Application of predictive model based on CT radiomics and machine learning in diagnosis for occult locally advanced esophageal squamous cell carcinoma before treatment: A two-center study.

PURPOSE: Development and validation of a radiomics model for predicting occult locally advanced esophageal squamous cell carcinoma (LA-ESCC) on computed tomography (CT) radiomic features before implementation of treatment. METHODS: The study retrospectively collected 574 patients with esophageal squamous cell carcinoma (ESCC) from two medical centers, which were divided into three cohorts for training, internal and external validation. After delineating volume of interest (VOI), radiomics features were extracted and subjected to feature selection using three robust methods. Subsequently, 10 machine learning models were constructed, among which the optimal model was utilized to establish a radiomics signature. Furthermore, a predictive nomogram incorporating both clinical and radiomics signatures was developed. The performance of these models was evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis as well as measures including accuracy, sensitivity, and specificity. RESULTS: A total of 19 radiomics features were selected. The multilayer perceptron (MLP), which was found to be optimal, achieved an AUC of 0.919, 0.864 and 0.882 in the training, internal and external validation cohorts, respectively. Similarly, MLP showed good accuracy in distinguish occult LA-ESCC in subgroup of cT1-2N0M0 diagnosed by clinicians with 0.803 and 0.789 in two validation cohorts respectively. By incorporating the radiomics signature with clinical signature, a predictive nomogram demonstrated superior prediction performance with an AUC of 0.877 and accuracy of 0.85 in external validation cohort. CONCLUSION: The radiomics and machine learning model can offers improved accuracy in prediction of occult LA-ESCC, providing valuable assistance to clinicians when choosing treatment plans.

Breast Cancer Incidence Among US Women Aged 20 to 49 Years by Race, Stage, and Hormone Receptor Status.

Importance: Breast cancer in young women has a less favorable prognosis compared with older women. Yet, comprehensive data on recent trends and how period and cohort effects may affect these trends among young women are not well-known. Objective: To evaluate breast cancer incidence among young women in the US over a 20-year period by race and ethnicity, hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]), tumor stage, and age at diagnosis, as well as how period and cohort effects may affect these trends. Design, Setting, and Participants: This cross-sectional study used data from Surveillance, Epidemiology, and End Results 17 registries (2000-2019). Women aged 20 to 49 years with a primary invasive breast cancer were included. Data were analyzed between February and June 2023. Main Outcomes and Measures: Age-standardized incidence rates (ASIR), incidence rate ratios (IRR), and average annual percent changes (AAPC) stratified by race and ethnicity, hormone receptor status, tumor stage, and age at diagnosis. Results: Out of 217 815 eligible women (1485 American Indian or Alaska Native [0.7%], 25 210 Asian or Pacific Islander [11.6%], 27 112 non-Hispanic Black [12.4%], 37 048 Hispanic [17.0%], 126 960 non-Hispanic White [58.3%]), the majority were diagnosed with an ER+/PR+ tumor (134 024 [61.5%]) and were diagnosed with a stage I tumor (81 793 [37.6%]). Overall, invasive breast cancer incidence increased (AAPC, 0.79; 95% CI, 0.42 to 1.15), with increasing trends across almost all racial and ethnic groups. ASIR increased for ER+/PR+ (AAPC, 2.72; 95% CI, 2.34 to 3.12) and ER+/PR- tumors (AAPC, 1.43; 95% CI, 1.00 to 1.87), and decreased for ER-/PR+ (AAPC, -3.25; 95% CI, -4.41 to -2.07) and ER-/PR- tumors (AAPC, -0.55; 95% CI, -1.68 to 0.60). For women aged 20 to 29 and 30 to 39 years, ASIRs were highest among non-Hispanic Black women (age 20-29 years: IRR, 1.53; 95% CI, 1.43 to 1.65; age 30-39 years: IRR, 1.15; 95% CI, 1.12 to 1.18). For women aged 40 to 49 years, ASIR was lower for non-Hispanic Black women (IRR, 0.96; 95% CI, 0.94 to 0.97) compared with non-Hispanic White women. Incidence rates increased for stages I and IV tumors but decreased for stage II and III tumors. Age-period-cohort analysis demonstrated both cohort and period effects on breast cancer incidence (P < .001). Conclusions and Relevance: In this population-based cross-sectional analysis, an increase in breast cancer incidence rates among young US women and age-related crossover between non-Hispanic White and Black women were observed. Prevention efforts in young women need to adopt a targeted approach to address racial disparities in incidence rates observed at different age phases.

