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Abstract We report multi-differential measurements of strange hadron production ranging from mid- to target-rapidity in Au+Au collisions at a center-of-momentum energy per nucleon pair of s NN $$ \sqrt{s_{\textrm{NN}}} $$ = 3 GeV with the STAR experiment at RHIC. K S 0 $$ {K}_S^0 $$ meson and Λ hyperon yields are measured via their weak decay channels. Collision centrality and rapidity dependences of the transverse momentum spectra and particle ratios are presented. Particle mass and centrality dependence of the average transverse momenta of Λ and K S 0 $$ {K}_S^0 $$ are compared with other strange particles, providing evidence of the development of hadronic rescattering in such collisions. The 4π yields of each of these strange hadrons show a consistent centrality dependence. Discussions on radial flow, the strange hadron production mechanism, and properties of the medium created in such collisions are presented together with results from hadronic transport and thermal model calculations.

As a vital economic and population agglomeration area in China, the Beijing-Tianjin-Hebei region has attracted considerable attention regarding population migration issues. Population migration not only directly affects the population size and structure of cities within the region but also has profound implications for economic development, social stability, and urban planning. This study extends the analysis to the "Spring Festival Travel Rush" period, using population migration data from January to March in the years 2020 to 2022 as the basis. By employing complex network theory and relevant statistical indicators, the study explores the peak period population migration patterns and their variations in the Beijing-Tianjin-Hebei region. The research firstly identifies significant changes in population migration patterns in the Beijing-Tianjin-Hebei region around 2021 and analyzes the changing patterns. Secondly, network statistical indicators indicate hierarchical population migration patterns based on city tiers. Furthermore, cities with unique migration patterns are identified. Finally, based on an in-depth exploration of population migration patterns and their variations in the Beijing-Tianjin-Hebei region, the study provides suggestions and prospects for future urban planning and development, offering important references for addressing the challenges posed by population migration in the region.

Abstract Background Human flourishing is an emerging concept, extending beyond the conventional boundaries of subjective well-being and evolving into a comprehensive capture of the diverse dimensions of human life within complex societal structures. Therefore, moving away from traditional approaches centered on the single latent construct, this study aims to explore the multiple aspects of human flourishing and the intricate interplay of their contributing factors. Methods Data were collected from the Health and Living Environments Survey of Taiwanese Retirees during 2023 (valid sample n = 1,111). Human flourishing was measured using the Secure Flourish Index developed by Harvard University, which includes 12 indicators: (1) life satisfaction, (2) happiness, (3) mental health, (4) physical health, (5) meaning in life, (6) sense of purpose, (7) promoting good, (8) delaying gratification, (9) content relationships, (10) satisfying relationships, (11) financial stability, and (12) material stability. A mixed graphical network analysis was employed to analyze the related determinants, divided into four groups: (a) sociodemographic factors, (b) physical functions and health status, (c) social and family engagement, and (d) community environmental characteristics as nodes. Results We analyzed 31 variables and identified 133 nonzero edges out of 465 potential connections in the comprehensive network. Results showed that happiness and promoting good were the two most critical indicators influencing retirees’ overall flourishing. Different flourishing indicators were also associated with various influential factors. For instance, personal characteristics, especially gender and education, emerged as central factors. Family caregiving negatively affected happiness and financial stability, whereas social engagement was positively associated with life satisfaction and meaning in life. Employment status had mixed effects, negatively associated with life satisfaction but positively associated with mental health. Community environments, such as a sense of community and neighborhood safety, generally enhanced flourishing. However, the accessibility of neighborhood resources was paradoxically associated with material stability, pointing to the complexity of environmental factors in human flourishing. Conclusion This study provides a comprehensive network analysis that reveals intricate connections between personal, behavioral, and environmental factors, offering profound insights for targeted interventions to foster human flourishing.

We report on the charged-particle multiplicity dependence of net-proton cumulant ratios up to sixth order from s=200 GeV p+p collisions at the Relativistic Heavy Ion Collider (RHIC). The measured ratios C4/C2, C5/C1, and C6/C2 decrease with increased charged-particle multiplicity and rapidity acceptance. Neither the Skellam baselines nor PYTHIA8 calculations account for the observed multiplicity dependence. In addition, the ratios C5/C1 and C6/C2 approach negative values in the highest-multiplicity events, which implies that thermalized QCD matter may be formed in p+p collisions.

To reduce the fluid resistance on the surface of flow-through components and improve energy utilization efficiency, a biomimetic fitting structure model is constructed based on the ridge-like features of beluga skin. The SST k-ω model is employed to numerically simulate the drag reduction characteristics of three biomimetic structures (fitting structure, V-shaped structure, and arc structure) included in the design. The variations of the fitting structure’s viscous resistance and pressure drop resistance with different widths and depths are compared. The drag reduction mechanism of the fitting structure surface is studied based on the pressure stress, velocity field, and shear stress. The results demonstrate that the fitting structure exhibits the best drag reduction performance. The fitting structure with a width of 30 mm and a depth of 0.7 mm achieves an optimal drag reduction effect of 4.18%. The fitting structure exhibits a large low shear stress region, which increases the thickness of the bottom boundary layer, thereby reducing surface velocity and viscous resistance.

Cloud detection is a necessary step before the application of remote sensing images. However, most methods focus on cloud detection in daytime remote sensing images. The ignored nighttime remote sensing images play more and more important role in many fields such as urban monitoring, population estimation and disaster assessment. The radiation intensity similarity between artificial lights and clouds is higher in nighttime remote sensing images than in daytime remote sensing images, which makes it difficult to distinguish artificial lights from clouds. Therefore, this paper proposes a deep learning-based method (MFFCD-Net) to detect clouds for day and nighttime remote sensing images. MFFCD-Net is designed based on the encoder-decoder structure. The encoder adopts Resnet-50 as the backbone network for better feature extraction, and a dilated residual up-sampling module (DR-UP) is designed in the decoder for up-sampling feature maps while enlarging the receptive field. A multi-scale feature extraction fusion module (MFEF) is designed to enhance the ability of the MFFCD-Net to distinguish regular textures of artificial lights and random textures of clouds. An Global Feature Recovery Fusion Module (GFRF Module) is designed to select and fuse the feature in the encoding stage and the feature in the decoding stage, thus to achieve better cloud detection accuracy. This is the first time that a deep learning-based method is designed for cloud detection both in day and nighttime remote sensing images. The experimental results on Suomi-NPP VIIRS DNB images show that MFFCD-Net achieves higher accuracy than baseline methods both in day and nighttime remote sensing images. Results on daytime remote sensing images indicate that MFFCD-Net can obtain better balance on commission and omission rates than baseline methods (92.3% versus 90.5% on F1-score). Although artificial lights introduced strong interference in cloud detection in nighttime remote sensing images, the accuracy values of MFFCD-Net on OA, Precision, Recall, and F1-score are still higher than 90%. This demonstrates that MFFCD-Net can better distinguish artificial lights from clouds than baseline methods in nighttime remote sensing images. The effectiveness of MFFCD-Net proves that it is very promising for cloud detection both in day and nighttime remote sensing images.

