The diagnostic utility of heparin-binding protein among patients with bacterial infections: a systematic review and meta-analysis.

BACKGROUND: Bacterial infections are considered a leading cause of hospitalization and death globally. There is still a need for a rapid and feasible biomarker for bacterial infections. Heparin-binding protein (HBP) was shown to be related to bacterial infections. The objective of the study is to investigate the diagnostic accuracy of HBP in bacterial infections. METHODS: Articles were screened in PubMed, SCOPUS, Web of Science, and Cochrane to recognize eligible studies. We included studies investigating the diagnostic accuracy of HBP and reported the necessary data to construct 2 × 2 tables. A univariate analysis was conducted to determine the pooled sensitivity and specificity, and a bivariate diagnostic random-effects model was used to calculate the optimal cut-off point. RESULTS: The analysis comprised sixteen studies in total. Plasma HBP showed a sensitivity of 0.90 (95% CI: [0.79, 0.96]) and a specificity of 0.87 (95% CI: [0.66, 0.96]) in diagnosing bacterial infections using blood samples. Pooling data from seven studies revealed that HBP in cerebrospinal fluid (CSF) has sensitivity and specificity of 96% (95% CI: [0.85, 0.99]), and 95% (95% CI: [0.89, 0.97]), respectively, for the diagnosis of bacterial meningitis. In urinary tract infections (UTI), urine-HBP was revealed to have a high diagnostic value in discriminating bacterial from non-bacterial UTI infection at a cut-off value of 32.868 ng/ml with sensitivity and specificity of 87%. CONCLUSION: HBP has shown a high diagnostic accuracy of bacterial infections, including UTI and meningitis. Further studies are needed to determine its prognostic value and whether it could guide antibiotic therapy.

Assessment of surgical, anesthesia, and obstetric workforce in Somalia.

BACKGROUND: One of the core indicators recommended by the Lancet Commission is surgical workforce density, aiming to improve the number of surgery, anesthetists, and obstetric (SAO) providers to 20 per 100,000 population by 2030. We assessed SAO workforce capacity in Somalia and made recommendations for improvement. METHOD: A cross-sectional study was conducted using a structured questionnaire from the WHO Program for Global Surgery and Social Change (PGSSC) Surgical Assessment Tool. All hospitals that offer surgical care services were included. A descriptive analysis was conducted using the statistical software SPSS. RESULTS: Of the 55 surveyed facilities providing surgical care services, 28 (50.9%) were public, mainly in urban areas. We found that there were 474 SAO specialists and non-specialists (SAO providers) and 446 other important personnel (e.g., midwives, radiologists, and pathologists). Out of 474 SAOs, Banadir had 288. Overall, surgery specialties were the most prevalent profession among SAO providers' workforce, accounting for 160 (33.7%) surgery specialists, with 1.2 per 100,000 population. The six states of Somalia have 54 OB/GYN specialists (0.4 per 100,000 population). There were a total of 22 anesthesia specialists, with a ratio of 0.2 anesthesia specialists per 100,000 population. CONCLUSION: We found a serious shortage of the SAO workforce in Somalia, and it is unlikely to meet the 2030 Lancet Commission on Global Surgery targets. There is a need for additional training of SAO providers who can offer effective leadership in surgical care services to combat the extremely avoidable surgical-related morbidities and mortalities.

Synthesis and molecular docking simulation of new benzimidazole-thiazole hybrids as cholinesterase inhibitors.

