Artificial intelligence augmented home sleep apnea testing device study (AISAP study).

STUDY OBJECTIVE: This study aimed to prospectively validate the performance of an artificially augmented home sleep apnea testing device (WVU-device) and its patented technology. METHODOLOGY: The WVU-device, utilizing patent pending (US 20210001122A) technology and an algorithm derived from cardio-pulmonary physiological parameters, comorbidities, and anthropological information was prospectively compared with a commercially available and Center for Medicare and Medicaid Services (CMS) approved home sleep apnea testing (HSAT) device. The WVU-device and the HSAT device were applied on separate hands of the patient during a single night study. The oxygen desaturation index (ODI) obtained from the WVU-device was compared to the respiratory event index (REI) derived from the HSAT device. RESULTS: A total of 78 consecutive patients were included in the prospective study. Of the 78 patients, 38 (48%) were women and 9 (12%) had a Fitzpatrick score of 3 or higher. The ODI obtained from the WVU-device corelated well with the HSAT device, and no significant bias was observed in the Bland-Altman curve. The accuracy for ODI > = 5 and REI > = 5 was 87%, for ODI> = 15 and REI > = 15 was 89% and for ODI> = 30 and REI of > = 30 was 95%. The sensitivity and specificity for these ODI /REI cut-offs were 0.92 and 0.78, 0.91 and 0.86, and 0.94 and 0.95, respectively. CONCLUSION: The WVU-device demonstrated good accuracy in predicting REI when compared to an approved HSAT device, even in patients with darker skin tones.

Three-years of dalbavancin use at a UK tertiary referral hospital serving a population with high numbers of people who inject drugs.

Background: Dalbavancin's unique properties have led to an increase in its off-licence use in complex infection and in vulnerable populations including people who inject drugs (PWID), but data remain limited. In this retrospective cohort study, we describe the characteristics, treatment rationale and outcomes for all adult inpatients treated with dalbavancin at a UK tertiary hospital. Results: Fifty-eight inpatients were treated with dalbavancin between 1 January 2018 and 1 January 2021, 98.3% for off-licence diagnoses. Acute bacterial skin and skin structure infection, infective endocarditis and endovascular infections were each diagnosed in 22.4% of patients. Bone and joint infections were diagnosed in 18.9%, discitis in 12.1% and central line-associated bloodstream infections in 5.2%. Sixty-nine percent of patients were bacteraemic; 52.5% Staphylococcus aureus, 5.0% MRSA. Two mild adverse reactions were attributed to dalbavancin. Treatment was successful in 43 (75.4%) patients, and failed in seven (12.3%). Seven (12.3%) were lost to follow-up.Thirty-five patients (60.3%) were PWID, with low median age (41.0 years) and Charlson Comorbidity scores (0). Self-discharge was taken by 17.1% of PWID, and 20.6% were lost to follow-up. At 90 days, three (8.6%) PWID were deceased. Conclusions: In this first UK cohort, dalbavancin was used off licence and in persons facing barriers to conventional therapies. Where data is available, it was safe and effective. Dalbavancin appears a potentially valuable tool in improving outcomes for PWID.

Polatuzumab vedotin, venetoclax, and an anti-CD20 monoclonal antibody in relapsed/refractory B-cell non-Hodgkin lymphoma.

The Phase 2 portion of this study evaluated safety and efficacy of polatuzumab vedotin 1.8 mg/kg and venetoclax 800 mg, plus fixed-dose obinutuzumab 1000 mg or rituximab 375 mg/m2 in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), respectively. Patients with complete response (CR) or partial response (PR)/stable disease (FL) or CR/PR (DLBCL) at end of induction (EOI; six 21-day cycles) received post-induction therapy with venetoclax and obinutuzumab or rituximab, respectively. Primary endpoint was CR rate at EOI. Safety-evaluable populations included 74 patients (FL cohort; median age 64 years; progression of disease within 24 months on first-line treatment, 25.7%; FL International Prognostic Index 3-5, 54.1%; ≥2 previous therapies, 74.3%) and 57 patients (DLBCL cohort; median age 65 years; International Prognostic Index 3-5, 54.4%; ≥2 previous therapies, 77.2%). The most common non-hematologic adverse events (mostly Grades 1-2) in the FL and DLBCL cohorts were diarrhea (55.4% and 47.4%, respectively) and nausea (47.3% and 36.8%); neutropenia was the most common Grades 3-4 toxicity (39.2% and 52.6%). Efficacy-evaluable populations included patients treated at the recommended Phase 2 dose (FL, n = 49; DLBCL, n = 48). CR rates at EOI were 59.2% (FL) and 31.3% (DLBCL); median progression-free survival was 22.8 months (95% confidence interval [CI], 14.5-not evaluable) and 4.6 months (95% CI, 3.6-8.1), respectively. Polatuzumab vedotin plus venetoclax and obinutuzumab/rituximab had acceptable safety in patients with R/R FL or DLBCL, with promising response rates in R/R FL, including high-risk patients.

