Miracle-dz/UniFAR-FTUs huggingface dataset:
Tregs integrate native and CAR-mediated costimulatory signals for control of allograft rejection

Tregs expressing chimeric antigen receptors (CAR-Tregs) are a promising tool to promote transplant tolerance. The relationship between CAR structure and Treg function was studied in xenogeneic, immunodeficient mice, revealing advantages of CD28-encoding CARs. However, these models could underrepresent interactions between CAR-Tregs, antigen-presenting cells (APCs), and donor-specific Abs. We generated Tregs expressing HLA-A2–specific CARs with different costimulatory domains and compared their function in vitro and in vivo using an immunocompetent model of transplantation. In vitro, the CD28-encoding CAR had superior antigen-specific suppression, proliferation, and cytokine production. In contrast, in vivo, Tregs expressing CARs encoding CD28, ICOS, programmed cell death 1, and GITR, but not 4-1BB or OX40, all extended skin allograft survival. To reconcile in vitro and in vivo data, we analyzed effects of a CAR encoding CD3ζ but no costimulatory domain. These data revealed that exogenous costimulation from APCs can compensate for the lack of a CAR-encoded CD28 domain. Thus, Tregs expressing a CAR with or without CD28 are functionally equivalent in vivo, mediating similar extension of skin allograft survival and controlling the generation of anti–HLA-A2 alloantibodies. This study reveals a dimension of CAR-Treg biology and has important implications for the design of CARs for clinical use in Tregs.
Utilizing the Correlation Between Constraints and Objective Function for Constrained Evolutionary Optimization

When solving constrained optimization problems by evolutionary algorithms, the core issue is to balance constraints and objective function. This paper is the first attempt to utilize the correlation between constraints and objective function to keep this balance. First of all, the correlation between constraints and objective function is mined and represented by a correlation index. Afterward, a weighted sum updating approach and an archiving and replacement mechanism are proposed to make use of this correlation index to guide the evolution. By the above process, a novel constrained optimization evolutionary algorithm is presented. Experiments on a broad range of benchmark test functions indicate that the proposed method shows better or at least competitive performance against other state-of-the-art methods. Moreover, the proposed method is applied to the gait optimization of humanoid robots.
Covid-19: Home Health Aides’ Perceived Preparedness and Self-Reported Availability for Work: Six Month Survey Results

Throughout the COVID-19 pandemic New York City home health aides continuously provided care, including to patients actively infected or recovering from COVID-19. Analyzing survey data from 1316 aides, we examined factors associated with perceptions of how well their employer prepared them for COVID-19 and their self-reported availability for work (did they “call out” more than usual). Organizational work environment and COVID-19-related supports were predominant predictors of self-reported perceptions of preparedness. Worker characteristics and COVID-19-related stressors were predominant predictors of self-reported availability. Mental distress, satisfaction with employer communications, and satisfaction with supervisor instructions were significantly associated with both outcomes. The study uniquely describes self-reported perceptions of preparedness and availability as two separate worker outcomes potentially modifiable by different interventions. Better public health emergency training and adequate protective equipment may increase aides’ perceived preparedness; more household supports could facilitate their availability. More effective employer communications and mental health initiatives could potentially improve both outcomes. Industry collaboration and systemic changes in federal, state, and local policies should enhance intervention impacts.
Is time an embodied property of concepts?

A haircut usually lasts under an hour. But how long does it take to recognize that something is an instance of a haircut? And is this “time-to-perceive” a part of the representation of concepts like haircut? Across three experiments testing lexical decision, word recognition, and semantic decision, we show that the amount of time people say it takes to perceive a concept in the world (e.g., haircut, dandelion, or merit) predicts how long it takes for them to respond to a word referring to that thing, over and above the effects of other lexical-semantic variables (e.g., word frequency, concreteness) and other variables related to conceptual complexity (e.g., how confusable a concept is with other, similar concepts, or the diversity of the contexts in which a concept appears). These results suggest that our experience of how long it takes to recognize an instance of a concept can become a part of its representation, and that we simulate this information when reading words. Consequently, we suggest that time may be an embodied property of concepts.
Radiation induces long‐term muscle fibrosis and promotes a fibrotic phenotype in fibro‐adipogenic progenitors

