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The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

Greenfield's theory linking sociodemographic change to dynamic cultural values for family interdependence versus individual independence is applied to sexual and gender role socialization and development. The theory explains how cultural pathways for sexual and gender-role development transform in concert with sociodemographic changes: urbanization, formal schooling, capitalism, and communication technologies. As environments become more urban, commercial, and technological, with more opportunities for formal education, sexual development moves away from the ideals of procreation and family responsibility and toward the ideals of personal pleasure and personal responsibility. At the same time, gender-role development moves away from the ideals of complementary and ascribed gender roles and toward chosen and equal gender roles. We present psychological, anthropological, and sociological evidence for these trends in a variety of communities undergoing social and ecological change. © 2014 by the American Anthropological Association.

Foam cell formation is the hallmark of early atherosclerosis. Lipid uptake by scavenger receptors (SR) in macrophages initiates chronic proinflammatory cascades linked to atherosclerosis. It has been reported that the upregulation of cholesterol efflux may be protective in the development of atherosclerosis. Ellagic acid, a polyphenolic compound mostly found in berries, walnuts, and pomegranates, possesses antioxidative, growth-inhibiting and apoptosis-promoting activities in cancer cells. However, the antiatherogenic actions of ellagic acid are not well defined. The current study elucidated oxidized LDL handling of ellagic acid in J774A1 murine macrophages. Noncytotoxic ellagic acid suppressed SR-B1 induction and foam cell formation within 6 h after the stimulation of macrophages with oxidized LDL, confirmed by Oil red O staining of macrophages. Ellagic acid at ≤5 μmol/L upregulated PPARγ and ATP binding cassette transporter-1 in lipid-laden macrophages, all responsible for cholesterol efflux. In addition, 5 μmol/L ellagic acid accelerated expression and transcription of the nuclear receptor of liver X receptor-α highly implicated in the PPAR signaling. Furthermore, ellagic acid promoted cholesterol efflux in oxidized LDL-induced foam cells. These results provide new information that ellagic acid downregulated macrophage lipid uptake to block foam cell formation of macrophages and boosted cholesterol efflux in lipid-laden foam cells. Therefore, dietary and pharmacological interventions with berries rich in ellagic acid may be promising treatment strategies to interrupt the development of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: The authors conducted a comprehensive review and integration of insights from 4 webinars hosted by the International Society for the Advancement of Spine Surgery (ISASS) to arrive at recommendations for best clinical practices for guideline development for endoscopic spine surgery. This perspective article discusses the limitations of traditional surgical trials and amalgamates surgeons' experience and research on various cutting-edge techniques., Methods: Data were extracted from surveys conducted during each webinar session involving 3639 surgeons globally. The polytomous Rasch model was employed to analyze responses, ensuring a robust statistical assessment of surgeon endorsements and educational impacts and focusing on operative nuances and experience-based outcomes. Bias detection was performed using the differential item functioning test., Results: The ISASS webinars provided a dynamic platform for discussing advances in endoscopic spine surgery, identifying a range of high-value procedures from basic discectomies to complex lumbar interbody fusions. Each high-value endoscopic spine surgery was highlighted in separate peer-reviewed publications, which form the basis for this summary document that synthesizes key takeaways from these webinars. High-value clinical applications of endoscopic spine surgery, primarily defined as higher-intensity endorsement transformation from the pre- to postwebinar survey with a shift to higher mean logit locations of test items both with unbiased and orderly threshold progression, were: (a) Percutaneous interlaminar endoscopic decompression for lateral canal stenosis, (b) transforaminal debridement of low-grade degenerative spondylolisthesis, (c) transforaminal full-endoscopic interbody fusion for hard disc herniation, (d) endoscopic