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Effective patient prognosis necessitates identification of novel tumor promoting drivers of gastric cancer (GC) which contribute to worsened conditions by analysing TCGA-gastric adenocarcinoma dataset. Small leucine-rich proteoglycans, asporin ( ASPN ) and decorin ( DCN ), play overlapping roles in development and diseases; however, the mechanisms underlying their interplay remain elusive. Here, we investigated the complex interplay of asporin, decorin and their interaction with TGFβ in GC tumor and corresponding normal tissues. The mRNA levels, protein expressions and cellular localizations of ASPN and DCN were analyzed using real-time PCR, western blot and immunohistochemistry, respectively. The protein-protein interaction was predicted by in-silico interaction analysis and validated by co-immunoprecipitation assay. The correlations between ASPN and EMT proteins, VEGF and collagen were achieved using western blot analysis. A significant increase in expression of ASPN in tumor tissue vs. normal tissue was observed in both TCGA and our patient cohort. DCN, an effective inhibitor of the TGFβ pathway, was negatively correlated with stages of GC. Co-immunoprecipitation demonstrated that DCN binds with TGFβ, in normal gastric epithelium, whereas in GC, ASPN preferentially binds TGFβ. Possible activation of the canonical TGFβ pathway by phosphorylation of SMAD2 in tumor tissues suggests its role as an intracellular tumor promoter. Furthermore, tissues expressing ASPN showed unregulated EMT signalling. Our study uncovers ASPN as a GC-promoting gene and DCN as tumor suppressor, suggesting that ASPN can act as a prognostic marker in GC. For the first time, we describe the physical interaction of TGFβ with ASPN in GC and DCN with TGFβ in GC and normal gastric epithelium respectively. This study suggests that prevention of ASPN-TGFβ interaction or overexpression of DCN could serve as promising therapeutic strategies for GC patients.

IntroductionThere is considerable variation in the practice of ventral hernia repair (VHR). Consequently, both short- and long-term outcomes are different. We report the first multicenter data from India on the variations in procedures and short-term outcomes after ventral hernia repair.MethodsA prospective study was planned under the aegis of the Indian Association of Gastrointestinal Endo Surgeons (IAGES). Participating surgeons prospectively recorded the data of patients who underwent VHR from January 21, 2021, to April 20, 2021. Patients were followed for 3–6 months.ResultsData from 648 patients were analyzed for demographics, hernia characteristics, technical variations, and outcomes. 375 (57.8%) were primary hernias (PH) and 273 (42.15%) were incisional hernias (IH), of which 63 (9.7%) were recurrent hernias. In the PH group, there were 171 minimal access (MAS) and 170 open repair. In descending order of frequency, there were 111 (32.6%) open onlay, 83 (24.3%) intraperitoneal onlay meshplasty (IPOM) Plus, 36 (10.6%) IPOM, 35 (10.3%) suture repair, 22 (6.5%) endoscopic Rives Stoppa (eRS), 11 (3.2%) open RS, 11 (3.2%) TAPP, 7 (2%) hybrid, 6 (1.8%) open preperitoneal, 19 (5.6%) others. There were 3.73% seroma, 3.2% SSI, 0% 90-day readmission, 0% recurrence, and 0.3% mortality. In the IH group, 164 patients underwent open repair and 104 MAS repair. In descending order of frequency, there were 90 (33.6%) open onlay, 47 (17.5%) IPOM Plus, 38 (14.1%) open sublay, 28 (10.4%) IPOM, 12 (4.5%) Transversus Abdominis Release (TAR), 11 (4.1%) suture repair, 9 (3.4%) open preperitoneal, 7 (2.6%) hybrid, 6 (2.2%) TAPP, 5 (1.9%) eRS, 4 (1.5%) TARM, 3 (1.1%) endoscopic TAR (eTAR), and 8 (3%) others. There were 13.92% seroma, 4.4% hematoma, 9.5% SSI, 1.1% mesh explantation, 0.4% wound sinus, 2.2% 90-day readmission, 0% recurrence, and 1.1% mortality.ConclusionOnlay meshplasty is the commonest procedure in India both in PH and IH. IPOM/IPOM plus is the second commonest procedure. TAR is the preferred component separation technique. Complication rates were comparable to published literature.Trial registrationThe study was registered with Clinical Trial Registry of India. CTRI number-CTRI/2021/01/030435.

