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1.
J Clin Exp Hepatol ; 14(5): 101410, 2024.
Article En | MEDLINE | ID: mdl-38716375

Background: Gallbladder cancer (GBC) is a biologically aggressive malignancy requiring appropriate biomarkers to improve its outcome. Role of ABC transporters (ABCB1 and ABCG2) has been linked to cancer aggressiveness, tumorigenesis and multidrug resistance. Herein, we studied the prognostic implication of ABCB1 and ABCG2 in GBC. Methods: Fresh tissue (tumour & normal) samples collected from 54 patients who underwent R0 resection, were analysed for mRNA and protein expression of ABCB1 and ABCG2 by quantitative Real-Time PCR and western blotting, respectively, in this prospective study. The molecular findings were correlated with clinical-pathological parameters using χ2 and fisher exact test. The molecular changes in ABCB1 and ABCG2 were analysed for predicting overall survival (OS), disease-free survival (DFS) and response to chemotherapy using Kaplan-Meier log-rank test and Cox regression multivariate analysis. Results: The mean age of the cohort was 50 ± 13.2 with 26 (48.1%) in patients having early stage gallbladder cancer (GBC). Over-expression of ABCB1 and ABCG2 was noted in 32/54 (59%) and 40/54 (74%) cases, respectively. The protein expression of ABCB1(P-glycoprotein) and ABCG2 (BCRP) was higher in 27/54 (50%) and 37/54 (59%) cases, respectively. The mean OS and DFS was 20.7 ± 11.5 and 19.3 ± 12.2 months at median follow-up of 24 months. The TNM stage, lymph node metastasis, and presence of gallstone were significant factors for predicting OS and DFS on multivariate analysis. Both ABCB1 and ABCG2 did not show any significant correlation with OS and DFS with similar incidences of late death and recurrence among over-expression and down-expression. Sub-group comparison suggests that change in expression pattern of ABCB1 and ABCG2 may not affect response to chemotherapy in GBC. Conclusion: Altered expression of ABCB1 and ABCG2 may not be a useful prognostic marker for survival or response to chemotherapy in GBC. Presently, histo-pathological characteristics and associated gallstones are the important predictors for survival and recurrence in GBC.

2.
PLoS One ; 19(5): e0296565, 2024.
Article En | MEDLINE | ID: mdl-38781195

Epigenetic silencing through methylation is one of the major mechanisms for downregulation of tumor suppressor miRNAs in various malignancies. The aim of this study was to identify novel tumor suppressor miRNAs which are silenced by DNA hypermethylation and investigate the role of at least one of these in oral squamous cell carcinoma (OSCC) pathogenesis. We treated cells from an OSCC cell line SCC131 with 5-Azacytidine, a DNA methyltransferase inhibitor, to reactivate tumor suppressor miRNA genes silenced/downregulated due to DNA methylation. At 5-day post-treatment, total RNA was isolated from the 5-Azacytidine and vehicle control-treated cells. The expression of 2,459 mature miRNAs was analysed between 5-Azacytidine and control-treated OSCC cells by the microRNA microarray analysis. Of the 50 miRNAs which were found to be upregulated following 5-Azacytidine treatment, we decided to work with miR-6741-3p in details for further analysis, as it showed a mean fold expression of >4.0. The results of qRT-PCR, Western blotting, and dual-luciferase reporter assay indicated that miR-6741-3p directly targets the oncogene SRSF3 at the translational level only. The tumor-suppressive role of miR-6741-3p was established by various in vitro assays and in vivo study in NU/J athymic nude mice. Our results revealed that miR-6741-3p plays a tumor-suppressive role in OSCC pathogenesis, in part, by directly regulating SRSF3. Based on our observations, we propose that miR-6741-3p may serve as a potential biological target in tumor diagnostics, prognostic evaluation, and treatment of OSCC and perhaps other malignancies.


