Improving Patient Outcomes Using Measures to Increase Discharge Rates to Home.

Background Post-acute care (PAC) centers are facilities used for recuperation, rehabilitation, and symptom management in an effort to improve the long-term outcomes of patients. PAC centers include skilled nursing facilities, inpatient rehabilitation facilities, and long-term care hospitals. In the 1990s, Medicare payment reforms significantly increased the discharge rates to PAC centers and subsequently increased the length of stay (LOS) among these patient populations. Over the last several years, there have been national initiatives and multidisciplinary approaches to improve safe discharge rates to home. Multiple studies have shown that patients who are discharged to home have decreased rates of 30-day readmissions, reduced short-term mortality, and an improvement in their activities of daily living.  Objectives This study aimed to investigate how multidisciplinary approaches could improve a single institution's discharge rates to home. In doing so, we aim to lower hospital readmission rates, hospital length of stay, morbidity and mortality rates, and healthcare-associated costs. Methods A retrospective single-institution cohort study was implemented at Jersey Shore University Medical Center (JSUMC). Data from January 2015 to December 2019 served as the control period, compared to the intervention period from January 2020 to January 2024. Patients were either admitted to JSUMC teaching faculty, hospitalists, or "others," which is composed of various medical and surgical subspecialists. Interventions performed to improve home discharge rates can be categorized into the following: physician education, patient education, electronic medical record (EMR) initiatives, accountability, and daily mobility initiatives. All interventions were performed equally across the three patient populations. The primary endpoint was the proportion of patients discharged to home. Results There were 190,699 patients, divided into a pre-intervention group comprising 98,885 individuals and a post-intervention group comprising 91,814 patients. Within the pre-intervention group, the faculty attended to 8,495 patients, hospitalists cared for 39,145 patients, and others managed 51,245 patients. In the post-intervention period, the faculty oversaw 8,014 patients, hospitalists attended to 35,094 patients, and others were responsible for 48,706 patients. After implementing a series of multidisciplinary interventions, there was a significant increase in the proportion of patients discharged home, rising from 74.9% to 80.2% across the entire patient population. Specifically, patients under the care of the faculty experienced a more substantial improvement, with a discharge rate increasing from 73.6% to 84.4%. Similarly, the hospitalists exhibited a rise from 69.4% to 74.3%, and the others demonstrated an increase from 79.3% to 83.7%. All observed changes yielded a p-value < 0.001. Conclusions By deploying a multifaceted strategy that emphasized physician education, patient education, EMR initiatives, accountability measures, and daily mobility, there was a statistically significant increase in the rate of patient discharges to home. These initiatives proved to be cost-effective and led to a tangible reduction in healthcare-associated costs and patient length of stay. Further studies are required to look into the effect on hospital readmission rates and morbidity and mortality rates. The comprehensive approach showcased its potential to optimize patient outcomes.

Surface-functionalised polymeric nanoparticles for breast cancer treatment: processes and advances.

The World Health Organization (WHO) reported that of all the non-communicable diseases, cancer is considered the second cause of death worldwide. This has driven the big pharma companies to prioritise anticancer products in their pipeline. In addition, research has focused on exploration of new anticancer molecules and design of suitable dosage forms to achieve effective drug delivery to the tumour site. Nanotechnology is a valuable tool to build nano delivery systems with controlled and targeted drug release properties. Nanoparticles can be fabricated by robust, scalable and economic techniques using various polymers. Moreover, specific functional groups can be introduced to the surface of nanoparticles enabling targeting to a specific tissue; besides, they exhibit versatile drug release patterns according to the rate of polymer degradation. This review outlines the processes and advances in surface functionalisation of nanoparticles employed for treatment of breast cancer. The therapeutic molecules, the polymers used to fabricate nanoparticles, the techniques used to prepare the nanoparticles have been reviewed with a focus on the processes employed to functionalise these nanoparticles with suitable ligands to target different types of breast cancer.

Suppression of Root Rot Fungal Diseases in Common Beans (Phaseolus vulgaris L.) through the Application of Biologically Synthesized Silver Nanoparticles.