Radiation‐induced muscle pathology, characterized by muscle atrophy and fibrotic tissue accumulation, is the most common debilitating late effect of therapeutic radiation exposure particularly in juvenile cancer survivors. In healthy muscle, fibro/adipogenic progenitors (FAPs) are required for muscle maintenance and regeneration, while in muscle pathology FAPs are precursors for exacerbated extracellular matrix deposition. However, the role of FAPs in radiation‐induced muscle pathology has not previously been explored.
“Discrimination is harder to live with than the disease”: an interview study of the perceptions and experiences of sexual and reproductive health and rights among women living with HIV in Sweden

Abstract Around 40% of people living with human immunodeficiency virus (HIV) in Sweden are women. However, little is known about their experiences, particularly those related to sexual and reproductive health and rights (SRHR). This study aims to explore perceptions and experiences of SRHR among women living with HIV (LWH). Twelve interviews were conducted with women LWH from September to October 2019 and analysed using thematic analysis. The central theme describing participants’ experiences of social relationships, intimate encounters and reproductive life, “Discrimination is harder to live with than the disease itself”, is based on three themes that contain subthemes. Theme 1 describes how participants reconsider and reorient their sexual and reproductive life after diagnosis. Theme 2 highlights how (mis)perceptions of HIV affect sexual and reproductive life and lead to abusive treatment and internalisation. Theme 3 describes a paradoxical shift of responsibilities where participants experience being compelled to take greater responsibility in some situations and stripped of the right to decide in others. This study suggests that despite notable progress in HIV treatment, stigma and discrimination stemming from outdated beliefs and (mis)conceptions, ambiguous policies and guidelines, and unequal access to information affect SRHR experiences of women LWH more than the virus itself. The results emphasise the need to: update knowledge within healthcare settings and among the public; clarify ambiguous legislations and guidelines; ensure equal access to information to enable all women LWH to take informed decisions, make fully informed choices and realise their SRHR; and consider the diversity of women LWH and enable shared decision-making.
MODELACIÓN DE TRANSPORTE REACTIVO: AVANCE DE UNA SOLUCIÓN HIPERALCALINA A LO LARGO DE UNA FRACTURA Y SU EFECTO EN LA MINERALOGÍA

En este trabajo se presentan los resultados que se extraen de los calculos realizados a partir del codigo de transporte reactivo Retraso (REactive TRAnsport of SOlutes). En estos calculos se han tenido en cuenta varias soluciones de pH elevado, varias velocidades de flujo y varias superficies de los minerales primarios.
Clinical Relevance of RSV and SARS-CoV-2 Coinfections in Infants and Young Children

We analyzed the frequency, clinical impact and severity of respiratory syncytial virus (RSV) and SARS-CoV-2 coinfections in a single pediatric center between March 2020 and January 2023. Compared to single RSV infections, RSV/SARS-CoV-2 coinfections were uncommon (2.1%), occurred more frequently during circulation of omicron, and were associated with increased disease severity as defined by longer hospitalization and increased need for high-flow nasal cannula.
Akses Masyarakat Miskin terhadap Air Minum Bersih di Provinsi Jawa Timur