standalone lumbar interbody fusion, (e) endoscopic debridement of spondylolytic spondylolisthesis, and (f) posterior cervical foraminotomy for herniated disc and bony stenosis., Conclusions: The ISASS webinar series has significantly impacted surgeons' education and contributed to the identification of high-value endoscopic spine surgery practices that may serve as a cornerstone for surgeon training standards, policy, and guidelines development. Ongoing research on technological advancements and expansions of clinical indications combined with systematic review is expected to refine the recommendations on high-value endoscopic spinal surgeries recommended for enhanced reimbursement., Clinical Relevance: Assessing surgeon confidence and acceptance of endoscopic spinal surgeries using polytomous Rasch analysis., Level of Evidence: Level 2 (inferential) and 3 (observational) evidence because Rasch analysis provides statistical validation of instruments rather than direct clinical outcomes., Competing Interests: Declaration of Conflicting Interests : The authors volunteered their time and internal resources to support the design and conduction of this research study. All authors aided in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The authors declare no conflict of interest relevant to this research, and there was no personal circumstance or interest that may be perceived as inappropriately influencing the representation or interpretation of reported research results. This research was not compiled to enrich anyone., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

The outcome of 221 patients with bulky (≥10 cm) classic Hodgkin lymphoma (cHL) treated with doxorubicin, bleomycin, vinblastine, dacarbazine and consolidative radiotherapy (RT) only in those with a positive end-of-treatment (EOT) positron emission tomography (PET) scan was evaluated. With a median follow-up of 9.6 years, 5- and 10-year progression-free survival (PFS) in EOT PET-negative cases were 94.0% and 90.4%, respectively, and in PET-positive cases, 5/10-year PFS was 64.6% (p < 0.001), with 15% overall receiving RT. Five-year PFS for Deauville (D) score DX/D1-3 was 93.6%, compared with D4 66.7% (p < 0.001) and D5 33.3% (p < 0.001). Omission of RT in EOT PET-negative cases is associated with excellent long-term outcomes in bulky cHL., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Prcis: A higher STOP-BANG score and loud snoring, observed breathing interruptions during sleep, hypertension, and wide neck circumference were individually and in combination associated with high intraocular pressure in Koreans aged 40 years and older., Purpose: To evaluate the relationship between intraocular pressure (IOP) and the risk of obstructive sleep apnea (OSA)., Methods: In this population-based, cross-sectional study, we included Korean adults aged 40 years or above recruited between 2019 and 2021. 6315 subjects were included from the Korea National Health and Nutrition Examination Survey Ⅷ database. The risk of OSA was measured by STOP-BANG questionnaire. The IOPs were measured using rebound tonometer. Logistic regression was used to analyze the association between IOP quartiles (highest quartile vs. lower 1-3rd quartiles) with OSA risk after adjusting for sociodemographic characteristics, lifestyle, and diabetes., Results: The adjusted odds ratio for high IOP, was 1.27 (95% CI 1.12 to 1.43) for participants with a STOP-BANG score of 3 to 8 compared with those with a score of 0 to 2. Participants with loud snoring, observed breathing interruptions during sleep, hypertension, or wide neck circumference had 24%-40% higher odds of high IOP than those without these components. The odds ratio for high IOP in the group with all four factors was 2.09 times higher (95% CI 1.26 to 3.46) than in the group without these factors., Conclusions: A higher STOP-BANG score was associated with an increased risk of high IOP in Koreans aged 40 years and older. Furthermore, among the STOP-BANG components, loud snoring, observed breathing interruptions during sleep, hypertension, and wide neck circumference were individually and in combination associated with high IOP., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The serine/threonine kinase 17B (STK17B) is involved in setting the threshold for T cell activation and its absence sensitizes T cells to suboptimal stimuli. Consequently, STK17B represents an attractive potential target for cancer immunotherapy., Methods: To assess the potential of STK17B as an immuno-oncology target, we developed potent and selective