Effective patient prognosis necessitates identification of novel tumor promoting drivers of gastric cancer (GC) which contribute to worsened conditions by analysing TCGA-gastric adenocarcinoma dataset. Small leucine-rich proteoglycans, asporin (ASPN) and decorin (DCN), play overlapping roles in development and diseases; however, the mechanisms underlying their interplay remain elusive. Here, we investigated the complex interplay of asporin, decorin and their interaction with TGFβ in GC tumor and corresponding normal tissues. The mRNA levels, protein expressions and cellular localizations of ASPN and DCN were analyzed using real-time PCR, western blot and immunohistochemistry, respectively. The protein-protein interaction was predicted by in-silico interaction analysis and validated by co-immunoprecipitation assay. The correlations between ASPN and EMT proteins, VEGF and collagen were achieved using western blot analysis. A significant increase in expression of ASPN in tumor tissue vs. normal tissue was observed in both TCGA and our patient cohort. DCN, an effective inhibitor of the TGFβ pathway, was negatively correlated with stages of GC. Co-immunoprecipitation demonstrated that DCN binds with TGFβ, in normal gastric epithelium, whereas in GC, ASPN preferentially binds TGFβ. Possible activation of the canonical TGFβ pathway by phosphorylation of SMAD2 in tumor tissues suggests its role as an intracellular tumor promoter. Furthermore, tissues expressing ASPN showed unregulated EMT signalling. Our study uncovers ASPN as a GC-promoting gene and DCN as tumor suppressor, suggesting that ASPN can act as a prognostic marker in GC. For the first time, we describe the physical interaction of TGFβ with ASPN in GC and DCN with TGFβ in GC and normal gastric epithelium respectively. This study suggests that prevention of ASPN-TGFβ interaction or overexpression of DCN could serve as promising therapeutic strategies for GC patients.

Annular pancreas is an uncommon congenital anomaly which usually presents itself in infants and newborn. Rarely it can present in late adult life with wide range of clinical severities thereby making its diagnosis difficult. Pre-operative diagnosis is often difficult. CT scan can illustrate the pancreatic tissue encircling the duodenum. ERCP and MRCP are useful in outlining the annular pancreatic duct. Surgery still remains necessary to confirm diagnosis and bypassing the obstructed segment.We report a case of 61 year female presenting with duodenal obstruction due to annular pancreas.

The value of standard Pancreaticoduodenectomy for Periampullary carcinomas has long been a matter of debate. Though the mortality has dramatically reduced in high volume centers with dedicated hepatobiliary surgery units, the rate is still high in peripheral institutes. In this study our aim was to access the overall post operative outcome associated with pancreaticoduodenectomy performed in a government medical college. A total of 44 patients who underwent pancreaticoduodenectomy for operable periampullary cancers were evaluated. The overall morbidity rate was 31.1%. A total of 13 (29.5%) died following the operation and of its complications though the rate has reduced drastically to 14.2% in2008. The average length of hospital stay was 22 days. The mean survival was 15 months. Pancreaticoduodenectomy can safely be performed in government medical colleges with good results. In view of the majority of the patients in rural and suburban communities, not all patients need referral to higher centers.

A '4D schedule' is a 3 dimensional CAD model attached to the fourth dimension of time via a schedule. This case study is a 4D scheduling effort for a large construction program. It appears that the benefits of 4D Scheduling that are driving the use of 4D scheduling and 3D modeling are in both tangible and intangible categories. While the savings in cost and schedule, risk reduction, improved quality, reduction of RFIs and claims are tangible, an important intangible gain seems to be in using the models to communicate project parameters to non technical stakeholders and get their buy-in. 4D scheduling is moving from being a buzzword to reality. Its value in saving cost and time has been confirmed with field data. This presents an additional opportunity to schedulers for enhancing their value to the project team.

Nanoscale drug delivery vehicles have been harnessed extensively as carriers for cancer chemotherapeutics. However, traditional pharmaceutical approaches for nanoformulation have been a challenge with molecules that exhibit incompatible physicochemical properties, such as platinum-based chemotherapeutics. Here we propose a paradigm based on rational design of active molecules that facilitate supramolecular assembly in the nanoscale dimension. Using cisplatin as a template, we describe the synthesis of a unique platinum (II) tethered to a cholesterol backbone via a unique monocarboxylato and O→Pt coordination environment that facilitates nanoparticle assembly with a fixed ratio of phosphatidylcholine and 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[amino (polyethylene glycol)-2000]. The nanoparticles formed exhibit lower IC ₅₀ values compared with carboplatin or cisplatin in vitro, and are active in cisplatin-resistant conditions. Additionally, the nanoparticles exhibit significantly enhanced in vivo antitumor efficacy in murine 4T1 breast cancer and in K-Ras ᴸSᴸ/⁺/Pten ᶠˡ/ᶠˡ ovarian cancer models with decreased systemic- and nephro-toxicity. Our results indicate that integrating rational drug design and supramolecular nanochemistry can emerge as a powerful strategy for drug development. Furthermore, given that platinum-based chemotherapeutics form the frontline therapy for a broad range of cancers, the increased efficacy and toxicity profile indicate the constructed nanostructure could translate into a next-generation platinum-based agent in the clinics.