Hypoplastic Left Heart Syndrome With Low Birth Weight or Prematurity: What Is the Optimal Approach?

BACKGROUND: Hypoplastic left heart syndrome with low birth weight or prematurity comprises a high-risk population with no optimal treatment pathway. Using the Pediatric Health Information System, we compared management approaches across the United States. METHODS: We analyzed neonates (≤30 days) with birth weight <2500 grams or gestational age <36 weeks between 2012 and 2021. Four strategies were identified: Norwood procedure, ductus arteriosus stent + pulmonary artery banding, pulmonary artery banding + prostaglandin infusion, or comfort care. Outcomes included hospital survival, discharge disposition, staged palliation completion, and 1-year transplant-free survival. RESULTS: Of 383 infants identified, 36.4% (n = 134) received comfort care, 43.9% (n = 165) Norwood, 12.4% (n = 49) ductal stent + pulmonary artery bands, and 8.8% (n = 34) pulmonary artery bands + prostaglandins. Neonates receiving comfort care had the lowest gestational age (35 weeks; interquartile range [IQR], 31.5-37 weeks) and birth weight (2.0 kg; IQR, 1.5-2.3 kg); 24.6% (33 of 134) had chromosomal anomalies. Infants undergoing primary Norwood had the highest birth weight (2.4 kg; IQR, 2.2-2.5 kg) and gestational age (37 weeks; IQR, 35-38 weeks). Glenn palliation was performed in 66.1% (109 of 165) compared with ductal stent + pulmonary artery band in 18.4% (9 of 49) and pulmonary artery band + prostaglandins in 35.3% (12 of 34). Only 11.3% (6 of 53) born <2 kg survived to 1 year, all after Norwood. Primary Norwood yielded higher hospital and 1-year transplant-free survival than hybrid strategies. CONCLUSIONS: Comfort care is routinely provided, particularly for infants with low birth weight, gestational age, or chromosomal anomalies. Primary Norwood offered the lowest hospital and 1-year mortality and highest palliation completion rates; birth weight was the most important factor determining 1-year survival.

Factors influencing the prevalence of cervical cancer screening in Malaysia: a nationwide survey.

BACKGROUND: In 2020, cervical cancer ranked fourth in terms of both frequency of diagnosis and the leading cause of cancer-related deaths among women globally. Among Malaysian women, it was the third most prevalent form of cancer. Published data on nationally representative cervical cancer screening in Malaysia have been limited. Therefore, this study aimed to determine the prevalence of receiving a Pap smear test in the past three years, its relationship with socio-demographic factors and physical activity. METHODS: Using a subset of survey data from the National Health and Morbidity Survey (NHMS) 2019, a secondary data analysis was performed. Trained research assistants collected data through face-to-face method using a mobile tablet questionnaire system application. Logistic regression analysis was performed to examine the relationship between sociodemographic factors, physical activity, and cervical cancer screening. The analyses were conducted using STATA version 14 (Stata Corp, College Station, Texas, USA), accounting for sample weighs and complex sampling design. RESULTS: The analysis included 5,650 female respondents, representing an estimated 10.3 million Malaysian female adults aged 18 and above. Overall, 35.2% (95%CI 33.2, 37.4) respondents had a Pap smear test within the past three years. Respondents who were physically active were 1.41 times more likely to have a Pap smear test. Similarly, respondents aged 35-59 (OR 1.84; 95%CI 1.46, 2.34) and those living in rural localities (OR 1.38; 95%CI 1.13, 1.70) had higher odds of receiving a Pap smear test. Compared to married respondents, single respondents (OR 0.04; 95%CI 0.02, 0.07) and widowed/divorcee respondents (OR 0.72; 95%CI 0.56, 0.82) were less likely to receive a Pap smear test. Educated respondents were more likely to have had a Pap smear test. CONCLUSIONS: The overall prevalence of cervical cancer screening in Malaysia remains low (35.2%). Efforts should be made to strengthen health promotion programs and policies in increasing awareness on the significance of cervical cancer screening. These initiatives should specifically target younger women, single women, and widowed/divorced individuals. The higher cervical screening uptake among rural women should be studied further, and the enabling factors in the rural setup should be emulated in urban areas whenever possible.

