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Abstract Charge Coupled Devices (CCD) are being used for reactor neutrino experiments and have already demonstrated their potential in constraining new physics models. The prospect of a Skipper-CCD experiment looking for standard and beyond standard model (BSM) physics in a nuclear reactor has been evaluated for different benchmark scenarios. Here, we report the first installation of a 2-g Skipper-CCD inside the containment building of a 2 GW th nuclear power plant and analyze its performance throughout its first 18 months of operation. The sensor was successfully deployed at Atucha II, in Argentina, 12 meters away from the center of the reactor core. We discuss the challenges involved in the commissioning of the detector and present data acquired during reactor ON and reactor OFF periods, with the sensor functioning with a sub-electron readout noise of 0.17 e−. Based on an exposure of 56.8 g day reactor ON and two reactor OFF data sets with a total exposure of 118.1 g day we characterize the system and evaluate the sensitivity to CEvNS. We achieved a background rate of 33 kdru and a low threshold of 45 eV ee . The ongoing efforts to improve sensitivities to CEvNS and BSM interaction are also discussed.

Se estimó la exactitud de la predicción (EP) de valores genómicos estimados (GEBV) para variables de peso vivo de ganado Charolais utilizando dos métodos de validación cruzada. Se ajustó un modelo BLUP y diferentes métodos de predicción genómica (PG) Genomic-based best linear unbiased prediction (GBLUP), Bayes C (BC) y Single-step Bayesian regression (SSBR). La EP fue comparada mediante grupos de validación (GV) formados aleatoriamente y mediante GC. Los resultados mostraron que los tres métodos de PG proporcionaron exactitudes de predicción similares entre los GV pero no exactitudes de predicción superiores a BLUP. La exactitud de predicción de GBLUP y BLUP fue 0.35 y 0.37 para PN, y de 0.30 y 0.41 para PD, respectivamente. Los resultados muestran bajas exactitudes de PG bajo los escenarios evaluados; por lo que para su correcta implementación es necesario incrementar el número de animales y usar valorees genéticos desregresados como variables de respuesta.

Gulf War Illness (GWI) afflicts US military personnel who served in the Persian Gulf War. Suspect causal agents include exposure to pyridostigmine (PB), permethrin (PM) and N , N -diethyl-m-toluamide (DEET). Prominent symptoms include cognitive deficits, such as memory impairment. In aging animal models, we have documented the beneficial effect of the flavanol (-)-epicatechin (Epi) on hippocampus structure and related function. Using a rat model of GWI, we examined the effects of Epi on hippocampus inflammation, oxidative stress, mitochondrial dysfunction, cell death/survival pathways, and memory endpoints. Male Wistar rats underwent 3 weeks of exposure to either vehicles or DEET, PM, PB, and stress. Subgroups of GWI rats were then allocated to receive orally 15 days of either water (vehicle) or 1 mg/kg/day of Epi treatment. Object recognition tasks were performed to assess memory. Hippocampus samples were analyzed. Epi treatment yields significant improvements in short- and long-term memory versus GWI rats. Hippocampus oxidative stress and pro-inflammatory cytokine levels showed significant increases with GWI that were largely normalized with Epi becoming comparable to controls. Significant increases in markers of hippocampus neuroinflammation and cell death were noted with GWI and were also largely reduced with Epi. Neuronal survival signaling pathways were adversely impacted by GWI and were partially or fully restored by Epi. Markers of mitochondrial function were adversely impacted by GWI and were fully restored by Epi. In conclusion, in an animal model of GWI, Epi beneficially impacts recognized markers of hippocampus neuroinflammation, oxidative stress, cell survival, neurotoxicity and mitochondrial function leading to improved memory.

