Advances in HER2-Targeted Therapies: From monoclonal antibodies to dual inhibitors developments in cancer treatment.

HER2 receptors, overexpressed in certain human cancers, have drawn significant attention in cancer research due to their correlation with poor survival rates. Researchers have developed monoclonal antibodies like Trastuzumab and Pertuzumab against HER2 receptors, which have proven highly beneficial in cancer therapy. Bispecific antibodies like Zanidatamab and antibody-drug conjugates like T-DM1 have been developed to overcome the resistance associated with monotherapy. Small molecules such as Lapatinib, Neratinib, and Pyrotinib were initially developed for treating breast cancer. However, ongoing research is investigating their potential use in other types of cancer, often in combination with other medications. EGFR/HER2 dual-targeted drugs have overcome drug resistance associated with HER2-targeted monotherapy. This comprehensive review covers the structural characteristics of HER2, the HER family signaling pathway mechanism, recent findings regarding HER2 receptor involvement in various cancers, and diverse HER2-targeted therapies. This information provides a comprehensive understanding of HER2-targeted strategies in the evolving field of cancer treatment.

High Lead Contamination in Mother's Breastmilk in Bihar (India): Health Risk Assessment of the Feeding Children.

Lead poisoning in the recent times has caused serious health threats in the exposed human population. It is estimated about 815 million people are exposed to lead poisoning worldwide and in India total 275 million children are exposed to blood lead contamination. In the present study, in 6 districts of Bihar was carried out to know the extent of lead exposure in the children through their mother's breastmilk. The biological samples such as breastmilk, mother's urine, child's urine, and mother's blood samples were collected for quantitative lead estimation. Moreover, the selected household water sources (handpump) and the food consumed by the individuals- wheat, rice and potato samples were also collected for lead quantification. The study reveals that the breastmilk had high lead content in 92% of the samples (highest value 1309µg/L), in blood presence of lead was observed in 87% studied samples (highest value 677.2µg/L). In mother's urine the highest value was 4168µg/L (62%) and in child's urine the highest value was 875.4µg/L (62%) of the studied samples. Moreover, in the studied food samples, wheat had lead content in 45% the studied samples (highest value 7910µg/Kg). In rice in 40% of the studied samples (highest value 6972µg/Kg) and in potato 90% of the studied samples (highest value= 13786 µg/Kg) were found with elevated lead content respectively. The hazard quotient (HQ) and the cancer risk (CR) for lead contamination was very much higher in mothers followed by their children. The entire study indicated that lead exposure through food (wheat, rice and potato) has reached the mother's breastmilk and from their it has reached their child's body. This could cause serious hazards in the exposed children causing serious neurological damages, low IQ, low memory, and low mental growth in them. Therefore, a strategic action is required to control the present problem.

HPV DNA status and clinical history of patients are supplements for accurate reporting of the cytological Pap smear.

The present study was aimed at showing the importance of HPV DNA status and the clinical history of the patients required by the cytologist for accurate reporting. A total of 1250 symptomatic women who attended the gynaecology outpatient department of the Mahavir Cancer Sansthan and Nalanda Medical College, Patna, for pap smear examinations were screened and recruited for the study. Due to highly clinical symptoms out of the negative with inflammatory smears reported, one hundred and ten patients were randomly advised for biopsy and HPV 16/18 DNA analysis by a gynaecologist to correlate negative smears included in the study. Pap smear reports revealed that 1178 (94.24%) were negative for intraepithelial lesions (NILM) with inflammatory smears, 23 (1.84%) smears showed low-grade squamous intraepithelial lesions (LSIL), 12 (0.96%) smears showed high-grade squamous intraepithelial lesions, and 37 (2.96%) smears showed an atypical squamous cell of undetermined significance (ASC-US). A biopsy of 110 out of 1178 (NILM) patients revealed that 15 (13.63%) women had cervical cancer, 29 women had CIN I, 17 women had CIN II + CIN III, 35 women had benign cervical changes, and 14 women had haemorrhages. On the other hand, HPV 16/18 DNA was detected as positive in 87 out of 110. The high positivity of HPV in biopsied cases where frank cervical cancer and at-risk cancer were also observed in the negative smear-screened patients reveals that the HPV status and clinical history of the patients will be quite helpful to the cytologist for accurate reporting, and suggests that a negative HPV DNA result may be a stronger predictor of cervical cancer risk than a negative Pap test.

