Predicting mechanical neck pain intensity in computer professionals using machine learning: identification and correlation of key features.

Introduction: Mechanical neck pain has become prevalent among computer professionals possibly because of prolonged computer use. This study aimed to investigate the relationship between neck pain intensity, anthropometric metrics, cervical range of motion, and related disabilities using advanced machine learning techniques. Method: This study involved 75 computer professionals, comprising 27 men and 48 women, aged between 25 and 44 years, all of whom reported neck pain following extended computer sessions. The study utilized various tools, including the visual analog scale (VAS) for pain measurement, anthropometric tools for body metrics, a Universal Goniometer for cervical ROM, and the Neck Disability Index (NDI). For data analysis, the study employed SPSS (v16.0) for basic statistics and a suite of machine-learning algorithms to discern feature importance. The capability of the kNN algorithm is evaluated using its confusion matrix. Results: The "NDI Score (%)" consistently emerged as the most significant feature across various algorithms, while metrics like age and computer usage hours varied in their rankings. Anthropometric results, such as BMI and body circumference, did not maintain consistent ranks across algorithms. The confusion matrix notably demonstrated its classification process for different VAS scores (mild, moderate, and severe). The findings indicated that 56% of the pain intensity, as measured by the VAS, could be accurately predicted by the dataset. Discussion: Machine learning clarifies the system dynamics of neck pain among computer professionals and highlights the need for different algorithms to gain a comprehensive understanding. Such insights pave the way for creating tailored ergonomic solutions and health campaigns for this population.

Correction: The ALK inhibitor AZD3463 effectively inhibits growth of sorafenib-resistant acute myeloid leukemia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Characterization of five-year observation data of fine particulate matter in the metropolitan area of Lahore.

This study aims to assess the long-term trend of fine particles (PM2.5; ≤2.5 µm) at two urban sites of Lahore during 2007-2011. These sites represent two distinct areas: commercial (Townhall) and residential cum industrial (Township). The highest daily mean concentrations of PM2.5 were noted as 389 and 354 µg m-3 at the Townhall and Township sites, respectively. As expected, the annual seasonal mean of PM2.5 was about 53 and 101% higher during winter compared with the summer and monsoon/post-monsoon seasons, respectively. On contrary to many observations seen in developing cities, the annual mean PM2.5 during the weekends was higher than weekdays at both monitoring sites. For example, these were 100 (142) and 142 µg m-3 (148) during the weekdays (weekends) at the Townhall and Township sites, respectively. The regression analysis showed a significant positive correlation of PM2.5 with SO2, NO2 and CO as opposed to a negative correlation with O3. The bivariate polar plots suggested a much higher influence of localized sources (e.g., road vehicles) at the Townhall site as opposed to industrial sources affecting the concentrations at the Township site. The imageries from the MODIS Aqua/Terra indicated long-range transport of PM2.5 from India to Pakistan during February to October whereas from Pakistan to India during November to January. This study provides important results in the form of multiscale relationship of PM2.5 with its sources and precursors, which are important to assess the effectiveness of pollution control mitigation strategies in Lahore and similar cities elsewhere. Graphical abstract.

Efficacy of the CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease of the blood affecting children, adolescents and adults. Although current treatment protocols for T-ALL have improved overall survival, a portion of T-ALL patients still experiences treatment failure. Thus, the development of novel therapies is needed. In this study, we used several patient-derived T-ALL cell lines to screen for an effective drug for T-ALL. Using a panel of 378 inhibitors against different kinases, we identified the CDK inhibitor dinaciclib as a potential drug for T-ALL. Dinaciclib treatment significantly reduced cell viability and completely blocked colony formation. Furthermore, cells treated with dinaciclib showed decreased expression of several pro-survival proteins including survivin, cyclin T1 and c-MYC. Dinaciclib treatment also increased accumulation of cells in G2/M phase and significantly induced apoptosis. Finally, dinaciclib extended survival of mice in a T-ALL cell xenograft model. Collectively, these data suggest that the CDK inhibitor dinaciclib is an active drug for T-ALL in the preclinical settings.

ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling.

The type III receptor tyrosine kinase FLT3 is one of the most commonly mutated oncogenes in acute myeloid leukemia (AML). Inhibition of mutated FLT3 in combination with chemotherapy has displayed promising results in clinical trials. However, one of the major obstacles in targeting FLT3 is the development of resistant disease due to secondary mutations in FLT3 that lead to relapse. FLT3 and its oncogenic mutants signal through associating proteins that activate downstream signaling. Thus, targeting proteins that interact with FLT3 and their downstream signaling cascades can be an alternative approach to treat FLT3-dependent AML. We used an SH2 domain array screen to identify novel FLT3 interacting proteins and identified ABL2 as a potent interacting partner of FLT3. To understand the role of ABL2 in FLT3-mediated biological and cellular events, we used the murine pro-B cell line Ba/F3 as a model system. Overexpression of ABL2 in Ba/F3 cells expressing an oncogenic mutant of FLT3 (FLT3-ITD) resulted in partial inhibition of FLT3-ITD-dependent cell proliferation and colony formation. ABL2 expression did not alter the kinase activity of FLT3, its ubiquitination or its stability. However, it partially blocked FLT3-induced AKT phosphorylation without affecting ERK1/2 and p38 activation. Taken together our data suggest that ABL2 acts as negative regulator of signaling downstream of FLT3.