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The grain amaranths ( sp.) are important pseudo-cereals native to the New World. During the last decade they have garnered increased international attention for their nutritional quality, tolerance to abiotic stress, and importance as a symbol of indigenous cultures. We describe the development of the first single nucleotide polymorphism (SNP) assays for amaranth. In addition, we report the characterization of the first complete genetic linkage map in the genus. The SNP assays are based on KASPar genotyping chemistry and were detected using the Fluidigm dynamic array platform. A diversity screen of 41 accessions of the cultivated amaranth species and their putative ancestor species ( L.) showed that the minor allele frequency (MAF) of these markers ranged from 0.05 to 0.5 with an average MAF of 0.27 per SNP locus. One hundred and forty-one of the SNP loci were considered highly polymorphic (MAF ≥ 0.3). Linkage mapping placed all 411 markers into 16 linkage groups, presumably corresponding to each of the 16 amaranth haploid chromosomes. The map spans 1288 cM with an average marker density of 3.1 cM per marker. The work reported here represents the initial first steps toward the genetic dissection of agronomically important characteristics in amaranth.

Abstract: Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for available salvage therapies have limited options for long-term disease control, necessitating novel treatments. Previously, magrolimab (anti-cluster-of-differentiation-47 antibody) plus rituximab (M+R) demonstrated ability to induce complete responses (CR) in R/R DLBCL. Here, we report 3-year follow-up data from this phase 1b/2 study assessing long-term safety and efficacy of M+R, and initial safety and efficacy of M+R plus gemcitabine-oxaliplatin (M+R-GemOx), in R/R DLBCL. After magrolimab priming, 4 groups of patients received M+R, 10 to 45 mg/kg magrolimab with 375 mg/m2 rituximab; patients receiving M+R-GemOx received 30 or 45 mg/kg magrolimab with 375 mg/m2 rituximab, 1000 mg/m2 gemcitabine, and 100 mg/m2 oxaliplatin. Primary end points were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Of 132 patients treated, 99 received M+R and 33 received M+R-GemOx. Most common any-grade TEAEs were fatigue (M+R, 40%; M+R-GemOx, 70%), infusion-related reactions (M+R, 39%), or anemia (M+R-GemOx, 70%). Treatment-related TEAEs led to magrolimab discontinuation in 7% (M+R) and 6% (M+R-GemOx). One death was considered treatment related (M+R-GemOx, colitis). M+R ORR was 24% (CR, 12%), and median DOR was 9.3 months. Median PFS and OS were 1.8 and 9.2 months, respectively. M+R-GemOx ORR was 52% (CR, 39%); 12-month DOR rate was 66.6% (95% confidence interval, 33.1-86.1). Median PFS and OS were 3.9 months and not reached, respectively. These results demonstrate that M+R with/without GemOx is well tolerated, and M+R-GemOx has clinical activity in patients with R/R DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT02953509., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Abstract: Relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) is generally considered incurable with current treatment options. Previous phase 1b/2 results showed combining magrolimab (anti-cluster-of-differentiation [CD] 47 antibody) with the anti-CD20 antibody rituximab (M+R) has antitumor activity against R/R iNHL. We report 3-year follow-up data from this phase 1b/2 study assessing long-term safety and efficacy of M+R in R/R iNHL. After magrolimab priming, 4 patient groups in phase 1b M+R received 10 to 45-mg/kg magrolimab doses with 375 mg/m2 rituximab. Phase 2 explored 30 and 45 mg/kg magrolimab. Primary end points were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory analysis included circulating tumor DNA, biomarkers of magrolimab tumor penetration, and drug target expression assessments. Of 46 patients treated in phase 1b/2, 42 had follicular lymphoma and 4 had marginal zone lymphoma. All patients experienced ≥1 any-grade TEAE, and 44 reported ≥1 treatment-related TEAE. No additional toxicities were reported during long-term follow-up, and there were no treatment-related deaths. Median follow-up was 36.7 (range, 1.2-62.3) months. The ORR was 52.2%, with 30.4% achieving a complete response. The median DOR was 15.9 months, and median time-to-response was 1.8 months. Median PFS and OS were 7.4 (95% confidence interval, 4.8-13.0) months and not reached, respectively. These results demonstrate the long-term safety and efficacy of M+R in patients with iNHL and support further exploration of CD47-based treatment combinations. This trial was registered at www.ClinicalTrials.gov as #NCT02953509., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Background: Erogenous sensation zones (ESZs) elicit sexual pleasure upon stimulation. General ESZ maps exist, but they do not assess internal areas of the body, differentiate between individual structures, or quantify the importance of individual ESZs to sexual pleasure. Maps of aversive sensation zones (ASZs), or bodily areas individuals dislike having touched during sex, have not been described., Aim: To create