Dementia is a cognitive disturbance that is generally correlated with central nervous system diseases, especially Alzheimer's disease. The limited number of medications available is insufficient to improve the lifestyle of the patients suffering from this disease. Thus, new benzimidazole-thiazole hybrids (3-10) were designed and synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory agents. The in vitro evaluation displayed that the derivatives 4b, 4d, 5b, 6a, 7a, and 8b demonstrated dual inhibitory efficiency against both AChE with IC50 ranging from 4.55 to 8.62 µM and BChE with IC50 ranging from 3.50 to 8.32 µM. By analyzing the Lineweaver-Burk plot, an uncompetitive form of inhibition was determined for the highly active compound 4d, revealing its inhibition type. The human telomerase reverse transcriptase-immortalized retinal pigment epithelial cell line was used to ensure the safety of the most potent cholinesterase inhibitors. Furthermore, compounds 4b, 4d, 5b, 6a, 7a, and 8b were evaluated for their neuroprotective and antioxidant properties, as well as their ability to suppress COX-2. The results demonstrated that compounds 4d, 5b, and 8b presented significant neuroprotection efficiency against H2 O2 -induced damage in SH-SY5Y cells with % cell viability of 67.42 ± 7.90%, 62.51 ± 6.71%, and 72.61 ± 8.10%, respectively, while the tested candidates did not reveal significant antioxidant activity. Otherwise, compounds 4b, 6a, 7a, and 8b displayed outstanding COX-2 inhibition effects with IC50 ranging from 0.050 to 0.080 µM relative to celecoxib (IC50 = 0.050 µM). In addition, molecular docking was carried out for the potent benzimidazole-thiazole hybrids with the active sites of both AChE (PDB ID: 4EY7) and BChE (PDB code: 1P0P). The tested candidates fit well in the active sites of both portions, with docking scores ranging from -8.65 to -6.64 kcal/mol (for AChE) and -8.71 to -7.73 kcal/mol (for BChE). In silico results show that the synthesized benzimidazole-thiazole hybrids have good physicochemical and pharmacokinetic properties with no Lipinski rule violations. The preceding results exhibited that compound 4d could be used as a new template for developing more significant cholinesterase inhibitors in the future.

Notch-based gene signature for predicting the response to neoadjuvant chemotherapy in triple-negative breast cancer.

BACKGROUND: While the efficacy of neoadjuvant chemotherapy (NACT) in treating triple-negative breast cancer (TNBC) is generally accepted, not all patients derive benefit from this preoperative treatment. Presently, there are no validated biomarkers to predict the NACT response, and previous attempts to develop predictive classifiers based on gene expression data have not demonstrated clinical utility. However, predictive models incorporating biological constraints have shown increased robustness and improved performance compared to agnostic classifiers. METHODS: We used the preoperative transcriptomic profiles from 298 patients with TNBC to train and test a rank-based classifier, k-top scoring pairs, to predict whether the patient will have pathological complete response (pCR) or residual disease (RD) following NACT. To reduce overfitting and enhance the signature's interpretability, we constrained the training process to genes involved in the Notch signaling pathway. Subsequently, we evaluated the signature performance on two independent cohorts with 75 and 71 patients. Finally, we assessed the prognostic value of the signature by examining its association with relapse-free survival (RFS) using Kaplan‒Meier (KM) survival estimates and a multivariate Cox proportional hazards model. RESULTS: The final signature consists of five gene pairs, whose relative ordering can be predictive of the NACT response. The signature has a robust performance at predicting pCR in TNBC patients with an area under the ROC curve (AUC) of 0.76 and 0.85 in the first and second testing cohorts, respectively, outperforming other gene signatures developed for the same purpose. Additionally, the signature was significantly associated with RFS in an independent TNBC patient cohort even after adjusting for T stage, patient age at the time of diagnosis, type of breast surgery, and menopausal status. CONCLUSION: We introduce a robust gene signature to predict pathological complete response (pCR) in patients with TNBC. This signature applies easily interpretable, rank-based decision rules to genes regulated by the Notch signaling pathway, a known determinant in breast cancer chemoresistance. The robust predictive and prognostic performance of the signature make it a strong candidate for clinical implementation, aiding in the stratification of TNBC patients undergoing NACT.

The prognostic significance of surgical resection margins for local recurrence, distant metastasis, and overall survival in sarcoma.