Objective: Intestinal gluconeogenesis (IGN) regulates adult energy homeostasis in part by controlling the same hypothalamic targets as leptin. In neonates, leptin exhibits a neonatal surge controlling axonal outgrowth between the different hypothalamic nuclei involved in feeding circuits and autonomic innervation of peripheral tissues involved in energy and glucose homeostasis. Interestingly, IGN is induced during this specific time-window. We hypothesized that the neonatal pic of IGN also regulates the development of hypothalamic feeding circuits and sympathetic innervation of adipose tissues., Methods: We genetically induced neonatal IGN by overexpressing G6pc1 the catalytic subunit of glucose-6-phosphatase (the mandatory enzyme of IGN) at birth or at twelve days after birth. The neonatal development of hypothalamic feeding circuits was studied by measuring Agouti-related protein (AgRP) and Pro-opiomelanocortin (POMC) fiber density in hypothalamic nuclei of 20-day-old pups. The effect of the neonatal induction of intestinal G6pc1 on sympathetic innervation of the adipose tissues was studied via tyrosine hydroxylase (TH) quantification. The metabolic consequences of the neonatal induction of intestinal G6pc1 were studied in adult mice challenged with a high-fat/high-sucrose (HFHS) diet for 2 months., Results: Induction of intestinal G6pc1 at birth caused a neonatal reorganization of AgRP and POMC fiber density in the paraventricular nucleus of the hypothalamus, increased brown adipose tissue tyrosine hydroxylase levels, and protected against high-fat feeding-induced metabolic disorders. In contrast, inducing intestinal G6pc1 12 days after birth did not impact AgRP/POMC fiber densities, adipose tissue innervation or adult metabolism., Conclusion: These findings reveal that IGN at birth but not later during postnatal life controls the development of hypothalamic feeding circuits and sympathetic innervation of adipose tissues, promoting a better management of metabolism in adulthood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Traveler's diarrhea (TD) is one of the most common travel-related health problems, largely interfering with planned activities and potentially contributing to antimicrobial resistance. This study aimed to characterize the knowledge about TD among pre-travel consultation users of one Portuguese travel clinic and determine the impact of the consultation on knowledge levels. Using a quasi-experimental, separate-sample pretest-posttest design, participants were randomly assigned to two groups: control/pre-consultation group (CG) or experimental/post-consultation group (EG). An anonymous self-administered questionnaire was used. A total of 470 participants were analyzed (227 CG; 243 EG). The EG/post-consultation group showed significant improvement in knowledge, with correct answers increasing from 63% to 75% ( p < 0.001). However, knowledge gaps persisted: over 50% were unaware of TD's self-limited nature, 30% did not recognize loperamide as a symptom reliever, and 36% believed all travelers should take antibiotics to prevent TD. The educational level and previous travel outside Europe influenced baseline knowledge; previous travel medicine consultations and information on TD improved knowledge in both groups and made it easier to acquire knowledge on the subject. Thus, a pre-travel consultation effectively increased travelers' TD knowledge. However, post-consultation knowledge levels remained suboptimal, indicating the need for targeted interventions to increase travelers' literacy and optimize pre-travel consultations.

Background: The Patient Protection and Affordable Care Act (ACA) allowed Americans aged 19-25 years to remain on their parents' health insurance plans until age 26 years (the Dependent Care Expansion [DCE]). Have those with cancer diagnoses benefited?, Methods: The ACE DCE 7-year age range of 19-25 years was compared for changes in cancer survival and mortality before and after enactment of the ACA with groups that were younger and older (in 7-year age spans: ages 12-18 and 26-32 years, respectively). Cancer death data for the entire United States were obtained from the Centers for Disease Control and Prevention, and relative survival data of patients who were diagnosed with cancer were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results regions representing 42%-44% of the country., Results: Joinpoint analysis identified the DCE-eligible cohort as the only age group of the three groups evaluated that have had improvements in both cancer survival and death rate trends after ACA implementation and that 2010, the year the ACA was passed, was the inflection year for both survival and deaths. By 6 years, the relative survival after cancer diagnosis was 2.6 and 3.9 times greater in the DCE-eligible age group than in the younger and older control groups, respectively (both p < .001), and the cancer death rate in the DCE-eligible age group improved 2.1 and 1.5 times greater than in the younger and older control age groups, respectively (both p < .01)., Conclusions: During the first decade of the ACA, eligible young adults with cancer have had significantly improved survival and mortality. Additional policies expanding insurance coverage and enabling earlier cancer diagnosis among young adults are needed., Plain Language Summary: The Patient Protection and Affordable Care Act (ACA) Dependent Care Expansion (DCE) that began in the United States in 2011 allowed young adults aged 19-25 years to remain on their parents' health insurance plans until age 26 years. The survival rate at 6 years in young adult patients diagnosed with cancer was 2.6 to 3.9 times greater in the DCE-eligible age group compared with the younger and older age groups, and the rate of deaths from cancer improved 1.5 to 2.1 times more. During the first decade of the ACA, young adults with cancer who were in the eligible group had significantly longer survival and reduced deaths from cancer. Additional policies that expand insurance coverage and allow the diagnosis of cancer sooner are needed in young adults., (© 2024 American Cancer Society.)

