Impact of age on central lymph nodes involvement in papillary thyroid cancer.

BACKGROUND: Total thyroidectomy is the main line of treatment for papillary thyroid cancer. Central lymph node dissection (CLND) is still debatable. In this study, we aimed to correlate the central lymph node status with the age of patients. METHODS: This is a retrospective study including patients with papillary thyroid cancer (PTC) who underwent total thyroidectomy and CLND at a tertiary cancer center during the period from January 2012 to September 2022. Patients were subdivided into 3groups: patients younger than 20 years old, patients between 20 and 40 years old, and patients older than 40 years old. Correlation between central lymph node status, lateral lymph node status, and harvest count with each other and between age groups was done. RESULTS: 315 patients were included. The younger the age group the higher the possibility of harboring positive central nodes, however, the positivity of lateral nodes was similar. Neither central nodal harvest nor positive central node count significantly differed between groups. The lateral nodal harvest was significantly higher in the < 20 years group with no affection to the number of positive nodes retrieved. The younger the age group the longer the disease-free survival (DFS). CONCLUSION: We can conclude that patients younger than twenty years had a higher probability of harboring malignancy in central nodes and higher lateral node harvest on dissection. In contrast, they do have a lower incidence of recurrence.

Exploring the properties of Zr2CO2/GaS van der Waals heterostructures for optoelectronic applications.

We investigate the structural, electronic, and optical properties of eight possible Zr2CO2/GaS van der Waals (vdW) heterostructures using first-principles calculations based on a hybrid functional. These structures display favorable stability, indicated by matching crystal structures and negative formation energies. In all considered configurations, these heterostructures act as indirect band gap semiconductors with a type-II band alignment, allowing efficient electron-hole separation. Optical studies reveal their suitability for optoelectronic applications. Zr2CO2/GaS under 4% biaxial compressive strain meets the criteria for photocatalytic water splitting, suggesting their potential for electronic and optoelectronic devices in the visible spectrum. Our findings present prospects for advanced photocatalytic materials and optical devices.

Construction and Docking Studies of Novel Pyrimido[4,5-b]quinolines as Antimicrobial Agents.

In order to develop novel antimicrobial agents, we prepared quinoline bearing pyrimidine analogues 2-7, 8 a-d and 9 a-d and their structures were elucidated by spectroscopic techniques. Furthermore, our second aim was to predict the interactions between the active compounds and enzymes (DNA gyrase and DHFR). In this work, fourteen pyrimido[4,5-b]quinoline derivatives were prepared and assessed for their antimicrobial potential by estimating zone of inhibition. All the screened candidates displayed antibacterial potential with zone of inhibition range of 9-24 mm compared with ampicillin (20-25 mm) as a reference drug. Moreover, the target derivatives 2 (ZI=16), 9 c (ZI=17 mm) and 9 d (ZI=16 mm) recorded higher antifungal activity against C. albicans to that exhibited by the antifungal drug amphotericin B (ZI=15 mm). Finally, the most potent pyrimidoquinoline compounds (2, 3, 8 c, 8 d, 9 c and 9 d) were docked inside DHFR and DNA gyrase active sites and they recorded excellent fitting within the active regions of DNA gyrase and DHFR. These outcomes revealed us that compounds (2, 3, 8 c, 8 d, 9 c and 9 d) could be lead compounds to discover novel antibacterial candidates.

A meta analysis on the utility of Anakinra in severe COVID-19 disease.