detailed erogenous and aversive sensory maps of the vulva, vagina, and breasts, and assess the importance of each erogenous structure to sexual pleasure., Methods: An anonymous online questionnaire was administered to 441 sexually active cisgender women (mean age 48.9 ± 15.5 years) from March to June 2020 via Qualtrics. Respondents selected ESZs and ASZs from anatomic illustrations and rated each ESZ's importance to their sexual pleasure. Respondents' reasoning for choosing each ASZ was queried., Outcomes: Heat maps of ESZ and ASZ selection frequency, ESZ importance ratings, and ASZ reasoning., Results: More respondents selected ≧1 areas of the vulva as erogenous (82.0%), in comparison to the breasts (77.4%) and vagina (59.4%). The two most erogenous areas of the breast were also the most aversive: breast tissue (57.8% ESZ selection; 5.4% ASZ) and nipples (42.7%; 6.5%). Respondents most commonly reported these areas as aversive due to: "It's overly sensitive" and "It hurts."The most frequently selected ESZs of the vulva were the vaginal introitus (50.8%), periurethra (42.6%), and glans clitoris (41.3%). The top ASZs were the anus (34.0%) and perineum (7.9%), with primary reasons being: "It's gross," "It hurts," and "I'm ashamed/embarrassed."Of the five ESZs of the vagina, the superficial anterior (48.1%) and superficial posterior (32.9%) regions were the most selected. The cervix (6.8%), superficial posterior (5%), and deep posterior (3.4%) regions were the top ASZs due to "It hurts" and/or "It's overly sensitive.", Clinical Implications: Erogenous and aversive sensory maps could help identify sexual concerns, inform preoperative counseling, and track sensory changes., Strengths and Limitations: This study captured detailed maps of internal and external ESZs and ASZs of the breasts, vulva, and vagina. Limitations include recall bias and inclusion of only cisgender women, rather than all people who share the same anatomy, irrespective of gender identity., Conclusions: Erogenous sensation was most prominent in the vulvar structures, including the vaginal introitus and glans clitoris, followed by the superficial surface of the vaginal canal. Aversive sensation associated with the anus primarily came from feelings of judgment and shame, while other ASZs were reportedly due to pain and sensitivity., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Potentially inappropriate medication (PIM) is associated with negative health outcomes and can serve as an indicator of treatment quality. Previous studies have identified social inequality in treatment but often relied on narrow understandings of social position or failed to account for mediation by differential disease risk among social groups. Understanding how social position influences PIM exposure is crucial for improving the targeting of treatment quality and addressing health disparities. This study investigates the association between social position and PIM, considering the mediation effect of long-term conditions., Methods and Findings: This cross-sectional study utilized data from the 2017 Danish National Health Survey, including 177,495 individuals aged 18 or older. Data were linked to national registers on individual-level. PIM was defined from the STOPP/START criteria and social position was assessed through indicators of economic, cultural, and social capital (from Bourdieu's Capital Theory). We analyzed odds ratios (ORs) and prevalence proportion differences (PPDs) for PIM using logistic regression, negative binomial regression, and generalized structural equation modeling. The models were adjusted for age and sex and analyzed separately for indicators of under- (START) and overtreatment (STOPP). The mediation analysis was conducted to separate direct and indirect effects via long-term conditions. Overall, 14.7% of participants were exposed to one or more PIMs, with START PIMs being more prevalent (12.5%) than STOPP PIMs (3.1%). All variables for social position except health education were associated with PIM in a dose-response pattern. Individuals with lower wealth (OR: 1.85 [95% CI 1.77, 1.94]), lower income (OR: 1.78 [95% CI 1.69, 1.87]), and lower education level (OR: 1.66 [95% CI 1.56, 1.76]) exhibited the strongest associations with PIM. Similar associations were observed for immigrants, people with low social support, and people with limited social networks. The association with PIM remained significant for most variables after accounting for mediation by long-term conditions. The disparities were predominantly related to overtreatment and did not relate to the number of PIMs. The study's main limitation is the risk of reverse causation due to the complex nature of social position and medical treatment., Conclusions: The findings highlight significant social inequalities in PIM exposure, driven by both economic, cultural, and social capital despite a universal healthcare system. Understanding the social determinants of PIM can inform policies to reduce inappropriate medication use and improve healthcare quality and equity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Paust 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.)

