Extraction of terminal ileal lipomas to cecum can facilitate endoscopic resection: A case series with video.

Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures.

Hypotensive effect of potent angiotensin-I-converting enzyme inhibitory peptides from corn gluten meal hydrolysate: Gastrointestinal digestion and transepithelial transportation modifications.

The study examined the antihypertensive effect of peptides derived from pepsin-hydrolyzed corn gluten meal, namely KQLLGY and PPYPW, and their in silico gastrointestinal tract digested fragments, KQL and PPY, respectively. KQLLGY and PPYPW showed higher angiotensin I-converting enzyme (ACE)-inhibitory activity and lower ACE inhibition constant (Ki) values when compared to KQL and PPY. Only KQL showed a mild antihypertensive effect in spontaneously hypertensive rats with -7.83 and - 5.71 mmHg systolic and diastolic blood pressure values, respectively, after 8 h oral administration. During passage through Caco-2 cells, KQL was further degraded to QL, which had reduced ACE inhibitory activity. In addition, molecular dynamics revealed that the QL-ACE complex was less stable compared to the KQL-ACE. This study reveals that structural transformation during peptide permeation plays a vital role in attenuating antihypertensive effect of the ACE inhibitor peptide.

Clinico-radiological and pulmonary function assessment of post-COVID-19 patients with respiratory symptoms.

Background: Respiratory symptoms may persist for several weeks following the initial coronavirus disease 2019 (COVID-19) infection. The aims and objectives were to assess the clinical symptoms, pulmonary functions, and radiological changes and to assess the cardio-vascular complications in post-COVID-19 patients. Methods: This observational study was conducted in the Department of Pulmonary Medicine in collaboration with the Department of Cardiology, SCBMCH, Cuttack, from March 2021 to August 2022 on 75 post-COVID-19 patients with respiratory symptoms from 4 weeks to 2 years after treatment for COVID-19 infection. Post-COVID patients having previous respiratory diseases were excluded from the study. Results: Among 75 patients, the most common age group was 18-30 years with a male-to-female ratio of 2.5:1. Based on O2 requirement, patients were divided into the mild symptomatic group and moderate to severe pneumonia group. The most common respiratory symptom was dyspnea, followed by cough with expectoration. Bilateral crepitations were found in 17% of cases. C-reactive protein (CRP) and D-dimer were increased in 38.6% and 32% of patients, respectively. 42.6% had abnormal chest X-ray, and the most common abnormal finding was reticular thickening. In spirometry, the restrictive pattern and mixed pattern were the predominant types documented in 49.3% and 13.3% of cases, respectively, which were significant in the moderate-severe group. Diffusion capacity of the lungs for carbon monoxide (DLCO) was performed in only 19 patients (mild group 13 and moderate-severe group 6). Twelve (63.2%) patients had abnormal DLCO. P- values were significant for RV (0.0482) and RV/TLC (0.0394). High-resolution computed tomography (HRCT) of the thorax was abnormal in 55.7% with the most common abnormalities as inter- and intra-lobular septal thickening. The left ventricular ejection fraction was preserved in all patients, with right atrium and right ventricle enlargement in 2.6% and pulmonary hypertension in 4.0% of participants. Conclusion: All post-COVID-19 patients having respiratory symptoms after recovery from acute COVID-19 may be referred by family care physicians to a dedicated post-COVID center for further evaluation, management, and early rehabilitation to decrease the morbidity in recovered patients. Persistent increased blood parameters like TLC, N/L ratio, RBS, CRP, and D-dimer seen in recovered post-COVID-19 patients. The long-term impact of CT findings on respiratory symptoms, pulmonary functions, and quality of life is unknown. Cardiovascular abnormalities in post-COVID-19 patients are infrequent.

Understanding pediatric snakebites: Clinical and epidemiological insights from a healthcare center in Bihar, India.