BACKGROUND AND OBJECTIVE: The most important presentation of COVID-19 is hyper inflammatory condition and cytokine storm that occurs due to excessive increase of the inflammatory mediators specially, pro-inflammatory interleukins such as IL-1ß, IL-6 and tumor necrosis factor-α which have an important role in the cytokine storm pathway. Up till now there is not a definitive treatment for COVID-19 disease, but according to the pathophysiology of the disease, Anakinra (Interleukin- 1 inhibitor) is an adjuvant treatment option in patients with severe COVID-19 by blocking the effect of IL-1. So, we aimed to summarize the studies that evaluated the safety and efficacy of Anakinra in patients diagnosed with COVID-19. METHODS: We performed a search in PubMed, Cochrane Library, Scopus, and Web of Science (WOS) databases from inception till 7 Jan 2022. Additionally, we searched randomized and non-randomized clinical trials, cohort, case series, case control, case report more than 3 patients which contain confirmed cases of COVID-19 who received Anakinra (Interleukin- 1 inhibitor) for the management of hyper-inflammatory condition associated with COVID-19 disease. A meta-analysis was conducted using review manager 5.4. RESULTS: We included 44 articles in the systematic review. Ultimately, 23 studies were incorporated in the meta-analysis with a total number of 3179 patients. Our analysis showed statistically significant difference in the following outcomes: duration of ICU stays [MD = -0.65, 95% CI (-1.09, -0.03), p = 0.04], the number of patients who needed invasive mechanical ventilation [RR = 0.57, 95% CI (0.39, 0.84), p = 0.004], and number of deaths [RR = 0.80, 95% CI (0.66, 0.99), p = 0.04]. Our analysis showed no statistically significant difference in the following outcomes: length of hospital stays [MD = -0.16, 95% CI (-0.42, 0.11), p = 0.26], oxygen-free days [MD = -0.81, 95% CI (-3.81, 2.20), p = 0.60], and the number of patients who needed non-invasive mechanical ventilation [RR = 1.09, 95% CI (0.47, 2.52), p = 0.84]. CONCLUSION: Anakinra showed some promising results in important outcomes related to COVID-19 as it significantly reduced the rate of mortality and the need of invasive mechanical ventilation. It should be used in severe cases more than mild and moderate cases to avoid possible immunosuppression complications. Anakinra use is safe in cases of COVID-19 at dose less than 100 mg. Another important outcome was significant reduction is the D-dimer level. Anakinra may be effective in the treatment of specific immunocompromised cases, but it should be used cautiously.

A Faster Prostate MRI: Comparing a Novel Denoised, Single-Average T2 Sequence to the Conventional Multiaverage T2 Sequence Regarding Lesion Detection and PI-RADS Score Assessment.

BACKGROUND: The T2 w sequence is a standard component of a prostate MRI examination; however, it is time-consuming, requiring multiple signal averages to achieve acceptable image quality. PURPOSE/HYPOTHESIS: To determine whether a denoised, single-average T2 sequence (T2 -R) is noninferior to the standard multiaverage T2 sequence (T2 -S) in terms of lesion detection and PI-RADS score assessment. STUDY TYPE: Retrospective. POPULATION: A total of 45 males (age range 60-75 years) who underwent clinically indicated prostate MRI examinations, 21 of whom had pathologically proven prostate cancer. FIELD STRENGTH/SEQUENCE: A 3 T; T2 w FSE, DWI with ADC maps, and dynamic contrast-enhanced images with color-coded perfusion maps. T2 -R images were created from the raw data utilizing a single "average" with iterative denoising. ASSESSMENT: Nine readers randomly assessed complete exams including T2 -R and T2 -S images in separate sessions. PI-RADS version 2.1 was used. All readers then compared the T2 -R and T2 -S images side by side to evaluate subjective preference. An additional detailed image quality assessment was performed by three senior level readers. STATISTICAL TESTS: Generalized linear mixed effects models for differences in lesion detection, image quality features, and overall preference between T2 -R and T2 -S sequences. Intraclass correlation coefficients (ICC) were used to assess reader agreement for all comparisons. A significance threshold of P = 0.05 was used for all statistical tests. RESULTS: There was no significant difference between sequences regarding identification of lesions with PI-RADS ≥3 (P = 0.10) or PI-RADS score (P = 0.77). Reader agreement was excellent for lesion identification (ICC = 0.84). There was no significant overall preference between the two sequences regarding image quality (P = 0.07, 95% CI: [-0.23, 0.01]). Reader agreement was good regarding sequence preference (ICC = 0.62). DATA CONCLUSION: Use of single-average, denoised T2 -weighted images was noninferior in prostate lesion detection or PI-RADS scoring when compared to standard multiaverage T2 -weighted images. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Novel 2-oxo-2-phenylethoxy and benzyloxy diaryl urea hybrids as VEGFR-2 inhibitors: Design, synthesis, and anticancer evaluation.