Radio pulsars show remarkable clock-like stability, which make them useful astronomy tools in experiments to test equation of state of neutron stars and detecting gravitational waves using pulsar timing techniques. A brief review of relevant astrophysical experiments is provided in this paper highlighting the current state-of-the-art of these experiments. A program to monitor frequently glitching pulsars with Indian radio telescopes using high cadence observations is presented, with illustrations of glitches detected in this program, including the largest ever glitch in PSR B0531+21. An Indian initiative to discover sub-\\[\\mu \\]Hz gravitational waves, called Indian Pulsar Timing Array (InPTA), is also described briefly, where time-of-arrival uncertainties and post-fit residuals of the order of \\[\\mu \\]s are already achievable, comparable to other international pulsar timing array experiments. While timing the glitches and their recoveries are likely to provide constraints on the structure of neutron stars, InPTA will provide upper limits on sub-\\[\\mu \\]Hz gravitational waves apart from auxiliary pulsar science. Future directions for these experiments are outlined.

Decades long monitoring of millisecond pulsars, which exhibit highly stable rotational periods, in pulsar timing array experiments is on the threshold of discovering nanohertz stochastic gravitational wave background. This paper describes the Indian Pulsar timing array (InPTA) experiment, which employs the upgraded Giant Metrewave Radio Telescope (uGMRT) for timing an ensemble of millisecond pulsars for this purpose. We highlight InPTA's observation strategies and analysis methods, which are relevant for a future PTA experiment with the more sensitive Square Kilometer Array (SKA) telescope. We show that the unique multi-sub-array multi-band wide-bandwidth frequency coverage of the InPTA provides Dispersion Measure estimates with unprecedented precision for PTA pulsars, e.g., ~ 2 x 10{-5} pc-cm{-3} for PSR J1909-3744. Configuring the SKA-low and SKA-mid as two and four sub-arrays respectively, it is shown that comparable precision is achievable, using observation strategies similar to those pursued by the InPTA, for a larger sample of 62 pulsars requiring about 26 and 7 hours per epoch for the SKA-mid and the SKA-low telescopes respectively. We also review the ongoing efforts to develop PTA-relevant general relativistic constructs that will be required to search for nanohertz gravitational waves from isolated super-massive black hole binary systems like blazar OJ 287. These efforts should be relevant to pursue persistent multi-messenger gravitational wave astronomy during the forthcoming era of the SKA telescope, the Thirty Meter Telescope, and the next-generation Event Horizon Telescope.

Pulsar radio emission undergoes dispersion due to the presence of free electrons in the interstellar medium (ISM). The dispersive delay in the arrival time of pulsar signal changes over time due to the varying ISM electron column density along the line of sight. Correcting for this delay accurately is crucial for the detection of nanohertz gravitational waves using Pulsar Timing Arrays. In this work, we present in-band and inter-band DM estimates of four pulsars observed with uGMRT over the timescale of a year using two different template alignment methods. The DMs obtained using both these methods show only subtle differences for PSR 1713+0747 and J1909\\(-\\)3744. A considerable offset is seen in the DM of PSR J1939+2134 and J2145\\(-\\)0750 between the two methods. This could be due to the presence of scattering in the former and profile evolution in the latter. We find that both methods are useful but could have a systematic offset between the DMs obtained. Irrespective of the template alignment methods followed, the precision on the DMs obtained is about \\(10^{-3}\\) pc cm\\(^{-3}\\) using only BAND3 and \\(10^{-4}\\) pc cm\\(^{-3}\\) after combining data from BAND3 and BAND5 of the uGMRT. In a particular result, we have detected a DM excess of about \\(5\\times10^{-3}\\) pc cm\\(^{-3}\\) on 24 February 2019 for PSR J2145\\(-\\)0750. This excess appears to be due to the interaction region created by fast solar wind from a coronal hole and a coronal mass ejection (CME) observed from the Sun on that epoch. A detailed analysis of this interesting event is presented.