Approximation in scour depth around spur dikes using novel hybrid ensemble data-driven model.

The scouring process near spur dikes poses a threat to riverbank stability, making it crucial for river engineering to accurately calculate the maximum scour depth. However, determining the maximum scour depth has been challenging due to the intricacy of scour phenomena surrounding these structures. This research introduces a reliable ensemble data-driven model by hybridizing random tree (RT) using additive regression (AR), bagging (B), and random subspace (RSS) for predicting scour depths around spur dikes. A database of 154 experimental observations was collected from literature, with 103 and 51 observations used for training and testing subsets, respectively. A dimensionless analysis was performed on the collected dataset, selecting four variables as input variables (v/vs, y/l, l/d50, and Fd50) and ds/l as response variables. The performance comparison demonstrates that B_AR_RT has a better coefficient of determination (R2) of 0.9693, root mean square error (RMSE) of 0.1305, and Nash-Sutcliffe efficiency (NSE) of 0.9692. Finally, a comparison of the best hybrid model has been done with previous studies, and sensitivity analysis is performed to determine the most influential parameter for predicting the scour depth around spur dikes.

Genetic Diversity and Population Structure Analyses in Bitter Gourd (Momordica charantia L.) Based on Agro-Morphological and Microsatellite Markers.

Bitter gourd (Momordica charantia L.) is an important vine crop of the Cucurbitaceae family and is well known for its high nutritional and medicinal values. However, the genetic variation remains largely unknown. Herein, 96 diverse bitter gourd genotypes were undertaken for diversity analysis using 10 quantitative traits, and 82 simple sequence repeat (SSR) markers. Out of 82 SSRs, 33 were polymorphic and the mean polymorphism information content (PIC) value was 0.38. Marker, JY-003 revealed a maximum (0.81) PIC value and, the number of alleles per locus ranged from 2 to 7 (average 3.46). The value of gene diversity showed the presence of a significant level of polymorphism among these genotypes. The unweighted pair group method (UPGMA) cluster analysis grouped the genotypes into two major clusters of which Cluster I comprised mostly small and medium-fruited genotypes of both M. charantia var. charantia and M. charantia var. muricata, whereas Cluster II included mostly long and extra-long fruited genotypes. Furthermore, these genotypes were divided into six distinct groups based on population structure analysis. The diversity analysis based on 10 quantitative traits revealed that earliness and high-yielding ability were exhibited by the predominantly gynoecious line DBGS-21-06 followed by DBGS-48-00. The principal component analysis (PCA) revealed that the first two components exhibited more than 50% of the total genetic variation. The present study deciphered a higher magnitude of agro-morphological and genetic diversity in 96 bitter gourd genotypes. Therefore, trait-specific genotypes identified in this study could be utilized in breeding programmes directed towards the development of improved cultivars and hybrids of bitter gourd.

Coagulation Abnormalities in Severe Scrub Typhus and Their Association with Complications.

AIM: To describe coagulation abnormalities and their association with complications in patients with severe scrub typhus. MATERIALS AND METHODS: A cohort study was conducted among all patients of severe scrub typhus [immunoglobulin M (IgM) positive] who reported to this facility from 1st August 2019 to 31st July 2020 and met our inclusion criteria. We estimated the incidence of severe thrombocytopenia (<50,000/µL) and overt disseminated intravascular coagulation (DIC) (DIC score of ≥5). We determined the association [risk (RR) ratios] of these abnormalities with complications of scrub typhus, namely-septic shock, multiple organ dysfunction syndrome (MODS), and septic shock with MODS. RESULTS: In total, 71 patients were studied with a mean age of 50 ± 15.5 years, of which 45 (63.4%) were females. On presentation, fever 70 (98.5%), myalgias 22 (31.0%), loose stools 13(18.3%), cough, vomiting, headache 11 (15.5%), altered sensorium 10(14.1%), and pain abdomen 9 (12.7%) were main symptoms. On examination, hypotension 31 (43.7%), eschar 25 (35.2%), icterus 17 (23.9%), and rash 16 (22.5%) were noted. The d-dimer (>0.5 µg/mL) levels were increased in all (100%) patients. Thrombocytopenia (91.5%) was the commonest hematological abnormality and 31 (43.6%) of them had severe thrombocytopenia, 25 (35.2%) patients had low fibrinogen levels (<200 mg/dL) and prothrombin time (PT >16.7 seconds) was prolonged in 20 (28.1%). A total of 42 (59.1%) patients developed MODS, 33 (46.4%) developed septic shock, 24 (33.8 %) had MODS with septic shock, 17 (23.9%) developed overt DIC, and eight (11.2%) died. Severe thrombocytopenia (p = -0.028) and overt DIC (p = 0.045) were significantly associated with septic shock development. CONCLUSION: In the patients admitted with severe scrub typhus; thrombocytopenia was the commonest hematological abnormality. The development of septic shock was significantly associated with severe thrombocytopenia and overt DIC.