BACKGROUND AND OBJECTIVES: Surgical resection with microscopically negative margins constitutes one of the key elements of a curative therapeutic approach for localized sarcomas. However, the prognostic value of quantitative margin width remains controversial. We sought to determine the prognostic significance of margin status and margin width for local recurrence (LR), distant recurrence (DR), and overall survival. METHODS: Retrospective analysis of 210 patients undergoing resection of localized sarcoma between 1997 and 2018 at a national sarcoma reference center. RESULTS: Logistic regression did not reveal an effect of metric margin width as a prognostic factor for LR (odds ratio [OR] = 0.98, p = 0.574), DR (OR = 1, p = 0.908), or overall survival (hazard ratio = 0.98, 95% confidence interval = 0.73-1.20, p = 0.609). Subgroup analysis revealed no differences between complete first resections (R0) and re-resections (re-R0) following unplanned R1-resections for LR (p = 0.727) and overall survival (p = 0.125), but a significantly higher DR-rate in re-R0 cases (p = 0.022). CONCLUSIONS: Achieving a negative margin is essential in sarcoma surgery, however, metric margin width was not associated with disease-specific outcomes. Re-resection of unplanned R1-resections should be performed to control for LR and overall survival rates. As re-R0 cases were at significantly higher risk of DR, these patients should be followed up closely in standardized surveillance protocols.

Understanding multilevel barriers to childhood vaccination uptake among Internally Displaced Populations (IDPs) in Mogadishu, Somalia: a qualitative study.

BACKGROUND: Disparities in vaccination coverage exist in Somalia with Internally Displaced Persons (IDPs) being among the groups with the lowest coverage. We implemented an adapted Participatory Learning and Action (PLA) intervention, which focused on routine vaccinations among displaced populations living in Mogadishu IDP camps. The intervention was successful in improving maternal knowledge and vaccination coverage but unsuccessful in improving timely vaccination. We conducted a qualitative study to understand this result and analyze the multi-level barriers to routine childhood immunization uptake. METHOD: In this qualitative study we used observation data from 40 PLA group discussions with female caregivers and purposively sampled nine vaccination service providers and six policy makers for interview. We also reviewed national-level vaccine policy documents and assessed the quality of health facilities in the study area. We used the socioecological framework to structure our analysis and analyzed the data in NVivo. RESULTS: The barriers to childhood vaccination among IDPs at the individual level were fear due to lack of knowledge, mistrust of vaccines, concerns about side effects and misinformation; opportunity costs; and costs of transportation. At the interpersonal level, family members played an important role as did the extent of decision-making autonomy. Community factors such as cultural practices, gender roles, and household evictions influenced vaccination. Organizational issues at health facilities such as waiting times, vaccine stock-outs, distance to the facility, language differences, and hesitancy of health workers to open multi-dose vials affected vaccination. At the policy level, confusion about the eligible age for routine vaccination and age restrictions for catch-up vaccination and certain antigens such as BCG were important barriers. CONCLUSION: Complex and interrelated factors affect childhood vaccination uptake among IDPs in Somalia. Interventions that address multiple barriers simultaneously will have the greatest impact given the complex nature of vulnerabilities in this population. There is a need to strengthen the health system and connect it with existing community structures to increase demand for services. Our research highlights the importance of formative research before implementing interventions. Further research on the integration of health service strengthening with PLA to improve childhood vaccination among IDPs is recommended. TRIAL REGISTRATION NUMBER: ISRCTN-83,172,390. Date of registration: 03/08/2021.

Onlay Pedicled Transverse Skin Flap versus One-Stage Inlay Buccal Mucosal Graft in Penile Urethroplasty: A Prospective Matched-Pair Analysis.