Bendamustine/Rituximab Plus Cytarabine/Rituximab, With or Without Acalabrutinib, for the Initial Treatment of Transplant-Eligible Mantle Cell Lymphoma Patients: Pooled Data From Two Pilot Studies.

INTRODUCTION: Mantle cell lymphoma (MCL) is a moderately aggressive lymphoma subtype, generally viewed as incurable. For younger, fit patients, the standard of care remains various high-dose cytarabine-based induction regimens followed by autologous hematopoietic cell transplant and 3 years of rituximab maintenance. Despite reasonably good outcomes, with median progression-free survival in the range of 7 to 9 years, most patients eventually relapse, indicating a need to improve the safety and tolerability of remission induction strategies. METHODS: Given the impressive activity of bendamustine/rituximab (BR) in older patients with MCL, we developed an induction regimen modeled after the Nordic Regimen but substituted BR in place of R-CHOP. In a second pilot study, we incorporated the second-generation Bruton tyrosine kinase inhibitor (BTKi), acalabrutinib, into the regimen. The primary endpoint of both studies was stem cell mobilization success rate. RESULTS: All patients successfully underwent stem cell harvest in both studies. CONCLUSION: The experience from our single institution pilot study suggested that sequential rather than alternating BR and cytarabine/rituximab (CR) was easier to administer from the standpoint of toxicities and subsequent dose modifications. Safety and efficacy data from the 2 pilot studies, FitMCL 1.0 and 2.0, were similar. The pilot studies provided preliminary safety data supporting the development of the NCTN trial EA4181, assessing three different induction regimens with or without acalabrutinib.

Outcomes of Treatment for Infective Endocarditis Following Transcatheter Pulmonary Valve Replacement.

BACKGROUND: Recipients of transcatheter pulmonary valve replacement (TPVR) have shown increased risk of infective endocarditis (IE). Little is known about the outcomes of different management strategies, particularly surgery, for IE after TPVR. METHODS: We queried the Pediatric Health Information System database for cases of IE after TPVR performed from 2010-2020. We described patient demographics, hospital courses, admission complications, and treatment outcomes based on therapy offered, surgical or medical only. We compared outcomes of initial therapy. Data are expressed as median or percent. RESULTS: Sixty-nine cases of IE were identified, accounting for 98 related hospital admissions; 29% of patients recorded IE-related readmissions. Of those readmitted after initial medical therapy only, 33% had relapse IE. Rates of surgery were 22% during initial admission and 36% overall. Likelihood of surgical intervention increased with each subsequent admission. Renal and respiratory failure were more common in those given initial surgery. Mortality rate was 4.3% overall and 8% in the surgical cohort. CONCLUSION: Initial medical therapy may result in relapses/readmissions and possible delay of surgical therapy, which appears to be most effective for treatment of IE. For those treated only medically, a more aggressive course of therapy may be more likely to prevent relapse. Mortality following surgical therapy for IE after TPVR appears higher than reported for surgical pulmonary valve replacement generally.

Prospective associations between accelerometry-derived physical activity and sedentary behaviors and mortality among cancer survivors.

