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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

Purpose of Review Myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) has played a central role in the non-invasive evaluation of patients with obstructive coronary artery disease (CAD) for decades. In this review, we discuss the key differences and advantages of positron emission tomography (PET) MPI over SPECT MPI as it relates to the diagnosis, prognosis, as well as clinical decision-making in patients with suspected CAD. Recent Findings Stress-induced perfusion abnormalities on SPECT help estimate presence, extent, and location of ischemia and flow-limiting obstructive CAD, help with risk stratification, and serve as a gatekeeper to identify patients who will benefit from downstream revascularization versus medical management. Some of the major limitations of SPECT include soft-tissue attenuation artifacts, underestimation of ischemia due to reliance on relative perfusion assessment, and longer protocols with higher radiation dose when performed with traditional equipment. PET MPI addresses most of these limitations and offers better quality images, higher diagnostic accuracy along with shorter protocols and lower radiation dose to the patient. A special advantage of PET scanning lies in the ability to quantify absolute myocardial blood flow and assess true extent of epicardial involvement along with identifying non-obstructive phenotypes of CAD such as diffuse atherosclerosis and microvascular dysfunction. In addition, stress acquisition at/near peak stress with PET allows us to measure left ventricular ejection fraction reserve and myocardial blood flow reserve, which help with identifying patients at a higher risk of future cardiac events and optimally select candidates for revascularization. Summary The several technical advantages of PET MPI position as a superior method to diagnose obstructive and non-obstructive phenotypes of ischemic heart disease affecting the entirety of the coronary circulation offer incremental value for risk stratification and guide post-test management strategy for patients with suspected CAD.

The remote sensing surveillance of maritime areas represents an essential task for both security and environmental reasons. Recently, learning strategies belonging to the field of machine learning (ML) have become a niche of interest for the community of remote sensing. Specifically, a major challenge is the automatic classification of ships from satellite imagery, which is needed for traffic surveillance systems, the protection of illegal fisheries, control systems of oil discharge, and the monitoring of sea pollution. Deep learning (DL) is a branch of ML that has emerged in the last few years as a result of advancements in digital technology and data availability. DL has shown capacity and efficacy in tackling difficult learning tasks that were previously intractable. Specifically, DL methods, such as convolutional neural networks (CNNs), have been reported to be efficient in image detection and recognition applications. In this paper, we focused on the development of an automatic ship detection (ASD) approach by using DL methods for assessing the Airbus ship dataset (composed of about 40 K satellite images). The paper explores and analyzes the distinct variations of the YOLO algorithm for the detection of ships from satellite images. A comparison of different versions of YOLO algorithms for ship detection, such as YOLOv3, YOLOv4, and YOLOv5, is presented, after training them on a personal computer with a large dataset of satellite images of the Airbus Ship Challenge and Shipsnet. The differences between the algorithms could be observed on the personal computer. We have confirmed that these algorithms can be used for effective ship detection from satellite images. The conclusion drawn from the conducted research is that the YOLOv5 object detection algorithm outperforms the other versions of the YOLO algorithm, i.e., YOLOv4 and YOLOv3 in terms accuracy of 99% for YOLOv5 compared to 98% and 97% respectively for YOLOv4 and YOLOv3.

This study focused on gemcitabine (GTB) delivery of cationic polymeric nanoparticles to treat ovarian cancer in order to promote effective localized delivery and drug retention during biological discharge. To begin, four GTB-loaded polymer nanoparticles were prepared: chitosan nanoparticles (CS-NPs), polysarcosin nanoparticles (PSar-NPs), poly-l-lysine & polysarcosin nanoparticles (PLL-PSar-NPs), and chitosan & polysarcosin nanoparticles (CS-PSar-NPs). Based on preliminary particle size, zeta potential, encapsulation efficiency, DSC, surface morphology, release profiling, and cellular internalization studies using rhodamine 123 and Nile red fluorescent markers, it was hypothesized that CS-PSar-NPs could be the best cationic formulation with strong biocompatibility and anticancer activity against the OVCAR-8 ovarian cancer cell line. To improve effective targeting, cellular penetration, and in vitro cytotoxicity, epidermal growth factor receptor variation III (EGFRvIII) is attached over all four polymeric nanoparticles. Confocal imaging revealed that EGFRvIII-conjugated cationic GTB polymeric nanoparticles had a greater cellular uptake and double internalization capabilities than unconjugated nanoparticles, as well as time-dependent cell entrance. GTB and EGFRvIII-conjugated polymer nanoparticles would have a stronger potential to infiltrate ovarian cancer cells during the first hour of incubation. According to TEM and FTIR findings, EGFRvIII conjugation across the non-target CS-PSar-NP surface was successful, making CS-PSar-NPS-EGFRvIII more target-specific and thus a safer drug delivery candidate for ovarian cancer treatment. Highlights GTB loaded non-target CS-PSar-NPs & active targeted CS-PSar-NPs-EGFRvII developed. SEM, AFM, DSC, particle size, zeta potential, internalization performed for CS-PSar-NPs. MTT & CLSM study confirmed CS-PSar-NPS-EGFRvII was binding specific to OVCAR-8 cells Fabrication of EGFRvII over nanoparticles confirmed by TEM. CS-PSar-NPS-EGFRvII safer candidate for ovarian cancer.

