Association of the social disorganization index with time to first septic shock event in children with acute myeloid leukemia.

BACKGROUND: Pediatric acute myeloid leukemia (AML) chemotherapy increases the risk of life-threatening complications, including septic shock (SS). An area-based measure of social determinants of health, the social disorganization index (SDI), was hypothesized to be associated with SS and SS-associated death (SS-death). METHODS: Children treated for de novo AML on two Children's Oncology Group trials at institutions contributing to the Pediatric Health Information System (PHIS) database were included. The SDI was calculated via residential zip code data from the US Census Bureau. SS was identified via PHIS resource utilization codes. SS-death was defined as death within 2 weeks of an antecedent SS event. Patients were followed from 7 days after the start of chemotherapy until the first of end of front-line therapy, death, relapse, or removal from study. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) comparing time to first SS by SDI group. RESULTS: The assembled cohort included 700 patients, with 207 (29.6%) sustaining at least one SS event. There were 233 (33%) in the SDI-5 group (highest disorganization). Adjusted time to incident SS did not statistically significantly differ by SDI (reference, SDI-1; SDI-2: HR, 0.84 [95% confidence interval (CI), 0.51-1.41]; SDI-3: HR, 0.70 [95% CI, 0.42-1.16]; SDI-4: HR, 0.97 [95% CI, 0.61-1.53]; SDI-5: HR, 0.72 [95% CI, 0.45-1.14]). Nine patients (4.4%) with SS experienced SS-death; seven of these patients (78%) were in SDI-4 or SDI-5. CONCLUSIONS: In a large, nationally representative cohort of trial-enrolled pediatric patients with AML, there was no significant association between the SDI and time to SS.

Epimedin A inhibits the PI3K/AKT/NF-κB signalling axis and osteoclast differentiation by negatively regulating TRAF6 expression.

BACKGROUND: Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. METHODS: Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. RESULTS: After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. CONCLUSIONS: The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.

Inverse Spin Hall Effect Dominated Spin-Charge Conversion in (101) and (110)-Oriented RuO_{2} Films.

Utilizing spin pumping, we present a comparative study of the spin-charge conversion in RuO_{2}(101) and RuO_{2}(110) films. RuO_{2}(101) shows a robust in-plane crystal-axis dependence, whereas RuO_{2}(110) exhibits an isotropic but stronger one. Symmetry-based analysis and first-principles calculations reveal that the spin-charge conversion in RuO_{2}(110) originates from the inverse spin Hall effect (ISHE) due to nodal lines splitting. In RuO_{2}(101), the ISHE also dominates although the inverse spin splitting effect (ISSE) may coexist. These findings, in sharp contrast to previously attributed ISSE, are further corroborated by the reciprocal relation between the spin pumping and the spin-torque ferromagnetic resonance measurements.

Search for a Sub-eV Sterile Neutrino Using Daya Bay's Full Dataset.

This Letter presents results of a search for the mixing of a sub-eV sterile neutrino with three active neutrinos based on the full data sample of the Daya Bay Reactor Neutrino Experiment, collected during 3158 days of detector operation, which contains 5.55×10^{6} reactor ν[over ¯]_{e} candidates identified as inverse beta-decay interactions followed by neutron capture on gadolinium. The analysis benefits from a doubling of the statistics of our previous result and from improvements of several important systematic uncertainties. No significant oscillation due to mixing of a sub-eV sterile neutrino with active neutrinos was found. Exclusion limits are set by both Feldman-Cousins and CLs methods. Light sterile neutrino mixing with sin^{2}2θ_{14}≳0.01 can be excluded at 95% confidence level in the region of 0.01 eV^{2}≲|Δm_{41}^{2}|≲0.1 eV^{2}. This result represents the world-leading constraints in the region of 2×10^{-4} eV^{2}≲|Δm_{41}^{2}|≲0.2 eV^{2}.

Observation of Strong Nuclear Suppression in Exclusive J/ψ Photoproduction in Au+Au Ultraperipheral Collisions at RHIC.

We report a measurement of exclusive J/ψ and ψ(2s) photoproduction in Au+Au ultraperipheral collisions at sqrt[s_{NN}]=200 GeV using the STAR detector. For the first time, (i) the ψ(2s) photoproduction in midrapidity at the Relativistic Heavy-Ion Collider has been experimentally measured; (ii) nuclear suppression factors are measured for both the coherent and incoherent J/ψ production. At average photon-nucleon center-of-mass energy of 25.0 GeV, the coherent and incoherent J/ψ cross sections of Au nuclei are found to be 71±10% and 36±7%, respectively, of that of free protons. The stronger suppression observed in the incoherent production provides a new experimental handle to study the initial-state parton density in heavy nuclei. Data are compared with theoretical models quantitatively.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Magnetic resonance imaging (MRI)-based intratumoral and peritumoral radiomics for prognosis prediction in glioma patients.