Carcinoma, Squamous Cell , Gene Expression Regulation, Neoplastic , MicroRNAs , Mouth Neoplasms , Serine-Arginine Splicing Factors , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Animals , Cell Line, Tumor , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Mice , Gene Expression Regulation, Neoplastic/drug effects , Serine-Arginine Splicing Factors/genetics , Serine-Arginine Splicing Factors/metabolism , DNA Methylation , Introns/genetics , Mice, Nude , Azacitidine/pharmacology , Oncogenes/genetics
3.
J Org Chem ; 2024 May 16.
Article En | MEDLINE | ID: mdl-38754107

The biological and medicinal importance of indolocarbazoles has been known for the past several decades. However, in recent times, these compounds have been emerging as potential candidates for optoelectronic applications, although several challenges are associated with their synthesis. We report here a Pd(II)-catalyzed process for the synthesis of indolo[3,2-a]carbazoles. The reaction proceeded under neat conditions and in the presence of aqueous nonmetallic oxidant TBHP, and the products were purified directly after the completion of the reaction. Also, the possibility of employing the present method for reaction with gram-scale feed was investigated. A detailed single-crystal analysis of several indolo[3,2-a]carbazoles revealed how the molecular arrangement can be tuned by altering the functionalization. Finally, the developed molecules were screened computationally to assess their potential for possible use as hole transport materials (HTMs) for organic light-emitting diodes (OLEDs).

4.
Lab Anim Res ; 40(1): 22, 2024 May 22.
Article En | MEDLINE | ID: mdl-38773665

BACKGROUND: Toxicity by pesticide has become a global health issue and leaves a harmful impact on human health via various ways. The people exposed to pesticides in the rural population get affected by the harmful effects of it as they enter the human body system through skin, inhalation, oral administration, food chain and many more ways. The present work is designed to study the toxic effect of endosulfan in male (n=30) and female (n=30) Swiss albino mice. Endosulfan was administered by oral gavage (oral administration) method, at the dose of 3.5 mg/Kg body weight daily for period of 3 weeks, 5 weeks and 7 weeks. After the completion of the treatment, the mice were sacrificed and their ovary and testis tissues were dissected out to check the degeneration. The blood was collected for karyotyping, biochemical and hormonal analysis of pesticide induced genotoxicity. After 7 weeks of administration with Endosulfan, various abnormalities were observed in male and female mice. RESULTS: Treatment with endosulfan at the dose of 3.5 mg/Kg body weight caused a higher degree of degeneration in the reproductive organ of Swiss albino mice . Treatment by this pesticide generated degeneration in long duration of dosage for 3,5 and 7 weeks. Ovaries of endosulfan administered groups showed degenerated germinal epithelium, Graffian follicles and corpus luteum. In testis of endosulfan treated mice, microscopic examination showed that there is significant damage and reduction in the tissue of seminiferous tubules and primordial germ cells. High degree of degeneration caused the disarrangement and deformation of spermatogonia with the decrease in the number of Sertoli cells. Biochemical and hormonal properties was also affected by endosulfan treatment. There was significant 5 folds decrease in the testosterone value of endosulfan in 7 weeks treated mice in comparison to control (p < 0.0001) and similarly there was significant elevation in the estrogen levels found in 7th week endosulfan treated mice. It also influenced the level of free radicals as there was significant decrease (p < 0.0001) in the value in catalase levels in 7 weeks endosulfan treated male and female mice, while significant (p < 0.0001) increase in the values of lipid peroxidation levels as 8 folds and 10 folds in 7 weeks endosulfan treated male and female Swiss albino mice respectively. This study hence speculates that the endosulfan exposed population are at the risk of reproductive health hazards. CONCLUSIONS: The present study thus concludes that, endosulfan after 7 weeks of exposure caused significant reproductive damage to both male and female Swiss albino mice groups. Moreover, the karyotyping study also correlated the genotoxic damage in the mice.

5.
Science ; 384(6695): 563-572, 2024 May 03.
Article En | MEDLINE | ID: mdl-38696572

A molecular clock network is crucial for daily physiology and maintaining organismal health. We examined the interactions and importance of intratissue clock networks in muscle tissue maintenance. In arrhythmic mice showing premature aging, we created a basic clock module involving a central and a peripheral (muscle) clock. Reconstituting the brain-muscle clock network is sufficient to preserve fundamental daily homeostatic functions and prevent premature muscle aging. However, achieving whole muscle physiology requires contributions from other peripheral clocks. Mechanistically, the muscle peripheral clock acts as a gatekeeper, selectively suppressing detrimental signals from the central clock while integrating important muscle homeostatic functions. Our research reveals the interplay between the central and peripheral clocks in daily muscle function and underscores the impact of eating patterns on these interactions.