Optical sensing for real-time detection of food-borne pathogens in fresh produce using machine learning.

Contaminated fresh produce remains a prominent catalyst for food-borne illnesses, prompting the need for swift and precise pathogen detection to mitigate health risks. This paper introduces an innovative strategy for identifying food-borne pathogens in fresh produce samples from local markets and grocery stores, utilizing optical sensing and machine learning. The core of our approach is a photonics-based sensor system, which instantaneously generates optical signals to detect pathogen presence. Machine learning algorithms process the copious sensor data to predict contamination probabilities in real time. Our study reveals compelling results, affirming the efficacy of our method in identifying prevalent food-borne pathogens, including Escherichia coli (E. coli) and Salmonella enteric, across diverse fresh produce samples. The outcomes underline our approach's precision, achieving detection accuracies of up to 95%, surpassing traditional, time-consuming, and less accurate methods. Our method's key advantages encompass real-time capabilities, heightened accuracy, and cost-effectiveness, facilitating its adoption by both food industry stakeholders and regulatory bodies for quality assurance and safety oversight. Implementation holds the potential to elevate food safety and reduce wastage. Our research signifies a substantial stride toward the development of a dependable, real-time food safety monitoring system for fresh produce. Future research endeavors will be dedicated to optimizing system performance, crafting portable field sensors, and broadening pathogen detection capabilities. This novel approach promises substantial enhancements in food safety and public health.

Early recognition and treatment of OSA in hospitalized patients and its impact on health care utilization in rural population: a real-world study.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a highly prevalent, yet under-diagnosed condition. Due to its adverse impact on risk for cardiopulmonary disorders, there is interest in pro-active screening of OSA in hospitalized patients. We studied the long-term outcome of such screened patients who were initiated on positive airway pressure (PAP) therapy. METHODS: Hospitalized patients who screened positive for OSA and were confirmed with post-discharge polysomnography (PSG) were dichotomized by PAP adherence and followed for a period of 12 months to evaluate for the composite endpoint of hospital readmissions and emergency room (ED) visits for cardiopulmonary reasons. Cost analysis between the two groups was also conducted. RESULTS: 2042 hospitalized patients were assessed for OSA as part of a hospital sleep medicine program from August 2019 to June 2023. Of these, 293 patients were diagnosed with OSA and prescribed PAP therapy. Of these 293 patients, 108 were adherent to therapy and 185 were non-adherent. The overall characteristics of the groups included a mean (SD) age: 58 years (12.82), mean BMI (kg/m2): 39.72 (10.71), male sex: 57%, and apnea-hypopnea index (AHI): 25.49 (26). 78%, 41% and 43% had hypertension, congestive heart failure, and diabetes mellitus, respectively.The composite endpoint of hospital readmissions and ED visits for cardiovascular and pulmonary reasons was significantly higher in the non-adherent group as compared to the adherent group (HR: 1.24, 95% CI: 1-1.54) (p=0.03). The cost of care for both hospital billing (HB) as well as professional billing(PB) was higher for the non-adherent group ($1455.6 vs $1723.5, p = 0.004) in HB cost and $130.9 vs $144.7, p<0.001) in PB. Length of stay was higher for non-adherent patients (2.7 ± 5.1 days vs. 2.3 ± 5.9 days). CONCLUSIONS: Hospitalized patients diagnosed with OSA and adherent to therapy have reduced readmissions and ED visits for cardiopulmonary reasons 12 months after discharge. Adherent patients have reduced cost of health care and length of stay during hospitalizations.

Flame retardant tetrabromobisphenol A (TBBPA) disrupts histone acetylation during zebrafish maternal-to-zygotic transition.

