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In the present paper, we examined Erebidae specimens collected from different parts of India, and describe a new species in Arctiinae, Miltochrista terrarega sp. nov. and report five species new to the Indian fauna: Ericeia sobria Walker, [1858] in Erebinae; Euproctis cryptosticta Collenette, 1934, Artaxa kanshireia (Wileman, 1910), Nygmia ganesa Kishida, 2020 and N. hanuman Kishida, 2020 in Lymantriinae. Genitalia of B. calopasa from India is also provided. We studied, for the first time, the females of N. ganesa and N. hanuman, and the female genitalia of A. kanshireia and E. cryptosticta. The diagnoses of all the seven species along with their habitus and genitalia illustrations are provided along with the distributions.

Abstract The present study investigated the relationship between MSH3 and MSH6 genes in lung cancer patients. Genotyping of lung cancer patients and healthy controls was performed. Odds ratio values were calculated and survival analysis performed. Patients with mutant genotype (TT) for MSH6 polymorphism have 1.5-fold risk for the development of lung cancer (p = 0.03). For non-smokers, the mutant-type genotype had a threefold increased risk of lung cancer (p = 0.01). Patients administered with docetaxel and carbo/cisplatin and carrying GT genotype for MSH6 polymorphism, patients reported a decrease in median survival time (4.9 vs 9.13 months). MSH3 and MSH6 polymorphisms are involved in modulating the risk towards lung cancer. MSH6 polymorphism is associated with high mortality rate for patients undergoing cisplatin and docetaxel chemotherapy.

Aim: There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses. Methods: Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy. Results: At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0–1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5–14] and 16 (IQR = 9–23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]. Conclusions: Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.

In most cancers, tumor hypoxia downregulates the expression of C‐C motif chemokine 2 (CCL2), and this downregulation has been implicated in monocyte infiltration and tumor progression; however, the molecular mechanism is not yet clear. We compared noncancerous and lung‐adenocarcinoma human samples for hypoxia‐inducible factor 1‐alpha (HIF‐1A), microRNA‐210‐3p (mir‐210‐3p), and CCL2 levels. Mechanistic studies were performed on lung adenocarcinoma cell lines and 3D tumor spheroids to understand the role of hypoxia‐induced miR‐210‐3p in the regulation of CCL2 expression and macrophage polarization. HIF‐1Α stabilization increases miR‐210‐3p levels in lung adenocarcinoma and impairs monocyte infiltration by inhibiting CCL2 expression. Mechanistically, miR‐210‐3p directly binds to the 3′untranslated region (UTR) of CCL2 mRNA and silences it. Suppressing miR‐210‐3p substantially downregulates the effect of hypoxia on CCL2 expression. Monocyte migration is significantly hampered in miR‐210‐3p mimic‐transfected HIF‐1A silenced cancer cells. In contrast, inhibition of miR‐210‐3p in HIF‐1A‐overexpressed cells markedly restored monocyte migration, highlighting a direct link between the miR‐210‐3p level and tumor monocyte burden. Moreover, miR‐210‐3p inhibition in 3D tumor spheroids promotes monocyte recruitment and skewing towards an antitumor M1 phenotype. Anti‐hsa‐miR‐210‐3p‐locked nucleic acid (LNA) delivery in a lung tumor xenograft zebrafish model caused tumor regression, suggesting that miR‐210‐3p could be a promising target for immunomodulatory therapeutic strategies against lung adenocarcinoma.

Introduction: Idiopathic pulmonary fibrosis is the most prevalent form of interstitial lung disease, which presents as usual interstitial pneumonia on histopathology and imaging. It leads to significant lung scarring, damage, and fibrosis and is associated with a high degree of mortality, repeated hospital admissions, and oxygen dependence. Many complications are associated with idiopathic pulmonary fibrosis, which further increases the morbidity of patients. High-resolution computed tomography chest is the imaging modality of choice for usual interstitial pneumonia tracking its progression, evaluating treatment response, and detecting potential complications. Methods: This descriptive cross-sectional study was approved by the institutional ethics committee (reference number: IEC INT/2023/Study-1256). Departmental computed tomography report database from November 2017 to June 2018 was reviewed and scans with imaging features consistent with the ‘usual interstitial pneumonia’ pattern were identified. Total sampling method was used and two independent radiologists, blinded to the patient's clinical information, reviewed the high- resolution computed tomography chest scans to assess for imaging features of usual interstitial pneumonia and associated complications. Results: There were 65 patients reported as unusual interstitial pneumonia pattern. Emphysema and pneumothorax were identified in four (6.15%) and one (1.53%) scans, respectively. Two (3.08%) scans showed features of pulmonary arterial hypertension. Ten (15.38%) scans exhibited findings consistent with co-existent or superimposed pulmonary infection. Additionally, features of lung malignancy were identified in high-resolution computed tomography scans of five (7.69%) patients. Conclusions: This study sheds light on imaging manifestations of usual interstitial pneumoniacomplications, aiding radiologists and pulmonologists in earlier diagnosis and improved patient management.

