Explore the vast range of titles available.

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.

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.

Background 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. Methods 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. Results 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. Conclusions 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.

Background 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. Methods 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. Results 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. Conclusions 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.

Natural killer (NK) cells play a vital role in early immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT). A literature search was performed on PubMed, Cochrane, and Clinical trials.gov through April 20, 2022. We included 21 studies reporting data on the impact of NK cells on outcomes after HSCT. Data was extracted following the PRISMA guidelines. Pooled analysis was done using the meta-package (Schwarzer et al.). Proportions with 95% confidence intervals (CI) were computed. We included 1785 patients from 21 studies investigating the impact of NK cell reconstitution post-HSCT (8 studies/1455 patients), stem cell graft NK cell content (4 studies/185 patients), therapeutic NK cell infusions post-HSCT (5 studies/74 patients), and pre-emptive/prophylactic NK cell infusions post-HSCT (4 studies/77 patients). Higher NK cell reconstitution was associated with a better 2-year overall survival (OS) (high: 77%, 95%CI 0.73-0.82 vs low: 55%, 95%CI 0.37-0.72; n=899), however, pooled analysis for relapse rate (RR) or graft versus host disease (GVHD) could not be performed due to insufficient data. Higher graft NK cell content demonstrated a trend towards a better pooled OS (high: 65.2%, 95%CI 0.47-0.81 vs low: 46.5%, 95%CI 0.24-0.70; n=157), lower RR (high: 16.9%, 95%CI 0.10-0.25 vs low: 33%, 95%CI 0.04-0.72; n=157), and lower acute GVHD incidence (high: 27.6%, 95%CI 0.20-0.36 vs low: 49.7%, 95%CI 0.26-0.74; n=157). Therapeutic NK or cytokine-induced killer (CIK) cell infusions for hematologic relapse post-HSCT reported an overall response rate (ORR) and complete response (CR) of 48.9% and 11% with CIK cell infusions and 82.8% and 44.8% with NK cell infusions, respectively. RR, acute GVHD, and chronic GVHD were observed in 55.6% and 51.7%, 34.5% and 20%, and 20.7% and 11.1% of patients with CIK and NK cell infusions, respectively. Pre-emptive donor-derived NK cell infusions to prevent relapse post-HSCT had promising outcomes with 1-year OS of 69%, CR rate of 42%, ORR of 77%, RR of 28%, and acute and chronic GVHD rates of 24.9% and 3.7%, respectively. NK cells have a favorable impact on outcomes after HSCT. The optimal use of NK cell infusions post-HSCT may be in a pre-emptive fashion to prevent disease relapse.

Background 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. Methods 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. Results 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. Conclusion 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.

Background 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. Methods 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. Results 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. Conclusion 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.

Background Central obesity has been associated with the risk of cardiovascular and metabolic disease in children and anthropometric indices predictive of central obesity include waist circumference (WC), waist-hip ratio (WHR) and waist-height ratio (WHtR). South Asian children have higher body fat distribution in the trunk region but the literature regarding WC and related indices is scarce in this region. The study was aimed to provide age- and gender-specific WC, WHR and WHtR smoothed percentiles, and to explore prevalence and correlates of central obesity, among Pakistani children aged five to twelve years. Methods A population-based cross-sectional study was conducted with a representative multistage random cluster sample of 1860 primary school children aged five to twelve years in Lahore, Pakistan. Smoothed percentile curves were constructed for WC, WHR and WHtR by the LMS method. Central obesity was defined as having both age- and gender-specific WC percentile ≥90 th and WHtR ≥0.5. Chi-square test was used as the test of trend. Multivariate logistic regression was used to quantify the independent predictors of central obesity and adjusted odds ratios (aOR) with 95% CI were obtained. Linear regression was used to explore the independent determinants of WC and WHtR. Statistical significance was considered at P < 0.05. Results First ever age- and gender-specific smoothed WC, WHR and WHtR reference curves for Pakistani children aged five to twelve years are presented. WC increased with age among both boys and girls. Fiftieth WC percentile curves for Pakistani children were higher as compared to those for Hong Kong and British children, and were lower as compared to those for Iranian, German and Swiss children. WHR showed a plateau pattern among boys while plateau among girls until nine years of age and decreased afterwards. WHtR was age-independent among both boys and girls, and WHtR cut-off of ≥0.5 for defining central obesity corresponded to 85 th WHtR percentile irrespective of age and gender. Twelve percent children (95% CI 10.1-13.0) had a WC ≥90 th percentile and 16.5% children (95% CI 14.7-18.1) had a WHtR ≥0.5 while 11% children (95% CI 8.9-11.6) had both WC ≥90 th percentile and WHtR ≥0.5. Significant predictors of central obesity included higher grade, urban area with high socioeconomic status (SES), high-income neighborhood and higher parental education. Children studying in higher grade (aOR 5.11, 95% CI 1.76-14.85) and those living in urban area with high SES (aOR 82.34, 95% CI 15.76-430.31) showed a significant independent association. Urban area with high SES and higher parental education showed a significant independent association with higher WC and higher WHtR while higher grade showed a significant independent association with higher WC. Conclusions Comprehensive worldwide reference values are needed to define central obesity and the present study is the first one to report anthropometric indices predictive of central obesity for Pakistani school-aged children. Eleven percent children were centrally obese and strong predictors included higher grade, urban area with high SES and higher parental education. These findings support the need for developing a National strategy for childhood obesity and implementing targeted interventions, prioritizing the higher social class and involving communities.