The biosynthesis of silver nanoparticles (AgNPs) using plant extracts has become a safe replacement for conventional chemical synthesis methods to fight plant pathogens. In this study, the antifungal activity of biosynthesized AgNPs was evaluated both in vitro and under greenhouse conditions against root rot fungi of common beans (Phaseolus vulgaris L.), including Macrophomina phaseolina, Pythium graminicola, Rhizoctonia solani, and Sclerotium rolfsii. Among the eleven biosynthesized AgNPs, those synthesized using Alhagi graecorum plant extract displayed the highest efficacy in suppressing those fungi. The findings showed that using AgNPs made with A. graecorum at a concentration of 100 µg/mL greatly slowed down the growth of mycelium for R. solani, P. graminicola, S. rolfsii, and M. phaseolina by 92.60%, 94.44%, 75.93%, and 79.63%, respectively. Additionally, the minimum inhibitory concentration (75 µg/mL) of AgNPs synthesized by A. graecorum was very effective against all of these fungi, lowering the pre-emergence damping-off, post-emergence damping-off, and disease percent and severity in vitro and greenhouse conditions. Additionally, the treatment with AgNPs led to increased root length, shoot length, fresh weight, dry weight, and vigor index of bean seedlings compared to the control group. The synthesis of nanoparticles using A. graecorum was confirmed using various physicochemical techniques, including UV spectroscopy, Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) analysis. Collectively, the findings of this study highlight the potential of AgNPs as an effective and environmentally sustainable approach for controlling root rot fungi in beans.

Serine metabolism is crucial for cGAS-STING signaling and viral defense control in the gut.

Inflammatory bowel diseases are characterized by the chronic relapsing inflammation of the gastrointestinal tract. While the molecular causality between endoplasmic reticulum (ER) stress and intestinal inflammation is widely accepted, the metabolic consequences of chronic ER stress on the pathophysiology of IBD remain unclear. By using in vitro, in vivo models, and patient datasets, we identified a distinct polarization of the mitochondrial one-carbon metabolism and a fine-tuning of the amino acid uptake in intestinal epithelial cells tailored to support GSH and NADPH metabolism upon ER stress. This metabolic phenotype strongly correlates with IBD severity and therapy response. Mechanistically, we uncover that both chronic ER stress and serine limitation disrupt cGAS-STING signaling, impairing the epithelial response against viral and bacterial infection and fueling experimental enteritis. Consequently, the antioxidant treatment restores STING function and virus control. Collectively, our data highlight the importance of serine metabolism to allow proper cGAS-STING signaling and innate immune responses upon gut inflammation.

A systematic review and meta-analysis of the efficacy and safety of Mavacamten therapy in international cohort of 524 patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.

Deep Learning-Based Metasurface Design for Smart Cooling of Spacecraft.

A reconfigurable metasurface constitutes an important block of future adaptive and smart nanophotonic applications, such as adaptive cooling in spacecraft. In this paper, we introduce a new modeling approach for the fast design of tunable and reconfigurable metasurface structures using a convolutional deep learning network. The metasurface structure is modeled as a multilayer image tensor to model material properties as image maps. We avoid the dimensionality mismatch problem using the operating wavelength as an input to the network. As a case study, we model the response of a reconfigurable absorber that employs the phase transition of vanadium dioxide in the mid-infrared spectrum. The feed-forward model is used as a surrogate model and is subsequently employed within a pattern search optimization process to design a passive adaptive cooling surface leveraging the phase transition of vanadium dioxide. The results indicate that our model delivers an accurate prediction of the metasurface response using a relatively small training dataset. The proposed patterned vanadium dioxide metasurface achieved a 28% saving in coating thickness compared to the literature while maintaining reasonable emissivity contrast at 0.43. Moreover, our design approach was able to overcome the non-uniqueness problem by generating multiple patterns that satisfy the design objectives. The proposed adaptive metasurface can potentially serve as a core block for passive spacecraft cooling applications. We also believe that our design approach can be extended to cover a wider range of applications.

