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This study addresses the critical challenges faced in cancer care, particularly in predicting survival times for patients with lung cancer and acute myeloid leukemia. Despite recent advancements in medical science, existing models often fall short in accurately capturing disease progression, leading to less effective clinical decision-making, and compromised patient outcomes. The need for advanced predictive models is urgent to improve survival time forecasts and enhance treatment strategies. In response to this, we introduce a novel probabilistic approach, the New Weibull (NEWE) model, which is part of a newly generated class designed to model cancer patient data more effectively. Our methodology includes using seven well-known estimation methods, each rigorously evaluated for consistency through Monte Carlo simulation studies focused on key metrics such as absolute bias, mean square error, and mean relative error. The datasets analyzed include survival times for twenty acute myeloid leukemia patients, 121 breast cancer patients from 1929 to 1938, 33 patients with acute myelogenous leukemia, data from eighteen individuals who died from causes unrelated to cancer, and survival times of advanced lung cancer patients undergoing standard chemotherapy. The NEWE model outperformed competing models, particularly in Anderson-Darling, Cramer-von Mises, and Kolmogorov-Smirnov tests, with significantly higher p-values. These findings highlight the NEWE model’s potential to transform predictive oncology by offering more precise survival time predictions, improving the quality of care and decision-making in cancer treatment.

Abstract Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle activity in vitro, in human cardiac slices, and in vivo. Mechanistically, LTCC inhibition by RRAD or nifedipine induced CM cell cycle by modulating calcineurin activity. Moreover, ectopic expression of RRAD/CDK4/CCND in combination induced CM proliferation in vitro and in vivo, improved cardiac function and reduced scar size post-myocardial infarction.

Background Reports on the long-term treatment of alopecia areata (AA) in children with diphenylcyclopropenone (DPCP) are few. Objective To assess response, side effects, and relapse rates during long-term follow-up in children with severe AA treated with DPCP. Effect of different patient and treatment-related factors on prognosis and value of maintenance therapy were also assessed. Patients and methods In this interventional prospective study, 144 patients of AA were treated with DPCP. Response was assessed according to sex, type of AA, age of onset, and duration of disease. Excellent response was defined as terminal hair covering more than 75% of the scalp. Maintenance therapy meant ongoing therapy once every 2–4 weeks after excellent response. Follow up for an average of 22 months was performed to detect any relapse of AA which meant more than 25% hair loss. Results Ninety-two patients completed 12 months of therapy. Thirty (32.6%) patients achieved excellent response, 33 (35.9%) moderate, and 29 (31.5%) poor response. Seventy-three patients completed 18 months of therapy. Fouty-eight (65.8%) achieved excellent response, 10 (13.7%) moderate, and 15 (20.5%) poor response. Different clinical variables did not affect the response, however, a significant difference in the beginning of terminal hair growth according to type of AA was found (P=0.002) where 10% of responders among alopecia universalis patients started to grow terminal hair more than 12 months after the onset of therapy. Side effects were few and tolerable. Relapse occurred in 47% of patients on maintenance and 78% of patients without maintenance therapy (P=0.048). Conclusion DPCP is an effective and safe treatment of severe AA in children. Prolonging the duration of therapy may improve the response in alopecia universalis and alopecia totalis. Maintenance therapy is recommended to reduce the risk of relapse.

