Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Class I–III obesity on driver seat belt fit

Abstract Objective Approximately 40% of the U.S. adult population are obese. An issue associated with this trend is proper seat belt fit for obese occupants. This study extends previous research, in which few individuals with high BMI (> 40 kg/m2) were included, by examining the relationship between participant and belt factors on belt fit for drivers with Class I-III obesity. Methods Posture and belt fit of 52 men and women with BMI from 31 to 59 kg/m2 (median 38 kg/m2) were measured in a laboratory vehicle mockup. Five seat belt configurations were achieved by manipulating the belt anchorage locations. Body and belt landmark locations were recorded using a three-dimensional coordinate measuring machine. Results Higher BMI was associated with a lap belt position further forward and higher relative to the pelvis. On average, the lap belt was positioned an additional 32 mm forward and 13 mm above the ASIS with each increasing level of obesity classification. Sex had a small effect after accounting for BMI and stature. The mean fore-aft location of the lap belt was 24 mm more forward for men vs. women and 12 mm higher for women vs. men at the same stature and BMI. On average, women used 50 mm more belt webbing in the lap and 92 mm more in the shoulder vs. men. Conclusions The results suggest that increasing levels of obesity class effectively introduces slack in the seat belt system by routing the belt further away from the skeleton. Because the belt is designed to engage the pelvis during a frontal crash, belt placements that are higher and further forward may increase injury risk by allowing excursions or submarining. Unique to this cohort, sex had an important effect on belt fit measures after taking into account stature and BMI. The participant and belt factors considered explained only about 40% of the variance in belt fit. The remaining variance may be due to preference or exogenous body shape effects. Further research is needed to assess methods for enhanced seat belt fit for people with obesity, including addressing sex differences in belt routing.
Camrelizumab plus Famitinib in Patients with Advanced or Metastatic Renal Cell Carcinoma: Data from an Open-label, Multicenter Phase II Basket Study

Purpose: Blockade of immune checkpoint and angiogenesis is an effective treatment strategy for advanced or metastatic renal cell carcinoma (RCC). We report the results of camrelizumab plus famitinib in the RCC cohort of an open-label, multicenter, phase II basket study. Patients and Methods: Eligible patients were enrolled to receive camrelizumab (200 mg i.v. every 3 weeks) and famitinib (20 mg orally once daily). Primary endpoint was objective response rate (ORR) per RECIST version 1.1. Results: Totally, 38 patients were recruited, including 13 (34.2%) treatment-naïve and 25 (65.8%) previously treated patients. With a median duration from enrollment to data cutoff of 16.5 months (range, 6.1–20.4), 23 patients achieved a confirmed objective response, and ORR was 60.5% [95% confidence interval (CI), 43.4–76.0]. Responses in 18 (78.3%) responders were still ongoing, and Kaplan–Meier estimated median duration of response had not been reached yet (range, 1.0+–14.8+ months). Median progression-free survival (PFS) was 14.6 months (95% CI, 6.2–not reached). ORR was 84.6% (95% CI, 54.6–98.1) in treatment-naïve patients and 48.0% (95% CI, 27.8–68.7) in pretreated patients; median PFS had not been reached and was 13.4 months (95% CI, 4.1–not reached), respectively. Most common grade 3 or 4 treatment-related adverse events included proteinuria (18.4%), hypertension (18.4%), decreased neutrophil count (13.2%), palmar-plantar erythrodysesthesia syndrome (10.5%), and hypertriglyceridemia (10.5%). No treatment-related deaths occurred, and no new safety signals were observed. Conclusions: Camrelizumab plus famitinib showed potent and enduring antitumor activity in patients with advanced or metastatic RCC, both in treatment-naïve and previously treated population.
Diel pCO2 fluctuations alter the molecular response of coral reef fishes to ocean acidification conditions