tool compounds from starting points in Blueprint Medicines Corporation's proprietary kinase inhibitor library. To characterize these molecules, enzyme and cellular assays for STK17A and STK17B were established to drive chemistry optimization. Mass spectrometry-based phosphoproteomics profiling with tool inhibitors led to the identification of Ser19 on myosin light chain 2 as STK17B substrate, which is then developed into a flow cytometry-based pharmacodynamic readout of STK17B inhibition both in vitro and in vivo ., Results: In a mouse T cell activation assay, STK17B inhibitors demonstrated the ability to enhance interleukin-2 (IL-2) production. Similarly, treatment with STK17B inhibitors resulted in stronger cytokine secretion in human T cells activated using a T cell bispecific antibody. Subsequent chemistry optimization led to the identification of a highly selective and orally bioavailable tool compound, BLU7482. In vivo , STK17B inhibition led to dose-dependent modulation of myosin light chain 2 phosphorylation and enhanced priming of naïve T cells, as determined by upregulation of CD69, IL-2 and interferon-γ secretion. In line with increased T cell activation, treatment with STK17B inhibitor enhanced antitumor activity of anti-PD-L1 antibody in the MCA205 model., Conclusions: In summary, we successfully identified and optimized STK17B kinase inhibitors which led to increased T cell responses in vitro and in vivo . This allowed us to evaluate the potential of STK17B inhibition as an approach for cancer immunotherapy., Competing Interests: Authors FS, JEC, RC, CDS, JG, JLK, CK, KM, RM, EP, YT, TT, RW, RW, and MD were employed by the company Blueprint Medicines Corporation at the time of the study. FS, JG, RC, JK, CK, KM, EP, YT, RM, TT, and RW hold stocks and shares in Blueprint Medicines Corporation. Authors FR, JE, HF, LG, PJ, AM, UH, ST, MT, and JRB were employed by the company F. Hoffmann-La Roche Ltd. at the time of the study. FR and JRB hold stocks in F. Hoffmann-La Roche Ltd. JEC is currently affiliated with Reverie Labs, Cambridge, MA, USA. CDS is currently affiliated with Curie.Bio, Boston, MA, USA. NP is currently affiliated with ROME therapeutics, Boston, MA, USA. ST is currently affiliated with Altos Labs, Los Altos, CA, USA. RW is currently an independent consultant. MD is currently affiliated with Atavistik Bio, Cambridge, MA, USA. The authors declare that this research received funding from Blueprint Medicines Corporation and F. Hoffmann-La Roche Ltd. The sponsor was involved in the study design, collection, analysis, and interpretation of data, as well as data checking of information provided in the manuscript., (Copyright © 2024 Scheuplein, Renner, Campbell, Campbell, De Savi, Eckmann, Fischer, Ge, Green, Jakob, Kim, Kinkema, McGinn, Medina, Müller, Perez, Perola, Timsit, Traore, Hopfer, Tyanova, Tzouros, Wang, Woessner, Dorsch and Bischoff.)

Background/objectives: UV radiation is a major factor contributing to DNA damage in skin cells, including stem cells and mesenchymal stem cells, leading to the depletion of these crucial cells. This study examined whether a mixture of Indian gooseberry and barley sprout (IB) could inhibit UVB irradiation and 3-isobutyl-1-methylxanthine (IBMX)-induced photoaging and oxidative stress in the skin using HaCaT, Hs27, and B16F10 cells., Materials/methods: The moisturizing-related factors, the collagen synthesis-related c-Jun N-terminal kinase (JNK)/c-Fos/c-Jun/matrix metalloproteinases (MMPs) pathway, and the melanogenesis-related cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-responsive binding protein (CREB)/melanocyte inducing transcription factor (MITF)/tyrosinase-related protein (TRP)/tyrosinase activation pathways were analyzed in vitro by an enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot analysis., Results: The IB complex increased the hyaluronic acid and sphingomyelin levels and the collagenase inhibitory activity, enhanced hydration-related factors, including collagen, hyaluronic acid synthase ( HAS ), elastin , long chain base subunit 1 ( LCB1 ) ( serine palmitoyltransferase ; SPT ), and delta 4-desaturase sphingolipid 1 ( DEGS1 ), modulated the inflammatory cytokines levels, antioxidant enzyme activities and the NF-κB/MMPs/cyclooxygenase-2 (COX-2) pathway in UVB-irradiated HaCaT cells, and inhibited wrinkle formation by down-regulation of the JNK/c-Fos/c-Jun/MMP pathway and up-regulation of the transforming growth factor-β receptor I ( TGFβR1 )/small mothers against decapentaplegic homolog (Smad3)/ procollagen type І pathway in UVB-irradiated Hs27 cells. Moreover, the IB complex prevented melanin production by down-regulating the PKA/CREB/MITF/TRP-1/TRP-2 pathway in IBMX-induced B16F10 cells., Conclusion: These findings suggest that the IB complex has the potential to serve as a safeguard, shielding the skin from UVB radiation-induced photo-damage., Competing Interests: Conflict of Interest: Mi-Ryeong Park, Soyoung Kim, and Jong-Lae Kim are current employees of a commercial company that holds a patent for the IB complex. Mi-Ryeong Park, Soyoung Kim, and Jong-Lae Kim are listed as inventors., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