Aging, Premature , Aging , Brain , Circadian Rhythm , Muscle, Skeletal , Animals , Male , Mice , Aging/genetics , Aging/physiology , Aging, Premature/genetics , Aging, Premature/prevention & control , Brain/physiology , Circadian Clocks/physiology , Circadian Rhythm/genetics , Circadian Rhythm/physiology , Homeostasis , Muscle, Skeletal/physiology , Mice, Knockout , ARNTL Transcription Factors/genetics
6.
Nat Commun ; 15(1): 3215, 2024 Apr 13.
Article En | MEDLINE | ID: mdl-38615096

Spatial compartmentalization is a key facet of protein quality control that serves to store disassembled or non-native proteins until triage to the refolding or degradation machinery can occur in a regulated manner. Yeast cells sequester nuclear proteins at intranuclear quality control bodies (INQ) in response to various stresses, although the regulation of this process remains poorly understood. Here we reveal the SUMO modification of the small heat shock protein Btn2 under DNA damage and place Btn2 SUMOylation in a pathway promoting protein clearance from INQ structures. Along with other chaperones, and degradation machinery, Btn2-SUMO promotes INQ clearance from cells recovering from genotoxic stress. These data link small heat shock protein post-translational modification to the regulation of protein sequestration in the yeast nucleus.


Heat-Shock Proteins, Small , Intranuclear Inclusion Bodies , Vesicular Transport Proteins , DNA Damage , Heat-Shock Proteins, Small/genetics , Heat-Shock Proteins, Small/metabolism , Intranuclear Inclusion Bodies/genetics , Intranuclear Inclusion Bodies/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Sumoylation , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolism
7.
Vet World ; 17(3): 645-657, 2024 Mar.
Article En | MEDLINE | ID: mdl-38680147

Background: Sialic acid-binding immunoglobulin-like lectin 1 (Siglec-1) is a transmembrane glycoprotein involved in the sialic acid (Sia)-dependent regulation of the immune system. Siglec-1 expression has recently been identified in the male reproductive tract (MRT) of several species, including humans, cattle, horses, and sheep, and may play a role in modulating fertility in a Sia-dependent manner. Materials and Methods: In this study, protein-protein interaction (PPI) analysis of Siglec-1 was conducted to identify associated network protein conservation, and the expression of Siglec-1 in the MRT of mice and rats, including their accessory sex glands and spermatozoa was determined by immunostaining. Results: Network analysis of proteins with Siglec-1 in mice and rats demonstrated significant similarity to human Siglec-1 networks, suggesting a similar conservation of network proteins between these species and, hence, a potential conservation role in immune modulation and function. Specific immunostaining patterns of mouse and rat testes, epididymis, ductus deferens, accessory sex gland tissues, and sperm were detected using human Siglec-1. These results confirmed that the human Siglec-1 antibody could cross-react with mouse and rat Siglec-1, suggesting that the specific expression patterns of Siglec-1 in the MRT and sperm of both mice and rats are similar to those observed in other species. Conclusions: The conservation of Siglec-1 expression patterns in sperm and within the MRT and the similarity of protein networks for Siglec-1 across species suggest that Siglec-1 may function in a similar manner across species. These results also suggest that rodents may serve as a valuable model system for exploring the function of Siglecs in the reproductive system across species and their potential role in modulating fertility in a Sia-dependent manner.

8.
Sci Total Environ ; 928: 172460, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38615781

Recently, a substantial increase in gallbladder cancer (GBC) cases has been reported in Bihar, India. The region's groundwater can naturally contain harmful concentrations of arsenic, which appears to be epidemiologically linked to the unusually high incidence. However, the root causes remain largely unexplored. Recent findings of uranium in the state's groundwater may also have associations. This study investigates the geo-spatial epidemiology of GBC in Bihar, India-with a focus on the correlation between environmental carcinogens, particularly arsenic and uranium in groundwater, and the incidence of GBC. Utilizing data from 8460 GBC patients' registration records over an 11-year period at a single health center, the research employs Semi-parametric Geographically Weighted Poisson Regression (S-GWPR) to account for non-stationarity associations and explores significant factors contributing to GBC prevalence at a subdistrict level. The S-GWPR model outperformed the standard Poisson regression model. The estimates suggest that arsenic and uranium concentrations in groundwater did not present significant associations; however, this could be due to the lower resolution of this data at the district level, necessitating higher resolution data for accurate estimates. Other socio-environmental factors included demonstrated significant regional heterogeneity in their association with GBC prevalence. Notably, each 1 % increase in the coverage of well- and canal-irrigated areas is associated with a maximum of 3.0 % and 5.2 % rise in the GBC incidence rate, respectively, likely attributable to carcinogen exposure from irrigation water. Moreover, distance to the health center and domestic electricity connections appear to influence the number of reported GBC cases. The latter suggests that access to electricity might have facilitated the use of groundwater pumps-increasing exposure to carcinogens. The results underscore the necessity for targeted health policies and interventions based on fine-resolution spatial analysis, as well as ongoing environmental monitoring and research to better understand the multifaceted risk factors contributing to GBC.