Background: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance., Objective: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg)., Design: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success., Results: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness., Conclusion: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness., Trial Registration Number: NCT02328131., Competing Interests: Competing interests: XC has received research grants and fees for lectures from Allergan. JPG has served as speaker, consultant and advisory member for or has received research funding from Mayoly Spindler, Allergan, Diasorin, Richen, Biocodex and Juvisé. OPN received research funding from Allergan, Mayoly Spindler, Richen, Biocodex and Juvisé. DSB served as a lecturer for Astellas, AstraZeneca, KRKA and Abbott. FM is a consultant for PHATHOM, DaVoltera and has received grants from Allergan, bioMerieux and Mobidiag. The remaining authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Prenatal alcohol exposure is a leading cause of permanent neurodevelopmental disability and can feature distinctive craniofacial deficits that partly originate from the apoptotic deletion of craniofacial progenitors, a stem cell lineage called the neural crest (NC). We recently demonstrated that alcohol causes nucleolar stress in NC through its suppression of ribosome biogenesis (RBG) and this suppression is causative in their p53/MDM2-mediated apoptosis. Here, we show that this nucleolar stress originates from alcohol's activation of AMPK, which suppresses TORC1 and the p70/S6K-mediated stimulation of RBG. Alcohol-exposed cells of the pluripotent, primary cranial NC line O9-1 were evaluated with respect to their S6K, TORC1, and AMPK activity. The functional impact of these signals with respect to RBG, p53, and apoptosis were assessed using gain-of-function constructs and small molecule mediators. Alcohol rapidly (<2 hr) increased pAMPK, pTSC2, and pRaptor, and reduced both total and pS6K in NC cells. These changes persisted for at least 12 hr to 18 hr following alcohol exposure. Attenuation of these signals via gain- or loss-of-function approaches that targeted AMPK, S6K, or TORC1 prevented alcohol's suppression of rRNA synthesis and the induction of p53-stimulated apoptosis. We conclude that alcohol induces ribosome dysbiogenesis and activates their p53/MDM2-mediated apoptosis via its activation of pAMPK, which in turn activates TSC2 and Raptor to suppress the TORC1/S6K-mediated promotion of ribosome biogenesis. This represents a novel mechanism underlying alcohol's neurotoxicity and is consistent with findings that TORC1/S6K networks are critical for cranial NC survival., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Two xyleborine ambrosia beetles, Eccoptopterusformosanus sp. nov . and E.intermedius sp. nov. are described from Taiwan and Thailand, respectively, based on DNA sequences (COI and CAD) and morphological characteristics. A key to the Eccoptopterus species of Southeast Asia is provided., Competing Interests: The authors have declared that no competing interests exist.

Background: Two classes of newer glucose-lowering drugs (GLDs), sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, improve cardiovascular and renal outcomes among patients with type 2 diabetes (T2D). However, racial and ethnic minority groups carry higher cardiovascular risks but have lower access to newer GLDs. Contextual-level social determinants of health (SDOH) may be the underlying factor associated with newer GLD adoption., Objective: To identify the association between contextual-level SDOH and real-world adoption of newer GLDs among Medicare beneficiaries and to examine the nonstationarity in the associations., Methods: Data were from 15% random samples of January 2017 to December 2018 nationwide Medicare beneficiaries. We identified patients with T2D who did not use newer GLDs in the year before the index date-January 1, 2018-and followed the cohort for 1 year to record their status of initiating a newer GLD. We used a geographically weighted multivariable Poisson regression model to determine to what extent the SDOH-newer GLD initiation association (β coefficient) varied geographically., Results: We identified 795,469 eligible Medicare beneficiaries with T2D during the study period from our dataset. Of the study cohort, mean age was 73.1 (SD = 10.5) years, 424,312 (53.3%) were female, 562,994 (70.8%) were non-Hispanic White, 96,891 (12.2%) were non-Hispanic Black, 84,744 (10.6%) were Hispanic, and 29,645 (3.7%) were Asian/Pacific Islander. Newer GLD initiation was negatively associated with the percentage of the population reporting non-Hispanic Black race, Hispanic ethnicity, and unemployment, as revealed by nonspatial regression analyses. The county-level median household income was also associated with higher newer GLD initiation. The spatial analysis presented distinct distributions of local parameter estimates for each contextual-level SDOH., Conclusions: We identified key contextual-level SDOH associated with real-world adoption of newer GLDs and explored their geographic variation through spatially explicit, data-driven analytical approaches. Identifying areas of strong association between SDOH and newer GLD initiation is crucial for policymakers to allocate resources and develop interventions that address structural inequities.

