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.

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.

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.

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.

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.

COVID-19 Infection and Arterial Thrombosis: Report of Three Cases.

Thrombotic complications associated with coronavirus disease 2019 (COVID-19) have been described; these have mainly included venous thromboembolic events. Limited literature is available regarding arterial thrombosis. Acute limb ischemia is associated with severe complications that can result in significant morbidity and mortality. Herein, we report 3 cases of COVID-19 infection complicated by arterial thrombosis in the form of acute limb ischemia. Our case series adds to the limited literature regarding arterial thrombosis.

Prevalence of obstructive sleep apnoea among patients admitted with acute coronary syndrome in a hill state of northern India.

Background Obstructive sleep apnoea (OSA) is one of the emerging non-traditional cardiovascular risk factors. Studying OSA may contribute towards a better understanding of current concepts of atherogenesis and in guiding therapy. Methods We conducted this cross-sectional study among 66 patients with acute coronary syndrome (ACS) in a tertiary care hospital from 1 January 2019 to 30 June 2020. We included patients of ST elevation myocardial infarction (STEMI)/ non-STEMI (on achieving Killip class I/II) and unstable angina and performed in-hospital overnight polysomnography (PSG) within 8 weeks of index event. Apnoea-hypoapnoea index (AHI) value 5-<15 was defined as mild OSA, AHI 15-<30 as moderate OSA and AHI >30 as severe OSA. We analysed data using Epi Info version 7.2.4 for Windows. Results The 66 patients had a mean (SD) age of 57.7 (11.1) years and 54 (81.8%) were men. Forty-three (65.1%) patients had STEMI, 19 (28.7%) had non-STEMI and 4 (6%) had unstable angina. On PSG, the prevalence of OSA (AHI>5) was 78.8% (95% CI 67.0-87.9). Of these, AHI >15 was significantly associated with diabetes, hypertension and different measures of obesity (p<0.05). Conclusions This study, conducted in a hill state of northern India, showed a high prevalence of OSA in patients with ACS. Obesity, diabetes mellitus and hypertension were significantly associated with severity of OSA (AHI>15).

Role of Various DW MRI and DCE MRI Parameters as Predictors of Malignancy in Solid Pulmonary Lesions.

PURPOSE: We aimed to evaluate various diffusion and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) parameters in differentiating malignant from benign pulmonary lesions. METHODS: We enrolled 31 (22 males) patients who had solid pulmonary lesion(s) >2 cm in our cross sectional study. Of these, 23 (74.2%) were found to be malignant on histopathology. Dynamic contrast-enhanced MRI was performed using 36 dynamic measurements (volumetric interpolated breath-hold examination). Diffusion-weighted MRI (DW MRI) performed at b value of 800 s/mm2. We measured different diffusion and perfusion parameters, for example, diffusion-weighted imaging (DWI) SI, mean apparent diffusion coefficient (ADC), minimum ADC, lesion-to-spinal cord ratio, DWI score, T2 score, Ktrans, Kep, and Ve. We stratified values of each parameter as high if it was >median of values observed in our data set and low if it was ≤median. Normally distributed data were compared by unpaired t test, whereas non-normal continuous data were compared by Kruskal Wallis-H test. We applied Wilson score method to calculate sensitivity, specificity, and predictive values of parameters that were statistically significant by type of lesion with reference to histopathological examination as gold standard. RESULTS: Diffusion-weighted imaging SI, mean ADC, minimum ADC, DWI score and Ktrans values were found to be significantly different (P value < .05) by type of lesion. Ktrans was found to have the highest diagnostic accuracy (74.2%) among these parameters. CONCLUSION: Ktrans and mean ADC had similar sensitivity of 65.2%. However, Ktrans had highest diagnostic accuracy among various DWI and DCE MRI parameters in predicting malignancy in solid pulmonary lesions. In our study, we found a cutoff value 0.251 min-1 for Ktrans as 100% specific.

Unprovoked Pulmonary Embolism in Factor VII Deficiency.

Thrombotic events in bleeding disorders such as hemophilia A or B, Von Willebrand disease, afibrinogenemia, factor VII deficiency, and factor XI deficiency are rare but have been reported. These events usually occur in the presence of prothrombotic risk factors such as recent surgery, trauma, or factor replacement therapy. We present a case of a 68-year-old Hispanic female with a history of factor VII deficiency who presented with shortness of breath, chest pain, and palpitations and was found to have pulmonary embolism. Our patient did not have any of the above-mentioned thrombotic risk factors. Our case and review of the literature show that factor VII deficiency does not provide protection against thrombosis.