Background: Snakebites are a common medical emergency and occupational hazard for children in India, particularly in rural areas where poverty is prevalent. However, there is limited data on the epidemiology of snakebites on the Indian subcontinent. Objective: This cross-sectional, observational study aims to investigate the epidemiology, major clinical manifestations, and outcomes of snakebites in children under the age of 15 who were admitted to a tertiary care center in Bihar, a state in East India, and draw attention to this public health concern. Methods: A cross-sectional observational study was conducted at the Department of Paediatrics, Patna Medical College and Hospital, Patna. The study included all cases of snakebites with features of envenomation involving patients less than 15 years of age who were brought to the department over a 2-year period. Data were collected using a data collection form and analyzed using the Statistical Package for the Social Sciences, version 11.0 (SPSS Inc., Chicago, IL, USA). Results: A total of 59 cases were recorded, with 62.71% (n = 37) being male and 37.28% (n = 22) being female. Kraits were responsible for 38.9% (n = 23) of cases, vipers for 42.3% (n = 25), and cobras for 5% (n = 3). Fang marks were present in 67.7% (n = 40) of cases, and the majority of bites (84.7%, n = 50) occurred on a lower limb during the day. The age distribution showed that 16.9% (n = 10) were below 5 years old, 44% (n = 26) were between 5 and 10 years old, and 22% (n = 13) were above 10 years old. Traditional treatment was used in 44.7% (n = 22) of cases, with the most common treatments being local incision + tourniquet (22%, n = 13) and no traditional treatment (55.9%, n = 33). The highest number of cases occurred during July-September (35.5%, n = 21). Conclusion: Snakebites are a significant public health issue in Bihar, India, with the majority of cases occurring in rural areas. The study highlights the importance of increased awareness and preparedness among healthcare providers and the general public, particularly during the monsoon season. Early hospital transfer, prehospital management, and prevention should be promoted through regular public health initiatives.

A novel GFP-based strategy to quantitate cellular spatial associations in HSV-1 viral pathogenesis.

Periodic reactivation of herpes simplex virus type 1 (HSV-1) triggers immune responses that result in corneal scarring (CS), known as herpes stromal keratitis (HSK). Despite considerable research, fully understanding HSK and eliminating it remains challenging due to a lack of comprehensive analysis of HSV-1-infected immune cells in both corneas and trigeminal ganglia (TG). We engineered a recombinant HSV-1 expressing green fluorescent protein (GFP) in the virulent McKrae virus strain that does not require corneal scarification for efficient virus replication (GFP-McKrae). Next-generation sequencing (NGS) analysis, along with in vitro and in vivo assays, showed that GFP-McKrae virus was similar to WT-McKrae virus. Furthermore, corneal cells infected with GFP-McKrae were quantitatively analyzed using image mass cytometry (IMC). The single-cell reconstruction data generated cellular maps of corneas based on the expression of 25 immune cell markers in GFP-McKrae-infected mice. Corneas from mock control mice showed the presence of T cells and macrophages, whereas corneas from GFP-McKrae-infected mice on days 3 and 5 post-infection (PI) exhibited increased immune cells. Notably, on day 3 PI, increased GFP expression was observed in closely situated clusters of DCs, macrophages, and epithelial cells. By day 5 PI, macrophages and T cells became prominent. Finally, immunostaining methods detected HSV-1 or GFP and gD proteins in latently infected TG. This study presents a valuable strategy for identifying cellular spatial associations in viral pathogenesis and holds promise for future therapeutic applications.IMPORTANCEThe goal of this study was to establish quantitative approaches to analyze immune cell markers in HSV-1-infected intact corneas and trigeminal ganglia from primary and latently infected mice. This allowed us to define spatial and temporal interactions between specific immune cells and their potential roles in virus replication and latency. To accomplish this important goal, we took advantage of the utility of GFP-McKrae virus as a valuable research tool while also highlighting its potential to uncover previously unrecognized cell types that play pivotal roles in HSV-1 replication and latency. Such insights will pave the way for developing targeted therapeutic approaches to tackle HSV-1 infections more effectively.

Reusable semi-IPN polymer networks as long-term antibacterial coatings.