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials. However, there remains challenges, including a shifting regulatory environment in recent decades. With the implementation of the New Drugs and Clinical Trial Rules in 2019, India's regulatory atmosphere seems to have stabilized. In this article, we present a review of the evolving clinical trial landscape in India, highlight the current regulatory scenario, and discuss the advantages and challenges of selecting India as a potential location for conducting global oncology clinical trials.

Pulmonary blastoma (PB) is an exceedingly rare and aggressive malignant lung neoplasm that has distinct biphasic morphology. In this report, we document rare manifestations and molecular alterations in PB. A 59-year-old non-smoker female, presented with cough and hemoptysis for 4 months. The high-resolution computed tomography chest scan showed a 3.5x2.7 cm mass in the basal segment of the left lung. Positron emission tomography and computed tomography revealed a fluorodeoxyglucose avid lobulated mass in the superior segment of the lower lobe of the left lung. On core biopsy, the diagnosis of pleomorphic carcinoma in a background of adenocarcinoma was made. A definite diagnosis of pulmonary blastoma was established on the left lung lobectomy specimen based on morphological and immunohistochemical findings. Post-surgical biopsy from the scalp swelling showed metastatic deposits. On Next Generation Sequencing (NGS), in addition to conventional CTNNB1 gene mutation, new pathogenic MYCN and ATM gene mutations were detected. Post-chemotherapy, the patient was doing well after 10 months of close follow-up. PB exhibited rare associations in the form of non-smoker status, scalp metastasis, and MYCN and ATM gene mutations on NGS in addition to conventional CTNNB1 gene mutation. Large cohort studies are required to discover the incidence, significance and therapeutic implications of these co-existing pathogenic molecular alterations in PB.

Abstract Pulmonary arterial hypertension (PAH) is characterized by endothelial cell (EC) dysfunction. There are no data from living patients to inform whether differential gene expression of pulmonary artery ECs (PAECs) can discern disease subtypes, progression and pathogenesis. We aimed to further validate our previously described method to propagate ECs from right heart catheter (RHC) balloon tips and to perform additional PAEC phenotyping. We performed bulk RNA sequencing of PAECs from RHC balloons. Using unsupervised dimensionality reduction and clustering we compared transcriptional signatures from PAH to controls and other forms of pulmonary hypertension. Select PAEC samples underwent single cell and population growth characterization and anoikis quantification. Fifty-four specimens were analyzed from 49 subjects. The transcriptome appeared stable over limited passages. Six genes involved in sex steroid signaling, metabolism, and oncogenesis were significantly upregulated in PAH subjects as compared to controls. Genes regulating BMP and Wnt signaling, oxidative stress and cellular metabolism were differentially expressed in PAH subjects. Changes in gene expression tracked with clinical events in PAH subjects with serial samples over time. Functional assays demonstrated enhanced replication competency and anoikis resistance. Our findings recapitulate fundamental biological processes of PAH and provide new evidence of a cancer-like phenotype in ECs from the central vasculature of PAH patients. This “cell biopsy” method may provide insight into patient and lung EC heterogeneity to advance precision medicine approaches in PAH.

Introduction: Variable transplant-related knowledge may contribute to inequitable access to living donor kidney transplant (LDKT). We compared transplant-related knowledge between African, Caribbean, and Black (ACB) versus White Canadian patients with kidney failure using the Knowledge Assessment of Renal Transplantation (KART) questionnaire. Methods: This was a cross-sectional cohort study. Data were collected from a cross-sectional convenience sample of adults with kidney failure in Toronto. Participants also answered an exploratory question about their distrust in the kidney allocation system. Clinical characteristics were abstracted from medical records. The potential contribution of distrust to differences in transplant knowledge was assessed in mediation analysis. Results: Among 577 participants (mean [SD] age 57 [14] years, 63% male), 25% were ACB, and 43% were White Canadians. 45% of ACB versus 26% of White participants scored in the lowest tertile of the KART score. The relative risk ratio to be in the lowest tertile for ACB compared to White participants was 2.22 (95% confidence interval [CI]: 1.11, 4.43) after multivariable adjustment. About half of the difference in the knowledge score between ACB versus White patients was mediated by distrust in the kidney allocation system. Conclusion: Participants with kidney failure from ACB communities have less transplant-related knowledge compared to White participants. Distrust is potentially contributing to this difference.