AIM: The purpose of this study was to identify robust radiological features from intratumoral and peritumoral regions, evaluate MRI protocols, and machine learning methods for overall survival stratification of glioma patients, and explore the relationship between radiological features and the tumour microenvironment. MATERIAL AND METHODS: A retrospective analysis was conducted on 163 glioma patients, divided into a training set (n=113) and a testing set (n=50). For each patient, 2135 features were extracted from clinical MRI. Feature selection was performed using the Minimum Redundancy Maximum Relevance method and the Random Forest (RF) algorithm. Prognostic factors were assessed using the Cox proportional hazards model. Four machine learning models (RF, Logistic Regression, Support Vector Machine, and XGBoost) were trained on clinical and radiological features from tumour and peritumoral regions. Model evaluations on the testing set used receiver operating characteristic curves. RESULTS: Among the 163 patients, 96 had an overall survival (OS) of less than three years postsurgery, while 67 had an OS of more than three years. Univariate Cox regression in the validation set indicated that age (p=0.003) and tumour grade (p<0.001) were positively associated with the risk of death within three years postsurgery. The final predictive model incorporated 13 radiological and 7 clinical features. The RF model, combining intratumor and peritumor radiomics, achieved the best predictive performance (AUC = 0.91; ACC = 0.86), outperforming single-region models. CONCLUSION: Combined intratumoral and peritumoral radiomics can improve survival prediction and have potential as a practical imaging biomarker to guide clinical decision-making.

Nomogram based on MRI and clinical features to predict progression-free survival in patients with stage IIIC1r cervical squamous cell carcinoma: A two-center study.

PURPOSE: To develop a nomogram based on MRI and clinical features to predict progression-free survival (PFS) of 2018 FIGO stage ⅢC1r cervical squamous cell carcinoma (CSCC). METHODS: 144 consecutive patients with stage ⅢC1r CSCC from two independent institutions were stratified into training cohort (from Institution 1, n=100) and independent validation cohort (from Institution 2, n=44). Univariate and multivariate Cox regression analyses of MRI and clinical features before treatment were performed to determine independent risk factors for PFS in training cohort. Nomogram was developed based on them. Concordance index (C-index), calibration curves, and receiver operating characteristic (ROC) analyses were performed to assess and validate the nomogram. RESULTS: In training cohort, 2009 FIGO stage, maximum length of the primary tumor, short diameter and roundness index of the maximum metastatic lymph node were independent risk factors of PFS in patients with stage IIIC1r CSCC (all P-values < 0.05). Nomogram based on them to predict 1- and 3-year PFS achieved C-indexes of 0.835 (95% confidence interval (CI): 0.809-0.862) and 0.789 (95%CI: 0.683-0.895) in the training and validation cohorts, respectively. Areas under ROC curves for the nomogram to predict 1- and 3-year PFS were 0.891 (95%CI: 0.829-0.954), 0.921 (95%CI: 0.861-0.981) in training cohort, and 0.902 (95%CI: 0.803-0.999), 0.885 (95%CI: 0.778-0.992) in validation cohort, respectively. Calibration curves indicated the nomogram predictions were in good agreement with actual observations. CONCLUSIONS: The nomogram based on MRI and clinical features has high accuracy and stability in predicting PFS of patients with stage IIIC1r CSCC.

[Analysis of changes in intrinsic neural timescales in male smoking addicts based on whole brain resting-state functional magnetic resonance imaging].

