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Escherichia coli infections in poultry cause significant morbidity and economic losses for producers each year. In a 3-year period, we collected and sequenced the whole genomes of E. coli disease isolates ( n = 91), isolates from presumed healthy birds ( n = 61), and isolates from 8 barn sites ( n = 93) on broiler farms in Saskatchewan.

Supplementary figure 1. Validation of synthetic lethal interaction between OGT inhibition and AT7519 in LNCaP cells. Supplementary figure 2. Validation of synthetic lethal interaction between OSMI-2 and AT7519 in additional cell lines. Supplementary figure 3. Combination of OSMI-2 with AT7519 induces cells death in prostate cancer cells but not in cells derived from normal prostate epithelia. Supplementary figure 4. Characterization of RNA-seq data of cells treated with OGT inhibitor OSMI-2. Supplementary figure 5. OGT inhibition decreases phosphorylation of the carboxyterminal domain of RNA polymerase II. Supplementary figure 6. AT7519 enhances the effects of OGT inhibition by blocking the upregulation of OGT in PC3 cells. Supplementary figure 7. Summary of the RNA-seq data. Supplementary figure 8. Specific CDK9 inhibitor NVP2 is synthetically lethal in combination with OGT inhibition to LNCaP prostate cancer cells. Supplementary figure 9. OGT inhibition potentiates the anti-proliferative effects of CDK9 inhibitors Dinaciclib and SB1317 on prostate cancer cells. Supplementary figure 10. Knockdown of CDK9 sensitizes LNCaP prostate cancer cells to OGT inhibition. Supplementary figure 11. Combination of OSMI-2 with AT7519 further decreases the mRNA abundance of most mRNAs with half-life less than 4 hours. Supplementary figure 12. Determination of CDK9 inhibitor dose suitable for organoid experiments. Supplementary figure 13. Validation of synthetic lethality between inhibitors of OGT and CDK9 using models of castration-resistant prostate cancer (CRPC).

O-GlcNAc transferase (OGT) is a nutrient-sensitive glycosyltransferase that is overexpressed in prostate cancer, the most common cancer in males. We recently developed a specific and potent inhibitor targeting this enzyme, and here, we report a synthetic lethality screen using this compound. Our screen identified pan-cyclin-dependent kinase (CDK) inhibitor AT7519 as lethal in combination with OGT inhibition. Follow-up chemical and genetic approaches identified CDK9 as the major target for synthetic lethality with OGT inhibition in prostate cancer cells. OGT expression is regulated through retention of the fourth intron in the gene and CDK9 inhibition blunted this regulatory mechanism. CDK9 phosphorylates carboxy-terminal domain (CTD) of RNA Polymerase II to promote transcription elongation. We show that OGT inhibition augments effects of CDK9 inhibitors on CTD phosphorylation and general transcription. Finally, the combined inhibition of both OGT and CDK9 blocked growth of organoids derived from patients with metastatic prostate cancer, but had minimal effects on normal prostate spheroids. We report a novel synthetic lethal interaction between inhibitors of OGT and CDK9 that specifically kills prostate cancer cells, but not normal cells. Our study highlights the potential of combining OGT inhibitors with other treatments to exploit cancer-specific vulnerabilities.Implications:The primary contribution of OGT to cell proliferation is unknown, and in this study, we used a compound screen to indicate that OGT and CDK9 collaborate to sustain a cancer cell–specific pro-proliferative program. A better understanding of how OGT and CDK9 cross-talk will refine our understanding of this novel synthetic lethal interaction.

Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.Patient summaryProstate cancers are very variable, including within a single tumour. Current genetic scoring systems, which are sometimes used to make decisions for how to treat patients with prostate cancer, are based on sampling methods which do not reflect these variations. We found, using state-of-the-art spatial genetic technology to simulate accurate assessment of variation in biopsies, that the current approaches miss important details which could negatively impact clinical decisions.Take home messageVirtual biopsies from spatial transcriptomic analysis of a whole prostate reveal that current genomic risk scores potentially deliver misleading results as they are based on bulk analysis of prostate biopsies and ignore tumour heterogeneity.

