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Phase change materials (PCMs) are important constituents for the storage of thermal energy available from the sun. It acts as a bridge between energy demand and supply while reducing the mismatch. Organic and inorganic constituents have been used for a long time for thermal energy storage applications. In recent years, the focus has been shifted to eutectics. A eutectic is a minimum melting substance of two or more constituents. It has the advantage of having a sharp melting temperature and possessing high volumetric heat storage density. The eutectics possess a wide range of temperatures and have the properties of all of their constituents. At present organic-organic, organic-inorganic, and organic-inorganic eutectics are widely studied. In the present paper, various eutectic PCMs for low and medium temperature ranges have been analyzed. Their thermophysical properties and thermal stability and reliability concerning thermal cycling have been thoroughly discussed. The melting temperature lies in the range of −23.50 °C to 80 °C and the latent heat of fusion can be as high as 280 kJ/kg. Thermal cycle tests of up to 30000 have been conducted by various research groups, but at least 300 melt/freeze cycles are recommended so that they can be stable for a year of application. The organic eutectic PCMs are found stable in terms of deviation in melting temperature with the maximum deviation in latent heat of fusion observed was ± 20 %. The inorganic eutectic PCMs are somewhat unstable having a large deviation in melting temperature and latent heat of fusion. The low thermal conductivity of organic eutectics can be eliminated with suitable nanoparticle additives. The leakage issue can be eliminated by providing shape stabilization to the PCMs. These PCMs are suitable for various photovoltaic/thermal, buildings, textiles, solar water heating, solar air heaters, and heat recovery systems applications.

Abstract Celestial amplitudes may be decomposed as weighted integrals of AdS3-Witten diagrams associated to each leaf of a hyperbolic foliation of spacetime. We show, for the Kleinian three-point MHV amplitude, that each leaf subamplitude is smooth except for the expected light-cone singularities. Moreover, we find that the full translationally-invariant celestial amplitude is simply the residue of the pole in the leaf amplitude at the point where the total conformal weights of the gluons equals three. This full celestial amplitude vanishes up to light-cone contact terms, as required by spacetime translation invariance, and reduces to the expression previously derived by Mellin transformation of the Parke-Taylor formula.

Abstract Celestial MHV amplitudes are comprised of non-distributional leaf amplitudes associated to an AdS3 leaf of a foliation of flat spacetime. It is shown here that the leaf amplitudes are governed by the same infinite-dimensional soft ‘S-algebra’ as their celestial counterparts. Moreover, taking the soft limit of the smooth three-point MHV leaf amplitude yields a nondegenerate minus-minus two-point leaf amplitude. The two- and three-point MHV leaf amplitudes are used to compute the plus-minus-minus leaf operator product coefficients.

PURPOSESquamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer, with approximately 225,419 new cases with over 125,000 deaths annually in India. This trial compared the efficacy and safety of biosimilar cetuximab versus innovator cetuximab (IC) in combination with platinum-based chemotherapy in patients with recurrent locoregional or metastatic SCCHN.METHODSThis phase III trial is a multicenter, randomized, double-blind and parallel group study performed in Indian patients with recurrent locoregional or metastatic SCCHN. Patients were randomly assigned in 2:1 ratio to receive biosimilar cetuximab and IC in combination with cisplatin and fluorouracil via intravenous infusions. The primary end points were disease control rate (DCR) and overall response rate (ORR) as per response evaluation criteria in solid tumors version 1.1. The secondary end points included pharmacokinetics (PK), immunogenicity, safety, and tolerability.RESULTSOf 180 patients enrolled, 120 patients received biosimilar cetuximab and 60 patients received IC treatment. No significant statistical difference was observed in the primary outcomes between two groups. Treatment difference in DCR and ORR response was found to be –5.21 (90% CI, –8.94 to –1.48) and –4.79 (90% CI, –19.42 to 9.84), respectively, indicating noninferiority to reference product. The incidence of treatment-emergent adverse events (AEs; biosimilar cetuximab: 89.2% v IC: 91.7%; P = .8364) and serious AEs (biosimilar cetuximab: 23.3% v IC: 13.3%; P = .0603) and PK parameters were comparable between treatment groups. The immunogenicity findings showed higher incidence of anticetuximab antibodies in the biosimilar cetuximab group compared with the IC group at the end of Study.CONCLUSIONThe findings of this study demonstrated noninferiority along with comparable PK, safety, and immunogenicity of biosimilar cetuximab and IC in patients with recurrent or metastatic SCCHN.

Abstract We study features of celestial CFT correlation functions when the bulk theory is itself a CFT. We show that conformal inversions in the bulk map boost eigenstates to shadow transformed boost eigenstates. This is demonstrated explicitly for the wavefunctions of free massless scalars, and finds interesting applications to building extrapolate dictionaries. Because inversions exchange null infinity and the light cone of the origin, one finds a relation between the massless extrapolate dictionary — involving correlators of operators inserted along null infinity — and the slice-by-slice extrapolate dictionary recently studied by Sleight and Taronna starting from the hyperbolic foliation of de Boer and Solodukhin. Namely, boundary correlators of Sleight and Taronna coincide with celestial amplitudes of shadow transformed boost eigenstates. These considerations are unified by lifting celestial correlators to the Einstein cylinder. This also sheds new light on the extraction of the 𝑆-matrix from the flat limit of AdS/CFT.

Background: There is mixed evidence on the extent of association between the allocation of public revenue for healthcare and its indicators of need. Objective: In this study, we examined the relationship between allocations through state health financing (SHF) and the Central Government with infant mortality. Materials and Methods: District-wise infant mortality rate (IMR) was computed using National Family Health Survey-4 data. State-wise data for health budgets through SHF and National Health Mission (NHM, a Centrally Sponsored Scheme), were obtained for the year 2015-16. We used a multivariable analysis through generalized linear model method using identity-link function. Results: We found per capita SHF (₹3169) to be more than 12 times that of public health spending per capita through NHM (₹261). IMR was lower in districts with higher SHF allocation, although statistically insignificant. The allocation through NHM was higher in districts with higher IMR, which is statistically significant. Every unit percentage increase in per capita net state domestic product and female literacy led to 0.31% and 0.54% decline, while a 1% increase in under-five diarrhoea prevalence led to 0.17% increase in IMR. Conclusion: The NHM has contributed to enhancing vertical equity in health-care financing. The States' need to be more responsive to the differences in districts while allocating health-care resources. There needs to be a focus on spending on social determinants, which should be the cornerstone for any universal health coverage strategy.

