Surface entrenched ß-sitosterol niosomes for enhanced cardioprotective activity against isoproterenol induced cardiotoxicity in rats.

Cardiotoxicity (CT) is a severe condition that negatively impacts heart function. ß-sitosterol (BS) is a group of phytosterols and known for various pharmacological benefits, such as managing diabetes, cardiac protection, and neuroprotection. This study aims to develop niosomes (NS) containing BS, utilizing cholesterol as the lipid and Tween 80 as the stabilizer. The research focuses on designing and evaluating both conventional BS-NS and hyaluronic acid (HA) modified NS (BS-HA-NS) to enhance the specificity and efficacy of BS within cardiac tissue. The resulting niosomal formulation was spherical, with a size of about 158.51 ± 0.57 nm, an entrapment efficiency of 93.56 ± 1.48 %, and a drug loading of 8.07 ± 1.62 %. To evaluate cytotoxicity on H9c2 heart cells, the MTT assay was used. The cellular uptake of BS-NS and BS-HA-NS was confirmed by confocal microscopy on H9c2 cardiac cells. Administering BS-NS and BS-HA-NS intravenously at a dose of 10 mg/kg showed the ability to significantly decrease the levels of cardiac troponin-I (cTn-I), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and lipid peroxidation (MDA). Tissue histopathology indicated a substantial potential for repairing cardiac tissue after treatment with BS-NS and BS-HA-NS and strong cardioprotection against ISO induced myocardial tissue damages. Thus, enhancing BS's therapeutic effectiveness through niosome surface modification holds promise for mitigating cardiac damage resulting from CT.

Revolution of nanotechnology in food packaging: Harnessing electrospun zein nanofibers for improved preservation - A review.

Zein, a protein-based biopolymer derived from corn, has garnered attention as a promising and eco-friendly choice for packaging food due to its favorable physical attributes. The introduction of electrospinning technology has significantly advanced the production of zein-based nanomaterials. This cutting-edge technique enables the creation of nanofibers with customizable structures, offering high surface area and adjustable mechanical and thermal attributes. Moreover, the electrospinning process allows for integrating various additives, such as antioxidants, antimicrobial agents, and flavoring compounds, into the zein nanofibers, enhancing their functionalities for food preservation. In this comprehensive review, the various electrospinning techniques employed for crafting zein-based nanofibers, and we delve into their enhanced properties. Furthermore, the review illuminates the potential applications of zein nanofibers in active and intelligent packaging materials by incorporating diverse constituents. Altogether, this review highlights the considerable prospects of zein-based nanocomposites in the realm of food packaging, offering sustainable and innovative solutions for food industry.

Ensemble of deep convolutional neural networks is more accurate and reliable than board-certified ophthalmologists at detecting multiple diseases in retinal fundus photographs.

AIMS: To develop an algorithm to classify multiple retinal pathologies accurately and reliably from fundus photographs and to validate its performance against human experts. METHODS: We trained a deep convolutional ensemble (DCE), an ensemble of five convolutional neural networks (CNNs), to classify retinal fundus photographs into diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and normal eyes. The CNN architecture was based on the InceptionV3 model, and initial weights were pretrained on the ImageNet dataset. We used 43 055 fundus images from 12 public datasets. Five trained ensembles were then tested on an 'unseen' set of 100 images. Seven board-certified ophthalmologists were asked to classify these test images. RESULTS: Board-certified ophthalmologists achieved a mean accuracy of 72.7% over all classes, while the DCE achieved a mean accuracy of 79.2% (p=0.03). The DCE had a statistically significant higher mean F1-score for DR classification compared with the ophthalmologists (76.8% vs 57.5%; p=0.01) and greater but statistically non-significant mean F1-scores for glaucoma (83.9% vs 75.7%; p=0.10), AMD (85.9% vs 85.2%; p=0.69) and normal eyes (73.0% vs 70.5%; p=0.39). The DCE had a greater mean agreement between accuracy and confident of 81.6% vs 70.3% (p<0.001). DISCUSSION: We developed a deep learning model and found that it could more accurately and reliably classify four categories of fundus images compared with board-certified ophthalmologists. This work provides proof-of-principle that an algorithm is capable of accurate and reliable recognition of multiple retinal diseases using only fundus photographs.