Lung cancer poses a global health challenge and stands as the leading cause of cancer-related deaths worldwide. However, its incidence, mortality, and characteristics are not uniform across all regions worldwide. Understanding the factors contributing to this diversity is crucial in a prevalent disease where most cases are diagnosed in advanced stages. Hence, prevention and early diagnosis emerge as the most efficient strategies to enhance outcomes. In Western societies, tobacco consumption constitutes the primary risk factor for lung cancer, accounting for up to 90% of cases. In other geographic locations, different significant factors play a fundamental role in disease development, such as individual genetic predisposition, or exposure to other carcinogens such as radon gas, environmental pollution, occupational exposures, or specific infectious diseases. Comprehensive clinical and molecular characterization of lung cancer in recent decades has enabled us to distinguish different subtypes of lung cancer with distinct phenotypes, genotypes, immunogenicity, treatment responses, and survival rates. The ultimate goal is to prevent and individualize lung cancer management in each community and improve patient outcomes.

Abstract Background We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH). Methods Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity. Results Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses. Conclusion These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses.

PURPOSETargeted therapies, such as crizotinib and ceritinib, have shown promising results in treating non–small cell lung cancer (NSCLC) with specific oncogenic drivers like anaplastic lymphoma kinase (ALK), c-ros (ROS1) oncogene, etc. This study aims to assess the cost-effectiveness of these therapies for patients with NSCLC in India.METHODSThe Markov model consisted of three health states: progression-free survival, progressive disease, and death. Lifetime costs and consequences were estimated for three treatment arms: crizotinib, ceritinib, and chemotherapy for patients with ALK- and ROS1-positive NSCLC. Incremental cost per quality-adjusted life-year (QALY) gained with crizotinib and ceritinib was compared to chemotherapy and assessed using a willingness-to-pay threshold of one-time per capita gross domestic product in India.RESULTSThe total lifetime cost per patient for ALK-positive NSCLC was ₹332,456 ($4,054 US dollars [USD]), ₹1,284,100 ($15,659 USD), and ₹2,337,779 ($28,509 USD) in the chemotherapy, crizotinib, and ceritinib arms, respectively. The mean QALYs lived per patient were 1.20, 2.21, and 3.34, respectively. For patients with ROS1-positive NSCLC, the total cost was ₹323,011 ($3,939 USD) and ₹1,763,541 ($21,507 USD) for chemotherapy and crizotinib, with mean QALYs lived per patient of 1.16 and 2.73, respectively. Nearly 92% and 81% reduction in the price of ceritinib and crizotinib is required to make it a cost-effective treatment option for ALK- and ROS1-positive NSCLC, respectively.CONCLUSIONOur study findings suggest that the prices of ceritinib and crizotinib need to be reduced significantly to justify their value for inclusion in India's publicly financed health insurance scheme for treatment of patients with locally advanced/metastatic ALK- and ROS1-positive NSCLC, respectively.

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, and Parkinson’s disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.

Introduction: A common neurosurgical condition, chronic subdural haematoma (cSDH) typically affects older people with other underlying health conditions. The care of this potentially vulnerable cohort is often, however, fragmented and suboptimal. In other complex conditions, multidisciplinary guidelines have transformed patient experience and outcomes, but no such framework exists for cSDH. This paper outlines a protocol to develop the first comprehensive multidisciplinary guideline from diagnosis to long-term recovery with cSDH. Methods: The project will be guided by a steering group of key stakeholders and professional organisations and will feature patient and public involvement. Multidisciplinary thematic working groups will examine key aspects of care to formulate appropriate, patient-centered research questions, targeted with evidence review using the GRADE framework. The working groups will then formulate draft clinical recommendations to be used in a modified Delphi process to build consensus on guideline contents. Conclusions: We present a protocol for the development of a multidisciplinary guideline to inform the care of patients with a cSDH, developed by cross-disciplinary working groups and arrived at through a consensus-building process, including a modified online Delphi.

Abstract Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are gaining ground in the treatment of lung cancer. Recent advances in adoptive cell therapy (CAR T, TCR, TIL), the associated clinical trials on lung cancer, and associated hurdles are discussed in this review. Recent trials on lung cancer patients (without a targetable oncogenic driver alteration) reveal significant and sustained responses when treated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockade immunotherapies. Accumulating evidence indicates that a loss of effective anti-tumor immunity is associated with lung tumor evolution. Therapeutic cancer vaccines combined with immune checkpoint inhibitors (ICI) can achieve better therapeutic effects. To this end, the present article encompasses a detailed overview of the recent developments in the immunotherapeutic landscape in targeting small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Additionally, the review also explores the implication of nanomedicine in lung cancer immunotherapy as well as the combinatorial application of traditional therapy along with immunotherapy regimens. Finally, ongoing clinical trials, significant obstacles, and the future outlook of this treatment strategy are also highlighted to boost further research in the field.