One of the most critical issues that the marine surveillance system has to address is the accuracy of its ship detection. Since it is responsible for identifying potential pirate threats, it has to be able to perform its duties efficiently. In this paper, we present a novel deep learning approach that combines the capabilities of a Graph Neural Network (GNN) and a You Only Look Once (YOLOv7) deep learning framework. The main idea of this method is to provide a better understanding of the ship’s presence in harbor areas. The three hyperparameters that are used in the development of this system are the learning rate, batch sizes, and optimization selection. The results of the experiments show that the Adam optimization achieves a 93.4% success rate when compared to the previous generation of the YOLOv7 algorithm. The High-Resolution Satellite Image Dataset (HRSID), which is a high-resolution image of a synthetic aperture radar, was used for the test. This method can be further improved by taking into account the various kinds of neural network architecture that are commonly used in deep learning.

To identify genetic mechanisms involved in the interplay of risky sexual behaviors (RSBs) and alcohol dependence (AD), we conducted genome-wide gene-by-AD (GW-GxAD) analyses of RSB in 3924 alcohol-exposed and sexually experienced subjects. RSBs were defined as a score based on lifetime experiences of unprotected sex and multiple sexual partners. Diagnosis of lifetime AD was defined by DSM-IV criteria. To follow-up the genetic findings, functional magnetic resonance imaging analyses were conducted in an independent sample. A trans-population genome-wide significant signal was identified in LHPP (rs34997829; z=-5.573, p=2.51 × 10 ) in the GxAD analysis that also showed associations in the AD-stratified association analysis (AD z=-2.032 and non-AD z=4.903). The clinical relevance of the result was confirmed by the significant interaction between LHPP rs34997829 and AD with respect to self-reported sexually transmitted disease (STD; z=-2.809, p=4.97 × 10 ). The neuroimaging follow-up analysis of LHPP rs34997829 showed reduced power of the left superior frontal gyrus (t=-3.386, p=9.56 × 10 ) and increased power at the right amygdala (t=3.287, p=1.33 × 10 ) in the resting amplitude of low frequency fluctuations analysis; and reduced activation of the anterior cingulate region (t=-2.961, p=3.69 × 10 ) in the monetary incentive delay task. In conclusion, LHPP locus is associated to AD-RSB interaction; and with brain circuitries previously implicated in the inhibition of risky behavior and impulsiveness, emotional regulation, and impulse control/error monitoring. Thus, LHPP is a strong candidate to influence RSB and STD risk in the context of AD.

One critical mechanism through which prostate cancer (PCa) adapts to treatments targeting androgen receptor (AR) signaling is the emergence of ligand-binding domain-truncated and constitutively active AR splice variants, particularly AR-V7. While AR-V7 has been intensively studied, its ability to activate distinct biological functions compared with the full-length AR (AR-FL), and its role in regulating the metastatic progression of castration-resistant PCa (CRPC), remain unclear. Our study found that, under castrated conditions, AR-V7 strongly induced osteoblastic bone lesions, a response not observed with AR-FL overexpression. Through combined ChIP-seq, ATAC-seq, and RNA-seq analyses, we demonstrated that AR-V7 uniquely accesses the androgen-responsive elements in compact chromatin regions, activating a distinct transcription program. This program was highly enriched for genes involved in epithelial-mesenchymal transition and metastasis. Notably, we discovered that SOX9, a critical metastasis driver gene, was a direct target and downstream effector of AR-V7. Its protein expression was dramatically upregulated in AR-V7-induced bone lesions. Moreover, we found that Ser81 phosphorylation enhanced AR-V7's pro-metastasis function by selectively altering its specific transcription program. Blocking this phosphorylation with CDK9 inhibitors impaired the AR-V7-mediated metastasis program. Overall, our study has provided molecular insights into the role of AR splice variants in driving the metastatic progression of CRPC.

Imipenem/cilastatin/relebactam has shown efficacy in complicated intra-abdominal and urinary tract infections in the RESTORE IMI-1 study, and it was recently approved by the US Food and Drug Administration. A press release announced that another Phase III study (RESTORE IMI-2) in patients with hospital-acquired and ventilator-associated pneumonia has met the primary end point. Critically ill patients with multidrug-resistant infections are expected to receive several pharmaceutical intravenous drugs while admitted in hospitals, warranting the need for Y-site compatibility studies. This study was conducted to evaluate the physical compatibility of imipenem/cilastatin/relebactam for injection during Y-site administration with common injectable intravenous medications. Imipenem/cilastatin/relebactam was prepared to the concentration of 5 mg/mL, and other intravenous tested drugs were reconstituted as per the package inserts. Y-site was simulated as a 2-drug combination by mixing 5 mL of each in a glass tube, with reversing of the order of mixing; physical characteristics were recorded, and pH changes and turbidity were measured at time intervals. Imipenem/cilastatin/relebactam was found to be compatible with a wide range of intravenous medications, facilitating co-administration with various IV medications. The compatibility reported is limited to a 2-h observation period in this study to adequately cover imipenem/cilastatin/relebactam infusion time. In addition, it is based on the measured turbidity with no chemical assay of the components of the admixture.

