A Multistep In Silico Approach Identifies Potential Glioblastoma Drug Candidates via Inclusive Molecular Targeting of Glioblastoma Stem Cells.

Glioblastoma (GBM) is the highest grade of glioma for which no effective therapy is currently available. Despite extensive research in diagnosis and therapy, there has been no significant improvement in GBM outcomes, with a median overall survival continuing at a dismal 15-18 months. In recent times, glioblastoma stem cells (GSCs) have been identified as crucial drivers of treatment resistance and tumor recurrence, and GBM therapies targeting GSCs are expected to improve patient outcomes. We used a multistep in silico screening strategy to identify repurposed candidate drugs against selected therapeutic molecular targets in GBM with potential to concomitantly target GSCs. Common differentially expressed genes (DEGs) were identified through analysis of multiple GBM and GSC datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). For identification of target genes, we selected the genes with most significant effect on overall patient survival. The relative mRNA and protein expression of the selected genes in TCGA control versus GBM samples was also validated and their cancer dependency scores were assessed. Drugs targeting these genes and their corresponding proteins were identified from LINCS database using Connectivity Map (CMap) portal and by in silico molecular docking against each individual target using FDA-approved drug library from the DrugBank database, respectively. The molecules thus obtained were further evaluated for their ability to cross blood brain barrier (BBB) and their likelihood of resulting in drug resistance by acting as p-glycoprotein (p-Gp) substrates. The growth inhibitory effect of these final shortlisted compounds was examined on a panel of GBM cell lines and compared with temozolomide through the drug sensitivity EC50 values and AUC from the PRISM Repurposing Secondary Screen, and the IC50 values were obtained from GDSC portal. We identified RPA3, PSMA2, PSMC2, BLVRA, and HUS1 as molecular targets in GBM including GSCs with significant impact on patient survival. Our results show GSK-2126458/omipalisib, linifanib, drospirenone, eltrombopag, nilotinib, and PD198306 as candidate drugs which can be further evaluated for their anti-tumor potential against GBM. Through this work, we identified repurposed candidate therapeutics against GBM utilizing a GSC inclusive targeting approach, which demonstrated high in vitro efficacy and can prospectively evade drug resistance. These drugs have the potential to be developed as individual or combination therapy to improve GBM outcomes.

NiOx/PANI nanocomposite doped carbon paste as electrode for long-term stable and highly efficient perovskite solar cells.

Carbon-based perovskite solar cells (PSCs) have emerged as a hopeful alternative in the realm of photovoltaics. They are considered promising due to their affordability, remarkable durability in humid environments, and impressive electrical conductivity. One approach to address the cost issue is to use affordable counter electrodes in PSCs that do not require organic hole transport materials (HTMs). This study utilized an innovative and economical method to create NiOx/PANI nanocomposites. Later, these nanoparticles were integrated into a carbon paste to act as an HTM. This incorporation is intended to optimize charge extraction, improve interfacial contact, align energy levels, reduce energy loss, minimize charge recombination, and protect the perovskite (FAPbI3) surface from degradation. The optoelectronic properties of these devices were investigated, and all cells showed improved efficiency compared to control cells. The NiOx/PANI doped carbon (NiOx/PANI+CE) exhibited excellent performance due to strong hole conductivity, well-aligned energy levels, and the formation of stepwise band alignment at the perovskite interface.

A comprehensive review on ecology, life cycle and use of Tecoma stans (bignoneaceae).

Tecoma stans is a widely distributed tall ornamental shrub in the plains of Indian subcontinent and is considered an invasive species across Argentina, Australia, South Africa, Pacific Islands and tropical regions of Asia. Besides having an ornamental significance, T. stans has been extensively investigated for its pharmaceutical applications as a source of bioactive compounds. In addition, the shrub is cultivated commercially as a potted flowering plant. We believe that T. stans, being a hardy, invasive and aggressively growing species, holds a considerable potential and a promising solution for re-greening waste and degraded lands outside its invasive range, due to its wider adaptability and drought tolerant characteristics. The shrub is an excellent source of pollen and nectar, that attracts diverse insect-pollinators and several species of birds. The prudent plantation of this shrub has the potential to restore the ecology of barren landscapes, that can change its perspective of 'being invasive' to 'being ecologically healthy' across the tropical, semi-arid and subtropical regions worldwide. This paper reviews the current updates on ecology, life cycle including morphology, plant growth characteristics, flowering phenology, reproductive biology, breeding system and fruiting of T. stans. In addition, details on insect-pollinator diversity and natural regeneration potential have also been discussed, besides highlighting its therapeutic and landscape use.