Objective: Concerns exist about clinical and operative skill decay in surgery residents when they dedicate time away from clinical training to pursue research. However, it remains undetermined how to best prevent these negative impacts. Our study evaluated the perspectives of surgical research residents on interventions to improve their reentry into clinical training., Design, Setting, and Participants: An anonymous web-based survey was distributed between 5/01/2023 and 6/01/2023 to 102 current and former (within the previous 3 years) general surgery research residents from 4 academic medical centers in Boston, MA., Results: Survey response rate was 35.3% (36/102 residents). About 22 of 36 residents (61.1%) felt that their clinical aptitude decreased during the research years, whereas 33 of 36 (91.7%) reported reduced surgical skills. When reflecting on their re-entry to residency, former research residents reported feeling anxious and less confident (3.84/5 on a 1-5 Likert scale) as well as being below the expected level of clinical performance (3.42/5). Most of them (12 of 17; 70.6%) reported that it took up to 6 months, whereas 5 of them (29.4%) up to 12 months to feel at the expected level. When compared to nonmoonlighting residents, those who moonlighted often and operated during moonlighting, denied a decrease in clinical and surgical skills, and reported less anxiety, higher confidence, and a quicker return to the expected level of performance. Interventions proposed for improving their clinical re-entry included individualized development plans for 3 months before returning to clinical training, established curriculum for clinical work throughout the research years, clinical preceptorships throughout the research years, and simulation curriculum throughout the research years., Conclusions: General surgery residents feel that their clinical and surgical skills decreased during the research years, leading to anxiety and lack of confidence when returning to residency. Therefore, comprehensive interventions are needed to improve the reentry of the research residents into clinical training., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

We compare the effects of burrowing behavior on appendicular bone structure in two Peromyscus (deer mouse) species. P. polionotus creates complex burrows in their territories, while P. eremicus is a non-burrowing nesting mouse. We examined museum specimens' bones of wild-caught mice of the two species and lab-reared P. polionotus not given the opportunity to burrow. Bones were scanned using micro-computed tomography, and cortical and trabecular bone structural properties were quantified. Wild P. polionotus mice had a larger moment of area in the ulnar and tibial cortical bone compared with their lab-reared counterparts, suggesting developmental adaptation to bending resistance. Wild P. polionotus had a larger normalized second moment of area and cross-sectional area in the tibia compared with P. eremicus. Tibial trabecular analysis showed lower trabecular thickness and spacing in wild P. polionotus than in P. eremicus and femoral analysis showed wild P. polionotus had lower thickness than P. eremicus and lower spacing than lab-reared P. polionotus, suggesting adaptation to high loads from digging. Results lay the groundwork for future exploration of the ontogenetic and evolutionary basis of mechanoadaptation in Peromyscus., (© 2024 American Association for Anatomy.)