Predictors of Severity in Scrub Typhus.

AIMS: To study predictors of severity in patients of scrub typhus admitted in a tertiary care hospital. MATERIAL AND METHODS: Total 92 patients of scrub typhus were included in the study. The diagnosis was established by presence of IgM antibodies by Indirect Immunofluorescence Assay (IFA) test which is currently the reference standard for the diagnosis of scrub typhus. The clinical and laboratory profile, course in hospital, and outcome were documented. Factors associated with severe disease were analyzed. OBSERVATIONS: 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. An eschar was present in 23% of patients. Common laboratory findings included elevated transaminases (61%), thrombocytopenia (39%), and leukocytosis (30%). Severe sepsis was present in 33% patients. Septic shock was present in 4% patients. Presence of one or more organ failure was seen in 34% of patients. The overall case-fatality rate was 4%. Factors significantly associated with organ failure (severe disease) were leucocytosis (p < 0.001), hyperbilirubinemia (p < 0.001), high SGOT levels (p 0.030), hypoalbuminemia (p < 0.001), high urea levels (p < 0.001), and high creatinine levels (p 0.012). Among the criteria used to classify severity of scrub typhus, presence of one or more organ failure was significantly associated with mortality (p 0.004). CONCLUSION: Scrub typhus can manifest with potentially life-threatening complications such as meningoencephalitis, septic shock, ARDS, acute liver failure, acute kidney injury, severe thrombocytopenia. Leukocytosis, hyperbilirubinemia, transaminitis, hypoalbuminemia, and uremia were associated with organ failure and were significantly associated with morbidity and mortality.

Pattern of Clinical Presentation, Laboratory Findings and Mortality Risk Among Patients of Scrub Typhus in Western Himalayas.

OBJECTIVE: To study the pattern of the clinical presentation, laboratory findings and mortality risk among patients infected by scrub typhus in Western Himalayan region of India. METHODS: We studied all serologically confirmed cases of scrub typhus admitted to our hospital from July 2010 through December 2011. Presence of IgM antibodies to scrub typhus antigens by ELISA was considered as serological confirmation of the diagnosis. We observed the symptoms, signs, laboratory findings, risk factors for death from the time of admission till discharge/death. We performed bivariate and logistic regression analysis to look for independent risk factors for death. RESULTS: Total 253 patients were studied. All patients came from rural areas. More than 2/3rd were women and below 50 years of age each. High grade fever (90%), chills and rigors (68%), conjunctival suffusion (50%), body aches (43%), headache (41%), myalgias (37%), abdominal pain (21%), lymphadenopathy (17%), splenomegaly (17%), cough (16%), altered sensorium (16%), vomiting (15%), hepatomegaly (13%) were main presenting features. Eschar was present in 112 (44%) patients. Transaminitis (49%); and abnormal renal functions (31%) were predominant biochemical abnormalities. All patients were empirically treated with doxycycline/azithromycin. Thirteen (5%) patients died. CONCLUSIONS: In our region, rural women below 50 years of age presenting with high grade fever with or without eschar should be strongly suspected to be having scrub typhus. Renal dysfunction and altered sensorium are significant mortality risk factors (p < 0.05) and need to be identified at early stage to improve the treatment outcomes.

Synthesis and characterization of novel histidine functionalized chitosan nanoformulations and its bioactivity in tomato plant.

The use of novel active ingredients for the functional modification of chitosan nanoformulations has attracted global attention. In this study, chitosan has been functionalized via histidine to craft novel chitosan-histidine nanoformulation (C-H NF) using ionic gelation method. C-H NF exhibited elite physico-biochemical properties, influencing physiological and biochemical dynamics in Tomato. These elite properties include homogenous-sized nanoparticles (314.4 nm), lower PDI (0.218), viscosity (1.43 Cps), higher zeta potential (11.2 mV), nanoparticle concentration/ml (3.53 × 108), conductivity (0.046 mS/cm), encapsulation efficiency (53%), loading capacity (24%) and yield (32.17%). FTIR spectroscopy revealed histidine interaction with C-H NF, while SEM and TEM exposed its porous structure. Application of C-H NF to Tomato seedling and potted plants through seed treatment and foliar spray positively impacts growth parameters, antioxidant-defense enzyme activities, reactive oxygen species (ROS) content, and chlorophyll and nitrogen content. We claim that the histidine-functionalized chitosan nanoformulation enhances physico-biochemical properties, highlighting its potential to elevate biochemical and physiological processes of Tomato plant.

Frequent exposure to suboptimal temperatures in vaccine cold-chain system in India: results of temperature monitoring in 10 states.