3,3',5.5'-Tetrabromobisphenol A (TBBPA) is a widely used brominated flame-retardant utilized in the production of electronic devices and plastic paints. The objective of this study is to use zebrafish as a model and determine the effects of TBBPA exposure on early embryogenesis. We initiated TBBPA exposures (0, 10, 20 and 40µM) at 0.75 h post fertilization (hpf) and monitored early developmental events such as cleavage, blastula and epiboly that encompass maternal-to-zygotic transition (MZT) and zygotic genome activation (ZGA). Our data revealed that TBBPA exposures induced onset of developmental delays by 3 hpf (blastula). By 5.5 hpf (epiboly), TBBPA-exposed (10-20 µM) embryos showed concentration-dependent developmental lag by up to 3 stages or 100% mortality at 40 µM. Embryos exposed to sublethal TBBPA concentrations from 0.75-6 hpf and raised in clean water to 120 hpf showed altered larval photomotor response (LPR), suggesting a compromised developmental health. To examine the genetic basis of TBBPA-induced delays, we conducted mRNA-sequencing on embryos exposed to 0 or 40 µM TBBPA from 0.75 hpf to 2, 3.5 or 4.5 hpf. Read count data showed that while TBBPA exposures had no overall impacts on maternal or maternal-zygotic genes, collective read counts for zygotically activated genes were lower in TBBPA treatment at 4.5 hpf compared to time-matched controls, suggesting that TBBPA delays ZGA. Gene ontology assessments for both time- and stage-matched differentially expressed genes revealed TBBPA-induced inhibition of chromatin assembly- a process regulated by histone modifications. Since acetylation is the primary histone modification system operant during early ZGA, we immunostained embryos with an H3K27Ac antibody and demonstrated reduced acetylation in TBBPA-exposed embryos. Leveraging in silico molecular docking studies and in vitro assays, we also showed that TBBPA potentially binds to P300- a protein that catalyzes acetylation- and inhibits P300 activity. Finally, we co-exposed embryos to 20 µM TBBPA and 50 µM n-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide (CTPB) -a histone acetyltransferase activator that promotes histone acetylation- and showed that TBBPA-CTPB co or pre-exposures significantly reversed TBBPA-only developmental delays, suggesting that TBBPA-induced phenotypes are indeed driven by repression of histone acetylation. Collectively, our work demonstrates that TBBPA disrupts ZGA and early developmental morphology, potentially by inhibiting histone acetylation. Future studies will focus on mechanisms of TBBPA-induced chromatin modifications.

Dynamic alterations in physiological and biochemical indicators of Cirrhinus mrigala hatchlings: A sublethal exposure of triclosan.

Triclosan (TCS), a biocide used in various day-to-day products, has been associated with several toxic effects in aquatic organisms. In the present study, biochemical and hematological alterations were evaluated after 14 d (sublethal) exposure of tap water (control), acetone (solvent control), 5, 10, 20, and 50 µg/L (environmentally relevant concentrations) TCS to the embryos/hatchlings of Cirrhinus mrigala, a major freshwater carp distributed in tropic and sub-tropical areas of Asia. A concentration-dependent increase in the content of urea and protein carbonyl, while a decrease in the total protein, glucose, cholesterol, triglycerides, uric acid, and bilirubin was observed after the exposure. Hematological analysis revealed a decrease in the total erythrocyte count, hemoglobin, and partial pressure of oxygen, while there was an increase in the total leucocyte count, carbon dioxide, and partial pressure of carbon dioxide and serum electrolytes. Comet assay demonstrates a concentration-dependent increase in tail length, tail moment, olive tail moment, and percent tail DNA. An amino acid analyzer showed a TCS-dose-dependent increase in various amino acids. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis revealed different proteins ranging from 6.5 to 200 kDa, demonstrating TCS-induced upregulation. Fourier transform infrared spectra analysis exhibited a decline in peak area percents with an increase in the concentration of TCS in water. Curve fitting of amide I (1,700-1600 cm-1) showed a decline in α-helix and turns and an increase in ß-sheets. Nuclear magnetic resonance study also revealed concentration-dependent alterations in the metabolites after 14 d exposure. TCS caused alterations in the biomolecules and heamatological parameters of fish, raising the possibility that small amounts of TCS may change the species richness in natural aquatic habitats. In addition, consuming TCS-contaminated fish may have detrimental effects on human health. Consequently, there is a need for the proper utilisation and disposal of this hazardous compound in legitimate quantities.