Abstract This study aims to investigate the factors influencing the work status of retirees after retirement, especially focusing on self-employment and unpaid work. Data was taken and analyzed from the “Taiwan Health and Retirement Study,” a nationally representative sample of retired personnel aged 50–74 in 2015–2016. Four types of work status were classified after retirement: Fully retired, Paid work, Self-employment, and Unpaid work. Multinomial regression analysis was used to explore the factors related to participation in paid, self-employed, and unpaid work. Results show that pre-retirement occupation was significantly associated with paid work after retirement. For example, retirees in Taiwan who were employed by private enterprises or self-employed before retirement were more likely to engage in paid work after retirement than civil servants before retirement. Two other factors, namely pre-retirement job stress and work flexibility, prolong the careers of retired workers, especially in self-employment and unpaid work after retirement. Gender also significantly affects the choice of work after retirement. These findings can be used as a reference for future policies on the aging labor force.

We report the first measurements of cumulants, up to 4th order, of deuteron number distributions and proton-deuteron correlations in Au+Au collisions recorded by the STAR experiment in phase-I of Beam Energy Scan (BES) program at the Relativistic Heavy Ion Collider. Deuteron cumulants, their ratios, and proton-deuteron mixed cumulants are presented for different collision centralities covering a range of center-of-mass energy per nucleon pair sNN=7.7 to 200 GeV. It is found that the cumulant ratios at lower collision energies favor a canonical ensemble over a grand canonical ensemble in thermal models. An anti-correlation between proton and deuteron multiplicity is observed across all collision energies and centralities, consistent with the expectation from global baryon number conservation. The UrQMD model coupled with a phase-space coalescence mechanism qualitatively reproduces the collision-energy dependence of cumulant ratios and proton-deuteron correlations.

The chiral magnetic effect (CME) is a phenomenon that arises from the QCD anomaly in the presence of an external magnetic field. The experimental search for its evidence has been one of the key goals of the physics program of the Relativistic Heavy-Ion Collider. The STAR Collaboration has previously presented the results of a blind analysis of isobar collisions (_{44}^{96}Ru+_{44}^{96}Ru, _{40}^{96}Zr+_{40}^{96}Zr) in the search for the CME. The isobar ratio (Y) of CME-sensitive observable, charge separation scaled by elliptic anisotropy, is close to but systematically larger than the inverse multiplicity ratio, the naive background baseline. This indicates the potential existence of a CME signal and the presence of remaining nonflow background due to two- and three-particle correlations, which are different between the isobars. In this postblind analysis, we estimate the contributions from those nonflow correlations as a background baseline to Y, utilizing the isobar data as well as Heavy Ion Jet Interaction Generator simulations. This baseline is found consistent with the isobar ratio measurement, and an upper limit of 10% at 95% confidence level is extracted for the CME fraction in the charge separation measurement in isobar collisions at sqrt[s_{NN}]=200 GeV.

The differential cross section for Z0 production, measured as a function of the boson's transverse momentum (pT), provides important constraints on the evolution of the transverse momentum dependent parton distribution functions (TMDs). The transverse single spin asymmetry (TSSA) of the Z0 is sensitive to one of the polarized TMDs, the Sivers function, which is predicted to have the opposite sign in p+p →W/Z+X from that which enters in semi-inclusive deep inelastic scattering. In this Letter, the STAR Collaboration reports the first measurement of the Z0/γ⁎ differential cross section as a function of its pT in p+p collisions at a center-of-mass energy of 510 GeV, together with the Z0/γ⁎ total cross section. We also report the measurement of Z0/γ⁎ TSSA in transversely polarized p+p collisions at 510 GeV.

Although electroconvulsive therapy (ECT) is one of the most effective treatments for severe mood and psychotic disorders, the mechanisms underlying its therapeutic effects remain unknown. Electroconvulsive stimulation (ECS), the animal model for ECT, can be used to investigate the potential therapeutic mechanisms of ECT in rodents. ECS produces numerous effects in the brain, such as increasing levels of growth factors, inducing dendritic sprouting, and stimulating neurogenesis. It also induces high-level expression of immediate early genes (IEGs) that have been implicated in the pathogenesis of schizophrenia, such as early growth response 3 (Egr3) and activity-regulated cytoskeleton-associated protein (Arc), a validated downstream target of Egr3 [1–3]. However, the effect of isoflurane anesthesia preceding ECS on IEG response in mice has not been well characterized. This article provides immunofluorescent data of the activity responsive IEG ARC in the dorsal and ventral dentate gyrus of wildtype (WT) mice following ECS with or without anesthesia, as well as following sham ECS. The data in this article relate to a published article that employed serial ECS in mice to investigate the requirement of Egr3 in the neurobiological effects of this model of ECT [4]. The ability to study the effects of serial ECS has been limited in mice due to high rates of mortality during seizure. Administration of isoflurane anesthesia prior to ECS significantly reduces rodent mortality, irrespective of the number of times ECS is applied [5]. Since general anesthesia is administered to patients prior to ECT, use of isoflurane prior to ECS also more closely models the clinical use of ECT [6].

Comprehensive observations of hydroxyl (OH) and hydroperoxy (HO2) radicals were conducted in October 2019 at a coastal continental site in the Pearl River Delta (YMK site, 22.55∘ N, 114.60∘ E). The daily maximum OH and HO2 concentrations were (4.7–9.5) × 106 and (4.2–8.1) × 108 cm−3, respectively. The synchronized air mass transport from the northern cities and the South China Sea exerted a time-varying influence on atmospheric oxidation. Under a typical ocean-atmosphere (OCM), reasonable measurement model agreement was achieved for both OH and HO2 using a 0-D chemical box model incorporating the regional atmospheric chemistry mechanism version 2-Leuven isoprene mechanism (RACM2-LIM1), with daily averages of 4.5 × 106 and 4.9 × 108 cm−3, respectively. Land mass (LAM) influence promoted more active photochemical processes, with daily averages of 7.1 × 106 and 5.2 × 108 cm−3 for OH and HO2, respectively. Heterogeneous uptake had certain effects on HOx chemistry, but the influence of the halogen mechanism was limited by NOx level. Intensive photochemistry occurred after precursor accumulation, allowing local net ozone production comparable with surrounding suburban environments (5.52 ppb h−1 during the LAM period). The rapid oxidation process was accompanied by a higher diurnal nitrous acid (HONO) concentration (> 400 ppt). After a sensitivity test, HONO-related chemistry elevated the ozone production rate by 33 % and 39 % during the LAM and OCM periods, respectively. The nitric acid (P(HNO3)) and sulfuric acid (P(H2SO4)) formation rates also increased simultaneously (∼ 43 % and ∼ 48 % for LAM and OCM sectors, respectively). In the ozone-prediction test, simulated O3 decreased from ∼ 75 ppb to a global background (∼ 35 ppb) without the HONO constraint, and daytime HONO concentrations were reduced to a low level (∼ 70 ppt). For coastal cities, the particularity of the HONO chemistry tends to influence the ozone-sensitive system and eventually magnifies the background ozone. Therefore, the promotion of oxidation by elevated precursors deserves a lot of attention when aiding pollution mitigation policies.