Two series of diaryl urea derivatives, 6a-k and 7a-n, were synthesized. All the newly synthesized compounds were tested against the NCI (US) cancer cell lines via SRB assay. The p-chloro-m-trifluoromethyl phenyl derivatives 6e-g and 7e-g showed the most potent cytotoxic activity with a GI50 value range of 1.2-15.9 µM. Furthermore, the p-fluorobenzyloxy diaryl urea derivative 7g revealed the most potent cytotoxicity against eight cancer cell lines in the MTT assay with IC50 values below 5 µM. Compounds 6a-k and 7a-n were tested for their vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitory activities. The p-chloro-m-trifluoromethyl diaryl urea benzyloxy derivatives 7e-i and the p-methoxydiaryl urea benzyloxy derivatives 7k, 7l, and 7n were found to be the most active compounds as VEGFR-2 inhibitors in the benzyloxy series 7, with an IC50 range of 0.09-4.15 µM. In the 2-oxo-2-phenylethoxy series 6, compounds 6e-g and 6i were reported with IC50 values of 0.94, 0.54, 2.71, and 4.81 µM, respectively. Moreover, compounds 7e and 7g induced apoptosis, causing cell cycle arrest in the G2/M phase. In addition, 7g showed an antimigratory effect in A-375 cells and inhibited the VEGFR-2 expression in an immunohistofluorescence study. Molecular docking simulations on VEGFR-2 as well as ADME properties prediction were also performed.

"Anosmia" the mysterious collateral damage of COVID-19.

COVID-19 pandemic spreads worldwide, with more than 100 million positive cases and more than 2 million deaths. From the beginning of the COVID-19 pandemic, several otolaryngologists described many cases of a sudden loss of smell (anosmia) associated with the disease with or without additional symptoms. Anosmia is often the first and sometimes the only sign in the asymptomatic carriers of COVID-19. Still, this disorder is underestimated, and it is not life-threatening. However, it significantly decreases the quality of life. This olfactory dysfunction continues in several cases even after the nasopharyngeal swab was negative. The occurrence of anosmia can be used as a screening tool for COVID-19 patients and can be used to identify these patients to accomplish the isolation and tracking procedures. In this review, we highlighted the possible mechanisms of anosmia in COVID-19 patients, major pathologies and features of anosmia, implications of anosmia in early diagnosis of COVID-19, evaluation of the smell function during COVID-19, and management and treatment options of COVID-19 anosmia.

Data-Driven Modification of the LI-RADS Major Feature System on Gadoxetate Disodium-Enhanced MRI: Toward Better Sensitivity and Simplicity.

BACKGROUND: The Liver Imaging Reporting and Data System (LI-RADS) is widely accepted as a reliable diagnostic scheme for hepatocellular carcinoma (HCC) in at-risk patients. However, its application is hampered by substantial complexity and suboptimal diagnostic sensitivity. PURPOSE: To propose data-driven modifications to the LI-RADS version 2018 (v2018) major feature system (rLI-RADS) on gadoxetate disodium (EOB)-enhanced magnetic resonance imaging (MRI) to improve sensitivity and simplicity while maintaining high positive predictive value (PPV) for detecting HCC. STUDY TYPE: Retrospective. POPULATION: Two hundred and twenty-four consecutive at-risk patients (training dataset: 169, independent testing dataset: 55) with 742 LR-3 to LR-5 liver observations (HCC: N = 498 [67%]) were analyzed from a prospective observational registry collected between July 2015 and September 2018. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted fast spin-echo, diffusion-weighted spin-echo based echo-planar and three-dimensional (3D) T1-weighted gradient echo sequences. ASSESSMENT: All images were evaluated by three independent abdominal radiologists who were blinded to all clinical, pathological, and follow-up information. Composite reference standards of either histopathology or imaging follow-up were used. STATISTICAL TESTS: In the training dataset, LI-RADS v2018 major features were used to develop rLI-RADS based on their associated PPV for HCC. In an independent testing set, diagnostic performances of LI-RADS v2018 and rLI-RADS were computed using a generalized estimating equation model and compared with McNemar's test. A P value <0.05 was considered statistically significant. RESULTS: The median (interquartile range) size of liver observations was 13 mm (7-27 mm). The diagnostic table for rLI-RADS encompassed 9 cells, as opposed to 16 cells for LI-RADS v2018. In the testing set, compared to LI-RADS v2018, rLI-RADS category 5 demonstrated a significantly superior sensitivity (76% vs. 61%) while maintaining comparably high PPV (92.5% vs. 94.1%, P = 0.126). DATA CONCLUSION: Compared with LI-RADS v2018, rLI-RADS demonstrated improved simplicity and significantly superior diagnostic sensitivity for HCC in at-risk patients. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Multicenter validation of the PREDICT score for prediction of local recurrence after total mesorectal excision of rectal cancer.

