Role of Machine Learning in Liquid Biopsy of Brain Tumours.

Liquid biopsy has multiple benefits and is used extensively in other fields of oncology, but its role in neuro-oncology has been limited so far. Multiple tumour-derived materials like circulating tumour cells (CTCs), tumour-educated platelets (TEPs), cell-free DNA (cfDNA), circulating tumour DNA (ctDNA), and miRNA are studied in CSF, blood (plasma, serum) or urine. Large and complex amounts of data from liquid biopsy can be simplified by machine learning using various algorithms. By using this technique, we can diagnose brain tumours and differentiate low versus highgrade glioma and true progression from pseudo-progression. The potential of liquid biopsy in brain tumours has not been extensively studied, but it has a bright future in the coming years. Here, we present a literature review on the role of machine learning in liquid biopsy of brain tumours.

Controlling Pericellular Oxygen Tension in Cell Culture Reveals Distinct Breast Cancer Responses to Low Oxygen Tensions.

In oxygen (O2)-controlled cell culture, an indispensable tool in biological research, it is presumed that the incubator setpoint equals the O2 tension experienced by cells (i.e., pericellular O2). However, it is discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2 consumption is the driving factor. RNA-seq analysis revealed that primary human hepatocytes cultured in physioxia experience ischemia-reperfusion injury due to cellular O2 consumption. A reaction-diffusion model is developed to predict pericellular O2 tension a priori, demonstrating that the effect of cellular O2 consumption has the greatest impact in smaller volume culture vessels. By controlling pericellular O2 tension in cell culture, it is found that hypoxia vs. anoxia induce distinct breast cancer transcriptomic and translational responses, including modulation of the hypoxia-inducible factor (HIF) pathway and metabolic reprogramming. Collectively, these findings indicate that breast cancer cells respond non-monotonically to low O2, suggesting that anoxic cell culture is not suitable for modeling hypoxia. Furthermore, it is shown that controlling atmospheric O2 tension in cell culture incubators is insufficient to regulate O2 in cell culture, thus introducing the concept of pericellular O2-controlled cell culture.

Promising Therapeutic Targets for Recurrent/Metastatic Anaplastic Thyroid Cancer.

OPINION STATEMENT: Anaplastic thyroid cancer presents formidable challenges, particularly in cases of recurrence or metastasis. Timely BRAF V600E testing is imperative at diagnosis, initially through immunohistochemistry, followed by comprehensive genomic profiling encompassing genes such as NTRK, RET, ALK, and assessment of tumor mutation burden (TMB). FDA-approved treatment options include dabrafenib and trametinib for patients with BRAF mutations, while those exhibiting high TMB may benefit from pembrolizumab. Further therapeutic decisions hinge upon mutational profile, urgency of response required, airway integrity, and access to targeted therapies There is growing use of immunotherapy for ATC based on published reports of activity, but currently there is no FDA approved agent for ATC. The off-label utilization of "precision medicine" combinations imposes a considerable financial strain, underscoring the necessity for further clinical trials to elucidate promising therapeutic avenues for this orphan disease. There is a pressing need for the development and support of clinical trials investigating genomically driven and immune-based therapies for anaplastic thyroid cancer.

Mortality Audit in the Head and Neck Surgery Ward: A Retrospective Study in a Tertiary Care Hospital of Pakistan.

Background Mortality audit is important for healthcare workers, but this data is lacking in developing countries. It helps to provide material about the cause of death, mortality rate, age, and gender. In a surgical department, such information can help identify key public health challenges that are contributing to morbidity and mortality, and this information can help healthcare workers better tackle those pathologies and focus on their prevention and treatment. Materials and methods A retrospective study was conducted at the Department of ENT - Head and Neck Surgery, Pakistan Institute of Medical Sciences Hospital, Islamabad. Five-year data was collected from the mortality register of the ward from January 2019 to December 2023, including the age, gender, surgical diagnosis, course of hospital stay, and cause of death. The collected data was statistically analyzed and presented in the form of tables and figures. Results A total of 53 deaths in 3890 admissions were found on record, with an overall mortality rate of 1.4%. The median age of participants was 61.5 years, with a preponderance of the male gender (n=34; 64.2%). The most common cause of death was head and neck malignancy (n=39; 73.6%), followed by head and neck abscesses (n=9; 17%). The least common cause of death was diphtheria (n=2; 3.8%). Conclusion Death was more common in old-age patients, with more prevalence in the male population. The most common cause of mortality was head and neck malignancy. The total death count almost remained constant through the years.