Background and objective: There is insufficient evidence on the oncologic risks of testosterone therapy for men with prostate cancer managed with active surveillance. We carried out a retrospective study to assess the effect of testosterone therapy on oncologic outcomes for men on active surveillance for prostate cancer. Methods: Surveillance, Epidemiology and End Results (SEER)-Medicare linked data were used to identify men diagnosed with prostate cancer from 2008 to 2017 who were managed with active surveillance and received testosterone (n = 167) or no testosterone (n = 6658) therapy. Outcomes included conversion from active surveillance to active treatment (radical prostatectomy, cryotherapy, radiation, or androgen deprivation therapy), prostate cancer–specific mortality, and overall mortality. Statistically significant factors on univariable analysis were included in a Cox proportional-hazards regression model for multivariable analysis. Key findings and limitations: The median age was 71 yr (interquartile range [IQR] 68–74) in the testosterone group and 72 yr (IQR 69–75) in the no-testosterone group, with corresponding median follow-up after prostate cancer diagnosis of 5.2 yr (IQR 3.4–7.8) and 4.7 yr (IQR 3.2–6.9). There were no prostate cancer–specific deaths in the testosterone group and 39 (0.6%) in the no-testosterone group. Testosterone therapy was not associated with conversion to active treatment (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.46–0.97; p = 0.033) or overall mortality (HR 1.02, 95% CI 0.68–1.53; p > 0.9). Conclusions and clinical implications: In the first population-based, nationally representative study of testosterone therapy for men on active surveillance for prostate cancer, testosterone therapy did not increase the risk of conversion to active therapy or worsen mortality. Prospective studies are needed to confirm these findings. Patient summary: For men on active surveillance for prostate cancer, we assessed the effect of testosterone therapy. We found that testosterone therapy did not increase the risk of proceeding to active therapy or of death from prostate cancer.

We report results on an elastic cross section measurement in proton–proton collisions at a center-of-mass energy s=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. This is the only measurement of the proton-proton elastic cross section in this t range for collision energies above the Intersecting Storage Rings (ISR) and below the Large Hadron Collider (LHC) colliders. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). This is the first measurement below the LHC energies for which the non-constant behavior B(t) is observed. The t dependence of B is also determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s=540 GeV for proton–antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σelfid=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.

Triple-negative breast cancer (TNBC), which constitutes 10–20 percent of all breast cancers, is aggressive, has high metastatic potential, and carries a poor prognosis due to limited treatment options. LT-IIc, a member of the type II subfamily of ADP-ribosylating—heat-labile enterotoxins that bind to a distinctive set of cell-surface ganglioside receptors—is cytotoxic toward TNBC cell lines, but has no cytotoxic activity for non-transformed breast epithelial cells. Here, primary TNBC cells, isolated from resected human tumors, showed an enhanced cytotoxic response specifically toward LT-IIc, in contrast to other enterotoxins that were tested. MDA-MB-231 cells, a model for TNBC, were used to evaluate potential mechanisms of cytotoxicity by LT-IIc, which induced elevated intracellular cAMP and stimulated the cAMP response element-binding protein (CREB) signaling pathway. To dissect the role of ADP-ribosylation, cAMP induction, and ganglioside ligation in the cytotoxic response, MDA-MB-231 cells were exposed to wild-type LT-IIc, the recombinant B-pentamer of LT-IIc that lacks the ADP-ribosylating A polypeptide, or mutants of LT-IIc with an enzymatically inactivated A1-domain. These experiments revealed that the ADP-ribosyltransferase activity of LT-IIc was nonessential for inducing the lethality of MDA-MB-231 cells. In contrast, a mutant LT-IIc with an altered ganglioside binding activity failed to trigger a cytotoxic response in MDA-MB-231 cells. Furthermore, the pharmacological inhibition of ganglioside expression protected MDA-MB-231 cells from the cytotoxic effects of LT-IIc. These data establish that ganglioside ligation, but not the induction of cAMP production nor ADP-ribosyltransferase activity, is essential to initiating the LT-IIc-dependent cell death of MDA-MB-231 cells. These experiments unveiled previously unknown properties of LT-IIc and gangliosides in signal transduction, offering the potential for the targeted treatment of TNBC, an option that is desperately needed.

AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop’s classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a “snow-capped” appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype–phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5′ truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3′ truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by “toxic” cellular effects of the mutant proteins.

Abstract Background Ultra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment. Methods A total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator’s discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival. Discussion The SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions. Trial registration ClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.

Background: Expert consensus recommends treatment of magnetic resonance imaging (MRI)-visible prostate cancer (PCa). Outcomes of partial-gland ablation (PGA) for MRI-invisible PCa remain unknown. Objective: To compare recurrence-free survival, adverse events, and health-related quality of life (HRQoL) outcomes following cryoablation of MRI-visible vs invisible PCa. Design, setting, and participants: We analyzed data for 75 men who underwent cryoablation therapy between January 2017 and January 2022. PCa identified on MRI-targeted and/or adjacent systematic biopsy cores was defined as MRI-visible, whereas PCa identified on systematic biopsy beyond the targeted zone was defined as MRI-invisible. Outcome measurements and statistical analysis: The primary outcome was recurrence at 12 mo after PGA, defined as the presence of clinically significant PCa (grade group [GG] ≥2) on surveillance biopsy. Adverse events were captured using the Clavien-Dindo classification and HRQoL was captured using the Expanded Prostate Cancer Index-Clinical Practice (EPIC-CP) tool. Results and limitations: Of the 58 men treated for MRI-visible and 17 treated for MRI-invisible lesions, 51 (88%) and 16 (94%), respectively, had at least one surveillance biopsy performed. There were no statistically significant differences in age, race, body mass index, biopsy GG, prostate-specific antigen, prostate volume, or treatment extent between the MRI-visible and MRI-invisible groups. Median follow-up was 44 mo (interquartile range 17–54) and did not significantly differ between the groups. The recurrence rate at 12 mo did not significantly differ between the groups (MRI-visible 39%, MRI-invisible 19%; p = 0.2), and log-rank survival analysis demonstrated no significant difference in recurrence-free survival (p = 0.15). Adverse event rates did not significantly differ (MRI-visible 29%, MRI-invisible 53%; p = 0.092); no man in the MRI-visible group had a Clavien-Dindo grade ≥III complication, while one subject in the MRI-invisible group had a Clavien-Dindo grade III complication. Median EPIC-CP urinary and sexual function scores were similar for the two groups at baseline and at 12 mo after PGA. Study limitations include the retrospective design and small sample size. Conclusions: We observed similar cancer control, adverse event, and HRQoL outcomes for MRI-visible versus MRI-invisible PCa in the first comparison of partial-gland cryoablation. Longer follow-up and external validation of our findings are needed to inform patient selection for PGA for MRI-invisible PCa. Patient summary: Patients with prostate cancer lesions that are not visible on magnetic resonance imaging (MRI) scans who undergo partial gland ablation may have similar treatment outcomes compared to patients with cancer lesions that are visible on MRI.