OBJECTIVE: To estimate the proportion of time the vaccines in the cold-chain system in India are exposed to temperatures of < 0 or > 8 °C. METHODS: In each of 10 states, the largest district and the one most distant from the state capital were selected for study. Four boxes, each containing an electronic temperature recorder and two vials of diphtheria, pertussis and tetanus vaccine, were placed in the state or regional vaccine store for each study state. Two of these boxes were then shipped - one per facility - towards the two most peripheral health facilities where vaccine was stored in each study district. The boxes were shipped, handled and stored as if they were routine vaccine supplies. FINDINGS: In state, regional and district vaccine stores and peripheral health facilities, respectively, the temperatures in the boxes exceeded 8 °C for 14.3%, 13.2%, 8.3% and 14.7% of their combined storage times and fell below 0 °C for 1.5%, 0.2%, 0.6% and 10.5% of these times. The boxes also spent about 18% and 7% of their combined times in transit at < 0 and > 8 °C, respectively. In shake tests conducted at the end of the study, two thirds of the vaccine vials in the boxes showed evidence of freezing. CONCLUSION: While exposure to temperatures above 8 °C occurred at every level of vaccine storage, exposure to subzero temperatures was only frequent during vaccine storage at peripheral facilities and vaccine transportation. Systematic efforts are needed to improve temperature monitoring in the cold-chain system in India.

Bioaugmented composting of Jatropha de-oiled cake and vegetable waste under aerobic and partial anaerobic conditions.

This study was conducted to assess the effect of microbial inoculation in Jatropha cake composting with different vegetable waste. The microbial inoculums composed of fungal strains (Aspergillus awamori, Aspergillus nidulans, Trichoderma viride, Phanerochaete chrysosporium) and bacterial inoculums (Pseudomonas striata as phosphorus solublizer and Azotobacter chroococcum as nitrogen fixer) were added to the compost mixture after the thermophilic phase was over for bioaugmenting of Jatropha cake under aerobic and partial anaerobic conditions. Addition of both fungal and bacterial inoculum with mixed substrate (Jatropha cake + vegetable waste) during composting (aerobic and partial anaerobic) showed, better results as compared to compost with only fungal inoculants. Increased enzymatic activity initially, during composting (like dehydrogenase, alkaline phosphatase activity and FDA) proved role of inoculated microbes in rapid decomposition. Analysis of compost (with both bacterial and fungal inoculum) showed presence of high humus (12.7%), humic acid (0.5%), fulvic acid (5.68%), soluble protein content and low C/N ratio. Decreased in concentration of extractable metals (Cu, Fe and Mn) were recorded at maturity in all the substrate composts. The C/N ratio was significantly correlated to parameters like humic acid, humus, fulvic acid, protein and also microbial activity parameters. We conclude that the composting of de-oiled Jatropha cake with different vegetables waste could be feasible and sustainable approach in recycling of agricultural and industrial residues in huge quantities.

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.

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.

Disseminated tumor cells predict survival after neoadjuvant therapy in primary breast cancer.

BACKGROUND: Tumor cells that disseminate to the bone marrow (disseminated tumor cells [DTCs]) have been identified in 30% of patients with stage I through II breast cancer (BC) and predict outcome. Neoadjuvant chemotherapy (NACT) is effective in reducing the size of primary tumors or eradicating lymph node metastases before surgery, but little is known regarding the presence or significance of DTCs after NACT. METHODS: The authors evaluated DTCs in 95 patients with clinical stage I through III BC. Bone marrow samples were collected after completion of NACT at the time they underwent surgery for primary BC. DTCs were assessed using an anticytokeratin antibody cocktail. Primary tumor markers, the extent of lymph node (LN) involvement, they type of NACT administered, and response to NACT were compared with presence of DTCs. Chi-square and Fisher exact tests were used for statistical analyses. RESULTS: The median patient age at diagnosis was 51 years, and the median follow-up was 24 months. Forty-six percent of patients had tumors classified as T1/T2, 20% had T3 tumors, 34.5% had T4 tumors, and 81% had lymph node metastasis before NACT. DTCs were identified in 26% of patients after NACT. No associations were observed between DTCs and primary tumor characteristics or LN involvement. A pathologic complete response was observed in 25 patients (26%) but was not predictive of DTCs after NACT (P = .83). DTCs after NACT predicted worse BC-specific survival (P < .02). CONCLUSIONS: The presence of DTCs was an independent predictor of outcome after NACT. The current results indicated that monitoring hematogenous micrometastatic disease after NACT may be useful in selecting patients who might benefit from additional systemic adjuvant therapies.

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.

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.