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Supplemental Table 1: A) Multivariable analysis for the association with biochemical recurrence comparing histopathologic and molecular lymph node status as categorical variables excluding 7 patients receiving adjuvant treatment for pN1-disease B) Multivariable analysis for the association with biochemical recurrence comparing histopathologic lymph node status and molecular maximum KLK3 expression in lymph nodes per patient as continuous variable excluding 7 patients receiving adjuvant treatment for pN1-disease Supplemental Figure 1: Distribution of the maximum KLK3 expression in lymph nodes per patient stratifying the study cohort in patients without lymph node metastases (pN0/molN0), patients with lymph node metastases detected exclusively by molecular analysis (pN0/molN1) or detected by both histopathologic and molecular analysis (pN1/molN1). Supplemental Figure 2: Biochemical recurrence-free survival according to lymph node status by (A) histopathology and (B) molecular analysis in a subgroup of 104 patients, who did not receive adjuvant treatment for pN1-status. Median biochemical recurrence-free survival was 3 months (95%CI 1.0-5.0) in 21 pN1-patients vs. not reached in 83 pN0-patients (p

Purpose: Molecular lymph node (LN) analysis using quantitative polymerase chain reaction (qPCR) detects LN metastases with higher sensitivity than histopathology. However, the prognostic role of molecular LN status in prostate cancer patients treated with radical prostatectomy (RP) and extended pelvic LN dissection (ePLND) is unclear. To investigate the association of molecular compared with histopathologic LN status with biochemical recurrence.Experimental Design: Patients with intermediate and high-risk prostate cancer were prospectively enrolled and underwent RP with ePLND, including the obturator, internal, external, and the common iliac region. LNs ≥3 mm were bisected and examined by standard histopathology and qPCR for Kallikrein3 (KLK3) expression. Biochemical recurrence was defined by confirmed postoperative PSA > 0.2 ng/mL.Results: In 111 patients, 2,411 of 3,173 removed LNs were examined by both methods. Histopathology detected 68 LN metastases in 28 (25%) patients. Molecular analysis confirmed elevated KLK3 expression in 65 histopathologic LN metastases of all 28 pN1 patients (pN1/molN1) and additionally reclassified 224 histopathologic negative LNs and 32 (29%) pN0 patients as LN-positive (pN0/molN1).At a median follow-up of 48 months, 52 (47%) patients developed biochemical recurrence. Median biochemical recurrence-free survival was 9 months [95% confidence interval (CI), 0.0–20.1] in pN1/molN1 patients, 24 months (95% CI, 1.7–46.3) in pN0/molN1 patients and was not reached in pN0/molN0 patients (P < 0.001). On multivariable Cox regression analysis, molecular LN status [HR 4.1 (95% CI, 1.9–8.8), P < 0.001] but not histopathologic LN status [HR 1.5 (95% CI, 0.8–3.0), P = 0.198] was confirmed as independent predictor of biochemical recurrence.Conclusions: Molecular LN analysis identified pN0 patients with a high risk of biochemical recurrence and provided superior prognostic information in comparison with histopathology alone. Clin Cancer Res; 24(10); 2342–9. ©2018 AACR.

1AbstractAntibodies can play an important role in innate and adaptive immune responses against cancer, and in preventing infectious disease. Flow cytometry analysis of sera of immune mice that were previously cured of their melanoma through a combined immunotherapy regimen with long-term memory showed strong antibody-binding against melanoma tumor cell lines. Using a high-density whole-proteome peptide array, we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by 2 or more of these 6 mice and exhibited strong antibody binding only by immune, not naive sera. Confirmatory studies were done to validate these results using 2 separate ELISA-based systems. To the best of our knowledge, this is the first study of the “immunome” of protein-based epitopes that are recognized by immune sera from mice cured of cancer via immunotherapy.summaryHoefges et al. utilized a whole-proteome peptide array approach to show that C57BL/6 mice develop a large repertoire of antibodies against linear peptide sequences of their melanoma after receiving a curative immunotherapy regimen consisting of radiation and an immunocytokine.

