Recent advances in our understanding of the dynamics of cellular cross-talk have highlighted the significance of host-versus-tumor effect that can be harnessed with immune therapies. Tumors exploit ...immune checkpoints to evade adaptive immune responses. Cancer immunotherapy has witnessed a revolution in the past decade with the development of immune checkpoint inhibitors (ICIs), monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or their ligands, such as PD1 ligand 1 (PD-L1). ICIs have been reported to have activity against a broad range of tumor types, in both solid organ and hematologic malignancy contexts. However, less than one-third of the patients achieve a durable and meaningful treatment response. Expression of immune checkpoint ligands (e.g., PD-L1), mutational burden and tumor-infiltrating lymphocytes are currently used as biomarkers for predicting response to ICIs. However, they do not reliably predict which patients will benefit from these therapies. There is dire need to discover novel biomarkers to predict treatment efficacy and to identify areas for development of combination strategies to improve response rates. Emerging evidence suggests key roles of tumor extracellular matrix (ECM) components and their proteolytic remodeling products in regulating each step of the cancer-immunity cycle. Here we review tumor matrix dynamics and matrix remodeling in context of anti-tumor immune responses and immunotherapy and propose the exploration of matrix-based biomarkers to identify candidates for immune therapy.
There is no data on diet- and activity-related behaviors associated with overweight and obesity among Pakistani school-aged children. The study aimed to explore dietary behaviors, physical activity ...and sedentary lifestyle associated with overweight and obesity, and their socio-demographic correlates, among Pakistani primary school children.
A population-based cross-sectional study was conducted with a representative multistage random cluster sample of 1860 children aged five to twelve years in Lahore, Pakistan. Overweight (>+1 SD) and obesity (>+2 SD) were defined using the World Health Organization reference 2007. Chi-square test was used as the test of trend. Linear regression was used to examine the predictive power of independent variables in relation to body mass index (BMI). Logistic regression was used to quantify the independent predictors and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained. Statistical significance was considered at P<0.05.
Children skipping breakfast (8%), eating fast food and snacks≥once a week (43%) and being involved in sedentary lifestyle>one hour a day (49%) were significantly more likely to be overweight and obese while those participating in physical activity>twice a week (53%) were significantly less likely to be overweight and obese (all P<0.01). Skipping breakfast (P<0.001), eating fast food and snacks (P=0.001) and sedentary lifestyle (P<0.001) showed an independent positive association with BMI while physical activity showed an independent inverse association (P=0.001). Skipping breakfast (aOR 1.82, 95% CI 1.22-2.71), eating fast food and snacks≥once a week (OR 1.41, 95% CI 1.07-1.86), physical activity>twice a week (aOR 0.49, 95% CI 0.34-0.70) and sedentary lifestyle>one hour a day (aOR 1.56, 95% CI 1.19-2.03) were independent predictors of being overweight. Skipping breakfast had independent inverse association with physical activity (aOR 0.63, 95% CI 0.45-0.89) and eating fast food and snacks had independent positive association with sedentary lifestyle (aOR 1.79, 95% CI 1.49-2.16). Female gender was independently associated with skipping breakfast (aOR 1.50, 95% CI 1.04-2.16). Male gender (aOR 1.64, 95% CI 1.33-2.02), urban area with high SES (aOR 5.09, 95% CI 3.02-8.60) and higher parental education (aOR 1.74, 95% CI 1.12-2.68) were significant independent predictors of eating fast food and snacks≥once a week. Living in the rural area was independently associated (aOR 2.51, 95% CI 1.71-3.68) with physical activity>twice a week. Male gender (aOR 1.60, 95% CI 1.31-1.95), urban area with low SES (aOR 1.46, 95% CI 1.02-2.09), high-income neighborhoods (aOR 1.52, 95% CI 1.02-2.25), higher parental education (aOR 1.55, 95% CI 1.03-2.34) and fewer siblings (aOR 1.38, 95% CI 1.10-1.73) were independent predictors of sedentary lifestyle>one hour a day.