Feasibility of awake craniotomy for brain arteriovenous malformations: A scoping review.

Background: Brain Arteriovenous Malformations (AVMs) located in proximity to eloquent brain regions are associated with poor surgical outcomes, which may be due to higher rates of postoperative neurological deterioration. Current treatment protocols include stereotactic radiosurgery, transarterial embolization, and surgical resection under general anesthesia. Awake Craniotomy (AC) allows intraoperative mapping of eloquent areas to improve post-operative neurologic outcomes. Objectives: We reviewed the current literature reporting surgical outcomes and assessed the feasibility of AC for AVM resection. Methods: The PRISMA guidelines were utilized as a template for the review. Three databases including PubMed, Scopus, and Cochrane Library were searched using a predefined search strategy. After removing duplicates and screening, full texts were analyzed. Outcomes including the extent of resection, intra-operative and post-operative complications, and long-term neurologic outcomes were assessed. Results: 12 studies were included with a total of 122 AVM cases. Spetzler-Martin grading was used for the classification of the AVMs. The asleep-awake-asleep protocol was most commonly used for AC. Complete resection was achieved in all cases except 5. Intraoperative complications included seizures (n = 2) and bleeding (n = 4). Short-term post-operative complications included hemorrhage (n = 3), neurologic dysfunctions including paresis (n = 3), hemiplegia (n = 10), dysphasia/aphasia (n = 6), cranial nerve dysfunction (n = 3), and pulmonary embolism (n = 1). Almost all neurological deficits after surgery gradually improved on subsequent follow-ups. Conclusion: AVMs may shift the anatomical location of eloquent brain areas which may be mapped during AC. All studies recommended AC for the resection of AVMs in close proximity to eloquent areas as mapping during AC identifies the eloquent cortex thus promoting careful tissue handling which may preserve neurologic function and/or predict the postoperative functional status of the patients We, therefore, conclude that AC is a viable modality for AVMs resection near eloquent language and motor areas.

Glioblastoma-Infiltrating CD8+ T Cells Are Predominantly a Clonally Expanded GZMK+ Effector Population.

Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared with matched blood, which was validated at the protein level. Furthermore, integration with other cancer types highlights the lack of a canonically exhausted CD8+ T-cell population in GBM TIL. These data suggest that GZMK+ effector T cells represent an important T-cell subset within the GBM microenvironment and may harbor potential therapeutic implications. SIGNIFICANCE: To understand the limited efficacy of immune-checkpoint blockade in GBM, we applied a multiomics approach to understand the TIL landscape. By highlighting the enrichment of GZMK+ effector T cells and the lack of exhausted T cells, we provide a new potential mechanism of resistance to immunotherapy in GBM. This article is featured in Selected Articles from This Issue, p. 897.

THE IMPACT OF ROUTINE CARDIAC TROPONIN I-BASED CARDIOTOXICITY SCREENING ON CLINICAL OUTCOMES IN PATIENTS ON CANCER IMMUNOTHERAPY.

Purpose: Immune checkpoint inhibitors (ICI) used as cancer therapy have been associated with a range of cardiac immune-related adverse events (irAEs), including fulminant myocarditis with a high case fatality rate. Early detection through cardiotoxicity screening by biomarker monitoring can lead to prompt intervention and improved patient outcomes. In this study, we investigate the association between cardiotoxicity screening with routine serial troponin I monitoring in asymptomatic patients receiving ICI, cardiovascular adverse event (CV AE) detection, and overall survival (OS). Methods: We instituted a standardized troponin I screening protocol at baseline and with each ICI dose (every 2-4 weeks) in all patients receiving ICI at our center starting Jan 2019. We subsequently collected data in 825 patients receiving ICI at our institution from January 2018 to October 2021. Of these patients, 428 underwent cardiotoxicity screening with serial troponin I monitoring during ICI administration (Jan 2019-Oct 2021) and 397 patients were unmonitored (Jan 2018-Dec 2018). We followed patients for nine months following their first dose of ICI and compared outcomes of CV AEs and OS between monitored and unmonitored patients. Additionally, we investigated rates of CV AEs, all-cause mortality, and oncologic time-to-treatment failure (TTF) between patients with an elevated troponin I value during the monitoring period versus patients without elevated troponin I. Results: We found a lower rate of severe (grades 4-5) CV AEs, resulting in critical illness or death, in patients who underwent troponin monitoring (0.5%) compared to patients who did not undergo monitoring (1.8%), (HR 0.17, 95% CI 0.02-0.79, p = 0.04). There was no difference in overall CV AEs (grades 3-5) or OS between monitored and unmonitored patients. In the entire cohort, patients with at least one elevated troponin I during the follow up period, during routine monitoring or unmonitored, had a higher risk of overall CV AEs (HR 10.96, 95% CI 4.65-25.85, p<0.001) as well as overall mortality (HR 2.67, 95% CI 1.69 - 4.10, p<0.001) compared to those without elevated troponin. Oncologic time-to-treatment failure (TTF) was not significantly different in a sub-cohort of monitored vs. unmonitored patients. Conclusions: Patients undergoing cardiotoxicity screening with troponin I monitoring during ICI therapy had a lower rate of severe (grade 4-5) CV AEs compared patients who were not screened. Troponin I elevation in screened and unscreened patients was significantly associated with increased CV AEs as well as increased mortality. Troponin I monitoring did not impact oncologic time-to-treatment-failure in a sub-cohort analysis of patients treated with ICI. These results provide preliminary evidence for clinical utility of cardiotoxicity screening with troponin I monitoring in patients receiving ICI therapy.