Optimized polarization-independent Chand-Bali nano-antenna for thermal IR energy harvesting.

A novel, polarization-independent, wide-angle reception Chand-Bali nano-antenna is proposed. An adjoint-based optimization algorithm is used to create the same resonance at both linear polarizations of the incident radiation. The nano-antenna optimal parameters reveal that two hot spots with a strong field enhancement are created. These hot-spots could be integrated with metal-insulator-metal (MIM) diodes to form a rectenna for infrared (IR) energy harvesting. The metallic resonators allow for selecting several materials to facilitate the fabrication of the nano-antenna and the MIM diode. The Chand-Bali-based IR rectennas are investigated and simulations demonstrate an improvement of more than one order of magnitude in efficiency compared to ones using traditional nano-antennas.

The Effects of Various Teaching Methods on Chest X-ray Interpretation Skills Among Medical Students and Interns: A Systematic Review.

Chest X-ray (CXR) is a common tool used in medical practice. Medical students and interns should acquire knowledge of CXR interpretation, as it is an essential diagnostic tool for a large spectrum of diseases. This systematic review aimed to compare the effect of different intervention techniques on the competency of medical students and interns to demonstrate the level of confidence and competence in interpreting common presentations of CXRs. The population, intervention, comparison, and outcomes (PICO) framework was used to formulate the review question. All related articles in five databases (PubMed, Web of Science, Scopus, Medline, and Embase) were retrieved and the search was completed in March 2023 with no limiters on date and time. The number of relevant studies was 469. A multi-level approach through the Rayyan platform was used for the screening and exclusion processes. Eleven articles were included in the systematic review consisting of eight randomized controlled trials, one quasi-experimental study, one cross-sectional study, and one interventional cohort. Results showed significant effects of teaching methods utilizing deductive or inductive approach, clinical history, patient care comfort survey, and SAFMEDS (Say-All-Fast-Minute-Every-Day-Shuffled). Contrarily, no significant effect was shown by flipped classroom models and mixed and blocked practice, peer-assisted learning vs. expert-assisted learning, and Chester, an artificial intelligence tool. This review identified beneficial approaches that may enhance the learning outcomes of interpreting CXRs for medical students and interns, highlighting the remarkable impact of SAFMEDS on medical students' ability to identify CXR findings as well as the availability and practicality of online and e-learning resources for students.

Enhanced Performance of Artificial-Neural-Network-Based Equalization for Short-Haul Fiber-Optic Communications.

This work proposes an efficient and easy-to-implement single-layer artificial neural network (ANN)-based equalizer with improved compensation performance. The proposed equalizer is used for effectively mitigating the distortions induced in the short-haul fiber-optic communication systems based on intensity modulation and direct detection (IMDD). The compensation performance of the ANN equalizer is significantly improved, exploiting an introduced advanced training scheme. The efficiency and robustness of the proposed ANN equalizer are illustrated through 10- and 28-Gbaud short-reach optical-fiber communication systems. Compared to the efficient but computationally expensive maximum likelihood sequence estimator (MLSE), the proposed ANN equalizer not only significantly reduces its computational equalization cost and storage memory requirements, but it also outperforms its bit error rate performance.

Telomerase RNA component lncRNA as potential diagnostic biomarker promotes CRC cellular migration and apoptosis evasion via modulation of ß-catenin protein level.