Fully Automated Agatston Score Calculation From Electrocardiography-Gated Cardiac Computed Tomography Using Deep Learning and Multi-Organ Segmentation: A Validation Study.

To evaluate deep learning-based calcium segmentation and quantification on ECG-gated cardiac CT scans compared with manual evaluation. Automated calcium quantification was performed using a neural network based on mask regions with convolutional neural networks (R-CNNs) for multi-organ segmentation. Manual evaluation of calcium was carried out using proprietary software. This is a retrospective study of archived data. This study used 40 patients to train the segmentation model and 110 patients were used for the validation of the algorithm. The Pearson correlation coefficient between the reference actual and the computed predictive scores shows high level of correlation (0.84; P < .001) and high limits of agreement (±1.96 SD; -2000, 2000) in Bland-Altman plot analysis. The proposed method correctly classifies the risk group in 75.2% and classifies the subjects in the same group. In total, 81% of the predictive scores lie in the same categories and only seven patients out of 110 were more than one category off. For the presence/absence of coronary artery calcifications, the deep learning model achieved a sensitivity of 90% and a specificity of 94%. Fully automated model shows good correlation compared with reference standards. Automating process reduces evaluation time and optimizes clinical calcium scoring without additional resources.

Enhancement of the photocatalytic activity of rGO/NiO/Ag nanocomposite for degradation of methylene blue dye.

The current study focuses on boosting the photocatalytic ability of reduced graphene oxide (rGO) by decorating the rGO nano-sheets with nickel oxide (NiOx) and silver (Ag) nanomaterials. The developed ternary nanomaterials were investigated using FTIR, XRD, FESEM, TEM, Raman, and UV-vis to evaluate the photo-degradation process. The rGO/NiOx/Ag ternary system showed promising photocatalytic dye degradation under simulated sunlight irradiance. The addition of NiOx and Ag nanomaterials widened the catalytic activity spectrum from the visible region to the UV-region. Besides, these materials hindered the electron-hole recombination, boosting the catalytic activity. The reusability results also clearly showed that the synthesized ternary nanomaterials have good reproducibility and stability for photocatalytic degradation of industrial wastewater.

Multicenter comparison of transcatheter aortic valve implantation with the self-expanding ACURATE neo2 versus Evolut PRO transcatheter heart valves.

BACKGROUND: New-generation self-expanding transcatheter aortic heart valves (THV) were designed to overcome technical constraints of their preceding generations. We sought to compare the efficacy and safety of the self-expanding ACURATE neo2 (Neo2) versus Evolut PRO (PRO) devices. METHODS: Seven hundred nine patients undergoing transfemoral transcatheter aortic valve implantation (TAVI) with either Neo2 (n = 496) or PRO (n = 213) were included. Propensity score matching (PSM) was performed to account for differences in baseline characteristics. In-hospital and 30-day clinical outcomes were evaluated according to Valve Academic Research Consortium-3 criteria. RESULTS: Baseline characteristics were comparable between both groups after PSM (Neo2: n = 155, Evolut Pro: n = 155). Technical success rates were high in both groups (Neo2: 94.8% vs PRO: 97.4%; p = 0.239). Need for permanent pacemaker implantation was less frequent with Neo2 compared with PRO (7.5% vs 20.6%; p = 0.002), whereas major vascular complications were more frequent with Neo2 (Neo2: 11.6% vs PRO: 4.5%; p = 0.022). Intended valve performance at discharge was high in both groups without relevant differences among groups (Neo2: 97.4% vs. 95.3%; p = 0.328). CONCLUSIONS: Short-term outcomes after TAVI using latest-generation self-expanding THV were excellent, with overall low rates of adverse events. However, Neo2 was associated with lower pacemaker rates and reduced the prevalence of moderate-severe paravalvular leakage. Transprosthetic gradients after TAVI were higher with Neo2 compared with PRO.

