalating environmental challenges. Plant epigenomics expands, the potential for sustainable agriculture by implementing advanced epigenetic approaches becomes increasingly evident. These developments lay the foundation for understanding the growing significance of epigenetics in plant stress biology and its potential to mitigate the detrimental effects of heavy metal and metalloid pollution on global agriculture.

Comparison of routine del Nido cardioplegia vs two types of modified del Nido cardioplegias for myocardial protection among patients undergoing coronary artery bypass grafting (CABG) surgeries: A randomized double-blind clinical trial.

BACKGROUND: The del Nido cardioplegia solution is a widely used method for myocardial protection in various settings. However, there is limited evidence of its effectiveness in adult cardiac surgery, and the baseline solution, Plasma Lyte A, is not readily available, leading to the use of alternative baseline solutions. This study aims to investigate the effectiveness of routine del Nido cardioplegia in adult cardiac surgery and the impact of different baseline solutions on myocardial protection and other perioperative outcomes. METHODS: This study was a prospective, double-blind randomized parallel group clinical trial conducted at a single tertiary care hospital in Iran. A total of 187 adult patients were evaluated for eligibility, of which 120 met the inclusion criteria for elective isolated CABG surgery. The patients were randomly assigned to three groups, with each group consisting of 40 patients. The control group received a normal saline-based routine del Nido cardioplegia, Intervention Group A received Ringer lactate-based del Nido cardioplegia, and Intervention Group B received plain Ringer-based del Nido cardioplegia. The levels of Creatine Kinase-MB (CK-MB), Troponin T, Troponin I, and lactate were primarily assessed at four different times: after anesthesia induction (Baseline), 2 h, 12 h, and 24 h. RESULTS: Preoperative demographic and clinical characteristics were the same among groups with insignificant differences (p > 0.05). There was no significant difference among groups based on CK-MB, Troponin T, Troponin I, and lactate levels (p = 0.078, 0.143, 0.311, and 0.129 respectively). However, there was a significant difference in the time effect of Troponin T and Lactate (p = 0.034, p = <0.001). CONCLUSION: Normal saline, Ringer lactate, and plain Ringer provide comparable myocardial protection in adult-isolated CABG surgery with modified del Nido cardioplegia. Larger studies are needed to identify the best alternative to Plasma Lyte A while maintaining del Nido cardioplegia as the control.

Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With Urothelial Carcinoma Treated With Immune Checkpoint Inhibitor.

BACKGROUND: Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI. METHODS: Patients from 15 institutions were treated with ICI monotherapy. Primary endpoint was overall survival and secondary endpoints included observed response rate (ORR), and progression-free (PFS) calculated from ICI initiation. TMB was analyzed as dichotomous (≥10 vs. <10 mut/Mb) and continuous variable. RESULTS: We identified 411 patients: 203 were treated with ICI 1L/upfront; 104 with 2 + L. For the 1L/upfront: median [m] OS was numerically longer in patients with TMB ≥10 versus TMB <10: mOS 35 versus 26 months (HR = 0.6) and with MSI-H and MSI-S (mOS NR vs. 22 months), though neither association was statistically significant. A statistically significant association was found between TMB (continuous variable) and OS (HR = 0.96, P = .01). For 2 + L: mOS was numerically longer in patients with TMB ≥10 versus TMB <10: (20 vs. 12 months; HR = 0.9); mOS was 12 and 17 months for patients with MSI-H and MSI-S, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB ≥10 versus TMB <10: 61 versus 17 months; (HR = 0.2, P = .02) and with MSI-H and MSI-S (NR vs. 24 months). CONCLUSIONS: Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed.

Fabrication of a ZnFe2O4@Co/Ni-MOF nanocomposite and photocatalytic degradation study of azo dyes.

This study addresses the critical issue of removing organic pollutants from water, focusing on the photocatalytic degradation of Congo red (CR) dye using a novel ZnFe2O4@Co-Ni metal-organic framework (MOF) nanocomposite (ZFCNM). The primary aim was to develop a photocatalyst with enhanced efficiency by combining the properties of ZnFe2O4 with Co/Ni-MOF, leading to a low band gap (2.89 eV) and a high surface area (723 m2 g-1). The ZFCNM nanocomposite, synthesized via a hydrothermal method, was characterized by X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM), confirming the formation of face-centered cubic ferrite and hexagonal MOF structures. Fourier-transform infrared spectroscopy (FTIR) verified the presence of carboxyl (-COOH) groups and Fe-O bonds in the composite. Photodegradation efficiency was evaluated under varying conditions, including reaction time, pH, catalyst dosage, contaminant concentration, and light intensity. The ZFCNM photocatalyst, with an equal mass ratio of Co/Ni-MOF and ZnFe2O4, achieved a 98% removal efficiency of CR (75 min reaction time, pH 5, at 25 °C, and visible-light intensity of a 50 W LED lamp) significantly outperforming Co/Ni-MOF (24%) and ZnFe2O4 (36%) alone. The estimated quantum yield (QY) was 3.00 × 10-6 molecules per photon, and kinetic studies revealed a first-order reaction pathway with an R 2 value of 0.9813. These results highlight the potential of ZFCNM as an effective photocatalyst for water purification applications.