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.

Characterization and biological evaluation of a novel flavonoid-collagen antioxidant hydrogel with cytoprotective properties.

Reactive oxygen species (ROS) play a critical and important role during wound healing but excess ROS at the wound site can lead to cellular damage and sub-optimal healing. Minimizing oxidative damage to the wound site and any supplemental therapeutic cells can be achieved by delivering exogenous antioxidants. Collagen hydrogels are ideal wound care materials due to their biocompatibility, high water content, and porous, three-dimensional architecture. Yet, they lack the inherent antioxidant activity that could help mitigate excess ROS at a wound site. This work formulates and evaluates the in vitro biocompatibility and antioxidant capabilities of collagen-fibroblast hydrogels combined with the polyphenolic antioxidant luteolin. Collagen solutions mixed with luteolin readily assembled into robust hydrogels with increasing gel strength due to increasing concentrations of luteolin. SEM images confirmed a mean pore size of 2.2 µm and a drastically different macromolecular ultrastructure with extensive fine crosslinking relative to collagen. Adequate cell viability and metabolic activity of dermal fibroblasts cultured within the gels were measured across all formulations, resulting in higher antioxidant activity and more than double the protection to cells from oxidative damage than traditional collagen hydrogels. Given these results, luteolin-collagen hydrogels demonstrate the potential for superior wound-healing properties when compared to collagen alone.

Machine learning (ML) techniques as effective methods for evaluating hair and skin assessments: A systematic review.

Machine Learning (ML) techniques provide the ability to effectively evaluate and analyze human skin and hair assessments. The aim of this study is to systematically review the effectiveness of applying Machine Learning (ML) methods and Artificial Intelligence (AI) techniques in order to evaluate hair and skin assessments. PubMed, Web of Science, IEEE Xplore, and Science Direct were searched in order to retrieve research publications between 1 January 2010 and 31 March 2020 using appropriate keywords such as "hair and skin analysis." Following accurate screening, 20 peer-reviewed publications were selected for inclusion in this systematic review. The analysis demonstrated that prevalent Machine Learning (ML) methods comprised of Support Vector Machine (SVM), k-nearest Neighbor, and Artificial Neural Networks (ANN). ANN's were observed to yield the highest accuracy of 95% followed by SVM generating 90%. These techniques were most commonly applied for drafting framework assessments such as that of Melanoma. Values of parameters such as Sensitivity, Specificity, and Area under the Curve (AUC) were extracted from the studies and with the help of comparisons, relevant inferences were also made. ANN's were observed to yield the highest sensitivity of 82.30% as well as a 96.90% specificity. Hence, with this systematic review, a summarization of the studies was drafted that encapsulated how Machine Learning (ML) techniques have been employed for the analysis and evaluation of hair and skin assessments.

Comparing Efficacy and Safety of Different Doses of Tirzepatide for the Treatment of Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.