BackgroundThe regenerative capacity of the heart after myocardial infarction is limited. Our previous study showed that ectopic introduction of 4 cell cycle factors (4F; CDK1 [cyclin-dependent kinase 1], CDK4 [cyclin-dependent kinase 4], CCNB [cyclin B1], and CCND [cyclin D1]) promotes cardiomyocyte proliferation in 15% to 20% of infected cardiomyocytes in vitro and in vivo and improves cardiac function after myocardial infarction in mice.MethodsUsing temporal single-cell RNA sequencing, we aimed to identify the necessary reprogramming stages during the forced cardiomyocyte proliferation with 4F on a single cell basis. Using rat and pig models of ischemic heart failure, we aimed to start the first preclinical testing to introduce 4F gene therapy as a candidate for the treatment of ischemia-induced heart failure.ResultsTemporal bulk and single-cell RNA sequencing and further biochemical validations of mature human induced pluripotent stem cell-derived cardiomyocytes treated with either LacZ or 4F adenoviruses revealed full cell cycle reprogramming in 15% of the cardiomyocyte population at 48 hours after infection with 4F, which was associated mainly with sarcomere disassembly and metabolic reprogramming (n=3/time point/group). Transient overexpression of 4F, specifically in cardiomyocytes, was achieved using a polycistronic nonintegrating lentivirus (NIL) encoding 4F; each is driven by a TNNT2 (cardiac troponin T isoform 2) promoter (TNNT2-4Fpolycistronic-NIL). TNNT2-4Fpolycistronic-NIL or control virus was injected intramyocardially 1 week after myocardial infarction in rats (n=10/group) or pigs (n=6-7/group). Four weeks after injection, TNNT2-4Fpolycistronic-NIL-treated animals showed significant improvement in left ventricular ejection fraction and scar size compared with the control virus-treated animals. At 4 months after treatment, rats that received TNNT2-4Fpolycistronic-NIL still showed a sustained improvement in cardiac function and no obvious development of cardiac arrhythmias or systemic tumorigenesis (n=10/group).ConclusionsThis study provides mechanistic insights into the process of forced cardiomyocyte proliferation and advances the clinical feasibility of this approach by minimizing the oncogenic potential of the cell cycle factors owing to the use of a novel transient and cardiomyocyte-specific viral construct.

A physiological culture system to electro-mechanically stimulate pig heart slices to assess the drug effects on the functionality, metabolic activity, and structural integrity of the heart tissue under physiological and hypertrophic condition.

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle activity in vitro, in human cardiac slices, and in vivo. Mechanistically, LTCC inhibition by RRAD or nifedipine induced CM cell cycle by modulating calcineurin activity. Moreover, ectopic expression of RRAD/CDK4/CCND in combination induced CM proliferation in vitro and in vivo, improved cardiac function and reduced scar size post-myocardial infarction. [ABSTRACT FROM AUTHOR]

This study focuses on the Bayesian inference of parameters for the generalized logistic distribution, utilizing a combined framework of generalized type-I and type-II hybrid censoring schemes. The research addresses limitations in existing censoring methods by proposing a flexible model that enhances practical applicability in reliability and life-testing studies. Key objectives include the development of maximum likelihood estimators and asymptotic confidence intervals, alongside Bayesian estimation techniques using Markov chain Monte Carlo methods. These advancements facilitate the computation of credible intervals under various loss functions, thereby improving estimation efficiency. The paper also includes a comprehensive analysis of real-world datasets and simulation experiments to validate the proposed methodologies. A comparative evaluation of different estimators highlights the superiority of the combined framework of generalized type-I and type-II hybrid censoring schemes, providing valuable insights into the reliability and performance of the estimators. Overall, this research contributes significantly to the understanding and application of the generalized logistic distribution, offering practical tools for researchers and practitioners in the field of reliability engineering. [ABSTRACT FROM AUTHOR]