We report our management of a 53-year-old female who suffered a wood planer hand-mutilating injury with significant dorsal soft tissue loss and partial metacarpophalangeal joint (MCPJ) amputations of the thumb, index, and middle fingers. The middle finger was deconstructed for \"spare parts\" and a vascularized osteochondral graft was utilized to reconstruct the metacarpal articular surface of the index finger proximal phalanx, allowing the pedicled transposition of the index finger to the third metacarpal. The middle finger's distal interphalangeal joint was transplanted non-vascularly to recreate the thumb MCPJ and the elevation of a middle finger fillet flap allowed dorsal wound coverage. The patient did well initially but required ulnar collateral ligament reconstruction with a palmaris longus tendon graft following MCPJ instability 10 months postoperatively. Nonetheless, she progressively regained thumb opposition and pinch grip and continues to have successful aesthetic and functional outcomes six years postoperatively, supporting the efficacy of non-vascularized joint transfers when vascularized options are superfluous or unavailable.

INTRODUCTION:Histoplasmosis is a mycotic disease that is most common in patients with a weakened immune system, including those on tumor necrosis factor inhibitors. We present a patient with ulcerative colitis (UC) on infliximab, who had recurrent Clostridium difficile infections (CDI) requiring fecal microbiota transplantation (FMT) and subsequently developed primary colonic histoplasmosis.CASE:We present a 34-year-old woman from Missouri with ulcerative pancolitis on infliximab complicated by recurrent CDI requiring FMT. She was diagnosed with UC at age 32 (March 2015). She failed Mesalamine, Adalimumab (primary non-responder), and developed Azathioprine-induced pancreatitis. Infliximab later replaced Adalimumab with subsequent dose escalation and frequent courses of Prednisone due to refractory disease. The first CDI was diagnosed March 2016. From initial diagnosis, she had 4 CDI positive stools, in addition to a course of diarrhea that was empirically treated as CDI. She completed 4 courses of oral Vancomycin and 2 courses of Fidaxomicin, with initial response but recurrence of diarrhea shortly after antibiotic completion. Due to recurrent CDI, she underwent FMT in April 2017. Two weeks following FMT, she was diagnosed with a pulmonary embolism. Two weeks later, she presented with high grade fevers, hypotension and altered mental status. Labs were notable for rising liver enzymes (peak values: ALP 1,009 u/L, ALT 120 u/L, AST 293 u/L). Abdominal ultrasound did not show signs of cholestatic or hepatic processes. Symptoms continued to worsen despite steroids, fluid resuscitation and broad-spectrum antibiotics. Her course was further complicated by hematochezia and refractory anemia requiring blood transfusions. Cross sectional imaging demonstrated circumferential wall thickening of the proximal ascending colon to the cecum in addition to the previously identified pulmonary embolism. There was no evidence of pneumonia, hilar/mediastinal lymphadenopathy, ground glass opacity, nodules, masses or cavitary lung lesions. Sigmoidoscopy with biopsies demonstrated diffuse colitis. Qualitative serum CMV PCR and urine Histoplasma were checked and resulted positive. Ganciclovir and Amphotericin B liposome were initiated and within 48 hours, liver enzymes began to improve. However, due to worsening clinical course she eventually underwent total abdominal colectomy and partial proctectomy. Both colonic biopsies from sigmoidoscopy and colectomy were positive for Histoplasma and negative for CMV. She was diagnosed with disseminated histoplasmosis, treated with IV Amphotericin B liposome followed by a course of itraconazole, and she fully recovered. Colonic specimens from 5 months and 12 months prior to FMT were retrospectively reviewed and stained negative for histoplasmosis.DISCUSSION:Histoplasmosis in immunocompromised hosts can develop through exogenous exposure or reactivation of latent infection, with the former being more common. Our patient had biopsies from a colonoscopy 5 months preceding FMT which were negative for histoplasmosis, and cross-sectional imaging unrevealing of latent or active pulmonary disease; this suggests that primary colonic histoplasmosis was most likely introduced via FMT, resulting in refractory colitis and requiring total colectomy. Testing FMT donors/stool for histoplasmosis is not standardized and can vary. However, given the frequency of FMT in IBD patients on anti-TNF with recurrent CDI, FMT histoplasmosis screening should be considered.