During the past century, bivalve populations across the globe have collapsed, resulting in negative ecosystem consequences due to their outsized impact on shallow estuaries. In response, there has been strong interest in the restoration of marine bivalve populations. Here, we present a decade-long restoration effort that sought to rebuild a collapsed (99.5% reduction in harvest) and recruitment-limited population of hard clams (Mercenaria mercenaria) in Shinnecock Bay, NY, USA, using spawner sanctuaries: no-harvest zones where adults were planted at high densities (~27 m-2). Between 2012 to 2019, more than 3.2 million clams were planted in 64 discrete sanctuary plots (~1,850 m2 each) located in zones with maximal larval retention and sediment and seawater characteristics that would maximize the conditioning and spawning of adults. Hydrodynamic models, quantification of hard clam larvae, and spatial recruitment patterns demonstrated larvae spawned within sanctuaries were transported to regions where clam densities significantly increased 18-fold over seven years (2015-2021; ppAureococcus anophagefferens, and chlorophyll a significantly decreased (pp

Lymph node metastases (LNMs) are common in intermediate- to high-risk prostate cancer (PC) and may be missed during extended pelvic lymph node dissection (ePLND). Here we report on the use of prostate-specific membrane antigen (PSMA)-radioguided surgery (RGS) during open radical prostatectomy (RP) with ePLND to resect locoregional LNMs identified on preoperative PSMA positron emission tomography (PET). Preoperative PSMA PET showed 78 LNMs in 35 patients undergoing RP with ePLND and RGS between January 2018 and June 2020. In 14 patients (40%), LNMs were located outside the ePLND template. RGS achieved resection of PSMA-positive LNMs in 33/35 patients (94%). On univariable analysis, lower metastatic burden with up to two PSMA-positive LNMs on preoperative PET was associated with better postoperative outcomes. Limitations include the retrospective analysis and the small sample size. RGS facilitates resection of PSMA-positive LNs in patients treated with RP. Our data indicate a favorable treatment outcome in patients with low metastatic LN burden on preoperative PSMA PET. PATIENT SUMMARY: We investigated the use of radioactive guidance to remove lymph nodes affected by prostate cancer during surgical removal of the prostate. This approach can help to identify cancerous lymph nodes that might otherwise be missed and could lead to better survival outcomes.

Sea surface temperature (SST) has increased worldwide since the beginning of the 20th century, a trend which is expected to continue. Changes in SST can have significant impacts on marine biota, including population-level shifts and alterations in community structure and diversity, and changes in the timing of ecosystem events. Seagrasses are a group of foundation species that grow in shallow coastal and estuarine systems, where they provide many ecosystem services. Eelgrass, Zostera marina L., is the dominant seagrass species in the Northeast United States of America (USA). Multiple factors have been cited for losses in this region, including light reduction, eutrophication, and physical disturbance. Warming has the potential to exacerbate seagrass loss. Here, we investigate regional changes in eelgrass presence and abundance in relation to local water temperature using monitoring data from eight sites in the Northeastern USA (New Hampshire to Maryland) where a consistent monitoring protocol, SeagrassNet, has been applied. We use a hurdle model consisting of a generalized additive mixed model (GAMM) with binomial and beta response distributions for modeling eelgrass presence and abundance, respectively, in relation to the local summer average water temperature. We show that summer water temperature one year prior to monitoring is a significant predictor of eelgrass presence, but not abundance, on a regional scale. Above average summer temperatures correspond to a decrease in probability of eelgrass presence (and increased probability of eelgrass absence) the following year. Cooler than average temperatures in the preceding year, down to approximately 0.5°C below the site average, are associated with the highest predicted probability of eelgrass presence. Our findings suggest vulnerability in eelgrass meadows of the Northeast USA and emphasize the value of unified approaches to seagrass monitoring, conservation and management at the seascape scale.

Part 1 of this series of two articles describes conventional and advanced MRI techniques that are useful for evaluating brainstem pathologies. In addition, it provides a review of the embryology, normal progression of myelination, and clinically and radiologically salient imaging anatomy of the normal brainstem. Finally, it discusses congenital diseases of the brainstem with a focus on distinctive imaging features that allow for differentiating pathologies. Part 2 of this series of two articles includes discussion of neoplasms; infections; and vascular, demyelinating, toxic and metabolic, and miscellaneous disease processes affecting the brainstem. The ultimate goal of this pair of articles is to empower the radiologist to add clinical value in the care of pediatric patients with brainstem pathologies.