The current study aimed to develop a reusable antibacterial coating that can be employed for efficient bacterial killing. We synthesized a water-soluble methacrylamide-based copolymer consisting of cationic and hydrophobic groups and coated it onto a glass surface through the formation of semi-interpenetrating polymer networks (semi-IPN) of aminopropyl triethoxysilane and glutaraldehyde. The coated surface was exposed to Gram-negative and Gram-positive bacteria, where the surface exhibited rapid bacterial killing ability within 5-15 min. The substrates displayed a minimal loss of antibacterial activity even after two water rinse cycles. The coatings were able to kill both the bacterial strains even after 5 weeks, suggesting excellent longevity. The surfaces were stable after repeated wiping cycles with 70% IPA using Kim wipes and 5 min sonication in DI water as no bactericidal activity was lost. Thus, a sustainable antibacterial copolymer coating was developed, and it is stable and reusable against bacterial contamination and could be employed as a long-term antibacterial coating.

The NF-κB Factor Relish maintains blood progenitor homeostasis in the developing Drosophila lymph gland.

Post-larval hematopoiesis in Drosophila largely depends upon the stockpile of progenitors present in the blood-forming organ/lymph gland of the larvae. During larval stages, the lymph gland progenitors gradually accumulate reactive oxygen species (ROS), which is essential to prime them for differentiation. Studies have shown that ROS triggers the activation of JNK (c-Jun Kinase), which upregulates fatty acid oxidation (FAO) to facilitate progenitor differentiation. Intriguingly, despite having ROS, the entire progenitor pool does not differentiate simultaneously in the late larval stages. Using expression analyses, genetic manipulation and pharmacological approaches, we found that the Drosophila NF-κB transcription factor Relish (Rel) shields the progenitor pool from the metabolic pathway that inducts them into the differentiation program by curtailing the activation of JNK. Although ROS serves as the metabolic signal for progenitor differentiation, the input from ROS is monitored by the developmental signal TAK1, which is regulated by Relish. This developmental circuit ensures that the stockpile of ROS-primed progenitors is not exhausted entirely. Our study sheds light on how, during development, integrating NF-κB-like factors with metabolic pathways seem crucial to regulating cell fate transition during development.

Mid-shaft Clavicle Fracture with Disguised Ipsilateral Type IV Acromioclavicular Joint Dislocation - A Rare Case Report.

Introduction: Clavicle fractures and acromioclavicular (AC) joint disruptions are very common injuries. However, both injuries occurring simultaneously are very rare entities. Case Report: In this article, we report a case of 21-year-old gentleman with a history of road traffic accident with a right mid-shaft clavicle fracture. We planned for the right clavicle plating. Intraoperatively incidentally, we found that the patient is having type 4 rockwood AC joint disruption with complete posterior displacement and gross instability. We repaired it after plating the clavicle using Ethibond with intraosseous sutures and augmented with trans acromion k wire. Later, k wire was removed, and the patient regained full range of motion shoulder after subsequent follow-up and physiotherapy. Conclusion: Clavicle fractures with ipsilateral AC joint disruptions are very rare. Diagnosing the AC joint disruption and appropriate management is very essential to regain the shoulder function and outcome.

Pooled endogenous protein tagging and recruitment for systematic profiling of protein function.

The emerging field of induced proximity therapeutics, which involves designing molecules to bring together an effector and target protein-typically to induce target degradation-is rapidly advancing. However, its progress is constrained by the lack of scalable and unbiased tools to explore effector-target protein interactions. We combine pooled endogenous gene tagging using a ligand-binding domain with generic small-molecule-based recruitment to screen for induction of protein proximity. We apply this methodology to identify effectors for degradation in two orthogonal screens: using fluorescence to monitor target levels and a cellular growth that depends on the degradation of an essential protein. Our screens revealed new effector proteins for degradation, including previously established examples, and converged on members of the C-terminal-to-LisH (CTLH) complex. We introduce a platform for pooled induction of endogenous protein-protein interactions to expand our toolset of effector proteins for protein degradation and other forms of induced proximity.