Dietary behaviors, physical activity and sedentary lifestyle are independent predictors of overweight and higher BMI among Pakistani primary school children, and are significantly affected by the child's socio-demographic characteristics. These findings support the urgent need to develop a National strategy for diet and physical activity and to implement culturally relevant behavioral interventions in the resource-poor developing country settings.
In this study, a pot experiment was piloted in a greenhouse to evaluate the potential of
Celosia argentea
var.
cristata
L. for tolerating/accumulating heavy metals in synthetic wastewater in the ...presence of
Pseudomonas japonica
and organic amendment, i.e., moss and compost. Two-week-old seedlings were transferred to pots, and after 4 weeks, the bacterial strain was inoculated, then watered with synthetic wastewater for 5 weeks and harvested after 9 weeks. After harvesting, physiological and biochemical parameters, as well as metal contents of plants, were quantified. The results indicated highest growth and biomass production in moss- and compost-associated plants while highest metal uptake has been found in the presence of
P. japonica
and synthetic wastewater–irrigated plants. Synthetic wastewater–irrigated plants have shown highest Pb uptake of 2899 mg kg
−1
DW, while with
P. japonica
in soil those plants have shown highest Cd, Cu, Ni, and Cr uptake of 962, 1479, 1042, and 956 mg kg
−1
DW, respectively. The production of antioxidant enzymes, i.e., catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and glutathione-s-transferase (GST), was high in
P. japonica
–amended plants because of increased uptake of metals. It is concluded that moss and compost have improved growth while
P. japonica
improved metal accumulation and translocation to aerial parts with little involvement in plant growth.
Child growth is internationally recognized as an important indicator of nutritional status and health in populations. This study was aimed to compare age- and gender-specific height, weight and BMI ...percentiles and nutritional status relative to the international growth references among Pakistani school-aged children.
A population-based study was conducted with a multistage cluster sample of 1860 children aged five to twelve years in Lahore, Pakistan. Smoothed height, weight and BMI percentile curves were obtained and comparison was made with the World Health Organization 2007 (WHO) and United States' Centers for Disease Control and Prevention 2000 (USCDC) references. Over- and under-nutrition were defined according to the WHO and USCDC references, and the International Obesity Task Force (IOTF) cut-offs. Simple descriptive statistics were used and statistical significance was considered at P < 0.05.
Height, weight and BMI percentiles increased with age among both boys and girls, and both had approximately the same height and a lower weight and BMI as compared to the WHO and USCDC references. Mean differences from zero for height-, weight- and BMI-for-age z score values relative to the WHO and USCDC references were significant (P < 0.001). Means of height-for-age (present study: 0.00, WHO: -0.19, USCDC: -0.24), weight-for-age (present study: 0.00, WHO: -0.22, USCDC: -0.48) and BMI-for-age (present study: 0.00, WHO: -0.32, USCDC: -0.53) z score values relative to the WHO reference were closer to zero and the present study as compared to the USCDC reference. Mean differences between weight-for-age (0.19, 95% CI 0.10-0.30) and BMI-for-age (0.21, 95% CI 0.11-0.30) z scores relative to the WHO and USCDC references were significant. Over-nutrition estimates were higher (P < 0.001) by the WHO reference as compared to the USCDC reference (17% vs. 15% overweight and 7.5% vs. 4% obesity) while underweight and thinness/wasting were lower (P < 0.001) by the WHO reference as compared to the USCDC reference (7% vs. 12% underweight and 10% vs. 13% thinness). Significantly lower overweight (8%) and obesity (5%) prevalence and higher thinness grade one prevalence (19%) was seen with use of the IOTF cut-offs as compared to the WHO and USCDC references. Mean difference between height-for-age z scores and difference in stunting prevalence relative to the WHO and USCDC references was not significant.
Pakistani school-aged children significantly differed from the WHO and USCDC references. However, z score means relative to the WHO reference were closer to zero and the present study as compared to the USCDC reference. Overweight and obesity were significantly higher while underweight and thinness/wasting were significantly lower relative to the WHO reference as compared to the USCDC reference and the IOTF cut-offs. New growth charts for Pakistani children based on a nationally representative sample should be developed. Nevertheless, shifting to use of the 2007 WHO child growth reference might have important implications for child health programs and primary care pediatric clinics.