Neurocognitive deficits have been associated with suicidal behavior in adults with major depressive disorder (MDD), but it is unclear if similar impairments are linked to youth suicidal behavior. This study compared neurocognitive functioning in suicidal and non-suicidal youth with a lifetime history of MDD and explored whether neurocognitive functioning predicted future suicide attempts. Neurocognition was examined using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and Iowa Gambling Task (IGT) in 309 youths ages 12-15 (117 suicide attempters; 132 suicidal ideators; 60 never-suicidal). Prospective analyses included 284 youths (41 youth with a future attempt; 243 without a future attempt). Multivariate analysis of variance (MANOVA) yielded a significant group-by-sex interaction effect [Wilks' Λ = 0.901, F (16, 560) = 1.87, p = .021] for the primary neurocognitive outcomes, guiding the decision to stratify the sample by sex. Female suicide attempters and ideators were slower to respond correctly to both positive and negative emotion words than never-suicidal controls on tests of affective bias. Male suicide attempters and ideators made significantly more total and between errors than never-suicidal subjects. Exploratory analyses found that total commission errors on the Affective Go/No-Go (AGN) test significantly predicted future suicide attempts in females, and that higher strategy scores on Spatial Working Memory (SWM) tests predicted future male attempts. Study findings identified sex-specific neurocognitive deficits that differentiate suicidal and non-suicidal youth with histories of MDD. Extended longitudinal studies are needed to elucidate the temporal association between neurocognitive impairments and suicidal behavior and frame targets for early preventive interventions.

Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.

N6-methyladenosine (m6A) is an abundant post-transcriptional modification that can impact RNA fate via interactions with m6A-specific RNA binding proteins. Despite accumulating evidence that m6A plays an important role in modulating pluripotency, the influence of m6A reader proteins in pluripotency is less clear. Here, we report that YTHDF2, an m6A reader associated with mRNA degradation, is highly expressed in induced pluripotent stem cells (iPSCs) and down-regulated during neural differentiation. Through RNA sequencing, we identified a group of m6A-modified transcripts associated with neural development that are directly regulated by YTDHF2. Depletion of YTHDF2 in iPSCs leads to stabilization of these transcripts, loss of pluripotency, and induction of neural-specific gene expression. Collectively, our results suggest YTHDF2 functions to restrain expression of neural-specific mRNAs in iPSCs and facilitate their rapid and coordinated up-regulation during neural induction. These effects are both achieved by destabilization of the targeted transcripts.

In a subset of patients with recurrent oligometastatic prostate cancer (PCa) salvage surgery with prostate-specific membrane antigen (PSMA)-targeted radioguidance (PSMA-RGS) might be of value.To evaluate the oncological outcomes of salvage PSMA-RGS and determine the predictive preoperative factors of improved outcomes.A cohort study of oligorecurrent PCa patients with biochemical recurrence (BCR) after radical prostatectomy and imaging with PSMA positron emission tomography (PET), treated with PSMA-RGS in two tertiary care centers (2014-2020), was conducted.PSMA-RGS.Kaplan-Meier and multivariable Cox regression models were used to assess BCR-free (BFS) and therapy-free (TFS) survival. Postoperative complications were classified according to Clavien-Dindo.Overall, 364 patients without concomitant treatment were assessed. At PSMA-RGS, metastatic soft-tissue PCa lesions were removed in 343 (94%) patients. At 2-16 wk after PSMA-RGS, 165 patients reached a prostate-specific antigen (PSA) level of0.2 ng/ml. Within 3 mo, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. At 2 yr, BFS and TFS rates were 32% and 58%, respectively. In multivariable analyses, higher preoperative PSA (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 1.02-1.12), higher number of PSMA-avid lesions (HR: 1.23, CI: 1.08-1.40), multiple (pelvic plus retroperitoneal) localizations (HR: 1.90, CI: 1.23-2.95), and retroperitoneal localization (HR: 2.04, CI: 1.31-3.18) of lesions in preoperative imaging were independent predictors of BCR after PSMA-RGS. The main limitation is the lack of a control group.As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach, careful patient selection is mandatory based on life expectancy, low PSA values, and low number of PSMA PET-avid lesions located in the pelvis.We looked at the outcomes from prostate cancer patients with recurrent disease after radical prostatectomy. We found that surgery may be an opportunity to prolong treatment-free survival, but patient selection criteria need to be very narrow.