Patellar Tendon Ruptures after Total Knee Arthroplasty.

Patellar tendon rupture following total knee arthroplasty (TKA) is a rare, but devastating complication. These injuries occur most frequently in the acute period following TKA due to trauma to the knee. Patellar tendon ruptures that disrupt the extensor mechanism create a marked functional deficit, impacting every facet of daily life. In complete ruptures of the patellar tendon, repair or reconstruction is typically indicated; however, complication rates following intervention remain high, between 25 to 63%. Operative intervention remains the mainstay of treatment, with only certain specific situations where nonoperative intervention is appropriate. Operative treatments include repair with or without augmentation or reconstruction. Augmentation does reduce the high risk of complications, bringing rates down from 63 to 25%. Augmentation options include autografts, allografts, synthetic grafts, or synthetic meshes. Despite advancements, outcomes are unpredictable, and complications are common, highlighting the need for further research to improve treatment protocols. Operative techniques are chosen based on the acuity, location of disruption, and status of the residual soft tissues. This article provides an overview of patellar tendon ruptures following TKA, the various treatment options, and the recommendations of the senior authors for each common type of patellar tendon injury encountered.

Effects of Sotagliflozin on Health Status in Patients With Worsening Heart Failure: Results From SOLOIST-WHF.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve health status in heart failure (HF) across the left ejection fraction ejection spectrum. However, the effects of SGLT1 and SGLT2 inhibition on health status are unknown. OBJECTIVES: These prespecified analyses of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trial examined the effects of sotagliflozin vs placebo on HF-related health status. METHODS: SOLOIST-WHF randomized patients hospitalized or recently discharged after a worsening HF episode to receive sotagliflozin or placebo. The primary endpoint was total number of HF hospitalizations, urgent HF visits, and cardiovascular death. Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) score was a prespecified secondary endpoint. This analysis evaluated change in the KCCQ-12 score from baseline to month 4. RESULTS: Of 1,222 patients randomized, 1,113 (91%) had complete KCCQ-12 data at baseline and 4 months. The baseline KCCQ-12 score was low overall (median: 41.7; Q1-Q3: 27.1-58.3) and improved by 4 months in both groups. Sotagliflozin vs placebo reduced the risk of the primary endpoint consistently across KCCQ-12 tertiles (Ptrend = 0.54). Sotagliflozin-treated patients vs those receiving placebo experienced modest improvement in KCCQ-12 at 4 months (adjusted mean change: 4.1 points; 95% CI: 1.3-7.0 points; P = 0.005). KCCQ-12 improvements were consistent across prespecified subgroups, including left ventricular ejection fraction <50% or ≥50%. More patients receiving sotagliflozin vs those receiving placebo had at least small (≥5 points) improvements in KCCQ-12 at 4 months (OR: 1.38; 95% CI: 1.06-1.80; P = 0.017). CONCLUSIONS: Sotagliflozin improved symptoms, physical limitations, and quality of life within 4 months after worsening HF, with consistent benefits across baseline demographic and clinical characteristics. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934).

Early diagnosis of lupus: A possibilty. A multicentric study from SLE Special Interest Group (SIG) of Indian Rheumatology Association (IRA).