Abstract We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (|y| < 0.7) in Au+Au collisions at s NN $$ \sqrt{s_{\textrm{NN}}} $$ = 200 GeV. Invariant yields of HFEs are measured for the transverse momentum range of 3.5 < p T < 9 GeV/c in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in p + p collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma.

Abstract Cryptococcal meningoencephalitis can occur in both previously healthy and immunocompromised hosts. Here, we describe a 55 year-old HIV-negative male with no known prior medical problems, who presented with three months of worsening headaches, confusion, and memory changes without fever. Magnetic resonance imaging of the brain demonstrated bilateral enlargement/enhancement of the choroid plexi, with hydrocephalus, temporal and occipital horn entrapments, as well as marked periventricular transependymal cerebrospinal fluid (CSF) seepage. CSF analysis yielded a lymphocytic pleocytosis and cryptococcal antigen titer of 1:160 but sterile fungal cultures. Despite standard antifungal therapy and CSF drainage, the patient had worsening confusion and persistently elevated intracranial pressures. External ventricular drainage led to improved mental status but only with valve settings at negative values. Ventriculoperitoneal shunt placement could thus not be considered due to a requirement for drainage into the positive pressure venous system. Due to this persistent CSF inflammation and cerebral circulation obstruction, the patient required transfer to the National Institute of Health. He was treated for cryptococcal post-infectious inflammatory response syndrome with pulse-taper corticosteroid therapy, with resultant reductions in CSF pressures along with decreased protein and obstructive material, allowing successful shunt placement. After tapering of corticosteroids, the patient recovered without sequelae. This case highlights (1) the necessity to consider cryptococcal meningitis as a rare cause of neurological deterioration in the absence of fever even in apparently immunocompetent individuals and (2) the potential for obstructive phenomena from inflammatory sequelae and the prompt response to corticosteroid therapy.

The nearby radio galaxy M87 is a very high-energy (VHE) gamma-ray emitter established by observations with ground-based gamma-ray detectors. Here we report the long-term monitoring of M87 from 2021 to 2024 with the Large High Altitude Air Shower Observatory (LHAASO). M87 has been detected by LHAASO with a statistical significance ∼ 9 σ . The observed energy spectrum extends to 20 TeV, with a possible hardening at ∼20 TeV and then a clear softening at higher energies. Assuming that the intrinsic spectrum is described by a single power law up to 20 TeV, a tight upper bound on the extragalactic background light intensity is obtained. A strong VHE flare lasting 8 days, with a rise time of ${\tau }_{r}^{\mathrm{rise}}=1.05\pm 0.49$ days and decay time of ${\tau }_{d}^{\mathrm{decay}}=2.17\pm 0.58$ days, was found in early 2022. A possible GeV flare is seen also in Fermi Large Area Telescope data during the VHE flare period. The variability time as short as 1 day seen in the LHAASO data suggests a compact emission region with a size of ∼3 × 10 ^15 δ cm ( δ being the Doppler factor of the emitting region), corresponding to a few Schwarzschild radii of the central supermassive black hole in M87. The continuous monitoring of the source reveals a duty cycle of ∼1% for VHE flares with a flux above 10 ^−11 erg cm ^−2 s ^−1 .

The first source catalog of the Large High Altitude Air Shower Observatory (LHAASO) reported the detection of a very high energy gamma-ray source, 1LHAASO J1219+2915. This Letter presents a further detailed study of the spectral and temporal behavior of this pointlike source. The best-fit position of the TeV source (R.A. = 185.°05 ± 0.°04, decl. = 29.°25 ± 0.°03) is compatible with NGC 4278 within ∼0.°03. Variation analysis shows an indication of variability on a timescale of a few months in the TeV band, which is consistent with low-frequency observations. Based on these observations, we report the detection of TeV γ -ray emissions from this low-luminosity active galactic nucleus. The observation by LHAASO's Water Cherenkov Detector Array during the active period has a significance level of 8.8 σ with a best-fit photon spectral index Γ = 2.56 ± 0.14 and a flux f _1–10 TeV = (7.0 ± 1.1 _sta ± 0.35 _syst ) × 10 ^−13 photons cm ^−2 s ^−1 , or approximately 5% of the Crab Nebula. The discovery of VHE gamma-ray emission from NGC 4278 indicates that compact, weak radio jets can efficiently accelerate particles and emit TeV photons.

Optical neural networks (ONNs) enable high speed, parallel, and energy efficient processing compared to their conventional digital electronic counterparts. However, realizing large scale ONN systems is an open problem. Among various integrated and non-integrated ONNs, free-space diffractive ONNs benefit from a large number of pixels of spatial light modulators to realize millions of neurons. However, a significant fraction of computation time and energy is consumed by the nonlinear activation function that is typically implemented using a camera sensor. Here, we propose a novel surface-normal photodetector (SNPD) with an optical-in–electrical-out (O–E) nonlinear response to replace the camera sensor that enables about three orders of magnitude faster (5.7 µs response time) and more energy efficient (less than 10 nW/pixel) response. Direct efficient vertical optical coupling, polarization insensitivity, inherent nonlinearity with no control electronics, low optical power requirements, and the possibility of implementing large scale arrays make the SNPD a promising O–E nonlinear activation function for diffractive ONNs. To show the applicability of the proposed neural nonlinearity, successful classification simulations of the MNIST and Fashion MNIST datasets using the measured response of SNPD with accuracy comparable to that of an ideal ReLU function are demonstrated.