Environmental partial pressure of CO2 (pCO2) variation can modify the responses of marine organisms to ocean acidification, yet the underlying mechanisms for this effect remain unclear. On coral reefs, environmental pCO2 fluctuates on a regular day–night cycle. Effects of future ocean acidification on coral reef fishes might therefore depend on their response to this diel cycle of pCO2. To evaluate the effects on the brain molecular response, we exposed two common reef fishes (Acanthochromis polyacanthus and Amphiprion percula) to two projected future pCO2 levels (750 and 1,000 µatm) under both stable and diel fluctuating conditions. We found a common signature to stable elevated pCO2 for both species, which included the downregulation of immediate early genes, indicating lower brain activity. The transcriptional programme was more strongly affected by higher average pCO2 in a stable treatment than for fluctuating treatments, but the largest difference in molecular response was between stable and fluctuating pCO2 treatments. This indicates that a response to a change in environmental pCO2 conditions is different for organisms living in a fluctuating than in stable environments. This differential regulation was related to steroid hormones and circadian rhythm (CR). Both species exhibited a marked difference in the expression of CR genes among pCO2 treatments, possibly accommodating a more flexible adaptive approach in the response to environmental changes. Our results suggest that environmental pCO2 fluctuations might enable reef fishes to phase‐shift their clocks and anticipate pCO2 changes, thereby avoiding impairments and more successfully adjust to ocean acidification conditions.
Circulating Protein Disulfide Isomerase Is Associated with Increased Risk of Thrombosis in JAK2-Mutated Myeloproliferative Neoplasms

Purpose: Thromboembolic events (TE) are the most common complications of myeloproliferative neoplasms (MPN). Clinical parameters, including patient age and mutation status, are used to risk-stratify patients with MPN, but a true biomarker of TE risk is lacking. Protein disulfide isomerase (PDI), an endoplasmic reticulum protein vital for protein folding, also possesses essential extracellular functions, including regulation of thrombus formation. Pharmacologic PDI inhibition prevents thrombus formation, but whether pathologic increases in PDI increase TE risk remains unknown. Experimental Design: We evaluated the association of plasma PDI levels and risk of TE in a cohort of patients with MPN with established diagnosis of polycythemia vera (PV) or essential thrombocythemia (ET), compared with healthy controls. Plasma PDI was measured at enrollment and subjects followed prospectively for development of TE. Results: A subset of patients, primarily those with JAK2-mutated MPN, had significantly elevated plasma PDI levels as compared with controls. Plasma PDI was functionally active. There was no association between PDI levels and clinical parameters typically used to risk-stratify patients with MPN. The risk of TE was 8-fold greater in those with PDI levels above 2.5 ng/mL. Circulating endothelial cells from JAK2-mutated MPN patients, but not platelets, demonstrated augmented PDI release, suggesting endothelial activation as a source of increased plasma PDI in MPN. Conclusions: The observed association between plasma PDI levels and increased risk of TE in patients with JAK2-mutated MPN has both prognostic and therapeutic implications.
The adaptation of educational expectations in response to ability tracking: Variations by migration background

Abstract In various educational systems, students are sorted into separate secondary schools on the basis of their academic ability. Research suggests that this type of tracking impacts students' educational expectations, as expectations generally align with students' ability track. However, most research is cross‐sectional and students with lower expectations are possibly also sorted into lower tracks. Moreover, the extent to which track placement influences expectations may vary across students. In this paper, we address the following research question: how does ability tracking impact the development of student expectations and how does this vary by students' migration background. Based on the literature on the immigrant aspiration–achievement paradox, we expect that students with a migration background are less likely to adapt expectations downwardly, and more likely to adapt expectations upward in response to track placement. Using German panel data, we examine the educational expectations of students with and without a migration background, before and after track placement. Moreover, we use variations in tracking procedures across German states to study how students who get tracked compare with students who do not get tracked in the development of their educational expectations. We show that students are more likely to upwardly adjust their expectations when their track placement exceeds their expectations and to downwardly adjust their expectations when their track placement is below their expectations. We find little support for the hypothesized variations by student migration background. Students whose parent(s) hold (a) Bachelor degree(s) are more likely to upwardly adjust their expectations when their track placement exceeds their expectations than students whose parent(s) maximally hold an upper secondary or vocational degree(s).
Raman Lidar Measurements During the International H2O Project

The amount of water vapor in the atmosphere helps to determine the likelihood that severe storms may develop. The concentration of water vapor, though, is highly variable in space and time. And yet small changes in water vapor concentration over a short period of time or over a short spatial distance can determine whether a storm may or may not develop. Therefore, in order to improve the ability to forecast severe weather such as thunderstorms it is important to measure water vapor in the atmosphere with high spatial and temporal resolution. One of the most attractive research tools for measuring water vapor in the atmosphere with high spatial and temporal resolution is a Raman lidar. A Raman lidar consists of a laser transmitter, a telescope receiver and optics and electronics for processing opticand electronic signals. A laser pulse is emitted into the atmosphere and it interacts with molecules in the atmosphere causing them to become excited and to emit, through the Raman process, photons of different wavelength than emitted by the laser. The molecule that emitted these emitted. This is the way that a Raman lidar identifies water vapor molecules in the atmosphere. can be identified based on the wavelength of the photons One of the great challenges in Raman lidar measurements has been to make useful daytime measurements of the water vapor profile under bright daytime conditions. In this first of two papers, we describe the instrumentation and analysis of the first documented Raman lidar that is able to measure water vapor in the daytime with sufficient quality to permit the study of developing storm systems.
FOXM1 Inhibitors as Potential Diagnostic Agents: First Generation of a PET Probe Targeting FOXM1 To Detect Triple‐Negative Breast Cancer in vitro and in vivo