BACKGROUND: Total mesorectal excision (TME) is the gold standard treatment for rectal cancer. Although TME has managed to decrease the rates of local recurrence after rectal cancer resection, local recurrence is still recorded at varying rates. The present study aimed to validate the PREDICT score in the prediction of local recurrence of rectal cancer after TME with curative intent. METHODS: This was a retrospective multicenter study on patients with nonmetastatic low or middle rectal cancer who underwent TME. The total PREDICT score was calculated for every patient and related to the onset of local recurrence. According to the final score, patients were allocated to one of three risk groups: low, moderate, and high, and the rates of local recurrence in each group were calculated and compared. RESULTS: The present study included 262 patients (50.4% males) with a mean age of 47.1 years. The overall local recurrence rate was 12.6%. 29.4% of patients were in the low-risk group, 63.7% in the moderate-risk group, and 6.9% in the high-risk group. The local recurrence rate was 3.9% (95% confidence interval [CI]: 0.8-10.9) in the low-risk group, 13.2% (95% CI: 8.4-19.3) in the moderate risk group, and 44.4% (95% CI: 21.5-69.2) in the high-risk group (p < 0.0001). The sensitivity of the PREDICT score was 72.7%, the specificity was 88.1%, and the accuracy was 86.3%. CONCLUSIONS: The PREDICT score had good diagnostic accuracy in the prediction of local recurrence after TME and a good discriminatory ability in the differentiation between patients at different risks to develop local recurrence.

Design, synthesis and anticancer activity of novel 2-arylbenzimidazole/2-thiopyrimidines and 2-thioquinazolin-4(3H)-ones conjugates as targeted RAF and VEGFR-2 kinases inhibitors.

In the current study, series of 2-arylbenzimidazole-thiopyrimidine and -thioquinazolin-4(3H)-ones conjugates 12a-d, 13a,b and 14a-l have been synthesized. All the synthesized compounds were tested in vitro for their anticancer activities against a panel of cancer cell lines at NCI - US and their growth inhibition (GI) % were determined at 10 µM. Compounds 14c and 14g-i were selected to be screened at the five dose assay and were found to exhibit GI50 values 1.1-30.0 µM. The benzimidazole-quinazolinone derivative 14c, in particular, showed potent anticancer activity against the tested cancer cell lines (GI50 of 1.3-4.2 µM). In addition, compounds 12a,b, 13a, 14a-e, 14g, 14i and 14j were selected to be tested against some cancer cell lines using MTT assay and the benzimidazole-quinazolinone 14g was found to have potent anticancer activities against melanoma (Mel-501 and A-375), breast (MCF-7), colon (HCT-116), prostate (PC-3), lung (A-549) and pancreas (Paca-2) cancer cell lines reporting IC50 values ranging between 0.1 and 6.2 µM. Moreover, the synthesized hybrids were tested in vitro on kinases; BRAF (wt), BRAF (V600E), CRAF and VEGFR-2. The benzimidazole-quinazolinone derivatives 14f,g revealed potent RAF kinases inhibitory activities on BRAF (wt), BRAF (V600E) and CRAF showing IC50 values 0.002-0.1 µM, whereas, the benzimidazole-quinazolinone derivatives 14i and 14k showed moderate VEGFR-2 inhibitory activity (IC50 = 20.60 and 6.14 µM, respectively). Moreover, the representative compounds 14g and 14i caused cell cycle arrest of A-375 melanoma cell line at G2/M phase and were found to induce late apoptosis. CRAF in the DFG-out inactive conformation homology modeling was first reported in this study and molecular docking studies on BRAF, CRAF and VEGFR-2 were also performed to investigate the binding modes of the target compounds and their interactions with the key amino acids; BRAF (Glu500, Cys531 and Asp593), CRAF (Glu393, Cys424 and Asp486) and VEGFR-2 (Glu885, Cys919 and Asp1046).