In medicine, difficulty integrating work and home can lead to decreased job satisfaction, diminished well-being, and increased turnover. Understanding the experience of pediatric hospitalists can provide insights into building a stable, long-term workforce. We aim to examine gender differences in work-life balance and parental leave for physicians practicing Pediatric Hospital Medicine., Methods: This was a cross-sectional survey study of 1096 pediatric hospitalists. Responses were collected via an online survey platform and summarized using descriptive statistics, including frequency distributions and measures of central tendency. A multivariable logistic regression was used to examine associated variables and work-life balance satisfaction. We analyzed free responses on parental leave to provide nuance to quantitative survey data., Results: Five hundred and sixty-five respondents (52% response rate) completed the survey with 71% women. 343 (62%) prioritize work-life balance in career decision-making. Women report taking on more household responsibilities than their partners (41.4% vs. 8.4%; p < .001) including a larger percentage of caregiving and domestic tasks. Female gender and performing <50% caregiving were associated with decreased work-life balance satisfaction; performing <50% domestic tasks increased satisfaction. Median parental leaves were 4 weeks, with men taking significantly shorter leaves (3.5 vs. 6 weeks; p < .001) and more "paid back" time off., Conclusion: Work-life balance is an important factor in career decisions for men and women. Women perceive carrying a larger load at home. Qualitative results suggest that parental leave may be inadequate in length and salary support for men and women. This study adds insights into work-life integration in PHM., (© 2024 Society of Hospital Medicine.)

Purpose: To compare the macular and optic disc vascular parameters in the unaffected fellow eyes of subjects with unilateral pseudoexfoliation syndrome (PXS) and controls using optical coherence tomography angiography (OCTA)., Methods: The medical records of 61 eyes of 61 patients were analyzed in a retrospective study. Of these, 30 eyes were unaffected fellow eyes and 31 eyes were control eyes. The vessel density (VD), perfusion density (PD) and foveal avascular zone (FAZ)-related parameters of the superficial capillary plexus (SCP) in the circumpapillary and macular area and the VD and PD of the deep capillary plexus (DCP) in the macular area were measured using OCTA after dilatation and were compared between two groups after adjustment for age, sex and axial length., Results: There were no statistically significant differences in sex ratio or mean age, central corneal thickness measurements, refractive errors, intraocular pressures and axial length between both groups (all P > 0.05). In the circumpapillary area, inferior VD and PD in the inner zone, as well as average, temporal, inferior, and nasal VD and PD in the outer zone were significantly reduced in the unaffected fellow eyes with unilateral PXS, while the circumpapillary retinal nerve fiber layer (RNFL) thicknesses were similar between groups. In the macular SCP, VDs were significantly lower in all sectors in the inner area and in the outer zones (p < 0.05 for all), PDs were significantly lower in all sectors (p < 0.05 for all) except the nasal sector of the outer zone (p = 0.003 for average, p = 0.029 for superior sector, p = 0.004 for temporal sector, p < 0.001 for inferior sector), and the FAZ circularity (p = 0.037) were significantly lower in the unaffected fellow eyes with unilateral PXS, whereas macular ganglion cell inner plexiform layer (GCIPL) thickness was similar between the two groups., Conclusions: Although circumpapillary RNFL and GCIPL thicknesses were similar between the two groups, VDs and PDs in the circumpapillary and macular SCP and FAZ circularity were significantly lower in the fellow eye of subjects with unilateral PXS., (© 2024. The Author(s).)