BackgroundApproximately 20%-25% of patients with metastatic castration-resistant prostate cancer (mCRPC) harbor a deleterious germline or somatic mutation in the homologous recombination repair (HRR) pathway genes, which is involved in the repair of double-stranded DNA damage. Half of these mutations are germline, while the remaining are exclusively somatic. While polyadenosine 5’diphosphoribose [poly (ADP-ribose)] polymerase inhibitors, such as olaparib and rucaparib, are effective in this subgroup, their widespread use is limited due to the associated high cost, especially in resource-constrained settings. Notably, platinum agents like carboplatin have exquisite sensitivity to cells with defective DNA repair machinery. Carboplatin, a conventional, inexpensive chemotherapeutic agent, offers a potential alternative treatment in such patients. Several retrospective small case series support this hypothesis. However, there are no prospective clinical trials of carboplatin in patients with mCRPC with HRR mutations. ObjectiveThe primary objective is to assess the objective response rate of 3 weekly carboplatin treatments in patients with mCRPC harboring deleterious mutations in the HRR pathway genes and previously treated with a taxane or a novel antiandrogen agent. The secondary objectives include progression-free survival, health-related quality of life, and safety profile of carboplatin. MethodsPatients diagnosed with mCRPC harboring HRR pathway mutations previously treated with docetaxel or novel antiandrogen agents (abiraterone, enzalutamide, apalutamide, or darolutamide) or both will be eligible. Genes involved directly or indirectly in the HRR pathway will be tested. In this single-arm phase II study, we will screen approximately 200 patients to enroll 49 patients, and carboplatin (dosing at the area under curve=5) will be administered every 3 weeks until progression or intolerable side effects. The primary end point will be assessed as the proportion of patients with a reduction of serum prostate-specific antigen by more than 50% from enrollment. Secondary outcomes include progression-free survival—soft-tissue disease progression (by response evaluation criteria in solid tumors, version 1.1, and bone lesion progression using Prostate Cancer Clinical Trials Working Group 3 criteria), health-related quality of life during carboplatin treatment using the Functional Assessment of Cancer Therapy—Prostate questionnaire and the European Organisation for Research and Treatment of Cancer questionnaire and safety profile of carboplatin (National Cancer Institute’s Common Terminology Criteria for Adverse Events version 5.0). ResultsThe trial started enrollment in September 2023. This trial is ongoing, and 12 patients have been recruited to date. All 49 participants will be enrolled according to plan. ConclusionsThis prospective phase II trial represents a critical step toward addressing the therapeutic gap in patients with mCRPC harboring HRR pathway mutations, particularly in demographic regions with limited access to poly (ADP-ribose) polymerase inhibitors. Outcomes from this study will inform clinical practice and guide future phase III randomized trials, ultimately improving patient outcomes globally. Trial RegistrationClinical Trials Registry of India CTRI/2023/04/051507; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Njc0NjU=&Enc=&userName= International Registered Report Identifier (IRRID)DERR1-10.2196/54086

Abstract We elaborate on various aspects of our top-down celestial holographic duality wherein the semiclassical bulk spacetime is a 4d asymptotically flat, self-dual Kähler geometry known as Burns space. The bulk theory includes an open string sector comprising a 4d WZW model and a closed string sector called “Mabuchi gravity” capturing fluctuations of the Kähler potential. Starting with the type I topological B-model on the twistor space of flat space, we obtain the twistor space of Burns space from the backreaction of a stack of N coincident D1 branes, while the chiral algebra is obtained from (a twist of) the brane worldvolume theory. One striking consequence of this duality is that all loop-level scattering amplitudes of the theory on Burns space can be expressed as correlation functions of an explicit 2d chiral algebra. We also present additional large-N checks, matching several 2 and 3-point amplitudes and their collinear expansions in the WZW4 sector, and the mixed WZW4-Mabuchi sector, of the bulk theory to the corresponding 2 and 3-point vacuum correlators and operator product expansions in the dual chiral algebra. Key features of the duality, along with our main results, are summarized in the introduction.

Abstract We determine tree level, all-order celestial operator product expansions (OPEs) of gluons and gravitons in the maximally helicity violating (MHV) sector. We start by obtaining the all-order collinear expansions of MHV amplitudes using the inverse soft recursion relations that they satisfy. These collinear expansions are recast as celestial OPE expansions in bases of momentum as well as boost eigenstates. This shows that inverse soft recursion for MHV amplitudes is dual to OPE recursion in celestial conformal field theory.

Objectives Biliary obstruction is a common problem encountered in postsurgical anatomy, which may lead to serious complications if not treated promptly. Endoscopic drainage is a minimally invasive and effective treatment option for such patients. However, the optimal route of endoscopic drainage, either SBE-ERCP (single-balloon enteroscopy with endoscopic retrograde cholangiopancreatography) or EUS-BD (endoscopic ultrasound-guided bile duct drainage), remains controversial. In this study, we aim to evaluate the feasibility and outcomes of endoscopic drainage using these two techniques in postsurgical biliary obstruction over a period of 7 years.

PURPOSESerial patient-reported outcome (PRO) measurements in clinical practice are associated with a better quality of life and survival. Recording electronic PROs using smartphones is an efficient way to implement this. We aimed to assess the feasibility of the electronically filled Edmonton Symptom Assessment System (e-ESAS) scale in the lower-middle–income country (LMIC) setting.METHODSBaseline clinical features and conventional paper-based ESAS (p-ESAS) were collected in newly diagnosed patients with solid organ tumors. Text message link was sent to these patients for filling e-ESAS. ESAS was categorized into physical, psychological, and total symptom domains. Scores were divided into none to mild (0-3) and moderate to severe (4-10). Intraclass correlation coefficients (ICCs) were used to determine the correlation between p-ESAS and e-ESAS. Multivariable logistic regression was used to identify independent factors affecting symptom burden.RESULTSOf 1,160 participants who filled out p-ESAS, 595 completed both e-ESAS and p-ESAS questionnaires and were included in the final analysis. Moderate to severe physical, psychological, and total symptom scores were seen in 39.8%, 40%, and 39% of participants. Tiredness and anxiety were the most common physical and psychological symptoms, respectively. ICCs between the p-ESAS and e-ESAS varied between 0.75 and 0.9. Total symptom scores were independently predicted by metastatic disease (odds ratio [OR], 1.83; 95% CI, 1.26 to 2.67; P = .001) and a higher level of education (OR, 0.42; 95% CI, 0.25 to 0.72; P = .001).CONCLUSIONPaper-based and electronically filled ESASs have good intraobserver reliability across individual symptoms and domain scores in a representative cohort at a tertiary care institute in the LMIC. This may help us incorporate e-ESAS in routine clinical care in the real-world setting with financial, infrastructural, and manpower limitations.

