Gene Therapy Targeting p53 and KRAS for Colorectal Cancer Treatment: A Myth or the Way Forward?
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ABSTRACT:
SUBMITTER: Hasbullah HH
PROVIDER: S-EPMC8584926 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The complexity of managing early stage breast cancer is well known. Optimal treatment is increasingly multidisciplinary and in the modern era informed by sophisticated molecular tools to help select and guide therapy. Major phase III trials have determined that the order of systemic therapy relative to surgery does not influence important endpoints such as event free survival and overall survival (OS), but questions remain as to how best to utilize these most essential services. For example, there is still uncertainty regarding the ideal timing, intensity, and duration of proposed therapy. For treating physicians, evidence based standardization of these practices is both possible and critically important. Optimization of care will increasingly rely on well-designed studies that have addressed the choice as well as the timing of the steps involved in multidisciplinary breast cancer treatment. Understanding when factors under the oncologist's control will influence outcome, cost and convenience is essential in the era of quality and value-based medical decision making. The timing of surgery before or after chemotherapy for breast cancer is one such factor. Investigators are to be commended for addressing these questions, which may generate additional hypotheses concerning the biology of metastasis and the nature of recurrence.
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Project description:Globally, it is estimated that one-quarter of the world's population is latently infected with Mycobacterium tuberculosis (Mtb), also known as latent tuberculosis infection (LTBI). Recently, this condition has been referred to as tuberculosis infection (TBI), considering the dynamic spectrum of the infection, as 5-10% of the latently infected population will develop active TB (ATB). The chances of TBI development increase due to close contact with index TB patients. The emergence of multidrug-resistant TB (MDR-TB) and the risk of development of latent MDR-TB has further complicated the situation. Detection of TBI is challenging as the infected individual does not present symptoms. Currently, there is no gold standard for TBI diagnosis, and the only screening tests are tuberculin skin test (TST) and interferon gamma release assays (IGRAs). However, these tests have several limitations, including the inability to differentiate between ATB and TBI, false-positive results in BCG-vaccinated individuals (only for TST), false-negative results in children, elderly, and immunocompromised patients, and the inability to predict the progression to ATB, among others. Thus, new host markers and Mtb-specific antigens are being tested to develop new diagnostic methods. Besides screening, TBI therapy is a key intervention for TB control. However, the long-course treatment and associated side effects result in non-adherence to the treatment. Additionally, the latent MDR strains are not susceptible to the current TBI treatments, which add an additional challenge. This review discusses the current situation of TBI, as well as the challenges and efforts involved in its control.
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Project description:The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries.
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Project description:BACKGROUND:With India preparing for the next decennial Census in 2021, we compared the disability estimates and data collection methodology between the Census 2011 and the most recent population-level survey for India and its states, to highlight the issues to be addressed to improve robustness of the disability estimates in the upcoming Census. METHODS:Data from the Census 2011 and from two complementary nationally representative household surveys that covered all Indian states with the same methodology and survey instruments-the District-Level Household Survey-4 (DLHS-4, 2012-2013) and the Annual Health Surveys (AHS three rounds, 2010-11, 2011-12 and 2012-13) were used. Data from DLHS-4 and AHS 2012-13 round were pooled to generate estimates for the year 2012-13. Data collection methodology between the sources was compared, including the review of definitions of each type of disability. The overall, mental, visual, hearing, speech, and movement disability rate (DR) per 100,000 population were compared between the sources for India and for each state, and the percent difference in the respective rates was calculated. We explored the reliability of these estimates comparing yearly data from the AHS for three successive rounds. RESULTS:Survey data were collected through proxy reporting, however, it is not entirely clear whether the data were proxy- or self-reported or a mix of both in the Census. The overall DR was 25.1% higher in the Census (2,242; 95% CI 2,241-2,243) than the survey (1,791; 95% CI 1,786-1,797) per 100,000 population, with the state-level difference ranging from -64% in Tamil Nadu to 107% in Sikkim state. Despite both sources using nearly similar definitions for overall disability and disability by type, the difference in DR was 125.5%, 54.2%, -25.7%, -19.7%, and 21.9% for hearing, speech, mental, movement, and visual DR, respectively. At the state-level, the difference in disability-specific estimates ranged from -84% to 450%. The extent of variations in the disability-specific estimates in AHS successive rounds ranged from -25% to 929% at the state-level. CONCLUSIONS:There is momentum globally towards building disability measurement that is consistent with the data required for monitoring of the Sustainable Development Goals to ensure robust estimation of disability. The current estimates from the Census and surveys seem much lower than would be expected at the population level. We make recommendations that India needs to take serious note of in order to improve the validity and reliability of India's disability estimates.
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Project description:For a number of years it has been widely assumed that measurement of serum 25-hydroxyvitamin D [25(OH)D] concentration is the best approach to assessing an individual's vitamin D status. However, it has also been recognized that there is substantial within-assay variation in 25(OH)D measurement and even greater between-assay variability. Such assay variation clearly confounds attempts to define what constitutes the diagnosis of hypovitaminosis D. Importantly, assay variability makes pooling of 25(OH)D results from different studies in systematic reviews for the specific purpose of determining dose-response and/or clinical cut points at best problematic. Therefore, to develop and implement evidence-based clinical guidelines, it is essential that 25(OH)D measurement be standardized in both clinical and research laboratories. In this Perspective we outline a way forward toward achieving this goal-the Vitamin D Standardization Program (VDSP).
| S-EPMC5443565 | biostudies-literature