Belle-II DEPFET and PXD Collaboration: et al., The Belle II experiment at the SuperKEKB accelerator has started its physics data taking with the full detector setup in March 2019. It aims to collect 40 times more e+ e- collision data compared with its predecessor Belle experiment. The Belle II pixel detector (PXD) is based on the Depleted P-channel Field Effect Transistor (DEPFET) technology. The PXD plays an important role in the tracking and vertexing of the Belle II detector. Its two layers are arranged at radii of 14 mm and 22 mm around the interaction point. The sensors are thinned down to 75 m to minimize multiple scattering, and each module has interconnects and ASICs integrated on the sensor with silicon frames for mechanical support. PXD showed good performance during data taking. It also faces several operational challenges due to the high background level from the SuperKEKB accelerator, such as the damage from beam loss events, the drift in the HV working point due to radiation effect, and the impact of the high background., This work is supported by MEXT, WPI, and JSPS (Japan); MSMT, GAUK 404316 (Czech Republic), MSCA-RISE project JENNIFER-2 (EU grant 822070); Federal Ministry of Education and Research (BMBF, Germany); CIDEGENT/2018/020 of Generalitat Valenciana (Spain); National Natural Science Foundation of China (No. 11435013); and research grants S-1440-0321, S-0256-1438, and S-0280-1439 (University of Tabuk, KSA, Saudi Arabia ).

PLOS ONE 17(6), e0269827 (2022). doi:10.1371/journal.pone.0269827, Published by PLOS, San Francisco, California, US

Objectives A new electroanatomic mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts) using a 64-electrode mapping basket is now available; we systematically assessed its use in complex congenital heart disease (CHD). Background The incidence of atrial arrhythmias post-surgery for CHD is high. Catheter ablation has emerged as an effective treatment, but is hampered by limitations in the mapping system’s ability to accurately define the tachycardia circuit. Methods Mapping and ablation data of 61 patients with CHD (35 males, age 45 ± 14 years) from 8 tertiary centers were reviewed. Results Causes were as follows: Transposition of Great Arteries (atrial switch) (n = 7); univentricular physiology (Fontans) (n = 8); Tetralogy of Fallot (n = 10); atrial septal defect (ASD) repair (n = 15); tricuspid valve (TV) anomalies (n = 10); and other (n = 11). The total number of atrial arrhythmias was 86. Circuits were predominantly around the tricuspid valve (n = 37), atriotomy scar (n = 10), or ASD patch (n = 4). Although the majority of peri-tricuspid circuits were cavo-tricuspid-isthmus dependent (n = 30), they could follow a complex route between the annulus and septal resection, ASD patch, coronary sinus, or atriotomy. Immediate ablation success was achieved in all but 2 cases; with follow-up of 12 ± 8 months, 7 patients had recurrence. Conclusions We demonstrate the feasibility of the basket catheter for mapping complex CHD arrhythmias, including with transbaffle and transhepatic access. Although the circuits often involve predictable anatomic landmarks, the precise critical isthmus is often difficult to predict empirically. Ultra–high-density mapping enables elucidation of circuits in this complex anatomy and allows successful treatment at the isthmus with a minimal lesion set.

Proceedings of the 29th International Workshop on Vertex Detectors (VERTEX2020), Tsukuba, Japan (Online); Journal of the Physical Society of Japan 34, 010002 (2021). doi:10.7566/JPSCP.34.010002, The Belle II experiment at the super KEK B factory (SuperKEKB) started its physics operation with the full detector setup in March 2019, and it aims at collecting 50 ab$^{���1}$ of $e^+e^���$ collision data. The vertex detector (VXD) of Belle II contains a 4-layer silicon vertex detector (SVD) using double sided silicon strips and an inner 2-layer pixel detector (PXD) that is based on the depleted P-channel Field Effect Transistor (DEPFET) technology. The signal generation and amplification are combined in pixels with a minimum pitch of 55 �� 50 ��m$^2$. The sensors are thinned down to 75 ��m, and each module has interconnects and ASICs integrated on the sensor with silicon frames for mechanical support. This approach led to a material budget of around 0.21% X$_0$ per layer including the cooling structure in the acceptance region. The PXD has an integration time of around 20 ��s, a signal-to-noise ratio of around 50 and a detecting efficiency of better than 99%. Its two layers are arranged at the radii of 14 and 22 mm around the interaction point, and an impact parameter resolution of better than 15 ��m has been achieved. Due to its close proximity to the beam line and its sensitivity to few-keV photons, the PXD also plays an important role in background studies., Published by The Physical Society of Japan, Tokyo