Research on medicinal plants is essential for their conservation, propagation, resistance to environmental stress, and domestication. The use of organic nutrition has been demonstrated to improve soil fertility and plant quality. It is also important to study the effects of the Basic Cation Saturation Ratio (BCSR) approach, which is a topic where there is currently controversy and limited scientific information. Evaluating the growth and yields of Agastache mexicana subsp. mexicana ( Amm ) in different environments is crucial for developing effective propagation and domestication strategies. This includes examining warm and subhumid environments with rain in summer in comparison to mild environments with summer rain. Significant differences were observed in the effects of cold, waterlogging, and heat stresses on the plant's biomass yield and the morphometric-quantitative modeling by means of isolines. The biomass yield was 56% higher in environment one compared to environment two, 19% higher in environment one with organic nutrition, and 48% higher in environment two with organic nutrition compared to using only BCSR nutrition. In the second harvesting cycle, the plants in environment one did not survive, while the plants in environment two managed to survive without needing additional nutrition. Statistical and mathematical analyses provided information about the population or sample. Additionally, further analysis using isolines as a new approach revealed new insights into understanding phenology and growth issues.

We introduce a new output amplifier for fully depleted thick p-channel CCDs based on double-gate MOSFETs. The charge amplifier is an n-type MOSFET specifically designed and operated to couple the fully depleted CCD with high charge-transfer efficiency. The junction coupling between the CCD and MOSFET channels has enabled high sensitivity, demonstrating readout noise of 0.74  e&#95;{rms}^{-}/pix in one pixel charge measurement. We have also demonstrated the nondestructive readout capability of the device. Single-electron and single-photon per pixel counting in the entire CCD pixel array has been made possible through the averaging of ten samples, achieving 0.15  e&#95;{rms}^{-}/pix in a pixel readout time of 2.74 ms. We have demonstrated fully depleted CCD readout with better performance than the floating diffusion and floating gate amplifiers available today, in both single and multisampling regimes, boasting at least 6 times the speed of floating gate amplifiers.

Although esogastric cancers often affect patients over 75, there are no specific age-related guidelines for the care of these patients. Esogastric cancers have a poor prognosis and require multimodal treatment to obtain a cure. The morbidity and mortality of these multimodal treatments can be limited if care is optimized by selecting patients for neoadjuvant treatment and surgery. This can include a geriatric assessment, prehabilitation, renutrition, and more extensive use of minimally invasive surgery. Denutrition is frequent in these patients and is particularly harmful in older patients. While older patients may be provided with neoadjuvant chemotherapy or radiotherapy, it must be adapted to the patient's status. A reduction in the initial dose of palliative chemotherapy should be considered in patients with metastases. These patients tolerate immunotherapy better than systemic chemotherapy, and a strategy to replace chemotherapy with immunotherapy whenever possible should be evaluated. Finally, better supportive care is needed in patients with a poor performance status. Prospective studies are needed to improve the care and prognosis of elderly patients., Competing Interests: T.A. is an Editorial Board Member of Therapeutic Advances in Medical Oncology and an author of this paper; therefore, the peer-review process was managed by alternative members of the board and the submitting editor has not been involved in the decision-making process. T.A. received honoraria from BMS, Pierre Fabre, Bayer, and MSD. P.H. received financial support from AstraZeneca and honoraria from Servier and Viatris. A.C.-T., A.A., J.E., G.B.-C., V.F.-D., and P.C. declare no conflict of interest., (© The Author(s), 2024.)