Air merupakan hak setiap orang. Negara menjamin hak setiap orang untuk mendapatkan air bagi kebutuhan pokok minimal sehari-hari guna memenuhi kehidupannya yang sehat, bersih, dan produktif (UUD No. 7 tahun 2004 pasal 5). Data WHO menunjukkan 2,1 Milyar penduduk dunia belum dapat mengakses air minum bersih. Sampai hari ini air minum bersih belum dapat diakses seluruh masyarakat khususnya masyarakat miskin. Sebagai provinsi dengan tingkat kontribusi terhadap kemiskinan tertinggi se-Indonesia sebesar 12,05% pada tahun 2016 maka Provinsi Jawa Timur dapat menjadi salah satu tolak ukur dalam pertumbuhan kemiskinan. Dalam penelitian ini akan menjelaskan faktor yang menyebabkan sebuah Rumah Tangga mendapat akses air minum bersih dengan metode analisis logistik biner. Dengan metode logit diharapkan bisa menjelaskan kecenderungan Rumah Tangga mendapat akses air minum bersih dengan beberapa faktor. Berdasarkan hasil penelitian ditemukan bahwa pendapatan dan lokasi tempat tinggal Rumah Tangga berpengaruh signifikan terhadap perolehan akses air minum bersih. Kata kunci: akses air minum bersih, pendapatan, lokasi tempat tinggal, model regresi logit, Jawa Timur.
Comparison of Ambulatory and Home Blood Pressure Variability for Cardiovascular Prognosis and Biomarkers

BACKGROUND: Although blood pressure variability (BPV) is reported to be associated with cardiovascular prognoses, it has not been established whether ambulatory BPV (ABPV; ie, short-term 24-hour BPV) or home BPV (HBPV; day-to-day BPV) is a superior clinical marker. METHODS: We analyzed the associations of ABPV and HBPV with cardiovascular prognoses and biomarkers in 1314 hypertensive outpatients who underwent both home and ambulatory BP measurements in the J-HOP study (Japan Morning-Surge Home Blood Pressure). BPV was evaluated by the SD, coefficient of variation, and average real variability of the patients’ 24-hour ambulatory and home systolic BP values. RESULTS: During the median 7.0-year follow-up, 109 cardiovascular events occurred. All SD, coefficient of variation, and average real variability values of the HBPV were significantly associated with cardiovascular risk even after adjusting by average 24-hour ambulatory systolic BP and each ABPV value: 1 SD of hazard ratio (95% CI) for the SD, 1.36 (1.14–1.63); coefficient of variation, 1.38 (1.16–1.66); and average real variability 1.29 (1.10–1.51) of HBPV. The ABPV parameters did not exhibit comparable relationships. The cardiovascular risk spline curves showed a trend toward increased risks with increasing HBPV parameters. There were no differences between ABPV and HBPV in the relationships with B-type natriuretic peptide and the urine albumin-creatine ratio. CONCLUSIONS: In this comparative analysis of ambulatory and home BP monitoring values in individuals with hypertension, ABPV was not significantly associated with cardiovascular prognosis adjusted by average BP level, and HBPV was suggested to have modest superiority in predicting cardiovascular prognosis compared with ABPV.
Phanerozoic flooding of North America and the Great Unconformity

Significance Marine sediments across North America record multiple flooding events over the Phanerozoic, starting with the Sauk Transgression that seals the Great Unconformity. Using Macrostrat, a geospatial database of stratigraphy, we demonstrate that these flooding events, except the Sauk, correspond temporally and spatially with subduction under North America, consistent with near-field dynamic subsidence. We suggest that the Sauk resulted from the migration of subduction zones from oceanic to continental arcs around Gondwana, which flattened global hypsometry and displaced ocean water onto North America. Our analysis links the Phanerozoic flooding of North America to local and global tectonics and suggests that sea level is set by the amount of oceanic spreading that is balanced by subduction under continental relative to oceanic lithosphere.
From Bimodal to Unimodal: The Transformed Incidence of Osteosarcoma in the United States