Background: Carcinoma penis is a rare neoplasm, and the literature is scarce on long-term survival and its predictors. The aim of the study was to determine the clinical profile and management patterns, identify predictors of survival, and the impact of education and rural/urban dwelling on survival. Methods: Patients with a histological diagnosis of carcinoma penis from January 2015 to December 2019 were included in the study. Demographics, clinical profile, education status, primary residence address, and outcomes were obtained from the case records. Distance from the treatment centre was obtained from the postal code. The primary objectives were to assess relapse-free survival (RFS) and overall survival (OS). The secondary objectives were to identify the predictors of RFS and OS and to determine the clinical profile and treatment patterns in patients with carcinoma penis in India. Time-to-event was calculated by Kaplan–Meir analysis and survival was compared by the log-rank test. Univariate and multivariable Cox regression analyses were used to find independent predictors of relapse and mortality. Logistic regression analyses to examine the associations of rural residence, education status, and distance from the treatment centre with the relapse adjusting for measured confounding variables. Results: Case records of 102 patients treated during the above period were retrieved. The median age was 55.5 (interquartile range [IQR] 42–65 years). Ulcero-proliferative growth (65%), pain (57%), and dysuria (36%) were the most common presenting features. Clinical examination or imaging revealed inguinal lymphadenopathy in 70.6% of patients, however, only 42% of these lesions were pathologically involved. A total of 58.8% of patients were from rural areas, 46.9% had no formal education, and 50.9% had a primary residence ≥100 km from the hospital. Patients with lower education and rural households had higher TNM stages and nodal involvement. Median RFS and OS were 57.6 months (15.8 months to not reached) and 83.9 months (32.5 months to not reached), respectively. On univariate analysis tumor stage, involvement of lymph nodes, T stage, performance status, and albumin was predictive for relapse and survival. However, on multivariate analysis, the stage remained the only predictor of RFS and nodal involvement, and metastatic disease was a predictor of OS. Education status, rural habitation, and distance from the treatment centre were not predictors for relapse or survival. Conclusions: Patients with carcinoma have locally advanced disease at presentation. Rural dwellings and lower education were associated with the advanced stage but did not have a significant bearing on the survival outcomes. The stage at diagnosis and nodal involvement is the most important predictor of RFS and OS.

Abstract On-shell kinematics for gluon scattering can be parametrized with points on the celestial sphere; in the limit where these points collide, it is known that tree-level gluon scattering amplitudes exhibit an operator product expansion (OPE)-like structure. While it is possible to obtain singular contributions to this celestial OPE, getting regular contributions from both holomorphic and anti-holomorphic sectors is more difficult. In this paper, we use twistor string theory to describe the maximal helicity violating (MHV) sector of tree-level, four-dimensional gluon scattering as an effective 2d conformal field theory on the celestial sphere. By organizing the OPE between vertex operators in this theory in terms of soft gluon descendants, we obtain all-order expressions for the celestial OPE which include all regular contributions in the collinear expansion. This gives new, all-order formulae for the collinear splitting function (in momentum space) and celestial OPE coefficients (in the conformal primary basis) of tree-level MHV gluon scattering. We obtain these results for both positive and negative helicity gluons, and for any incoming/outgoing kinematic configuration within the MHV sector.

The production of fruits and vegetables has increased significantly over the past few decades which has resulted in a rise of their waste products. The present work focuses on the promising development of fruit waste-derived activated carbon, FWAC, and its binary metal oxide hybrid nanocomposite, Fe-Ni/FWAC, for the sorptive removal of Methylene blue. The two synthesised materials have been characterized with different analytical techniques, like PXRD, FT-IR, TGA-DTG, BET, UV-DRS, and SEM-EDAX to confirm the physico-chemical properties. The Surface area ofthe composite, Fe-Ni/FWAC, reduced significantly from 952 m2 g−1 to 873 m2 g−1 suggesting successful loading of binary metal oxide particles in void space of FWAC framework. The sorption parameters, pH, dye concentration, material dosages, for the both materials have been optimized and sorption data has been analyzed with isotherms, kinetics, and thermodynamics models in the temperature range 303-323 K. As a result, the synthesized FWAC and Fe-Ni/FWAC served as an affordable, and sustainable materials for comprehensive water purification.

Ammonia (NH3) offers benefits over molecular hydrogen as an energy vector because it can be liquefied, transported, and stored more easily using the existing infrastructure. NH3 can react with CO2 to produce syngas (H2 +CO) as a feedstock for circular chemical production. In the conventional process design, this involves: 1) cracking of NH3 to N2 and H2, 2) subsequent product gas separation, and 3) CO production through the reverse water gas shift (RWGS) reaction. Herein, a novel approach referred to as “NH3-RWGS” is presented, which integrates these three steps into a two-reactor process utilizing the chemical-looping principle. In the first reactor, NH3 is cracked over a catalytically active bed material, and H2 reacts further with the metal oxide bed material, producing H2O and N2 as gaseous products and reduced metal oxide/metal. This reduced metal oxide is then moved to the second reactor, where it reacts with CO2 or a mixture of CO2 and H2O, forming CO and H2 as the desired product gas and the re-oxidized metal oxide, which is returned to the first reactor. This process can be favorably implemented in two gas–solid countercurrent flow moving beds. Herein, the underlying design principles are developed, and the maximum achievable gas conversion with an iron-based bed material is established. The feasibility of the underlying chemistry was demonstrated using a supported Fe/MgAl2O4 bed material that exhibited fast kinetics and cyclic stability for the relevant reactions.

Abstract We start by constructing a conformally covariant improvement of the celestial light transform which keeps track of the mixing between incoming and outgoing states under finite Lorentz transformations in ℝ2,2. We then compute generic 2, 3 and 4-point celestial amplitudes for massless external states in the ambidextrous basis prepared by composing this SL(2, ℝ) intertwiner with the usual celestial map between momentum and boost eigenstates. The results are non-distributional in the celestial coordinates (z, z ¯ $$ \overline{z} $$ ) and conformally covariant in all scattering channels. Finally, we focus on the tree level 4-gluon amplitude where we present a streamlined route to the ambidextrous correlator based on Grassmannian formulae and examine its alpha space representation. In the process, we gain insights into the operator dictionary and CFT data of the holographic dual.

Introduction: Sheehan syndrome is a common cause of hypopituitarism in developing countries. Among risk factors, in addition to post-partum haemorrhage, a smaller sellar volume is also believed to predispose to pituitary necrosis. Some earlier studies have reported smaller sellar volume in these patients but involved a small number of patients and lacked matched controls. The main of the present study was to study the sellar volume in a large cohort of patients with Sheehan syndrome and compare it with age- and parity-matched controls. Methods: Fifty women with Sheehan syndrome and an equal number of age- and parity-matched controls were studied. Baseline investigations, relevant hormonal assay, and MRI of pituitary were studied in all. Results: Sellar volume was significantly lower in patients with Sheehan syndrome (334.50 ± 129.08 mm3 in patients as against 456.64 ± 169.25 mm3 in controls, P = 0.000). Far more women with Sheehan syndrome than controls had decreased sellar volume (40% vs. 12%). Conclusions: Patients with Sheehan syndrome have a smaller sellar volume that may be a non-modifiable risk factor for the development of post-partum pituitary necrosis.

Background: A “pay-for-performance” (P4P) intervention model for improved tuberculosis (TB) outcomes, called “Mukti,” has been implemented in an underdeveloped tribal area of central India. The target of this project is to improve nutritional status, quality of life (QoL), and treatment outcomes of 1000 TB patients through four interventions: food baskets, personal counseling, peer-to-peer learning and facilitation for linkage to government schemes. The current study aims to assess the success of this model by evaluating its impact and cost-effectiveness using a quasi-experimental approach. Methods: Data for impact assessment have been collected from 1000 intervention and control patients. Study outcomes such as treatment completion, sputum negativity, weight gain, and health-related QoL will be compared between matched samples. Micro costing approach will be used for assessing the cost of routine TB services provision under the national program and the incremental cost of implementing our interventions. A decision and Markov hybrid model will estimate long-term costs and health outcomes associated with the use of study interventions. Measures of health outcomes will be mortality, morbidity, and disability. Cost-effectiveness will be assessed in terms of incremental cost per quality-adjusted life-years gained and cost per unit increase in patient weight in intervention versus control groups. Results: The evidence generated from the present study in terms of impact and cost-effectiveness estimates will thus help to identify not only the effectiveness of these interventions but also the optimal mode of financing such measures. Our estimates on scale-up costs for these interventions will also help the state and the national government to consider scale-up of such interventions in the entire state or country. Discussion: The study will generate important evidence on the impact of nutritional supplementation and other complementary interventions for TB treatment outcomes delivered through P4P financing models and on the cost of scaling up these to the state and national level in India.