The Effect of COVID Convalescent Plasma on Hospital Stay: A Retrospective Observational Study from a Tertiary Care Hospital in North India.

INTRODUCTION: COVID convalescent plasma (CCP) has been used as standard of care in patients all over the world. CCP is plasma collected from recently infected and currently recovered COVID-19 patients, which contains antiviral antibodies that can be used to treat patients with COVID-19. Several studies have shown a shorter hospital stay and lower mortality in patients treated with convalescent plasma in comparison with those not treated with it. OBJECTIVES: This study aims to determine the effect of COVID convalescent plasma (CCP) on the length of hospital stay in symptomatic patients and to determine outcome of the disease in patients who were administered CCP. METHODS: This was a retrospective observational study done at a tertiary health care centre from July 2020 to May 2021, including patients who received CCP during the course of their stay in the hospital. RESULTS: Among 257 participants, the patients with multiple comorbidities who were administered CCP had the longest average length of stay in the hospital which was 15 days, out of which, 92 (35.8%) patients were discharged while 9 (3.5%) patients died. Also, the maximum number of deaths was observed in those patients who had no associated comorbidity, being 11 (4.3%). It was observed that earlier administration of CCP in patients (< 5 days from symptom onset) was associated with a higher number of discharges as compared to deaths. CONCLUSION: Our study indicates that CCP may be efficient in treating COVID-19 patients if given in early course of the disease.

I-JAMM-(I): A survey providing an insight into the practices of isoagglutinin titration in ABO incompatible kidney and liver transplantation.

BACKGROUND AND OBJECTIVES: ABO-incompatible transplantations allow patients to receive timely transplants. Isoagglutinin titration to ascertain levels of incompatible antibodies in the recipient is important in determining patient selection and transplant survivability. To find out the prevalent trends in India, the largest, first of its kind survey was carried out among the transplant centers regarding their practices in isoagglutinin titration. METHODS: The survey was drafted by a working group of Transfusion and Transplant Immunology specialists from six different centers. Data was obtained via the use of an online questionnaire. RESULTS: Results were categorized into four categories, Hospital information, Titration methodology, Role of transfusion specialists and cut-off titers. Most centers had a well-established solid-organ transplant program with considerable number of ABO-incompatible transplantations. Most centers performed isoagglutinin titration in Transfusion Medicine department. Column Agglutination Technique (CAT) was the most common method, using EDTA blood samples and freshly-prepared in-house pooled cells. Most centers had a turn-around time of less than 12 h. While the policy for ascertaining baseline and threshold titers is well-defined in ABO-incompatible renal transplants, variations from center to center still exist for ABO-incompatible liver transplants. Most centers required a Transfusion Medicine consultation for the patients before such transplants. CONCLUSION: With increasing ABO-incompatible kidney and liver transplants across the country, the role of Transfusion medicine specialists has become vital in pre-conditioning regimes enabling the viability and success of such transplants. This was a unique survey that provided a snapshot of current trends and practices of isoagglutinin titration for ABO-incompatible transplants in India.

Pentapeptide cRGDfK-Surface Engineered Nanostructured Lipid Carriers as an Efficient Tool for Targeted Delivery of Tyrosine Kinase Inhibitor for Battling Hepatocellular Carcinoma.