Design and synthesis of novel quinazolinone-based fibrates as PPARα agonists with antihyperlipidemic activity.

Aiming to discover new antihyperlipidemic agents, a new set of quinazolinone-fibrate hybrids 9a-r bearing the essential features for peroxisome proliferator-activated receptor-α (PPARα) agonistic activity was synthesized and the structures were confirmed by different spectral data. All the target compounds were screened for their PPARα agonistic activity. Compounds 9o and 9q exhibited potent activity, with EC50 values better than that of fenofibrate by 8.7- and 27-fold, respectively. Molecular docking investigations were performed for all the newly synthesized compounds in the active site of the PPARα receptor to study their interactions and energies in the receptor. Moreover, the antihyperlipidemic and antioxidant activities of compounds 9o and 9q were determined using Triton WR-1339-induced hyperlipidemic rats. Compound 9q exhibited effective hypolipidemic activity in a dose-dependent manner, where it significantly reduced the serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol and increased the level of high-density lipoprotein cholesterol. Furthermore, it possesses a powerful antioxidant profile where it significantly elevated the levels of reduced glutathione as well as the total antioxidant capacity and significantly decreased the malondialdehyde level. The histopathological studies revealed that compound 9q improved the aortic architecture and hepatic steatosis. These findings support that compound 9q could be a promising lead compound for the development of new antihyperlipidemic agents.

Professional and Organizational Leadership Role in Ethics Management: Avoiding Reliance on Ethical Codification and Nurturing Ethical Culture.

The engineering profession has experienced some ethical cases that were rarely reported, scrutinized, or discussed because: they did not necessarily represent violations of existing codes even if they breached ethical principles; those within the organization were not prepared to take steps to address the issues or impose sanction; an/or some of the personnel associated with these cases resorted to silence to avoid being labeled as trouble-makers in their organizations and, perhaps, more broadly, in society. The goal of this paper is to heighten managerial awareness of ethical issues, interrelated ethical lapses, and appropriate responsive actions within professional engineering communities. As such, the authors reviewed recent well-known professional and organizational ethical cases including impact of leadership role and existing standards, and critically analyzed interrelated literature. The paper's case studies exemplify that because ethical issues are complex, intricate, and nuanced; bylaws are insufficient for establishing the inclusive culture for handling potential ethical situations. In fact, through what is known as the codification of ethics, it is possible that someone's conduct can totally fulfill all professional responsibilities but still be unethical. As such, ethical leadership is needed to provide the means for establishing appropriate norms so as to set the proper structures for addressing the diverse ethical matters. Perceptions about the responses of leaders to potential ethical lapses are a critical factor in formulating, changing, and maintaining ethical values at the individual and organizational levels. A leader's passive attitude toward ethical issues can be the signal for the ignored lapses to become the norm at not only the organizational level but also the society. Guided by the new Code of Ethics by the American Society of Civil Engineers, this paper aims to trigger the proper ethical behavior and expectations for the welfare of the engineering profession both in the present and future.

Molecular identification of white spot syndrome virus (WSSV) and associated risk factors for white spot disease (WSD) prevalence in shrimp (Penaeus monodon) aquaculture in Bangladesh.