Background/Aims Gastric varices (GV) are present in 25% of cirrhotic patients with high rates of rebleeding and mortality. Data on endoscopic ultrasound (EUS)-guided treatment in severe liver disease (model for end stage liver disease sodium [MELD-Na] >18 and Child-Turcotte-Pugh [CTP] C with GV) are scarce. Thus, we performed a retrospective comparison of endoscopic glue injection with EUS-guided therapy in cirrhotic patients with large GV. Methods A retrospective study was performed in the tertiary hospitals of India. A total of 80 patients were recruited. The inclusion criteria were gastroesophageal varices type 2, isolated gastric varices type 1, bleeding within 6 weeks, size of GV >10 mm, and a MELD-Na >18. Treatment outcomes and complications of endoscopic glue injection and EUS-guided GV therapy were compared. Results In this study, the patients’ age, sex, liver disease severity (CTP, MELD-Na) and clinical parameters were comparable. The median number of procedures, injected glue volume, complications, and GV obturation were better in the EUS group, respectively. On subgroup analysis of the EUS method (e.g., direct gastric fundus vs. paragastric collateral [PGC] coil placement), PGC coil placement showed decreased coil requirement, less injected glue volume, decreased luminal coil extrusion, and increased successful GV obturation. Conclusions EUS-guided treatment is more efficient and safer, and requires a smaller number of treatment sessions, as compared to endoscopic treatment in severe liver disease patients with large GV. Furthermore, PGC coil placement increases the complete obliteration of GV.

Abstract The main aim of this simulation work is to assess the financial possibility analysis of 10 MWP grid-associated solar photovoltaic (PV) power plants in seven cities i.e. Lucknow, Agra, Meerut, Gorakhpur, Kanpur, Allahabad, and Varanasi of Uttar Pradesh (UP) state of India with the RETScreen Software. The presented research work demonstrates the method of selection of profitable locations for solar PV power plants according to financial viability indicators. It is found that Allahabad city is the most profitable site with values of 16,686 MWh of electricity exported to the grid (EEG), US$20,896.30/year of electricity export revenue (EER), 9.4 years of simple payback period (SPP), 7.7 years of equity payback period (EPP), 19545.9 tCO2/year of GHG emission reduction, US$3492.82/year of the annual life cycle savings (ALCS), 1.5 benefit-cost (B-C) ratio, US$27394.59 of net present value (NPV), 16.5% internal rate of return on equity (IRR-equity), 12.3% modified internal rate of return on equity (MIRR-equity), 5.4% internal rate of return on assets (IRR-assets), and 7% modified internal rate of return on assets (MIRR-assets). The second most profitable site is found in Gorakhpur city and Varanasi city is found the least profitable site. The other two cities, Agra and Kanpur are not found suitable because of the negative values of NPV and ALCS.

Abstract Colorectal cancer (CRC) is a predominant life‐threatening cancer, with liver and peritoneal metastases as the primary causes of death. Intestinal inflammation, a known CRC risk factor, nurtures a local inflammatory environment enriched with tumor cells, endothelial cells, immune cells, cancer‐associated fibroblasts, immunosuppressive cells, and secretory growth factors. The complex interactions of aberrantly expressed cytokines, chemokines, growth factors, and matrix‐remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes. Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment, which is partly achieved by the recruitment of immunosuppressive cells. These cells impart features such as cancer stem cell‐like properties, drug resistance, invasion, and formation of the premetastatic niche in distant organs, promoting metastasis and aggressive CRC growth. A deeper understanding of the cytokine‐ and chemokine‐mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC. Here, we summarized the current knowledge of cytokine‐ and chemokine‐mediated crosstalk in the inflammatory tumor microenvironment, which drives immunosuppression, resistance to therapeutics, and metastasis during CRC progression. We also outlined the potential of this crosstalk as a novel therapeutic target for CRC. The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.

Background: Nationwide lockdown was enforced due to the spread of the new Coronavirus-19. This resulted in cessation of all sports training across the country, including elite athletes. This COVID-19 lockdown was hypothesized to result in detraining effects on elite athletes. Aim: We aimed to study the impact of COVID-19 lockdown on athletes’ physiological and anthropometric sports performance parameters. Methodology: Seventy-five athletes (age: 23.25 ± 3.9 years, training experience 7.49 ± 3.5 years) from different sports participated voluntarily. International Physical Activity Questionnaire was used to grade home-based non-supervised physical activity undertaken during COVID-19 lockdown (137.81 ± 39.20 days). We compared the measured anthropometric, aerobic, and anaerobic performance parameters post-lockdown with pre-lockdown competitive phase recordings using Kruskal Wallis non-parametric test. Parameters were expressed as mean ± SD with level of significance fixed at p < .05. Results: Statistically significant reduction of 33.28% was observed in aerobic capacity post- COVID-19 lockdown (p = .01). We did not find any statistically significant variation in the other anthropometric and physiological performance parameters, namely weight (↑17.50 %), body mass index (↑20.69 %), body fat mass (↑20.76 %), waist (↑21.07 %), hip (↑19.13 %), waist: hip ratio (↑10.71 %), peak power (↑11.32 %) and mean power (↑5.17 %). Conclusions: We found that the athletes exhibited generalized detraining features despite maintaining home-based physical activity. Compared to other performance parameters, there was a significant decrease in the aerobic capacity post-lockdown. This shows the importance of incorporating an indoor-based supervised program including aerobic exercises to guide and monitor athletes. Practical Implications: Off-season/home confinement requires a remotely supervised tailored exercise program with optimal stimuli to maintain training adaptations. Awareness and incorporation of these findings would aid coaches and trainers in designing training programs to promote athletes’ injury-free gradual return to sports.

Abstract We compute the operator product expansions of gluons and gravitons in celestial CFT from the worldsheet OPE of vertex operators of four-dimensional ambitwistor string theories. Remarkably, the worldsheet OPE localizes on the short-distance singularity between vertex operator insertions which in turn coincides with the OPE limit of operator insertions on the celestial sphere. The worldsheet CFT dynamically produces known celestial OPE coefficients — as well as infinite towers of SL(2, ℝ) descendant contributions to the celestial OPE — without any truncations or approximations. We obtain these results for all helicities and incoming/outgoing configurations. Furthermore, the worldsheet OPE encodes the infinite-dimensional symmetry algebras associated with the conformally soft sectors of gauge theory and gravity. We provide explicit operator realizations of the currents generating these symmetries on ambitwistor space in terms of vertex operators for soft gluons and gravitons, also computing their actions on hard particles of all helicities. Lastly, we show that the worldsheet OPE for momentum eigenstates produces the collinear splitting functions of gluons and gravitons.