Aim: Long non-coding RNA (LncRNA) telomerase RNA component (TERC) has telomerase-dependent and independent activity in numerous cancer types. The present study purposes to demonstrate the role of lncRNA TERC as a diagnostic serum biomarker in colorectal cancer (CRC) patients and the molecular mechanism of lncRNA TERC in inducing tumor in CRC cell lines. Materials and methods: PCR array was performed to examine lncRNAs dysregulated in CRC. LncRNA TERC expression level was evaluated in 70 CRC patients and 35 control subjects using RT-qPCR. Then transfection was performed to build down-expression models of lncRNA TERC. ROC curve analysis was applied to assess the diagnostic value of serum LncRNA CRC. In addition, RT-qPCR was used to detect expression level of lncRNA TERC and ß-catenin mRNA. Moreover, ELISA and Western blot were used to detect the level of ß-catenin protein in sera of CRC patients and cell lines. The biological functions such as cell growth and migration of CRC cells were assessed using a wound healing assay. Cell cycle analysis and apoptosis analysis were performed using flow cytometry. Results: The lncRNA TERC is overexpressed in the sera of CRC patients with high diagnostic and stage discrimination accuracy. Furthermore, lncRNA TERC expression was upregulated in CRC cell lines and lncRNA TERC silencing induced cell arrest and apoptosis and inhibited cell migration. Furthermore, inhibition of lncRNA TERC reduces ß-catenin protein levels. Conclusion: The lncRNA TERC could be considered as an early stages CRC diagnostic biomarker with a good ability to discriminate between CRC stages. lncRNA TERC induces CRC by promoting cell migration and evading apoptosis by elevating the level of ß-catenin protein.

Effect of reperfusion strategy on QT dispersion in patients with acute myocardial infarction: Impact on in-hospital arrhythmia.

BACKGROUND: Myocardial ischemia and ST-elevation myocardial infarction (STEMI) increase QT dispersion (QTD) and corrected QT dispersion (QTcD), and are also associated with ventricular arrhythmia. AIM: To evaluate the effects of reperfusion strategy [primary percutaneous coronary intervention (PPCI) or fibrinolytic therapy] on QTD and QTcD in STEMI patients and assess the impact of the chosen strategy on the occurrence of in-hospital arrhythmia. METHODS: This prospective, observational, multicenter study included 240 patients admitted with STEMI who were treated with either PPCI (group I) or fibrinolytic therapy (group II). QTD and QTcD were measured on admission and 24 hr after reperfusion, and patients were observed to detect in-hospital arrhythmia. RESULTS: There were significant reductions in QTD and QTcD from admission to 24 hr in both group I and group II patients. QTD and QTcD were found to be shorter in group I patients at 24 hr than those in group II (53 ± 19 msec vs 60 ± 18 msec, P = 0.005 and 60 ± 21 msec vs 69+22 msec, P = 0.003, respectively). The occurrence of in-hospital arrhythmia was significantly more frequent in group II than in group I (25 patients, 20.8% vs 8 patients, 6.7%, P = 0.001). Furthermore, QTD and QTcD were higher in patients with in-hospital arrhythmia than those without (P = 0.001 and P = 0.02, respectively). CONCLUSION: In STEMI patients, PPCI and fibrinolytic therapy effectively reduced QTD and QTcD, with a higher observed reduction using PPCI. PPCI was associated with a lower incidence of in-hospital arrhythmia than fibrinolytic therapy. In addition, QTD and QTcD were shorter in patients not experiencing in-hospital arrhythmia than those with arrhythmia.

The Incidence of Sudden Sensorineural Hearing Loss (SSNHL) in COVID-19 Patients in Tertiary Care Referral Units.

COVID-19 is a new pandemic infectious disease that emerged in Wuhan, China, at the end of 2019. We aimed to evaluate the sudden sensorineural hearing loss (SSNHL) prevalence after COVID-19 infection or even vaccination. This is a two-center retrospective, observational cross-sectional study performed at tertiary care referral Audiovestibular Medicine Units at the period between August 1, 2020, and October 31, 2021. All SSNHL patients diagnosed in a period of a month with COVID-19 or vaccinated with a COVID-19 vaccine were included in this study. Fifty-three cases with confirmed COVID-19 and one patient vaccinated with a COVID-19 vaccine 1 week before, who reported sudden sensory neural hearing loss, were included in this study. Forty-eight patients had unilateral hearing loss and 6 patients had bilateral hearing loss. Forty-nine patients had typical COVID-19 symptoms; one patient discovered them after complaining of anosmia and ageusia and one patient after COVID-19 vaccination; and three patients were complaining only from hearing loss and had a PCR test for nasopharyngeal swabs to prove infection. Different degrees of SSNHL ranged from mild to severe and most of the patients had severe hearing loss. With more patients, COVID-19 may be a potential factor in sudden sensorineural hearing loss. It should be kept in mind that SSNHL may be the only indicator used to identify COVID-19 cases.