Background: Antitumor research aims to efficiently target hepatocarcinoma cells (HCC) for drug delivery. Nanostructured lipid carriers (NLCs) are promising for active tumour targeting. Cell-penetrating peptides are feasible ligands for targeted cancer treatment. Methods: In this study, we optimized gefitinib-loaded NLCs (GF-NLC) for HCC treatment. The NLCs contained cholesterol, oleic acid, Pluronic F-68, and Phospholipon 90G. The NLC surface was functionalized to enhance targeting with the cRGDfK-pentapeptide, which binds to the αvß3 integrin receptor overexpressed on hepatocarcinoma cells. Results: GF-NLC formulation was thoroughly characterized for various parameters using differential scanning calorimetry and X-ray diffraction analysis. In-vitro and in-vivo studies on the HepG2 cell line showed cRGDfK@GF-NLC's superiority over GF-NLC and free gefitinib. cRGDfK@GF-NLC exhibited significantly higher cytotoxicity, growth inhibition, and cellular internalization. Biodistribution studies demonstrated enhanced tumour site accumulation without organ toxicity. The findings highlight cRGDfK@GF-NLC as a highly efficient carrier for targeted drug delivery, surpassing non-functionalized NLCs. These functionalized NLCs offer promising prospects for improving hepatocarcinoma therapy outcomes by specifically targeting HCC cells. Conclusion: Based on these findings, cRGDfK@GF-NLC holds immense potential as a highly efficient carrier for targeted drug delivery of anticancer agents, surpassing the capabilities of non-functionalized NLCs. This research opens up new avenues for effective treatment strategies in hepatocarcinoma.

Emission color tuning and dual-mode luminescence thermometry design in Dy3+/Eu3+co-doped SrMoO4phosphors.

The challenge of building a highly reliable contactless temperature probe with high sensitivity, good temperature-induced color discriminability, and economical synthesis has prompted the research community to work in the field of rare-earth-based luminescence thermometry. Moreover, the fast-growing market for optoelectronic devices has increased the demand for tunable color-emitting phosphors. In this study, Dy3+/Eu3+co-doped SrMoO4phosphors were developed as tunable color-emitting source and dual-mode luminescence thermometer. A facile and cost-effective auto-combustion method was used to synthesize the phosphors. Our work demonstrates a viable scheme for tailoring the emission of single-phase phosphors by precisely controlling the dopant concentrations and by modulating excitation wavelength. The overall emission is tuned from greenish-yellow to white and greenish-yellow to reddish-orange. A detailed energy transfer process from the host to the Ln3+ions and between the Ln3+ions is discussed. Further, anti-thermal quenching in the emission of Dy3+ion is observed when excited with 297 nm. The dual-mode luminescence thermometry has been studied by analyzing the fluorescence intensity ratio of Dy3+and Eu3+ions upon excitation at 297 nm. The maximum relative sensitivity value for 4% Eu3+co-doped SrMoO4:4%Dy3+phosphor is 1.46% K-1at 300 K. Furthermore, the configurational coordinate diagram is presented to elucidate the nature of temperature-dependent emission. Therefore, our research opens up new avenues for the development of color-tunable luminescent materials for various optoelectronic and temperature-sensing applications.

A Promising Approach of Dermal Targeting of Antipsoriatic Drugs via Engineered Nanocarriers Drug Delivery Systems for Tackling Psoriasis.

Psoriasis is a complex autoimmune skin condition with a significant genetic component. It causes skin inflammation and is characterized by flaky, silvery reddish spots that can worsen with age. This condition results from an impaired immunological response of T-cells and affects 2-5% of the global population. The severity of the illness determines the choice of treatment. Topical treatments are commonly used to treat psoriasis, but they can have several adverse effects. Biological therapy is another option for treating specific types of psoriasis. Recently, new nanoformulations have revolutionized psoriasis treatment. Various nanocarriers, such as liposomes, nanostructured lipid nanoparticles, niosomes, and nanoemulsions, have been developed and improved for drug delivery. The use of nanocarriers enhances patient compliance, precise drug delivery, and drug safety. This review aims to suggest new nanocarrier-based drug delivery systems for treating psoriasis. It discusses the importance of nanocarriers and compares them to traditional treatments. Anti-psoriatic drugs have also been investigated for cutaneous delivery using nanocarriers. The review also covers various factors that influence dermal targeting. By highlighting several relevant aspects of psoriasis treatment, the review emphasizes the current potential of nanotechnology. Using nanocarriers as a drug delivery technique may be a promising alternative treatment for psoriasis.