Background: Osteosarcoma is the most common primary bone malignancy. It has classically been described as having a bimodal incidence by age, with the first peak in the second decade of life and the second peak after 65 years of age. We sought to identify whether the bimodal incidence distribution still exists for osteosarcoma using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) and the National Inpatient Sample (NIS) (Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality) database. Methods: Incidence rates of osteosarcoma between 1975-2020 were analyzed by age, year of occurrence, sex, race, and primary tumor site using the SEER program data. The age of maximum incidence in patients 40 years of age and older was analyzed by calendar year to observe for a consistent second peak. Fisher's Exact test was also conducted with the SEER data to assess if there was a significant association between the occurrence of osteosarcoma in patients 35-64 years old and those 65+ years old. Incidence of tumors of the long bones of the lower limbs using ICD-9 and 10 diagnosis codes from the NIS discharge database 2012-2019 were also analyzed for comparison. Results: A total of 1,779 cases of osteosarcoma were reported in the SEER database from 1975-2020. Across the 46 calendar year span, a consistent first peak appeared in the second decade of life alternating between the 10-14 and 15-19 age groups. In the 40+ cohort, the age of the highest incidence varied widely each calendar year: being found in age groups 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, & 85+ years old (5, 3, 5, 1, 2, 1, 2, 1, & 1 times respectively). For 25 years of the 46-year span, the max was shared by more than one age group. Overall, no single age group from the 40+ age group held a consistent maximum from 1975-2020. Using the NIS program and similar methodology, we analyzed 86,100 discharges of lower limb long bone tumors from 2012-2019 as a reference. The NIS data exhibited nearly identical patterns, with a unimodal incidence in adolescence and no obvious second peak. Conclusion: Our analysis shows that the incidence of osteosarcoma is no longer bimodally distributed. This may be due to the increased use of bisphosphonates in recent years for the effective management of Paget's disease, leading to a decline in late-age bone tumors. Our findings suggest the need to update our understanding of the epidemiology of osteosarcoma, as it should be considered more as a disease of adolescence with only sporadic incidence later on in older age.
Divergent amplifications of CYP9A cytochrome P450 genes provide two noctuid pests with differential protection against xenobiotics

Significance We provide mechanistic evidence linking a cluster of rapidly diverging cytochrome P450 genes in two insect pests to their ability to utilize diverse host plants and their propensity to evolve insecticide resistance. CRISPR-Cas9 technology, bioassays, and biochemical assays show that amplified CYP9As in Spodoptera exigua and Spodoptera frugiperda collectively metabolize furanocoumarin plant defense compounds and pyrethroid, avermectin, and oxadiazine insecticides but with many differences between the species in the particular CYP9As with activity against these compounds. Further, pyrethroid resistance in both species cosegregates with the amplified gene cluster in genetic crosses. We suggest that the cluster has contributed to both the long-term macroevolution of these polyphagous insects to diverse hosts and preadapted them for short-term microevolution of insecticide resistance.
Large-scale and stacked transfer of bilayers MoS2 devices on a flexible polyimide substrate

Two-dimensional transition metal dichalcogenides (TMDs), as flexible and stretchable materials, have attracted considerable attention in the field of novel flexible electronics due to their excellent mechanical, optical, and electronic properties. Among the various TMD materials, atomically thin MoS2 has become the most widely used material due to its advantageous properties, such as its adjustable bandgap, excellent performance, and ease of preparation. In this work, we demonstrated the practicality of a stacked wafer-scale two-layer MoS2 film obtained by transferring multiple single-layer films grown using chemical vapor deposition. The MoS2 field-effect transistor cell had a top-gated device structure with a (PI) film as the substrate, which exhibited a high on/off ratio (108), large average mobility (∼8.56 cm2 V−1 s−1), and exceptional uniformity. Furthermore, a range of flexible integrated logic devices, including inverters, NOR gates, and NAND gates, were successfully implemented via traditional lithography. These results highlight the immense potential of TMD materials, particularly MoS2, in enabling advanced flexible electronic and optoelectronic devices, which pave the way for transformative applications in future-generation electronics.
Calprotectin is a contributor to and potential therapeutic target for vascular calcification in chronic kidney disease