Gallbladder Neoplasms , Groundwater , Water Pollutants, Chemical , India/epidemiology , Humans , Gallbladder Neoplasms/epidemiology , Groundwater/chemistry , Water Pollutants, Chemical/analysis , Environmental Exposure/statistics & numerical data , Arsenic/analysis , Female , Uranium/analysis , Male , Incidence , Middle Aged , Adult , Spatial Analysis
9.
ACS Appl Mater Interfaces ; 16(17): 22421-22432, 2024 May 01.
Article En | MEDLINE | ID: mdl-38634639

Lanthanides are largely used in optoelectronics as dopants to enhance the physical and optical properties of semiconducting devices. In this study, lanthanum(III)hydroxide nanoparticles (La(OH)3NPs) are used as a dopant of polyethylenimine (PEI)-functionalized nitrogen (N)-doped graphene quantum dots (PEI-NGQDs). The La(OH)3NPs-dopedPEI-NGQDs nanocomposites are prepared from La(NO)3 in a single step by a green novel method and are characterized by Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-vis), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Deposited over an n-type Si wafer, the La(OH)3NPs-dopedPEI-NGQDs nanocomposites form Schottky diodes. The I-V characteristics and the photoresponse of the diodes are investigated as a function of the illumination intensity in the range 0-110 mW cm-2 and at room temperature. It is found that the rectification ratio and ideality factor of the diode decrease, while the Schottky barrier and series resistance increase with the enhancing illuminations. As a photodetector, the La(OH)3NPs-dopedPEI-NGQDs/n-Si heterojunction exhibits an appreciable responsivity of 3.9 × 10-3 AW-1 under 22 mW cm-2 at -0.3 V bias and a maximum detectivity of 8.7 × 108 Jones under 22 mW cm-2 at -0.5 V. This study introduces the green synthesis and presents the structural, electrical, and optoelectronic properties of La(OH)3NPs-dopedPEI-NGQDs, demonstrating that these nanocomposites can be promising for optoelectronic applications.

10.
Mater Horiz ; 11(10): 2397-2405, 2024 May 20.
Article En | MEDLINE | ID: mdl-38470088

Black phosphorus (BP) field-effect transistors with ultrathin channels exhibit unipolar p-type electrical conduction over a wide range of temperatures and pressures. Herein, we study a device that exhibits mobility up to 100 cm2 V-1 s-1 and a memory window up to 1.3 µA. Exposure to a supercontinuum white light source reveals that negative photoconductivity (NPC) and positive photoconductivity (PPC) coexist in the same device. Such behavior is attributed to the chemisorbed O2 molecules, with a minor role of physisorbed H2O molecules. The coexistence of NPC and PPC can be exploited in neuromorphic vision sensors, requiring the human eye retina to process the optical signals through alerting and protection (NPC), adaptation (PPC), followed by imaging and processing. Our results open new avenues for the use of BP and other two-dimentional (2D) semiconducting materials in transistors, memories, and neuromorphic vision sensors for advanced applications in robotics, self-driving cars, etc.

11.
Langmuir ; 40(14): 7310-7327, 2024 Apr 09.
Article En | MEDLINE | ID: mdl-38426447

A thixotropic colloidal gel constituting an aqueous dispersion of synthetic clay Laponite with varying concentrations of salt has been studied for its rheological and tribological performance as a lubricant. We observed that the incorporation of NaCl induces notable enhancements in the colloidal gel's relaxation time, elastic modulus, and yield stress. Although an increase in NaCl concentration decreases the material's relaxation time dependence on waiting time (tw), overall, the strength of its thixotropic character has been observed to increase with an increase in salt concentration. The analysis of friction and wear indicated that the utilization of a thixotropic colloidal gel of Laponite with a higher concentration of NaCl resulted in progressively greater reductions in both the coefficient of friction and specific wear rates under various load-speed conditions. Severe abrasive wear on disc surface under dry test, gradually mitigated upon the introduction of these lubricants. Two simultaneous lubricating mechanisms, first, the smooth sliding of the friction pair, facilitated by the alignment of Laponite particles in the direction of shear forces, and second, the stable structure of Laponite, coupled with the addition of NaCl, enabling continuous replenishment of the wear track with lubricant, are attributed to lubrication effectiveness.