The objective was to evaluate increasing standard ileal digestible (SID) lysine (Lys) and metabolizable energy (ME) above recommended inclusion levels fed to young (parity 1-2) and mature (parity 3-5) lactating sows. A total of 741 sows (371 parity 1-2, 370 parity 3-5) were fed in a 2×2 factorial arrangement of treatments in a randomized complete block design. Factors included SID Lys (0.85% vs 1.11%) and ME (3.18 Mcal/kg vs 3.33 Mcal/kg). Diets were formulated to deliver 62 g of SID Lys at 0.85% inclusion and 23.2 Mcal of energy to sows that consume 7.30 kg of complete feed per day. Overall, sows consumed 61 g/d SID Lys and 22.6 Mcal/kg, but because of nutrient intake differences between young and mature sows, outcome variables were analyzed separately and not statistically compared. There were no differences for either SID Lysine or ME treatment in lactation feed intake (P ≥ 0.27) or change in body weight (P ≥ 0.19) for young sows. Young sows fed 3.33 Mcal/kg ME had 0.31 fewer post-cross foster mortalities (P < 0.01) resulting in weaned litters that were 4.06 kg heavier (P < 0.01) than litters from young sows fed 3.18 Mcal/kg ME. Young sows fed 1.11% SID Lys and 3.33 Mcal/kg ME had the fewest (P ≤ 0.03) sows bred by d 7 compared to all other treatments. There was an interaction (P = 0.03) for wean-to-estrus-interval for young sows were young sows fed 1.11% SID Lys and 3.33 Mcal/kg ME were at least 3.27 days longer than young sows fed 0.85% SID Lys and 3.33 Mcal/kg ME or 1.11% SID Lys and 3.18 Mcal/kg ME. Young sows fed 3.33 Mcal/kg ME had a nearly 7% improvement in lactation G:F (0.40 vs 0.43; P < 0.01) compared to young sows fed 3.18 Mcal/kg ME. The percentage of mature sows fed 1.11% SID Lys bred by day 7 was 7.0 percentage units less (P = 0.06) when fed 3.33 Mcal/kg ME compared to 3.18 Mcal/kg ME. Feed efficiency of mature sows fed 1.11% SID Lys (0.38) was 7.89% greater (P < 0.01) than mature sows fed 0.85% SID Lys (0.35). Increasing either SID Lys or ME energy to young and mature sows had little influence on sow or pig performance, but simultaneously increasing both SID Lys and metabolizable energy negatively impacted subsequent breeding performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Millicharged particles appear in several extensions of the standard model, but have not yet been detected. These hypothetical particles could be produced by an intense proton beam striking a fixed target. We use data collected in 2020 by the SENSEI experiment in the MINOS cavern at the Fermi National Accelerator Laboratory to search for ultrarelativistic millicharged particles produced in collisions of protons in the NuMI beam with a fixed graphite target. The absence of any ionization events with 3 to 6 electrons in the SENSEI data allow us to place world-leading constraints on millicharged particles for masses between 30 to 380 MeV. This work also demonstrates the potential of utilizing low-threshold detectors to investigate new particles in beam-dump experiments, and motivates a future experiment designed specifically for this purpose.

Background: Doege-Potter syndrome is a rare paraneoplastic phenomenon associated with solitary fibrous tumors of the pleura (SFTPs). It is characterized by the presence of severe, sustained, and treatment-refractory hypoglycemia. Hypoglycaemia, which may be the sole symptom at disease onset, is mediated by the secretion of high-molecular-weight insulin-like growth factor (IGF-2). Most tumors exhibit benign behavior, with a 100% survival rate at 5 years. However, 10% of these tumors may display aggressive behavior with local or metastatic recurrence. We present a clinical case of a patient with a benign solitary fibrous tumor of the pleura who presented with symptomatic hypoglycemia and required pulmonary and pleural surgical resection to control the paraneoplastic phenomenon., Case Presentation: A Hispanic 46-year-old man presented with a 15-day history of transient alterations in consciousness worsened by fasting. The relevant medical history included obstructive sleep apnea treated with continuous positive air pressure (CPAP) and previous smoking. In-hospital studies revealed noninsulinemic hypoglycemia and a benign SFTP. Complete surgical resection was performed while the patient received dextrose fluids and corticosteroids perioperatively for hypoglycemia. Subsequently, the hypoglycemia resolved, and the patient was followed-up without disease recurrence., Conclusion: Doege-Potter syndrome is challenging to recognize. However, effective treatment can be achieved with a high survival rate. Raising awareness among healthcare professionals about the recognition of this paraneoplasic syndrome patients will improve diagnostic suspicion, biochemical confirmation, the development of diagnostic and therapeutic guidelines, and the creation of predictive indices for aggressive presentations requiring closer monitoring., (© 2024. The Author(s).)