The phytohormone strigolactone (SL) inhibits shoot branching, whereas the signalling metabolite trehalose 6-phosphate (Tre6P) promotes branching. How Tre6P and SL signalling may interact and which molecular mechanisms might be involved remains largely unknown. Transcript profiling of Arabidopsis SL mutants revealed a cluster of differentially expressed genes highly enriched in the Tre6P pathway compared with wild-type (WT) plants or brc1 mutants. Tre6P-related genes were also differentially expressed in axillary buds of garden pea (Pisum sativum) SL mutants. Tre6P levels were elevated in the SL signalling mutant more axillary (max) growth 2 compared with other SL mutants or WT plants indicating a role of MAX2-dependent SL signalling in regulating Tre6P levels. A transgenic approach to increase Tre6P levels demonstrated that all SL mutant lines and brc1 flowered earlier, showing all of these mutants were responsive to Tre6P. Elevated Tre6P led to increased branching in WT plants but not in max2 and max4 mutants, indicating some dependency between the SL pathway and Tre6P regulation of shoot branching. By contrast, elevated Tre6P led to an enhanced branching phenotype in brc1 mutants indicating independence between BRC1 and Tre6P. A model is proposed whereby SL signalling represses branching via Tre6P and independently of the BRC1 pathway., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Large B-cell lymphoma, the prototype of aggressive non-Hodgkin lymphomas, is both the most common lymphoma and accounts for the highest global burden of lymphoma-related deaths. For nearly 4 decades, the goal of treatment has been "cure", first based on CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and subsequently with rituximab plus CHOP. However, there is significant clinical, pathologic, and biologic heterogeneity, and not all patients are cured. Understanding and incorporating this biologic heterogeneity into treatment decisions unfortunately is not yet standard of care. Despite this gap, we now have significant advances in frontline, relapsed, and refractory settings. The POLARIX trial shows, for the first time, improved progression-free survival in a prospective randomized phase 3 setting. In the relapsed and refractory settings, there are now many approved agents/regimens, and several bispecific antibodies poised to join the arsenal of options. While chimeric antigen receptor T-cell therapy is discussed in detail elsewhere, it has quickly become an excellent option in the second-line setting and beyond. Unfortunately, special populations such as older adults continue to have poor outcomes and be underrepresented in trials, although a new generation of trials aim to address this disparity. This brief review will highlight the key issues and advances that offer improved outcomes to an increasing portion of patients., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Introduction: Helicobacter pylori infection is a major issue worldwide, with widespread prevalence, combined with its link to gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Meanwhile, effectiveness of current treatment protocols is limited by increasing antibiotic resistance and patient compliance issues due to long regimens and side effects. Plukenetia volubilis , or sacha inchi, is a valuable source of bioactive molecules. However, studies on its antimicrobial activity, especially against H. pylori , are lacking., Methods: In this study, the anti- H. pylori activity of P. volubilis leaves water extract was explored using in vitro and in silico approaches. High-Performance Liquid Chromatography coupled to Electrospray Ionisation and Quadrupole Time-of-Flight Mass Spectrometry (HPLC-ESI- QTOF-MS-MS) analysis of the water extract from the leaves was used to characterise the chemical composition of the plant and allowed identification of some flavonoids, such as astragalin, and some phenolic compounds. Then, high-speed counter current chromatography (HSCCC) was used to fractionate the ethyl acetate partition obtained from the water extract from the leaves., Results and Discussion: The presence of flavonoids derived from kaempferol was confirmed and astragalin was isolated for the first time in P. volubilis . The P. volubilis water infusion, ethyl acetate extract and the isolated astragalin exhibited anti-bacterial activity against H. pylori J99 and two clinical isolates (e.g., minimum inhibitory concentrations of 0.53, 0.51 and 0.49 μg/mL, respectively, for clarithromycin-resistant clinical isolate SSR366). Then, using molecular docking for potential protein targets for H. pylori , it was verified that astragalin could interact with these proteins by in silico analysis., Conclusion: These findings highlight that P. volubilis and astragalin produce a bacteriostatic activity against H. pylori and may have potential to be used in treatment against H. pylori , after further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tan, Scortecci, Cabral De Medeiros, Kukula-Koch, Butler, Smith and Boylan.)

