Cross-sections for 43Sc, 44mSc, and 44gSc from two heavy ion reactions.

Two different heavy ion reactions were used to produce 43Sc (t12 = 3.891 h), 44gSc (t12 = 4.042 h), and 44mSc (t12 = 58.61 h) among other stable or long-lived chemically separable products. Production cross sections for 19F + 27Al and the reverse kinematic reaction 35Cl + natB were measured using an MC-SNICS ion source and the Notre Dame FN Tandem Accelerator. 19F beams from 35 to 60 MeV were produced with beam currents between 40-80 pnA and 35Cl beams were produced at six entrance energies with comparable beam currents. This work reports nuclear reaction cross sections 27Al (19F, x) 43Sc, 27Al (19F, pn) 44gSc, and 27Al (19F, pn) 44mSc at six energies between 35 and 60 MeV lab energy. Cross sections within the same energy range were measured for 27Al (19F, 3pn) 42K and 27Al (19F, 3p) 43K. Comparative measurements were performed for the same compound nucleus produced from natB(35Cl, x) 43Sc, natB(35Cl, pn) 44gSc, and natB(35Cl, pn) 44mSc. The measured thin target cross sections show an overestimation by several statistical models for the scandium radioisotopes. This is corroborated by the measured thick target production rates for both entrance channels. This may be due to angular momentum effects of a heavy ion entrance channel compared to light-ion production, but additional work is required to understand this discrepancy. These measurements demonstrate that the medically useful 43Sc, 44gSc, and 44mSc radioisotopes can be free of the long-lived contaminant 46Sc without the use of enriched targets, using heavy ion beams and robust target materials.

Intramedullary nail fixation versus open reduction and internal fixation for treatment of adult diaphyseal forearm fractures: a systematic review and meta-analysis.

BACKGROUND: Diaphyseal radius and ulna fractures require surgical fixation in adults. Open reduction and internal fixation (ORIF) have been considered the gold standard of treatment. The recent development of an interlocking intramedullary nail (IMN) has provided an alternative treatment method for these fractures. The objective of this meta-analysis is to compare the outcomes and complications of IMN versus ORIF for diaphyseal forearm fractures in adults. METHODS: MEDLINE and Embase were searched from January 1, 2000, through January 7, 2024. All English-language studies were included comparing radiographic and functional outcomes for interlocking IMN fixation and ORIF of diaphyseal forearm fractures in adults (age ≥ 18 years). Study demographics, fracture data, functional outcomes, radiographic outcomes, and complications were extracted. Study quality was determined using the ROBINS-I criteria for cohort studies and the Cochrane risk of bias 2.0 (RoB 2) tool for randomized controlled trials. Meta-analysis of included studies used odds ratios and standardized mean difference when appropriate. Data was analyzed using subgroups of all diaphyseal fractures (including isolated radius or ulna fractures) and those with BBFFs. RESULTS: Nine studies were included for analysis. There were 42 isolated radius, 80 isolated ulna, and 116 both-bone fractures (BBFF) treated with IMN and 36 radius, 81 ulna, and 116 both-bone fractures treated with ORIF. Compared to ORIF, IMN of diaphyseal forearm fractures appeared to be associated with shorter operative times and a lower overall complication rate. Time-to-union and the rate of nonunion following IMN were similar to ORIF. According to the Grace-Eversmann score, functional outcomes tended to be better following IMN, but DASH scores were similar between fixation strategies. CONCLUSIONS: Our findings suggest that interlocking IMN can be a safe and effective treatment option for simple and complex diaphyseal forearm fractures in adults. Further high-quality studies are needed to define indications for treating diaphyseal fractures with an interlocking IMN. LEVEL OF EVIDENCE: Therapeutic Level IV.

Widespread pain phenotypes impact treatment efficacy results in randomized clinical trials for interstitial cystitis/bladder pain syndrome: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain network study.

ABSTRACT: Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori primary outcome statistical significance criteria. Importantly, these studies also collected symptom questionnaire data that allowed us to retrospectively identify participants with and without widespread pain. Analyzing the treatment by the degree of widespread pain revealed a difference in outcome and statistical significance level for each trial. Participants with predominately local pain (ie, limited widespread pain symptoms) responded to therapy targeting local symptoms, whereas those with widespread pain did not. Alternatively, participants with widespread pain beyond their local pelvic pain responded to more centrally acting treatments. Our results suggest that differentiating patients based on widespread vs more localized pain is a key consideration for designing future clinical trials for conditions with variable pain profiles, such as IC/BPS and potentially other pain-based syndromic disorders.