Congenital Pseudoarthrosis of Tibia With Anterolateral Bowing Treated With Ilizarov Ring Fixator: A Case Report.

Congenital pseudarthrosis of the tibia (CPT) is a rare, dysplastic condition that is characterized by a "false joint" in the tibia, leading to potential disability. We present a rare case report of a 12-year-old male from India with a history of neurofibromatosis type 1 (NF1) and anterolateral bowing of the tibia since birth. He sustained a tibial fracture during play. X-ray evaluation confirmed the fracture, and a clinical diagnosis of CPT was established. The treatment involved corticotomy for deformity correction and stabilization using Ilizarov's ring fixation. The procedure was successful, with post-operative radiological evaluations showing significant improvement in the center of rotation of angulation (CORA) from 60° pre-operatively to 25° post-operatively. The patient was discharged with an external fixator and after seven months, transitioned to full weight-bearing ambulation with a specialized brace. The Ilizarov procedure proved to be a safe and effective treatment for CPT, offering benefits such as limb lengthening and ankle stabilization.

Might Diet, APOE-APOA1 Axis, and Iron Metabolism Provide Clues About the Discrepancy in Alzheimer's Disease Occurrence Between Humans and Chimpanzees? A Bioinformatics-Based Re-Analysis of Gene Expression Data on Mice Fed with Human and Chimpanzee Diets.

The emergence of conflicting reports on the natural occurrence of Alzheimer's disease (AD) in non-human primates has prompted research on the comparison of the role of diet-associated changes in gene expression between humans and non-human primates. This article analyzes the effects of different human and chimpanzee diets and their link with apolipoproteins, lipid, and iron (Fe) metabolism, starting from available data, to find out any gap in the existing knowledge. By using a system biology approach, we have re-analyzed the liver and brain RNA seq data of mice fed with either human or chimpanzee diet for 2 weeks to look for genetic differences that may explain the differences in AD occurrence between those two classes. In liver samples of mice fed with the chimpanzee diet in comparison to the human diet, apolipoprotein A-1, ceruloplasmin, and 10 other genes were upregulated while 21 genes were downregulated. However, brain apolipoprotein E4 gene expression was not changed upon diet. Genetic, structural, and functional differences in apolipoprotein E protein, along with differences in Fe metabolisms and a longer lifespan of humans during evolution may account for the observed disparity.

Hyponatremia and Outcome: Is Severity More Important Than Etiology?

BACKGROUND AND OBJECTIVE: Hyponatremia is the most common electrolyte abnormality encountered in a hospital setting, and the data regarding the contribution of hyponatremia to overall mortality are conflicting. The study objective was to determine patients' clinical profiles and outcomes with hyponatremia. METHODS:  This prospective cross-sectional study was conducted at Dayanand Medical College and Hospital, Ludhiana, and included 375 adult patients aged more than 18 years with a confirmed diagnosis of hyponatremia. Patients were subdivided into three groups based on the severity of hyponatremia: mild (130-135 mmol/L), moderate (125-129 mmol/L), and profound (<125 mmol/L). RESULTS: The most common symptom was confusion (57.3%) followed by deep somnolence (40%) and nausea (36.8%). The most common cause of hyponatremia was diuretics (30.7%), followed by the syndrome of inappropriate antidiuretic hormone secretion (SIADH) (17.8%) and chronic liver disease (CLD) (14.1%). The severity of hyponatremia did not significantly influence the outcome. Patients with CLD and chronic kidney disease (CKD) as the etiology of hyponatremia had significantly worse outcomes compared to other causes of hyponatremia. The most common type was hypovolemic hypotonic followed by euvolemic hypotonic and hypervolemia hypotonic hyponatremia. Nearly half of the total deaths were observed in the hypervolemic hyponatremia group and were significantly higher compared to the other two groups (p=0.001). Correction of hyponatremia (i.e., serum sodium >135 mmol/L) was significantly linked with good outcomes (p=0.003). CONCLUSION: Our study showed that the etiology of hyponatremia was a more important prognostic indicator rather than the severity of hyponatremia. Normalization of serum sodium was associated with improved survival.