Hemodynamic evaluation of biomaterial-based surgery for Tetralogy of Fallot using a biorobotic heart, in silico, and ovine models.

Tetralogy of Fallot is a congenital heart disease affecting newborns and involves stenosis of the right ventricular outflow tract (RVOT). Surgical correction often widens the RVOT with a transannular enlargement patch, but this causes issues including pulmonary valve insufficiency and progressive right ventricle failure. A monocusp valve can prevent pulmonary regurgitation; however, valve failure resulting from factors including leaflet design, morphology, and immune response can occur, ultimately resulting in pulmonary insufficiency. A multimodal platform to quantitatively evaluate the effect of shape, size, and material on clinical outcomes could optimize monocusp design. This study introduces a benchtop soft biorobotic heart model, a computational fluid model of the RVOT, and a monocusp valve made from an entirely biological cell-assembled extracellular matrix (CAM) to tackle the multifaceted issue of monocusp failure. The hydrodynamic and mechanical performance of RVOT repair strategies was assessed in biorobotic and computational platforms. The monocusp valve design was validated in vivo in ovine models through echocardiography, cardiac magnetic resonance, and catheterization. These models supported assessment of surgical feasibility, handling, suturability, and hemodynamic and mechanical monocusp capabilities. The CAM-based monocusp offered a competent pulmonary valve with regurgitation of 4.6 ± 0.9% and a transvalvular pressure gradient of 4.3 ± 1.4 millimeters of mercury after 7 days of implantation in sheep. The biorobotic heart model, in silico analysis, and in vivo RVOT modeling allowed iteration in monocusp design not now feasible in a clinical environment and will support future surgical testing of biomaterials for complex congenital heart malformations.

Computational and biological approaches in repurposing ribavirin for lung cancer treatment: Unveiling antitumorigenic strategies.

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule.

Advancements in combining targeted therapy and immunotherapy for colorectal cancer.

Colorectal cancer (CRC) is a prevalent gastrointestinal cancer posing significant clinical challenges. CRC management traditionally involves surgery, often coupled with chemotherapy. However, unresectable or metastatic CRC (mCRC) presents a complex challenge necessitating innovative treatment strategies. Targeted therapies have emerged as the cornerstone of treatment in such cases, with interventions tailored to specific molecular attributes. Concurrently, immunotherapies have revolutionized cancer treatment by harnessing the immune system to combat malignant cells. This review explores the evolving landscape of CRC treatment, focusing on the synergy between immunotherapies and targeted therapies, thereby offering new avenues for enhancing the effectiveness of therapy for CRC.

A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer's Disease Risk in Older Men with Prostate Cancer.

Prostate cancer (PCa) is one of the most prevalent malignancies affecting males worldwide. Despite reductions in mortality rates due to advances in early identification and treatment methods, PCa remains a major health concern. Recent research has shed light on a possible link between PCa and Alzheimer's disease (AD), which is a significant neurological ailment that affects older males all over the world. Androgen deprivation therapy (ADT), a cornerstone therapeutic method used in conjunction with radiation and palliative care in advanced metastatic PCa cases, is critical for disease management. Evidence reveals a relationship between ADT and cognitive impairment. Hormonal manipulation may cause long-term cognitive problems through processes such as amyloid beta (Aß) aggregation and neurofibrillary tangles (NFTs). Fluctuations in basal androgen levels can upset the delicate balance of genes that are sensitive to androgen levels, contributing to cognitive impairment. This detailed review dives into the various aspects of PCa aetiology and its relationship with cognitive decline. It investigates the discovery of particular biomarkers, as well as microRNAs (miRNAs), which play important roles in pathogenic progression. The review attempts to identify potential biomarkers associated with ADT-induced cerebral changes, including Aß oligomer buildup, NFT formation, and tauopathy, which can contribute to early-onset dementia and cognitive impairment. Besides it further aims to provide insights into innovative diagnostic and therapeutic avenues for alleviating PCa and ADT-related cognitive sequelae by unravelling these complicated pathways and molecular mechanisms.

Design, synthesis and evaluation of new thiazolidin-4-ones as LPA1 receptor antagonists for breast cancer therapy.