Primordial germ cells (PGCs) in avian species exhibit unique developmental features, including the ability to migrate through the bloodstream and colonize the gonads, allowing their isolation at various developmental stages. Several methods have been developed for the isolation of avian PGCs, including density gradient centrifugation, size-dependent separation, and magnetic-activated cell sorting (MACS) or fluorescence-activated cell sorting (FACS) using a stage-specific embryonic antigen-1 (SSEA-1) antibody. However, these methods present limitations in terms of efficiency and applicability across development stages. In particular, the specificity of SSEA-1 decreases in later developmental stages. Furthermore, surface markers that can be utilized for isolating or utilizing PGCs are lacking for wild birds, including zebra finches, and endangered avian species. To address this, we used single-cell RNA sequencing (scRNA-seq) to uncover novel PGC-specific surface markers in chicken and zebra finch. We screened for genes that were primarily expressed in the PGC population within the gonadal cells. Analyses of gene expression patterns and levels based on scRNA-seq, coupled with validation by RT-PCR, identified NEGR1 and SLC34A2 as novel PGC-specific surface markers in chickens and ESYT3 in zebra finches. Notably, these newly identified genes exhibited sustained expression not only during later developmental stages but also in reproductive tissues., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia., Methods: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer's disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses., Results: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18-7.18) and AD (HR, 3.22; 95% CI, 1.14-9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females., Conclusion: Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: The caregiving burden of the spousal caregivers (SCGs) to individuals with cognitive impairment poses public health challenges with adverse psychosocial and physiological effects. However, few studies have investigated the neurobiological impact of caregiving, particularly through the investigation of neuroinflammation and neurodegeneration., Methods: Using data from a longitudinal cohort at Chungnam National University Hospital, the relationship between caregiving burden, neuroinflammation and neurodegeneration was examined in 38 older adult couples over a 16-month period. Caregiving burden was assessed through a multifaceted approach. For factors related to the care recipient, we assessed cognitive function and neuropsychiatric symptoms. Factors regarding the SCGs included the measurement of perceived depression. Glial fibrillary acidic protein (GFAP) was used as a plasma biomarker for neuroinflammation and neurofilament light chain (NfL) for neurodegeneration. Regression analyses were adjusted for age, sex, apolipoprotein E status, follow-up interval, vascular risk factors, and physical activity., Results: Changes in depression among SCGs were significantly correlated with increased GFAP levels (p = 0.003), indicating that greater depressive symptoms during caregiving are associated with increased neuroinflammation. In contrast, no significant correlations were found between changes in cognitive function or neuropsychiatric symptoms in care recipients and the plasma biomarker levels of SCGs. Additionally, there was no significant association between changes in depression and NfL levels in SCGs., Conclusions: The psychological stress experienced by SCGs while caring for partners with cognitive impairment actively contributes to neuroinflammation, a well-known risk factor for various diseases. This study emphasizes the need to address psychological stress experienced by older adult caregivers., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Purpose: To represent 24-2 visual field (VF) losses of individual patients using a hybrid approach of archetypal analysis (AA) and fuzzy c-means (FCM) clustering., Methods: In this multicenter retrospective study, we classified characteristic patterns of 24-2 VF using AA and decomposed them with FCM clustering. We predicted the change in mean deviation (MD) through supervised machine learning from decomposition coefficient change. In addition, we compared the areas under the receiver operating characteristic curves (AUCs) of the decomposition coefficient slopes to detect VF progression using three criteria: MD slope, Visual Field Index slope, and pointwise linear regression analysis., Results: We identified 16 characteristic patterns (archetypes or ATs) of 24-2 VF from 132,938 VFs of 18,033 participants using AA. The hybrid approach using FCM revealed a lower mean squared error and greater correlation coefficient than the AA single approach for predicting MD change (all P ≤ 0.001). Three of 16 AUCs of the FCM decomposition coefficient slopes outperformed the AA decomposition coefficient slopes in detecting VF progression for all three criteria (AT5, superior altitudinal defect; AT10, double arcuate defect; AT13, total loss) (all P ≤ 0.028)., Conclusion: A hybrid approach combining AA and FCM to analyze 24-2 VF can visualize VF tests in characteristic patterns and enhance detection of VF progression with lossless decomposition., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