Heavy metals (HMs) being the notorious and toxic are being introduced into the environment credited to natural and anthropogenic activities. The use of ornamental plants is being ignored as potential ...candidates for HMs phytoremediation. In this study, pot experiments were conducted on
Catharanthus roseus
(L.) G.Don to evaluate selected heavy metals tolerance and accumulation potential with reference to the bacterial endophyte (
Bacillus cereus
) and organic amendments (moss and compost at 5% v
/
v). Results indicated improvement in uptake of Cd (230 mg kg
−1
), Cu (229 mg kg
−1
), and Cr (458 mg kg
−1
) by
C. roseus
with
B. cereus
. The concentration of Ni and Pb was found highest in controls (without strain) that were 420 and 904 mg kg
−1
, respectively. Conversely, the addition of organic amendments enhanced biomass production, as compared to controls, 441, 471, and 763% by peat moss (T3), compost (T4), and peat moss + compost + inoculum treatments (T6), respectively, while reduction of plant HMs content was observed. Microbial-aided phytoremediation/phytoextraction could be a potential method for removal of Cd, Cr, and Cu, while organic amendments can significantly improve plant growth in the presence of heavy metals.
Childhood obesity is becoming an equally challenging, yet under-recognized, problem in developing countries including Pakistan. Children and adolescents are worst affected with an estimated 10% of ...the world's school-going children being overweight and one quarter of these being obese. The study aimed to assess prevalence and socioeconomic correlates of overweight and obesity, and trend in prevalence statistics, among Pakistani primary school children.
A population-based cross-sectional study was conducted with a representative multistage cluster sample of 1860 children aged 5-12 years in Lahore, Pakistan. Overweight (> + 1SD) and obesity (> + 2SD) were defined using the World Health Organization child growth reference 2007. Chi-square test was used as the test of trend. Linear regression was used to examine the predictive power of independent variables in relation to BMI. Logistic regression was used to quantify the independent predictors for overweight and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained. All regression analyses were controlled for age and gender and statistical significance was considered at P < 0.05.
Seventeen percent (95% CI 15.4-18.8) children were overweight and 7.5% (95% CI 6.5-8.7) were obese. Higher prevalence of obesity was observed among boys than girls (P = 0.028), however, there was no gender disparity in overweight prevalence. Prevalence of overweight showed a significantly increasing trend with grade (P < 0.001). Children living in the urban area with high socioeconomic status (SES) were significantly at risk for being overweight and obese (both P < 0.001) as compared to children living in the urban area with lower SES and rural children. Being in higher grade (aOR 2.39, 95% CI 1.17-4.90) and living in the urban area with higher SES (aOR 18.10, 95% CI 10.24-32.00) independently predicted the risk of being overweight.
Alarmingly rapid rise in overweight and obesity among Pakistani primary school children was observed, especially among the affluent urban population. The findings support the urgent need for National preventive strategy for childhood obesity and targeted interventions tailored to local circumstances with meaningful involvement of communities.
Child growth is internationally recognized as an important indicator of nutritional status and health in populations. Child under-nutrition is estimated to be the largest contributor to global burden ...of disease, and it clusters in South Asia but literature on under-nutrition among school-aged children is difficult to find in this region. The study aimed to assess the prevalence and socio-demographic correlates of stunting and thinness among Pakistani primary school children.
A population-based cross-sectional study was conducted with a representative multistage cluster sample of 1860 children aged 5-12 years in Lahore, Pakistan. Stunting (< -2 SD of height-for-age z-score) and thinness (< -2 SD of BMI-for-age z-score) were defined using the World Health Organization reference 2007. Chi-square test was used as the test of trend. Logistic regression was used to quantify the independent predictors of stunting and thinness and adjusted odds ratios (aOR) with 95% confidence interval (CI) were obtained. Linear regression was used to explore the independent determinants of height- and BMI-for-age z-scores. Statistical significance was considered at P < 0.05.