Our study assessed the efficacy and safety of the three primary tirzepatide (TZP) doses, 5 mg, 10 mg, and 15 mg using network meta-analysis to assess their relative impact on type 2 diabetes mellitus (T2DM) treatment. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Two authors independently screened online databases, including PubMed, Cochrane Library, and Embase. We employed the keywords "Type 2 diabetes OR T2DM or diabetes" AND "Tirzepatide OR LY3298176 OR twincretin OR dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist" AND "randomized controlled trial". The outcomes evaluated in this study comprised changes in hemoglobin (Hb)A1c levels from baseline (%), changes in weight from baseline (Kg), changes in fasting serum glucose from baseline (mg/dL), and occurrences of serious adverse events (SAE), adverse events (AE) and major adverse cardiovascular events (MACE). A total of eight studies met the inclusion criteria and were included in this meta-analysis. Our findings suggest that among the evaluated doses, TZP at 15 mg demonstrated superior effectiveness in reducing HbA1c, weight, and fasting serum glucose compared to doses of 10 mg and 5 mg. Notably, the reduction in HbA1c and weight showed a dose-dependent trend, with the 15 mg dose achieving the most substantial benefits. The safety analysis indicated that while serious adverse events and major adverse cardiovascular events (MACE) did not significantly differ among the three doses, the risk of overall adverse events was notably higher in the 10 mg and 15 mg TZP groups compared to the 5 mg group.

Controlling pericellular oxygen tension in cell culture reveals distinct breast cancer responses to low oxygen tensions.

Oxygen (O2) tension plays a key role in tissue function and pathophysiology. O2-controlled cell culture, in which the O2 concentration in an incubator's gas phase is controlled, is an indispensable tool to study the role of O2 in vivo. For this technique, it is presumed that the incubator setpoint is equal to the O2 tension that cells experience (i.e., pericellular O2). We discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0.0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2 consumption is the driving factor. RNA-seq revealed that primary human hepatocytes cultured in physioxia experience ischemia-reperfusion injury due to anoxic exposure followed by rapid reoxygenation. To better understand the relationship between incubator gas phase and pericellular O2 tensions, we developed a reaction-diffusion model that predicts pericellular O2 tension a priori. This model revealed that the effect of cellular O2 consumption is greatest in smaller volume culture vessels (e.g., 96-well plate). By controlling pericellular O2 tension in cell culture, we discovered that MCF7 cells have stronger glycolytic and glutamine metabolism responses in anoxia vs. hypoxia. MCF7 also expressed higher levels of HIF2A, CD73, NDUFA4L2, etc. and lower levels of HIF1A, CA9, VEGFA, etc. in response to hypoxia vs. anoxia. Proteomics revealed that 4T1 cells had an upregulated epithelial-to-mesenchymal transition (EMT) response and downregulated reactive oxygen species (ROS) management, glycolysis, and fatty acid metabolism pathways in hypoxia vs. anoxia. Collectively, these results reveal that breast cancer cells respond non-monotonically to low O2, suggesting that anoxic cell culture is not suitable to model hypoxia. We demonstrate that controlling atmospheric O2 tension in cell culture incubators is insufficient to control O2 in cell culture and introduce the concept of pericellular O2-controlled cell culture.

The Golden Patient Initiative: A Systematic Review.

Operating theatres and surgical resource consumption comprise a significant proportion of healthcare costs. Inefficiencies in theatre lists remain an important focus for cost management, along with reducing patient morbidity and mortality. With the emergence of the coronavirus disease 2019 (COVID-19) pandemic, the number of patients on theatre waiting lists has surged. Hence, there is a pressing need to utilise the already limited theatre time and fraught resources with innovative methods. In this systematic review, we discuss the Golden Patient Initiative (GPI), in which the first patient on the operating list is pre-assessed the day prior to surgery, and we aim to assess its impact and overall efficacy. A literature search using the following four databases was conducted to identify and select all clinical research concerning the GPI: Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE), and the Cochrane library. Two independent authors screened articles against the eligibility criteria, using a process adapted from the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data extracted included outcomes measured, follow-up period, and study design. The results showed significant heterogeneity, and hence a narrative review was conducted; 13 of the 73 eligible articles were included for analysis. Outcomes included delay in theatre start time, number of surgical case cancellations, and changes to total case numbers. Across the studies, a 19-30-minute improvement in theatre start time was reported (p<0.05), as well as a statistically significant decrease in case cancellations. Our analysis provides encouraging conclusions with regard to greater theatre efficiency following the application of GPI, a low-cost solution that can easily be implemented to help improve patient safety and lead to cost savings. However, at present, it is largely implemented among local trusts, and hence larger multi-centre studies are required to gather conclusive evidence about the efficacy of the initiative.

Prevention of atrial fibrillation after open-chest surgery with extracellular vesicle therapy.