Objective: To investigate the abnormal changes of intrinsic neural time scale (INT) in male smoking addicts based on whole brain resting state functional magnetic resonance imaging (rs-fMRI). Methods: A case-control study. The clinical data and whole brain rs-fMRI data of 139 male subjects, aged (34.1±8.8) years, recruited through the online platform from January 2019 to December 2021 were retrospectively analyzed. According to the existence of smoking addiction, they were divided into smoking addiction group (n=83) and healthy control group (n=56).INT was calculated to reflect the brain neural activity dynamics. Single sample t test was used to obtain the whole brain spatial distribution maps of INT in smoking addiction group and the control group. Then two-sample t test was conducted to explore the difference of INT between the smoking addition group and the healthy control group, with age and years of education as covariates. Finally, Spearman correlation analysis was used to explore the relationship between INT and nicotine dependence scale score and smoking index. Results: Subjects with smoking addiction and healthy control group showed a similar pattern of hierarchical neural timescales, namely shorter INT in sensorimotor areas and longer INT in parietal lobe, posterior cingulate cortex. In addition, in the smoking addiction group, the left medial occipital gyrus (peak t=-3.18), left suproccipital gyrus (peak t=-3.66), bilateral pericalar cleft cortex (left: peak t=-3.02, right: peak t=-3.22), bilateral lingual gyrus (left: peak t=-3.10, right: t peak=-3.04), left cuneus (peak t=-2.97), default network associated brain region [left anterior cuneus(peak t=-3.23), left angular gyrus (peak t=-3.07), and left posterior cingulate cortex (peak t=-3.54) were significantly lower than those of healthy controls (gaussian random field correction, voxel level all P<0.005, mass level all P<0.05). However, there was no significant correlation between INT and nicotine dependence scale score and smoking index (both P>0.05 after Bonferroni correction). Conclusion: Compared with healthy controls, smoking addicts showed abnormal changes in the dynamics of neural activity in the visual cortex and the default network.

[Effect of baseline LH/FSH ratio in PCOS on IVF-ET outcomes: a retrospective cohort study].

Objective: To exlplore the association between the baseline luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio of polycystic ovary syndrome (PCOS) and in vitro fertilisation-embryo transfer outcomes. Methods: This was a retrospective cohort study. A total of 2 868 PCOS patients were enrolled, all of the participants were patients in The First Affiliated Hospital of Anhui Medical University Hospital from October 2015 to October 2021. Propensity score matching (1∶2.5) was conducted to regulate the non-random allocation of patients. Data were extracted from the hospital's medical records. Patients with baseline LH/FSH ratio>2 were deemed as study group, patients with baseline LH/FSH ratio≤2 were deemed as control group. Single factor analysis was applied to compare the differences of pregnancy outcomes between two groups. Results: After propensity score matching (1∶2.5), there were no statistically significant differences in baseline data between the two groups (all P>0.05), indicating that the data were comparable. In the study group, the total dose of gonadotropin (Gn) and duration of Gn were lower than those of the control group (t=4.989, P<0.001; t=3.267, P=0.001), the rate of in vitro maturation was higher than that of the control group (χ2=4.938, P=0.026), the number of retrieved oocytes and cleavage were higher than those of the control group (t=-2.305, P=0.021; t=-2.816, P=0.005), but there were no differences in the number and rate of high-quality embryos between the two groups (t=-1.636, P=0.102; t=-0.123, P=0.902). The incidence of moderate to severe ovarian hyperstimulation syndrome in the study group was significantly higher than that in the control group (χ2=17.277, P<0.001). Regardless of fresh embryo transfer or frozen-thawed embryo transfer cycles, the incidences of gestational diabetes mellitus in the study group were higher than those in the control group (χ2=9.174, P=0.002; χ2=4.204, P=0.040) of singleton pregnancy. In the fresh embryo transfer cycle, the clinical pregnancy rate [30.30% (20/66) vs 47.75% (53/111)] and delivery rate [30.30% (20/66) vs 46.85% (52/111)] in the study group were lower than those in the control group (χ2=5.198, P=0.023; χ2=4.695, P=0.030). In the frozen-thawed embryo transfer cycle, the delivery rate in the study group was higer than that in the control group [59.41% (423/712) vs 55.04% (1 053/1 913); χ2=7.526, P=0.023]. The clinical pregnancy rate and delivery rate of fresh embryo transfer cycle in the study group were significantly lower than those of frozen-thawed embryo transfer cycle (χ2=21.308, P<0.001; χ2=20.871, P<0.001), but there were no significant differences in the control group (all P>0.05). Conclusions: PCOS patients with a higher basal LH/FSH ratio are more likely to develop moderate to severe ovarian hyperstimulation syndrome after controlled ovarian stimulation and have a higher incidence of gestational diabetes mellitus. Better pregnancy outcome could be obtained by frozen-thawed embryo transfer.

[Relationship between serum 1, 5-anhydroglucitol level and insulin resistance, microvascular complications in type 2 diabetes mellitus].