Background: Despite being one of the safest, most effective treatments for severe mood disorders, the therapeutic mechanisms of electroconvulsive therapy remain unknown. Electroconvulsive seizure (ECS) induces rapid, high-level expression of immediate early genes (IEGs) and brain-derived neurotrophic factor (BDNF), in addition to stimulation of neurogenesis and dendritic remodeling of dentate gyrus (DG) neurons. We have previously shown that this upregulation of BDNF fails to occur in the hippocampus of mice lacking the IEG Egr3. Since BDNF influences neurogenesis and dendritic remodeling, we hypothesized that Egr3−/− mice will exhibit deficits in neurogenesis and dendritic remodeling in response to ECS. Objective: To test this hypothesis, we examined dendritic remodeling and cellular proliferation in the DG of Egr3−/− and wild-type mice following repeated ECS. Methods: Mice received 10 daily ECSs. Dendritic morphology was examined in Golgi-Cox-stained tissue and cellular proliferation was analyzed through bromodeoxyuridine (BrdU) immunohistochemistry and confocal imaging. Results: Serial ECS in mice results in dendritic remodeling, increased spine density, and cellular proliferation in the DG. Loss of Egr3 alters the dendritic remodeling induced by serial ECS but does not change the number of dendritic spines or cellular proliferation consequences of ECS. Conclusion: Egr3 influences the dendritic remodeling induced by ECS but is not required for ECS-induced proliferation of hippocampal DG cells.

Abstract Dentin sialophosphoprotein (DSPP) is primarily expressed by differentiated odontoblasts (dentin-forming cells), and transiently expressed by presecretory ameloblasts (enamel-forming cells). Disease-causing DSPP mutations predominantly fall into two categories: 5’ mutations affecting targeting and trafficking, and 3’ − 1 frameshift mutations converting the repetitive, hydrophilic, acidic C-terminal domain into a hydrophobic one. We characterized the dental phenotypes and investigated the pathological mechanisms of Dspp P19L and Dspp −1fs mice that replicate the two categories of human DSPP mutations. In Dspp P19L mice, dentin is less mineralized but contains dentinal tubules. Enamel mineral density is reduced. Intracellular accumulation and ER retention of DSPP is observed in odontoblasts and ameloblasts. In Dspp −1fs mice, a thin layer of reparative dentin lacking dentinal tubules is deposited. Odontoblasts show severe pathosis, including intracellular accumulation and ER retention of DSPP, strong ubiquitin and autophagy activity, ER-phagy, and sporadic apoptosis. Ultrastructurally, odontoblasts show extensive autophagic vacuoles, some of which contain fragmented ER. Enamel formation is comparable to wild type. These findings distinguish molecular mechanisms underlying the dental phenotypes of Dspp P19L and Dspp −1fs mice and support the recently revised Shields classification of dentinogenesis imperfecta caused by DSPP mutations in humans. The Dspp −1fs mice may be valuable for the study of autophagy and ER-phagy.

Atmospheric CH4 is the second-largest anthropogenic contributor to global warming. However, its emissions, components, spatial–temporal variations and projected changes still remain largely uncertain from city to national scales. CH4 emissions from waste treatment (including solid waste landfills, solid waste incineration and sewage) account for >50 % of total anthropogenic CH4 emissions at the city scale, and considering the high temperature sensitivity of CH4 emission factors (EFs) to biological-process-based sources such as waste treatment, large differences will occur when estimating future CH4 emissions under different global warming scenarios. Furthermore, the relationships between temperature and waste treatment CH4 emissions have only been studied in a few site-specific studies and lack representativity for whole cities, which contain various biophysical conditions and show heterogeneous distribution. The above factors cause uncertainty in the evaluation of city-scale CH4 emissions (especially from waste treatments), and projected changes still remain unexplored. Here we conduct the first tower-based CH4 observation network with three sites in Hangzhou, which is located in the developed Yangtze River Delta (YRD) area and ranks as one of the largest megacities in China. We found the a priori total annual anthropogenic CH4 emissions and those from waste treatment were overestimated by 36.0 % and 47.1 % in Hangzhou, respectively. In contrast, the total emissions in the larger region, i.e., Zhejiang Province or the YRD area, were slightly underestimated by 7.0 %. Emissions from waste treatment showed obvious seasonal patterns following air temperature. By using the linear relationship constructed between monthly waste treatment CH4 emissions and air temperature, we find the waste treatment EFs increase by 38 %–50 % with temperature increases of 10 ∘C. Together with projected temperature changes from four climate change scenarios, the global-warming-induced EFs in Hangzhou will increase at the rates of 2.2 %, 1.2 %, 0.7 % and 0.5 % per decade for IPCC AR5 (Intergovernmental Panel on Climate Change, the Fifth Assessment Report) RCP (Representative Concentration Pathway) 8.5, RCP6.0, RCP4.5 and RCP2.6 scenarios, respectively. And the EFs will finally increase by 17.6 %, 9.6 %, 5.6 % and 4.0 % at the end of this century. Additionally, the derived relative changes in China also show high heterogeneity and indicate large uncertainty in projecting future national total CH4 emissions. Hence, we strongly suggest temperature-dependent EFs and the positive feedback between global warming and CH4 emissions should be considered in future CH4 emission projections and climate change models.

Abstract Background Gender bias is behavior that shows favoritism towards one gender over another. Microaggressions are defined as subtle, often unconscious, discriminatory, or insulting actions that communicate demeaning or negative attitudes. Our objective was to explore how female otolaryngologists experience gender bias and microaggressions in the workplace. Methods Anonymous web-based cross-sectional Canadian survey was distributed to all female otolaryngologists (attendings and trainees) using the Dillman’s Tailored Design Method from July to August of 2021. Quantitative survey included demographic data, validated 44-item Sexist Microaggressions Experiences and Stress Scale (MESS) and validated 10-item General Self-efficacy scale (GSES). Statistical analysis included descriptive and bivariate analysis. Results Sixty out of 200 participants (30% response rate) completed the survey (mean age 37 ± 8.3 years, 55.0% white, 41.7% trainee, 50% fellowship-trained, 50% with children, mean 9.2 ± 7.4 years of practice). Participants scored mild to moderate on the Sexist MESS—Frequency (mean ± standard deviation) 55.8 ± 24.2 (42.3% ± 18.3%), Severity 46.0 ± 23.9 (34.8% ± 18.1%), Total 104.5 ± 43.7 (39.6% ± 16.6%) and high on GSES (32.7 ± 5.7). Sexist MESS score was not associated with age, ethnicity, fellowship-training, having children, years of practice, or GSES. In the sexual objectification domain, trainees had higher frequency (p = 0.04), severity (p = 0.02) and total MESS (p = 0.02) scores than attendings. Conclusions This was the first multicenter, Canada-wide study exploring how female otolaryngologists experience gender bias and microaggressions in the workplace. Female otolaryngologists experience mild to moderate gender bias, but have high self-efficacy to manage this issue. Trainees had more severe and frequent microaggressions than attendings in the sexual objectification domain. Future efforts should help develop strategies for all otolaryngologists to manage these experiences, and thereby improve the culture of inclusiveness and diversity in our specialty. Graphical Abstract