Aim: Breast cancer has been a leading cause of mortality among women worldwide in recent years. Targeting the lysophosphatidic acid (LPA)-LPA1 pathway using small molecules could improve breast cancer therapy. Materials & methods: Thiazolidin-4-ones were developed and tested on MCF-7 cancer cells, and active compounds were analyzed for their effects on apoptosis, migration angiogenesis and LPA1 protein and gene expression. Results & conclusion: Compounds TZ-4 and TZ-6 effectively reduced the migration of MCF-7 cells, and induced apoptosis. TZ-4, TZ-6, TZ-8 and TZ-14 significantly reduced the LPA1 protein, LPA1 and angiogenesis gene expression in treated MCF-7 cells. Molecular docking and molecular dynamic simulation studies reveal the ligand interactions and stability of the LPA1-ligand complex. Developed thiazolidin-4-ones showed great potential as an LPA1-targeted approach to combating breast cancer.

Breast cancer is a major cause of death for women worldwide. Using small molecules to target the lysophosphatidic acid (LPA)­LPA₁ pathway could improve breast cancer treatment. We tested a type of molecule called thiazolidin-4-ones on breast cancer cells in the lab. We looked at how these molecules affected cell death, movement, blood vessel growth and the activity of the LPA₁ gene and protein. Some of these molecules, such as TZ-4 and TZ-6, reduced the movement of cancer cells and caused them to die. They also decreased the levels of LPA₁ protein and gene activity in the cells. We used computer simulations to see how these molecules interacted with the LPA₁ protein. Our findings suggest that thiazolidin-4-ones could be a promising treatment for breast cancer by targeting LPA₁.

Curcumin-loaded liposomes modulating the synergistic role of EpCAM and estrogen receptor alpha in lung cancer management.

Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, necessitating the exploration of innovative therapeutic strategies. This study delves into the in vitro potential of liposomal therapeutics utilizing Curcumin-loaded PlexoZome® (CUR-PLXZ) in targeting EpCAM/TROP1 and Estrogen Receptor Alpha (ERα) signalling pathways for LC management. The prevalence of LC, particularly non-small cell lung cancer (NSCLC), underscores the urgent need for effective treatments. Biomarkers like EpCAM/TROP1 and ERα/NR3A1 play crucial roles in guiding targeted therapies and influencing prognosis. EpCAM plays a key role in cell-cell adhesion and signalling along with ERα which is a nuclear receptor that binds estrogen and regulates gene expression in response to hormonal signals. In LC, both often get overexpressed and are associated with tumour progression, metastasis, and poor prognosis. Curcumin, a phytochemical with diverse therapeutic properties, holds promise in targeting these pathways. However, its limited solubility and bioavailability necessitate advanced formulations like CUR-PLXZ. Our study investigates the biological significance of these biomarkers in the A549 cell line and explores the therapeutic potential of CUR-PLXZ, which modulates the expression of these two markers. An in vitro analysis of the A549 human lung adenocarcinoma cell line identified that CUR-PLXZ at a dose of 5 µM effectively inhibited the expression of EpCAM and ERα. This finding paves the way for targeted intervention strategies in LC management.

Evaluating Static Bone Cysts (SBCs) Through Long-Term Volumetric Analysis Using CBCT: A Study with 6-Month Follow-Up.

Background: Salivary gland bone defects are static lesions which are rare entities, generally asymptomatic and found in routine imaging exams. However, in atypical cases or when misdiagnosed, surgical intervention is carried out. Purpose: a) The study is intended to investigate the frequency of SBC's and to describe the radiological characteristics of its subtypes; b) To evaluate the efficacy of volumetric analysis tool in CBCT and; c) To describe the confirmative role of CBCT in the diagnosis of SBC's without the need for surgical intervention. Material and Methods: The study was conducted on 11 subjects with SBC detected on 3304 panoramic radiographs. CBCT images for each patient were captured at baseline and at an interval of 6 months. Radiographic sub-types of SBC based on the relationship to mandibular canal and bucco-lingual expansion were studied. Files in DICOM format were transferred into OnDemand 3D program (Cybermed Co, Seoul, Korea) and volumes in mm3 of the cavities were measured by 2 observers at both intervals. Inter and intra reliability of volumetric measurements between observers was compared using correlation coefficient and student t test. Results: There were 8 males and 3 females who had SBC in this study (age range: 22-70 years). According to the relationship of SBC with mandibular canal, most SBCs were Type 1 (63.5 %) followed by Type 2 & 3 (18.5 %) each. The total volume of SBC in patients ranged from 146 mm3 to 650 mm3 (mean: 332.5 mm3). There was no significant difference between observers for volume measurements at baseline and at 6 months interval (p>0.05). Conclusions: Based on the results of this study, CBCT should be considered as a definitive diagnostic modality for volumetric analysis of SBCs. Over diagnosis, unnecessary surgical exploration and agony to patients can be avoided using this tool. Key words:Stafne bone cavity, CBCT, Volumetric analysis, salivary gland, panoramic radiography.