Driver mutations associated with signatures of platinum sensitivity in germ cell tumors.

We sought to evaluate the genomic and transcriptomic landscapes in primary and metastatic germ cell tumors (GCTs; N = 138) to uncover factors that drive cisplatin resistance. Prevalence was calculated for platinum-resistant alterations (PRAs; KRAS, TP53, and KIT mutations, and MDM2 amplification) and high copy number amplifications (CNA ≥ 6 copies). Tumors were designated as chemo-naïve (PreC, N = 66) or post-chemotherapy (PostC, N = 17). A transcriptomic signature associated with platinum sensitivity (PSS, high suggests increased sensitivity) was applied. KIT mutations were observed in 14.5% of primary versus 1.8% of met and 0% of lymph. TP53 mutations were identified in 10% of primary GCTs versus 17% of met and 16.7% of lymph. MDM2 CNAs were similar between sites. PRA-positive PreC GCTs had significantly lower average PSS scores compared to PRA-negative tumors. Lower PSS scores in chemo-naïve tumors were associated with PRAs, suggesting a potential mechanism for platinum resistance.

Undiagnosed West Nile virus lineage 2d infection in a febrile patient from South-west Uganda, 2018.

We report the retrospective identification and subsequent recovery of a near-complete West Nile Virus lineage 2 genomes from a hospitalized patient with acute febrile illness in Uganda, using a combination of degenerate primer polymerase chain reaction screening and a novel 1200bp nanopore-based whole-genome amplicon sequencing scheme. This represents the first West Nile virus genome to be recovered from a human in Uganda since its discovery in 1937. Basic molecular rather than serological surveillance methods could be more widely deployed in the region to better diagnose febrile infections.

Single cell transcriptional analysis of human adenoids identifies molecular features of airway microfold cells.

The nasal, oropharyngeal, and bronchial mucosa are primary contact points for airborne pathogens like Mycobacterium tuberculosis (Mtb), SARS-CoV-2, and influenza virus. While mucosal surfaces can function as both entry points and barriers to infection, mucosa-associated lymphoid tissues (MALT) facilitate early immune responses to mucosal antigens. MALT contains a variety of specialized epithelial cells, including a rare cell type called a microfold cell (M cell) that functions to transport apical antigens to basolateral antigen-presenting cells, a crucial step in the initiation of mucosal immunity. M cells have been extensively characterized in the gastrointestinal (GI) tract in murine and human models. However, the precise development and functions of human airway M cells is unknown. Here, using single-nucleus RNA sequencing (snRNA-seq), we generated an atlas of cells from the human adenoid and identified 16 unique cell types representing basal, club, hillock, and hematopoietic lineages, defined their developmental trajectories, and determined cell-cell relationships. Using trajectory analysis, we found that human airway M cells develop from progenitor club cells and express a gene signature distinct from intestinal M cells. Surprisingly, we also identified a heretofore unknown epithelial cell type demonstrating a robust interferon-stimulated gene signature. Our analysis of human adenoid cells enhances our understanding of mucosal immune responses and the role of M cells in airway immunity. This work also provides a resource for understanding early interactions of pathogens with airway mucosa and a platform for development of mucosal vaccines.

Type-I IFNs induce GBPs and lysosomal defense in hepatocytes to control malaria.

Plasmodium parasites undergo development and replication within the hepatocytes before infecting the erythrocytes and initiating clinical malaria. Although type-I interferons (IFNs) are known to hinder Plasmodium infection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers a pathway of lysosomal fusion with the parasitophorous vacuole (PV) to help clear Plasmodium . Second, guanylate-binding protein (GBP) 1 disruption of the PV activates caspase-1 inflammasome, inducing pyroptosis to remove the infected host cells. Remarkably, both human and mouse hepatocytes enlist these cell-autonomous immune programs to eliminate Plasmodium ; their pharmacologic or genetic inhibition led to profound malarial susceptibility, and are essential in vivo . In addition to identifying the IFN-I-mediated cell-autonomous immune circuits controlling Plasmodium infection in the hepatocytes, this study extends our understanding of how non-immune cells are integral to protective immunity against malaria.

Health inequities, bias, and artificial intelligence.