The ultrafast manipulation of quantum material has led to many novel and significant discoveries. Among them, the light-induced transient superconductivity in cuprates achieved by melting competing stripe orders represents a highly appealing accomplishment. However, recent investigations have shown that the notion of photoinduced superconductivity remains a topic of controversy, and its elucidation solely through c-axis time-resolved terahertz spectroscopy remains an arduous task. Here, we measure the in-plane and out-of-plane transient terahertz responses simultaneously in the stripe-ordered nonsuperconducting La_{2-x}Ba_{x}CuO_{4} after near-infrared excitations. We find that although a pump-induced reflectivity edge appears in the c-axis reflectance spectrum, the reflectivity along the CuO_{2} planes decreases simultaneously, indicating an enhancement in the scattering rate of quasiparticles. This in-plane transient response is clearly distinct from the features associated with superconducting condensation. Therefore, we conclude the out-of-plane transient responses cannot be explained by an equivalent of Josephson tunneling. Notably, those pump-induced terahertz responses remain consistent even when we vary the near-infrared optical pump wavelengths and hole concentrations. Our results provide critical evidence that transient three-dimensional superconductivity cannot be induced by melting the competing stripe orders with pump pulses whose photon energy is much higher than the superconducting gap of cuprates.

Alkali antimonide semiconductor photocathodes provide a promising platform for the generation of high-brightness electron beams, which are necessary for the development of cutting-edge probes, including x-ray free electron lasers and ultrafast electron diffraction. Nonetheless, to harness the intrinsic brightness limits in these compounds, extrinsic degrading factors, including surface roughness and contamination, must be overcome. By exploring the growth of CsxSb thin films monitored by in situ electron diffraction, the conditions to reproducibly synthesize atomically smooth films of CsSb on 3C–SiC (100) and graphene-coated TiO2 (110) substrates are identified, and detailed structural, morphological, and electronic characterization is presented. These films combine high quantum efficiency in the visible (up to 1.2% at 400 nm), an easily accessible photoemission threshold of 566 nm, low surface roughness (down to 600 pm on a 1 μm scale), and a robustness against oxidation up to 15 times greater than Cs3Sb. These properties lead us to suggest that CsSb has the potential to operate as an alternative to Cs3Sb in electron source applications where the demands of the vacuum environment might otherwise preclude the use of traditional alkali antimonides.

Density fluctuations near the QCD critical point can be probed via an intermittency analysis in relativistic heavy-ion collisions. We report the first measurement of intermittency in Au+Au collisions at sNN = 7.7-200 GeV measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The scaled factorial moments of identified charged hadrons are analyzed at mid-rapidity and within the transverse momentum phase space. We observe a power-law behavior of scaled factorial moments in Au+Au collisions and a decrease in the extracted scaling exponent (ν) from peripheral to central collisions. The ν is consistent with a constant for different collisions energies in the mid-central (10-40%) collisions. Moreover, the ν in the 0-5% most central Au+Au collisions exhibits a non-monotonic energy dependence that reaches a minimum around sNN = 27 GeV. The physics implications on the QCD phase structure are discussed.

We report on new measurements of elliptic flow (v2) of electrons from heavy-flavor hadron decays at mid-rapidity (|y|

Minimally invasive radical nephroureterectomy (RNU) decreases length of hospital stay compared to open RNU. We describe and demonstrate with video the first report of an outpatient robotic RNU.

Background: Despite the historic association of higher prostate cancer volume with worse oncologic outcomes, little is known about the impact of tumor volume on cancer biology. Objective: To characterize the relationship between tumor volume (measured by percent positive cores [PPC]) and cancer biology (measured by Decipher genomic risk classifier [GC]) in men who underwent prostate biopsy. Design, setting, and participants: Prostate biopsies from 52 272 men profiled with Decipher captured in a population-based prospective tumor registry were collected from 2016 to 2021. Outcome measurements and statistical analysis: The degree of distribution and correlation of PPC with a GC score across grade group (GG) strata were examined using the Mann-Whitney U test, Pearson correlation coefficient, and multivariable linear regression controlled for clinicopathologic characteristics. Results and limitations: A total of 38 921 (74%) biopsies passed quality control (14 331 GG1, 16 159 GG2, 5661 GG3, 1775 GG4, and 995 GG5). Median PPC and GC increased with sequentially higher GG. There was an increasingly positive correlation (r) between PPC and GC in GG2–5 prostate cancer (r [95% confidence interval {CI}]: 0.07 [0.5, 0.8] in GG2, 0.15 [0.12, 0.17] in GG3, 0.20 [0.15, 0.24] in GG4, and 0.25 [0.19, 0.31] in GG5), with no correlation in GG1 disease (r = 0.01, 95% CI [–0.001, 0.03]). In multivariable linear regression, GC was significantly associated with higher PPC for GG2–5 (all p

In order to acquire precise depth maps, depth completion is a fundamental method for autonomous vehicles and robotics. Recent methods mainly focus on fusing multi-model information from sparse depth maps and color images to recover dense depth maps. Previous researches have made remarkable contributions in predicting depth values, but how to better fuse multi-model features, and how to better restore details are still two main issues. Aiming at these two issues, we propose a fusion net composed of two-branch backbone and depth refinement module. The backbone aims to extract and combine the features of sparse depths and color images, in which we adopt the strategies of symmetric gated fusion and pixel-shuffle for cross-branch and branch-wise fusion respectively. Then, we designed a new module named dilation-pyramid convolution spatial propagation network (DP-CSPN) for depth refinement which enlarges the propagation neighborhoods and obtains more local affinities than CSPN. Finally, to better process details, we designed loss functions to achieve clearer edges as well as to be aware of tiny structures. Our method achieves the state-of-the-art (SoTA) performance in NYU-Depth-v2 Dataset and KITTI Depth Completion Dataset, and we got the achievement of top 5 in mobile intelligent photography and imaging (MIPI) challenge held by European Conference on Computer Vision (ECCV) 2022.