Biodegradable nanocarrier of gemcitabine and tocopherol succinate synergistically ameliorates anti-proliferative response in MIA PaCa-2 cells.

Gemcitabine (GEM) is an important chemotherapeutic agent used alone or in combination with other anticancer agents for the treatment of various solid tumors. In this study, the potential of a dietary supplement, α-tocopherol succinate (TOS) was investigated in combination with GEM by utilizing human serum albumin-based nanoparticles (HSA NPs). The developed nanoparticles were characterized using DLS, SEM and FTIR and evaluated in a panel of cell lines to inspect cytotoxic efficacy. The ratio metric selected combination of the NPs was further investigated in human pancreatic cancer cell line (MIA PaCa-2 cells) to assess the cellular death mechanism via a myriad of biochemical and bio-analytical assays including nuclear morphometric analysis by DAPI staining, ROS generation, MMP loss, intracellular calcium release, in vitro clonogenic assay, cell migration assay, cell cycle analysis, immunocytochemical staining followed by western blotting, Annexin V-FITC and cellular uptake studies. The desolvation-crosslinking method was used to prepare the NPs. The average size of TOS-HSA NPs and GEM-HSA NPs was found to be 189.47 ± 5 nm and 143.42 ± 7.4 nm, respectively. In combination, the developed nanoparticles exhibited synergism by enhancing cytotoxicity in a fixed molar ratio. The selected combination also significantly triggered ROS generation and mitochondrial destabilization, alleviated cell migration potential and clonogenic cell survival in MIA PaCa-2 cells. Further, cell cycle analysis, Annexin-V FITC assay and caspase-3 activation, up regulation of Bax and down regulation of Bcl-2 protein confirmed the occurrence of apoptotic event coupled with the G0/G1 phase arrest. Nanocarriers based this combination also offered approximately 14-folds dose reduction of GEM. Overall, the combined administration of TOS-HSA NPs and GEM-HSA NPs showed synergistic cytotoxicity accompanied with dose reduction of the gemcitabine. These encouraging findings could have implication in designing micronutrient based-combination therapy with gemcitabine and demands further investigation.

Circulatory Maternal Endothelin 1 and Matrix Metalloproteinase-9 Gene Expression in PREECLAMPSIA: A Study in Western Uttar Pradesh, India.

Introduction: Preeclampsia (PE) is a multiorgan disease of pregnant women. The main pathophysiology of PE is a trophoblastic invasion into maternal circulation leading to alterations in circulatory levels of matrix metalloproteinases (MMPs), inflammatory markers, and endothelin 1(ET1) levels. Therefore, the present study has explored the role of MMP-9 and ET1 and their association in PE. The advantage of the study is to provide insight into the pathology of PE. These markers may help in the early diagnosis and prognosis of PE. Objective: To investigate MMP-9 gene expression, ET1 level in PE cases and their correlation with blood pressure (BP), gestational age, weight, and height. Methods: The study design was a case-control observational study, which included 70 subjects in each case (PE) and controls (normal pregnant women (NPW)). Whole blood (250 ul) was utilized for RNA extraction (Trizol method) and synthesized cDNA as per manufacturer protocol. MMP-9 gene expression was analyzed by real-time PCR. Serum was utilized for ET1 estimation by sandwich ELISA. Results: The ET1 levels and MMP-9 gene expression were significantly increased in preeclamptic women as compared to controls. There was no significant correlation between MMP-9 gene expression and serum ET1 levels. However, a significant moderate association between systolic BP and diastolic BP with ET1 levels and MMP9 gene expression was seen in both PE and NPW. Conclusion: A significantly increased circulatory concentration of ET1 and MMP-9 gene expression in PE might be used as an early diagnostic as well as a prognostic marker of PE.

Restoration of p53 functions by suppression of mortalin-p53 sequestration: an emerging target in cancer therapy.