Sensitization of Resistant Cells with a BET Bromodomain Inhibitor in a Cell Culture Model of Deep Intrinsic Resistance in Breast Cancer.

We treated highly metabolically adaptable (SUM149-MA) triple-negative inflammatory breast cancer cells and their control parental SUM149-Luc cell line with JQ1 for long periods to determine its efficacy at inhibiting therapy-resistant cells. After 20 days of treatment with 1-2 µM of JQ1, which killed majority of cells in the parental cell line, a large number of SUM149-MA cells survived, consistent with their pan-resistant nature. Interestingly, though, the JQ1 treatment sensitized resistant cancer cells in both the SUM149-MA and SUM149-Luc cell lines to subsequent treatment with doxorubicin and paclitaxel. To measure JQ1-mediated sensitization of resistant cancer cells, we first eradicated approximately 99% of relatively chemotherapy-sensitive cancer cells in culture dishes by long treatments with doxorubicin or paclitaxel, and then analyzed the remaining resistant cells for survival and growth into colonies. In addition, combination, rather than sequential, treatment with JQ1 and doxorubicin was also effective in overcoming resistance. Notably, Western blotting showed that JQ1-treated cancer cells had significantly lower levels of PD-L1 protein than did untreated cells, indicating that JQ1 treatment may reduce tumor-mediated immune suppression and improve the response to immunotherapy targeting PD-L1. Finally, JQ1 treatment with a low 62.5 nM dose sensitized another resistant cell line, FC-IBC02-MA, to treatment with doxorubicin and paclitaxel.

Applications of Circulating Tumor Cells and Circulating Tumor DNA in Precision Oncology for Breast Cancers.

Liquid biopsies allow for the detection of cancer biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Elevated levels of these biomarkers during cancer treatment could potentially serve as indicators of cancer progression and shed light on the mechanisms of metastasis and therapy resistance. Thus, liquid biopsies serve as tools for cancer detection and monitoring through a simple, non-invasive blood draw, allowing multiple longitudinal sampling. These circulating markers have significant prospects for use in assessing patients' prognosis, monitoring response to therapy, and developing precision medicine. In addition, single-cell omics of these liquid biopsy markers can be potential tools for identifying tumor heterogeneity and plasticity as well as novel therapeutic targets. In this review, we focus on our current understanding of circulating tumor biomarkers, especially in breast cancer, and the scope of novel sequencing technologies and diagnostic methods for better prognostication and patient stratification to improve patient outcomes.

Managed pollination is a much better way of increasing productivity and essential oil content of dill seeds crop.

Dill seeds (Anethum graveolens L.) is the most valuable medicinal seed spice crop of Apiaceae. It bears small yellow flowers in the form of umbels. Being a cross-pollinated crop, floral visitors play vital role in pollination and seed sets. Hence, the present study was conducted at the ICAR-National Research Centre on Seed Spices, Ajmer (Rajasthan), India to discover the pollinator's community, foraging behaviour and abundance of most frequent pollinators and different modes of pollination on seed yield and quality of this seed spice crop. The insect visitors community of dill seeds was composed of 28 insect species belonging to 14 families of 6 orders. Most of floral visitors started their foraging activity at 8.00 h, reached peak activity between 12.00 and 14.00 h and their activity ceased at 18.00 h. Apis florea, A. dorsata, A. mellifera, solitary bee, Halictus sp. and two unidentified species of Hymenoptera; Episyrphus balteatus (DeGeer), Episyrphus sp., Eristalis sp and two other Musca species of Diptera were identified as potential and regular floral visitors of dill seeds. The highest seed yield of 1505.63 kg/ha was recorded in the treated plots provided with only 10% jaggery solution and was at par with the open pollination. A lower seed yield of 1432.5 kg/ha was recorded in plots pollinated only with A. mellifera inside insect cages. Open pollination with 10% jaggery solution spray increased the seed yield of dill seed crop by 57%, one-thousand seed test weight by 96% and the essential oil content by 27% over control plots. These results show that managed pollination is a much better way to enhance yields and quality of dill seed crop than other treatments including only honeybee-based pollination.