Background An increasing number of nonbinary patients are receiving gender-affirming procedures due to improved access to care. However, the preferred treatments for nonbinary patients are underdescribed. The purpose of this study was to investigate the goals and treatments of nonbinary patients. Methods A retrospective study of patients who self-identified as nonbinary from our institutional Gender Health Program was conducted. Patient demographics, clinical characteristics, surgical goals, and operative variables were analyzed. Results Of the 375 patients with gender dysphoria, 67 (18%) were nonbinary. Over half of the nonbinary patients were assigned male at birth (n = 57, 85%) and nearly half preferred the gender pronoun they/them/theirs (n = 33, 49%). A total of 44 patients (66%) received hormone therapy for an average of 2.5 ± 3.6 years, primarily estrogen (n = 39). Most patients (n = 46, 69%) received or are interested in gender-affirming surgery, of which, almost half were previously on hormone therapy (n = 32, 48%). The most common surgeries completed or desired were facial feminization surgery (n = 15, 22%), vaginoplasty (n = 15, 22%), mastectomy (n = 11, 16%), and orchiectomy (n = 9, 13%). Nonbinary patients who were assigned male at birth (NB-AMAB) were more often treated with hormones compared to nonbinary patients assigned female at birth (NB-AFAB) (72% vs. 30%, p = 0.010). Conversely, patients who were AFAB were more likely to complete or desire surgical intervention than those who were AMAB (100% vs. 63.0%, p

A global in situ data set for validation of ocean colour products from the ESA Ocean Colour Climate Change Initiative (OC-CCI) is presented. This version of the compilation, starting in 1997, now extends to 2021, which is important for the validation of the most recent satellite optical sensors such as Sentinel 3B OLCI and NOAA-20 VIIRS. The data set comprises in situ observations of the following variables: spectral remote-sensing reflectance, concentration of chlorophyll-a, spectral inherent optical properties, spectral diffuse attenuation coefficient, and total suspended matter. Data were obtained from multi-project archives acquired via open internet services or from individual projects acquired directly from data providers. Methodologies were implemented for homogenization, quality control, and merging of all data. Minimal changes were made on the original data, other than conversion to a standard format, elimination of some points, after quality control and averaging of observations that were close in time and space. The result is a merged table available in text format. Overall, the size of the data set grew with 148 432 rows, with each row representing a unique station in space and time (cf. 136 250 rows in previous version; Valente et al., 2019). Observations of remote-sensing reflectance increased to 68 641 (cf. 59 781 in previous version; Valente et al., 2019). There was also a near tenfold increase in chlorophyll data since 2016. Metadata of each in situ measurement (original source, cruise or experiment, principal investigator) are included in the final table. By making the metadata available, provenance is better documented and it is also possible to analyse each set of data separately. The compiled data are available at https://doi.org/10.1594/PANGAEA.941318 (Valente et al., 2022).

Abstract Partons traversing the strongly interacting medium produced in heavy-ion collisions are expected to lose energy depending on their color charge and mass. We measure the nuclear modification factors for charm- and bottom-decay electrons, defined as the ratio of yields, divided by the number of binary nucleon–nucleon collisions, in $$\sqrt{s_{\textrm{NN}}}=200$$ s NN = 200 GeV Au+Au collisions to p+p collisions ( $$R_{\textrm{AA}}$$ R AA ), or in central to peripheral Au+Au collisions ( $$R_{\textrm{CP}}$$ R CP ). We find the bottom-decay electron $$R_{\textrm{AA}}$$ R AA and $$R_{\textrm{CP}}$$ R CP to be significantly higher than those of charm-decay electrons. Model calculations including mass-dependent parton energy loss in a strongly coupled medium are consistent with the measured data. These observations provide evidence of mass ordering of charm and bottom quark energy loss when traversing through the strongly coupled medium created in heavy-ion collisions.

Abstract How well a surgery is performed impacts a patient’s outcomes; however, objective quantification of performance remains an unsolved challenge. Deconstructing a procedure into discrete instrument-tissue “gestures” is a emerging way to understand surgery. To establish this paradigm in a procedure where performance is the most important factor for patient outcomes, we identify 34,323 individual gestures performed in 80 nerve-sparing robot-assisted radical prostatectomies from two international medical centers. Gestures are classified into nine distinct dissection gestures (e.g., hot cut) and four supporting gestures (e.g., retraction). Our primary outcome is to identify factors impacting a patient’s 1-year erectile function (EF) recovery after radical prostatectomy. We find that less use of hot cut and more use of peel/push are statistically associated with better chance of 1-year EF recovery. Our results also show interactions between surgeon experience and gesture types—similar gesture selection resulted in different EF recovery rates dependent on surgeon experience. To further validate this framework, two teams independently constructe distinct machine learning models using gesture sequences vs. traditional clinical features to predict 1-year EF. In both models, gesture sequences are able to better predict 1-year EF (Team 1: AUC 0.77, 95% CI 0.73–0.81; Team 2: AUC 0.68, 95% CI 0.66–0.70) than traditional clinical features (Team 1: AUC 0.69, 95% CI 0.65–0.73; Team 2: AUC 0.65, 95% CI 0.62–0.68). Our results suggest that gestures provide a granular method to objectively indicate surgical performance and outcomes. Application of this methodology to other surgeries may lead to discoveries on methods to improve surgery.

Abstract Objectives To report the results of a pooled analysis evaluating the cancer detection rates, complications, and tolerability of prostate biopsies performed using the PrecisionPoint Transperineal Access System. Patients and Methods The medical literature was reviewed to identify studies published prior to 1 October 2021 evaluating the PrecisionPoint device for performance of transperineal prostate biopsy. Pooled analyses were performed to assess overall and clinically significant cancer detection rates. Additionally, data on complications as well as patient tolerability of the procedure when performed under local anaesthesia were extracted. Results Transperineal biopsy with the PrecisionPoint Transperineal Access System achieved overall and clinically significant cancer detection rates of 67.9% and 42.6%, respectively. Among patients with Prostate Imaging Reporting and Data System 3, 4, and 5 lesions on prostate magnetic resonance imaging, clinically significant disease was found in 31.7%, 55.7%, and 71.8% of patients, respectively. Complications were rare, with sepsis reported in 4 (0.1%) of 3411 procedures despite frequent omission of antibiotic prophylaxis. Patients reported acceptable tolerability of the procedure when performed under local anaesthesia. Conclusions Within the available medical literature, there is uniform evidence supporting the use of the PrecisionPoint Transperineal Access System for performing prostate biopsy procedures. The reported cancer detection and infectious complication rates with this device are in line with other methods for performing transperineal prostate biopsy. A unique aspect of the PrecisionPoint device is its ability to facilitate performing transperineal prostate biopsy under local anaesthesia. This factor will likely lead to increased adoption of the beneficial transperineal approach to prostate biopsy.