White spot disease has caused significant economic losses in the shrimp farming industry of Bangladesh over the last two decades. The responsible virus, WSSV, may show severe disease with significant mortality depending on farm management and environmental and seasonal changes. Data on farm management and environmental parameters were collected from the southwest region of Bangladesh in 2018, and WSSV infection was confirmed by the species-specific gene VP28 using conventional PCR, real-time PCR and sequencing. Through bivariate analysis, nine significant risk factors for WSD were identified, viz. farm age, presence of nursery pond, reservoir of PL, weed in farm area, control of weed, stocking density, stocking frequency, ammonia and oxygen concentration. This study detected 46 WSSV-infected shrimp farms by conventional PCR, whereas real-time PCR identified 47 WSSV-positive out of 49 farms. WSSV prevalence was highest in the Khulna region, with 100% positivity in all seasons. WSSV loads ranged from 5.62 × 109 to 2.01 × 1015 copies/g of shrimp tissue. The VP28 gene sequence confirmed that 15 representative samples were 100% identical to the 2018 WSSV strain of India. The relationships among risk factors, prevalence and severity of disease, and origin of WSSV strains could be impactful for WSD management.

Reconstruction of Oromandibular Defect After Tumor Resection by Sternomastoid-clavicular Flap.

ABSTRACT: The study aims to evaluate sternocleidomastoid-clavicular osteo-myocutaneous flap (SCM-OMCF) for reconstruction of mandibular defects after tumor resection. In the period between 2010 and 2018, thirteen patients with primary mandibular tumors underwent mandibular resection and reconstruction with SCM-OMCF. Patients were followed up for 10 to 66 months. Hospital was 13 ±â€Š4 days. All patients started fluid in the 2nd day. The mean time to start oral fluid was 7.5 ±â€Š0.8 day. Four (30.8%) patients suffered from complications (infection and salivary leak in 1 case due to partial flap loss, donor wound dehiscence in 1 case, deep venous thrombosis in 1 case and chest infection in 1 case). None of our cases experienced motor disability. Two cases (15.9%) underwent reoperations. The overall aesthetic outcome was found excellent in 5 cases, satisfactory in 5 cases and fair in 3 cases. The functional outcomes were satisfactory. Tumor recurrences were detected in 2 (15.9%) patients. Two patients died during follow up within 2 years after 1st surgery due to local and distant recurrences. SCM-OMCF is a versatile, safe and simple technique for reconstructing mandibular defects less than 11 cm.

Water resources pollution associated with risks of heavy metals from Vatukoula Goldmine region, Fiji.

Although mining is essential for human economic development, is amongst the most polluting anthropogenic sources that influence seriously in water resources. Thus, understanding the presence and concentration of heavy metals in water and sediment in the vicinity of mines is important for the sustainability of the ecosystem. In this work, a multidisciplinary approach was developed to characterize the contamination level, source apportionment, co-existence, and degree of ecological and human health risks of HMs on water resources in the Vatukoula Goldmine region (VGR), Fiji. The outcomes suggested significant contamination by Cd (range: 0.01-0.95 g/L), Pb (range: 0.03-0.53 g/L), and Mn (range: 0.01-3.66 g/L) in water samples surpassed the level set by Fiji and international laws, whereas higher concentration of Cd (range: 2.60-23.16 mg/kg), Pb (range: 28.50-200.90 mg/kg) and Zn (range: 36.50-196.66 mg/kg) were detected in sediment samples. Lead demonstrated a strong significant co-existence network with other metals (e.g., Mn, Ni). Source apportionment recognized four source patterns (Cd, Pb, Ni, and Mn) for water and (Cr, Cd-Pb, Mn, and Zn) for sediment which was further confirmed by principal component analysis. The mine inputs source mainly contributed to Cd (66.07%) for water, while mineral processing mostly contributed to Zn (76.10%) for sediment. High non-carcinogenic (>1) and carcinogenic (>10-4) health risks, particularly in children, are related to the elevated Cd, Pb and Cr contents from the VGR. Uncertainty analysis demonstrates that the 90th quantile of Cd led to higher carcinogenic risk. Pollution indices disclosed a moderate to extremely contamination status mainly along the Toko dam which poses high ecological risks identified by index calculation. However, sediment quality indicators based on probable effect levels showed that there was a 75% of likelihood that the concentrations of Cd and Pb adjacent to the VGR have a severe toxic impact on aquatic lives.