12.
J Sport Health Sci ; 2024 Feb 29.
Article En | MEDLINE | ID: mdl-38428731

PURPOSE: There exist few maximal oxygen uptake (VO2max) non-exercise-based prediction equations, fewer using machine learning (ML), and none specifically for older adults. Since direct measurement of VO2max is infeasible in large epidemiologic cohort studies, we sought to develop, validate, compare, and assess the transportability of several ML VO2max prediction algorithms. METHODS: The Baltimore Longitudinal Study of Aging (BLSA) participants with valid VO2max tests were included (n = 1080). Least absolute shrinkage and selection operator, linear- and tree-boosted extreme gradient boosting, random forest, and support vector machine (SVM) algorithms were trained to predict VO2max values. We developed these algorithms for: (a) for the overall BLSA, (b) by sex, (c) using all BLSA variables, and (d) for variables common in aging cohorts. Finally, we quantified the associations between measured and predicted VO2max and mortality. RESULTS: The age was 69.0 ± 10.4 years (mean ± SD) and the measured VO2max was 21.6 ± 5.9 mL/kg/min. Least absolute shrinkage and selection operator, linear- and tree-boosted extreme gradient boosting, random forest, and support vector machine yielded root mean squared errors of 3.4 mL/kg/min, 3.6 mL/kg/min, 3.4 mL/kg/min, 3.6 mL/kg/min, and 3.5 mL/kg/min, respectively. Incremental quartiles of measured VO2max showed an inverse gradient in mortality risk. Predicted VO2max variables yielded similar effect estimates but were not robust to adjustment. CONCLUSION: Measured VO2max is a strong predictor of mortality. Using ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to adjustment. Future studies should seek to reproduce these results so that VO2max, an important vital sign, can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

13.
Indian J Crit Care Med ; 28(3): 200-250, 2024 Mar.
Article En | MEDLINE | ID: mdl-38477011

End-of-life care (EOLC) exemplifies the joint mission of intensive and palliative care (PC) in their human-centeredness. The explosion of technological advances in medicine must be balanced with the culture of holistic care. Inevitably, it brings together the science and the art of medicine in their full expression. High-quality EOLC in the ICU is grounded in evidence, ethical principles, and professionalism within the framework of the Law. Expert professional statements over the last two decades in India were developed while the law was evolving. Recent landmark Supreme Court judgments have necessitated a review of the clinical pathway for EOLC outlined in the previous statements. Much empirical and interventional evidence has accumulated since the position statement in 2014. This iteration of the joint Indian Society of Critical Care Medicine-Indian Association of Palliative Care (ISCCM-IAPC) Position Statement for EOLC combines contemporary evidence, ethics, and law for decision support by the bedside in Indian ICUs. How to cite this article: Mani RK, Bhatnagar S, Butola S, Gursahani R, Mehta D, Simha S, et al. Indian Society of Critical Care Medicine and Indian Association of Palliative Care Expert Consensus and Position Statements for End-of-life and Palliative Care in the Intensive Care Unit. Indian J Crit Care Med 2024;28(3):200-250.

14.
Sci Rep ; 14(1): 6976, 2024 03 23.
Article En | MEDLINE | ID: mdl-38521842

Smart hospitals are poised to greatly enhance life quality by offering persistent health monitoring capabilities. Remote healthcare and surgery, which are highly dependent on low latency, have seen a transformative improvement with the advent of 5G technology. This has facilitated a new breed of healthcare services, including monitoring and remote surgical procedures. The enhanced features of 5G, such as Enhanced Mobile Broadband (eMBB) and Ultra-Reliable Low Latency Communications (URLLC), have enabled the development of advanced healthcare systems. These systems reduce the need for direct patient contact in hospitals, which is especially pertinent as 5G becomes more widespread. This research presents novel hybrid detection algorithms, specifically QR decomposition with M-algorithm maximum likelihood-minimum mean square error (QRM-MLD-MMSE) and QRM-MLD-ZF (zero forcing), for use in Massive MIMO (M-MIMO) technology. These methods aim to decrease the latency in MIMO-based Non-Orthogonal Multiple Access (NOMA) waveforms while ensuring optimal bit error rate (BER) performance. We conducted simulations to evaluate parameters like BER and power spectral density (PSD) over Rician and Rayleigh channels using both the proposed hybrid and standard algorithms. The study concludes that our hybrid algorithms significantly enhance BER and PSD with lower complexity, marking a substantial improvement in 5G communication for smart healthcare applications.