BACKGROUND: Survival benefits of self-reported recreational physical activity (PA) during cancer survivorship are well-documented in common cancer types, yet there are limited data on the associations between accelerometer-derived PA of all domains, sedentary behavior, and mortality in large, diverse cohorts of cancer survivors. METHODS: Participants included adults who reported a cancer diagnosis in the National Health and Nutrition Examination Survey and wore an accelerometer for up to 7 days in 2003-2006. Participants were followed for subsequent mortality through 2015. We examined the association of light PA, moderate to vigorous PA, total PA, and sedentary behavior, with all-cause mortality. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics and health indicators. RESULTS: A total of 480 participants (mean age of 68.8 years [SD = 12.4] at the time of National Health and Nutrition Examination Survey assessment) reported a history of cancer. A total of 215 deaths occurred over the follow-up period. For every 1-h/d increase in light PA and moderate to vigorous PA (MVPA), cancer survivors had 49% (HR = 0.51, 95% CI = 0.34 to 0.76) and 37% (HR = 0.63 , 95% CI = 0.40 to 0.99) lower hazards of all-cause mortality, respectively. Total PA demonstrated similar associations with statistically significantly lower hazards of death for each additional hour per day (HR = 0.68, 95% CI = 0.54 to 0.85), as did every metabolic equivalents of task-hour per day increase in total PA estimations of energy expenditure (HR = 0.88, 95% CI = 0.82 to 0.95). Conversely, more sedentary time (1 h/d) was not associated with statistically significantly higher hazards (HR = 1.08, 95% CI = 0.94 to 1.23). CONCLUSIONS: These findings reinforce the current recommendations for cancer survivors to be physically active and underscore the continued need for widespread PA promotion for long-term survival in older cancer survivors.

d-Mannose for Recurrent Urinary Tract Infection Prevention in Postmenopausal Women Using Vaginal Estrogen: A Randomized Controlled Trial.

IMPORTANCE: Further research is needed to determine whether d-mannose plus vaginal estrogen therapy (VET) is beneficial over VET alone for recurrent urinary tract infection (rUTI) prevention. OBJECTIVE: The aim of this study was to evaluate d-mannose efficacy for rUTI prevention in postmenopausal women using VET. STUDY DESIGN: We conducted a randomized controlled trial comparing d-mannose (2 g/d) with control. Participants were required to have a history of uncomplicated rUTIs and to remain on VET throughout the trial. They were followed up 90 days for incident UTIs. Cumulative UTI incidences were calculated by the Kaplan-Meier method and compared by Cox proportional hazards regression. For the planned interim analysis, P < 0.001 was considered statistically significant. Futility analysis was performed by generating post hoc conditional power for multiple scenarios. RESULTS: We evaluated 545 patients for frequent/recurrent UTIs from March 1, 2018, to January 18, 2020. Of these women, 213 had culture-proven rUTIs, 71 were eligible, 57 enrolled, 44 began their planned 90-day study period, and 32 completed the study. At interim analysis, the overall cumulative UTI incidence was 46.6%; 41.1% in the treatment arm (median time to first UTI, 24 days) and 50.4% in the control arm (median, 21 days); hazard ratio, 0.76; 99.9% confidence interval, 0.15-3.97. d-Mannose was well tolerated with high participant adherence. Futility analysis suggested the study lacked power to detect the planned (25%) or observed (9%) difference as statistically significant; the study was halted before conclusion. CONCLUSIONS: d-Mannose is a well-tolerated nutraceutical, but further research is needed to determine whether d-mannose in combination with VET has a significant, beneficial effect beyond VET alone in postmenopausal women with rUTIs.

National Trends and Outcomes in Adolescents Undergoing Bariatric Surgery.

BACKGROUND: In the US, obesity continues to be a severe health issue now affecting adolescents. Bariatric surgery remains the most effective treatment for obesity, but use among adolescents remains low. The objective of this study was to identify current national trends in bariatric surgery among adolescents. STUDY DESIGN: Using the Nationwide Inpatient Sample database, adolescents aged 9 to 19 with a diagnosis of morbid obesity who underwent a laparoscopic gastric bypass (Roux-en-Y gastric bypass) or laparoscopic sleeve gastrectomy (SG) between 2015 and 2018 were identified. Demographics, comorbidities, and in-hospital complications were collected. National estimates were calculated. The trend of annual number of operations was determined by Kruskal-Wallis rank test. RESULTS: Between 2015 and 2018, 1,203 adolescents were identified, resulting in a nationwide estimate of 4,807 bariatric cases. The number of bariatric operations increased annually from 1,360 in 2015 to 1,740 operations in 2018 (p = 0.0771). The majority of patients were female (76%), 17 to 19 years old (84.1%), and White (47.9%). Most patients underwent SG (82.0%). Black and Hispanic patients comprised 40.2% of the cohort. Significant comorbidities included diabetes, dyslipidemia, nonalcoholic fatty liver disease, hypertension, and sleep apnea. The average length of stay decreased from 2.12 days to 1.64 days. There were no in-hospital mortalities, and complications were less than 1%. CONCLUSIONS: With the increasing prevalence of obesity among adolescents in the US, bariatric surgery increased over time but was performed less in patients younger than 16 years of age and racial minorities. Bariatric surgery among adolescents remains safe, with extremely low complication rates and zero in-hospital mortality.