A retrospective observational study to estimate the risk of HLA alloimmunization with blood transfusion: Can the risk be reduced by leucodepletion?

BACKGROUND: In this retrospective study, our aim was to find the effect of leucodepleted (LD) blood transfusions on the formation of anti-HLA-antibodies when compared to non-leucodepleted (non-LD) transfusions using Luminex-based method. METHODS: In this study, Luminex single antigen bead assay (L-SAB) and HLA typing were performed on 310 patients. Test positivity rates (as MFI - Mean florescence intensity) were analyzed according to the different sensitization events and gender. RESULTS: Of the 310 patients included in the study, 58.06% (180) patients were male and 41.93% (130) were female. The average age of the patients was 42.86 (±12.37) years. In this study, test positivity rates were significantly lower in the patients who received LD RBC units than in those who received non-LD RBC units (28.43% = 29 of 102 Vs 55.22% = 74 of 134, p < 0.05). In our study, transfusion combined with a history of pregnancy had higher number of significant HLA antibodies compared to cases where transfusion was the only sensitization event (81.81% = 18/22 Vs 39.71% = 85/214, p < 0.05). In addition, anti-HLA-antibodies-MFI were significantly (p < 0.01) higher in non-LD patients compared to LD patients. CONCLUSION: Patients who received LD RBC units had a significantly lower rate of transfusion-associated alloimmunization compared to those who received non-LD RBC units. Multiparous women had a high risk for transfusion-related alloimmunization compared to both nulliparous women and male patient. Furthermore, class I-anti-HLA-antibodies (HLA-B and HLA-A + B) were significantly associated with pregnancy sensitization and/or blood transfusion as a single sensitization.

Single-cell transcriptome analysis identifies novel biomarkers involved in major liver cancer subtypes.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two aggressive subtypes of liver cancer (LC). Immense cellular heterogeneity and cross-talk between cancer and healthy cells make it challenging to treat these cancer subtypes. To address these challenges, the study aims to systematically characterize the tumor heterogeneity of LC subtypes using single-cell RNA sequencing (scRNA-seq) datasets. The study combined 51,927 single cells from HCC, ICC, and healthy scRNA-seq datasets. After integrating the datasets, cell groups with similar gene expression patterns are clustered and cluster annotation has been performed based on gene markers. Cell-cell communication analysis (CCA) was implemented to understand the cross-talk between various cell types. Further, differential gene expression analysis and enrichment analysis were carried out to identify unique molecular drivers associated with HCC and ICC. Our analysis identified T cells, hepatocytes, epithelial cells, and monocyte as the major cell types present in the tumor microenvironment. Among them, abundance of natural killer (NK) cells in HCC, epithelial cells, and hepatocytes in ICC was detected. CCA revealed key interaction between T cells to NK cells in HCC and smooth muscle cells to epithelial cells in the ICC. Additionally, SOX4 and DTHD1 are the top differentially expressed genes (DEGs) in HCC, while keratin and CCL4 are in ICC. Enrichment analysis of DEGs reveals major upregulated genes in HCC affect protein folding mechanism and in ICC alter pathways involved in cell adhesion. The findings suggest potential targets for the development of novel therapeutic strategies for the treatment of these two aggressive subtypes of LC.

Immunohematological challenges in COVID infected patients.