Eight percent (95% CI 6.9-9.4) children were stunted and 10% (95% CI 8.7-11.5) children were thin. Stunting and thinness were not significantly associated with gender. Prevalence of stunting significantly increased with age among both boys and girls (both P < 0.001) while thinness showed significant increasing trend with age among boys only (P = 0.034). Significant correlates of stunting included age > 8 years, rural area and urban area with low SES, low-income neighborhoods, lower parental education, more siblings, crowded housing and smoking in living place (all P < 0.001). Significant correlates of thinness included rural area and urban area with low SES, low-income neighborhoods and lower parental education (all P < 0.001), and age > 10 years (P = 0.003), more siblings (P = 0.016) and crowded housing (P = 0.006). In multivariate logistic regression analyses adjusted simultaneously for all factors, older age (aOR 3.60, 95% CI 1.89-6.88), urban area with low SES (aOR 2.58, 95% CI 1.15-5.81) and low-income neighborhoods (aOR 4.62, 95% CI 1.63-13.10) were associated with stunting while urban area with low SES (aOR 2.28, 95% CI 1.21-4.30) was associated with thinness. In linear regression analyses adjusted for all factors, low-income neighborhoods and older age were associated with lower height-for-age z-score while rural area with low/disadvantaged SES was associated with lower BMI-for-age z-score.
Relatively low prevalence of stunting and thinness depicted an improvement in the nutritional status of school-aged children in Pakistan. However, the inequities between the poorest and the richest population groups were marked with significantly higher prevalence of stunting and thinness among the rural and the urban poor, the least educated, the residents of low-income neighborhoods and those having crowded houses. An increasing trend with age was observed in prevalence of stunting and thinness. Smoking in living place was associated with stunting. Findings suggest the need to implement evidence-based child health policy and strategies, prioritizing the poor and socially disadvantaged population.
We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML).
We performed ...a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.
We analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I
=65%) and 65.2% (95% CI 0.36-0.91, I
=57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I
=77%), 3.9% (95% CI 0.00-0.19, I
=22%), and 1.6% (95%CI 0.00-0.21, I
=33%), respectively.
CAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.
Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and ...is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients. We report a case wherein systemic and hematological manifestations completely resolved in a patient with VEXAS and associated myelodysplastic syndrome (MDS), following the administration of fludarabine and cyclophosphamide as part of the preparation for allo-HSCT. We conducted a systematic literature review and included 86 patients with VEXAS syndrome and associated MDS. Most cases presented with musculoskeletal involvement (71%) and anemia (72%) with lower-risk MDS. Most patients responded to corticosteroids (CS) but had a recurrence of symptoms with CS taper and were refractory to other immunosuppressive agents. Hypomethylating agents and Janus kinase inhibitors achieved a complete response in some cases. Further research is needed to develop more effective treatment strategies.
In order to achieve high strength in concrete composites, various fiber reinforcements in plain concrete composites (PCC) are used. Steel is widely used for this purpose but the main issue in using ...steel as a reinforcement member is rusting, which results into structure deterioration. So, the alternative is to use a durable, environment friendly, and cost-effective natural fiber. Jute Fiber is used in this study for the reinforcement of plain concrete composites while, the plain concrete composites were made with cement, sand, and bricks waste. The comparative study of using bricks waste as an alternative material to crush bricks is also presented in this research study. Bricks waste and its disposal is becoming an environmental challenge. This study proposes jute fibers as a reinforcement element and uses bricks waste as an alternative material to crushed stone. M20 grade concrete with various volumetric percentages (0.05%, 0.10%, 0.25%, 0.50%, and 1.00%) of 10 mm long jute fibers are produced. An increase of 39% and 37% in compressive strength and split tensile strength, respectively, was observed after the addition of jute fibers. Therefore, the use of jute fibers and bricks waste to replace crushed stone is an effective way to mitigate environmental pollution and sustainability issues.
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