The human fetal liver is a critical organ for prenatal hematopoiesis, the study of which offers insights into niche signals that regulate the fates of hematopoietic stem and progenitor cells (HSPCs) during fetal development. Here, we demonstrate that human fetal liver endothelium uniquely supports the maturation and expansion of multilineage HSPCs. Specifically, co-culture of fetal liver-derived immature CD43+CD45− hematopoietic cells with human fetal liver endothelial cells (ECs) led to a profound increase in the numbers of phenotypic CD45+CD34+ HSPCs and multilineage colony-forming progenitors generated in vitro, when compared to co-culture with ECs derived from other organs. We further identified a supportive role for EC-derived WNT5A in this process via gain- and loss-of-function studies within ECs. Our study emphasizes the importance of the organ-specific endothelial niche in supporting hematopoietic development and provides novel insight into signals that may facilitate HSPC expansion in vitro for clinical applications.

Background The Micra VA (leadless) pacemaker was approved by the FDA for use in 2016. Whilst initial studies evaluated the safety and efficacy of the device for a mean follow up of 12 months, very few studies have evaluated complications and device function beyond 1 year.Objective: To evaluate the short and long term complication rate and device function associated with the Micra VA (leadless) pacemaker at our centre. Methods A prospective analysis of all Micra VA implants performed at Royal Papworth Hospital was carried out. This included pacing checks for up to 24 months post device insertion, evaluating complications and specifically noting thresholds and R-wave amplitude changes. Results A total of 24 Micra leadless pacemakers were implanted at our centre between 2017 and 2020. The age range for the patients was 37 to 92 years, mean age 71 ± 13 yrs. 8 out of 24 (33%) patients had poor venous access, with bilateral subclavian obstruction, requiring the use of a leadless pacemaker. 2 out of 24 had bilateral previous pacemaker infections and extraction. For the remaining patients, 12/24 (50%) had atrial fibrillation with slow ventricular response as the primary indication for the device. 6 out of 24 (25%) patients had a history of LV impairment (4 patients severe LVSD, 2 moderate LVSD). One patient had a previous cardiac transplant.The implant was successful for all patients. One patient required the procedure to be repeated under general anaesthetic as she did not tolerate the insertion of the femoral sheath under sedation. 2 patients (8%) required repositioning of the device during the case, as initial placement was unsatisfactory. 23/24 patients had the device placed in the septum and 1 patient in the RV apex. This patient had undergone multiple previous tricuspid valve surgeries, which made septal positioning challenging, and so an apical placement was accepted. Mean procedure time was 62 ± 16 mins. Mean fluoroscopy time was 5.8 ± 4.2 mins. Implant threshold was 0.6 V ± 0.4 V. Threshold at 1 year follow up was 0.5 V ± 0.2 V and 0.6 V ± 0.2 V at 2 years. Paired T testing showed no statistically significant difference in threshold values at implant, and year 1 (p = 0.7, n =13), or implant and year 2 (p = 0.78, n =6). The R wave at implant was 9.5 ± 4.1mV, and 9.8 mV ± 2.5mV at year 1, again with no statistically significant difference (p = 0.87, n = 13). Mean battery life at 2 year follow up was 7 ± 0.5 years. Pacing percentages varied from 0.1% to 99.99%. Conclusion Although are numbers are small, particularly for follow up over 2 years (n = 6), the initial results are encouraging, and support a low complication rate, and no evidence of premature battery failure or issues with device threshold requiring re intervention. It is imperative that further studies are carried out to give a picture of longer term follow up for the leadless Micra VA pacemaker focussing on these two key issues. Conflict of Interest nil