Introduction: Trauma patients return to the emergency department (ED) at alarmingly high rates, despite not all patients requiring hospital resources. Reasons for ED re-presentation and associated risk factors have not been fully investigated., Methods: Retrospective cohort study of adult trauma admissions at an urban safety net level 1 trauma center (1/12018-12/312021). Risk factors for ED re-presentation were identified using purposeful selection and modeled using multivariable logistic regression., Results: Of 2491 patients, 19% returned within 30 d (N = 475). Most patients presented for uncontrolled pain (37%, N = 175), medical concerns (25%, N = 119), and infection (10%, N = 49). The readmission rates varied as follows: 18% for uncontrolled pain (N = 32), 42% for medical concerns (N = 50), and 67% for infection (N = 33). Risk factors for uncontrolled pain included depression/anxiety (adjusted odds ratio [aOR] 2.06, 95% confidence interval [CI] 1.39-3.05), substance use disorder (SUD) (aOR 1.65, 95% CI 1.12-2.43), and penetrating mechanism of injury (aOR 2.25, 95% CI 1.59-3.18). Risk factors for medical concerns included number of medical comorbidities (aOR 1.34, 95% CI 1.18-1.52), depression/anxiety (aOR 1.97, 95% CI 1.28-3.01), SUD (aOR 2.48, 95% CI 1.65-3.74), and nonhome discharge disposition (aOR 1.56, 95% CI 1.07-2.28). Risk factors for infection included non-English primary language (aOR 3.41, 95% CI 1.82-6.39), SUD (aOR 2.00, 95% CI 1.03-3.88), and nonhome discharge disposition (aOR 2.06, 95% CI 1.15-3.67)., Conclusions: Uncontrolled pain was the most common reason for re-presentation, although only a small fraction required readmission. Patients with penetrating injury may benefit from improved pain control. Primary care provider follow-up may help mitigate risk of medical disease exacerbation, and wound care instructions for non-English speaking patients may decrease re-presentation for infection., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin's lymphoma, including in preliminary studies involving previously untreated patients., Methods: We conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin's lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause., Results: Of 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P = 0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation., Conclusions: N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin's lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.)., (Copyright © 2024 Massachusetts Medical Society.)

Zinc hydroxide nitrate (Zn5) is one of the layered metal hydroxide materials, which has been extensively reported as an effective bifunctional catalyst for biodiesel production from acidic oils. This report gives a comprehensive summary of the reactivity of Zn5 in the methanolysis of various oil feedstocks, plant oils, free fatty acids, and other acidic oils. Notably, as evidenced by this work, Zn5 is highly effective in converting acidic oils [palmitic acid/palm oil (PO)] to fatty acid methyl ester (FAME or biodiesel) at high yields ranging from 80 to 95%, withstanding acid content up to 10% without soap formation. The high FAME yields result from complex methanolysis and hydrolysis processes, e.g., transesterification of triglycerides in the PO, esterification of palmitic acid, and hydrolysis of the triglycerides. Despite this, Zn5 is nonrecyclable because it is unstable in the reaction media and transforms into zinc hydroxide nitrate/zinc palmitate (Zn5/ZnP) composites. The Zn5/ZnP composites were suitable for use in FAME production from PO at 100 °C for 2 h by using a methanol-to-oil molar ratio of 30:1, yielding high FAME yields of 97 and 70.7% in the first and fourth cycles, respectively. This study added better insight into how to effectively produce FAME from oil feedstocks of varying acidity by using zinc layered hydroxide- or zinc carboxylate-based materials., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: This study aimed to identify and describe links between pain medication use and self-reported pain among people aged ≥ 50 years with osteoarthritis (OA) in an Irish population, and to examine the relationships between pain, medication usage and socioeconomic and clinical characteristics., Methods: Secondary data analysis of wave 1 cross-sectional data from The Irish Longitudinal Study on Ageing (TILDA) was undertaken of 1042 people with self-reported doctor-diagnosed OA. We examined use of medications typically included in OA clinical guidelines, including non-opioid analgesics (e.g. paracetamol), topical and oral non-steroidal anti-inflammatory drugs (NSAIDs), opioids and nutraceuticals. Latent Class Analysis (LCA) was used to identify underlying clinical subgroups based on medication usage patterns, and self-reported pain severity. Multinomial logistic regression was used to explore sociodemographic and clinical characteristic links to latent class membership., Results: A total of 358 (34.4%) of the 1042 people in this analysis were taking pain medications including oral NSAIDs (17.5%), analgesics (11.4%) and opioids (8.7%). Nutraceutical (glucosamine/chondroitin) use was reported by 8.6% and topical NSAID use reported by 1.4%. Three latent classes were identified: (1) Low medication use/no pain (n = 382, 37%), (2) low medication use/moderate pain (n = 523, 50%) and (3) moderate medication use/high pain (n = 137, 13%). Poorer self-rated health and greater sleep disturbance were associated with classes 2 and 3; depressive symptoms and female gender were associated with class 2, and retirement associated with class 3., Conclusions: Whilst pain medication use varied with pain severity, different medication types reported broadly aligned with OA guidelines. The two subgroups exhibiting higher pain levels demonstrated poorer self-rated health and greater sleep disturbance., (© 2024. The Author(s).)