Cellulose Sulfate Nanofibers for Enhanced Ammonium Removal.

In this study, a sulfonation approach using chlorosulfonic acid (CSA) to prepare cellulose sulfate nanofibers (CSNFs) from raw jute fibers is demonstrated. Both elemental sulfur content and zeta potential in the CSNFs are found to increase with increasing CSA content used. However, the corresponding crystallinity in the CSNFs decreases with the increasing amount of CSA used due to degradation of cellulose chains under harsh acidic conditions. The ammonium adsorption results from the CSNFs with varying degrees of sulfonation were analyzed using the Langmuir isotherm model, and the analysis showed a very high maximum ammonium adsorption capacity (41.1 mg/g) under neutral pH, comparable to the best value from a synthetic hydrogel in the literature. The high ammonium adsorption capacity of the CSNFs was found to be maintained in a broad acidic range (pH = 2.5 to 6.5).

Pre-clinical and cellular safety assessment of oral administered DHA rich microalgae oil from Schizochytrium sp. (Strain ATCC-20889): acute, sub-chronic and genotoxicity.

The lack of toxicity data for DHA-rich oil from Schizochytrium sp. (Strain ATCC-20889) leads to its exclusion from the Qualified Presumption of Safety list. Therefore, present study addresses toxicity evaluation of DHA-rich microalgae oil using ex-vivo (cytotoxicity assay) and in-vivo methods (acute (OECD 423 guidelines), sub-chronic (OECD 452 guidelines), and genotoxicity assay). The ex-vivo results showed >90% cell viability of Caco-2 cells after 48 h of treatment (200 µg/mL of DHA). Additionally, the in-vivo acute toxicity study found that microalgae oil was nontoxic and classified under category 5 molecule according to OECD 423 guidelines with a highest degree of safety at 2000 mg/kg b.w. The in-vivo sub-chronic study revealed no significant mortality and changes in feed intake, body weight, haematological, biochemical, neurological, and urine parameters after repeated 180-days administration of DHA-rich microalgae oil at 250 mg/kg, 500 mg/kg, and 1000 mg/kg. Moreover, histopathology evaluation, comet assay, chromosomal aberration, and micronuclei assay also confirmed the nontoxic behavior of DHA-rich oil. Thus, the results from the ex-vivo and in-vivo studies indicate that DHA-rich oil from Schizochytrium sp. (Strain ATCC-20889) is safe for use as a novel food, and can be included in infants, adults, pregnant women, and children formula.

Secondary Structure Analysis of Fasciola from Semi-wild Ruminants of Northeast India.

PURPOSE: The objective of this study is to study the secondary structure analysis of Fasciola flukes from a rare mithun host from Manipur. Fascioliasis, a neglected tropical trematodiasis, is poorly studied in India and is widely believed to be predominantly caused by F. gigantica. Through this study, we want to assess the flukes from the rare semi-wild ruminants of Northeast India. This study is important as the mithun population is semi-wild and its population is declining in Manipur. METHODS: Sample collected from the difficult and challenging terrain of Northeast India. The sample was collected from mithun and observed under the microscope. DNA was isolated, sequenced, and analyzed using various bioinformatics tools. The secondary structure analysis of the Internal Transcribed Spacer 2 (ITS2) region was also performed. RESULTS: The secondary structure species tree corroborated the Bayesian inference and, hence, strengthened the phylogeny reconstructed. The annotated ITS2 sequence and RNA secondary of the Manipur isolate displayed the typical four-helix or four-domain model. Helix III reveals the presence of the UGGU motif with other deviations like UGG and GGU. CONCLUSION: This is an in-depth analysis of the secondary structure of Fasciola species. The present study has demonstrated the usefulness of ITS2 and its secondary structures for characterizing parasites. The information on fascioliasis in the mithun's population presents itself useful with regards to their conservation strategy as their populations in both Manipur and Nagaland are dwindling.

Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors.

Purpose: To report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. Materials and Methods: In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of MTD determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer. Results: A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥3 adverse events (AEs) were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The overall response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in 2 out of 6 patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%. Conclusion: The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile. (NCT01497704 and NCT02711969).