Higher Levels of Stress and Neuropsychological Symptoms Are Associated With a High Nausea Profile in Patients With Cancer Receiving Chemotherapy.

OBJECTIVES: To evaluate differences in the severity of global, cancer-specific, and cumulative life stress, resilience, and common neuropsychological symptoms among four subgroups of patients with distinct chemotherapy-induced nausea (CIN) profiles. SAMPLE & SETTING: Adult patients with cancer (N = 1,343) receiving chemotherapy. METHODS & VARIABLES: Patients completed stress, resilience, and neuropsychological symptom severity measures. The Memorial Symptom Assessment Scale was used to assess CIN occurrence six times over two cycles of chemotherapy. Parametric and nonparametric statistics were used to evaluate differences among subgroups of patients with distinct CIN profiles. RESULTS: The high class had significantly higher levels of global, cancer-specific, and cumulative life stress; significantly higher levels of depression, anxiety, sleep disturbance, morning and evening fatigue, and pain; and lower levels of morning and evening energy and cognitive dysfunction. IMPLICATIONS FOR NURSING: Clinicians need to evaluate CIN occurrence across each cycle of chemotherapy and assess patients for various types of stress and common neuropsychological symptoms.

Phase 2 Trial of Atezolizumab in Bacillus Calmette-Guérin-unresponsive High-risk Non-muscle-invasive Bladder Cancer: SWOG S1605.

BACKGROUND: Although radical cystectomy (RC) is the standard of care for patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC), many patients are ineligible for surgery or elect bladder preservation. OBJECTIVE: To evaluate the efficacy and safety of atezolizumab in BCG-unresponsive high-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm phase 2 trial in patients with BCG-unresponsive high-risk NMIBC who were ineligible for or declined RC. INTERVENTION: Intravenous atezolizumab every 3 wk for 1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the pathological complete response (CR) rate for patients with carcinoma in situ (CIS) determined via mandatory biopsy at 6 mo. Event-free survival (EFS) at 18 mo for patients with non-CIS tumors and treatment-related adverse events (TRAEs) were key secondary endpoints. RESULTS AND LIMITATIONS: Of 172 patients enrolled in the trial, 166 received at least one dose of atezolizumab (safety analysis) and 129 were eligible (efficacy analysis). Of the 74 patients with CIS, 20 (27%) experienced a CR at 6 mo. The median duration of response was 17 mo, and 56% (95% confidence interval [CI] 34-77%) of the responses were durable to at least 12 mo. The 18-mo actuarial EFS rate among 55 patients with Ta/T1 disease was 49% (90% CI 38-60%). Twelve of 129 eligible patients experienced progression to muscle-invasive or metastatic disease. Grade 3-5 TRAEs occurred in 26 patients (16%), including three treatment-related deaths. The study was limited by the small sample size and a high rate of patient ineligibility. CONCLUSIONS: The efficacy of atezolizumab observed among patients with BCG-unresponsive NMIBC is similar to results from similar trials with other agents, but did not meet the prespecified efficacy threshold. Modest efficacy needs to be balanced with a significant rate of TRAEs and the risk of disease progression when considering systemic immunotherapy in early-stage bladder cancer. PATIENT SUMMARY: We tested intravenous immunotherapy (atezolizumab) in patients with high-risk non-muscle-invasive bladder cancer that recurred after BCG (bacillus Calmette-Guérin) treatment. Although we found similar outcomes to previous trials, the benefit of this therapy is modest and needs to be carefully balanced with the significant risk of side effects. This trial is registered on ClinicalTrials.gov as NCT02844816.

Approaches to Prevent and Manage Cardiovascular Disease in Patients Receiving Therapy for Prostate Cancer.

PURPOSE OF REVIEW: Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy. RECENT FINDINGS: While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover, more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.

Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Preventative and therapeutic potential of animal milk components against COVID-19: A comprehensive review.