BACKGROUND: Several autoimmune disorders have been reported to be related with COVID infection. In continuation to these autoimmune phenomenon, autoimmune hemolytic anaemia (AIHA) also has been noted in COVID infected patients. The aim of the study was to find out the prevalence of red cell alloimmunization, ABO discrepancy and positive direct antiglobulin test (DAT) results in COVID infected patients hospitalised in a tertiary care centre in North India. METHODOLOGY: This was a retrospective observational study done from July 2020 to June 2021. All symptomatic patients admitted to ICU tested positive for SARS CoV-2 whose blood samples were received in the immunohematology laboratory of department of Transfusion Medicine for determination of blood group and issue of packed red cells, and found to have positive antibody screen, blood group discrepancy and positive DAT results, were included in the study. RESULTS: A total of 10,568 tests were run, out of which 4437 were for determination of blood group, 5842 were for antibody screen and 289 were for direct antiglobulin test. Included in this study were 146 patients who either had blood group discrepancy, or had a positive antibody screen or had a positive DAT. Out of 115 positive antibody screen, 66 patients had only alloantibodies, 44 patients had only autoantibodies while only 5 patients had both auto as well as alloantibodies. Total number of positive DAT cases was 50 (50/289 = 17.3 %). There were 26 ABO discrepancies (26/4437 =0.58 %) found. CONCLUSION: Our results also indicate that there is rise in rate of alloimmunization and DAT positivity among COVID patients.

c(RGDfK) anchored surface manipulated liposome for tumor-targeted tyrosine kinase inhibitor (TKI) delivery to potentiate liver anticancer activity.

Current anticancer drug research includes tumor-targeted administration as a critical component because it is the best strategy to boost efficacy and decrease toxicity. Low drug concentration in cancer cells, nonspecific distribution, rapid clearance, multiple drug resistance, severe side effects, and other factors contribute to the disappointing results of traditional chemotherapy. As an innovative technique of treatments for hepatocellular carcinoma (HCC) in recent years, nanocarrier-mediated targeted drug delivery systems can overcome the aforesaid limitations via enhanced permeability and retention effect (EPR) and active targeting. Epidermal growth factor receptor (EGFR) inhibitor Gefitinib (Gefi) has dramatic effects on hepatocellular carcinoma. Herein, we developed and assessed an αvß3 integrin receptor targeted c(RGDfK) surface modified liposomes for better targeting selectivity and therapeutic efficacy of Gefi on HCC cells. The conventional and modified Gefi loaded liposomes, i.e., denoted as Gefi-L and Gefi-c(RGDfK)-L, respectively, were prepared through the ethanol injection method and optimized via Box Behnken design (BBD). The FTIR and 1H NMR spectroscopy verified that the c(RGDfK) pentapeptides had formed an amide bond with the liposome surface. In addition, the particle size, Polydispersity index, zeta potential, encapsulation efficiency, and in-vitro Gefi release of the Gefi-L and Gefi-c(RGDfK)-L were measured and analyzed. As indicated by the MTT assay on HepG2 cells, Gefi-c(RGDfK)-L displayed considerably higher cytotoxicity than Gefi-L or Gefi alone. Throughout the incubation period, HepG2 cells took up significantly more Gefi-c(RGDfK)-L than Gefi-L. According to the in vivo biodistribution analysis, Gefi-c(RGDfK)-L accumulated more strongly at the tumor site than Gefi-L and free Gefi. Furthermore, HCC-bearing rats treated with Gefi-c(RGDfK)-L showed a substantial drop in liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and total bilirubin levels) compared to the disease control group. Gefi-c(RGDfK)-L suppresses tumour growth more effectively than Gefi-L and free Gefi, according to an in vivo analysis of their anticancer activities. Thus, c(RGDfK)-surface modified liposomes, i.e., Gefi-c(RGDfK)-L may serve as an efficient carrier for the targeted delivery of anticancer drugs.

Plastic waste management for sustainable environment: techniques and approaches.