The impact of tocilizumab treatment for cytokine release syndrome on the incidence of early blood stream infections after peripheral blood haploidentical hematopoietic cell transplantation.

Cytokine release syndrome (CRS) is a potentially fatal systemic inflammatory response that can occur in patients undergoing peripheral blood haploidentical hematopoietic cell transplantation (haplo-HCT). Severe CRS has previously been associated with increased infection risk. IL-6 inhibitors, such as tocilizumab, are useful in moderate to severe CRS, but their effect on infection risk has not been established in this setting. We examined the effect of tocilizumab on blood stream infections (BSIs) in the early post-transplant period in 235 patients who underwent haplo-HCT from 2013 to 2020. Mild CRS was associated with a lower incidence of BSI than severe CRS (OR 0.31, 95% CI 0.13-0.74). In the tocilizumab group, 31% of patients had positive blood cultures versus 14% in the non-tocilizumab group (OR 1.61, 95% CI 0.30-8.60, p = 0.58). However, when controlling for CRS grade, tocilizumab was not independently associated with increased rates of BSIs, suggesting it does not further increase infection risk.

The burden of premature mortality among older adults: a population-based study in Malaysia.

BACKGROUND: The populations of many countries-including Malaysia-are rapidly growing older, causing a shift in leading causes of disease and death. In such rapidly ageing populations, it is critical to monitor trends in burden of disease and health of older adults by identifying the leading causes of premature mortality and measuring years of life lost (YLL) to these. The objective of this study, therefore, is to describe the burden (quantified by YLL) associated with major causes of premature mortality among older adults in Malaysia in 2019. METHODS: All deaths that occurred in older adults aged 60 and above in Malaysia in the year 2019 were included in this study. YLL was calculated by summing the number of deaths for the disease category at 5-year age intervals, multiplied by the remaining life expectancy for the specific age and sex group. Both life expectancy and mortality data were obtained from the Department of Statistics Malaysia. RESULTS: In 2019, older adults accounted for 67.4% of total deaths in Malaysia (117,102 out of 173,746). The total number of YLL among older adults in Malaysia in 2019 was estimated at 1.36 million YLL, accounting for 39.6% of the total YLL (3.44 million) lost to all premature deaths in that year. The major causes of premature mortality among older adults were ischaemic heart disease (29.5%) followed by cerebrovascular disease (stroke) (20.8%), lower respiratory infections (15.9%), diabetes mellitus (8.1%) and trachea, bronchus and lung cancers (5.0%). CONCLUSIONS: Non-communicable diseases (NCD) remained the largest contributor to premature mortality among older adults in Malaysia. Implementation of population-level NCD health promotion programmes, screening programmes among high-risk groups and holistic intervention programmes among populations living with NCD are critical in reducing the overall burden of premature mortality.

3,4-Seco-Isopimarane Diterpenes from the Twigs and Leaves of Isodon Flavidus.

Three isopimarane diterpenes [fladins B (1), C (2), and D (3)] were isolated from the twigs and leaves of Chinese folk medicine, Isodon flavidus. The chemical structures were determined by the analysis of the comprehensive spectroscopic data, and the absolute configuration was confirmed by X-ray crystallographic analysis. The structures of 1-3 were formed from isopimaranes through the rearrangement of ring A by the bond break at C-3 and C-4 to form a new δ-lactone ring system between C-3 and C-9. This structure type represents the first discovery of a natural isopimarane diterpene with an unusual lactone moiety at C-9 and C-10. In the crystal of 1, molecules are linked to each other by intermolecular O-H···O bonds, forming chains along the b axis. Compounds 1-3 were evaluated for their bioactivities against different diseases. None of these compounds displayed cytotoxic activities against HCT116 and A549 cancer cell lines, antifungal activities against Trichophyton rubrum and T. mentagrophytes, or antiviral activities against HIV entry at 20 µg/mL (62.9-66.7) µM. Compounds 1 and 3 did not show antiviral activities against Ebola entry at 20 µg/mL either; only 2 was found to show an 81% inhibitory effect against Ebola entry activity at 20 µg/mL (66.7 µM). The bioactivity evidence suggested that this type of compound could be a valuable antiviral lead for further structure modification to improve the antiviral potential.

Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia.

Natural killer (NK) cells are innate lymphoid cells that eliminate cancer cells, produce cytokines, and are being investigated as a nascent cellular immunotherapy. Impaired NK cell function, expansion, and persistence remain key challenges for optimal clinical translation. One promising strategy to overcome these challenges is cytokine-induced memory-like (ML) differentiation, whereby NK cells acquire enhanced antitumor function after stimulation with interleukin-12 (IL-12), IL-15, and IL-18. Here, reduced-intensity conditioning (RIC) for HLA-haploidentical hematopoietic cell transplantation (HCT) was augmented with same-donor ML NK cells on day +7 and 3 weeks of N-803 (IL-15 superagonist) to treat patients with relapsed/refractory acute myeloid leukemia (AML) in a clinical trial (NCT02782546). In 15 patients, donor ML NK cells were well tolerated, and 87% of patients achieved a composite complete response at day +28, which corresponded with clearing high-risk mutations, including TP53 variants. NK cells were the major blood lymphocytes for 2 months after HCT with 1104-fold expansion (over 1 to 2 weeks). Phenotypic and transcriptional analyses identified donor ML NK cells as distinct from conventional NK cells and showed that ML NK cells persisted for over 2 months. ML NK cells expressed CD16, CD57, and high granzyme B and perforin, along with a unique transcription factor profile. ML NK cells differentiated in patients had enhanced ex vivo function compared to conventional NK cells from both patients and healthy donors. Overall, same-donor ML NK cell therapy with 3 weeks of N-803 support safely augmented RIC haplo-HCT for AML.

Magnetic CoNi alloy particles embedded N-doped carbon fibers with polypyrrole for excellent electromagnetic wave absorption.

Increasing electromagnetic (EM) radiation has driven the rapid development of carbon-based EM wave absorption materials, but the design of light-weight and efficient carbon-based materials remains a huge challenge. Herein, N-doped carbon fibers embedded with CoNi alloy particles (CoNi/C fibers) were synthesized via electrospinning technology and carbonization. Then, conductive polypyrrole-coated CoNi/C fibers (CoNi/C@PPy composites) were synthesized by chemical polymerization. As-synthesized CoNi/C@PPy composites showed outstanding EM wave absorption property due to the synergistic effect between CoNi, N-doped carbon fibers and PPy. The optimal reflection loss (RL) is -68.78 dB (12.90 GHz) with the thickness of 2.43 mm and the low filler loading of 15 wt%. The widest effective absorption bandwidth (EAB) is 5.62 GHz with the thickness of 2.10 mm and the low filler loading of 20 wt%. The outstanding EM wave absorption property is mainly attributed to 3D network structure, great impedance matching and strong dielectric loss. The results showed that embedding magnetic alloy particles in carbon fibers coated with conductive polymers is an effective strategy for constructing efficient lightweight EM wave absorption materials.

Preparation and Properties of Waterborne Polypyrrole/Cement Composites.

The electrical properties of cement are gaining importance for the application in building construction. Polypyrrole (PPy) has been widely applied in most fields because of its excellent conductivity performance, environmental friendliness, easy fabrication, and other specialties. These features made them useful for self-sensing applications. In this work, waterborne polypyrrole (WPPy) was prepared via the chemical oxidative polymerization with three kinds of hydrophilic agents: sodium lignosulfonate (LGS), sodium dodecyl sulfonate (SDS), and sodium dodecyl sulfate (SLS), and then WPPy/cement composites were prepared by mixing cement with it. The contact angle, conductivity, and microstructure of WPPy were characterized by contact angle tester, four-point probes, and SEM. The composition, microstructure, and properties of WPPy/cement composites were characterized by FTIR, TGA, XRD, and SEM. The content of LGS was 40 wt%, WPPy got the optimal comprehensive performance, the conductivity was 15.06 times of the control sample and the contact angle was reduced by 69.95%. SEM analysis showed that hydrophilic agent content had great effect on the particle size of WPPy, the average diameter of WPPy particles decreased from 200 nm to 50 nm with the increase of LGS content. The results also showed that the adding of WPPy in WPPy/cement composites can significantly improve the conductivity and compactness, optimize the microstructure of cement composite. When the content of WPPy was 1.25 wt%, WPPy/cement composite showed the lowest resistivity and saturated water content of cement composite was 8 wt%. In addition, it could also inhibit the formation of Ca(OH)2 in the early hydration process.