Almost half of patients recovering from open-chest surgery experience atrial fibrillation (AF) that results principally from inflammation in the pericardial space surrounding the heart. Given that postoperative AF is associated with increased mortality, effective measures to prevent AF after open-chest surgery are highly desirable. In this study, we tested the concept that extracellular vesicles (EVs) isolated from human atrial explant-derived cells can prevent postoperative AF. Middle-aged female and male rats were randomized to undergo sham operation or induction of sterile pericarditis followed by trans-epicardial injection of human EVs or vehicle into the atrial tissue. Pericarditis increased the probability of inducing AF while EV treatment abrogated this effect in a sex-independent manner. EV treatment reduced infiltration of inflammatory cells and production of pro-inflammatory cytokines. Atrial fibrosis and hypertrophy seen after pericarditis were markedly attenuated by EV pretreatment, an effect attributable to suppression of fibroblast proliferation by EVs. Our study demonstrates that injection of EVs at the time of open-chest surgery shows prominent antiinflammatory effects and prevents AF due to sterile pericarditis. Translation of this finding to patients might provide an effective new strategy to prevent postoperative AF by reducing atrial inflammation and fibrosis.

Activin A-Expressing Polymorphonuclear Myeloid-Derived Suppressor Cells Infiltrate Skeletal and Cardiac Muscle and Promote Cancer Cachexia.

Cachexia is a major cause of death in cancer and leads to wasting of cardiac and skeletal muscle, as well as adipose tissue. Various cellular and soluble mediators have been postulated in driving cachexia; however, the specific mechanisms behind this muscle wasting remain poorly understood. In this study, we found polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) to be critical for the development of cancer-associated cachexia. Significant expansion of PMN-MDSCs was observed in the cardiac and skeletal muscles of cachectic murine models. Importantly, the depletion of this cell subset, using depleting anti-Ly6G Abs, attenuated this cachectic phenotype. To elucidate the mechanistic involvement of PMN-MDSCs in cachexia, we examined major mediators, that is, IL-6, TNF-α, and arginase 1. By employing a PMN-MDSC-specific Cre-recombinase mouse model, we showed that PMN-MDSCs were not maintained by IL-6 signaling. In addition, PMN-MDSC-mediated cardiac and skeletal muscle loss was not abrogated by deficiency in TNF-α or arginase 1. Alternatively, we found PMN-MDSCs to be critical producers of activin A in cachexia, which was noticeably elevated in cachectic murine serum. Moreover, inhibition of the activin A signaling pathway completely protected against cardiac and skeletal muscle loss. Collectively, we demonstrate that PMN-MDSCs are active producers of activin A, which in turn induces cachectic muscle loss. Targeting this immune/hormonal axis will allow the development of novel therapeutic interventions for patients afflicted with this debilitating syndrome.

TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma.

Triggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. Here, we found that TREM2 is highly expressed in myeloid subsets, including macrophages and microglia in human and mouse GBM tumors and that high TREM2 expression correlates with poor prognosis in patients with GBM. TREM2 loss of function in human macrophages and mouse myeloid cells increased interferon-γ-induced immunoactivation, proinflammatory polarization, and tumoricidal capacity. In orthotopic mouse GBM models, mice with chronic and acute Trem2 loss of function exhibited decreased tumor growth and increased survival. Trem2 inhibition reprogrammed myeloid phenotypes and increased programmed cell death protein 1 (PD-1)+CD8+ T cells in the TME. Last, Trem2 deficiency enhanced the effectiveness of anti-PD-1 treatment, which may represent a therapeutic strategy for patients with GBM.

Trends and correlates of low HIV knowledge among ever-married women of reproductive age: Evidence from cross-sectional Bangladesh Demographic and Health Survey 1996-2014.