Belle II DEPFET, PXD, and SVD Collaborations: et al., The Belle II experiment comes with a substantial upgrade of the Belle detector and will operate at the SuperKEKB energy-asymmetric ee collider with energies tuned to ϒ(4S) resonance s=10.588 GeV. The accelerator has successfully completed the first phase of commissioning in 2016 and the first electron–positron collisions in Belle II took place in April 2018. Belle II features a newly designed silicon vertex detector based on DEPFET pixel and double-sided strip layers. Currently, a subset of the vertex detector is installed (Phase 2 of the experiment). Installation of the full detector (Phase 3) will be completed by the end of 2018. This paper describes the Phase 2 arrangement of the Belle II silicon vertex detector, with focus on the interconnection of detectors and their integration with the software framework of Belle II. Alignment issues are discussed based on detector simulations and first acquired data., This work is supported by MSCA-RISE, European Union project JENNIFER (EU grant n. 644294), MEXT, Japan, WPI, and JSPS (Japan); ARC (Australia); BMWFW (Austria); MSMT, Czech Republic, GAUK 404316 (Czech Republic); AIDA-2020 (Germany); DAE, India and DST (India); INFN (Italy); NRF-2016K1A3A7A09005605 and RSRI (Korea); MNiSW (Poland); Federal Ministry of Education and Research (BMBF, Germany); and MINECO, Spain grant FPA2015-71292-C2-1-P (Spain).

BACKGROUND Adolescent suicide is a major public health concern worldwide. However, evidence regarding the effectiveness of interventions targeting youth suicide risk is limited. The purpose of this study was to assess the feasibility, acceptability, and clinical outcomes of Intensive Crisis Intervention (ICI), a cognitive-behavioral, family-centered treatment that provides an alternative to longer inpatient care. METHOD Intensive Crisis Intervention was piloted over a two-year period with 50 adolescents (Mage = 15.1 years; 86% Female; 78% Caucasian) admitted to an intensive crisis stabilization unit presenting with suicidal ideation and/or attempts. Data were collected at admission, 30 days, and 3 months post-admission to evaluate changes in suicidal ideation and functioning over time. RESULTS Follow-up data were provided by 88% of study participants. At 3 months, the mean Suicidal Ideation Questionnaire-Junior score improved 34.2 points relative to baseline (effect size of 2.2, p

Health-risk behaviors associated with increased risk of suicide are more prevalent in old-for-grade students compared to age-appropriate-for-grade peers; however, the association between old-for-grade status and suicidal behavior is largely unknown. This study investigated sex-specific differences in suicidal ideation, planning, attempts, and other risk behaviors by old-for-grade status. Secondary analyses utilizing bivariate and logistic regression methods for complex samples were conducted using data from the 2011, 2013, and 2015 National Youth Risk Behavior Survey for 16,579 female and 17,282 male high school students in grades 9 through 11. Among both males and females, students considered old-for-grade reported increased drug use, feeling sad/hopeless, violence, sexual activity, and limited/no seatbelt use compared with their peers. Old-for-grade students were also more likely to report a suicide attempt with increased suicidal ideation and planning observed only in old-for-grade males. Associations between old-for-grade status and suicide risk-related outcomes were attenuated in both sexes after adjusting for demographic characteristics and other health-risk behaviors. Findings suggest that common risk factors (e.g., sadness, substance use) may explain increased rates of suicidal behaviors in old-for-grade students.

SUMMARYDuring embryogenesis, waves of hematopoietic progenitors develop from hemogenic endothelium (HE) prior to the emergence of self-renewing hematopoietic stem cells (HSC). Although previous studies have shown that yolk sac-derived erythromyeloid progenitors and HSC emerge from distinct populations of HE, it remains unknown whether the earliest lymphoid-competent progenitors, multipotent progenitors, and HSC originate from common HE. Here we demonstrate by clonal assays and single cell transcriptomics that rare HE with functional HSC potential in the early murine embryo are distinct from more abundant HE with multilineage hematopoietic potential that fail to generate HSC. Specifically, HSC-competent HE are characterized by expression of CXCR4 surface marker and by higher expression of genes tied to arterial programs regulating HSC dormancy and self-renewal. Together, these findings suggest a revised model of developmental hematopoiesis in which the initial populations of multipotent progenitors and HSC arise independently from HE with distinct phenotypic and transcriptional properties.