Purpose Given the growing prominence of voice-activated artificial intelligent devices (VAIs) as the strategic market-facing technology for grocery purchases, this article aims to bring together theories on anthropomorphism, trust, emotional attachment, self-connection and self-disclosure in one conceptual framework establishing that consumer–VAI relationship has significant implications for grocery purchase satisfaction and intention to repurchase using VAIs. Design/methodology/approach The study tested seven hypotheses through a survey-based approach comprising of two studies. Findings The study empirically supports VAI anthropomorphism and trust in VAIs as predictors of consumer–VAI emotional attachment and establishes the moderating role of consumer self-disclosure. Consumer–VAI self-connection resulting from emotional attachment results in grocery purchase satisfaction and intention to repurchase using VAIs. Research limitations/implications The article offers a novel perspective on consumer–VAI relationships and the use of VAIs for grocery purchases. It establishes an agentic role of consumers when ordering groceries using VAIs, creating a deeper understanding of how consumer–VAI emotional attachment results in extensions of consumers’ self-identity, resulting in purchase satisfaction and repurchase intention using VAIs. Practical implications Establishing a consumer–VAI relationship, the article brings out the strategic importance of VAIs for marketers in grocery purchases and repurchases, which can be extended to other purchases. Originality/value The article offers a new perspective on establishing VAIs as strategically important market-facing devices by examining consumer relationships with VAIs and offering valuable insights on how consumer emotional attachment with VAIs results in satisfaction and intention to repurchase using VAIs.

Accumulation of misfolded proteins in endoplasmic reticulum (ER) generates a stress condition in the cell. The cell combats ER stress by activating unfolded protein response (UPR) and ERAD (ER stress-associated degradation) pathway. Failure to restore favorable folding environment results in cell dysfunction and apoptosis. Various neurodegenerative disorders are characterized by the accumulation of misfolded protein, protein aggregates, and ER stress. GNE myopathy (GNEM) is a neuromuscular disorder pathologically characterized by rimmed vacuole formation due to the accumulation of protein aggregates. More than 200 mutations in key sialic acid biosynthetic enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) have been identified worldwide in the muscle biopsies of GNE myopathy patients. However, the cellular and molecular pathomechanism leading to the disease ar poorly understood. In the present study, the phenomenon of ER stress has been elucidated in GNE mutant cells overexpressing GNE mutations of Indian origin. The effect of GNE mutations on activation of UPR signaling via inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE-1), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor-6 (ATF6) were deciphered to understand the effect of GNE mutations on these proteins. GRP78 was upregulated with increased X-box-binding protein-1 (XBP-1) splicing and CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) upregulation leading to increased apoptosis of GNE mutant cells. Insulin-like growth factor 1 (IGF-1) ligand rescued the cells from apoptotic phenotype by supporting cell survival mechanism. Our study indicates a balance of cell death and survival that decides cell fate and offers potential therapeutic targets to combat ER stress in diseases associated with dysfunctional UPR pathway.

Management of Acute Promyelocytic Leukemia (APML) has improved drastically after the introduction of ATRA (All-trans-retinoic acid) and Arsenic trioxide (ATO). The use of APML-4 protocol has shown its effectiveness in Australian population. We know that high-risk APML represents a subset with poor outcomes. There is scarcity of literature reporting outcomes of high-risk APML from India. We present a 5-year retrospective analysis of the safety and efficacy of APML-4 protocol in our 28 high-risk patients. Of 28 patients, there were 8(28.5%) early deaths; all 20 patients (100%) who were alive achieved hematologic complete remission post-induction and molecular complete remission post-consolidation. The 5-year disease free survival, failure free survival (FFS) and overall survival were 100%, 69% and 69% respectively. Factors affecting FFS were age > 45 years (p = 0.008), baseline ECOG-PS > 1 (p