Excessive exploitation, negligence, non-degradable nature, and physical and chemical properties of plastic waste have resulted in a massive pollution load into the environment. Consequently, plastic entres the food chain and can cause serious health issues in aquatic animals and humans. The present review summarizes currently reported techniques and approaches for the removal of plastic waste. Many techniques, such as adsorption, coagulation, photocatalysis, and microbial degradation, and approaches like reduction, reuse and recycling are potentially in trend and differ from each other in their efficiency and interaction mechanism. Moreover, substantial advantages and challenges associated with these techniques and approaches are highlighted to develop an understanding of the selection of possible ways for a sustainable future. Nevertheless, in addition to the reduction of plastic waste from the ecosystem, many alternative opportunities have also been explored to cash plastic waste. These fields include the synthesis of adsorbents for the removal of pollutants from aqueous and gaseous stream, their utility in clothing, waste to energy and fuel and in construction (road making). Substantial evidence can be observed in the reduction of plastic pollution from various ecosystems. In addition, it is important to develop an understanding of factors that need to be emphasized while considering alternative approaches and opportunities to cash plastic waste (like adsorbent, clothing, waste to energy and fuel). The thrust of this review is to provide readers with a comprehensive overview of the development status of techniques and approaches to overcome the global issue of plastic pollution and the outlook on the exploitation of this waste as resources.

Mechanism, Kinetics, and Potential of Mean Force of Evaporation of Water from Aqueous Sodium Chloride Solutions of Varying Concentrations.

The mechanism, kinetics, and potential of mean force of evaporation of water from aqueous NaCl solutions are investigated through both unbiased molecular dynamics simulations and also biased simulations using the umbrella sampling method. The results are obtained for aqueous solutions of three different NaCl concentrations ranging from 0.6 to 6.0 m and also for pure water. The rate of evaporation is found to decrease in the presence of ions. It is found that the process of evaporation of a surface water molecule from ionic solutions can be triggered through its collision with another water or chloride ion. Such collisions provide the additional kinetic energy that is required for evaporation. However, when the collision takes place with a Cl- ion, the evaporation of the escaping water also involves a collision with water in the vicinity of the ion at the same time along with the ion-water collision. These two collisions together provide the required kinetic energy for escape of the evaporating water molecule. Thus, the mechanism of evaporation process of ionic solutions can be more complex than that of pure water. The potential of mean force (PMF) of evaporation is found to be positive and it increases with increasing ion concentration. Also, no barrier in the PMF is found to be present for the condensation of water from vapor phase to the surfaces of the solutions. A detailed analysis of the unsuccessful evaporation attempts by surface water molecules is also made in the current study.

A prospective observational study to evaluate effect of heat inactivation on ABO titers performed by column agglutination technology and conventional tube technique.

BACKGROUND AND AIMS: When determining ABO antibody titers, immunoglobulin G (IgG) antibodies can be masked by immunoglobulin M (IgM) antibodies. Hence, the measurement of actual concentration of IgG requires methods like heat inactivation (HI) of plasma. This study was aimed at determining the effects of HI on IgM and IgG titers performed by conventional tube technique (CTT) and column agglutination technique (CAT). MATERIALS AND METHODS: This was a prospective, observational study conducted from October 2019 to March 2020. All consecutive A, B, and O group donors who gave consent for participation were included. All samples were consecutively tested by CTT and CAT, before and after HI (pCTT, pCAT). RESULTS: A total of 300 donors were included. IgG titers were found to be more than IgM titers. For group O, IgG titer results were higher for both anti-A and anti-B compared to group A and B. For group A, B, and O, pretreatment results were higher than posttreatment IgG titer results. Median anti-A titers were similar to median anti-B titers across all categories. Median IgM and IgG titers were higher for group O individuals than nongroup O individuals. There was reduction in IgG and IgM titers after HI of plasma. One log reduction in median titers was observed when ABO titers were performed by CAT and CTT. CONCLUSION: There is one log difference between median antibody titers estimated using heat inactivated and nonheat inactivated plasma. The use of HI for ABO isoagglutinin titer estimation can be considered in low resource settings.

Using molecular straps to engineer conjugated porous polymer growth, chemical doping, and conductivity.