Non-small cell lung cancer comprises 85% of the global lung cancer cases. Conventional chemotherapeutics possess certain limitations like systemic toxicity and drug resistance that requires the development of new therapeutic agents for successful treatment of lung cancer. Actinonin, a human peptide deformylase inhibitor, has demonstrated anti-cancerous properties in various leukemias and solid cancer types. However, it has limited therapeutic application because of its low bioavailability and systemic toxicity if administered in free form. This limitation can be overcome by using nano-delivery systems that will increase the therapeutic efficacy of actinonin. In the present study, human serum albumin actinonin nanoparticles were prepared using a desolvation technique and folic acid was conjugated to lysine residues of albumin for effective delivery to the lung. The lung adenocarcinoma model was established 24 weeks after intraperitoneal administration of urethane and chemotherapeutic efficacy of free as well as nanoencapsulated actinonin was evaluated. This study demonstrated anti-proliferative potential of folic acid conjugated human serum albumin nanoparticles encapsulating actinonin. The intraperitoneally administered nanoformulation exhibited sustain release profile of actinonin with longer half-life and mean retention time. The reduced dose frequency resulted in therapeutic efficacy comparable to free drug in vivo in terms of 100% survival and reduced tumor burden along with downregulation of epidermal growth factor receptor, folate receptor α and peptide deformylase expression in lung adenocarcinoma mice model. Therefore, actinonin encapsulated albumin nanoparticles-based therapy holds great potential as an alternative strategy to improve its anti-cancerous activity against lung adenocarcinoma.

A new species, Psaphis gerhardi N. Singh, Ahmad & Joshi, sp. nov. is described and illustrated from the Great Nicobar Island, India. The new species represents the second species of Psaphis Walker, 1854 from India and also the first record of the genus from Nicobar Islands. Apart from this a checklist of the known species of the genus is also provided.

View on Scopus The Chinese species, Lophoptera trigonoprocessa Qi & Xue, 2011 is reported for the first time from India. Apart from this, L. squammigera Guenée, 1852 and L. illucida (Walker, 1865) are illustrated from the Indian region. Images of the adults and genitalia are provided. A checklist of all the known species of the genus from India is also provided.

Abstract Here, we report a novel comparative assessment of preparation and characterization of thyme oil nanoemulsion and its chitosan encapsulation using high energy approach for the management of three major mosquito species viz., Anopheles stephensi (Liston,1901), Aedes aegypti (Linn., 1762) and Culex tritaeniorhynchus (Giles, 1901). The synthesized formulations were analysed for thermodynamic stability, indicating 1:0.5 (oil: surfactant) ratio to be the most stable of thyme oil nanoemulsion while 1:1 (nanoemulsion: chitosan solution) ratio of its chitosan encapsulation. These were further characterized by dynamic light scattering and transmission electron microscopy which revealed the size and morphology of the droplets which measured 52.18 ± 4.53 nm for thyme oil nanoemulsion and 50.18 ± 2.32 nm for its chitosan encapsulation. All the droplets were well dispersed with distinct flower-shaped nanoemulsion and somewhat mitochondria like chitosan encapsulation. In-vitro release study of thyme essential oil from its nanoemulsion and chitosan encapsulation showed that 91.68% and 73.41% of the total oil concentration in water was released respectively to the environment after 48 h clearly depicting controlled release in the encapsulation. Assessment of insecticidal potential against selected mosquito species revealed that both the nanoemulsion and its chitosan encapsulation were effective on the major mosquito species. Maximum activity of thyme oil nanoemulsion was noticed against C. tritaeniorhynchus (LC50—22.58 ppm) after 24 h of exposure while it was observed that its chitosan encapsulation was most effective on A. stephensi (LC50—18.88 ppm) after 24 h of exposure. Consistent morphological alterations could be noticed in the larvae of mosquito species. Hence, these nanoemulsions and encapsulations could be further tested for their applications against other insect pests in agriculture.

Abstract Majority of the pollination related studies are based on the diurnal pollinators, and the nocturnal pollinators received less scientific attention. We reveal the significance of settling moths in pollination of angiosperm families in Himalayan ecosystem of North-East India. The refined and novel method of pollen extraction from the proboscides provides a more robust assessment of the pollen carrying capacity. The study is based on one of the largest data sets (140 pollen transporter moth species (PTMS)), with interpretation based on seasonal as well as altitudinal data. In the present study about 65% moths (91 species) carried sufficient quantities of pollen grains to be considered as potential pollinators (PPMS). Teliphasa sp. (Crambidae) and Cuculia sp. (Noctuidae) are found to carry the highest quantity of pollen. We found pollen grains of 21 plant families and the abundant pollen are from Betulaceae, Fabaceae, Rosaceae and Ericaceae. Species composition of PTMS and PPMS in pre-monsoon, monsoon, and post-monsoon revealed the dominance of Geometridae. Maximum diversity of PTMS and PPMS is found from 2000 to 2500 m altitude. The nocturnal pollen transfer network matrices exhibited high degree of selectivity (H2ʹ = 0.86).