Since the introduction of Cetuximab as a biological molecule against Epidermal Growth Factor Receptor (EGFR), its use in the cancers of head and neck region is widely explored. With the recognition that EGFR expression is associated with radioresistance and poor prognosis, incorporation of an anti-EGFR agent along with Radiotherapy (RT) is a logical and attractive option. Cetuximab in combination with RT as Bio-Radiotherapy (BRT) is considered one of the standard treatment modalities in Locally Advanced Head and Neck Squamous Cell Cancers (LA-HNSCC). Many important phase-III clinical trials were undertaken simultaneously, where the use of Cetuximab BRT was tested in various clinical scenarios with different hypothesis. With the studies still ongoing and the results awaited, its use was continued in clinical practice. Today the results are out and definitely not encouraging. After the initial success, Cetuximab has miserably failed to win over cisplatin based chemoradiation which is the current standard of care in LA-HNSCC. Hence, it is the need of the hour to re-evaluate and define the present role of Cetuximab in the definitive management of LA-HNSCC in the light of the latest clinical evidence..

Abstract Introduction Hand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven strategies for the prevention of HFS. However, celecoxib is associated with significant cardiotoxicity. To date, no study has evaluated the role of topical COX inhibitor, diclofenac. In this study, we aim to compare topical 1% diclofenac gel with placebo in the prevention of capecitabine-induced HFS. Methods This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the Diclofenac Topical in Reducing Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal malignancies will be randomly allocated (stratified by sex and type of therapy [monotherapy or combination regimen with capecitabine]) to receive either 1% topical diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily whilst taking capecitabine for 12 weeks. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported), capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS) Discussion The D-TORCH study aims to determine if 1% topical diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine. To date, there have been a lot of trials for hand-foot syndrome prevention using agents like pyridoxine, vitamin E, carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical diclofenac will be the new standard of care for HFS prevention. Trial registration Clinical Trials Registry of India CTRI/2021/01/030592 . Prospectively registered on January 19, 2021

In the present two-dimensional numerical study, we investigate the roles of geometrical parameters of a hydrofoil (shape/curvature of the leading and trailing edges and thickness) and kinematic parameters (phase difference between heave and pitch (ϕ)) on the propulsive performance of different-shaped hydrofoils oscillating at maximum angles of attack up to αmax=30∘. The study was carried out at a fixed non-dimensional maximum heave to chord ratio h∘/C=0.75, Strouhal number St=0.25, and Reynolds number Re=5000. Our findings reveal that hydrofoil performance and stability improve with leading and trailing edge curvatures but decline as thickness increases. By analyzing the near-wake structure, we establish that even minimal flow separation increases power consumption while moderate flow separation enhances thrust. Over the range of different-shaped hydrofoils at different αmax and ϕ, maximum propulsion efficiency occurs for those parameters for which there is a small degree of flow separation but with no roll-up of a separating vortex. In comparison, maximum thrust generation occurs when there is a moderately strong flow separation but without induction of a significant amount of fluid around the trailing edge. These insights offer valuable knowledge for understanding fish propulsion efficiency and have applications in designing autonomous underwater vehicles (AUVs) and micro-air vehicles (MAVs).

Metastases to the testis are uncommon. Signet-ring cell carcinomas from the gastrointestinal tract (GIT) can rarely disseminate to the testicles, mimicking primary testicular malignancies with signet-ring cells. We hereby describe a case of a 26-year-old male who presented with left testicular swelling, multiple lymphadenopathies, and normal serum tumor markers. Lymph node biopsy revealed clusters and singly lying signet-ring cells. Judicious use of immunohistochemistry confirmed the tumor to be GIT primary. Further investigations confirmed a gastric tumor extending to the duodenum. Although rare, metastatic tumors to the testis should be considered in differential diagnoses of testicular masses in a young patient, particularly when serum germ cell tumor markers are normal or mildly deranged.

Abstract Background Sequencing technologies are prone to errors, making error correction (EC) necessary for downstream applications. EC tools need to be manually configured for optimal performance. We find that the optimal parameters (e.g., k-mer size) are both tool- and dataset-dependent. Moreover, evaluating the performance (i.e., Alignment-rate or Gain) of a given tool usually relies on a reference genome, but quality reference genomes are not always available. We introduce Lerna for the automated configuration of k-mer-based EC tools. Lerna first creates a language model (LM) of the uncorrected genomic reads, and then, based on this LM, calculates a metric called the perplexity metric to evaluate the corrected reads for different parameter choices. Next, it finds the one that produces the highest alignment rate without using a reference genome. The fundamental intuition of our approach is that the perplexity metric is inversely correlated with the quality of the assembly after error correction. Therefore, Lerna leverages the perplexity metric for automated tuning of k-mer sizes without needing a reference genome. Results First, we show that the best k-mer value can vary for different datasets, even for the same EC tool. This motivates our design that automates k-mer size selection without using a reference genome. Second, we show the gains of our LM using its component attention-based transformers. We show the model’s estimation of the perplexity metric before and after error correction. The lower the perplexity after correction, the better the k-mer size. We also show that the alignment rate and assembly quality computed for the corrected reads are strongly negatively correlated with the perplexity, enabling the automated selection of k-mer values for better error correction, and hence, improved assembly quality. We validate our approach on both short and long reads. Additionally, we show that our attention-based models have significant runtime improvement for the entire pipeline—18 $$\times$$ × faster than previous works, due to parallelizing the attention mechanism and the use of JIT compilation for GPU inferencing. Conclusion Lerna improves de novo genome assembly by optimizing EC tools. Our code is made available in a public repository at: https://github.com/icanforce/lerna-genomics .

Abstract Low multiplicity celestial amplitudes of gluons and gravitons tend to be distributional in the celestial coordinates z, z ¯ $$ \overline{z} $$ . We provide a new systematic remedy to this situation by studying celestial amplitudes in a basis of light transformed boost eigenstates. Motivated by a novel equivalence between light transforms and Witten’s half-Fourier transforms to twistor space, we light transform every positive helicity state in the coordinate z and every negative helicity state in z ¯ $$ \overline{z} $$ . With examples, we show that this “ambidextrous” prescription beautifully recasts two- and three-point celestial amplitudes in terms of standard conformally covariant structures. These are used to extract examples of celestial OPE for light transformed operators. We also study such amplitudes at higher multiplicity by constructing the Grassmannian representation of tree-level gluon celestial amplitudes as well as their light transforms. The formulae for n-point N k−2MHV amplitudes take the form of Euler-type integrals over regions in Gr(k, n) cut out by positive energy constraints.

The purpose of this study is to explore the design of a robust control strategy for regulating the magnetic levitation system, which is affected by model uncertainty and surrounding disturbance. This paper integrates a fixed-time extended state observer (ESO) with a fixed-time integral sliding mode control (ISMC) design. The fixed-time ESO is employed to estimate the total disturbance within the system in a fixed time. The estimated output is then fed to the composite control law to cancel the actual disturbance in the system. Consequently, it avoids large gain for switching function in the ISMC law, thus suppressing the chattering from the control input. It also avoids employing a conservative condition on the advance information of disturbance bound. In addition, the proposed ISMC design ensures fixed time convergence of closed-loop signals. Moreover, since the integral sliding surface has no reaching phase; therefore the proposed composite scheme has a better invariance behavior from the initial time. The Lyapunov stability theory proves the fixed time stability of sliding variable and relative states. Furthermore, the effectiveness of the presented methodology is validated using numerical analysis with a comparative performance of state-of-the-art control schemes. The numerical results of these schemes are judged based on convergence time, residual bound, energy consumption, and total input variation.