Spatiotemporal single-cell RNA sequencing reveals the role of steroid hormone pathway during chicken primordial follicle formation.

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.

Targeting glucosyltransferases to combat dental caries: Current perspectives and future prospects.

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.

Orbital malignant peripheral nerve sheath tumor: A case report and review.

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.

Phosphofructokinase-1 in Cancer: A Promising Target for Diagnosis and Therapy.

Tumor cells have distorted enzymatic houses, which change the metabolic state from oxidative phosphorylation to glycolysis with high lactate levels in a hypoxic environment. Redrafting the metabolic profile is an emerging hallmark of cancer. Glycolytic enzyme amplification occurs in about 70% of all malignancies. Current studies have found that PFK-1 overexpression is linked to cell migration, proliferation, and Overall Survival (OS) rate in various human cancer cell lines. This review intended to uncover the bona fide therapeutic target for cancer therapy and elucidate the role of PFK-1 in cancer. Furthermore, this review has outlined the listed pharmacological and genetic inhibitors of PFK-1. Following this review, future studies on PFK-1 should emphasize the molecular pathways implicated in PFK-1 overexpression in cancer development. The terms "PFK-1", "PFKP-1", "PFKL-1", "PFKM-1", "PFKM-1 and cancer", "PFKP-1 and cancer", "PFKL-1 and cancer", and "inhibitors of PFK-1" were used to retrieve the information from a variety of databases, including PubMed, Scopus, Google Scholar, and ScienceDirect. In a variety of malignancies, inhibiting the expression of PFK-1 isoforms has been reported to be the most effective therapeutic method. Overexpression of PFK-1 isoforms induces the Warburg effect, cell proliferation, and carcinogenesis by downregulating apoptotic proteins, such as active caspase-3, caspase-9, and caspase-8. YY1, synoviolin, Sh-RNA-507, SNAI, miR-520a/b/e, miR-128, and ß-miR-6517 are some of the putative genetic inhibitors against PFK-1 that have been used to manage the development of malignancies. Pharmacological inhibitors, such as penfluridol, synoviolin/HRD1, quercetin, ginsenoside 20(S)-Rg3, triptolide, worenine, acetylsalicylic acid, and salicylic acid, can regulate the advancement of malignancies by inhibiting PFK-1. Thus, PFK-1 is a promising molecular biomarker for cancer treatment. A prospective investigation can validate the unbiased approaches for discovering brandnew PFK-1 inhibitors for cancer treatment.

A Theoretical Investigation for Exploring the Potential Performance of Non-Fullerene Organic Solar Cells Through Side-Chain Engineering Having Diphenylamino Groups to Enhance Photovoltaic Properties.

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.

An assessment of the direct and indirect costs of bladder cancer preceding and following a cystectomy: a real-world evidence study.

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.

Chia seed-mediated fabrication of ZnO/Ag/Ag2O nanocomposites: structural, antioxidant, anticancer, and wound healing studies.

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.

Baeyer-Villiger oxidation: a promising tool for the synthesis of natural products: a review.

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.

Mechanistic insight into the mode of inhibition of dietary flavonoids; targeting macrophage migration inhibitory factor.

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.

Lack of awareness of secondary rheumatic prevention in preoperative candidates for mitral valve surgery - alarming situation.

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.

Shift in SARS-CoV-2 variants of concern from Delta to Omicron was associated with reduced hospitalizations, increased risk of breakthrough infections but lesser disease severity.

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.

A theoretical investigation for improving the performance of non-fullerene organic solar cells through side-chain engineering of BTR non-fused-ring electron acceptors.

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.

Radiolabeling and preclinical animal model evaluation of DTPA coupled 99mTc-labelled flutamide complex ([99mTc]DTPA-FLUT) as a potential radiotracer for cancer imaging.

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-99 m (99mTc) and to evaluate its binding efficiency with rhabdomyosarcoma (RMS) cancer cells. MATERIAL AND METHODS: Radiolabeling of FLUT with 185 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 6 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.