BCR-ABL Tyrosine kinase inhibitors (TKI's) are most successful of targeted therapies and are currently considered the cornerstone in the management of patients with chronic myeloid leukemia (CML). A recent study reported excellent outcomes of Dasatinib 50mg with better sustained response. Therefore, we aim to evaluate the molecular responses and safety of upfront Dasatinib 50mg in Indian CML-Chronic Phase patients.It was an observational single-centre study. CML-CP patients started on Dasatinib 50mg daily were offered to participate in this study. Data of imatinib was collected retrospectively as a comparator group.Between June 2020 to Feb 2022, fifty patients were included in the dasatinib 50mg once daily group. Median age was 40 yrs. ranging from (19 to73) years. At a median follow up of 9.2 months, 49 patients completed three months treatment, out of which 48 patients were evaluated as one patient stopped medication after a month due to financial constraints. The response rate at three months for dasatinib 50mg daily and Imatinib were 68.75% and 69.7% respectively. At 12 months, 68% and 66.6% patients achieved major molecular response [MMR] in dasatinib 50mg and imatinib groups respectively.In conclusion, low dose dasatinib is safe and effective as an upfront therapy in CML-CP. Early molecular response [EMR] rates were comparable in low dose dasatinib and imatinib arm but deep molecular responses were significantly higher in low dose dasatinib arm. Dasatinib, taken daily at a dose of 50mg, may offer a new, alternative choice as generic versions are available now for frontline therapy in CML-CP.

COVID-19, caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization on March 9, 2020. Hematopoietic stem-cell transplantation (HSCT) recipients may be highly susceptible to infection and related pulmonary complications due to nascent immune systems or organ damage from treatment-related toxicities. Poor outcomes in such group of patients were linked to older age, steroid therapy at the time of COVID-19 infection, and COVID-19 infection within a year of HSCT. We studied a cohort of 28 hematopoietic stem cell transplant recipients (male 17, M:F ratio of 1.5) with COVID-19 infection from 1st June 2020, through 31st December 2020 for outcome. Fever was the most common symptom at the time of presentation in 22 (78.5%) patients. Mortality rate at Day 28 and Day 42 was found to be 4/28 (14.3%) and 7/28 (25%) respectively. Patients within one year of HSCT and severe infection had higher day 28 mortality (with p values = 0.038)". There was no relation of mortality with type of transplant.

Busulfan and cyclophosphamide (BuCy)-based regimen has been used as a standard myeloablative chemotherapy for haematopoietic stem cell transplantation in thalassemia. However, treosulfan-based conditioning regimen has emerged due to concerns of toxicities. We retrospectively analysed the safety and efficacy of fludrabine/Bu/Cy/antithymocyte globulin (ATG) versus treosulfan/thiotepa/fludrabine regimens for Hematopoietic Stem Cell Transplant (HSCT) in transfusion-dependent thalassemia (TDT) conducted at our institute (2013-2021). In 75 patients, 36 (48%) received Flu/Bu/Cy/ATG whereas 39 (52%) received Treo/Thio/Flu. Median age was 6 (1-12) and 9 (1-15) years, respectively. Number of patients with Classes I, II, and III were 14, 10, and 12 in Flu/Bu/Cy/ATG versus 2, 19, and 18 in Treo/Thio/Flu group, respectively. Graft was growth factor mobilized bone marrow in Flu/Bu/Cy/ATG versus peripheral blood stem cell in Treo/Thio/Flu group. Mean stem cell dose was 3.82 (2.2-9.1) versus 5 (1.65-8.01) 10

Pharmacokinetics of cyclophosphamide has been explored to optimize conditioning dosing. We hypothesized that post-transplant cyclophosphamide (PTCy) metabolite carboxy-ethyl phosphoramide mustard (CEPM) pharmacokinetics might impact haploidentical transplantation (haplo-HCT) outcomes. CEPM area under the curve (AUCsub0-48/sub) was determined by eleven sampling timepoints on day +3/+4 using LC-MS/MS. The median CEPM AUCsub0-48/subin a cohort of 30 patients was 14.2 (14) mg·hr/L. The incidence of severe chronic graft-versus-host disease (GVHD) (73% vs. 11%,ip/i = 0.02), and GVHD-/relapse-free survival (GRFS) was significantly inferior in the CEPM AUCsub0-48/sublt; 14 mg·hr/L group (54 days vs. 344 days,ip/i = 0.02). There was, however, no difference in grade III-IV acute GVHD (38% vs. 14%,ip/i = 0.12) and overall survival (295 days vs. not reached,ip/i = 0.2). CEPM AUCsub0-48,/subis associated with severe chronic GVHD and GRFS post-haplo-HCT in this exploratory study. There is scope for personalizing day + 4 PTCy dose based on day + 3 CEPM AUCsub0-8/sub.