Abstract Human ACP4 (OMIM*606362) encodes a transmembrane protein that belongs to histidine acid phosphatase (ACP) family. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J, OMIM#617297). While ACP activity has long been detected in developing teeth, its functions during tooth development and the pathogenesis of ACP4-associated AI remain largely unknown. Here, we characterized 2 AI1J families and identified a novel ACP4 disease-causing mutation: c.774_775del, p.Gly260Aspfs*29. To investigate the role of ACP4 during amelogenesis, we generated and characterized Acp4 R110C mice that carry the p.(Arg110Cys) loss-of-function mutation. Mouse Acp4 expression was the strongest at secretory stage ameloblasts, and the protein localized primarily at Tomes’ processes. While Acp4 heterozygous (Acp4 +/R110C) mice showed no phenotypes, incisors and molars of homozygous (Acp4 R110C/R110C) mice exhibited a thin layer of aplastic enamel with numerous ectopic mineralized nodules. Acp4 R110C/R110C ameloblasts appeared normal initially but underwent pathology at mid-way of secretory stage. Ultrastructurally, sporadic enamel ribbons grew on mineralized dentin but failed to elongate, and aberrant needle-like crystals formed instead. Globs of organic matrix accumulated by the distal membranes of defective Tomes’ processes. These results demonstrated a critical role for ACP4 in appositional growth of dental enamel probably by processing and regulating enamel matrix proteins around mineralization front apparatus.

Abstract Regulatory guidelines for tissue engineered products require stringent characterization during production and necessitate the development of novel, non-destructive methods to quantify key functional parameters for clinical translation. Traditional assessments of engineered tissues are destructive, expensive, and time consuming. Here, we introduce a non-destructive, inexpensive, and rapid sampling and analysis system that can continuously monitor the mechanical, biochemical, and structural properties of a single sample over extended periods of time. The label-free system combines the imaging modalities of fluorescent lifetime imaging and ultrasound backscatter microscopy through a fiber-based interface for sterile monitoring of tissue quality. We tested the multimodal system using tissue engineered articular cartilage as an experimental model. We identified strong correlations between optical and destructive testing. Combining FLIm and UBM results, we created a novel statistical model of tissue homogeneity that can be applied to tissue engineered constructs prior to implantation. Continuous monitoring of engineered tissues with this non-destructive system has the potential for in-process monitoring of tissue engineered products, reducing costs and improving quality controls in research, manufacturing, and clinical applications.

ABSTRACT As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, mutations arise that will allow the virus to evade immune defenses and therapeutics. Assays that can identify these mutations can be used to guide personalized patient treatment plans. Digital PCR (dPCR) is a fast and reliable complement to whole-genome sequencing that can be used to discriminate single nucleotide polymorphisms (SNPs) in template molecules. Here, we developed a panel of SARS-CoV-2 dPCR assays and demonstrate its applications for typing variant lineages and therapeutic monoclonal antibody resistance. We first designed multiplexed dPCR assays for SNPs located at residue 3395 in the orf1ab gene that differentiate the Delta, Omicron BA.1, and Omicron BA.2 lineages. We demonstrate their effectiveness on 596 clinical saliva specimens that were sequence verified using Illumina whole-genome sequencing. Next, we developed dPCR assays for spike mutations R346T, K444T, N460K, F486V, and F486S, which are associated with host immune evasion and reduced therapeutic monoclonal antibody efficacy. We demonstrate that these assays can be run individually or multiplexed to detect the presence of up to 4 SNPs in a single assay. We perform these dPCR assays on 81 clinical saliva SARS-CoV-2-positive specimens and properly identify mutations in Omicron subvariants BA.2.75.2, BM.1.1, BN.1, BF.7, BQ.1, BQ.1.1, and XBB. Thus, dPCR could serve as a useful tool to determine if clinical specimens contain therapeutically relevant mutations and inform patient treatment. IMPORTANCE Spike mutations in the SARS-CoV-2 genome confer resistance to therapeutic monoclonal antibodies. Authorization for treatment options is typically guided by general trends of variant prevalence. For example, bebtelovimab is no longer authorized for emergency use in the United States due to the increased prevalence of antibody-resistant BQ.1, BQ.1.1, and XBB Omicron subvariants. However, this blanket approach limits access to life-saving treatment options to patients who are otherwise infected with susceptible variants. Digital PCR assays targeting specific mutations can complement whole-genome sequencing approaches to genotype the virus. In this study, we demonstrate the proof of concept that dPCR can be used to type lineage defining and monoclonal antibody resistance-associated mutations in saliva specimens. These findings show that digital PCR could be used as a personalized diagnostic tool to guide individual patient treatment.

The deconfined quark-gluon plasma (QGP) created in relativistic heavy-ion collisions enables the exploration of the fundamental properties of matter under extreme conditions. Noncentral collisions can produce strong magnetic fields on the order of 10^{18} G, which offers a probe into the electrical conductivity of the QGP. In particular, quarks and antiquarks carry opposite charges and receive contrary electromagnetic forces that alter their momenta. This phenomenon can be manifested in the collective motion of final-state particles, specifically in the rapidity-odd directed flow, denoted as v_{1}(y). Here, we present the charge-dependent measurements of dv_{1}/dy near midrapidities for π^{±}, K^{±}, and p(p[over ¯]) in Au+Au and isobar (_{44}^{96}Ru+_{44}^{96}Ru and _{40}^{96}Zr+_{40}^{96}Zr) collisions at sqrt[s_{NN}]=200 GeV, and in Au+Au collisions at 27 GeV, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The combined dependence of the v_{1} signal on collision system, particle species, and collision centrality can be qualitatively and semiquantitatively understood as several effects on constituent quarks. While the results in central events can be explained by the u and d quarks transported from initial-state nuclei, those in peripheral events reveal the impacts of the electromagnetic field on the QGP. Our data put valuable constraints on the electrical conductivity of the QGP in theoretical calculations.

We present the first catalog of very-high-energy and ultra-high-energy gamma-ray sources detected by the Large High Altitude Air Shower Observatory. The catalog was compiled using 508 days of data collected by the Water Cherenkov Detector Array from 2021 March to 2022 September and 933 days of data recorded by the Kilometer Squared Array from 2020 January to 2022 September. This catalog represents the main result from the most sensitive large coverage gamma-ray survey of the sky above 1 TeV, covering decl. from −20° to 80°. In total, the catalog contains 90 sources with an extended size smaller than 2° and a significance of detection at >5 σ . Based on our source association criteria, 32 new TeV sources are proposed in this study. Among the 90 sources, 43 sources are detected with ultra-high energy ( E > 100 TeV) emission at >4 σ significance level. We provide the position, extension, and spectral characteristics of all the sources in this catalog.