Musculoskeletal (MSK) pain leads to significant healthcare utilization, decreased productivity, and disability globally. Due to its complex etiology, MSK pain is often chronic and challenging to manage effectively. Disparities in pain management-influenced by provider implicit biases and patient race, gender, age, and socioeconomic status-contribute to inconsistent outcomes. Interventional radiology (IR) provides innovative solutions for MSK pain through minimally invasive procedures, which can alleviate symptoms and reduce reliance on opioids. However, IR services may be underutilized, especially due to current treatment paradigms, referral patterns, and in areas with limited access to care. Artificial intelligence (AI) presents a promising avenue to address these inequities by analyzing large datasets to identify disparities in pain management, recognizing implicit biases, improving cultural competence, and enhancing pain assessment through multimodal data analysis. Additionally, patients who may benefit from an IR pain procedure for their MSK pain may then receive more information through their providers after being identified as a candidate by AI sifting through the electronic medical record. By leveraging AI, healthcare providers can potentially mitigate their biases while ensuring more equitable pain management and better overall outcomes for patients.

APOA2 Increases Cholesterol Efflux Capacity to Plasma HDL by Displacing the C-terminus of Resident APOA1.

The ability of high-density lipoprotein (HDL) to promote cellular cholesterol efflux is a more robust predictor of cardiovascular disease protection than HDL-cholesterol levels in plasma. Previously, we found that lipidated HDL containing both apolipoprotein A-I (APOA1) and A-II (APOA2) promotes cholesterol efflux via the ATP-binding cassette transporter (ABCA1). In the current study, we directly added purified, lipid-free APOA2 to human plasma and found a dose-dependent increase in whole plasma cholesterol efflux capacity (CEC). APOA2 likewise increased the CEC of isolated HDL with the maximum effect occurring when equal masses of APOA1 and APOA2 coexisted on the particles. Follow-up experiments with reconstituted HDL corroborated that the presence of both APOA1 and APOA2 were necessary for the increased efflux. Using limited proteolysis and chemical cross-linking mass spectrometry, we found that APOA2 induced a conformational change in the N- and C-terminal helices of APOA1. Using reconstituted HDL with APOA1 deletion mutants, we further showed that APOA2 lost its ability to stimulate ABCA1 efflux to HDL if the C-terminal domain of APOA1 was absent, but retained this ability when the N-terminal domain was absent. Based on these findings, we propose a model in which APOA2 displaces the C-terminal helix of APOA1 from the HDL surface which can then interact with ABCA1 - much like it does in lipid-poor APOA1. These findings suggest APOA2 may be a novel therapeutic target given this ability to open a large, high-capacity pool of HDL particles to enhance ABCA1-mediated cholesterol efflux.

The Major League Baseball Pitch Clock: one year position player injury analysis.

BACKGROUND: In 2023, Major League Baseball (MLB)implemented the pitch clock. The effects of the pitch clock on player injuryrates is largely unknown, and some, including the major league baseball playersassociation, have suggested that pitchers may be at an increased risk of injurywith its implementation. Position players have received little attention inthese discussions, even though they may be at the same theorized risk ofinjuries. The aim of this study is to determine if implementation of the 2023MLB pitch clock influenced the incidence of injuries in position players. It ishypothesized that implementation of the MLB pitch clock will lead to a rise ininjuries due to a reduction of time for the primary biological energy systemused by baseball to restore to normal levels. METHODS: Injury data was collected from thefangraphs.com injury database, the most comprehensive MLB data and statisticaldatabase website, for the 2021, 2022, and 2023 MLB seasons. The incidence rateratio was calculated and used to compare the injury rate for the 2023 season tothe 2021 and 2022 seasons for both major anatomical categories and anatomicalsubcategories. A z-test for proportions was used to determine significance. RESULTS: Incidence rate ratio comparison of the2023 MLB pitch clock season versus the 2021 MLB season showed a decrease in thetotal incidence of injuries (p < .001), lower extremity injuries (p < .001),and hamstring injuries (p = .032). Incidence rate ratio comparison of the 2023MLB pitch clock season versus the 2022 MLB season showed a decrease in thetotal incidence of injuries (p = .010), undisclosed injuries (p < .001), andknee injuries (p = .035). CONCLUSIONS: Following the implementation of thepitch clock during the 2023 MLB season, the total number of injuries andseveral lower extremity injury categories decreased. Due to a decrease in theoverall time spent on the field in a single game and over a season, it could behypothesized that the pitch clock decreased the workload for position players,leading to this drop in injuries. Further longitudinal investigation must bedone to investigate if this influence of the MLB pitch clock persists overtime.