O-GlcNAc transferase (OGT) is a nutrient-sensitive glycosyltransferase that is overexpressed in prostate cancer, the most common cancer in males. We recently developed a specific and potent inhibitor targeting this enzyme, and here, we report a synthetic lethality screen using this compound. Our screen identified pan-cyclin-dependent kinase (CDK) inhibitor AT7519 as lethal in combination with OGT inhibition. Follow-up chemical and genetic approaches identified CDK9 as the major target for synthetic lethality with OGT inhibition in prostate cancer cells. OGT expression is regulated through retention of the fourth intron in the gene and CDK9 inhibition blunted this regulatory mechanism. CDK9 phosphorylates carboxy-terminal domain (CTD) of RNA Polymerase II to promote transcription elongation. We show that OGT inhibition augments effects of CDK9 inhibitors on CTD phosphorylation and general transcription. Finally, the combined inhibition of both OGT and CDK9 blocked growth of organoids derived from patients with metastatic prostate cancer, but had minimal effects on normal prostate spheroids. We report a novel synthetic lethal interaction between inhibitors of OGT and CDK9 that specifically kills prostate cancer cells, but not normal cells. Our study highlights the potential of combining OGT inhibitors with other treatments to exploit cancer-specific vulnerabilities.Implications:The primary contribution of OGT to cell proliferation is unknown, and in this study, we used a compound screen to indicate that OGT and CDK9 collaborate to sustain a cancer cell–specific pro-proliferative program. A better understanding of how OGT and CDK9 cross-talk will refine our understanding of this novel synthetic lethal interaction.

Purpose This study aims to assess factors influencing customers’ online grocery shopping experiences, and it evaluates the central role of customer service and consumers’ responses to satisfying grocery shopping. Design/methodology/approach A mixed-methods approach was used; linguistic inquiry and the word count (LIWC) method captured qualitative aspects of consumers’ grocery shopping experience, whereas partial least square-structure equation modeling tested hypotheses regarding antecedents to consumers’ overall online grocery shopping experience. Findings The PLS-based analysis confirmed the qualitative insights, establishing the significance of customer service, which accounted for 68% variance in the overall experience and 42% variance in customer satisfaction, along with other experience antecedents such as website, product and delivery. Research limitations/implications Future researchers could further analyze experience as a dynamic process focusing on consumer and retailer brand-focused constructs, specifically focusing on creating a holistic understanding of customer service that establishes coherence between retailers’ marketing values and their customer service. Practical implications Managers should acknowledge the importance of customer service in creating a satisfying customer experience, and they should respond to consumer concerns, resulting in enhanced brand-related experience. Originality/value Responding to the call for a better understanding of customer service, this study brings out the challenges online grocery shoppers are facing in terms of customer service and empirically establishes customer service as a key driver of customer experience, thereby extending the earlier work on customer service and online customer experience.

We have developed a graphical user interface for our Gen2Epi computational pipeline named Gen2EpiGUI. A total of 594 published whole-genome sequence datasets of Neisseria gonorrhoeae were used to validate the program. Gen2Epi facilitates an understandable analysis of N. gonorrhoeae whole-genome sequence data for users with limited bioinformatics skills.

Purpose The purpose of this paper is to add to current knowledge of online customer experience (OCE) by examining various drivers and outcomes of online grocery shopping experience that can help researchers and retailers answer the pressing question: “Why do online grocery customers stay or switch?” Design/methodology/approach This study applied netnography and critical incident analysis to a pool of 1,004 reviews captured from forum and review sites dedicated to online grocery shopping. Findings Two broad dimensions of OCE, four attributes and 13 factors corresponding to shoppers’ psychological states and their utilitarian and hedonic orientations emerged from the data analysis. The proposed framework, containing these four attributes and corresponding 13 factors, captures the consumers’ intention to stay with the current retailer or switch. Research limitations/implications The study contributes to existing knowledge of OCE by providing a dynamic and yet holistic framework that encompasses experiential states and utilitarian or hedonic orientations in an online grocery context. Although its contributions are valuable to both researchers and practitioners, further quantitative analysis is needed to validate the findings. Practical implications In addition to providing superior customer experience by implementing the various drivers of OCE identified here, online grocery retailers can use the study findings as a strategic guide toward building a frictionless and pleasurable shopping experience. Originality/value The study employs netnography and critical incident technique to identify experiential attributes such as reliability, responsiveness, return and refund, which are unique OCE attributes in online grocery, a relatively unexamined field of retailing.