Synthesis of triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones as anticancer agents and their in silico docking studies.

In the pursuit of novel therapeutic agents, we present a comprehensive study on the design, synthesis, and evaluation of a diverse library of triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones, employing a microwave-assisted synthetic approach via 'click chemistry'. This methodology offers efficient and accelerated access to the glycohybrids, showcasing improved reaction conditions that yield high-quality products. In this research endeavor, we have successfully synthesized a series of twenty-seven triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones. Our investigation extends beyond synthetic endeavors to explore the potential therapeutic relevance of these compounds. We subjected them to rigorous in vitro screening against prominent breast cancer cell lines MCF-7, MDA-MB231, and MDA-MB453. Among the library of compounds synthesized, (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-((5-(4-methoxyphenyl)-7-oxopyrazolo[1,5-a]pyrimidin-1(7H)-yl)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerged as a potent compound, exhibiting remarkable anti-cancer activity with an IC50 value of 27.66 µM against the MDA-MB231 cell line. Additionally, (2S,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-((7-oxo-5-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyrimidin-1(7H)-yl)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate displayed notable inhibitory potential against the MCF-7 cell line, with an IC50 value of 4.93 µM. Furthermore, in silico docking analysis was performed to validate our experimental findings. These findings underscore the promise of our triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones as potential anti-cancer agents. This research not only enriches the field of glycohybrid synthesis but also contributes valuable insights into the development of novel anti-cancer therapeutics.

Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study.

BACKGROUND: Diffuse large B-cell lymphoma comprises nearly 30% of non-Hodgkin lymphoma cases and patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for stem-cell transplantation have few treatment options and poor prognoses. We aimed to determine whether the novel combination of polatuzumab vedotin in combination with rituximab and lenalidomide (Pola+R+Len) would provide a tolerable treatment option with enhanced antitumour response in patients with relapsed or refractory diffuse large B-cell lymphoma. METHODS: This completed phase 1b/2, open-label, multicentre, single-arm study (GO29834) evaluated the safety and efficacy of Pola+R+Len in patients with relapsed or refractory diffuse large B-cell lymphoma at 19 sites in three countries (USA, Spain, and UK). Patients (≥18 years old) were eligible for inclusion if they had histologically documented CD20-positive relapsed or refractory diffuse large B-cell lymphoma and Eastern Cooperative Oncology Group performance status of 2 or lower, had received at least one previous line of chemoimmunotherapy, including an anti-CD20 agent, and were ineligible for stem-cell transplantation. The dose-escalation phase (1b) used escalating doses of lenalidomide to find the recommended phase 2 dose. Patients received six 28-day cycles of induction treatment with intravenous rituximab 375 mg/m2 and intravenous polatuzumab vedotin 1·8 mg/kg (all cohorts) plus oral lenalidomide at the following doses: 10 mg (cohort A); 15 mg (cohort B); and 20 mg (cohort C). Rituximab and polatuzumab vedotin were administered on day 1 and lenalidomide on days 1-21 of each 28-day cycle. During the dose-expansion phase (2), patients received six 28-day cycles of Pola+R+Len at the recommended phase 2 dose established during dose escalation. In both phases, patients with a complete response or partial response at the end of induction were eligible for post-induction therapy with rituximab 375 mg/m2 on day 1 and lenalidomide 10 mg/day on days 1-21 of each 28-day cycle for a maximum of 6 cycles. The primary safety objective of the dose-escalation phase was identification of the maximum tolerated dose through incidence of dose-limiting toxic effects. The primary efficacy outcome of the dose-expansion phase was Independent Review Committee-assessed complete response rate at end of induction, based on PET-CT. Analyses were conducted in the safety population, which included all patients who received at least one dose of any study drug, and the efficacy population, which included all patients who received at least one dose of any study drug at the recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02600897. FINDINGS: Between July 11, 2017 and Feb 3, 2020, 57 patients were enrolled (median age 71 years [IQR 60-75]; 38 [67%] were male and 19 (33%) were female; 47 [82%] were not Hispanic or Latino; and the median previous lines of therapy was 2 [IQR 1-3]). 18 participants were included in phase 1b and 39 were included in phase 2. Phase 1b confirmed a 20 mg recommended phase 2 dose for lenalidomide. After a median follow-up of 11·8 months (IQR 4·7-25·8), the complete response rate, as assessed by the Independent Review Committee, was 31% (90% CI 20-43). The most common grade 3-4 adverse events were neutropenia (35 [61%] of 57) and thrombocytopenia (eight [14%] of 57). Serious adverse events were reported in 23 (40%) of 57 patients and one patient died due to a treatment-related adverse event (neutropenic sepsis). INTERPRETATION: Although the combination of Pola+R+Len did not meet the prespecified activity threshold, some patients derived clinical benefit and the regimen had a tolerable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma. FUNDING: Genentech/F Hoffmann-La Roche.