The FOXM1 protein controls the expression of essential genes related to cancer cell cycle progression, metastasis, and chemoresistance. We hypothesize that FOXM1 inhibitors could represent a novel approach to develop 18F‐based radiotracers for Positron Emission Tomography (PET). Therefore, in this report we describe the first attempt to use 18F‐labeled FOXM1 inhibitors to detect triple‐negative breast cancer (TNBC). Briefly, we replaced the original amide group in the parent drug FDI‐6 for a ketone group in the novel AF‐FDI molecule, to carry out an aromatic nucleophilic (18F)‐fluorination. AF‐FDI dissociated the FOXM1‐DNA complex, decreased FOXM1 levels, and inhibited cell proliferation in a TNBC cell line (MDA‐MB‐231). [18F]AF‐FDI was internalized in MDA‐MB‐231 cells. Cell uptake inhibition experiments showed that AF‐FDI and FDI‐6 significantly decreased the maximum uptake of [18F]AF‐FDI, suggesting specificity towards FOXM1. [18F]AF‐FDI reached a tumor uptake of SUV=0.31 in MDA‐MB‐231 tumor‐bearing mice and was metabolically stable 60 min post‐injection. These results provide preliminary evidence supporting the potential role of FOXM1 to develop PET radiotracers.
When culture and health collide: feminine honor endorsement and attitudes toward catch-up HPV vaccinations in college women

Abstract Objective: Sexual promiscuity stigma constitutes a significant barrier which prevents young women from receiving catch-up human papillomavirus (HPV) vaccinations. Our objective was to explore how this stigma may be particularly detrimental to women in cultures of honor, where women are expected to maintain a reputation of sexual purity. Participants: Participants were a sample of 182 young women who had not previously received an HPV vaccination. Methods: We measured feminine honor endorsement, HPV sexual promiscuity stigma, HPV vaccination shame, HPV vaccination intentions, and a set of covariates. Results: Analyses revealed that the significant association between feminine honor endorsement and HPV vaccination intentions is fully explained by HPV sexual purity stigma and HPV vaccination shame. Conclusions: These findings indicate that honor-endorsing women are significantly impacted by sexual purity stigma, minimizing intentions to receive HPV vaccinations. These findings also highlight the need for the inclusion of cultural factors in the study of HPV vaccine uptake.
An omni-directional model of injury risk in planar crashes with application for autonomous vehicles

Abstract Objective: Automated driving systems (ADS) are actively being deployed within the driving fleet. ADS are designed to safely navigate roadways, which entails an expectation of encountering varying degrees of potential conflict with other road users. The ADS design and evaluation process benefits from estimating injury severity probabilities for collisions that may occur. Current regression models in the literature are typically bespoke analyses involving targeted principal directions of force (PDOFs) and occupant positions. It is preferable to rely on injury severity models derived from a single source to provide a continuous function of risk for all planar collisions, while also accounting for specific vehicle and occupant characteristics. The novel feature of the proposed models is continuous, parametric injury risk surfaces that encompass the full spectrum of available United States field data. Methods: We used years 2001–2015 of the National Automotive Sampling System, Crashworthiness Data System (NASS-CDS) and years 2017–2019 of the Crash Investigation Sampling System (CISS) to estimate injury risk at the maximum abbreviated injury scale (MAIS) 3 and higher (3+) and 5 and higher (5+) levels for all adult occupants traveling in 2002 or newer passenger vehicles which were less than 10 years old at the time of the crash. The models account for occupant, vehicle, and crash characteristics. Interactions with vulnerable road users (e.g., pedestrian, bicyclist) were not considered. Results: We present statistical models suitable to predict injury in all non-rollover crashes at the maximum MAIS3+ and 5+ levels, and show that these models can be comparable to similar single scenario (e.g., frontal) crash models. We discuss challenges with imputing missing field data, and discuss handling of covariates that may not be known at the time of the crash. Conclusions: Collision severity assessment is a vital component of the ADS design process. We developed a novel injury risk function that can assess occupant injury risks across the spectrum of foreseeable planar collisions. These models can provide insight on potential outcomes of counterfactual simulations, injury risk and crashworthiness considerations for human driven vehicles, and provide an evaluation tool that can be applied in ADS safety impact evaluation.
Resource stratified guidelines for cancer: Are they all the same? Interguideline concordance for systemic treatment recommendations