The global pandemic of COVID-19 is considered one of the most catastrophic events on earth. During the pandemic, food ingredients may play crucial roles in preventing infectious diseases and sustaining people's general health and well-being. Animal milk acts as a super food since it has the capacity to minimize the occurrence of viral infections due to inherent antiviral properties of its ingredients. SARS-CoV-2 virus infection can be prevented by immune-enhancing and antiviral properties of caseins, α-lactalbumin, ß-lactoglobulin, mucin, lactoferrin, lysozyme, lactoperoxidase, oligosaccharides, glycosaminoglycans, and glycerol monolaurate. Some of the milk proteins (i.e., lactoferrin) may work synergistically with antiviral medications (e.g., remdesivir), and enhance the effectiveness of treatment in this disease. Cytokine storm during COVID-19 can be managed by casein hydrolyzates, lactoferrin, lysozyme, and lactoperoxidase. Thrombus formation can be prevented by casoplatelins as these can inhibit human platelet aggregation. Milk vitamins (i.e., A, D, E, and B complexes) and minerals (i.e., Ca, P, Mg, Zn, and Se) can have significantly positive effects on boosting the immunity and health status of individuals. In addition, certain vitamins and minerals can also act as antioxidants, anti-inflammatory, and antivirals. Thus, the overall effect of milk might be a result of synergistic antiviral effects and host immunomodulator activities from multiple components. Due to multiple overlapping functions of milk ingredients, they can play vital and synergistic roles in prevention as well as supportive agents during principle therapy of COVID-19.

Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial.

Talimogene laherparepvec (T-VEC) plus ipilimumab has demonstrated greater antitumor activity versus ipilimumab alone, without additional toxicity, in patients with advanced melanoma. Here, we report the 5-year outcomes from a randomized phase II study. These data provide the longest efficacy and safety follow-up for patients with melanoma treated with a combination of an oncolytic virus and a checkpoint inhibitor.Eligible patients with unresectable stage IIIB‒IV melanoma were randomized 1:1 to receive T-VEC plus ipilimumab or ipilimumab alone. T-VEC was administered intralesionally at 106 plaque-forming units (PFU)/mL in week 1, followed by 108 PFU/mL in week 4 and every 2 weeks thereafter. Ipilimumab (3 mg/kg every 3 weeks; ≤4 doses) was administered intravenously starting at week 1 in the ipilimumab arm and week 6 in the combination arm. The primary end point was investigator-assessed objective response rate (ORR) per immune-related response criteria; key secondary end points included durable response rate (DRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.Overall, 198 patients were randomized to receive the combination (n=98) or ipilimumab (n=100). The combination improved the ORR versus ipilimumab (35.7% vs 16.0%; OR 2.9; 95% CI 1.5 to 5.7; p=0.003). DRR was 33.7% and 13.0% (unadjusted OR 3.4; 95% CI 1.7 to 7.0; descriptive p=0.001), respectively. Among the objective responders, the median DOR was 69.2 months (95% CI 38.5 to not estimable) with the combination and was not reached with ipilimumab. Median PFS was 13.5 months with the combination and 6.4 months with ipilimumab (HR 0.78; 95% CI 0.55 to 1.09; descriptive p=0.14). Estimated 5-year OS was 54.7% (95% CI 43.9 to 64.2) in the combination arm and 48.4% (95% CI 37.9 to 58.1) in the ipilimumab arm. Forty-seven (48.0%) and 65 (65.0%) patients in the combination and ipilimumab arms, respectively, received subsequent therapies. No new safety signals were reported.At the 5-year follow-up, the improved response rates observed with T-VEC plus ipilimumab were durable. This is the first randomized controlled study of the combination of an oncolytic virus and a checkpoint inhibitor that meets its primary end point.Trial registration number: NCT01740297.

Workflow in transgenic mice for the study of specific cancers associated with the post-menopausal state.

Beta-hCG is associated with poor patient prognosis in several cancers, but the particular pathophysiology of beta-hCG in post-menopausal women remains unaddressed. Specific steps to culture Lewis lung carcinoma (LLC1) tumor cells are enumerated. Ovariectomy of syngeneic, beta-hCG transgenic mice is discussed, employing a protocol designed to ensure high survival. Implantation of LLC1 tumor cells in these mice is also described. The workflow can be easily adapted in the study of other cancers associated with the post-menopausal stratum. For complete details on the use and execution of this protocol, please refer to Sarkar et al. (2022).1.