Background: Annual global data on mental disorders prevalence and firearm death rates for 2000-2019, enables the U.S. to be compared with comparable counties for these metrics., Methods: The Institute for Health Metrics and Evaluation (IHME) Global Health Burden data were used to compare the prevalence of mental disorders with overall, homicide and suicide firearm death rates including homicides and suicides, in high sociodemographic (SDI) countries., Results: Overall and in none of the nine major categories of mental disorders did the U.S. have a statistically-significant higher rate than any of 40 other high SDI countries during 2019, the last year of available data. During the same year, the U.S. had a statistically-significant higher rate of all deaths, homicides, and suicides by firearm (all p<<0.001) than all other 40 high SDI countries. Suicides accounted for most of the firearm death rate differences between the U.S. and other high SDI countries, and yet the prevalence of mental health disorders associated with suicide were not significantly difference between the U.S. and other high SDI countries., Conclusion: Mental disorder prevalence in the U.S. is similar in all major categories to its 40 comparable sociodemographic countries, including mental health disorders primarily associated with suicide. It cannot therefore explain the country's strikingly higher firearm death rate, including suicide. Reducing firearm prevalence, which is correlated with the country's firearm death rate, is a logical solution that has been applied by other countries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bleyer 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.)

The ependyma lining the third ventricle (3V) in the mediobasal hypothalamus plays a crucial role in energy balance and glucose homeostasis. It is characterized by a high functional heterogeneity and plasticity, but the underlying molecular mechanisms governing its features are not fully understood. Here, 5481 hypothalamic ependymocytes were cataloged using FACS-assisted scRNAseq from fed, 12h-fasted, and 24h-fasted adult male mice. With standard clustering analysis, typical ependymal cells and β2-tanycytes appear sharply defined, but other subpopulations, β1- and α-tanycytes, display fuzzy boundaries with few or no specific markers. Pseudospatial approaches, based on the 3V neuroanatomical distribution, enable the identification of specific versus shared tanycyte markers and subgroup-specific versus general tanycyte functions. We show that fasting dynamically shifts gene expression patterns along the 3V, leading to a spatial redistribution of cell type-specific responses. Altogether, we show that changes in energy status induce metabolic and functional switches in tanycyte subpopulations, providing insights into molecular and functional diversity and plasticity within the tanycyte population., (© 2024. The Author(s).)

Background: Indications for reverse total shoulder arthroplasty(rTSA) continue to expand making it challenging to predict whether patients will benefit more from anatomic TSA(aTSA) or rTSA. The purpose of this study was to determine which factors differ between aTSA and rTSA patients that achieve meaningful outcomes and may influence surgical indication., Methods: Random Forest dimensionality reduction was applied to reduce 23 features into a model optimizing substantial clinical benefit (SCB) prediction of the American Shoulder and Elbow Surgeon score using 1117 consecutive patients with 2-year follow up. Features were compared between aTSA patients stratified by SCB achievement and subsequently with rTSA SCB achievers., Results: Eight combined features optimized prediction (accuracy = 87.1%, kappa = 0.73): (1) age, (2) body mass index (BMI), (3) sex, (4) history of rheumatic disease, (5) humeral head subluxation (HH) on computed tomography (CT), (6) HH-acromion distance on X-ray, (7) glenoid retroversion on CT, and (8) Walch classification on CT. A higher proportion of males (65.6% vs. 54.9%, p  = 0.022), Walch B-C glenoid morphologies (49.5% vs. 37.9%, p  < 0.001), and greater BMI (30.1 vs. 26.5 kg/m 2 , p  = 0.038) were observed in aTSA nonachievers compared with aTSA achievers, while aTSA nonachievers were statistically similar to rTSA achievers., Discussion: Patients with glenohumeral osteoarthritis and intact rotator cuffs that have a BMI > 30 kg/m 2 and exhibit Walch B-C glenoids may be less likely to achieve the SCB following aTSA and should be considered for rTSA., (© The Author(s) 2023.)