Synthesis of C3-symmetric star shaped amphiphiles for drug delivery applications.

C 3-symmetric star-shaped aromatic compounds are known to possess unique characteristics which facilitate their industrial and biomedical applications. Herein, we report the design, synthesis, self-assembly and drug/dye delivery capabilities of C3-symmetric, hexa-substituted benzene-based amphiphiles. The synthesis of the hexa-substituted C3-symmetric core involves C-acetylation of phloroglucinol to yield the corresponding tri-acetyl derivative. This was further subjected to O-propargylation, followed by the carbonyl reduction of acetyl groups to yield the central core. Various hydrophilic (mPEG) and lipophilic units were then incorporated into this core via click and esterification reactions, respectively, to produce a new type of star shaped amphiphiles. So the obtained amphiphilic architectures have a tendency to aggregate in an aqueous medium forming nanosized assemblies with an inner hydrophobic core, allowing the substituents to control the tension-active properties. The critical aggregation concentration of the amphiphiles was evaluated by fluorescence measurement using the dye Nile red as a fluorescent probe. The hydrodynamic diameter of self-assembled aggregates in aqueous solution was studied by dynamic light scattering, while the actual size and morphology were determined by cryo-transmission electron microscopy (cryo-TEM) analysis. The physicochemical properties of the amphiphiles suggested their suitability for exploring their drug delivery applications. In this endeavor, the amphiphiles were utilized for the encapsulation of model hydrophobic entities and studying their subsequent release from their hydrophobic core in a controlled manner. The transport potential of the synthesised amphiphiles was explored for transdermal drug delivery. Furthermore, cytotoxicity studies were conducted using MCF7 and HeLa cells, which indicated that the nanocarriers had no toxic effect on the cells.

Preclinical efficacy of targeting epigenetic mechanisms in AML with 3q26 lesions and EVI1 overexpression.

AML with chromosomal alterations involving 3q26 overexpresses the transcription factor (TF) EVI1, associated with therapy refractoriness and inferior overall survival in AML. Consistent with a CRISPR screen highlighting BRD4 dependency, treatment with BET inhibitor (BETi) repressed EVI1, LEF1, c-Myc, c-Myb, CDK4/6, and MCL1, and induced apoptosis of AML cells with 3q26 lesions. Tegavivint (TV, BC-2059), known to disrupt the binding of nuclear ß-catenin and TCF7L2/LEF1 with TBL1, also inhibited co-localization of EVI1 with TBL1 and dose-dependently induced apoptosis in AML cell lines and patient-derived (PD) AML cells with 3q26.2 lesions. TV treatment repressed EVI1, attenuated enhancer activity at ERG, TCF7L2, GATA2 and MECOM loci, abolished interactions between MYC enhancers, repressing AML stemness while upregulating mRNA gene-sets of interferon/inflammatory response, TGF-ß signaling and apoptosis-regulation. Co-treatment with TV and BETi or venetoclax induced synergistic in vitro lethality and reduced AML burden, improving survival of NSG mice harboring xenografts of AML with 3q26.2 lesions.

Assessment of tympanic membrane perforation size using ImageJ software by ENT clinicians of different grades.

OBJECTIVE: To compare visual estimation versus ImageJ calculation of tympanic membrane perforation size in the paediatric population between clinicians of different experience. METHODS: Five images of tympanic membrane perforations in children, captured using an otoendoscope, were selected. The gold standard was the ImageJ results by one consultant otologist. Consultants, registrars and Senior House Officers or equivalent were asked to visually estimate and calculate the perforation size using ImageJ software. RESULTS: The mean difference in variation from gold standard between visual estimation and ImageJ calculation was 12.16 per cent, 95 per cent CI (10.55, 13.78) p < 0.05, with ImageJ providing a more accurate estimation of perforation. Registrars were significantly more accurate at visual estimation than senior house officers. There was no statistically significant difference in ImageJ results between the different grades. CONCLUSION: Using ImageJ software is more accurate at estimating tympanic membrane perforation size than visual assessment for all ENT clinicians regardless of experience.