INTRODUCTION: Systemic Lupus Erythematosus (SLE) warrants an early diagnosis and prompt management. Delay in diagnosis can result in repeated flares, permanent damage, and even death. There is a large variability in the time taken to diagnose SLE across the world. We undertook this study to determine the time taken for diagnosis of SLE in India and to identify the factors associated. METHODS: Patients with SLE diagnosed within the previous 1 year as per Systemic Lupus Erythematosus International Collaborating Clinics criteria (SLICC) 2012 criteria were included in a cross-sectional multicentre questionnaire-based survey. Demographic profile, self-reported socioeconomic status as per Kuppuswamy classification of socioeconomic status (version 2022) (SES), and several healthcare related parameters including referral pattern were recorded. Median time taken for diagnosis was used to demarcate early or late diagnosis and associated factors were explored. RESULTS: We included 488 patients with SLE from 10 rheumatology centres. The median time to diagnosis was 6 months Interquartile Range (IQR 3,14.7) and within 3 months in about one third [150(30.7%)]. Very early diagnosis (<1 month) was established in 78(16.0%) patients. The mean SLE Disease Activity Index (SLEDAI) at diagnosis was 10.28+7.24. In univariate analysis, an older age, lower SES, non-southern state of residence and larger family size were significantly associated with late diagnosis. In the multivariate analysis, higher SES (AOR 0.95, 95% CI: 0.92-0.98), multiple organ system involvement at initial presentation (AOR1.75 95%CI: 1.08-2.84) and place of residence in south Indian states (AOR1.92 95%CI: 1.24-2.97) had lesser odds of being associated with late diagnosis. Distance from the closest medical centre/professional did not influence the time to diagnosis. Majority of patients had first consulted a medical graduate (42.5%) or postgraduate doctor (48.2%), and referral to rheumatologist was largely done by postgraduate (65%) doctors. More than half of our patients (61%) self-finance their treatment. CONCLUSION: Median time to diagnosis of SLE was 6 months, 1/3rd being diagnosed within 3 months and 78(16.0%) with 1 month of symptom onset. Delay in diagnosis was noted in those belonging to lower socioeconomic strata and those with single organ disease. Distance to the health care facility did not influence time to diagnosis.

Interface-Centric Strategies in Kesterite Solar Cells: Addressing Challenges, solutions, and Future Directions for Efficient Solar-Harvesting Technologies.

As reserves of non-renewable energy sources decline, the search for sustainable alternatives becomes increasingly critical. Next-generation energy materials play a key role in this quest by enabling the manipulation of properties for effective energy solutions and understanding interfaces to enhance energy yield. Studying these interfaces is essential for managing charge transport in optoelectronic devices, yet it presents significant challenges. This review emphasizes the critical role of interfaces in kesterite solar cells (KSCs), focusing on interfacial architecture, carrier losses, and non-radiative recombination. This review highlights the importance of addressing interface issues and utilizing advanced characterization tools to reveal interface properties. Current interface problems are addressed, recent advancements in interface engineering are summarized, and perspectives on future challenges and prospects are offered. The goal is to illuminate the nature of interfaces and tackle interface losses, which are crucial for improving device design and performance. Despite their pivotal role in device operation, comprehensive reviews on interfaces are lacking, underscoring the relevance of the work for researchers in material interfaces and device engineering. It is hoped that this article will spark interest and inspire further research into interface studies and the mitigation of interface losses.

Endoscopic ultrasound-guided biliary interventions.

Endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) includes EUS-guided hepaticogastrostomy (EUS-HGS), EUS-guided choledochoduodenostomy (EUS-CDS), EUS-guided gallbladder drainage (EUS-GBD), EUS-guided antegrade stenting (EUS-AG) and EUS-guided rendezvous (EUS-RV). While EUS-HGS, EUS-CDS and EUS-GBD are transluminal drainage procedures, EUS-AG is a traspapillary drainage procedure and EUS-RV is a procedure intended to facilitate endoscopic retrograde cholangio pancreatography (ERCP) in instances of failed cannulation. These procedures were initially developed as options for endoscopic salvage of failed ERCP, but have evolved to become first-line interventions also for select indications over time as the technique and expertise improved. Several randomised controlled trials have demonstrated EUS-BD, especially EUS-CDS has similar or even better outcomes as compared to ERCP in malignant biliary obstruction. However, widespread adoption of these modalities is limited by the availability of expertise, steep learning curve, lack of standardization of techniques and cost. In this review, we aim to provide an overview of various EUS-BD procedures including the indications, accessories, technique, outcomes and follow-up of each of these procedures.

Trichorhinophalangeal syndrome 1 expression in breast and nonbreast metastases from Müllerian, lung, gastrointestinal tract, and pancreatic primary tumors by immunohistochemistry with cytology cell block specimens.