Osteoarticular tuberculosis of the wrist is a very rare subset of skeletal Tuberculosis. Diagnosing the tuberculosis wrist in its early stage poses a major challenge to the clinicians because of its atypical and vague presentations and a close resemblance to many relatively benign pathologies. Clinicians from developed parts of the world having less exposure to the myriad forms of osteoarticular tuberculosis are more likely to miss it. We hereby report one such case who presented with wrist pain of short duration, which after thorough examination and investigations, turned out to be tuberculous. It was successfully managed with anti-tuberculosis drugs alone without any debridement or synovectomy. Familiarity with the clinical profile of this entity, in its early stages, is valuable for primary care physicians, rheumatologists, internal medicine specialists, and orthopaedicians alike, who may confuse it with one of the many more common inflammatory, degenerative, or traumatic causes of wrist pain. Within normal range or near normal erythrocyte sedimentation rate and C-reactive protein, and normal looking X-ray does not preclude the diagnosis of tuberculosis wrist. The role of a high index of suspicion and a low threshold for getting higher radiological investigation like MRI in non-responding cases of wrist joint pain cannot be overstated.

Restoration of missing oral tissues in patients with cleft lip and palate is the biggest challenge in their rehabilitation. In this report, we described the postdistraction rehabilitation and 1-year follow-up of the regenerated bone by implant-supported prosthesis and orthodontic tooth movement. A novel distraction appliance regenerated natural bone which is compatible for both implant placement and orthodontic tooth movement, thereby restoring adequate function and esthetics.

Objective: Determination of the molecular status is mandatory for personalized treatment of patients with non-small cell lung carcinoma. The present study was performed to detect anaplastic lymphoma kinase (ALK) rearrangements in pulmonary adenocarcinoma on cytology samples, using immunocytochemistry (ICC) and fluorescence in situ hybridization (FISH) on cell-blocks to assess the diagnostic reliability of these two techniques. Material and Method: A total of 50 confirmed lung adenocarcinoma cases were included. In all the 50 cases, ICC was performed for ALK protein expression by using the D5F3 clone on Ventana platform. On the basis of ALK protein expression on ICC, the cases were categorized as ALK positive (2+ or 3+ strong cytoplasmic granular positivity) or negative (negative or 1+ cytoplasmic granular positivity). FISH for detection of ALK gene rearrangement was performed in 7 ALK ICC positive cases and 7 ALK ICC negative cases using the Vysis ALK break apart FISH probe kit. Results: Based on ICC, 7(14%) cases were ALK positive and 43(86%) were ALK negative. ALK gene rearrangements in lung adenocarcinoma were more commonly seen in non-smokers (31.25%) as compared to smokers (6.25%). Among the ALK-ICC positive cases, FISH demonstrated break apart signal in 5 cases (ALK- ICC positive); however, no break-apart signals were seen in 2 ALK-ICC positive and all the seven ALK-ICC negative cases. Conclusion: Immunocytochemistry on cell- blocks using DF53 clone is a highly sensitive and specific method for the detection of ALK gene rearrangements in lung adenocarcinoma with a greater number of ALK positive cases being detected on ICC as compared to the ALK-FISH.

Introduction: A proximal femur fracture is the most serious complication of osteoporosis, due to the high mortality and morbidity associated with it. Its risk in the elderly is a function of multiple factors, including bone mineral density, muscle strength, and balance, all of which have been related to Vitamin D status and function. Materials and Methods: This was a prospective hospital-based study conducted over 2 years in the hilly state of Himachal Pradesh, India, to evaluate any correlation between Vitamin D levels and proximal femur fractures (PFFs). We also studied the influence of age and sex on Vitamin D levels in PFFs. Results: In our study, the female patients had lower Vitamin D levels (19.85 ± 5.28) as compared to males (20.436 ± 9.36), but this decrease was not found to be statistically significant (P = 0.2374). There was an average decrease of Vitamin D levels in patients of higher age group (20.770 ± 6.57 vs. 19.692 ± 8.40), but this was not statistically significant (P = 0.613). Thirty-four patients, i.e., 68%, had hypocalcemia, while 16 patients, i.e., 32%, had normal levels of serum calcium. Similarly, 30 patients, i.e., 70%, had hypomagnesemia, while 20 patients, i.e., 40%, had normal serum magnesium levels. The mean level of alkaline phosphatase in PFF was found to be 116.36 IU/L, i.e., within normal limits. The average Vitamin D level in our patients who were adequately exposed to sunlight was 22.5 ± 8.80 ng/ml, while the average Vitamin D level in patients who were inadequately exposed was 16.925 ± 5.98 ng/ml. The mean Vitamin D levels in vegetarian and nonvegetarian patients were 19.17 ± 6.05 ng/ml and 19.83 ± 9.56 ng/ml, respectively. We found that vitamin levels were relatively low (19.46 ng/dL) in patients from high altitudes as compared to patients from low altitudes (22.62 ng/dL), but the difference was insignificant (P = 0.3925). Conclusion: In our study, almost all patients (96%) were suffering from hypovitaminosis D (Vitamin D levels