Background: Wireless Sensor Network (WSN) is among the most promising technologies that can be used to monitor crucial ambient conditions. WSNs are capable of effectively monitoring the environmental parameters and any habitat necessary to be investigated. Sometimes, it is very important to periodically monitor the critical environmental parameters such as humidity, temperature, soil moisture, fire, volcanic eruptions, Tsunamis, seismic waves and many more to react proactively to save lives and assets. This research work is an endeavor to present the importance and to determine the precise inter- nodal distance required for distinct applications. The networks of the different terrain area and internodal distance are deployed to evaluate and analyze the performance metrics such as a number of messages received average end to end delay (secs), throughput (bps) and jitter (secs). The influence of varying inter-nodal distance on the performance of WSN is determined to select the most appropriate value of the distance between nodes in particular monitoring application. The patents related to the topology based analysis of wireless nodes are reconsidered. Methods: The placement of nodes and inter-nodal distance significantly influences the operation and performance of WSNs by diverging the ability of sensors to observe an event of interest and transmission of information to data aggregation nodes (sink nodes). Moreover, effective sensor placement also affects the resource management. The investigation of specific regions and habitats has peculiar constraints of node placement and inter-nodal distance making it highly application specific. In this research work, the intent is to monitor an entire area to attain optimum coverage to detect the occurrence of a significant event. The node placement and inter-nodal distance can be classified on the basis of the role played by the deployed nodes, like, placement of ordinary sensor nodes/Reduced Function Devices (RFDs) and relay nodes/Full Function Devices (FFDs), respectively. The sensors are compatible with IEEE 802.15.4/ZigBee protocol and application implemented is Constant Bit Rate (CBR) generator. This paper analyzed and evaluated the influence of placement and inter-nodal distance of RFDs to the data aggregation ability of sink node. The terrain area (m2) of different sensor networks deployed are 110×110, 200×200, 300×300, 400×400 and 500×500, respectively. The number of sensor nodes is constant equal to 100 to evaluate their ability to provide optimum performance. The parameter internodal distance is varied, keeping all other parameters constant to effectively evaluate its influence. The simulations are carried out on QualNet 6.1 simulator. Results: The variation in inter-nodal distance significantly influences the performance metrics of the network such as the number of messages received, average end to end delay, throughput and jitter. In this paper, the distance between sensor nodes and terrain areas of grid topology is varied accordingly to deduce that which value of the inter-nodal distance and network provides optimum performance. The thorough evaluation of the simulation results presented that the inter-nodal distance of 30 m and terrain area of 300×300 m2 has generated optimum performance by providing the highest number of messages received (208) and highest throughput (2544.34 bps). It is also capable of providing minimum end to end delay (14.45 secs) and lowest jitter (6.67 secs). Conclusion: The objective of this paper to determine the optimum inter-nodal distance and terrain area of a WSN of 100 nodes is successfully achieved. It is analyzed and evaluated that the inter-nodal distance of 30 m and terrain area of 300×300 m2 enhance and optimize the network performance significantly.

BackgroundSeven structurally related β-lactamase-producing plasmids have been characterized in penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates. We characterized a variant (i.e. pJRD20, Canada type) of the Africa-type (pJD5) plasmid isolated from N. gonorrhoeae strain 8903.ObjectivesTo compare the DNA sequence of pJRD20 with that of pJD5 and pJD4 (Asia-type) and their TEM-1 β-lactamases.MethodsN. gonorrhoeae 8903 was identified as part of the Gonococcal Antimicrobial Surveillance Program in Canada. β-Lactamase production was assessed using nitrocefin. MICs were determined by agar dilution and Etest methods (CLSI). The DNA sequences of pJRD20, pJD5 and pJD4 were assembled and annotated. The structure of TEM-1 and its penicillin-binding properties were determined by in silico molecular modelling and docking. TEM-1 proteins were characterized by western blot, mass spectrometry and ampicillin hydrolysis assays.ResultsN. gonorrhoeae 8903 exhibited intermediate susceptibility to penicillin with slow β-lactamase activity (i.e. 35 min to hydrolyse nitrocefin). Except for a novel 6 bp deletion starting at the G of the ATG start codon of blaTEM-1, the DNA sequence of pJRD20 was identical to that of pJD5. The TEM-1 β-lactamase produced by pJRD20 is 24 kDa and hydrolyses ampicillin only after several hours.ConclusionsThis unusual PPNG isolate might have been characterized as a non-PPNG owing to its low MIC of penicillin and its very slow hydrolysis of nitrocefin. Given the unusual nature of its TEM-1 β-lactamase, laboratories might consider extending the duration of nitrocefin hydrolysis assays.