Spatiotemporal nexus between vegetation change and extreme climatic indices and their possible causes of change.

Climate extremes have a significant impact on vegetation. However, little is known about vegetation response to climatic extremes in Bangladesh. The association of Normalized Difference Vegetation Index (NDVI) with nine extreme precipitation and temperature indices was evaluated to identify the nexus between vegetation and climatic extremes and their associations in Bangladesh for the period 1986-2017. Moreover, detrended fluctuation analysis (DFA) and Morlet wavelet analysis (MWA) were employed to evaluate the possible future trends and decipher the existing periodic cycles, respectively in the time series of NDVI and climate extremes. Besides, atmospheric variables of ECMWF ERA5 were used to examine the casual circulation mechanism responsible for climatic extremes of Bangladesh. The results revealed that the monthly NDVI is positively associated with extreme rainfall with spatiotemporal heterogeneity. Warm temperature indices showed a significant negative association with NDVI on the seasonal scale, while precipitation and cold temperature extremes showed a positive association with yearly NDVI. The DEA revealed a continuous increase in temperature extreme in the future, while no change in precipitation extremes. NDVI also revealed a significant association with extreme temperature indices with a time lag of one month and with precipitation extreme without time lag. Spatial analysis indicated insensitivity of marshy vegetation type to climate extremes in winter. The study revealed that elevated summer geopotential height, no visible anticyclonic center, reduced high cloud cover, and low solar radiation with higher humidity contributed to climatic extremes in Bangladesh. The nexus between NDVI and climatic extremes established in this study indicated that increasing warm temperature extremes due to global warming might have severe implications on Bangladesh's ecology and the environment in the future.

Facile One-Pot Multicomponent Synthesis of Pyrazolo-Thiazole Substituted Pyridines with Potential Anti-Proliferative Activity: Synthesis, In Vitro and In Silico Studies.

Pyrazolothiazole-substituted pyridine conjugates are an important class of heterocyclic compounds with an extensive variety of potential applications in the medicinal and pharmacological arenas. Therefore, herein, we describe an efficient and facile approach for the synthesis of novel pyrazolo-thiazolo-pyridine conjugate 4, via multicomponent condensation. The latter compound was utilized as a base for the synthesis of two series of 15 novel pyrazolothiazole-based pyridine conjugates (5-16). The newly synthesized compounds were fully characterized using several spectroscopic methods (IR, NMR and MS) and elemental analyses. The anti-proliferative impact of the new synthesized compounds 5-13 and 16 was in vitro appraised towards three human cancer cell lines: human cervix (HeLa), human lung (NCI-H460) and human prostate (PC-3). Our outcomes regarding the anti-proliferative activities disclosed that all the tested compounds exhibited cytotoxic potential towards all the tested cell lines with IC50 = 17.50-61.05 µM, especially the naphthyridine derivative 7, which exhibited the most cytotoxic potential towards the tested cell lines (IC50 = 14.62-17.50 µM) compared with the etoposide (IC50 = 13.34-17.15 µM). Moreover, an in silico docking simulation study was performed on the newly prepared compounds within topoisomerase II (3QX3), to suggest the binding mode of these compounds as anticancer candidates. The in silico docking results indicate that compound 7 was a promising lead anticancer compound which possesses high binding affinity toward topoisomerase II (3QX3) protein.

New 1,2,3-Triazole-Containing Hybrids as Antitumor Candidates: Design, Click Reaction Synthesis, DFT Calculations, and Molecular Docking Study.