INTRODUCTION: The aim of this study was to compare urethroplasty using onlay pedicled transverse skin flap (PSF) versus one-stage inlay buccal mucosa graft (BMG) in repair of penile urethral strictures. METHODS: We conducted a prospective matched-pair analysis of 44 male patients receiving penile urethroplasty between June 2016 and June 2019. There were 22 patients who received PSF and 22 patients who received BMG. Matching was performed according to stricture length. Patients with strictures caused by lichen sclerosus, prior hypospadias repair, or failed prior urethroplasty were excluded. Treatment was considered successful if no recurrence was observed. Successful repair, complication rates, patients' satisfaction, and quality of life improvement were endpoints of this study. RESULTS: Mean follow-up was 40.3 months. PSF and BMG showed comparable success rates (90.9% vs. 86.4%, p = 0.713). Recurrent stricture occurred in 2 patients (9.1%) who received PSF and in 3 patients (13.6%) who received BMG. Operation time was significantly longer for PSF than for BMG (108.4 min vs. 78.1 min, p = 0.01). Univariable logistic regression analysis revealed no relevant risk factors for stricture recurrence. CONCLUSION: Early results indicate comparable success rates of PSF and BMG in penile urethroplasty. Further studies with larger sample size and longer follow-up periods are required to evaluate subtle differences between both techniques.

Discovery of novel thioquinazoline-N-aryl-acetamide/N-arylacetohydrazide hybrids as anti-SARS-CoV-2 agents: Synthesis, in vitro biological evaluation, and molecular docking studies.

In the current investigation, two novel series of (tetrahydro)thioquinazoline-N-arylacetamides and (tetrahydro)thioquinazoline-N-arylacetohydrazides were designed, synthesized and investigated for their antiviral activity against SARS-CoV-2. The thioquinazoline-N-arylacetamide 17g as well as the tetrahydrothioquinazoline-N-arylacetohydrazides 18c and 18f showed potent antiviral activity with IC50 of 21.4, 38.45 and 26.4 µM, respectively. In addition, 18c and 18f demonstrated potential selectivity toward the SARS-CoV-2 over the host cells with SI of 10.67 and 16.04, respectively. Further evaluation of the mechanism of action of the three derivatives 17g, 18c, and 18f displayed that they can inhibit the virus at the adsorption as well as at the replication stages, in addition to their virucidal properties. In addition, 17g, 18c, and 18f demonstrated satisfactory physicochemical properties as well as drug-likeness properties to be further optimized for the discovery of novel antiviral agents. The docking simulation on Mpro binding site predicted the binding pattern of the target compounds rationalizing their differential activity based on their hydrophobic interaction and fitting in the hydrophobic S2 subsite of the binding site.

Role of Low-Risk HPV PCR Monoinfection in Screening for HSIL and Anal Cancer in Men Who Have Sex with Men Living with HIV.

To determine the value of low-risk human papillomavirus (HPV) PCR to screen for "high-grade anal squamous intraepithelial lesion and anal cancer" (HSIL-plus), rate of patients with low-grade anal squamous intraepithelial lesion (LSIL) progressing to HSIL-plus, and progression-related factors. Prospective, longitudinal study of consecutive MSM-LHIV attended between May 2010 and December 2021 and followed for 43 months (IQR: 12-76). HIV-related variables were gathered at baseline, performing anal cytology for HPV detection/genotyping, thin-layer cytological study, and high-resolution anoscopy (HRA). Follow-up was annual when HRA was normal or LSIL, and post-treatment in cases of HSIL-plus, re-evaluating sexual behavior, viral-immunological status, and HPV infection of anal mucosa. The 493 participants had mean age of 36 years: CD4 nadir < 200 cells/uL in 23.1%, virological failure in 4.1%, and tetravalent HPV vaccine > 5 years earlier in 15%. HSIL-plus was ruled out in patients with monoinfection by low-risk HPV genotype and normal cytology (100% sensitivity, 91.9% specificity, PPV 2.9%, and NPV 100%). Progression from LISL to HSIL-plus occurred in 4.27% of patients within 12 months (IQR: 12-12): risk factors were acquisition of high-risk (HR: 4.15; 95% CI: 1.14-15.03) and low-risk (HR: 3.68 95% CI: 1.04-12.94) HPV genotypes, specifically genotype 6 (HR: 4.47, 95% CI: 1.34-14.91), and history of AIDS (HR: 5.81 95% CI: 1.78-18.92). Monoinfection by LR-HPV genotypes in patients with normal cytology is not associated with anal cancer or precursor lesions. Progression from LSIL to HSIL-plus, observed in <5% of patients, was related to acquisition of HR and LR HPV genotypes, especially 6, and a history of AIDS.