BACKGROUND: The human immunodeficiency virus (HIV) burden has frequently been changing over time due to epidemiological and demographic transitions. To safeguard people, particularly women of reproductive age, who can be exposed to transmitting this burden to the next generation, knowledge regarding this life-threatening virus needs to be increased. This research intends to identify the trends and associated correlates of "low" HIV knowledge among ever-married women of reproductive age in Bangladesh from 1996 to 2014. METHODS: We analyzed data derived from six surveys of Bangladesh Demographic and Health Surveys conducted in 1996, 1999, 2004, 2007, 2011, and 2014. Analyses were primarily restricted to ever-married women aged 15-49 years who had ever heard of HIV. The correlates of "low" HIV knowledge were investigated using multiple binary logistic regression models. RESULTS: The study found that the proportion of women with "low" HIV knowledge decreased from 72% in 1996 to 58% in 2014. In adjusted models, age at first marriage, level of education, wealth quintile, and place of residence (except in the survey year 2011) were found to be potential correlates of "low" HIV knowledge in all survey years. In the pooled analysis, we found lower odds of "low" HIV knowledge in the survey years 1999 (Adjusted Odds Ratio: 0.67; 95% CI: 0.57, 0.78), 2004 (AOR: 0.60; 95% CI: 0.52, 0.70), 2007 (AOR: 0.51; 95% CI: 0.44, 0.60), 2011 (AOR: 0.36; 95% CI: 0.32, 0.42) and 2014 (AOR: 0.47; 95% CI: 0.41, 0.54) compared to the survey year 1996. CONCLUSION: The proportion of "low" HIV knowledge has declined over time, although the proportion of women with "low" HIV knowledge still remains high. The prevention of early marriage, the inclusion of HIV-related topics in the curricula, reduction of disparities between urban-rural and the poorest-richest groups may help to improve the level of HIV knowledge among ever-married Bangladeshi women.

Prioritized mass spectrometry increases the depth, sensitivity and data completeness of single-cell proteomics.

Major aims of single-cell proteomics include increasing the consistency, sensitivity and depth of protein quantification, especially for proteins and modifications of biological interest. Here, to simultaneously advance all these aims, we developed prioritized Single-Cell ProtEomics (pSCoPE). pSCoPE consistently analyzes thousands of prioritized peptides across all single cells (thus increasing data completeness) while maximizing instrument time spent analyzing identifiable peptides, thus increasing proteome depth. These strategies increased the sensitivity, data completeness and proteome coverage over twofold. The gains enabled quantifying protein variation in untreated and lipopolysaccharide-treated primary macrophages. Within each condition, proteins covaried within functional sets, including phagosome maturation and proton transport, similarly across both treatment conditions. This covariation is coupled to phenotypic variability in endocytic activity. pSCoPE also enabled quantifying proteolytic products, suggesting a gradient of cathepsin activities within a treatment condition. pSCoPE is freely available and widely applicable, especially for analyzing proteins of interest without sacrificing proteome coverage. Support for pSCoPE is available at http://scp.slavovlab.net/pSCoPE .

Association between Multiple Myeloma and Ulcerative Colitis: A Cross-Sectional Analysis.

BACKGROUND AND AIMS: Multiple myeloma (MM) is a plasma cell dyscrasia that is common among patients with autoimmune diseases. However, the association between ulcerative colitis (UC) and multiple myeloma (MM) is yet to be established. We aimed to evaluate the prevalence of MM among patients with UC in the United States. METHODS: This cross-sectional cohort analysis used the National Inpatient Sample from 2015-2018 to assess the overall MM prevalence among patients with and without UC, and within specific demographic subgroups. Prevalences were compared using a logistic regression model controlling for sex and age. RESULTS: The crude prevalence of MM among patients with UC (n = 1750) compared with patients without UC (n = 366,265) was 0.44% vs. 0.37%, respectively. Patients with UC had increased overall odds of having MM (odds ratio (OR), 1.26). Males with UC had higher prevalence of MM (53.7% vs. 46.3%, respectively) than females. Patients with UC and MM were more likely to be African American than White (15.6% vs. 9.2%, respectively). Patients with UC age >64 had a higher prevalence of MM than those aged below 65 (70.9% vs. 29.1%, respectively). Patients with UC who were obese (BMI > 30) had a higher prevalence of MM than those who were non-obese (12.6% vs. 8.3%). CONCLUSIONS: Overall, UC appears to be associated with MM. This association can be particularly observed in specific demographic groups, such as obese, African American males, or patients >64 years of age. Thus, a high degree of clinical suspicion for MM is warranted, even with minimal symptomatology, in patients with UC, in particular among elder, obese, and African American males.

Extranodal Diffuse Large B-Cell Lymphoma (DLBCL) Presenting as Diffuse Joint Pain: A Diagnostic Dilemma.

Diffuse Large B-Cell Lymphoma (DLBCL) of bone is a rare presentation of Non-Hodgkin Lymphoma (NHL), which remains asymptomatic or present late in clinical course as bone pain or pathological fracture. We report a case of a 15-year-old male child presenting with diffuse joint pain and swelling over his left shoulder and elbow, associated with B symptoms. Radiological examination revealed lytic lesions in multiple bones along with collection along the left iliopsoas and hip joint, suggestive of infective etiology. The diagnostic dilemma was resolved on biopsy, which confirmed DLBCL involving bones and soft tissue.