We conducted a bibliometric analysis to identify scholarly impact and factors associated with the top 100 cited articles on clinical hematopoietic stem cell transplantation (HSCT). In January 2021, a title-specific search was conducted. Non-HSCT and pre-clinical ( in-vitro and animal) studies were excluded. A total of 39,406 records were identified and a list of the top 100 articles was made. Articles included in our study were characterized by the citations received, publication year, topic, study design, authors, h-index, and institutions. Linear regression analyses were performed. The 100 most cited articles were published over 52 years from 1968 to 2020, with a maximum number of articles ( n = 40) published in the 1990s decade. Top-100 articles were cited 62,002 times with a median citation count of 465 (range 336–2240). The top-cited articles originated from 12 countries. United States contributed 69 articles. The University of Washington Fred Hutchinson Cancer Center ( n = 15) was the leading institution. Blood ( n = 32) and New England Journal of Medicine ( n = 31) made the greatest contribution, and 52 manuscripts were clinical trials. The first author's H-index significantly correlated with citation count while journal impact factor, years since publication, first author's gender, and the number of authors did not have a significant association with the number of citations. In a multivariate regression model, the first author's h-index (regression coefficient 5.46, 95% confidence interval 2.99 to 7.93, p < 0.001) independently correlated with the citation count. Our study highlights the most influential articles on clinical HSCT and provides valuable insight for future research needs of the specialty.

Background Childhood obesity epidemic is now penetrating the developing countries including Pakistan, especially in the affluent urban population. There is no data on association of family-based factors with overweight and obesity among school-aged children in Pakistan. The study aimed to explore the family-based factors associated with overweight and obesity among Pakistani primary school children. Methods A population-based cross-sectional study was conducted with a representative multistage cluster sample of 1860 children aged five to twelve years in Lahore, Pakistan. Overweight (> +1SD BMI-for-age z-score) and obesity (> +2SD BMI-for-age z-score) 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 BMI. Logistic regression was used to quantify the independent predictors of 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. Results Significant family-based correlates of overweight and obesity included higher parental education (P < 0.001), both parents working (P = 0.002), fewer siblings (P < 0.001), fewer persons in child's living room (P < 0.001) and residence in high-income neighborhoods (P < 0.001). Smoking in living place was not associated with overweight and obesity. Higher parental education (P < 0.001) and living in high-income neighborhoods (P < 0.001) showed a significant independent positive association with BMI while greater number of siblings (P = 0.001) and persons in child's living room (P = 0.022) showed a significant independent inverse association. College-level or higher parental education as compared to high school-level or lower parental education (aOR 2.54, 95% CI 1.76-3.67), living in high-income neighborhoods as compared to low-income neighborhoods (aOR 2.13, 95% CI 1.31-3.46) and three or less siblings as compared to more than three siblings (aOR 1.75, 95% CI 1.26-2.42) were significant independent predictors of overweight. Conclusion Family-based factors were significantly associated with overweight and obesity among school-aged children in Pakistan. Higher parental education, living in high-income neighborhoods and fewer siblings were independent predictors of overweight. These findings support the need to design evidence-based child health policy and implement targeted interventions, considering the impact of family-based factors and involving communities.