CHRNA1 and its correlated-myogenesis/cell cycle genes are prognosis-related markers of metastatic melanoma.

Nicotinic acetylcholine receptors (CHRNs) expression and their critical role in various types of cancer have been reported. However, it is still unclear which CHRNs and their associated genes play essential roles in metastasis in melanoma patients. Here, we performed bioinformatics analyses on publicly available bulk RNA sequencing (RNA-seq) data of patients with melanoma to identify the CHRNs highly expressed in metastatic melanoma. We found that CHRNA1 was highly expressed in metastatic melanoma samples compared to primary melanoma samples and was strongly associated with CHRNB1 and CHRNG. These muscle-type CHRNs (CHRNA1, CHRNB1, and CHRNG) were correlated with the ZEB1 and Rho/ROCK pathway-related genes in metastatic melanoma samples. Pairwise correlations and enrichment analyses revealed that CHRNA1 was significantly associated with myogenesis/muscle contraction and cell cycle genes. Kaplan-Meier curves illustrated the involvement of CHRNA1, four of its correlated genes (DES, FLNC, CDK1, and CDC20), and the myogenesis gene signature in the prognosis of melanoma patients. Following the bulk RNA-seq analysis, single-cell RNA-seq (scRNA-seq) analysis showed that the CHRNA1-expressing melanoma cells are primarily metastatic and had high expression levels of CHRNB1, CHRNG, and myogenesis/cell cycle-related genes. Our bioinformatics analyses of the bulk RNA-seq and scRNA-seq data of patients with melanoma revealed that CHRNA1 and its correlated myogenesis/cell-related cycle genes are critical prognosis-related markers of metastatic melanoma.

Adaptive digital back propagation exploiting adjoint-based optimization for fiber-optic communications.

This work proposes a novel and powerful adaptive digital back propagation (A-DBP) method with a fast adaption process. Given that the total transmission distance is known, the proposed A-DBP algorithm blindly compensates for the linear and nonlinear distortions of optical fiber transmission systems and networks, without knowing the launch power and channel parameters. An adjoint-based optimization (ABO) technique is proposed to significantly accelerate the parameters estimation of the A-DBP. The ABO algorithm utilizes a sequential quadratic programming (SQP) method coupled with an adjoint sensitivity analysis (ASA) approach to rapidly solve the A-DBP training problem. The design parameters are optimized using the minimum overhead of only one extra system simulation. Regardless of the number of A-DBP design parameters, the derivatives of the training objective function with respect to all parameters are estimated using only one extra adjoint system simulation per optimization iterate. This is contrasted with the traditional finite-difference (FD)-based optimization methods whose sensitivity analysis calculations cost per iterate scales linearly with the number of parameters. The robustness, performance, and efficiency of the proposed A-DBP algorithm are demonstrated through applying it to mitigate the distortions of 4-span and 20-span optical fiber communication systems. Coarse-mesh A-DBPs with less number of virtual spans are also used to significantly reduce the computational complexity of the equalizer, achieving compensation performance higher than that obtained using the coarse-mesh DBP with the exact channel parameters and full number of virtual spans.

Effect of Al2O3 on Nanostructure and Ion Transport Properties of PVA/PEG/SSA Polymer Electrolyte Membrane.