In an effort to improve and achieve biologically active anticancer agents, a novel series of 1,2,3-triazole-containing hybrids were designed and efficiently synthesized via the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction of substituted-arylazides with alkyne-functionalized pyrazole-[1,2,4]-triazole hybrids. The structure geometry of these new clicked 1,2,3-triazoles was explored by density functional theory (DFT) using the B3LYP/6-311++G(d,p) level; also, the potential activity of the compounds for light absorption was simulated by time-dependent DFT calculations (TD-DFT). The antitumor impacts of the newly synthesized compounds were in vitro estimated to be towards the human liver cancer cell line (HepG-2), the human colon cancer cell line (HCT-116), and human breast adenocarcinoma (MCF-7). Among the tested compounds, conjugate 7 was the most potent cytotoxic candidate towards HepG-2, HCT-116, and MCF-7, with IC50 = 12.22, 14.16, and 14.64 µM, respectively, in comparison to that exhibited by the standard drug doxorubicin (IC50 = 11.21, 12.46, and 13.45 µM). Finally, a molecular docking study was conducted within the epidermal growth factor receptor (EGFR) active site to suggest possible binding modes. Hence, it could conceivably be hypothesized that analogies 7, 6, and 5 could be considered as decent lead candidate compounds for anticancer agents.

Relative Sarcopenia With Excess Adiposity Predicts Survival After Transjugular Intrahepatic Portosystemic Shunt Creation.

OBJECTIVE. The purpose of this study was to assess the impact of relative sarcopenia with excess adiposity on mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS. In this single-institution retrospective study, patients underwent abdominal CT scans within 100 days before or 30 days after TIPS creation. Subcutaneous and visceral adipose tissue and muscle were segmented at the L3 vertebral level. Relative sarcopenia with excess adiposity was defined as the lowest sex-specific quartile of muscle area divided by muscle plus adipose. Dates of death, liver transplantation, TIPS occlusion, and hepatic encephalopathy (HE) after TIPS creation were identified. Mortality was evaluated using competing risks survival analysis. Number of HE episodes and time to first episode were analyzed using negative binomial regression and competing risks survival analysis, respectively. RESULTS. A total of 141 patients (91 men; mean age, 56 years) were included in this study. In univariate analyses, Model for End-Stage Liver Disease (MELD) score (hazard ratio [HR], 1.09 per point; CI, 1.05-1.13; p < 0.001) and relative sarcopenia with excess adiposity (HR, 2.70; CI, 1.55-4.69; p < 0.001) were significant risk factors for shorter survival after TIPS. In multivariate analysis, both MELD score (HR, 1.09; CI, 1.03-1.15; p = 0.003) and relative sarcopenia with excess adiposity (HR, 2.65; CI, 1.56-4.51; p < 0.001) were significant predictors of worse survival. The C-index at 30 days was 0.71 for MELD score, 0.72 for relative sarcopenia with excess adiposity, and 0.80 for a model including both. There was no association between relative sarcopenia with excess adiposity and number of HE episodes (incidence rate ratio, 1.08; CI, 0.49-2.40; p = 0.84) or time to first HE episode (HR, 0.89; CI, 0.51-1.54; p = 0.67). CONCLUSION. Relative sarcopenia with excess adiposity is a risk factor for mortality after TIPS and contributes additional prognostic information beyond MELD score.

Preoperative localization of sentinel lymph node in breast cancer patients by silver wire insertion or liquid charcoal injection guided by CT lymphography.

Dual localization of SLN in breast cancer patients using isotope & dye is the best-approved modality with limitations such as high cost of radioactive materials, complex logistic preparations & scheduling issues, especially in developing countries. We investigated the feasibility & accuracy of a novel technique for SLN localization using silver wire insertion or liquid charcoal injection guided by CT lymphography. 120 patients with clinically node-negative breast cancer were enrolled. In the test group, SLN was localized using preoperative CTLG guided injection of liquid charcoal or by placing a 3 cm silver wire. In addition, intraoperative SLN mapping was performed using methylene blue dye followed by searching for the SLN localized by both methods. In the control group, SLN was localized by the blue dye only. Feasibility, accuracy, detection rates, and number of SLNs retrieved were reported as well as matching between the LN detected with the CTLG and that detected with the dye technique. SLN could be detected in 59 out of 60 patients (98.3%) in the test group and in 54 out of 60 patients (90%) in the control group (P = .057). In self-controlled analysis of the test group comparing CTLG only to dye only was significant (P = .050). Comparing charcoal to silver wire in detection was statistically insignificant (P = .5). This novel method can offer advantages which are as follows: being more accurate than the dye alone, saving operative time, abandoning complex logistic preparations for the radioisotope, and solving the problem of timing.