Background: Various molecular underpinnings of lung cancer have been noted in Asian populations, especially with targetable oncogenic drivers such as EGFR mutations and ALK rearrangements, although they have been lesser described in South Asian/Indian patients. Methods: Tumour molecular testing results from non-small cell lung cancer (NSCLC) patients with a name of South Asian origin and diagnosed from 2005 to 2019 at the Stanford Cancer Center in the United States were retrospectively reviewed and compared to the results of molecular testing from PGIMER in Chandigarh, India, from the patients diagnosed from 2011 to 2019. Results: We identified 72 patients of South Asian (largely Indian) origin, of whom 64 patients (51% female) had mutational testing at Stanford. Of the tested patients, 33% of cases harboured either an EGFR exon 19 deletion or exon 21 L858R mutation, and 12.5% had ALK rearrangements. At PGIMER, a larger sample of 1,264 patients was identified (33% female), with 22.5% of patients having two main EGFR activating mutations, and 9.5% harbouring an ALK rearrangement. Conclusions: South Asian, largely Indian, patients with NSCLC appear to have a higher chance of harbouring EGFR mutations and ALK translocation as compared to Caucasians. The percentage of South Asian patients with these molecular abnormalities was largely similar in two different geographical locations. These findings corroborate prior single-institution findings and emphasise the importance of molecular testing.

Introduction: Advanced non-small cell lung cancer (aNSCLC) is an incurable disease. The effort to develop treatments with more effective systemic agents continues. This has led to the FDA approval of one antibody–drug conjugate (ADC) and eight immune checkpoint inhibitors (ICIs) for patients with aNSCLC. Areas covered: Due to the demonstrated efficacy of ADCs and ICIs in aNSCLC, treatment combining both agents merits attention. This article, therefore, explores the use of ADCs and ICIs in patients with NSCLC, assesses the scientific rationale for combination treatment, and provides an overview of ongoing trials. It also presents some early efficacy and safety results of such combination use. Expert opinion: It is not clear whether ADC-immunotherapy has a significant impact on those with a targetable oncogenic driver alteration since targeted therapies are effective. However, in aNSCLC without a targetable oncogenic driver alteration, the combination of ADCs and ICIs has potential and remains an area of active clinical research.

Background: An ipsilateral bicondylar Hoffa's fracture having the simultaneous involvement of both the medial and the lateral femoral condyle on the same side is very rare. Choosing a surgical approach with limited access to fix Hoffa's fracture may lead to a non-anatomical reduction, ultimately ending up with sub-optimal results like malunion, non-union, knee stiffness, and early osteoarthritis. Case report: We herein discuss the successful management of an ipsilateral bicondylar Hoffa's fracture having a metaphyseal spike in a 37-year-old male with AP screws via the Medial Para Patellar approach (MPPA). We limited the fixation to only two 6.5 mm screws with washers through each condyle to minimize the damage to the intra-osseous blood supply. An apical screw was used instead of adding a plate posteriorly to minimize the iatrogenic damage to the extra-osseous blood supply of the condyles. The whole procedure was done without a tourniquet. The entry point of all the screws was from an extra-articular area anteriorly so there was no need to countersink the screw heads. The benefit of MPPA is that if arthroplasty of the knee is ever required, it can be performed through the original incision without damaging the skin's vascularity. Conclusion: Computed Tomography (CT) scan is indispensable for the exact fracture characterization of Hoffa's fracture, planning of surgical approach, and screw trajectory. In our experience, the medial parapatellar approach is dependable to deal with such fractures and provides adequate exposure for fracture fixation even if it is accompanied by a metaphyseal spike.

Background Data on the prevalence of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in non–small cell lung cancer (NSCLC) and their clinical significance in Indian patients are limited. Methods Newly diagnosed NSCLC cases (adenocarcinoma or squamous cell carcinoma [SqCC] histology) were included in the present study. The TILs were evaluated based on morphology on hematoxylin and eosin–stained slides. PD-L1 expression in tumors was assessed using immunohistochemistry with rabbit monoclonal antibody (SP263) on the Ventana automated immunostainer. Tumors with PD-L1 expression > 50% on tumor cells were considered PD-L1–positive. Tumors in which TILs occupy > 25% of stroma were considered to have high TILs. The association of PD-L1 expression and TILs with various clinical parameters including overall survival (OS) was investigated. Results The present study included 128 cases of NSCLC (67 adenocarcinoma, 61 SqCC). PD-L1 positivity was observed in 17.2% of the patients with NSCLC. Baseline characteristics of PD-L1–positive subjects were similar to PD-L1–negative subjects except for a higher prevalence of liver metastasis (18.2% vs. 2.8%; p = .018) and a higher probability of diagnosis from extrapulmonary biopsies. High TILs were observed in 26.6% of the subjects. However, PD-L1 expression and high TIL did not affect OS. Conclusions PD-L1 positivity and high TILs were observed in 20% and 25% of the patients with NSCLC, respectively, however, neither were predictors of survival in SqCC.