Clinical Factors That Affect Fiducial Tracking in Robotic SABR for Lung Tumors.

Purpose: SABR is a treatment option for patients with lung tumors that employs fiducials to track tumors during the breathing cycle. Currently, there is a paucity of data on how relative fiducial location and patient clinical characteristics affect fiducial tracking and clinical outcomes. This study aimed to identify factors that reduce the number of fiducials tracked with respiratory motion management during SABR. Methods and Materials: An institutional review board-approved retrospective review was performed of patients receiving robotic SABR for lung tumors at our institution from 2016 to 2019. Clinical data including demographics, medical history, treatment data, and follow-up were collected. Fiducial geometries were obtained with Velocity contouring software and MATLAB. Mann-Whitney U, χ2, and t tests were completed using MedCalc. Results: A total of 73 patients with 77 treatments were identified. The χ2 analysis revealed that chronic obstructive pulmonary disease was associated with having 3 or more fiducials tracked (P = .034). Tumors in lower lobes were associated with higher rates of uncertainty errors (P = .015). The number of fiducials tracked had no effect on local tumor control or overall survival, with a median of 36 months of follow-up. A total of 28 treatments had fiducial centroid data available for geometric analysis. The most common tracking errors were rigid body error (RBE; 57%) and spacing errors (36.4%). Spacing errors had a shorter average minimum interfiducial distance than nonspacing errors (1.0 cm vs 1.7 cm, respectively; P = .017). RBE treatments had a longer average maximum distance than non-RBE treatments (4.0 cm vs 3.0 cm; P = .022). Conclusions: Greater motion in lower lobes can contribute to certain tracking errors that prevent more fiducials from being tracked. Maintaining interfiducial distance between experimentally determined guidelines may limit spacing errors and RBEs, the 2 most common tracking errors. An increased number of patients in a data set may result in stronger correlations between patient and tumor factors and outcomes.

Leveraging immunoliposomes as nanocarriers against SARS-CoV-2 and its emerging variants.

The global COVID-19 pandemic arising from SARS-CoV-2 has impacted many lives, gaining interest worldwide ever since it was first identified in December 2019. Till 2023, 752 million cumulative cases and 6.8 million deaths were documented globally. COVID-19 has been rapidly evolving, affecting virus transmissibility and properties and contributing to increased disease severity. The Omicron is the most circulating variant of concern. Although success in its treatment has indicated progress in tackling the virus, limitations in delivering the current antiviral agents in battling emerging variants remain remarkable. With the latest advancements in nanotechnology for controlling infectious diseases, liposomes have the potential to counteract SARS-CoV-2 because of their ability to employ different targeting strategies, incorporating monoclonal antibodies for the active and passive targeting of infected patients. This review will present a concise summary of the possible strategies for utilizing immunoliposomes to improve current treatment against the occurrence of SARS-CoV-2 and its variants.

Acute incarcerated intrathoracic sleeve herniation after laparoscopic sleeve gastrectomy: an uncommon yet urgent complication-a comprehensive case report and literature review.

Laparoscopic sleeve gastrectomy (LSG) stands as one of the most frequently performed bariatric procedures in the USA. While hiatal hernia or intrathoracic migration of the staple line is frequently described as a chronic complication, this review article sheds light on the seldom-discussed acute presentation of this alarming complication. We present a compelling case of a young female who experienced sudden and intractable vomiting shortly after LSG. Utilizing a multidisciplinary approach, upper gastrointestinal imaging (UGI) and computed tomography (CT) scans unequivocally confirmed incarcerated intrathoracic migration of the gastric sleeve, necessitating immediate surgical intervention. Radiologists must be equipped with the knowledge to recognize subtle yet crucial imaging findings from UGI and CT scans to ensure timely intervention, thus mitigating the risks associated with this underreported acute complication of LSG and ultimately improving patient outcomes and safety.