BACKGROUND: Trichorhinophalangeal syndrome 1 (TRPS1) expression in primary breast and other solid tumors has been investigated but its role as a marker in metastatic tumors is unclear. The objective of this study was to evaluate the sensitivity and specificity of TRPS1 as a breast cancer immunomarker in metastatic tumors that originated from breast, Müllerian, lung, gastrointestinal (GI), and pancreatic primary tumors with cell blocks from fine-needle aspiration (FNA) and effusion specimens. METHODS: Cell blocks were immunostained with anti-TRPS1 monoclonal antibody (clone EPR16171). Histochemical scores (H scores) (proportion × intensity; range, 0-300) were assigned; H scores of ≥10 were considered positive. Overall, 160 specimens were examined, including 127 FNAs (35 breast, 25 Müllerian, 36 lung, and 31 GI and pancreatic carcinomas) and 33 effusion specimens (18 breast, 12 Müllerian, one lung, and two GI carcinomas). RESULTS: TRPS1 was positive in 51 of 53 (96%) metastatic breast carcinomas and in 28 of 107 (26.2%) nonbreast metastatic tumors. Metastatic breast carcinoma showed the highest mean H score of 247.35, compared to 45.36 in Müllerian, 8.4 in lung, and 5.88 in GI tumors. The sensitivity and specificity of TRPS1 for identifying a breast origin in metastatic tumors was 96.22% and 72.89%, respectively. CONCLUSIONS: Despite high overall sensitivity, TRPS1 showed lower specificity as a breast immunomarker because of its expression in nonbreast tumors. The mean H score in nonbreast tumors was significantly lower than in metastatic breast tumors. It is important to recognize the broad range of expression of TRPS1 in metastatic breast and nonbreast tumors to avoid an incorrect determination of a metastatic tumor's organ of origin.

Complexity-Building Exhaustive Dearomatization of Benzenoid Aromatics within an ESIPT-Initiated Three-Step Photochemical Cascade.

Dearomative cycloadditions offer rapid access to complex 3D molecular architectures, commonly via a sp2-to-sp3 rehybridization of two atoms of an aromatic ring. Here we report that the 6e π-system of a benzenoid aromatic pendant could be exhaustively depleted within a single photochemical cascade. An implementation of this approach involves the initial dearomative [4+2] cycloaddition of the Exited State Intramolecular Proton Transfer (ESIPT)-generated azaxylylene, followed by two consecutive [2+2] cycloadditions of auxiliary π moieties strategically positioned in the photoprecursor. Such photochemical cascade fully dearomatizes the benzenoid aromatic ring, saturating all six sp2 atoms to yield a complex sp3-rich scaffold with high control of its 3D molecular shape, rendering it a robust platform for rapid systematic mapping of underexplored chemical space. Significant growth of molecular complexity - starting with a modular synthesis of photoprecursors from readily available building blocks - is quantified by Böttcher score calculations.

Advances in CRISPR-Cas systems for blood cancer.

CRISPR-Cas systems have revolutionised precision medicine by enabling personalised treatments tailored to an individual's genetic profile. Various CRISPR technologies have been developed to target specific disease-causing genes in blood cancers, and some have advanced to clinical trials. Although some studies have explored the in vivo applications of CRISPR-Cas systems, several challenges continue to impede their widespread use. Furthermore, CRISPR-Cas technology has shown promise in improving the response of immunotherapies to blood cancers. The emergence of CAR-T cell therapy has shown considerable success in the targeting and correcting of disease-causing genes in blood cancers. Despite the promising potential of CRISPR-Cas in the treatment of blood cancers, issues related to safety, ethics, and regulatory approval remain significant hurdles. This comprehensive review highlights the transformative potential of CRISPR-Cas technology to revolutionise blood cancer therapy.

Drug response-based precision therapeutic selection for tamoxifen-resistant triple-positive breast cancer.