Objective: To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data of 836 patients with T2DM admitted to the Changsha Central Hospital Affiliated to University of South China from May to December 2023 were retrospectively and cross-sectionally analyzed. Serum 1, 5-AG levels were detected by pyranose oxidase method. According to the microvascular complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy), the patients were divided into simple group (no microvascular complications, n=490), complication group 1 (1 microvascular complications, n=217), and complication group 2 (2 or more microvascular complications, n=129). The relationship between serum 1, 5-AG level and the related indicators of insulin resistance in T2DM patients were explored by Spearman correlation analysis, and the influencing factors of microvascular complications in T2DM patients were explored by multiple ordered logistic regression analysis. Results: The levels of FBG(fasting blood glucose) [(7.37±0.56) mmol/L], FINS(fasting insulin) [(11.34±1.86) mU/L] and HOMA-IR(homeostatic model assessment of insulin resistance) (0.96±0.31) in simple group were lower than those in complication group 1 [(8.37±1.02) mmol/L, (16.26±2.32) mU/L, (1.32±0.41)], complication group 2 [(10.25±2.13) mmol/L, (18.53±2.67) mU/L, (1.54±0.44)], and FBG, FINS and HOMA-IR in complication group 1 were lower than those in complication group 2, and the differences were statistically significant (F=537.470, 791.690, 136.340, P<0.001). Serum 1, 5-AG level in simple group [77.16 (16.30, 128.07) µg/ml] was higher than that in complication group 1 [51.05 (14.67, 63.18) µg/ml] and complication group 2 [30.42 (12.53, 47.26) µg/ml], and the serum level of 1, 5-AG in complication group 1 was higher than that in complication group 2, and the difference was statistically significant (H=210.020, P<0.001). The results of Spearman correlation analysis showed that serum 1, 5-AG level was negatively correlated with FBG, FINS and HOMA-IR in T2DM patients (r=-0.431, -0.372, -0.546, P<0.001). The results of multiple ordered logistic regression analysis showed that Longer duration of diabetes (OR=2.261, 95%CI: 1.564-3.269), increased HbA1c (OR=2.040, 95%CI: 1.456-2.858), and increased HOMA-IR (OR=2.158, 95%CI: 1.484-3.137) and decreased 1, 5-AG (OR=2.512, 95%CI: 1.691-3.732) were independent risk factors for microvascular complications in T2DM patients (P<0.05). The results of ROC curve analysis showed that the area under the curve of serum 1, 5-AG in the identification of one microvascular complication was 0.763 (95%CI: 0.731-0.795), and the area under the curve of serum 1, 5-AG in the identification of two or more microvascular complications was 0.730 (95%CI: 0.692-0.767). Conclusion: Serum 1, 5-AG level is negatively correlated with insulin resistance in T2DM patients. Low serum 1, 5-AG level may be an independent risk factor for microvascular complications in T2DM patients.

[Angiomatosis of the breast: a clinicopathological analysis of six cases].

Objective: To investigate the clinicopathological features and differential diagnosis of breast angiomatosis. Methods: Six cases of breast angiomatosis diagnosed at the Department of Pathology, the Seventh Medical Center, People's Liberation Army General Hospital and the Department of Pathology, Dongzhimen Hospital, Beijing University of Chinese Medicine from January 2011 to December 2023 were evaluated and reviewed. Results: All patients were female with an average age of 46 years at presentation, ranging from 25 to 62 years. The most common clinical presentation was a palpable unilateral breast mass with diameter ranging from 7 to 14 cm, and the average size was 11 cm. Histologically, all cases were composed of variably-sized ectatic, thin-walled blood vessels with minimal to no apparent smooth muscle, lined by flat normochromic endothelium without atypia, and diffusely infiltrating the breast stroma. Where present, the lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Immunohistochemical staining for CD31, CD34, Factor Ⅷ, Fli-1 and D2-40 revealed positive expression in vascular and/or lymphatic endothelial cells. Additionally, the Ki-67 proliferation index was found to be less than 1%. Conclusions: Angiomatosis of the breast is a rare benign vascular lesion. Distinguishing it from low-grade angiosarcoma requires careful consideration of the growth pattern, atypical features, and Ki-67 proliferation index.

[A comparative study of rigid gas permeable corneal contact lenses versus frame glasses for refractive correction of postoperative aphakic eyes after congenital cataract surgery in infants and children].