Polymer electrolyte membrane (PEM) fuel cells have the potential to reduce our energy consumption, pollutant emissions, and dependence on fossil fuels. To achieve a wide range of commercial PEMs, many efforts have been made to create novel polymer-based materials that can transport protons under anhydrous conditions. In this study, cross-linked poly(vinyl) alcohol (PVA)/poly(ethylene) glycol (PEG) membranes with varying alumina (Al2O3) content were synthesized using the solvent solution method. Wide-angle X-ray diffraction (XRD), water uptake, ion exchange capacity (IEC), and proton conductivity were then used to characterize the membranes. XRD results showed that the concentration of Al2O3 affected the degree of crystallinity of the membranes, with 0.7 wt.% Al2O3 providing the lowest crystallinity. Water uptake was discovered to be dependent not only on the Al2O3 group concentration (SSA content) but also on SSA, which influenced the hole volume size in the membranes. The ionic conductivity measurements provided that the samples were increased by SSA to a high value (0.13 S/m) at 0.7 wt.% Al2O3. Furthermore, the ionic conductivity of polymers devoid of SSA tended to increase as the Al2O3 concentration increased. The positron annihilation lifetimes revealed that as the Al2O3 concentration increased, the hole volume content of the polymer without SSA also increased. However, it was densified with SSA for the membrane. According to the findings of the study, PVA/PEG/SSA/0.7 wt.% Al2O3 might be employed as a PEM with high proton conductivity for fuel cell applications.

Materials Perspectives of Integrated Plasmonic Biosensors.

With the growing need for portable, compact, low-cost, and efficient biosensors, plasmonic materials hold the promise to meet this need owing to their label-free sensitivity and deep light-matter interaction that can go beyond the diffraction limit of light. In this review, we shed light on the main physical aspects of plasmonic interactions, highlight mainstream and future plasmonic materials including their merits and shortcomings, describe the backbone substrates for building plasmonic biosensors, and conclude with a brief discussion of the factors affecting plasmonic biosensing mechanisms. To do so, we first observe that 2D materials such as graphene and transition metal dichalcogenides play a major role in enhancing the sensitivity of nanoparticle-based plasmonic biosensors. Then, we identify that titanium nitride is a promising candidate for integrated applications with performance comparable to that of gold. Our study highlights the emerging role of polymer substrates in the design of future wearable and point-of-care devices. Finally, we summarize some technical and economic challenges that should be addressed for the mass adoption of plasmonic biosensors. We believe this review will be a guide in advancing the implementation of plasmonics-based integrated biosensors.

Tularemia: The Resurgence of a Diagnostic Challenge and Clinical Dilemma in the United States.

Tularemia is a rare, life-threatening zoonotic infection with low, naturally occurring transmission rates in the United States. Classified as a Category A bioterrorism agent, this disease is highly infectious and has the potential to be fatal if left untreated. Making the diagnosis is difficult due to the non-specific symptomatology patients present with. Considering the increase in the prevalence of this diagnosis over the past two decades, this condition has the potential to become a public health crisis. This case report details a pediatric patient who was found to have fever, ulceration, and lymphadenopathy on hospital admission. After a prolonged and protracted course of illness, tularemia was diagnosed with laboratory testing. The purpose of this case report is to increase awareness of tularemia as a potential cause of non-specific flu-like symptoms, especially during the summer months. Moreover, our goal is to propose suggestions for healthcare professionals who encounter patients with clinical suspicion of tularemia.

Analysis of Melanoma Gene Expression Signatures at the Single-Cell Level Uncovers 45-Gene Signature Related to Prognosis.

Since the current melanoma clinicopathological staging system remains restricted to predicting survival outcomes, establishing precise prognostic targets is needed. Here, we used gene expression signature (GES) classification and Cox regression analyses to biologically characterize melanoma cells at the single-cell level and construct a prognosis-related gene signature for melanoma. By analyzing publicly available scRNA-seq data, we identified six distinct GESs (named: "Anti-apoptosis", "Immune cell interactions", "Melanogenesis", "Ribosomal biogenesis", "Extracellular structure organization", and "Epithelial-Mesenchymal Transition (EMT)"). We verified these GESs in the bulk RNA-seq data of patients with skin cutaneous melanoma (SKCM) from The Cancer Genome Atlas (TCGA). Four GESs ("Immune cell interactions", "Melanogenesis", "Ribosomal biogenesis", and "Extracellular structure organization") were significantly correlated with prognosis (p = 1.08 × 10-5, p = 0.042, p = 0.001, and p = 0.031, respectively). We identified a prognostic signature of melanoma composed of 45 genes (MPS_45). MPS_45 was validated in TCGA-SKCM (HR = 1.82, p = 9.08 × 10-6) and three other melanoma datasets (GSE65904: HR = 1.73, p = 0.006; GSE19234: HR = 3.83, p = 0.002; and GSE53118: HR = 1.85, p = 0.037). MPS_45 was independently associated with survival (p = 0.002) and was proved to have a high potential for predicting prognosis in melanoma patients.