Pesticides and prostate cancer incidence and mortality: An environment-wide association study.

BACKGROUND: Prostate cancer is the most common cancer among men in the United States, yet modifiable risk factors remain elusive. In this study, the authors investigated the potential role of agricultural pesticide exposure in prostate cancer incidence and mortality. METHODS: For this environment-wide association study (EWAS), linear regression was used to analyze county-level associations between the annual use of 295 distinct pesticides (measured in kg per county) and prostate cancer incidence and mortality rates in the contiguous United States. Data were analyzed in two cohorts: 1997-2001 pesticide use with 2011-2015 outcomes (discovery) and 2002-2006 use with 2016-2020 outcomes (replication). The reported effect sizes highlight how a 1-standard-deviation increase in log-transformed pesticide use (kg per county) corresponds to changes in incidence. Analyses were adjusted for county-level demographics, agricultural data, and multiple testing. RESULTS: Twenty-two pesticides showed consistent, direct associations with prostate cancer incidence across both cohorts. Of these, four pesticides were also associated with prostate cancer mortality. In the replication cohort, each 1-standard-deviation increase in log-transformed pesticide use corresponded to incidence increases per 100,000 individuals (trifluralin, 6.56 [95% confidence interval (CI), 5.04-8.07]; cloransulam-methyl, 6.18 [95% CI, 4.06-8.31]; diflufenzopyr, 3.20 [95% CI, 1.09-5.31]; and thiamethoxam, 2.82 [95% CI, 1.14-4.50]). Limitations included ecological study design, potential unmeasured confounding, and lack of individual-level exposure data. CONCLUSIONS: The results of this study suggest a potential link between certain pesticides and increased prostate cancer incidence and mortality. These findings warrant further investigation of these specific pesticides to confirm their role in prostate cancer risk and to develop potential public health interventions.

Mumps Epidemic in Navi Mumbai in 2023-24: Lessons for the Health Management System.

A pan-India epidemic of mumps was witnessed in 2023-24. An outbreak investigation by pediatricians in Navi Mumbai, Maharashtra, India, investigated 217 documented cases of mumps. Among them 197 (90.78%) had never received mumps vaccine, and 20 had received Measles-Mumps-Rubella vaccine (MMR) in the private sector. 185 children had been immunised with Measles-Rubella Vaccine (MR) in the national immunisation programme. The opportunity to vaccinate with the additional component of mumps had been missed during immunisation with MR vaccine. This outbreak investigation highlights the need to establish a Public Health Division in the Government for monitoring all contagious diseases in the community and the timely detection and control of all outbreaks.

Learning to direct one's care: barriers and facilitators reported by people with tetraplegia.

STUDY DESIGN: Qualitative analysis of focus group data. OBJECTIVE: Identifying barriers to and facilitators of learning to direct one's own care as a person with tetraplegia due to spinal cord injury (SCI). SETTING: Community, in New Jersey and Georgia, USA. METHODS: Three focus groups of veterans and civilians with SCI, involving 26 people with chronic (≥1 year) tetraplegia due to SCI who provided direction to caregivers on a daily basis. Content analysis was used to identify barriers and facilitators. RESULTS: Challenges to learning to direct one's care included: (1) lack of acceptance of lasting effects of SCI; (2) not yet understanding one's body post-SCI; (3) embarrassment; (4) being overwhelmed with information; (5) differences between the inpatient rehabilitation setting and the "real world"; (6) lack of capable and willing assistants; and (7) hesitance to criticize caregivers. Factors that helped participants become successful directors of care included: (1) experience living with SCI; (2) being observant; (3) communicating effectively; (4) developing confidence to advocate for one's own needs; (5) learning when to "let go" and when to speak up; and (6) learning from peers. CONCLUSIONS: Direction of care is a complex skill that is developed over time, and requires awareness of one's needs and preferences, self-confidence, and strong communication skills. Rehabilitation clinicians' efforts to prepare people with SCI to direct their own care effectively should cultivate awareness of one's body, identify strategies for communicating successfully with caregivers, and provide opportunities for practice of care direction skills and discussion with experienced peers.

Postprostatectomy Radiotherapy Timing and Long-Term Health-Related Quality of Life.