The recognition of cerambycids as frequent and damaging invaders led to an increase in the interest in the chemical ecology of the group with the identification of pheromones and pheromone-like attractants for well over 100 species. Pheromone components of the Cerambycidae are often phylogenetically conserved, with a single compound serving as a pheromone component for several related species. In the subfamily Lamiinae, the compound 2-(undecyloxy)ethanol (monochamol) has been identified as an aggregation-sex pheromone for several species of the genus Monochamus. In other species, including Monochamus maculosus Haldeman, field trials have demonstrated that monochamol is a pheromone attractant, but at that point it was still unknown as to whether it was a pheromone for this species. Here we report the identification, and laboratory and field trials of a pheromone component produced by adult male M. maculosus. Chemical analyses of headspace volatile collections sampled from field collected beetles of both sexes revealed the presence of one male-specific compound that was identified as 2-(undecyloxy)ethanol. Electroantennography analyses showed that monochamol elicited responses from the antennae of female beetles. Traps baited with monochamol in the field captured M. maculosus adults of both sexes corroborating the identification of monochamol as the sex-aggregation pheromone of this species. The attractivity of monochamol to adult M. maculosus in our field trapping experiment was synergized by the addition of the host volatile α-pinene., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

CRTC1::TRIM11 cutaneous tumor (CTCT) is a rare skin tumor of uncertain differentiation. In the 49 reported cases, only four cases showed regional or distant metastasis, but follow-up remains limited. Herein, we present a case of metastatic CTCT with ulceration, a histological feature that has not been previously described. A 75-year-old male with a 2-month history of toe ulceration underwent a shave biopsy, which showed a dermal nodular neoplasm that was immunoreactive for SOX10 and S100, negative for Melan-A, and was initially diagnosed as melanoma. Upon pathology review at our institution, the tumor was composed of intersecting fascicles and nests of epithelioid and spindle cells. Additional immunohistochemistry revealed immunoreactivity of the tumor for MiTF and NTRK and negativity for HMB-45 and PRAME. Next-generation sequencing identified CRTC1::TRIM11 fusion, leading to a revised diagnosis of CTCT. The patient proceeded to a toe amputation and sentinel lymph node (SLN) biopsy 5 months after the shave biopsy. The amputation showed residual CTCT and a focus on lymphovascular invasion. The SLN revealed multifocal subcapsular metastases. The patient was started on adjuvant nivolumab and showed biopsy-proven recurrence in the right inguinal lymph nodes and imaging findings suspicious for pulmonary metastases 8 months after the excision. In summary, we present a case of CTCT with ulceration and lymphovascular invasion. We also provide additional evidence that a subset of CTCT behaves aggressively. The optimal surgical and medical treatments are unknown., (© 2024 The Author(s). Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19. Severity of the initial infective insult, postacute psychiatric symptoms and a history of encephalopathy were associated with the greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies., Competing Interests: Competing interests R.A.I.B. holds equity and serves as a director for Centile Bioscience Inc. P.J.H. holds equity and serves as director for H2 Cognitive Designs LTD. R.U. was speaker at a promotional educational event for Otuska; and reports consultancy for Vitaris and Springer Healthcare in the past 3 years. T.A.P. reports consultancy for Arialys Therapeutics Inc. and speaker honoraria from Janssen. A.C. is President of the FND Society, Associate Editor of JNNP, and gives independent testimony in court on a range of neuropsychiatric topics. E.B. consults for GSK, SR One, Boehringer Ingelheim and Sosei Heptares. T.S. is Director of The Pandemic Institute, which has received funding from Innova and CSL Seqirus, and Aviva and DAM Health. T.S. was an advisor to the GSK Ebola Vaccine program and the Siemens Diagnostic Program. T.S. chaired the Siemens Healthineers Clinical Advisory Board. T.S. co-chaired the WHO Neuro-COVID task force and sat on the UK Government Advisory Committee on Dangerous Pathogens, and the Medicines and Healthcare Products Regulatory Agency (MHRA) Expert Working Group on COVID-19 vaccines. T.S. advised to the UK COVID-19 Therapeutics Advisory Panel. T.S. was a member of the COVID-19 Vaccines Benefit Risk Expert Working Group for the Commission on Human Medicines committee of the MHRA. T.S. has been a member of the Encephalitis Society since 1998 and President of the Encephalitis Society since 2019. The remaining authors declare no competing interests., (© 2024. The Author(s).)