Objective: The aim of this paper is to compare the refractive correction effects of rigid gas permeable contact lenses (RGPCL) and spectacle correction in children with aphakia after congenital cataract surgery. Methods: This was a prospective non-randomized controlled trial. Children with aphakic eyes after congenital cataract surgery, who underwent vision correction in the Strabismus and Pediatric Ophthalmology Clinic of Beijing Tongren Hospital affiliated with Capital Medical University from April 2012 to November 2019, were continuously collected. Those who voluntarily chose to wear RGPCL for refractive correction were included in the experimental group. Patients with monocular disease were in trial group 1, and patients with binocular disease were in trial group 2. Patients who chose to wear frame glasses for refractive correction were included in the control group. Patients with monocular disease were in control group 1, and patients with binocular disease were in control group 2. Regional origin, medical history, and family information were collected at the first diagnosis. During the follow-up, adverse reactions occurring during the process of wearing glasses were recorded. The Teller acuity card was used for visual examination to obtain the best-corrected visual acuity and convert it into the logarithm of the minimum resolution angle. The degree of nystagmus was determined according to the amplitude and frequency of nystagmus. Treatment cost, treatment compliance, and the reasons for adopting or not adopting RGPCL were analyzed through a questionnaire completed by the parents of children with RGPCL. Results: A total of 203 children (344 eyes) who underwent congenital cataract surgery were included, including 124 males (210 eyes) and 79 females (134 eyes). The age range was 3 to 36 months. There were 28 cases in the experimental group, including 19 cases in trial group 1 and 9 cases in trial group 2. There were 175 cases in the control group, including 43 cases in control group 1 and 132 cases in control group 2. Except for 6 months of age, the visual acuity of the experimental group was better than that of the control group, and the differences were statistically significant (P<0.05). The visual acuity of children in trial group 1 was better than that of children in control group 1 at the same age. Among them, at 12 months of age [1.54 (1.27, 1.97), 1.84 (0.97, 2.12)], 18 months of age [1.27 (0.97, 1.84), 1.84 (0.97, 2.12)], 24 months of age [1.54 (1.27, 1.84), 1.84 (0.97, 2.12)], and 30 months old [0.97 (0.66, 1.27), 1.54 (0.66, 2.12)], the difference was statistically significant (P<0.001). The visual acuity of children in trial group 2 was better than that in control group 2 at the same age. Among them, at 18 months old [1.27 (0.97, 1.54), 1.27 (0.66, 2.12)], 24 months old [0.97 (0.66, 1.27), 1.27 (0.66, 2.12)], and 30 months old [1.27 (0.66, 2.12)], the difference was statistically significant (P<0.05). The remission rate of nystagmus in the experimental group was 8/9 (8 cases), the remission rate of nystagmus in the control group was 34.40% (32 cases), and the exacerbation rate was 29.03% (27 cases). The average annual cost of the experimental group was 25 125 yuan, and that of the control group was 2 511 yuan. Conclusions: RGPCL is a well-tolerated, safe, and effective treatment for infants and young children. The visual acuity and degree of nystagmus were significantly improved in children who wore RGPCL for aphakia refractive correction after congenital cataract surgery compared with spectacle correction.

Circulating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030.

BACKGROUND: We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy. PATIENTS AND METHODS: We identified responders (RCB 0/1) and matched non-responders (RCB 2/3) from the phase II TBCRC 030 prospective study of neoadjuvant paclitaxel versus cisplatin in TNBC. We collected plasma samples at baseline, 3 weeks and 12 weeks (end of therapy). We created personalized ctDNA assays utilizing MAESTRO mutation enrichment sequencing. We explored associations between ctDNA and RCB status and disease recurrence. RESULTS: Of 139 patients, 68 had complete samples and no additional neoadjuvant chemotherapy. Twenty-two were responders and 19 of those had sufficient tissue for whole-genome sequencing. We identified an additional 19 non-responders for a matched case-control analysis of 38 patients using a MAESTRO ctDNA assay tracking 319-1000 variants (median 1000 variants) to 114 plasma samples from 3 timepoints. Overall, ctDNA positivity was 100% at baseline, 79% at week 3 and 55% at week 12. Median tumor fraction (TFx) was 3.7 × 10-4 (range 7.9 × 10-7-4.9 × 10-1). TFx decreased 285-fold from baseline to week 3 in responders and 24-fold in non-responders. Week 12 ctDNA clearance correlated with RCB: clearance was observed in 10 of 11 patients with RCB 0, 3 of 8 with RCB 1, 4 of 15 with RCB 2 and 0 of 4 with RCB 3. Among six patients with known recurrence, five had persistent ctDNA at week 12. CONCLUSIONS: Neoadjuvant chemotherapy for TNBC reduced ctDNA TFx by 285-fold in responders and 24-fold in non-responders. In 58% (22/38) of patients, ctDNA TFx dropped below the detection level of a commercially available test, emphasizing the need for sensitive tests. Additional studies will determine whether ctDNA-guided approaches can improve outcomes.