Vascular calcification is an important risk factor for cardiovascular (CV) mortality in patients with chronic kidney disease (CKD). It is also a complex process involving osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) and abnormal deposition of minerals in the vascular wall. In an observational, multicenter European study, including 112 patients with CKD from Spain and 171 patients on dialysis from France, we used serum proteome analysis and further validation by ELISA to identify calprotectin, a circulating damage-associated molecular pattern protein, as being independently associated with CV outcome and mortality. This was confirmed in an additional cohort of 170 patients with CKD from Sweden, where increased serum calprotectin concentrations correlated with increased vascular calcification. In primary human VSMCs and mouse aortic rings, calprotectin exacerbated calcification. Treatment with paquinimod, a calprotectin inhibitor, as well as pharmacological inhibition of the receptor for advanced glycation end products and Toll-like receptor 4 inhibited the procalcifying effect of calprotectin. Paquinimod also ameliorated calcification induced by the sera of uremic patients in primary human VSMCs. Treatment with paquinimod prevented vascular calcification in mice with chronic renal failure induced by subtotal nephrectomy and in aged apolipoprotein E–deficient mice as well. These observations identified calprotectin as a key contributor of vascular calcification, and increased circulating calprotectin was strongly and independently associated with calcification, CV outcome, and mortality in patients with CKD. Inhibition of calprotectin might therefore be a promising strategy to prevent vascular calcification in patients with CKD. Description Calprotectin blockade can prevent development of vascular calcification in vitro and in vivo. Editor’s summary Chronic kidney disease (CKD) is associated with increased vascular calcification, but the underlying mechanisms are poorly understood. Here, Amaya-Garrido and colleagues performed a proteomic analysis on two cohorts of patients, one with stage 3-4 CKD and one with stage 5 CKD on dialysis, finding that increased calprotectin was associated with increased risk of CV complications and mortality. In a 5/6 nephrectomy mouse model of CKD on a high-phosphate diet, administration of the calprotectin inhibitor paquinimod could prevent increased vascular calcification without affecting renal function or calprotectin abundance, with similar findings observed after treatment of aged apolipoprotein E–deficient mice on a high-phosphate diet. These findings suggest that inhibition of calprotectin might help to prevent vascular calcification in high-risk patients. —Melissa Norton
Method-Level Bug Severity Prediction using Source Code Metrics and LLMs

In the past couple of decades, significant research efforts are devoted to the prediction of software bugs. However, most existing work in this domain treats all bugs the same, which is not the case in practice. It is important for a defect prediction method to estimate the severity of the identified bugs so that the higher-severity ones get immediate attention. In this study, we investigate source code metrics, source code representation using large language models (LLMs), and their combination in predicting bug severity labels of two prominent datasets. We leverage several source metrics at method-level granularity to train eight different machine-learning models. Our results suggest that Decision Tree and Random Forest models outperform other models regarding our several evaluation metrics. We then use the pre-trained CodeBERT LLM to study the source code representations’ effectiveness in predicting bug severity. CodeBERT fine-tuning improves the bug severity prediction results significantly in the range of 29%-140% for several evaluation metrics, compared to the best classic prediction model on source code metric. Finally, we integrate source code metrics into CodeBERT as an additional input, using our two proposed architectures, which both enhance the CodeBERT model effectiveness1.
Massive Optically Dark Galaxies Unveiled by JWST Challenge Galaxy Formation Models

Over the past decade, the existence of a substantial population of optically invisible, massive galaxies at $z\gtrsim3$ has been implied from mid-infrared to millimeter observations. With the unprecedented sensitivity of the JWST, such extremely massive galaxy candidates have immediately been identified even at $z>7$, in much larger numbers than expected. These discoveries raised a hot debate. If confirmed, early, high-mass galaxies challenge the current models of galaxy formation. However, the lack of spectroscopic confirmations leads to uncertain stellar mass ($M_{\star}$) estimates, and the possible presence of active galactic nuclei (AGN) adds further uncertainty. Here, we present the first sample of 36 dust-obscured galaxies with robust spectroscopic redshifts at $z_{\rm spec}=5-9$ from the JWST FRESCO survey. The three most extreme sources at $z\sim5-6$ ($\sim$1 billion years after the Big Bang) are so massive (log$M_{\star}/M_{\odot}$ $\gtrsim11.0$) that they would require, on average, about 50% of the baryons in their halos to be converted into stars -- two to three times higher than even the most efficient galaxies at later times. The extended emission of these galaxies suggests limited contribution by AGN. This population of ultra-massive galaxies accounts for 20% of the total cosmic star formation rate density at $z\sim5-6$, suggesting a substantial proportion of extremely efficient star formation in the early Universe.