PURPOSEGlobally, colorectal cancer (CRC) ranks third in terms of incidence and second in terms of mortality. A relatively low burden of CRC has been reported from low- and middle-income countries (LMIC), and there is a paucity of publications related to CRC from LMIC.PATIENTS AND METHODSA computerized comprehensive structured CRC clinical database was developed. All the patients with histopathologically proven CRC undergoing either curative and palliative multimodality management or surgical interventions between 2000 and 2019 were included in the study. A descriptive analysis of the demographic profile and clinical spectrum was performed.RESULTSA total of 970 patients of CRC were treated between 2000 and 2019. Of these, 401 patients (41.3%) had colon cancer and 569 (58.7%) had rectal cancer. The male-to-female ratio was 1.79:1. The mean age at presentation was 47.7 years. A total of 337 (34.7%) patients qualified as young CRC (≤ 40 years of age at diagnosis). The commonest symptom among patients with colon cancer was abdominal pain; 55.6% of patients had a right-sided primary tumor as compared with 42.2% with left-sided tumors. The commonest symptom among patients with rectal cancer was bleeding per rectum. The predominant location of the tumor was in the lower rectum (58%). Majority of patients with CRC presented with locally advanced stage II and III disease. The most common histologic subtype encountered for both colon and rectal cancers was adenocarcinoma (84.8% and 81.2%, respectively).CONCLUSIONThis study has revealed certain important findings related to CRC in LMIC including a higher burden of young colorectal cancer, a relatively higher proportion of rectal cancers in comparison with colon cancer, a high percentage of patients with low-rectal cancer, and advanced stage at presentation.

PURPOSEFor unresectable gallbladder cancer (GBC), gemcitabine and platinum is standard combination; however, outcome is poor. We conducted this study to find feasibility of modified flourouracil, oxaliplatin, and irinotecan in this group.MATERIALS AND METHODSWe conducted a prospective, phase II single-arm pilot study. Inclusion criteria were histologically proven GBC and Eastern Cooperative Oncology Group 0-1. Primary end points were overall response rates and overall survival. The following treatment was given: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and irinotecan 150 mg/m2, all once on day 1, fluorouracil 2,400 mg/m2 continuous intra-venous infusion over 46 hours repeated every 2 weeks, and maximum 12 doses, with primary granulocyte colony-stimulating factor prophylaxis.RESULTSBetween February 2019 and July 2020, 29 patients with unresectable GBC were enrolled. The median age was 52 years, and 18 were females. The Eastern Cooperative Oncology Group was 0 in 4. Five had bilirubin > normal, and 15 each had high serum alkaline phosphatase and carbohydrate antigen 19-9. Twenty-five patients had stage IV disease, and remaining unresectable locally advanced disease. A median of 8.5 cycles was given, and 11 completed treatment. Nine stopped chemotherapy because of progression, and one because of toxicity, and treatment is ongoing in three. Twenty-two required dose reduction. A treatment delay of 1-2 weeks was seen in 25 patients. Best response was complete response 1, partial response 13 (overall response rate 48.2%), and stable disease 9. Four patients with metastatic disease underwent R0 resection. As on cutoff date, nine are surviving (three without disease). Eighteen died of PD, and in two, cause was unknown. There was no toxic death. The median overall survival and progression-free survival were 309 and 252 days, respectively. Twenty-three patients experienced grade III or IV toxicity, and common were diarrhea (13), vomiting (12), and anemia (7).CONCLUSIONFirst-line modified flourouracil, oxaliplatin, and irinotecan is feasible in unresectable GBC with encouraging responses. Toxicities are higher but manageable. Higher response rates make this an option to explore in borderline resectable cases.

Abstract Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has recently emerged as a viable management option for peritoneal surface malignancy (PSM). CRS and HIPEC is a complex, multidisciplinary and resource-intensive surgical procedure. It has a steep learning curve and is associated with significant morbidity and mortality. The expertise is mostly limited to few dedicated high-volume centers located in developed countries. We present a single institutional experience of 232 cases of CRS and HIPEC performed at a tertiary care cancer center in a low- and middle-income country (LMIC). Methods A multidisciplinary PSM program was initiated in 2015 at a high-volume public-sector tertiary care cancer center in North India catering largely to patients belonging to low- and middle-income groups. Perioperative protocols were developed, and a prospective structured database was created to capture data. All patients undergoing CRS and HIPEC between January 2015 and December 2020 were identified, and the data was retrospectively analyzed for clinical spectrum, surgical details, and perioperative morbidity and mortality. Results Two hundred and thirty-two patients underwent CRS and HIPEC during the study period. Epithelial ovarian carcinoma (56.5%) was the most common malignancy treated, followed by pseudomyxoma peritonei (18.5%), colorectal carcinoma (13.4%), and malignant mesothelioma (5.6%). Optimal CRS could be achieved in 94.4% of patients. Cisplatin and mitomycin were the most common drugs used for HIPEC. A total of 28.0% of patients had morbidity including deep vein thrombosis, subacute intestinal obstruction, sepsis, burst abdomen, lymphocele, urinoma, acute renal failure, and enterocutaneous fistula. The overall treatment-related mortality was 3.5%. Conclusions Results of the current study indicate that it is feasible to establish a successful CRS and HIPEC program for PSM in government-funded hospitals in LMIC facing resource constraints. The most common indication for CRS and HIPEC were carcinoma of the ovary followed by pseudomyxoma peritonei and colorectal carcinoma. Overall morbidity and mortality in the current series are comparable to global standards, reported from high-income countries. A protocol-based multidisciplinary team approach, optimal patient selection, and surgical expertise can help achieve optimal outcomes in government-funded hospitals in LMIC.

Abstract Despite their protective antimicrobial function, neutrophil extracellular traps (NETs) have been implicated in propagation of inflammatory responses in several disease conditions including sepsis. Highly diffusible exogenous ROS produced under such inflammatory conditions, can induce exuberant NETs, thus making inhibition of NETs desirable in inflammatory diseases. Here we report that helminth parasite excretory/secretory factors termed as parasitic ligands (PL) inhibit ROS-induced NETs by blocking the activation of nonselective calcium permeable channel Transient Receptor Potential Melastatin 2 (TRPM2). Therapeutic implication of PL mediated blockage of NET formation was tested in preclinical model of septic peritonitis, where PL treatment regulated neutrophil cell death modalities including NET formation and mitigated neutrophil mediated inflammatory response. This translated into improved survival and reduced systemic and local bacterial load in infected mice. Overall, our results posit PL as an important biological regulator of neutrophil functions with implications to a variety of inflammatory diseases including peritonitis.