CD73 is a cell-surface ectoenzyme that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine, which in turn can promote resistance to immune checkpoint blockade therapy. Immune response may therefore be improved by targeting tumor CD73, and this possibility underlines the need to non-invasively assess tumor CD73 level. In this study, we developed a cysteine site-specific 89 Zr-labeled anti-CD73 ( 89 Zr-CD73) IgG immuno-PET technique that can image tumor CD73 expression in living bodies. Anti-CD73 IgG was reduced with tris(2-carboxyethyl)phosphine, underwent sulfohydryl moiety-specific conjugation with deferoxamine-maleimide, and was radiolabeled with 89 Zr. CT26 mouse colon cancer cells, CT26/CD73 cells engineered to constitutively overexpress CD73, and 4T1.2 mouse breast cancer cells underwent cell binding assays and western blotting. Balb/c nude mice bearing tumors underwent 89 Zr-CD73 IgG PET imaging and biodistribution studies. 89 Zr-CD73 IgG showed 20-fold higher binding to overexpressing CT26/CD73 cells compared to low-expressing CT26 cells, and moderate expressing 4T1.2 cells showed uptake that was 38.9 ± 1.51% of CT26/CD73 cells. Uptake was dramatically suppressed by excess unlabeled antibody. CD73 content proportionately increased in CT26 and CT26/CD73 cell mixtures was associated with linear increases in 89 Zr-CD73 IgG uptake. 89 Zr-CD73 IgG PET/CT displayed clear accumulation in CT26/CD73 tumors with greater uptake compared to CT26 tumors (3.13 ± 1.70%ID/g vs. 1.27 ± 0.31%ID/g at 8 days; P = 0.04). Specificity was further supported by low CT26/CD73 tumor-to-blood ratio of 89 Zr-isotype-IgG compared to 89 Zr-CD73 IgG (0.48 ± 0.08 vs. 2.68 ± 0.52 at 4 days and 0.53 ± 0.07 vs. 4.81 ± 1.02 at 8 days; both P < 0.001). Immunoblotting and immunohistochemistry confirmed strong CD73 expression in CT26/CD73 tumors and low expression in CT26 tumors. 4T1.2 tumor mice also showed clear 89 Zr-CD73 IgG accumulation at 8 days (3.75 ± 0.70%ID/g) with high tumor-to-blood ratio compared to 89 Zr-isotype-IgG (4.91 ± 1.74 vs. 1.20 ± 0.28; P < 0.005). 89 Zr-CD73 IgG specifically targeted CD73 on high expressing cancer cells in vitro and tumors in vivo. Thus, 89 Zr-CD73 IgG immuno-PET may be useful for the non-invasive monitoring of CD73 expression in tumors of living subjects., (© 2024. The Author(s).)

Background: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype., Methods: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems., Findings: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (β = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (β = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression., Interpretation: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: Gender-based disparities in salary exist in multiple fields of medicine. However, there is limited data examining gender inequities in salary in pediatric hospital medicine (PHM). Our primary objective was to assess whether gender-based salary differences exist in PHM. The secondary objective was to assess if, among women, the differences in salary varied on the basis of leadership positions or self-identified race and ethnicity., Methods: We conducted a survey-based, cross-sectional study of pediatric hospitalists in December 2021. Our primary outcomes were base and total salary, adjusted for the reported number of average weekly work hours. We performed subanalyses by presence of a leadership position, as well as race. We used a weighted t test using inverse probability weighting to compare the outcomes between genders., Results: A total of 559 eligible people responded to our survey (51.0%). After propensity score weighting, women's mean base salary was 87.7% of men's base (95% confidence interval [CI] 79.8%-96.4%, P < .01), and women's total salary was 85.6% of men's total (95% CI 73.2%-100.0%, P = .05) salary. On subgroup analysis of respondents with a leadership position, women's total salary was 80.6% of men's total salary (95% CI 68.7%-94.4%, P < .01). Although women who identified as white had base salaries that were 86.6% of white men's base salary (95% CI 78.5%-95.5%, P < .01), there was no gender-based difference noted between respondents that identified as nonwhite (88.4% [69.9%-111.7%] for base salary, 80.3% [57.2% to 112.7%])., Conclusions: Gender-based discrepancies in salary exists in PHM, which were increased among those with leadership roles. Continued work and advocacy are required to achieve salary equity within PHM., (Copyright © 2024 by the American Academy of Pediatrics.)