This study questions the unharmonious ways of product displays in online grocery retailing and aims to find if visual complexity of the product display has any impact on behavioral outcomes of onli...

Pneumocystis jirovecii pneumonia (PJP) is infrequently found in patients with acute myeloid leukemia (AML) whereas its more commonly found in lymphoid malignancies like acute lymphoblastic leukemia and various lymphomas. AML patients are conventionally treated with intensive chemotherapeutic regimen which includes Daunorubicin, Idarubicin, Cytarabine and various other drugs. Trimethoprim/Sulfamethoxazole prophylaxis is not routinely administered to such patients. In recent years, targeted therapies like Venetoclax which is a Bcl-2 inhibitor have been introduced for AML treatment which is given in combination with other chemotherapy and targeted molecules. There is tremendous use of Venetoclax for AML recently specially in unfit and elderly population. We are witnessing this uncommon infection more commonly in those patients treated with Venetoclax based therapy. We report the case series of five patients of AML who were treated with Venetoclax based therapy and had subsequently developed PJP leading to death in four of them. The incidence of PJP was 13.2% among the patients treated with Venetoclax based treatment at our institution in that timeframe. The low index of suspicion led to delay in diagnosis and thereby treatment. Such an association of Venetoclax and Pneumocystis jirovecii pneumonia has not been reported till date, so this prompts for early detection and treatment of this potentially life threatening but treatable infection. So the role of routine prophylaxis with Trimethoprim/Sulfamethoxazole in those receiving Venetoclax based therapy in AML patients merits a thought.

Whole-genome sequencing (WGS) data are well established for the investigation of gonococcal transmission, antimicrobial resistance prediction, population structure determination and population dynamics. A variety of bioinformatics tools, repositories, services and platforms have been applied to manage and analyze Neisseria gonorrhoeae WGS datasets. This review provides an overview of the various bioinformatics approaches and resources used in 105 published studies (as of 30 April 2021). The challenges in the analysis of N. gonorrhoeae WGS datasets, as well as future bioinformatics requirements, are also discussed.

In the Bénard convection governed nanofluid confined between two horizontal infinite free-free boundaries, the effect of Hall current is investigated when it is subjected to the constant vertical magnetic field. The Buongiorno mathematical model for hydromagnetic flow with Hall currents has been considered. The Brownian motion effects and thermophoresis of nanoparticles have been included in the energy equation. A realistic boundary condition based on zero nanoparticle mass flux at the walls is incorporated for the analysis. The impacts of Brownian motion, convective heat transfer, thermophoresis of nanoparticles and zero mass flux conditions are also deliberated through the behaviour of the related parameters. The parameters representing the model incorporate the consequences of newly introduced physically realistic boundary conditions and Hall currents. For comprehensive physical interpretation the embedded parameters have been plotted and deliberated graphically. It is found that Hall current is responsible to enhances the instability of the system and sets the convection earlier. A rigorous comparison has been made with the existing results. The results are shown graphically and verified numerically.