Abstract Fetal liver hematopoietic stem and progenitor cells (HSPCs) have been considered appropriate for the management of aplastic anemia owing to their proliferative potential. Bone marrow recovery was possible in some cases; the engraftment potential of these cells, however was unsatisfactory, possibly due to the availability of a smaller number of these cells from a single fetus. The present study explores how we can expand fetal liver hematopoietic stem cells under in vitro conditions. We isolated mononuclear cells from fetal liver and hematopoietic stem cells were identified and analyzed by cell surface marker CD34. CD34+ fetal liver HSPCs cells were separated by magnetic cell sorting positive selection method. HSPCs (CD34+) were cultured by using 5 cytokines, stem cell factor (SCF), granulocyte macrophages-colony stimulating factor (GM-CSF), interleukin-6 (IL-6), Fms-related tyrosine kinase 3 (FLT-3) and erythropoietin (EPO), in 4 different combinations along with supplements, in serum-free culture media for 21 days. Cell viability continued to be greater than 90% throughout 21 days of culture. The cells expanded best in a combination of media, supplements and 5 cytokines, namely SCF, FLT-3, IL6, EPO and GM-CSF to yield a large number of total (CD34+ & CD34-) cells. Even though the total number of nucleated cells increased in culture significantly, levels of CD34 antigen expression declined steadily over this period.

In this work, we study the effect of two spectrally simple nonharmonic inline forcing waveforms on the wake response of a square cylinder. The characteristics of wake response under nonharmonic forcing were studied and compared to wake response under harmonic forcing for a constant Reynolds number 100. By varying the relative strength of the spectral components and the secondary frequency of the nonharmonic forcing of the inflow, an asymmetric modulated wake and an asymmetric 2P + 2S wake were observed for a two-tone nonharmonic forcing. These modes combine the features of the wake response of individual spectral components. In some regions of the parameter space, the wake response did not correlate well with the spectral components of harmonic forcing. An amplitude-modulated forcing was also studied. For amplitude-modulated forcing, the additional frequency component did not affect the wake structure. This observation indicates that the wake may act as a low pass filter for inline flow frequency components above the natural vortex shedding frequency.

Abstract Using the ambitwistor string, we compute tree-level celestial amplitudes for biadjoint scalars, Yang-Mills and gravity to all multiplicities. They are presented in compact CHY-like formulas with operator-valued scattering equations and numerators acting on a generalized hypergeometric function. With these we extend the celestial double copy to tree-level amplitudes with arbitrary number of external states. We also show how color-kinematics duality is implemented in celestial amplitudes and its interpretation in terms of a generalized twisted cohomology theory.

Abstract Background No data exist for the long-term outcome of metastatic colorectal cancer (mCRC) from the Southern part of Asia. The primary objective of the study is to evaluate the survival outcome of mCRC from an Indian tertiary care center. The study also aims to highlight the treatment pattern practiced and the unique clinico-pathologic characteristics. Methods This is a single-center retrospective observational study done at a large referral tertiary care center in North India. All patients with synchronous or metachronous mCRC who received at least one dose of chemotherapy for metastatic disease, registered between 2003 to 2017 were included. Primary outcome measures were overall survival and progression-free survival and prognostic factors of overall survival. Descriptive analysis was done for the clinicopathological characteristics and treatment patterns. Kaplan Meier method for overall survival and progression-free survival. Cox regression analysis was performed for the determination of the prognostic factors for overall survival. Result Out of 377 eligible patients, 256 patients (68%) had de novo metastatic disease and the remaining 121 (32%) progressed to metastatic disease after initial treatment. The cohort was young (median age, 46 years) with the most common primary site being the rectum. A higher proportion of signet (9%) and mucinous histology (24%). The three common sites of metastasis were the liver, peritoneum, and lung. In the first line, most patients received oxaliplatin-based chemotherapy (70%). Only 12.5% of patients received biologicals in the first-line setting. The median follow-up and median overall survival of study cohort were 17 months and 18.5 months. The factors associated with poor outcome for overall survival on multivariate analysis were ECOG performance status of > 1, high CEA, low albumin, and the number of lines of chemotherapy received (

Abstract Multiple myeloma (MM) is a plasma cell malignancy with diverse clinical phenotypes and molecular heterogeneity not completely understood. Differentially expressed genes (DEGs) and miRNAs (DEMs) in MM may influence disease pathogenesis, clinical presentation / drug sensitivities. But these signatures overlap meagrely plausibly due to complexity of myeloma genome, diversity in primary cells studied, molecular technologies/ analytical tools utilized. This warrants further investigations since DEGs/DEMs can impact clinical outcomes and guide personalized therapy. We have conducted genome-wide meta-analysis of DEGs/DEMs in MM versus Normal Plasma Cells (NPCs) and derived unified putative signatures for MM. 100 DEMs and 1,362 DEGs were found deranged between MM and NPCs. Signatures of 37 DEMs (‘Union 37’) and 154 DEGs (‘Union 154’) were deduced that shared 17 DEMs and 22 DEGs with published prognostic signatures, respectively. Two miRs (miR-16–2-3p, 30d-2-3p) correlated with survival outcomes. PPI analysis identified 5 topmost functionally connected hub genes (UBC, ITGA4, HSP90AB1, VCAM1, VCP). Transcription factor regulatory networks were determined for five seed DEGs with ≥ 4 biomarker applications (CDKN1A, CDKN2A, MMP9, IGF1, MKI67) and three topmost up/ down regulated DEMs (miR-23b, 195, let7b/ miR-20a, 155, 92a). Further studies are warranted to establish and translate prognostic potential of these signatures for MM.

Background Prognosis of metastatic colorectal cancer (mCRC) is poor and goal of treatment is mainly palliative unless there is limited metastatic disease which is surgically resectable. Here, we report a case series of long-term survivors treated predominantly with chemotherapy. Methods This is a single-center retrospective analysis of patients of mCRC. Records of metastatic colorectal cancer patients registered at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, between the year 2005 and 2015 were retrieved and reviewed. Inclusion criteria were patients who survived 5 years or more, treated mainly by chemotherapy, with either initial presentation as metastatic disease or those who progressed after initial surgery with or without adjuvant therapy. The details about the patient characteristics, treatment, and outcome were collected. The data were censored on September 30, 2020. Results Records of 370 mCRC patients were reviewed. Thirty-one patients with all the available details fulfilled the criteria for inclusion in the study. Median age was 53 years (range, 22–74 years). Sixteen were women (51.6%). Twenty-four (77%) were newly diagnosed cases with initial presentation as metastatic disease. Commonest site of primary was on the left (21, 67.6%) followed by right side and transverse colon in 5 patients each. Liver was the most common site of metastasis (n = 18, 58.06%). In metastatic setting, the most common chemotherapy regimen used in the first line was CAPOX (n = 11, 35.48%). Only three patients could undergo metastatectomy. Monoclonal antibodies could be used only in 14 patients. Median overall survival (OS) of this cohort is 81.6 months (95% confidence interval [CI], 69.73–117.9). Conclusion A small but significant proportion of mCRC patients may achieve and maintain durable responses and long term survival with use of combination of chemotherapy with or without biologics.