Importance: The association between radiotherapy (RT) timing after radical prostatectomy and long-term patient-reported health-related quality of life (HRQOL) in men with prostate cancer is unknown. Objective: To measure long-term HRQOL in men with prostate cancer up to 15 years after prostatectomy with or without RT and examine whether early vs late postprostatectomy RT is associated with differences in sexual, urinary, and bowel HRQOL. Design, Setting, and Participants: A prospective, multicenter, longitudinal cohort analysis using HRQOL data from the PROST-QA (2003-2006) and RP2 consortium (2010-2013) studies was conducted. Men with localized prostate cancer undergoing radical prostatectomy were included. Data were analyzed between May 8, 2023, and March 1, 2024. The study was conducted in 12 high-volume academic medical centers in the US. Exposures: Men were stratified based on receipt and timing of postprostatectomy RT: prostatectomy only, early RT (<12 months), and late RT (≥12 months). Main Outcomes and Measures: Longitudinal sexual, incontinence, urinary irritation, bowel, and hormonal/vitality HRQOL were measured via the Expanded Prostate Cancer Index Composite at baseline; months 2, 6, and 12; and annually thereafter. Treatment groups were compared using multivariable linear mixed-effects models of change in longitudinal domain scores. Pad use for incontinence was measured longitudinally among men receiving postprostatectomy RT. Results: A total of 1203 men were included in the study: prostatectomy only (n = 1082), early RT (n = 57), and late RT (n = 64). Median age for the entire cohort was 60.5 (range, 38.8-79.7) years, and 1075 men (92.0%) were White. Median follow-up was 85.6 (IQR, 35.8-117.2) months. Compared with men receiving prostatectomy alone, those receiving postprostatectomy RT had significantly greater decreases in sexual, incontinence, and urinary irritation HRQOL. However, timing of postprostatectomy RT, specifically early vs late, was not associated with a long-term decrease in any HRQOL domain. There was evidence of improved recovery of sexual, continence, and urinary irritation scores among men receiving early RT compared with those receiving late RT after prostatectomy. Before the start of postprostatectomy RT, 39.3% of men in the early RT cohort and 73.4% of men in the late RT cohort were pad-free. By the sixth visit post-RT, 67.4% in the early RT cohort and 47.6% in the late RT cohort were pad-free. Conclusions and Relevance: In this multicenter, prospective analysis, postprostatectomy RT appeared to be negatively associated with long-term HRQOL across all domains. However, receipt of early vs late postprostatectomy RT may result in similar long-term HRQOL outcomes.

Atypical Exon 2/3 Mutants G48C, Q43K, and E37K Present Oncogenic Phenotypes Distinct from Characterized NRAS Variants.

NRAS belongs to the RAS family of GTPases. In colorectal cancer (CRC), NRAS mutations are rare compared to KRAS, but may lead to worse outcomes. We report the functional characterization of the novel NRAS mutants-G48C, Q43K, and E37K-identified in Filipino young-onset CRC patients. Unlike previously characterized NRAS mutants with no apparent effects on cell proliferation, these mutants enhanced proliferation of both HCT116 and NIH3T3 cells. This was confirmed in 3D spheroid assays to mimic the spatial organization of cells. G48C and E37K showed apoptosis resistance in both cell lines, and Q43K showed resistance in HCT116 cells. All three showed no effect on cellular migration in NIH3T3, but G48C enhanced the migration rate of HCT116 cells. Actin staining of NIH3T3 cells expressing the mutants showed a shrunken cytoplasm and transient structures associated with motility and invasiveness. Docking simulations show that GDP is only able to bind fully within the binding pocket of wild-type NRAS, but not in the mutants. Further, G48C, Q43K, and E37K all have less negative ΔG values, indicating a weaker GDP-binding affinity compared to wild-type NRAS. Taken together, the results suggest that oncogenic readouts of NRAS mutants are codon- and mutation-specific, with potential repercussions on the aggressiveness, resistance, and therapeutic response.

Osteoporosis is not associated with reoperation or pseudarthrosis after anterior cervical discectomy and fusion through 4-years' follow-up: a retrospective cohort study of US academic health centers.