Health Facilities , Hospitals , Humans , Algorithms , Breeding , Communication
15.
Discov Nano ; 19(1): 57, 2024 Mar 25.
Article En | MEDLINE | ID: mdl-38528187

Mechanically exfoliated multilayer WS2 flakes are used as the channel of field effect transistors for low-power photodetection in the visible and near-infrared (NIR) spectral range. The electrical characterization as a function of the temperature reveals devices with n-type conduction and slightly different Schottky barriers at the drain and source contacts. The WS2 phototransistors can be operated in self-powered mode, yielding both a current and a voltage when exposed to light. The spectral photoresponse in the visible and the NIR ranges shows a high responsivity (4.5 µA/W) around 1250 nm, making the devices promising for telecommunication applications.

16.
Article En | MEDLINE | ID: mdl-38546423

Diabetes mellitus (DM) is the most common endocrine disorder characterized by increased blood glucose levels resulting from defective insulin secretion, resistance to insulin action, or both. DM is often associated with severe complications, and there is an increasing appreciation that cognitive function declines in DM. The aim of this research work was to evaluate Kigelia pinnata root bark extract in Streptozotocin (STZ)-induced type-2 diabetes. Experimental diabetes was induced by a single administration of STZ (60 mg/kg, intraperitoneal [i.p.]), immediately after the STZ administration, and all animals were fed with normal food and water. Nicotinamide was administered (120 mg/kg, i.p.) 15 min before STZ. The development of hyperglycemia was confirmed by the elevated blood glucose levels determined at fixed intervals, which was confirmed by measuring fasting blood glucose levels in rats' blood taken from the tail vein. Supplementation with ethanolic extract of K. pinnata root bark (EEKP) significantly reduced the elevated blood glucose in STZ-induced hyperglycemia in rats. EEKP significantly restored the biochemical and antioxidant defense system. On the final day of the protocol, the extract also reduced inflammatory cytokines in the blood serum.

17.
Haematologica ; 2024 Feb 29.
Article En | MEDLINE | ID: mdl-38426294

TOURMALINE-MM1, the only blinded randomized study in patients with relapsed and/or refractory multiple myeloma (RRMM; ≥1 prior therapy) in the last 10 years, investigated ixazomib+lenalidomide+dexamethasone (IRd) versus lenalidomide+dexamethasone (Rd). Final overall survival (OS) data were based on a median follow-up of 85 months. In RRMM trials where patients have had 1-3 relapses after initial treatment, a high proportion receive subsequent therapy. Application of salvage therapies in blinded trials and newer modes of therapy can increasingly complicate the interpretation of OS. This analysis explores the impact of subsequent therapies on OS outcomes in TOURMALINE-MM1. The inverse probability of censoring weights (IPCW) method, marginal structural model (MSM), and rank preserving structural failure time model (RPSFTM) were utilized to adjust for confounding on OS, introduced by subsequent therapies. Analyses were conducted for the intentto-treat (ITT) population and ≥2 prior lines subgroup. Unadjusted hazard ratio (HR) for IRd versus Rd was 0.94 (95% confidence interval [CI]: 0.78-1.13) in the ITT population. After adjusting for the impact of subsequent therapies by the RPSFTM method, estimated HR for IRd versus Rd in the ITT population was 0.89 (95% CI: 0.74-1.07). Adjusting with IPCW and MSM methods also showed an improvement in HR, favoring IRd. IRd may be particularly beneficial in patients with ≥2 prior lines of therapy (IPCW and MSM HR=0.52, 95% CI: 0.30-0.88; RPSFTM HR=0.68, 95% CI: 0.51-0.91). These analyses highlight the growing challenge of demonstrating OS benefit in multiple myeloma patients and the importance of assessing confounding introduced by subsequent therapies when interpreting OS.