Association between weight gain and knee osteoarthritis: a systematic review.

OBJECTIVE: Although weight loss is recommended to manage knee osteoarthritis (KOA), adults tend to gain weight with age which may affect KOA symptoms and progression. We conducted a systematic review and data synthesis to investigate the association between weight gain and KOA, defined by clinical features, structural progression, and total knee replacement (TKR). DESIGN: MEDLINE and EMBASE were systematically searched for controlled trials and cohort studies of participants with (or at risk of) KOA examining the relationship between weight gain and KOA clinical features (pain, function, quality of life), structural progression, and TKR. Risk of bias was assessed using the ROBINS-I tool. Results were organised by outcome, with meta-analyses performed where appropriate. RESULTS: Twenty-three studies were included. Results showed significant detrimental effects of weight gain on pain (4 of 7 studies), stiffness (2 of 2 studies), function (5 of 6 studies), and the single studies examining quality of life, and clinical and radiographic KOA. Weight gain adversely affected cartilage (6 of 9 studies), bone marrow lesions (1 of 4 studies), meniscal damage (1 of 3 studies) and effusion/synovitis (1 of 1 study). Weight gain significantly increased TKR (3 of 6 studies): meta-analysis of 2 with available data demonstrated significant increases in TKR/5 kg weight gain in women, HR 1.34 (95% CI 1.18-1.51), and in men, HR 1.25 (95% CI 1.16-1.34). CONCLUSIONS: Weight gain in adults is associated with increased clinical and structural KOA and TKR. Prevention of weight gain should be considered to improve outcomes in KOA.

Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia.

NUP98 fusions comprise a family of rare recurrent alterations in AML, associated with adverse outcomes. In order to define the underlying biology and clinical implications of this family of fusions, we performed comprehensive transcriptome, epigenome, and immunophenotypic profiling of 2,235 children and young adults with AML and identified 160 NUP98 rearrangements (7.2%), including 108 NUP98-NSD1 (4.8%), 32 NUP98-KDM5A (1.4%) and 20 NUP98-X cases (0.9%) with 13 different fusion partners. Fusion partners defined disease characteristics and biology; patients with NUP98-NSD1 or NUP98-KDM5A had distinct immunophenotypic, transcriptomic, and epigenomic profiles. Unlike the two most prevalent NUP98 fusions, NUP98-X variants are typically not cryptic. Furthermore, NUP98-X cases are associated with WT1 mutations, and have epigenomic profiles that resemble either NUP98-NSD1 or NUP98-KDM5A. Cooperating FLT3-ITD and WT1 mutations define NUP98-NSD1, and chromosome 13 aberrations are highly enriched in NUP98-KDM5A. Importantly, we demonstrate that NUP98 fusions portend dismal overall survival, with the noteworthy exception of patients bearing abnormal chromosome 13 (clinicaltrials gov. Identifiers: NCT00002798, NCT00070174, NCT00372593, NCT01371981).

Improved Measurement of the Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

Measurement of the

The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E_{α}=474.0±1.1 keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.

Hyperon Polarization along the Beam Direction Relative to the Second and Third Harmonic Event Planes in Isobar Collisions at sqrt[s_{NN}]=200 GeV.

The polarization of Λ and Λ[over ¯] hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at sqrt[s_{NN}]=200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild p_{T} dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagrees with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and p_{T} dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.

Observation of Directed Flow of Hypernuclei _{Λ}

We report here the first observation of directed flow (v_{1}) of the hypernuclei _{Λ}^{3}H and _{Λ}^{4}H in mid-central Au+Au collisions at sqrt[s_{NN}]=3 GeV at RHIC. These data are taken as part of the beam energy scan program carried out by the STAR experiment. From 165×10^{6} events in 5%-40% centrality, about 8400 _{Λ}^{3}H and 5200 _{Λ}^{4}H candidates are reconstructed through two- and three-body decay channels. We observe that these hypernuclei exhibit significant directed flow. Comparing to that of light nuclei, it is found that the midrapidity v_{1} slopes of _{Λ}^{3}H and _{Λ}^{4}H follow baryon number scaling, implying that the coalescence is the dominant mechanism for these hypernuclei production in the 3 GeV Au+Au collisions.