Controlling network growth and architecture of 3D-conjugated porous polymers (CPPs) is challenging and therefore has limited the ability to systematically tune the network architecture and study its impact on doping efficiency and conductivity. We have proposed that π-face masking straps mask the π-face of the polymer backbone and therefore help to control π-π interchain interactions in higher dimensional π-conjugated materials unlike the conventional linear alkyl pendant solubilizing chains that are incapable of masking the π-face. Herein, we used cycloaraliphane-based π-face masking strapped monomers and show that the strapped repeat units, unlike the conventional monomers, help to overcome the strong interchain π-π interactions, extend network residence time, tune network growth, and increase chemical doping and conductivity in 3D-conjugated porous polymers. The straps doubled the network crosslinking density, which resulted in 18 times higher chemical doping efficiency compared to the control non-strapped-CPP. The straps also provided synthetic tunability and generated CPPs of varying network size, crosslinking density, dispersibility limit, and chemical doping efficiency by changing the knot to strut ratio. For the first time, we have shown that the processability issue of CPPs can be overcome by blending them with insulating commodity polymers. The blending of CPPs with poly(methylmethacrylate) (PMMA) has enabled them to be processed into thin films for conductivity measurements. The conductivity of strapped-CPPs is three orders of magnitude higher than that of the poly(phenyleneethynylene) porous network.

BCA101 Is a Tumor-Targeted Bifunctional Fusion Antibody That Simultaneously Inhibits EGFR and TGFß Signaling to Durably Suppress Tumor Growth.

The EGFR and TGFß signaling pathways are important mediators of tumorigenesis, and cross-talk between them contributes to cancer progression and drug resistance. Therapies capable of simultaneously targeting EGFR and TGFß could help improve patient outcomes across various cancer types. Here, we developed BCA101, an anti-EGFR IgG1 mAb linked to an extracellular domain of human TGFßRII. The TGFß "trap" fused to the light chain in BCA101 did not sterically interfere with its ability to bind EGFR, inhibit cell proliferation, or mediate antibody-dependent cellular cytotoxicity. Functional neutralization of TGFß by BCA101 was demonstrated by several in vitro assays. BCA101 increased production of proinflammatory cytokines and key markers associated with T-cell and natural killer-cell activation, while suppressing VEGF secretion. In addition, BCA101 inhibited differentiation of naïve CD4+ T cells to inducible regulatory T cells (iTreg) more strongly than the anti-EGFR antibody cetuximab. BCA101 localized to tumor tissues in xenograft mouse models with comparable kinetics to cetuximab, both having better tumor tissue retention over TGFß "trap." TGFß in tumors was neutralized by approximately 90% in animals dosed with 10 mg/kg of BCA101 compared with 54% in animals dosed with equimolar TGFßRII-Fc. In patient-derived xenograft mouse models of head and neck squamous cell carcinoma, BCA101 showed durable response after dose cessation. The combination of BCA101 and anti-PD1 antibody improved tumor inhibition in both B16-hEGFR-expressing syngeneic mouse models and in humanized HuNOG-EXL mice bearing human PC-3 xenografts. Together, these results support the clinical development of BCA101 as a monotherapy and in combination with immune checkpoint therapy. SIGNIFICANCE: The bifunctional mAb fusion design of BCA101 targets it to the tumor microenvironment where it inhibits EGFR and neutralizes TGFß to induce immune activation and to suppress tumor growth.

Single center experience of therapeutic plasma exchange in a resource-constrained setting: A study of trends in scope and complications.