Abstract Multi-collinear factorization limits provide a window to study how locality and unitarity of scattering amplitudes can emerge dynamically from celestial CFT, the conjectured holographic dual to gauge and gravitational theories in flat space. To this end, we first use asymptotic symmetries to commence a systematic study of conformal and Kac-Moody descendants in the OPE of celestial gluons. Recursive application of these OPEs then equips us with a novel holographic method of computing the multi-collinear limits of gluon amplitudes. We perform this computation for some of the simplest helicity assignments of the collinear particles. The prediction from the OPE matches with Mellin transforms of the expressions in the literature to all orders in conformal descendants. In a similar vein, we conclude by studying multi-collinear limits of graviton amplitudes in the leading approximation of sequential double-collinear limits, again finding a consistency check against the leading order OPE of celestial gravitons.

Newer molecular diagnostics and improved understanding of cancer pathogenesis have identified multiple pathways that can be potentially targeted with the use of novel therapeutics in development. These developments have ushered cancer therapeutics in newer era of personalized medicine. Same is reflected on current management strategies for advanced gastrointestinal malignancies. Molecular profiling for BRAF and RAS is standard for colorectal cancer while Her2 and PDL1 status is needed for planning therapy of advanced gastroesophageal cancers. Tissue agnostic markers like MSI, TMB and NTRK are making headways in therapeutic armamentarium. While newer targeted therapies against FGFR, EGFR, PI3K-AKT, DDR pathways are showing promising results in initial studies. Here we review traditional as well as upcoming molecular markers in field of GI malignancies, methods of testing and evidence for rational use in clinical practice.

Background: Aggressive pancreatobiliary tumors often require oxaliplatin-based therapies, instead of standard gemcitabine-based therapy and biomarker studies at diagnosis to decide the appropriate therapeutic regimen. The ribonucleotide Reductase catalytic subunit M1 (RRM1) and excision repair cross-complementing gene-1 (ERCC1) are related to DNA synthesis and repair and essential in this regard. However, apart from the therapeutic benefit, their prognostic implication is controversial. Methods: In this retrospective study, paraffin-embedded tissue from 51 cases of pancreatic cancer and 29 cases of cholangiocarcinoma were evaluated for RRM1 and ERCC1 expression by immunohistochemical technique along with 18 control pancreatic and biliary tissues. The semiquantitatively H score was calculated based on stain distribution and stain intensities. Results: Both RRM1 and ERCC1 expression were high in tumor epithelium than in controls (RRM1: the difference was statistically significant in cholangiocarcinoma (P = 0.008); ERCC1: the difference was statistically significant both in pancreatic and cholangiocarcinoma (P < 0.05)]. However, no correlation was noted between RRM1 and ERCC1-low and high tumors with histological markers of prognosis and overall survival in these patients. Conclusions: The present study adds further evidence against the controversy that if RRM1 and ERCC1 expression in pancreatic and biliary carcinomas have any prognostic significance apart from their proven therapeutic benefits in these tumors.

IntroductionWorldwide gastric cancer is the 5th most commonly diagnosed cancer and the leading cause of gastrointestinal cancer-related deaths. Alone surgery provides long-term survival improvements in 20% of the patients with local advanced gastric cancer. The results can be improved considering multimodal management including chemotherapy and radiotherapy. However, in low middle-income countries like India, multimodal management is challenging. Herein, we evaluated the experience of multimodal management of gastric cancer and the long-term outcome.MethodsRetrospective analysis of the data of 372 patients was done from a prospectively maintained computerized database from 1994 to 2021. Records were analyzed for demographic details, treatment patterns, recurrences, and long-term outcomes (DFS and OS). Statistical analysis was done with the package SPSS version 26 (IBM Corp, Chicago, Illinois, USA).ResultsThis study included 372 patients. The mean age of the patients was 54.07. A total of 307 patients (82.5%) were operated upfront, 45 (12%) received NACT, and 20 (5.5%) underwent the palliative procedure. A total of 53.2% underwent curative resection. R0 resection rate was achieved in 95% of patients. A total of 72.58% of patients required adjuvant treatment, and the majority of the patients underwent chemoradiotherapy. The most common site of metastasis was the liver. Median follow-up was 50.16 months. The 3-year disease-free survival and overall survival were 36.28% and 67.8%, and the 5-year disease-free survival and overall survival were 30.15% and 37.7%, respectively.ConclusionOur study suggested that multimodal management is required in locally advanced gastric cancer to achieve good long-term outcomes. The treatment sequence can be tailored based on the available resources.

PURPOSEPublished experience with autologous stem-cell transplantation (ASCT) in non-Hodgkin lymphoma (NHL) from the Indian subcontinent is extremely limited. Here, we describe the activity and outcomes of this treatment modality at a large tertiary care center in India.PATIENTS AND METHODSWe retrospectively analyzed adult patients with NHL who were eligible for ASCT and autografted between January 1, 2002, and December 15, 2020, at our transplant unit. Toxicities, complications, and long-term outcomes were compared between patients who underwent transplant during 2002-2012 (group A) and 2013-2020 (group B).RESULTSOverall, 80 patients (group A, n = 37; group B, n = 43) underwent ASCT using peripheral blood stem cells. At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients. More recently (group B), patients had reduced 100-day transplant-related mortality (2.3% v 21.6%, P < .01), improved 3-year EFS (52.9% v 37.3%, P = .04), and superior OS (at 3-year; 63.4% v 43.2%, P = .02). Patients in group B also tolerated the procedure better, with improved resource utilization. In multivariate analysis, an International Prognostic Index (IPI) ≥ 3 at diagnosis adversely affected EFS (hazard ratio [HR] = 2.82, P = .009) and OS (HR = 2.84, P = .01) after ASCT. Low pretransplant serum albumin levels were associated with inferior EFS (HR = 2.68, P = .02) and transplant-related mortality (odds ratio = 10.80, P = .02) after ASCT.CONCLUSIONIt is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive care and expertise of the transplant team and center.

Neutrophils are an important component of the innate immune response against various pathogens. However, there is a lack of research concerning the effects of short intensive training on neutrophil functions, especially neutrophil extracellular traps (NET) formation. The study aim was to determine the effects of a 19-day training cycle on innate immunity among young male athletes. Six male ice hockey players (< 20 years old) from the Polish national team were monitored across a five-day training camp and after a return to normal club training. The first blood collection took place before training (T1), the second after the training camp (T2) and the third 14 days later (T3). The counts/concentrations of blood biochemical, immune and endocrine markers were compared across each training period. Creatine kinase activity tended to increase at T2 (546 ± 216 U·L-1) when compared to T1 (191 ± 111 U·L-1; p=0.063). Neutrophil extracellular traps formation and neutrophil counts also differed between training periods (p=0.042 and p=0.042, respectively). Neutrophil counts tended to decrease, in contrast to NET formation which tended to rise, at T2 in comparison to T1 (2.51 ± 0.45 vs 3.04 ± 0.47 109 ·L-1; 24 ± 13 vs 8 ± 15%, respectively). No significant differences in other leucocyte counts were observed. A short period of intensive training was accompanied by some muscle damage and inflammation, as evidenced by CK and NET up-regulation, whilst neutrophil counts were diminished in the blood. Thus, neutrophils and NET could be involved in muscle damage and local inflammatory processes following intensive physical training in young male athletes