Breast cancer adaptability to the drug environment reduces the chemotherapeutic response and facilitates acquired drug resistance. Cancer-specific therapeutics can be more effective against advanced-stage cancer than standard chemotherapeutics. To extend the paradigm of cancer-specific therapeutics, clinically relevant acquired tamoxifen-resistant MCF-7 proteome was deconstructed to identify possible druggable targets (N = 150). Twenty-eight drug inhibitors were used against identified druggable targets to suppress non-resistant (NC) and resistant cells (RC). First, selected drugs were screened using growth-inhibitory response against NC and RC. Seven drugs were shortlisted for their time-dependent (10-12 days) cytotoxic effect and further narrowed to three effective drugs (e.g., cisplatin, doxorubicin, and hydroxychloroquine). The growth-suppressive effectiveness of selected drugs was validated in the complex spheroid model (progressive and regressive). In the progressive model, doxorubicin (RC: 83.64 %, NC: 54.81 %), followed by cisplatin (RC: 76.66 %, NC: 68.94 %) and hydroxychloroquine (RC: 68.70 %, NC: 61.78 %) showed a significant growth-suppressive effect. However, in fully grown regressive spheroid, after 4th drug treatment, cisplatin significantly suppressed RC (84.79 %) and NC (40.21 %), while doxorubicin and hydroxychloroquine significantly suppressed only RC (76.09 and 76.34 %). Our in-depth investigation effectively integrated the expression data with the cancer-specific therapeutic investigation. Furthermore, our three-step sequential drug-screening approach unbiasedly identified cisplatin, doxorubicin, and hydroxychloroquine as an efficacious drug to target heterogeneous cancer cell populations. SIGNIFICANCE STATEMENT: Hormonal-positive BC grows slowly, and hormonal-inhibitors effectively suppress the oncogenesis. However, development of drug-resistance not only reduces the drug-response but also increases the chance of BC aggressiveness. Further, alternative chemotherapeutics are widely used to control advanced-stage BC. In contrast, we hypothesized that, compared to standard chemotherapeutics, cancer-specific drugs can be more effective against resistant-cancer. Although cancer-specific treatment identification is an uphill battle, our work shows proteome data can be used for drug selection. We identified multiple druggable targets and, using ex-vivo methods narrowed multiple drugs to disease-condition-specific therapeutics. We consider that our investigation successfully interconnected the expression data with the functional disease-specific therapeutic investigation and selected drugs can be used for effective resistant treatment with higher therapeutic response.

Spinal subdural abscess following chronic meningitis - A rare manifestation of Mucormycosis.

A 57-year old man with uncontrolled diabetes presented with features suggestive of chronic meningitis. Cerebrospinal fluid (CSF) analysis revealed a polymorphonuclear pleocytosis with low glucose and high protein levels in the CSF. Bacterial and fungal cultures and tests for M. tuberculosis were negative. MRI spine showed leptomeningeal enhancement. On ruling out other causes, fungal meningitis was considered. The patient developed paraparesis in the hospital. MRI showed peripherally enhancing subdural lesion with dorsal cord involvement at the level of D4 and D5 vertebrae. On laminectomy and exploration, an intradural extramedullary abscess and a granuloma were noticed at T4--T5 spinal levels causing compression of the cord below. Histopathological examination of the lesions revealed acute on chronic inflammatory infiltrates interspersed by broad, aseptate, ribbon-like fungal elements highlighted by PAS stain, diagnostic of mucormycosis. Intravenous amphotericin B and oral posaconazole were administered for more than 8 weeks. On follow-up, he had complete neurological recovery without sequelae.

Painless Nodular Cheek Skin Swelling: A Clinical Challenge.

Basaloid neoplasms of the head and neck region pose a specific challenge both for clinicians and pathologists. It is a diverse group of neoplasms that include benign as well as malignant entities. These neoplasms can arise from various head and neck subsites such as skin, salivary gland, and sinonasal tract. Cytological diagnosis of these tumors is extremely difficult due to morphological overlap with other biphasic tumors and within the basaloid group itself. Here, we are presenting a case of basaloid neoplasm which turned out to be a basal cell adenocarcinoma of the left parotid gland on postoperative histopathological examination.