Background and Objectives: Gender-based communication differences are described in educational online communities, but have not been rigorously evaluated in medical online communities. Understanding gender differences in communication may provide insight into gender disparities in the medical profession. Our objective was to describe gender differences in post frequency, content, and language styles on the American Academy of Pediatrics Section on Hospital Medicine (SOHM) listserv., Methods: Posts were obtained from publicly available SOHM listserv archives. The first month of every quarter of 2019 and 2020 were reviewed. Two reviewers assigned a post topic (clinical, research, etc) and format (question vs statement) to all deidentified original posts (K = 1.0 topic, 0.89 format). Six trained reviewers assigned language styles (intraclass coefficient = 0.73, indicating good agreement)., Results: We analyzed 1592 posts: 287 original posts and 1305 responses. Frequency: Women authored 50% of posts. The 9 most frequent posters (7 men, 2 women) accounted for 19.5% of posts. Content: Men's posts had more words than women's (132.51 vs 112.3, P ≤ .01). Men were more likely to post about health policy and research (P < .001). Men were more likely to post statements compared with women (39% vs 21%, P < .001). Style: Men's posts were more likely to be coded adversarial (12.3% vs 5.5%, P < .001) authoritative (12.2% vs 6.5%, P < .001) or self-amplifying (6.5% vs 3.6%, P < .001)., Conclusions: Women contribute disproportionately fewer posts to the American Academy of Pediatrics SOHM listserv compared with their percentage in the subspecialty. We noted significant gender differences in language style and content, which may impact career development and online community inclusion., (Copyright © 2024 by the American Academy of Pediatrics.)

Objectives: Lung transplant warm ischemia-reperfusion injury (IRI) results in cellular injury, inflammation, and poor graft function. Mitsugumin 53 (MG53) is an endogenous protein with cell membrane repair properties and the ability to modulate the inflammasome. We hypothesize that the absence of circulating MG53 protein in the recipient increases IRI, and higher levels of circulating MG53 protein mitigate IRI associated with lung transplantation., Methods: To demonstrate protection, wild-type (wt) lung donor allografts were transplanted into a wt background, a MG53 knockout (mg53-/-), or a constitutively overexpressed MG53 (tissue plasminogen activator-MG53) recipient mouse after 1 hour of warm ischemic injury. Mice survived for 5 days after transplantation. Bronchioalveolar lavage, serum, and tissue were collected at sacrifice. Bronchioalveolar lavage, serum, and tissue markers of apoptosis and a biometric profile of lung health were analyzed., Results: mg53-/- mice had significantly greater levels of markers of overall cell lysis and endothelial cell injury. Overexpression of MG53 resulted in a signature similar to that of wt controls. At the time of explant, tissue plasminogen activator-MG53 recipient tissue expressed significantly greater levels of MG53, measured by immunohistochemistry, compared with mg53-/-, demonstrating uptake of endogenous overexpressed MG53 into donor tissue., Conclusions: In a warm IRI model of lung transplantation, the absence of MG53 resulted in increased cell injury and inflammation. Endogenous overexpression of MG53 in the recipient results in protection in the wt donor. Together, these data suggest that MG53 is a potential therapeutic agent for use in lung transplantation to mitigate IRI., Competing Interests: Conflict of Interest Statement J.M. is a founder of TRIM-edicine, Inc, a university spin-off biotechnology company that develops MG53 for regenerative medicine application. B.A.W. serves on the Clinical Events Committee of TransMedics OCS. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Lung transplantation is hampered by the lack of suitable donors. Previously, donors that were thought to be marginal or inadequate were discarded. However, new and exciting technology, such as ex vivo lung perfusion (EVLP), offers lung transplant providers extended assessment for marginal donor allografts. This dynamic assessment platform has led to an increase in lung transplantation and has allowed providers to use donors that were previously discarded, thus expanding the donor pool. Current perfusion techniques use cellular or acellular perfusates, and both have distinct advantages and disadvantages. Perfusion composition is critical to maintaining a homeostatic environment, providing adequate metabolic support, decreasing inflammation and cellular death, and ultimately improving organ function. Perfusion solutions must contain sufficient protein concentration to maintain appropriate oncotic pressure. However, current perfusion solutions often lead to fluid extravasation through the pulmonary endothelium, resulting in inadvertent pulmonary edema and damage. Thus, it is necessary to develop novel perfusion solutions that prevent excessive damage while maintaining proper cellular homeostasis. Here, we describe the application of a polymerized human hemoglobin (PolyhHb)-based oxygen carrier as a perfusate and the protocol in which this perfusion solution can be tested in a model of rat EVLP. The goal of this study is to provide the lung transplant community with key information in designing and developing novel perfusion solutions, as well as the proper protocols to test them in clinically relevant translational transplant models.