BACKGROUND CONTEXT: Osteoporosis has been proposed as a risk factor for reoperation after anterior cervical discectomy and fusion (ACDF), yet this potential association has been understudied, with conflicting results to date. PURPOSE: This study examines the hypothesis that adults with osteoporosis would have an increased risk of reoperation after ACDF compared to matched adults without osteoporosis. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Two matched cohorts (mean age: 62 years; 75% female), each with 1,019 patients, who underwent primary ACDF. Cohorts were determined by the presence or absence of a diagnosis of osteoporosis. OUTCOME MEASURES: Incidence of reoperation occurring over 4 years postoperatively, with our primary outcome being the risk ratio (RR) of reoperation with 95% confidence intervals (CI). Secondary outcomes included risk and mean count of oral opioid prescriptions and risk of pseudoarthrosis. METHODS: We utilized the TriNetX network to identify adults undergoing their first ACDF from 2004 to 2020, excluding those with serious pathology, and divided patients into 2 cohorts: osteoporosis and nonosteoporosis. Patients were propensity matched according to key risk factors for reoperation. RESULTS: Patients with osteoporosis had no statistically significant or meaningful difference in risk of reoperation compared to nonosteoporotic patients over 4-years' follow-up [95% CI] (17.3% vs. 16.5%; RR: 1.05 [0.86, 1.27]; p=.6361). Similarly, there were no significant differences in the risk of pseudoarthrosis (26.5% vs. 29.1%; RR: 0.91 [0.79, 1.05]; p=.1820), oral opioid prescription (75.0% vs. 76.0%; RR: 0.99 [0.94, 1.04]; p=.6067), or mean oral opioid prescription count (11.5 vs. 11.8; p=.7040). CONCLUSION: Compared to matched nonosteoporosis controls, osteoporosis was not associated with a statistically significant or clinically meaningful increase in risk of reoperation in adults over 4 years after ACDF. Furthermore, osteoporosis was not associated with a significant or meaningful risk of pseudoarthrosis or oral opioid prescription after ACDF, although more research is needed for corroboration. Additional research is needed to clarify whether those with osteoporosis have meaningful differences in pain and function compared to those without osteoporosis following ACDF.

Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions.

Stem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.

Megastudy testing 25 treatments to reduce antidemocratic attitudes and partisan animosity.

Scholars warn that partisan divisions in the mass public threaten the health of American democracy. We conducted a megastudy (n = 32,059 participants) testing 25 treatments designed by academics and practitioners to reduce Americans' partisan animosity and antidemocratic attitudes. We find that many treatments reduced partisan animosity, most strongly by highlighting relatable sympathetic individuals with different political beliefs or by emphasizing common identities shared by rival partisans. We also identify several treatments that reduced support for undemocratic practices-most strongly by correcting misperceptions of rival partisans' views or highlighting the threat of democratic collapse-which shows that antidemocratic attitudes are not intractable. Taken together, the study's findings identify promising general strategies for reducing partisan division and improving democratic attitudes, shedding theoretical light on challenges facing American democracy.

Characteristics and Predictors of Fluctuating Attention-Deficit/Hyperactivity Disorder in the Multimodal Treatment of ADHD (MTA) Study.

Objectives: Recent studies report a fluctuating course of attention-deficit/ hyperactivity disorder (ADHD) across development characterized by intermittent periods of remission and recurrence. In the Multimodal Treatment of ADHD (MTA) study, we investigated fluctuating ADHD including clinical expression over time, childhood predictors, and between- and within-person associations with factors hypothesized as relevant to remission and recurrence.Methods: Children with DSM-5 ADHD, combined type (N = 483), participating in the MTA adult follow-up were assessed 9 times from baseline (mean age = 8.46) to 16-year follow-up (mean age = 25.12). The fluctuating subgroup (63.8% of sample) was compared to other MTA subgroups on variables of interest over time.Results: The fluctuating subgroup experienced multiple fluctuations over 16 years (mean = 3.58, SD = 1.36) with a 6- to 7-symptom within-person difference between peaks and troughs. Remission periods typically first occurred in adolescence and were associated with higher environmental demands (both between- and within-person), particularly at younger ages. Compared to other groups, the fluctuating subgroup demonstrated moderate clinical severity. In contrast, the stable persistent group (10.8%) was specifically associated with early and lasting risk for mood disorders, substance use problems in adolescence/ young adulthood, low medication utilization, and poorer response to childhood treatment. Protective factors were detected in the recovery group (9.1%; very low parental psychopathology) and the partial remission group (15.6%; higher rates of comorbid anxiety).Conclusions: In the absence of specific risk or protective factors, individuals with ADHD demonstrated meaningful within-individual fluctuations across development. Clinicians should communicate this expectation and monitor fluctuations to trigger as-needed return to care. During remission periods, individuals with ADHD successfully manage increased demands and responsibilities.Trial Registration: ClinicalTrials.gov identifier: NCT00000388.