In Vitro Evaluation and Bioinformatics Analysis of Schiff Bases Bearing Pyrazole Scaffold as Bioactive Agents: Antioxidant, Anti-Diabetic, Anti-Alzheimer, and Anti-Arthritic.

In continuation of our research programs for the discovery, production, and development of the pharmacological activities of molecules for various disease treatments, Schiff bases and pyrazole scaffold have a broad spectrum of activities in biological applications. In this context, this manuscript aims to evaluate and study Schiff base-pyrazole molecules as a new class of antioxidant (total antioxidant capacity, iron-reducing power, scavenging activity against DPPH, and ABTS radicals), anti-diabetic (α-amylase% inhibition), anti-Alzheimer's (acetylcholinesterase% inhibition), and anti-arthritic (protein denaturation% and proteinase enzyme% inhibitions) therapeutics. Therefore, the Schiff bases bearing pyrazole scaffold (22a, b and 23a, b) were designed and synthesized for evaluation of their antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic properties. The results for compound 22b demonstrated significant antioxidant, anti-diabetic (α-amylase% inhibition), and anti-Alzheimer's (ACE%) activities, while compound 23a demonstrated significant anti-arthritic activity. Prediction of in silico bioinformatics analysis (physicochemical properties, bioavailability radar, drug-likeness, and medicinal chemistry) of the target derivatives (22a, b and 23a, b) was performed. The molecular lipophilicity potential (MLP) of the derivatives 22a, b and 23a, b was measured to determine which parts of the surface are hydrophobic and which are hydrophilic. In addition, the molecular polar surface area (PSA) was measured to determine the polar surface area and the non-polar surface area of the derivatives 22a, b and 23a, b. This study could be useful to help pharmaceutical researchers discover a new series of potent agents that may act as an antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic.

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases.

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study.

5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine (1). The reaction of the latter compound (1) with a series of halogenated derivatives under conditions of phase transfer catalysis solid-liquid (CTP) allows the isolation of the expected regioisomers compounds (2-8). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data (1H NMR, 13C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4, were tested in vitro for their antibacterial activity against Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Escherichia coli). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

Efficacy of Kinesio Taping Compared to Other Treatment Modalities in Musculoskeletal Disorders: A Systematic Review and Meta-Analysis.