Introduction: Metacarpal fractures account for upto 10% of all body fractures and 36% of all hand fractures in adolescents, young adults, and active adults. Among metacarpal fractures, fracture of the metacarpal shaft and neck are most common after direct trauma, roadside accidents, or sports injuries. The ratio of the shaft to the neck is 1:2. Closed reduction and plaster of paris cast can be used to treat the majority of these fractures conservatively. Unstable and comminuted fractures necessitate surgery. Aim: To compare the clinical, functional and radiological outcomes in antegrade intramedullary fixation and transverse pinning of metacarpal fractures in patients of unstable and displaced metacarpal shaft and neck fractures. Materials and Methods: A single-institutional prospective interventional study identified 60 cases of metacarpal fractures between November 2019 to August 2021 in the Maharishi Markandeshwar Medical college and Hospital, Kumarhatti, Himachal Pradesh, India. Each of the cases met the inclusion criteria for closed extra-articular fractures, displaced and unstable fractures of the metacarpal bone. The patients were divided into two groups having 30 subjects each, randomly allotted to two groups (Antegrade intramedullary K-wiring and Transverse Pinning). Outcomes were compared for range of movement by the American Society of Hand Surgeons Total Active Motion score (ASSH TAM), Visual Analog Scale (VAS), and radiological parameters (Angulation). Patients were followed-up for 12 weeks. Complications were listed in terms of pin site infection. Results: Most of the patients were found to be in the third decade of life. The fracture union was achieved at 8±2 weeks. Clinical evaluation done by VAS score which was found to be statistically insignificant between two groups (p-value=0.243). Radiological assessment evaluated by measuring postoperative angulation between two groups was found to be statistically insignificant (p-value=0.248). Difference in functional evaluation between the two groups done by ASSH TAM was found to statistically significant between the groups (p-value=0.036). Conclusion: Both antegrade intramedullary K-wiring and transverse pinning demonstrate good and comparable results for extra-articular neck and shaft metacarpal fractures. However, the former is superior in terms of final range of motion as per ASSH TAM score.

Heterogeneity is a characteristic feature of solid tumors. Intra-tumor heterogeneity includes phenotypic diversity, epigenetic abnormalities, cell proliferation, and plasticity that eventually drives disease progression. Studying tumor heterogeneity in 2D culture is challenging as it cannot simulate the microenvironmental features, such as hypoxia, nutrient unavailability, and cell-ECM interactions. We propose the development of multicellular (tri-culture) 3D spheroids using a hanging drop method to study the non-tumorigenic (BEAS-2B) vs. tumorigenic NSCLC (A549/NCI-H460)cells’ interaction with lung fibroblasts (MRC-5) and monocytes (THP-1). Unlike the non-tumorigenic model, the tumorigenic 3D spheroids show significant induction of cell proliferation, hypoxia, pluripotency markers, notable activation of cancer-associated fibroblasts, and tumor-associated macrophages. CD68+ macrophages isolated from tumorigenic spheroids exhibited profound induction of phenotypic endothelial characteristics. The results are zebrafish tumor xenograft model and by using human patient samples. This multicellular 3D tumor model is a promising tool to study tumor-stroma interaction and cellular plasticity, targeting tumor heterogeneity, and facilitating cancer therapy success against NSCLC.

ABSTRACT The sudden shift to online learning due to the COVID-19 pandemic left many instructors wondering how to minimize anxiety while keeping students engaged in their virtual courses. In this study, we explored (i) specific online instructional tasks that caused students to experience anxiety, (ii) factors that hindered student engagement with online instruction, and (iii) changes in student anxiety and engagement between spring 2020 and fall 2020. Students enrolled in STEM classes were surveyed at the end of spring 2020 (N = 425) and fall 2020 (N = 347) semesters. Our results show that the majority of student respondents had more anxiety in fall 2020 than in spring 2020 with online learning in general, and less anonymous class activities tended to cause the greatest anxiety. Distractions from the environment and personal technologies commonly prevented engagement in both semesters, but no significant differences were observed between the spring and fall. In contrast, more students reported that health-related stress, work-related stress, and issues with technology prevented participation in fall 2020 than in spring 2020. As institutions consider expanding their online course offerings post-pandemic, these data provide valuable insight into the challenges students experienced with online instruction that can inform future pedagogical choices.