Constitutive activation of NF-κB inducing kinase (NIK) in the mesenchymal lineage using Osterix (Sp7)- or Fibroblast-specific protein 1 (S100a4)-Cre drives spontaneous soft tissue sarcoma.

Aberrant NF-κB signaling fuels tumor growth in multiple human cancer types including both hematologic and solid malignancies. Chronic elevated alternative NF-κB signaling can be modeled in transgenic mice upon activation of a conditional NF-κB-inducing kinase (NIK) allele lacking the regulatory TRAF3 binding domain (NT3). Here, we report that expression of NT3 in the mesenchymal lineage with Osterix (Osx/Sp7)-Cre or Fibroblast-Specific Protein 1 (FSP1)-Cre caused subcutaneous, soft tissue tumors. These tumors displayed significantly shorter latency and a greater multiple incidence rate in Fsp1-Cre;NT3 compared to Osx-Cre;NT3 mice, regardless of sex. Histological assessment revealed poorly differentiated solid tumors with some spindled patterns, as well as robust RelB immunostaining, confirming activation of alternative NF-κB. Even though NT3 expression also occurs in the osteolineage in Osx-Cre;NT3 mice, we observed no bony lesions. The staining profiles and pattern of Cre expression in the two lines pointed to a mesenchymal tumor origin. Immunohistochemistry revealed that these tumors stain strongly for alpha-smooth muscle actin (αSMA), although vimentin staining was uniform only in Osx-Cre;NT3 tumors. Negative CD45 and S100 immunostains precluded hematopoietic and melanocytic origins, respectively, while positive staining for cytokeratin 19 (CK19), typically associated with epithelia, was found in subpopulations of both tumors. Principal component, differential expression, and gene ontology analyses revealed that NT3 tumors are distinct from normal mesenchymal tissues and are enriched for NF-κB related biological processes. We conclude that constitutive activation of the alternative NF-κB pathway in the mesenchymal lineage drives spontaneous sarcoma and provides a novel mouse model for NF-κB related sarcomas.

Cytokine release syndrome after haploidentical hematopoietic cell transplantation: an international multicenter analysis.

Haploidentical related donor transplantation (haplo-HCT) is associated with cytokine release syndrome (CRS). We conducted a multicenter retrospective study to analyze risk factors for CRS and outcomes after haplo-HCT. We included 451 patients from four academic centers receiving both peripheral blood and bone marrow grafts. Severe CRS was more common with PB vs. BM grafts (19.5% vs 4.9%, OR 2.9, p = 0.05). Multivariable analysis identified recipient CMV sero-positivity, prior transplant, HCT-CI score and donor-recipient sex mismatch as risk factors for severe CRS. Outcomes were analyzed with no CRS as the comparison group. Overall survival (OS) was superior with mild CRS (HR 0.64, p = 0.05) and worst with severe CRS (HR 2.12, p = 0.0038). Relapse risk was significantly decreased in both mild CRS (HR 0.38, p < 0.0001) and severe CRS (HR 0.17, p < 0.0001) groups. The risk of non-relapse mortality was notably higher in severe CRS group (HR 8.0, p < 0.0001), but not in mild CRS group. Acute GVHD was similar among groups. Chronic GVHD at 1 year was 18.5% for no CRS, 23% for mild CRS, and 4.3% for severe CRS (p = 0.0023), with the competing risk of early mortality and short follow up of surviving patients contributing to the low chronic GVHD rates in the severe CRS group.