Kinesio taping is widely used in musculoskeletal conditions. We performed a systematic review and meta-analysis on the efficacy of kinesio taping in musculoskeletal disorders compared to other interventions. Twelve electronic databases were used for systemic search and data relevant to pain and disability were extracted. The protocol was registered in PROSPERO (CRD42018087606). Meta-analysis was performed to compare the efficacy of kinesio taping to other modalities of musculoskeletal disorders. As a result, 36 studies were included in the quantitative analysis. Kinesio taping was found to provide an improvement of both pain and disability when applied to any region of the body. In the first five days of application, kinesio taping significantly reduced the pain in all body regions (SMD = -0.63, 95%CI: -0.87, -0.39). This was also noted after four-to-six weeks of application (SMD = -0.76, 95%CI: -1.07, -0.45). When kinesio taping was used for disability in low back pain patients, it significantly reduced the disability within five days of application (SMD = -0.70, 95%CI: -1.29, -0.11). Finally, kinesio taping has shown an improvement of the disability in all body regions after four-to-six weeks of application (SMD = -0.59, 95%CI: -0.96, -0.22). Our findings support kinesio taping as an adjuvant to other treatments for musculoskeletal disorders. Abbreviations KT = Kinesio taping; MSK = musculoskeletal; SD = standard deviation; CR = conventional rehabilitation; NDI = Neck Disability Index; NPS = Numerical Pain Scale; CTM = Cervical Thrust Manipulation; PIR = Post-isometric muscle relaxation; NPRS Numerical Pain Rating Scale; OA = osteoarthritis; ROM = Range of motion; VAS = visual analogue scale; VAS-W = visual analogue scale-worst pain; VAS-U = visual analogue scale-usual pain; VAS-R = visual analogue scale-resting pain; VAS-A = visual analogue scale-activity pain; VAS-N = visual analogue scale-night pain; NPDS = Neck Pain Disability Scale; QA = Quality assessment.

A robust and interpretable gene signature for predicting the lymph node status of primary T1/T2 oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OSCC) affects more than 30 000 individuals in the United States annually, with smoking and alcohol consumption being the main risk factors. Management of early-stage tumors usually includes surgical resection followed by postoperative radiotherapy in certain cases. The cervical lymph nodes (LNs) are the most common site for local metastasis, and elective neck dissection is usually performed if the primary tumor thickness is greater than 3.5 mm. However, postoperative histological examination often reveals that many patients with early-stage disease are negative for neck nodal metastasis, posing a pressing need for improved risk stratification to either avoid overtreatment or prevent the disease progression. To this end, we aimed to identify a primary tumor gene signature that can accurately predict cervical LN metastasis in patients with early-stage OSCC. Using gene expression profiles from 189 samples, we trained K-top scoring pairs models and identified six gene pairs that can distinguish primary tumors with nodal metastasis from those without metastasis. The signature was further validated on an independent cohort of 35 patients using real-time polymerase chain reaction (PCR) in which it achieved an area under the receiver operating characteristic (ROC) curve and accuracy of 90% and 91%, respectively. These results indicate that such signature holds promise as a quick and cost effective method for detecting patients at high risk of developing cervical LN metastasis, and may be potentially used to guide the neck treatment regimen in early-stage OSCC.

Donor-derived acute myeloid leukemia in solid organ transplantation.

We report the transmission of acute myeloid leukemia (AML) undetected at donation from a deceased organ donor to two kidneys and one liver recipients. We reviewed the medical records, and performed molecular analyses and whole exome sequencing (WES) to ascertain AML donor origin and its molecular evolution. The liver recipient was diagnosed 11 months after transplantation and died from complications 2 months later. The two kidney recipients (R1 and R2) were diagnosed 19 and 20 months after transplantation and both received treatment for leukemia. R1 died of complications 11 months after diagnosis, while R2 went into complete remission for 44 months, before relapsing. R2 died 10 months later of complications from allogenic bone marrow transplantation. Microsatellite analysis demonstrated donor chimerism in circulating cells from both kidney recipients. Targeted molecular analyses and medical records revealed NPM1 mutation present in the donor and recipients, while FLT3 was mutated only in R1. These findings were confirmed by WES, which revealed additional founder and clonal mutations, and HLA genomic loss in R2. In conclusion, we report the first in-depth genomic analysis of AML transmission following solid organ transplantation, revealing distinct clonal evolution, and providing a potential molecular explanation for tumor escape.