During embryogenesis, waves of hematopoietic progenitors develop from hemogenic endothelium (HE) prior to the emergence of self-renewing hematopoietic stem cells (HSC). Although previous studies have shown that yolk sac-derived erythromyeloid progenitors and HSC emerge from distinct populations of HE, it remains unknown whether the earliest lymphoid-competent progenitors, multipotent progenitors, and HSC originate from common HE. Here we demonstrate by clonal assays and single cell transcriptomics that rare HE with functional HSC potential in the early murine embryo are distinct from more abundant HE with multilineage hematopoietic potential that fail to generate HSC. Specifically, HSC-competent HE are characterized by expression of CXCR4 surface marker and by higher expression of genes tied to arterial programs regulating HSC dormancy and self-renewal. Together, these findings suggest a revised model of developmental hematopoiesis in which the initial populations of multipotent progenitors and HSC arise independently from HE with distinct phenotypic and transcriptional properties.

Computer physics communications 259, 107610 (2021). doi:10.1016/j.cpc.2020.107610, This paper describes the track-finding algorithm that is used for event reconstruction in the Belle II experiment operating at the SuperKEKB B-factory in Tsukuba, Japan. The algorithm is designed to balance the requirements of a high efficiency to find charged particles with a good track parameter resolution, a low rate of spurious tracks, and a reasonable demand on CPU resources. The software is implemented in a flexible, modular manner and employs a diverse selection of global and local track-finding algorithms to achieve an optimal performance., Published by North Holland Publ. Co., Amsterdam

The dialogue management component of a task-oriented dialogue system is typically optimised via reinforcement learning (RL). Optimisation via RL is highly susceptible to sample inefficiency and instability. The hierarchical approach called Feudal Dialogue Management takes a step towards more efficient learning by decomposing the action space. However, it still suffers from instability due to the reward only being provided at the end of the dialogue. We propose the usage of an intrinsic reward based on information gain to address this issue. Our proposed reward favours actions that resolve uncertainty or query the user whenever necessary. It enables the policy to learn how to retrieve the users' needs efficiently, which is an integral aspect in every task-oriented conversation. Our algorithm, which we call FeudalGain, achieves state-of-the-art results in most environments of the PyDial framework, outperforming much more complex approaches. We confirm the sample efficiency and stability of our algorithm through experiments in simulation and a human trial.

Belle-II DEPFET and PXD Collaboration: et al., The Belle II experiment at the SuperKEKB energy-asymmetric e+ e- collider has completed a series of substantial upgrades and started collecting data in 2019. The experiment is expected to accumulate a data set of 50 ab−1 to explore new physics beyond the Standard Model at the intensity frontier. The pixel detector (PXD) of Belle II plays a key role in vertex determination. It has been developed using the DEpleted P-channel Field Effect Transistor (DEPFET) technology, which combines low power consumption in the active pixel area and low intrinsic noise with a very small material budget. In this paper, commissioning and performance of the PXD measured with first collision data are presented., This work is supported by MEXT, Japan, WPI, Japan, and JSPS (Japan); MSMT, GAUK 404316, MSCA-RISE project JENNIFER-2 (EU grant n. 822070) (Czech Republic); Federal Ministry of Education and Research (BMBF, Germany) and MINECO, Spain grant FPA2015-71292-C2-1-P (Spain).

During embryonic development, sequential waves of hematopoiesis give rise to blood-forming cells with diverse lineage potentials and self-renewal properties. This process must accomplish two important yet divergent goals: the rapid generation of differentiated blood cells to meet the needs of the developing embryo and the production of a reservoir of hematopoietic stem cells to provide for life-long hematopoiesis in the adult. Vascular beds in distinct anatomical sites of extraembryonic tissues and the embryo proper provide the necessary conditions to support these divergent objectives, suggesting a critical role for specialized vascular niche cells in regulating disparate blood cell fates during development. In this review, we will examine the current understanding of how organ- and stage-specific vascular niche specialization contributes to the development of the hematopoietic system.

The objective of this retrospective study was to assess the detection rate (DR), positive predictive value (PPV), and correct detection rate (CDR) of