Background: Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis., Methods: In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables., Results: Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay., Conclusions: This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Surgical excision with margin of 2 cm is the treatment of choice in malignant cutaneous melanoma when Breslow index is >1 mm. When located on the lower limb, these resections can lead to large defects that require complex reconstruction in order to salvage the limb. The use of propeller-perforator flaps has multiple advantages such as the preservation of adjacent muscles, decrease in morbidity in the donor site, and good aesthetic and functional results. Our objective is to expose our experience and results with the use of propeller-perforator flaps for coverage of this kind of defects. Materials and Methods: Patients with malignant cutaneous melanoma of the lower limb who required reconstruction with a propeller-perforator flap between the years 2015 and 2021 in our plastic surgery department were included in this retrospective research. Demographic, reconstructive, oncologic, and functional data were collected and analyzed. Results: The cohort of 22 patients showed 100% of successful reconstructive outcomes. Only 2 patients experienced distal necrosis of the flap that was resolved with local dressings. Fast recovery and early capacity to walk were achieved in the majority of the patients with an average of 10.1 days until weight-baring walking. The 2-year overall and progression-free survival rates were 86.37% and 81.82%, respectively. Conclusion: The use of propeller perforator flaps for oncological defects coverage in the lower limb location has to be considered as a reliable choice as it takes less surgical time and a faster recovery. It allows limb salvage with an adequate length and functionality, with minimal donor site morbidity and a lower index of complications, contributing to improve patient's quality of life and not delaying other oncological treatments., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 The Author(s).)

Attack of donor tissues by pre-formed anti-pig antibodies is well known to cause graft failure in xenotransplantation. Genetic engineering of porcine donors to eliminate targets of these pre-formed antibodies coupled with advances in immunosuppressive medicines have now made it possible to achieve extended survival in the pre-clinical pig-to-non-human primate model. Despite these improvements, antibodies remain a risk over the lifetime of the transplant, and many patients continue to have pre-formed donor-specific antibodies even to highly engineered pigs. While therapeutics exist that can help mitigate the detrimental effects of antibodies, they act broadly potentially dampening beneficial immunity. Identifying additional xenoantigens may enable more targeted approaches, such as gene editing, to overcome these challenges by further eliminating antibody targets on donor tissue. Because we have found that classical class I swine leukocyte antigens are targets of human antibodies, we now examine whether related pig proteins may also be targeted by human antibodies. We show here that non-classical class I swine leukocyte proteins (SLA-6, -7, -8) can be expressed at the surface of mammalian cells and act as antibody targets., (© 2024 The Author(s). Xenotransplantation published by John Wiley & Sons Ltd.)

Prolonged survival in preclinical renal xenotransplantation demonstrates that early antibody mediated rejection (AMR) can be overcome. It is now critical to evaluate and understand the pathobiology of late graft failure and devise new means to improve post xenograft outcomes. In renal allotransplantation the most common cause of late renal graft failure is transplant glomerulopathy-largely due to anti-donor MHC antibodies, particularly anti-HLA DQ antibodies. We evaluated the pig renal xenograft pathology of four long-surviving (>300 days) rhesus monkeys. We also evaluated the terminal serum for the presence of anti-SLA class I and specifically anti-SLA DQ antibodies. All four recipients had transplant glomerulopathy and expressed anti-SLA DQ antibodies. In one recipient tested for anti-SLA I antibodies, the recipient had antibodies specifically reacting with two of three SLA I alleles tested. These results suggest that similar to allotransplantation, anti-MHC antibodies, particularly anti-SLA DQ, may be a barrier to improved long-term xenograft outcomes., (© 2024 The Authors. Xenotransplantation published by John Wiley & Sons Ltd.)

Background: Delays in COVID-19 testing may increase the risk of secondary household and community transmission. Little is known about what patient characteristics and symptom profiles are associated with delays in test seeking., Methods: We conducted a retrospective cohort study of all symptomatic patients diagnosed with COVID-19 and assessed in a COVID Expansion to Outpatients (COVIDEO) virtual care program between March 2020 and June 2021. The primary outcome was later test seeking more than 3 days from symptom onset. Multivariable logistic regression was used to examine predictors of later testing including patient characteristics and symptoms (30 individual symptoms or 7 symptom clusters)., Results: Of 5,363 COVIDEO patients, 4,607 were eligible and 2,155/4,607 (46.8%) underwent later testing. Older age was associated with increased odds of late testing (adjusted odds ratio [aOR] 1.007/year; 95% CI 1.00 to 1.01), as was history of recent travel (aOR 1.4; 95% CI 1.01 to 1.95). Health care workers had lower odds of late testing (aOR 0.50; 95% CI 0.39 to 0.62). Late testing was associated with symptoms in the cardiorespiratory (aOR 1.2; 95% CI 1.05, 1.36), gastrointestinal (aOR = 1.2; 95% CI 1.04, 1.4), neurological (aOR 1.1; 95% CI 1.003, 1.3) and psychiatric (aOR 1.3; 95% CI 1.1, 1.5) symptom clusters. Among individual symptoms, dyspnea, anosmia, dysgeusia, sputum, and anorexia were associated with late testing; pharyngitis, myalgia, and headache were associated with early testing., Conclusion: Certain patient characteristics and symptoms are associated with later testing, and warrant further efforts to encourage earlier testing to minimize transmission., Competing Interests: The authors have nothing to disclose., (© Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada), 2023.)