Functional inactivation of wild-type p53 is a major trait of cancerous cells. In many cases, such inactivation occurs by either TP53 gene mutations or due to overexpression of p53 binding partners. This review focuses on an overexpressed p53 binding partner called mortalin, a mitochondrial heat shock protein that sequesters both wild-type and mutant p53 in malignant cells due to changes in subcellular localization. Clinical evidence suggests a drastic depletion of the overall survival time of cancer patients with high mortalin expression. Therefore, mortalin-p53 sequestration inhibitors could be game changers in improving overall survival rates. This review explores the consequences of mortalin overexpression and challenges, status and strategies for accelerating drug discovery to suppress mortalin-p53 sequestration.

Development of an Anthropomorphic Heterogeneous Female Pelvic Phantom and Its Comparison with a Homogeneous Phantom in Advance Radiation Therapy: Dosimetry Analysis.

BACKGROUND: Accurate dosimetry is crucial in radiotherapy to ensure optimal radiation dose delivery to the tumor while sparing healthy tissues. Traditional dosimetry techniques using homogeneous phantoms may not accurately represent the complex anatomical variations in cervical cancer patients, highlighting the need to compare dosimetry results obtained from different phantom models. PURPOSE: The aim of this study is to design and evaluate an anthropomorphic heterogeneous female pelvic (AHFP) phantom for radiotherapy quality assurance in cervical cancer treatment. MATERIALS AND METHOD: Thirty RapidArc plans designed for cervical cancer patients were exported to both the RW3 homogeneous phantom and the anthropomorphic heterogeneous pelvic phantom. Dose calculations were performed using the anisotropic analytic algorithm (AAA), and the plans were delivered using a linear accelerator (LA). Dose measurements were obtained using a 0.6 cc ion chamber. The percentage (%) variation between planned and measured doses was calculated and analyzed. Additionally, relative dosimetry was performed for various target locations using RapidArc and IMRT treatment techniques. The AHFP phantom demonstrated excellent agreement between measured and expected dose distributions, making it a reliable quality assurance tool in radiotherapy. RESULTS: The results reveal that the percentage variation between planned and measured doses for all RapidArc quality assurance (QA) plans using the AHFP phantom is 10.67% (maximum value), 2.31% (minimum value), and 6.89% (average value), with a standard deviation (SD) of 2.565 (t = 3.21604, p = 0.001063). Also, for the percentage of variation between homogeneous and AHFP phantoms, the t-value is -11.17016 and the p-value is <0.00001. The result is thus significant at p < 0.05. We can see that the outcomes differ significantly due to the influence of heterogeneous media. Also, the average gamma values in RapidArc plans are 0.29, 0.32, and 0.35 (g ≤ 1) and IMRT plans are 0.45, 0.44, and 0.42 (g ≤ 1) for targets 1, 2, and 3, respectively. CONCLUSION: The AHFP phantom results show more dose variability than homogenous phantom outcomes. Also, the AHFP phantom was found to be suitable for QA evaluation.

Arsenic causing gallbladder cancer disease in Bihar.

In recent times Gallbladder cancer (GBC) incidences increased many folds in India and are being reported from arsenic hotspots identified in Bihar. The study aims to establish association between arsenic exposure and gallbladder carcinogenesis. In the present study, n = 200 were control volunteers and n = 152 confirmed gallbladder cancer cases. The studied GBC patient's biological samples-gallbladder tissue, gallbladder stone, bile, blood and hair samples were collected for arsenic estimation. Moreover, n = 512 gallbladder cancer patients blood samples were also evaluated for the presence of arsenic to understand exposure level in the population. A significantly high arsenic concentration (p < 0.05) was detected in the blood samples with maximum concentration 389 µg/L in GBC cases in comparison to control. Similarly, in the gallbladder cancer patients, there was significantly high arsenic concentration observed in gallbladder tissue with highest concentration of 2166 µg/kg, in gallbladder stones 635 µg/kg, in bile samples 483 µg/L and in hair samples 6980 µg/kg respectively. Moreover, the n = 512 gallbladder cancer patient's blood samples study revealed very significant arsenic concentration in the population of Bihar with maximum arsenic concentration as 746 µg/L. The raised arsenic concentration in the gallbladder cancer patients' biological samples-gallbladder tissue, gallbladder stone, bile, blood, and hair samples was significantly very high in the arsenic exposed area. The study denotes that the gallbladder disease burden is very high in the arsenic exposed area of Bihar. The findings do provide a strong link between arsenic contamination and increased gallbladder carcinogenesis.

Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma-A Review.

Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors of the upper aerodigestive tract, and a significant proportion of these tumors tend to exhibit unfavorable therapeutic responses to the existing treatment options. Comprehending the immunopathology of these tumors and choosing an appropriate immunotherapeutic maneuver seems to be a promising avenue for solving this problem. The current review provides a detailed overview of the strategies, targets, and candidates for therapeutic vaccination in HNSCC. The classical principle of inducing a potent, antigen-specific, cell-mediated cytotoxicity targeting a specific tumor antigen seems to be the most effective mechanism of therapeutic vaccination, particularly against the human papilloma virus positive subset of HNSCC. However, approaches such as countering the immunosuppressive tumor microenvironment of HNSCC and immune co-stimulatory mechanisms have also been explored recently, with encouraging results.

On-Demand Cell Sheet Release with Low Density Peptide-Functionalized Non-LCST Polymer Brushes.

Cell sheet harvesting offers a great potential for the development of new therapies for regenerative medicine. For cells to adhere onto surfaces, proliferate, and to be released on demand, thermoresponsive polymeric coatings are generally considered to be required. Herein, an alternative approach for the cell sheet harvesting and rapid release on demand is reported, circumventing the use of thermoresponsive materials. This approach is based on the end-group biofunctionalization of non-thermoresponsive and antifouling poly(2-hydroxyethyl methacrylate) (p(HEMA)) brushes with cell-adhesive peptide motifs. While the nonfunctionalized p(HEMA) surfaces are cell-repellant, ligation of cell-signaling ligand enables extensive attachment and proliferation of NIH 3T3 fibroblasts until the formation of a confluent cell layer. Remarkably, the formed cell sheets can be released from the surfaces by gentle rinsing with cell-culture medium. The release of the cells is found to be facilitated by low surface density of cell-adhesive peptides, as confirmed by X-ray photoelectron spectroscopy. Additionally, the developed system affords possibility for repeated cell seeding, proliferation, and release on previously used substrates without any additional pretreatment steps. This new approach represents an alternative to thermally triggered cell-sheet harvesting platforms, offering possibility of capture and proliferation of various rare cell lines via appropriate selection of the cell-adhesive ligand.

Empirical Antitubercular Treatment for Lymphadenopathy: Are We Missing Lymphoma?

OBJECTIVE: To evaluate the proportion of patients who received empirical treatment with antitubercular therapy (ATT) prior to the diagnosis of Hodgkin lymphoma (HL) in the first multicentric, prospective study on HL from India, and to assess its impact on extent of disease at diagnosis and outcomes. METHODS: Children < 18 y with biopsy proven HL were enrolled in InPOG-HL-15-01. Along with other clinical and epidemiological data, history of prior treatment with ATT was documented. All patients received treatment as per a risk-stratified, response-adapted strategy. RESULTS: Out of 396, 115 (29%) children had received ATT prior to establishing a definitive diagnosis of HL. This cohort presented with advanced-stage disease (p = 0.001) and B symptoms (p = 0.001) in a higher proportion of cases. Consequently, those children were more likely to receive 6 rather than 4 cycles of chemotherapy (p = 0.001). They were more likely to have infradiaphragmatic involvement (p = 0.001). Overall survival and event-free survival were not different. CONCLUSION: Empirical treatment with ATT in children presenting with lymphadenopathy continues to be practiced widely in India. The delay in diagnosis may contribute to children presenting with advanced-stage disease warranting more intensive treatment for successful outcomes.

Kidney Pathology Education for Nephrology Fellows: Past, Present, and Future.

Kidney pathology education is a critical component in training of nephrology fellows, as well as for continuing medical education for practicing nephrologists. Kidney pathology images are included on nephrology fellow board exams, and clinicopathologic correlation of kidney biopsy findings is critical in everyday clinical practice. Nephropathology training is a requirement by the American College of Graduate Medical Education within nephrology fellowship curricula. However, greater than one-third of fellowship program directors believe that nephropathology training for their fellows is not sufficient. During the Coronavirus Disease-19 pandemic, the use of digital learning has become commonplace with virtual conferences (local, national, and international) and online meetings becoming the norm for education. Nephrology has become a leader in free open-access online medical education, both prior to and, to even a greater extent, during the pandemic. Here, we review available resources to nephrology fellows and other learners to supplement nephropathology training, which includes medical blogs, journal clubs, interactive quizzes and games, online conferences, podcasts, and mentorship opportunities. These resources are archived and provide durable content to learners of all stages of training, even beyond the pandemic.