Effect of Omega-3 fatty acids supplementation on serum level of C-reactive protein in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Omega-3 may alleviate the severity of coronavirus disease 2019 (COVID-19) by reducing the C-reactive protein (CRP) level, a marker for systemic inflammation. Because the scientific evidence indicating such a role is inconsistent, we aimed to evaluate the effect of Omega-3 on CRP change and CRP level in patients with COVID-19. METHODS: We conducted a comprehensive search on four databases (PubMed, Web of Science, EMBASE, and Scopus). We included all RCTs comparing Omega-3 with a control group regarding their effect on the CRP levels in patients with COVID-19. We used version two of the Cochrane risk of bias assessment tool to appraise the included studies. We extracted data to an online data extraction sheet. The primary outcomes were CRP change from baseline and CRP serum levels. RESULTS: We included four randomized controlled trials (RCTs) with 274 patients in this study. The overall effect estimate favored Omega-3 over the control group in terms of CRP change from baseline (mean difference (MD) =- 2.53, 95% confidence interval (CI): - 4.40, - 0.66) and CRP serum levels at the end of the study (MD =- 6.24, 95% CI: - 11.93, - 0.54). CONCLUSION: Omega-3 showed promising effects on systemic inflammation by reducing CRP levels in COVID-19 patients. Based on this finding, we recommend Omega-3 for COVID-19 patients for its anti-inflammatory actions.

Randomized comparison of 4.5/6 Fr versus 6/7.5 Fr ureteroscopes for laser lithotripsy of lower/middle ureteral calculi: towards optimization of efficacy and safety of semirigid ureteroscopy.

BACKGROUND AND PURPOSE: To compare 4.5/6 Fr versus 6/7.5 Fr semirigid ureteroscopes in terms of safety and efficacy in adult non-obese patients with middle or lower ureteric stones. MATERIALS AND METHODS: A total of 198 patients with middle/lower ureteric stone and a BMI ≤ 30 kg/m2 were recruited. Patients were randomized according to the size of ureteroscope into two groups: group 1 where a 4.5/6 Fr semi-rigid ureteroscope was used, and group 2 where a 6/7.5 Fr semi-rigid ureteroscope was used. Patient's demographic, stone characteristics, intraoperative and postoperative outcomes including stone-free rate (SFR) and complications were compared. RESULTS: Preoperative characteristics in terms of age, sex, BMI, and stone location, side, size, and HU were comparable between both groups (p values > 0.05). The overall SFR was significantly higher in group 1 (0.004). Balloon dilatation was not required in all patients of group-1 compared with 33% of group-2 (p = 0.0001). The JJ stent was required in 10% of group-1 compared with 30% of group-2 (p = 0.0004). Failure to reach the stone due to tight ureter occurred in 8% of group 2 (p = 0.003), respectively. Traxer's grade 1 ureteral injury occurred in 2% of group-1 versus 14% of group-2 (p = 0.001). Consequently, hematuria was significantly lower in group-1 (1% vs. 8%; p = 0.01), respectively. The hospital stay < 9 h was significantly higher in group 1 (p = 0.0001). CONCLUSIONS: The 4.5/6 Fr semi-rigid Ureteroscope was associated with significantly higher SFR and shorter hospital stay, with lower ureteral injury, fewer double-J stenting, and without the need for intraoperative balloon dilatation for the ureter.

Synchronous transurethral cystolitholapaxy and TURP reveals better results than transurethral cystolitholapaxy plus medical therapy for BPH: a randomized prospective study on 100 patients with concomitant urinary bladder stone(s) and BPH.