Sensitization of Resistant Breast Cancer Cells with a Jumonji Family Histone Demethylase Inhibitor.

In the present study, we evaluated JIB-04, a small-molecule epigenetic inhibitor initially discovered to inhibit cancer growth, to determine its ability to affect deep intrinsic resistance in a breast cancer model. The model was based on a function-based approach to the selection of cancer cells in a cell culture that can survive a variety of challenges in prolonged, but reversible, quiescence. These resistant cancer cells possessed a variety of mechanisms, including modifications of the epigenome and transcriptome, for generating a high degree of cellular heterogeneity. We found that long pretreatment with JIB-04 sensitized resistant triple-negative inflammatory breast cancer cells and their parental cell line SUM149 to the chemotherapeutic drugs doxorubicin and paclitaxel. Resistant cancer cells derived from another inflammatory breast cancer cell line, FC-IBC02, were considerably more sensitive to JIB-04 than the parental cell line. Investigating a mechanism of sensitization, we found that JIB-04 exposure increased the expression of PD-L1 in resistant cells, suggesting that JIB-04 may also sensitize resistant breast cancer cells to anti-PD-L1 immune therapy. Finally, these results support the usefulness of a cell culture-based experimental strategy for evaluating anticancer agents, such as JIB-04, that may halt cancer evolution and prevent the development of cancer resistance to currently used therapies.

Tetrad of DKA, Hypertriglyceridemia Induced Pancreatitis and Splenic Vein Thrombosis.

Patients with diabetes mellitus have diabetic dyslipidemia that occurs due to disturbances in glucose metabolism and can lead to hypertriglyceridemia (HPTG). Severe HPTG is associated with significantly increased risk of developing acute pancreatitis (AP). Acute pancreatitis (AP) is characterized as an inflammatory condition where inactive digestive enzymes become activated causing pancreatic tissue destruction. Hypertriglyceridemia and the inflammatory state that ensues therein also gives rise to a hypercoagulable state in patients with AP. Splenic vein thrombosis (SVT) is a rare complication of both AP and chronic pancreatitis (CP). We report a Case of 55-year-old Filipino male with past medical history of hypertension and uncontrolled type 2 diabetes mellitus (T2D), who presented with abdominal pain and was found to have diabetic ketoacidosis (DKA), and severe HPTG which led to acute pancreatitis, further complicated by SVT requiring anticoagulation. Our case highlights the importance of strict glycemic control among diabetic patients, the prompt management of AP in the setting of HPTG, and treatment of SVT.

Paroxysmal nocturnal hemoglobinuria clone in a patient with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia which is clonal in nature due to somatic mutation. PNH may evolve to aplastic anemia, and more rarely, to a myelodysplastic syndrome or to AML. The literature review showed that AML is derived from the PNH clone as the leukemic cells lack the expression of glycosylphosphatidylinositol-linked proteins and PNH phenotype disappeared with the onset of acute leukemia. Herein, we report an unusual presentation of the coexistence of two clonal disorders PNH and APL. Our case contributes to the literature that AML in the setting of PNH is a separate disorder.

Is Hyperuricemia a Marker of Severity of Disease in Scrub Typhus?