The tumor-associated antigen STEAP1 is a potential therapeutic target that is expressed in most prostate tumors and at increased levels in metastatic castration-resistant prostate cancer (mCRPC). We developed a STEAP1-targeted XmAb 2+1 T-cell engager (TCE) molecule, AMG 509 (also designated xaluritamig), that is designed to redirect T cells to kill prostate cancer cells that express STEAP1. AMG 509 mediates potent T cell-dependent cytotoxicity of prostate cancer cell lines in vitro and promotes tumor regression in xenograft and syngeneic mouse models of prostate cancer in vivo. The avidity-driven activity of AMG 509 enables selectivity for tumor cells with high STEAP1 expression compared with normal cells. AMG 509 is the first STEAP1 TCE to advance to clinical testing, and we report a case study of a patient with mCRPC who achieved an objective response on AMG 509 treatment., Significance: Immunotherapy in prostate cancer has met with limited success due to the immunosuppressive microenvironment and lack of tumor-specific targets. AMG 509 provides a targeted immunotherapy approach to engage a patient's T cells to kill STEAP1-expressing tumor cells and represents a new treatment option for mCRPC and potentially more broadly for prostate cancer. See related commentary by Hage Chehade et al., p. 20. See related article by Kelly et al., p. 76. This article is featured in Selected Articles from This Issue, p. 5., (©2023 American Association for Cancer Research.)

Background The Dermatology Life Quality Index (DLQI) is a valuable tool for assessing the quality of life in adult patients with psoriasis. Aims To analyse the reliability and validity of the DLQI to measure the quality of life in patients with mild to moderate-severe psoriasis. Methods This was a secondary validation study nested in a follow-up study. The Rasch-Andrich model was utilised to perform response function, item and person fit, differential item functioning, dimensionality, and reliability analyses. Results A total of 1439 patients were analysed, 52.1% male, mean age of 48.7 years (SD 16.1). Psoriasis vulgaris was the phenotype in 43.1% of patients, and 86% had a mild Psoriasis Area Severity Index (PASI). Adequate adjustment of the response function and the items was observed in the best-fit sample, except for item 7 (work and study). The measure explained 60.9% of the variance and presented a reliability of 0.86. Differential item functioning was identified by age, with a relevant bias in the estimation for older adults. Item-person maps are provided. Limitations This study was performed at a single centre, with most patients presenting a mild PASI score, limiting generalisation of the findings. Conclusion The validity evidence favours the use of the DLQI in moderate-severe psoriasis. However, the instrument biases the estimate of older adults. This population group should consider a specific version of the instrument.

Background: Food addiction (FA) is a construct that has gained interest in recent years, but its relevance in the Ecuadorian population has not yet been explored. The aims of this study were to explore the differences in the psychological profile (including FA) between university students from Ecuador and to identify the underlying structure of the relationships of the FA severity level through a mediational model., Methods: The sample consisted of 972 university students, women and men (mean age: 20.1 years old, SD = 2.6), recruited from four Ecuadorian regions. The assessment tools included a unidimensional scale of FA, eating-related measures, emotion regulation state, impulsivity, and psychopathology state. Path analysis modeled the direct and indirect effects explaining the FA severity level., Results: The results indicated that higher psychopathological levels were associated with FA. Similarly, no differences in FA were observed between the Ecuadorian regions. The path analysis suggested that older age, female sex, and higher difficulties in emotional regulation, impulsivity, negative mood, and anxiety trigger disordered eating; subsequently, more impaired eating behavior impacted the FA level., Conclusion: FA is a complex clinical entity that includes multiple components related to eating disorders (EDs) and other mental health problems. The results of this study provide empirical knowledge for designing evidence-based prevention and treatment strategies., 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., (Copyright © 2024 Reivan Ortiz, Campoverde, Vinañzaca, Estrada, Yanza and Granero.)