Medhat A Bakr,1 Naif K Al-Mutairi2 1Immam Abdulrahman Bin Faisal University, King Fahd University Hospital, Ophthalmology Department (Glaucoma Section), Al Khobar, Eastern Province, Kingdom of Saudi Arabia; 2Jeddah Eye Hospital, Jeddah, Kingdom of Saudi ArabiaCorrespondence: Medhat A BakrKing Fahd University Hospital, Immam Abdulrahman Bin Faisal University, Alaqrabia, Al Khobar, Kingdom of Saudi ArabiaTel +966559753252Email medhat_6@hotmail.comPurpose: To evaluate the long-term surgical outcomes of endoscopic cyclophotocoagulation (ECP) after four years follow-up in cataract and glaucoma patients that needed combined phacoemulsification and ECP (phaco-ECP) in comparison to combined phacoemulsification with trabeculectomy (phaco-trabeculectomy) with mitomycin C (MMC).Patients and Methods: Retrospective case–control study of 34 patients (34 eyes) with glaucoma who underwent phaco-ECP compared with phaco-trabeculectomy in tertiary eye specialist hospital in Saudi Arabia from 2010 to 2012. Participants were enrolled in two groups; ECP and trabeculectomy with MMC when combined with phacoemulsification. Success is defined as complete success when the IOP ≤ 21 mmHg without medication, qualified success when the IOP ≤ 21 mmHg with aid of topical medication.Results: Mean IOP decreased from 25.76 SD ± 8.227 to 15.24 SD ± 7.049 at last visit in phaco-trabeculectomy group and from 21.47 SD ± 4.215 to 12.88 SD ± 3.480 in phaco-ECP group. Mean medication use reduced from 2.89 SD ± 0.3 preoperatively to 1.50 SD ± 1.1 postoperatively (P< 0.001) in phaco-trabeculectomy group. It reduced in phaco-ECP group from 2.24 SD ± 0.8 preoperatively to 2.00 SD ± 0.9 postoperatively, 35.3% of phaco-trabeculectomy group developed vision-threatening complications while 0% in phaco-ECP group (P< 0.001), 29.4% in phaco-trabeculectomy group required second surgical intervention compared to 17.6% in phaco-ECP group. In phaco-trabeculectomy group, 29.4% reached complete success, meanwhile in phaco-ECP group, 64.7% reached qualified success (P=0.026).Conclusion: ECP illustrates significant reduction of IOP and less postoperative complications if associated with phacoemulsification. Furthermore, it is safe and effective as a primary procedure alternative to combined cataract and trabeculectomy surgery for glaucoma patients having cataract and requiring surgical intervention.Keywords: cataract, extraction, phacoemulsification, trabeculectomy, glaucoma; ECP Endoscopic cyclophotocoagulation

The aim of this research is to estimate the parameters of the modified Frechet-exponential (MFE) distribution using different methods when applied to progressive type-II censored samples. These methods include using the maximum likelihood technique and the Bayesian approach, which were used to determine the values of parameters in addition to calculating the reliability and failure functions at time t. The approximate confidence intervals (ACIs) and credible intervals (CRIs) are derived for these parameters. Two bootstrap techniques of parametric type are provided to compute the bootstrap confidence intervals. Both symmetric loss functions such as the squared error loss (SEL) and asymmetric loss functions such as the linear-exponential (LINEX) loss are used in the Bayesian method to obtain the estimates. The Markov Chain Monte Carlo (MCMC) technique is utilized in the Metropolis–Hasting sampler approach to obtain the unknown parameters using the Bayes approach. Two actual datasets are utilized to examine the various progressive schemes and different estimation methods considered in this paper. Additionally, a simulation study is performed to compare the schemes and estimation techniques. [ABSTRACT FROM AUTHOR]

Based on joint progressive Type-II censored data, we examined the statistical inference of the generalized logistic distribution with different shape and scale parameters in this research. Wherever possible, we explored maximum likelihood estimators for unknown parameters within the scope of the joint progressive censoring scheme. Bayesian inferences for these parameters were demonstrated using a Gamma prior under the squared error loss function and the linear exponential loss function. It was important to note that obtaining Bayes estimators and the corresponding credible intervals was not straightforward; thus, we recommended using the Markov Chain Monte Carlo method to compute them. We performed real-world data analysis for demonstrative purposes and ran Monte Carlo simulations to compare the performance of all the suggested approaches. [ABSTRACT FROM AUTHOR]