Depending on each institution's laboratory test, mean serum calcium levels range between 8.8 and 10.8 mg/dL and hypercalcemia is defined as two standard deviations above the mean. According to recent epidemiological studies, 90% of cases of hypercalcemia are due to hyperparathyroidism or malignancy. Milk Alkali syndrome (MAS) also known as Calcium Alkali syndrome (CAS) is the third biggest cause of hypercalcemia, but its incidence seems to be higher than previously thought. Here we present a case of Calcium Alkali Thiazide syndrome (CATS) in a 57-year-old female who was on calcium and vitamin D supplements (after parathyroidectomy) while also taking thiazide diuretic for hypertension. She was brought to the ED with nausea, vomiting, confusion, difficulty walking along with numbness in extremities. She had parathyroidectomy three weeks ago. During history taking, patient reported intake of calcium carbonate 1 g three times daily, calcitriol 0.5 mcg twice daily, cholecalciferol (vitamin D3) 10,000 units once daily, chlorthalidone 25 mg once daily and irbesartan 300 mg once daily. At admission, her calcium level was 23 mg/dL, ionized calcium 12.03 mg/dL, pH was 7.59 and HCO3 was 33. She was in renal failure with creatinine of 1.9 mg/dL (baseline 0.8 mg/dL). Her parathyroid hormone (PTH) level was 0. A diagnosis of CATS was made. She was treated with intravenous fluids and furosemide and discharged home on hospital day 5 after her calcium and creatinine levels normalized. A triad of hypercalcemia, acute kidney injury and metabolic alkalosis comprises MAS. Traditional MAS was caused by "Sippy diet" (containing milk and alkali) used for the treatment of peptic ulcer disease. Over the decades, the same triad of symptoms occurred in patients using excess calcium and vitamin D, hence changing the name to CAS. A subset of patients at risk for CAS also use thiazide diuretics for hypertension, making them more vulnerable to hypercalcemia and acute kidney injury. In such subset of patients, it is preferable to use the term CATS rather than MAS or CAS.

Human genital infections are one of the most concerning issues worldwide and can be categorized into sexually transmitted, urinary tract and vaginal infections. These infections, if left untreated, can disseminate to the other parts of the body and cause more complicated illnesses such as pelvic inflammatory disease, urethritis, and anogenital cancers. The effective treatment against these infections is further complicated by the emergence of antimicrobial resistance in the genital infection causing pathogens. Furthermore, the development and applications of single-cell sequencing technologies have open new possibilities to study the drug resistant clones, cell to cell variations, the discovery of acquired drug resistance mutations, transcriptional diversity of a pathogen across different infection stages, to identify rare cell types and investigate different cellular states of genital infection causing pathogens, and to develop novel therapeutical strategies. In this chapter, I will provide a complete review of the applications of single-cell sequencing in human genital infections before discussing their limitations and challenges.

A significant proportion of T cell acute lymphoblastic leukemia (T-ALL) patients do not achieve complete remission after 4 weeks of induction chemotherapy or relapse early. Salvage chemotherapy for such patients usually results in poor outcome which can be up to 20–30% survival with allogeneic BMT. Nelarabine combined with chemotherapy, in COG AALL0434 study, showed 4-year disease-free survival of 54.8% in patients with primary refractory T ALL. An allogeneic BMT in such patients may further improve outcome. In this report, three patients with primary refractory T cell ALL including a case of ETP-ALL and near ETP-ALL were treated with Nelarabine combined with COG based regime and thereafter an allogeneic stem cell transplantation. All three patients achieved a complete remission with negative minimal residual disease status with one course of therapy, received allo SCT (MSD = 2, Haplo = 1) and are surviving in complete remission at 12 months, 14 months and 25 months of follow up. This report highlights that primary refractory T ALL patient can be successfully treated with Nelarabine in combination with chemotherapy and consolidation with allogeneic SCT to provide maximum chances of long-term survival and cure.

Soret–Dufour phenomenon in a Darcy–Maxwell Brownian nanofluid is performed using a macroscopic filtration model, suggested by Alishayev (Hydromechanics 3:166–174, 1974). For nanoparticle flux at the boundaries passive management, influenced by the management of concentration flux assumed in Stefan’s flow, is considered. Normal mode technique is used to analyse the stationary and oscillatory convections under the linear stability theory. The effects of different phenomenon are quantified by dimensionless parameters. It is found that the Soret parameter has dual behaviour for stationary convection and destabilizing behaviour for oscillatory convection, whereas the Dufour parameter has a stabilizing effect for both stationary and oscillatory convections. Nonlinear stability analysis provides the behaviour of flux of heat, salt and nanoparticles in the flow field through $${\text{Nu}}$$ , $${\text{Nu}}_{C}$$ and $${\text{Nu}}_{\phi }$$ . Steady and unsteady convections are discussed. A graphical representation of streamlines, isotherms, isohalines and flow lines of nanoparticles concentrations is presented.