Oncogenic kinase inhibitors show short-lived responses in the clinic due to high rate of acquired resistance. We previously showed that pharmacologically exploiting oncogene-induced proteotoxic stress can be a viable alternative to oncogene-targeted therapy. Here, we performed extensive analyses of the transcriptomic, metabolomic and proteostatic perturbations during the course of treatment of Her2+ breast cancer cells with a Her2 inhibitor covering the drug response, resistance, relapse and drug withdrawal phases. We found that acute Her2 inhibition, in addition to blocking mitogenic signaling, leads to significant decline in the glucose uptake, and shutdown of glycolysis and of global protein synthesis. During prolonged therapy, compensatory overexpression of Her3 allows for the reactivation of mitogenic signaling pathways, but fails to re-engage the glucose uptake and glycolysis, resulting in proteotoxic ER stress, which maintains the protein synthesis block and growth inhibition. Her3-mediated cell proliferation under ER stress during prolonged Her2 inhibition is enabled due to the overexpression of the eIF2 phosphatase GADD34, which uncouples protein synthesis block from the ER stress response to allow for active cell growth. We show that this imbalance in the mitogenic and proteostatic signaling created during the acquired resistance to anti-Her2 therapy imposes a specific vulnerability to the inhibition of the endoplasmic reticulum quality control machinery. The latter is more pronounced in the drug withdrawal phase, where the de-inhibition of Her2 creates an acute surge in the downstream signaling pathways and exacerbates the proteostatic imbalance. Therefore, the acquired resistance mechanisms to oncogenic kinase inhibitors may create secondary vulnerabilities that could be exploited in the clinic.

In a multicentric, observational, investigator-blinded, and longitudinal clinical study of 764 ART-naïve subjects, we identified nine different promoter variant strains of HIV-1 subtype C (HIV-1C) emerging in the Indian population, with some of these variants being reported for the first time. Unlike several previous studies, our work here focuses on the evolving viral regulatory elements, not the coding sequences. The emerging viral strains contain additional copies of the existing transcription factor binding sites (TFBS), including TCF-1α/LEF-1, RBEIII, AP-1, and NF-κB, created by sequence duplication. The additional TFBS are genetically diverse and may blur the distinction between the modulatory region of the promoter and the viral enhancer. In a follow-up analysis, we found trends, but no significant associations between any specific variant promoter and prognostic markers, probably because the emerging viral strains might not have established mono infections yet. Illumina sequencing of four clinical samples containing a coinfection indicated the domination of one strain over the other and establishing a stable ratio with the second strain at the follow-up time points. Since a single promoter regulates viral gene expression and constitutes the master regulatory circuit with Tat, the acquisition of additional and variant copies of the TFBS may significantly impact viral latency and latent reservoir characteristics. Further studies are urgently warranted to understand how the diverse TFBS profiles of the viral promoter may modulate the characteristics of the latent reservoir, especially following the initiation of antiretroviral therapy.

Per and polyfluoroalkyl substances (PFAS) are of concern to environmental regulators due to their widespread occurrence, persistence and reported toxicity. However, little data exist on the effects of PFAS at environmentally relevant concentrations. The development of molecular markers for PFAS exposure would therefore be useful to better understand the environmental risks of these compounds. In this study, we assessed if such markers could be developed using Gas Chromatography–Mass Spectrometry-based metabolomics. We exposed the freshwater amphipod Austrochiltonia subtenuis to a range of environmentally relevant concentrations of perfluoro-octane sulfonic acid (PFOS), hexafluoropropylene oxide dimer acid (GenX) and perfluorohexanesulphonic acid (PFHxS) for 7 days at five concentrations. A metabolic response was detected in all concentrations and treatments even though the survival rates only differed significantly at the highest exposure levels. The metabolic response differed between compounds but all three PFAS induced changes in the levels of amino acids, fatty acids, and cholesterol, in line with the literature. PFOS was found to bioaccumulate. Both GenX and PFHxS were eliminated from the amphipods, but PFHxS was eliminated at a slower rate than GenX. This information improves our understanding of the sublethal effects of PFAS as well as their environmental fate and behaviour.

Location-based indoor applications with high quality of services require a reliable, accurate, and low-cost position prediction for target device(s). The widespread availability of WiFi received signal strength indicator (RSSI) makes it a suitable candidate for indoor localization. However, traditional WiFi RSSI fingerprinting schemes perform poorly due to dynamic indoor mobile channel conditions including multipath fading, non-line-of-sight path loss, and so forth. Recently, machine learning (ML) or deep learning (DL)-based fingerprinting schemes are often used as an alternative, overcoming such issues. This paper presents an extreme gradient boosting-based ML indoor localization scheme, simply termed as XGBLoc, that accurately classifies (or detects) the positions of mobile devices in multi-floor multi-building indoor environments. XGBLoc not only effectively reduces the RSSI dataset dimensionality but trains itself using structured synthetic labels (also termed as relational labels), rather than conventional independent labels, that classify such complex and hierarchical indoor environments well. We numerically evaluate the proposed scheme on the publicly available datasets and prove its superiority over existing ML or DL-based schemes in terms of classification and regression performance.