BACKGROUND: Therapeutic apheresis procedures are becoming an increasingly integral part of modern medical practice, be it as a part of therapy or pre-conditioning regimes for solid organ transplants. In our center, we follow the American Society for Apheresis (ASFA) guidelines for categorizing these procedures. However, lack of a centralized registry for therapeutic apheresis in India, lack of consolidated data as well as a resource-constrained setting prevent it from being utilized to its full potential. STUDY DESIGN AND METHODS: This study was a retrospective analysis of therapeutic plasma exchange (TPE) procedures performed from January 2015 to October 2022 in the Department of Transfusion Medicine at a large tertiary care hospital in North India. All consecutive TPE procedures were included. Overall and specialty-wise scoring for all patients was performed. Mean scores were calculated. RESULTS: A total of 1434 procedures were performed during the study duration of 7 years. These procedures were performed for 284 different patients. Majority of the procedures were referred from nephrology (895 of 1434, 62.4%), followed by neurology, gastroenterology, and liver transplant teams, hematology, critical care, rheumatology, pediatrics, and internal medicine. Complete response, partial response, and no-response were observed in 1077 (75.1%), 201 (14%), and 156 (10.9%) procedures respectively. Only 14 procedures reported adverse effects. DISCUSSION: Increasing effectiveness of TPE in a number of procedures and a variety of indications has broadened its scope, while the small number of adverse events, when supervised by trained Transfusion Medicine physicians has made TPE a more viable and safer alternative to other treatment modalities.

Multilayered nanofibrous scaffold of Polyvinyl alcohol/gelatin/poly (lactic-co-glycolic acid) enriched with hemostatic/antibacterial agents for rapid acute hemostatic wound healing.

Electrospun nanofibers scaffolds show promising potential in wound healing applications. This work aims to fabricate nanofibrous wound dressing as a novel approach for a topical drug delivery system. Herein, the electrospinning technique is used to design and fabricate bioabsorbable nanofibrous scaffolds of Polyvinyl alcohol/gelatin/poly (lactic-co-glycolic acid) enriched with thrombin (TMB) as hemostatic agent and vancomycin (VCM) as anti-bacterial agent for a multifunctional platform to control excessive blood loss, inhibit bacterial growth and enhance wound healing. SEM, FTIR, XRD, in vitro drug release, antimicrobial studies, biofilm, cell viability assay, and in vivo study in a rat model were used to assess nanofiber's structural, mechanical, and biological aspects. SEM images confirms the diameter of nanofibers which falls within the range from 150 to 300 nm for all the batches. Excellent swelling index data makes it suitable to absorb wound exudates. In-vitro drug release data shows sustained release behavior of nanofiber. Nanofibers scaffolds showed biomimetic behavior and excellent biocompatibility. Moreover, scaffolds exhibited excellent antimicrobial and biofilm activity against Staphylococcus aureus. Nanofibrous scaffolds showed less bleeding time, rapid blood coagulation, and excellent wound closure in a rat model. ELISA study demonstrated the decreasing level of inflammatory markers, such as TNF-α, IL1ß, and IL-6, making formulation promising for hemostatic wound healing applications. Finally, the study concludes that nanofibrous scaffolds loaded with TMB and VCM have promising potential as a dressing material for hemostatic wound healing applications.

Robust Prototypical Few-Shot Organ Segmentation With Regularized Neural-ODEs.

Despite the tremendous progress made by deep learning models in image semantic segmentation, they typically require large annotated examples, and increasing attention is being diverted to problem settings like Few-Shot Learning (FSL) where only a small amount of annotation is needed for generalisation to novel classes. This is especially seen in medical domains where dense pixel-level annotations are expensive to obtain. In this paper, we propose Regularized Prototypical Neural Ordinary Differential Equation (R-PNODE), a method that leverages intrinsic properties of Neural-ODEs, assisted and enhanced by additional cluster and consistency losses to perform Few-Shot Segmentation (FSS) of organs. R-PNODE constrains support and query features from the same classes to lie closer in the representation space thereby improving the performance over the existing Convolutional Neural Network (CNN) based FSS methods. We further demonstrate that while many existing Deep CNN-based methods tend to be extremely vulnerable to adversarial attacks, R-PNODE exhibits increased adversarial robustness for a wide array of these attacks. We experiment with three publicly available multi-organ segmentation datasets in both in-domain and cross-domain FSS settings to demonstrate the efficacy of our method. In addition, we perform experiments with seven commonly used adversarial attacks in various settings to demonstrate R-PNODE's robustness. R-PNODE outperforms the baselines for FSS by significant margins and also shows superior performance for a wide array of attacks varying in intensity and design.