OBJECTIVE: This report presents the results of a randomized prospective study comparing synchronous transurethral cystolitholapaxy and transurethral resection of the prostate (TURP) with transurethral cystolitholapaxy plus medical treatment for benign prostatic hyperplasia (BPH) in patients with concomitant vesical stone(s) and BPH. PATIENTS AND METHODS: The study included 100 patients with bladder stone(s) < 2.5 cm associated with BPH. Eligible patients were divided randomly into two groups: group I (n = 50 patients) underwent simultaneous transurethral cystolitholapaxy and TURP, and group II (n = 50 patients) underwent transurethral cystolitholapaxy and received postoperative tamsulosin plus finasteride. RESULTS: The mean follow-up was 20.1 ± 5.3 months. No statistically significant differences were found between the 2 groups regarding the preoperative parameters (age, prostatic volume, bladder stone characteristics, prostate-specific antigen level, International Prostate Symptom Score, peak urinary flow rate, and post-void residual urine volume). Both groups experienced statistically significant postoperative improvement in IPSS, post-void residual (PVR) urine volume, and peak flow rate compared with the preoperative parameters (P < 0.001 for all parameters). However, patients in group 1 had a more pronounced improvement (P < 0.001 for all parameters). Thus, 15 patients in group 2 underwent TURP during follow-up. PVR urine and prostate volume predicted the failure of medical therapy and the need for TURP. CONCLUSION: Synchronous transurethral cystolitholapaxy and TURP revealed better results than transurethral cytolitholapaxy plus medical therapy. Cystolitholapaxy without TURP should not be indicated especially in patients with significant PVR urine volumes and larger prostates.

Novel 2-substituted thioquinazoline-benzenesulfonamide derivatives as carbonic anhydrase inhibitors with potential anticancer activity.

A novel series of 2-thioquinazoline-benzenesulfonamide hybrids were designed as carbonic anhydrase (CA) inhibitors. The design approach relies on molecular hybridization between the benzenesulfonamide scaffold as a Zn2+ binding group and 2-substituted thioquinazolines as a tail. Assaying the thioquinazoline-benzenesulfonamide conjugates against four different CA isoforms revealed that compounds 12f and 12p are the most potent derivatives. They exhibit Ki = 0.09 and 0.05 µM on CA II, 0.32 and 0.47 µM on CA IX, and 0.58 and 0.46 µM on CA XII, respectively. In addition, 12p demonstrated high selectivity for CA II over CA I with selectivity index (SI) = 92, and slightly higher specificity for CA II over CA IX and CA XII with SI = 9.40 and 9.20, respectively. The synthesized compounds were screened for their cytotoxic activity at 10 µM concentration and derivatives 12o, 12n, and 12f turned out to be the most potent ones from the synthesized series; they exhibit mean growth inhibition % values of 89.38%, 58.75%, and 54.71%, respectively, while 12p demonstrated moderate activity against the NCI cancer cell lines, with mean growth inhibition % = 29.62%. The analysis of the MCF-7 cell cycle after treatment with 5.0 µM of 12f displayed that it arrests the cell cycle at the G2/M phase. Molecular docking simulation of the thioquinazoline-benzenesulfonamide hybrids in the CA II active site rationalized the potent activity to the settlement of the sulfonamide moiety at the depth of the CA II active site and its stabilization by performing the important interactions with the Zn2+ ion as well as with the key amino acids Thr199 and/or Thr200, while the thioquinazoline moiety with different (un)substituted phenyl tails is stabilized by the formation of various hydrogen bonding and hydrophobic interactions with the surrounding amino acids in the binding site.

Improved Optical Flow Estimation Method for Deepfake Videos.

Creating deepfake multimedia, and especially deepfake videos, has become much easier these days due to the availability of deepfake tools and the virtually unlimited numbers of face images found online. Research and industry communities have dedicated time and resources to develop detection methods to expose these fake videos. Although these detection methods have been developed over the past few years, synthesis methods have also made progress, allowing for the production of deepfake videos that are harder and harder to differentiate from real videos. This research paper proposes an improved optical flow estimation-based method to detect and expose the discrepancies between video frames. Augmentation and modification are experimented upon to try to improve the system's overall accuracy. Furthermore, the system is trained on graphics processing units (GPUs) and tensor processing units (TPUs) to explore the effects and benefits of each type of hardware in deepfake detection. TPUs were found to have shorter training times compared to GPUs. VGG-16 is the best performing model when used as a backbone for the system, as it achieved around 82.0% detection accuracy when trained on GPUs and 71.34% accuracy on TPUs.