AIMS: To study association of hyperuricemia with severity of scrub typhus. METHODS: We studied clinical features, laboratory profile, in hospital course and outcome of 92 patients of scrub typhus and association of hyperuricemia with severity of disease. RESULTS: Of total 92 patients in study group, 66 (71.7%) were females and 26(28.3%) were males. Fever (100%), cough (37%), headache (33%), vomiting (31%), altered sensorium (23%), diarrhea (18%), abdominal pain (16%), myalgia (14%), and seizures (3%) were common clinical features. Eschar was present in 23%. Of total 92 patients 34 (37%) patients had hyperuricemia (HU) and 58 patients had normal serum uric acid levels. The patients of scrub typhus with HU had significantly higher presentation with altered sensorium (35.3%). In HU group, mean TLC, mean serum urea and serum creatinine were higher and mean serum albumin and mean HDL cholesterol were lower than patients of scrub typhus without hyperuricemia. These differences between two groups were statistically significant. Neurological dysfunction, severe sepsis, serum creatinine >3.5mg/dL and involvement of at least single organ was significantly higher in HU group. Total 4 patients (4.3%) died and all had HU. CONCLUSION: Hyperuricemia in patients of scrub typhus was associated with severe scrub typhus. The serum uric acid levels should be done in early course of all patients suffering from scrub typhus. The patients showing hyperuricemia should be monitored closely for early recognition of complications and management aggressively.

Dynamic contrast-enhanced magnetic resonance perfusion volumetrics can differentiate tuberculosis of the spine and vertebral malignancy.

BACKGROUND: There is considerable overlap in radiologic features of tubercular and malignant spinal lesions on conventional magnetic resonance imaging (MRI). PURPOSE: To evaluate the role of dynamic contrast-enhanced (DCE) MRI perfusion parameters in differentiating vertebral malignancy from spinal tuberculosis. MATERIAL AND METHODS: This was a prospective study and we enrolled consecutive patients presenting with a clinical/radiologic evidence of vertebral lesions. DCE-MRI of the spine was performed using 3D volume interpolated breath-hold examination (VIBE) sequence after intravenously injecting 0.1 mmol/kg body weight of gadopentetate dimeglumine. We used Tofts model to calculate DCE parameters that included Ktrans (transfer constant), kep (rate constant), ve (fractional volume of extracellular extravascular space), and iAUC (initial area under the curve). We compared the mean value of each perfusion parameter by type of lesion (tubercular/malignant) at 0.05 significance level and performed receiver operating characteristic curve analysis. RESULTS: We could confirm histologic/cytologic diagnosis in 35 of the 45 patients recruited. Of these, 19 were tubercular and 16 were malignant lesions. The mean (± standard deviation) of kep (min-1) was significantly higher (2.89 ± 3.3) in malignant compared to tubercular lesions (0.81 ± 0.19), whereas ve was significantly lower in malignant (0.27 ± 0.13 mL/g) compared to benign lesions (0.47 ± 0.12 mL/g) at 0.05 significance level. kep cutoff of ≥1.17 min-1 had a sensitivity of 93.8% and specificity of 100% with a diagnostic accuracy of 94.4% in detecting malignant disease. CONCLUSION: High kep is the single best predictor of malignant vertebral lesions. We recommend kep cutoff value of ≥1.17 min-1 that has high diagnostic accuracy in identifying malignant lesions.

Leukocytosis and Spurious Hypoxemia.

Abnormally low pO2 and oxygen saturations on arterial blood gases (ABGs) test have been reported in the patients who have very high WBC and platelet counts; generally in the setting of hematological malignancies. This is presumably related to the consumption of oxygen by the active cellular elements in the arterial blood sample during the process of ABG analysis. This phenomenon which is also known as "spurious hypoxemia" or "oxygen steal" or "leukocyte/platelet larceny" is suspected when there is no other obvious explanation for hypoxemia on ABG, especially in the setting of normal oxygen saturations by the pulse oximetry. It is important for medical professionals to be aware of this condition so that appropriate workup and triage can be performed on such patients, which may otherwise lead to unnecessary hospitalization and escalation of care.

Checkpoint Inhibitors in Relapsed/Refractory Classical Hodgkin Lymphoma.