18.
Meat Sci ; 212: 109469, 2024 Jun.
Article En | MEDLINE | ID: mdl-38428152

The present study examines the bioactive potential of sheep plasma protein hydrolysates (SPPH) produced by in-vitro gastrointestinal digestion as antioxidants, antimicrobials, anti-obesity agents, and inhibitors of lipid oxidation in sausage to address the oxidative stability and shelf-life issues of mutton. The antioxidant and antimicrobial activities, indicate a positive relationship between the degree of hydrolysis and digestion duration. The study finds that SPPH has a potent inhibitory effect on pancreatic lipase and cholesterol esterase. It has higher oil holding capacity than sheep plasma protein, observed at one hour of hydrolysis time. SPPH exhibit an improved behavior in foaming properties along alkaline pH and digestion time while display lower emulsifying activity and stability with hydrolysis advancement. The SPPH act as a natural preservative in developing functional mutton sausage by inhibiting lipid-oxidation. This study showed that the recovery of SPPH can be a cost-effective and sustainable strategy for generating available ingredients for enhanced shelf-life of meat products.


Meat Products , Protein Hydrolysates , Animals , Sheep , Protein Hydrolysates/chemistry , Antioxidants/chemistry , Hydrolysis , Lipids
19.
J Sci Food Agric ; 104(7): 4286-4295, 2024 May.
Article En | MEDLINE | ID: mdl-38308402

BACKGROUND: Muffins are delightful baked food products that have earned a prominent place in the daily diet of a majority of people around the world. The incorporation of microgreens juice powder (MJP) into muffins boosts their nutritional value. The influence of the incorporation of wheatgrass, fenugreek and basil MJP at 1.5% and 3.0% levels on the nutritional composition, physical properties, pasting, sensory, textural and phenolic profile of functional muffins was evaluated. RESULTS: The results indicated a significant increase in the protein content, ash content, dietary fiber and total phenolic content of MJP incorporated muffins. The incorporation of MJP to the muffins led to a gradual reduction in the L*, a* and b* values. Baking characteristic such as bake loss decreased significantly as a result of MJP incorporation. Furthermore, the incorporation of various MJPs resulted in a significant decrease in the peak viscosity of the flour-MJP blends. Regarding texture, the hardness and chewiness of the muffins increased progressively with an increase in the level of MJP incorporation. The highest hardness (10.15 N) and chewiness (24.45 mJ) were noted for 3% fenugreek MJP incorporated muffins (FK 3.0). The sensory score of MJP incorporated muffins was acceptable and satisfactory. Additionally, 3% basil MJP incorporated muffins (BL 3.0) marked the dominant presence of majority of the detected phenolic acids such as ferulic acid, sinapic acid, chlorogenic acid, caffeic acid, quercetin, cinnamic acid, isothymosin and rosamarinic acid. The highest concentration of p-coumaric acid (11.95 mg kg-1), vanillic acid (26.07 mg kg-1) and kaempferol (8.04 mg kg-1) was recorded for FK 3.0 muffin. CONCLUSION: MJP incorporated muffins revealed the pool of phenolic acids and the reduced bake loss is of industrial interest. The present study concludes that wheatgrass, fenugreek and basil MJP can be incorporated by up to 3% into baked products as a source of functional ingredients for health benefits. © 2024 Society of Chemical Industry.


Lactones , Ocimum basilicum , Trigonella , Humans , Powders , Phenols
20.
Spat Spatiotemporal Epidemiol ; 48: 100634, 2024 Feb.
Article En | MEDLINE | ID: mdl-38355258

SARS-CoV-2, the virus responsible for COVID-19, posed a significant threat to the world. We analyzed COVID-19 dissemination data in the top ten Indian provinces by infection incidences using the Susceptible-Infectious-Removed (SIR) model, an Autoregressive Integrated Moving Average (ARIMA) time series model, a machine learning model based on the Random Forest, and distribution fitting. Outbreaks are expected to continue if the Basic Reproduction Number (R0) > 1, and infection waves are anticipated to end if the R0 < 1, as determined by the SIR model. Different parametric probability distributions are also fitted. Data collected from December 12, 2021, to March 31, 2022, encompassing data from both before and during the implementation of strict control measures. Based on the estimates of the model parameters, health agencies and government policymakers can develop strategies to combat the spread of the disease in the future, and the most effective technique can be recommended for real-world application for other outbreaks of COVID-19. The best method out of these could be also implemented further on the epidemiological data of other similar infectious agents.


COVID-19 , Humans , COVID-19/epidemiology , Cues , Machine Learning , Models, Statistical , SARS-CoV-2 , Time Factors , India/epidemiology
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