Impact of forced diuresis on retropulsion of disintegrated ureteral calculi during semi-rigid ureteroscopy: a double-blind randomized-controlled study.

The objective of this study is to assess the safety and efficacy of forced diuresis as an antiretropulsion strategy during the pneumatic disintegration of solitary lower ureteric stones with semi-rigid ureteroscopy (URS). A prospective randomized double-blind study was carried out from March 2019 to June 2021 for patients presented with unilateral solitary radiopaque lower ureteric stones ≤ 20 mm. Patients were randomized for URS into two groups, according to the use of forced diuresis using furosemide 1 mg/kg (GII) or not (GI). Perioperative parameters were compared between both groups, including retropulsion rate, stone-free rate (SFR), and need for auxiliary procedures and complications. A total of 148 patients were included; 72 (48.6%) in GI and 76 in the GII (51.4%), with respective stone size of 11.8 ± 2.6 vs.12.1 ± 2.4 mm. Both groups were comparable in demographic and baseline data, with a mean age of 47 ± 16 and 50 ± 14 years for GI and GII, respectively. GII had a significantly shorter disintegration time (10.5 ± 1.3 vs. 4.2 ± 2.1 min, p < 0.001), shorter operative time (33.1 ± 10.1 vs. 40.8 ± 9.1 min, p < 0.001), lower stone fragments migration rate during disintegration (6.5% vs. 18.1%, p = 0.04), lower retropulsion rate (1.3% vs. 11%, p = 0.02), higher SFR (96.1% vs. 86.1%, p = 0.04), and lower auxiliary procedures (3.9% vs. 13.8%, p = 0.03). Intraoperative and 6-h postoperative changes in heart rate and mean systolic blood pressure were comparable between both groups. Ephedrine injection (6-18 mg) was needed in significantly more GII patients (39.5% vs. 20.8%, p ≤ 0.01). It seems that forced diuresis during pneumatic lithotripsy of the lower ureteric stones is a safe and effective antiretropulsion technique. This would expand the alternative options to the antiretropulsion strategy, especially in centers where the laser and flexible ureteroscopes are not available.

Scrutinizing the Feasibility of Nonionic Surfactants to Form Isotropic Bicelles of Curcumin: a Potential Antiviral Candidate Against COVID-19.

Investigating bicelles as an oral drug delivery system and exploiting their structural benefits can pave the way to formulate hydrophobic drugs and potentiate their activity. Herein, the ability of non-ionic surfactants (labrasol®, tween 80, cremophore EL and pluronic F127) to form curcumin loaded bicelles with phosphatidylcholine, utilizing a simple method, was investigated. Molecular docking was used to understand the mechanism of bicelles formation. The % transmittance and TEM exhibited bicelles formation with labrasol® and tween 80, while cremophor EL and pluronic F127 tended to form mixed micelles. The surfactant-based nanostructures significantly improved curcumin dissolution (99.2 ± 2.6% within 10 min in case of tween 80-based bicelles) compared to liposomes and curcumin suspension in non-sink conditions. The prepared formulations improved curcumin ex vivo permeation over liposomes and drug suspension. Further, the therapeutic antiviral activity of the formulated curcumin against SARS-CoV-2 was potentiated over drug suspension. Although both Labrasol® and tween 80 bicelles could form bicelles and enhance the oral delivery of curcumin when compared to liposomes and drug suspension, the mixed micelles formulations depicted superiority than bicelles formulations. Our findings provide promising formulations that can be utilized for further preclinical and clinical studies of curcumin as an antiviral therapy for COVID-19 patients. Graphical Abstract.