Even though classical Hodgkin lymphoma is highly curable, the outcome of patients with a refractory or relapsed disease has been disappointing. Multiple lines of therapy are available for patients after their first failure, and most respond to subsequent therapies. However, there is a sizable proportion that remains relapsing/recurrent even after several lines of therapy. The overall prognosis of patients with relapsing and recurrent classical Hodgkin lymphoma (rrcHL) has been very disappointing until recently. Immune checkpoint inhibitors such as the anti-programmed death 1 (PD-1) receptor antibodies have recently been approved to treat relapsed and refractory cHL and have significantly improved the outcome of patients with rrcHL. The approved immune checkpoint inhibitors for relapsed and refractory cHL are nivolumab and pembrolizumab. In the Checkmate 205 study nivolumab demonstrated an objective response rate of 69% with an acceptable safety profile. Similarly, pembrolizumab demonstrated an overall response rate (ORR) of 69% with a complete remission rate (CRR) of 22.4% in the KEYNOTE-087 study in heavily pretreated patients with rrcHL.

Usage of Direct Acting Oral Anticoagulants in Cirrhotic and Non-Cirrhotic Portal Vein Thrombosis: A Systematic Review.

Thrombosis of the portal vein (PVT) is generally seen in the setting of liver cirrhosis and to a lesser extent in the absence of cirrhosis. There is no clear guidance in relation to approaching treatment with anticoagulation in this condition. The professional societies and guidelines recommend treatment with traditional anticoagulation like low-molecular-weight heparin and vitamin-K antagonists in patients presenting with acute portal vein thrombosis. There is no clarity in relation to treatment in the setting of chronic PVT and in patients with cirrhosis. Also, the role of direct-acting oral anticoagulants (DOACs) that are becoming a preferred choice for anticoagulation for various other indications is not clear in the case of PVT. There are a very few studies in the medical literature that have investigated the role of DOACs in patients with PVT in different settings. Thus, we performed a systematic review of the literature to study the use of DOACs in PVT in patients with and without cirrhosis. The results of the available studies show that DOACS appears to be a promising choice for the treatment of patients with PVT. The availability of more data in the future along with better availability of the approved reversal agents for various DOACs is expected to make DOACS a preferred choice for the clinicians to treat patients with PVT.

Emphysematous cholecystitis: A deadly disguise of a common culprit.

Emphysematous cholecystitis is a critical differential diagnosis for physicians to consider when evaluating patients with acute abdomen. Patients who are unable to undergo emergency surgery can benefit from percutaneous cholecystostomy.

Complete Response With Immunotherapy: A Case of Metastatic Bladder Cancer.

Bladder cancer is the most common urinary tract malignancy. Platinum-based chemotherapy is the first line of treatment in locally advanced or metastatic bladder cancer. Immunotherapy has become a novel therapy option in a broad variety of malignancies including bladder cancer. Immunotherapy is approved as first line of treatment in patients who are ineligible for platinum-based chemotherapy and second-line treatment for metastatic urothelial cancer who progressed after platinum-based treatments. We present the case of an 83-year-old female with metastatic bladder cancer who was chemotherapy ineligible and had complete response with immune checkpoint inhibitor pembrolizumab.

Does Baseline Diuretics Use Affect Prognosis in Patients With COVID-19?

The rapid emergence of coronavirus disease 2019 (COVID-19) has become the biggest healthcare crisis of the last century, resulting in thousands of deaths worldwide. There have been studies that evaluated the role of angiotensin-converting enzyme (ACE) inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in treating patients with COVID-19. However, the prior use of diuretics and their effect on mortality in this setting remains unknown. The aim of the study was to evaluate the effect of diuretics in patients admitted with COVID-19. The current study was conducted between March 15, 2020, and April 30, 2020, during the COVID-19 pandemic in three different hospitals in Northern New Jersey, USA. The primary outcome was survival or in-hospital mortality from COVID-19 from the day of admission. The secondary outcome was severe or non-severe illness from COVID-19. This retrospective study included a total of 313 patients with a median age of 61.3 ± 14.6 years. There was a total of 68 patients taking diuretics at home and 245 patients who were not taking diuretics. There was a total of 39 (57.35%) deaths in patients taking diuretics as compared to 93 (37.96%) deaths in patients not taking diuretics (p-value 0.0042). Also, 54 (79.41%) patients who took diuretics had severe COVID-19 illness as compared to 116 (47.35%) who did not take diuretics (p-value <.0001). However, after adjusting for the confounding factors, there was no difference in mortality or severity of illness in COVID-19 patients taking diuretics at the time of admission. In conclusion, there was no effect of the baseline use of diuretics in the prognosis of COVID-19.