Non-Ceruloplasmin Copper Identifies a Subtype of Alzheimer's Disease (CuAD): Characterization of the Cognitive Profile and Case of a CuAD Patient Carrying an RGS7 Stop-Loss Variant.

Alzheimer's disease (AD) is a type of dementia whose cause is incompletely defined. Copper (Cu) involvement in AD etiology was confirmed by a meta-analysis on about 6000 participants, showing that Cu levels were decreased in AD brain specimens, while Cu and non-bound ceruloplasmin Cu (non-Cp Cu) levels were increased in serum/plasma samples. Non-Cp Cu was advocated as a stratification add-on biomarker of a Cu subtype of AD (CuAD subtype). To further circumstantiate this concept, we evaluated non-Cp Cu reliability in classifying subtypes of AD based on the characterization of the cognitive profile. The stratification of the AD patients into normal AD (non-Cp Cu ≤ 1.6 µmol/L) and CuAD (non-Cp Cu > 1.6 µmol/L) showed a significant difference in executive function outcomes, even though patients did not differ in disease duration and severity. Among the Cu-AD patients, a 76-year-old woman showed significantly abnormal levels in the Cu panel and underwent whole exome sequencing. The CuAD patient was detected with possessing the homozygous (c.1486T > C; p.(Ter496Argext*19) stop-loss variant in the RGS7 gene (MIM*602517), which encodes for Regulator of G Protein Signaling 7. Non-Cp Cu as an add-on test in the AD diagnostic pathway can provide relevant information about the underlying pathological processes in subtypes of AD and suggest specific therapeutic options.

CADNet: an advanced architecture for automatic detection of coronary artery calcification and shadow border in intravascular ultrasound (IVUS) images.

Intravascular Ultrasound (IVUS) is a medical imaging modality widely used for the detection and treatment of coronary heart disease. The detection of vascular structures is extremely important for accurate treatment procedures. Manual detection of lumen and calcification is very time-consuming and requires technical experience. Ultrasound imaging suffers from the generation of artifacts which obstructs the clear delineation among structures. Considering, the need, to provide special attention to crucial areas, convolutional block attention modules (CBAM) is integrated into an encoder-decoder-based U-Net architecture along with Atrous Spatial Pyramid Pooling (ASPP) to detect vessel components: lumen, calcification and shadow borders. The attention modules prove effective in dealing with areas of special attention by assigning additional weights to crucial channels and preserving spatial features. The IVUS data of 12 patients undergoing the treatment is taken for this study. The novelty of the model design is such that it is able to detect the lumen area in the presence/absence of calcification and bifurcation artifacts too. Also, the model efficiently detects the calcification area even in case of severely complex lesions with shadows behind them. The main contribution of the work is that IVUS images of varying degrees of calcification till 360° are also considered in this work, which is usually neglected in previous studies. The experimental results of 1097 IVUS images of 12 patients resulted in meanIoU (0.7894 ± 0.011), Dice Coefficient (0.8763 ± 0.070), precision (0.8768 ± 0.069) and recall (0.8774 ± 0.071) of the proposed model CADNet which show the model's effectiveness relative to other state-of-the art methods.

Calcification Detection in Intravascular Ultrasound (IVUS) Images Using Transfer Learning Based MultiSVM model.

Cardiovascular disease serves as the leading cause of death worldwide. Calcification detection is considered an important factor in cardiovascular diseases. Currently, medical practitioners visually inspect the presence of calcification using intravascular ultrasound (IVUS) images. The study aims to detect the extent of calcification as belonging to class I, II as mild calcification, and class III, IV as dense calcification from IVUS images acquired at 40 MHz. To detect calcification, the features were extracted using improved AlexNet architecture and then were fed into machine learning classifiers. The experiments were carried out using 14 real IVUS pullbacks of 10 patients. Experimental results show that the combination of traditional machine learning with deep learning approaches significantly improves accuracy. The results show that support vector machines outperform all other classifiers. The proposed model is compared with two other pre-trained models GoogLeNet (98.8%), SqueezeNet (99.2%), and exhibits considerable improvement in classification accuracy (99.8%). In the future other models such as Vision Transformers could be explored with additional feature selection methods such as ReliefF, PSO, ACO, etc. to improve the overall accuracy of diagnosis.