This study investigated the protective effects of a complex of Indian gooseberry and barley sprout (IB complex) on oxidative stress and skin damage caused by ultraviolet B irradiation in SHK-I hairless mice. The study examined the impact of IB complex on skin hydration, wrinkle formation, and melanogenesis using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and western blot analysis. The IB complex reduced skin hydration loss and wrinkle formation, while also demonstrating enhanced antioxidant activities. The IB complex maintained skin hydration via upregulation of hyaluronic acid and ceramide synthesis, including the regulation of hyaluronic acid synthase, long-chain ceramide formation, dihydroceramide desaturase 1 activity, and type I collagen production. The IB complex prevented wrinkle formation via downregulating JNK and upregulating TGF-β pathways. Moreover, IB complex blocked melanin production via inhibition of protein kinase A, cAMP response element-binding protein, and microphthalmia-associated transcription factor pathways. These results suggest that IB complex is a potential agent to protect the skin against photodamage caused by exposure to UVB radiation. The research protocols underwent approval from the Institutional Animal Care and Use Committee of Kyung Hee University (KHGASP-21-577), ensuring compliance with ethical standards.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease driven by gain-of-function variants in activin receptor-like kinase 2 (ALK2), the most common variant being ALK2 R206H . In FOP, ALK2 variants display increased and dysregulated signaling through the bone morphogenetic protein (BMP) pathway resulting in progressive and permanent replacement of skeletal muscle and connective tissues with heterotopic bone, ultimately leading to severe debilitation and premature death. Here, we describe the discovery of BLU-782 (IPN60130), a small-molecule ALK2 R206H inhibitor developed for the treatment of FOP. A small-molecule library was screened in a biochemical ALK2 binding assay to identify potent ALK2 binding compounds. Iterative rounds of structure-guided drug design were used to optimize compounds for ALK2 R206H binding, ALK2 selectivity, and other desirable pharmacokinetic properties. BLU-782 preferentially bound to ALK2 R206H with high affinity, inhibiting signaling from ALK2 R206H and other rare FOP variants in cells in vitro without affecting signaling of closely related homologs ALK1, ALK3, and ALK6. In vivo efficacy of BLU-782 was demonstrated using a conditional knock-in ALK2 R206H mouse model, where prophylactic oral dosing reduced edema and prevented cartilage and heterotopic ossification (HO) in both muscle and bone injury models. BLU-782 treatment preserved the normal muscle-healing response in ALK2 R206H mice. Delayed dosing revealed a short 2-day window after injury when BLU-782 treatment prevented HO in ALK2 R206H mice, but dosing delays of 4 days or longer abrogated HO prevention. Together, these data suggest that BLU-782 may be a candidate for prevention of HO in FOP.

Lung transplantation is the only definitive therapy for end-stage pulmonary disease. Less than 20 % of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality manifested by pulmonary edema, hypoxia, or trauma. Therefore, poor donor organ recovery and utilization are significant barriers to wider implementation of the life-saving therapy of transplantation. While ischemia reperfusion injury (IRI) is often identified as the underlying molecular insult leading to immediate poor lung function in the post-operative period, this injury encompasses several pathways of cellular injury in addition to the recruitment of the innate immune system to the site of injury to propagate this inflammatory cascade. Pyroptosis is a central molecular inflammatory pathway that is the most significant contributor to injury in this early post-operative phase. Pyroptosis is another form of programmed cell death and is often associated with IRI. The mitigation of pyroptosis in the early post-operative period following lung transplantation is a potential novel way to prevent poor allograft function and improve outcomes for all recipients. Here we detail the pyroptotic pathway, its importance in lung transplantation, and several therapeutic modalities that can mitigate this harmful inflammatory pathway., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)