Variation in feed intake results in nearly 20% of sows consuming less than the recommended lysine (Lys) intake for lactating sows. The Lys requirement for lactating sows is based on litter size and piglet average daily gain which influences milk production. Litter size continues to increase every year causing the need for routine reevaluation of nutrient requirements. If dietary inclusion levels are not continuously adjusted this can lead to inadequate daily Lys and energy intake and may negatively impact sow body condition and litter performance. The objective was to characterize the average daily feed intake (ADFI) of sows and define feed intake patterns and their effects on sow body weight, farrowing performance, litter performance, and subsequent farrowing performance. ADFI during lactation was recorded for 4,248 sows from 7 independent research studies. Data collection occurred from November 2021 through November 2023 at a commercial breed-to-wean facility in western Illinois. Each sow was categorized as: consistently low intake (< 5.5 kg/d) throughout the lactation (LLL); low intakes (< 5 kg/d) in the first week, then gradually increased throughout the rest of the lactation period (LHH); gradual increase in intake throughout lactation with no drop and a peak intake after day 10 of lactation (gradual); rapid increase in intake with no drop and the peak intake met before day 10 (rapid); a major drop in feed intake (> 1.6 kg decrease for ≥ 2 d) any time during lactation (MAJOR); minor drop (≤ 1.6 kg for ≥ 2 d; MINOR). Sows were also separated into low (quartile 1; ≤ 25%), average (quartile 2 through 3), or high feed intake (quartile 4; ≥ 75%) by parity (P1, P2, P3+). Sows in the LLL category were younger in parity, had the greatest preweaned mortality, weaned the lightest average pigs, and experienced the greatest loss in body weight percentage compared with sows in all other feed intake categories. Furthermore, sows in the LLL and LHH categories had one fewer subsequent pig born compared with sows in the other four categories. These data support historical findings that feed intake patterns directly contribute to current litter farrowing performance. Lactation intake patterns also influence subsequent farrowing performance. Identifying under-consuming sows that are likely Lys and energy deficient allows producers opportunities to promote consistent, adequate daily intakes to these groups and mitigate negative impacts on sow and litter performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: There is a lack of randomized controlled trial data regarding differences in immunogenicity of varying coronavirus disease 2019 (COVID-19) mRNA vaccine regimens in CKD populations., Methods: We conducted a randomized controlled trial at three kidney centers in Toronto, Ontario, Canada, evaluating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response after third dose vaccination. Participants ( n =273) with CKD not on dialysis or receiving dialysis were randomized 1:1 to third dose 30- µ g BNT162b2 (Pfizer-BioNTech) or 100- µ g mRNA-1273 (Moderna). The primary outcome of this study was SARS-CoV-2 IgG-binding antibodies to the receptor-binding domain (anti-RBD). Spike protein (antispike), nucleocapsid protein, and vaccine reactogenicity were also evaluated. Serology was measured before third dose and 1, 3, and 6 months after third dose. A subset of participants ( n =100) were randomly selected to assess viral pseudovirus neutralization against wild-type D614G, B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1)., Results: Among 273 participants randomized, 94% were receiving maintenance dialysis and 59% received BNT162b2 for initial two dose COVID-19 vaccination. Third dose of mRNA-1273 was associated with higher mean anti-RBD levels (1871 binding antibody units [BAU]/ml; 95% confidence interval [CI], 829 to 2988) over a 6-month period in comparison with third dose BNT162b2 (1332 BAU/ml; 95% CI, 367 to 2402) with a difference of 539 BAU/ml (95% CI, 139 to 910; P = 0.009). Neither antispike levels nor neutralizing antibodies to wild-type, Delta, and Omicron BA.1 pseudoviruses were statistically different. COVID-19 infection occurred in 10% of participants: 15 (11%) receiving mRNA-1273 and 11 (8%) receiving BNT162b2. Third dose BNT162b2 was not associated with a significant different risk for COVID-19 in comparison with mRNA-1273 (hazard ratio, 0.78; 95% CI, 0.27 to 2.2; P = 0.63)., Conclusions: In patients with CKD, third dose COVID-19 mRNA vaccination with mRNA-1273 elicited higher SARS-CoV-2 anti-RBD levels in comparison with BNT162b2 over a 6-month period., Clinical Trial Registry Name and Registration Number: COVID-19 Vaccine Boosters in Patients With CKD (BOOST KIDNEY), NCT05022329 ., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)