A number of organizations are producing resource stratified guidelines (RSGs) for cancer. Despite using similar definitions of resource levels, systemic treatment recommendations often differ between organizations. We systematically searched for RSGs focusing on solid tumors. We qualitatively compared the methods used to generate guidelines using the AGREE‐II appraisal tool. We extracted systemic treatment recommendations and assessed interguideline concordance using the Gwet AC1 coefficient, stratified by resource level, treatment setting and cancer type. We identified 69 RSGs cancer covering 15 solid tumors produced by four organizations. Despite using common resource‐level definitions (Basic, Core/Limited, Enhanced and Maximal), recommendations differed between organizations. Concordance for chemotherapy recommendations was poor in Basic (58.3%, Gwet 0.20), fair in Core (58.3%, Gwet 0.32) and excellent in Enhanced (92.4%, Gwet 0.92) and Maximal settings (95.4%, Gwet 0.95). Concordance rates for endocrine therapy were good in Basic (80% Gwet 0.61), and excellent in Core (90%, Gwet 0.87), Enhanced (90%, Gwet 0.89) and Maximal settings (90%, Gwet 0.89). There was moderate to excellent concordance in targeted therapy recommendations across all resource levels. Differences in recommendations appeared driven by different opinions among the chosen panel of experts regarding what is resource appropriate. Overall, we found that countries looking to base treatment and health‐policy on RSGs will find conflicting information depending on which guidelines are used, particularly for chemotherapy in Basic and Core settings. Improved transparency regarding the methods used to determine the value of a therapy for a given resource level is needed.
Long-standing effect of cholecystectomy in patients with metabolic-associated fatty liver disease

Objective The role of cholecystectomy as a risk factor in patients with metabolic-associated fatty liver disease (MAFLD) remains unclear. This study aimed to investigate if long-standing cholecystectomy is associated with advanced liver fibrosis and cirrhosis in patients with recently diagnosed MAFLD. Methods A retrospective observational study was performed in four hospitals in Mexico including patients with recently diagnosed MAFLD and a history of cholecystectomy. Subjects were divided into those with cholecystectomy ≥6 months before MAFLD diagnosis (ChBM), and those with cholecystectomy at the time of MAFLD diagnosis (ChAM). Odds ratios (OR) for the association of advanced liver fibrosis and cirrhosis with the timing of cholecystectomy were calculated. Results Mean age of 211 participants was 49.06 ± 15.12 years and the majority were female (72.5%). Patients from the ChBM (n = 70) group were significantly older (53.14 vs. 47.03 years; P = 0.003), had higher BMI (30.54 vs. 28.52 kg/m2; P = 0.011) and lower platelet count (236.23 vs. 266.72 × 103/µL; P = 0.046) compared with patients from ChAM group (n = 141). In multivariable-adjusted analysis, age (OR = 2.37; P = 0.024), dyslipidemia (OR = 4.28; P = 0.005) and severe liver fibrosis (OR = 4.68; P = 0.0) were independent risk factors associated with long-standing cholecystectomy. Conclusion Patients with long-standing cholecystectomy (≥6 months) are at increased risk of severe liver fibrosis and cirrhosis at the time of MAFLD diagnosis compared to those with recently done cholecystectomy. Advanced age (>50 years) and dyslipidemia are also commonly found in these subjects.
Prolonging photoperiod promotes testosterone synthesis of Leydig cells by directly targeting local melatonin system in rooster testes

Abstract The study investigated the effects of prolonging photoperiod on the synthesis of testosterone and melatonin in roosters, and the effect of melatonin on testosterone synthesis in rooster Leydig cells as well as its molecular mechanisms. We randomly divided one hundred and twenty 20-week-old roosters into three groups and provided 6, 12.5 and 16 h light, respectively. The results showed that prolonging photoperiod promoted testosterone synthesis, decreased melatonin production, and inhibited the expression of melatonin membrane receptors MEL1A, MEL1B, MEL1C, and aralkylamine N-acetyltransferase (AANAT) in rooster testes. Subsequently, rooster Leydig cells were isolated and treated with 0, 0.1, 1, 10, and 100 ng/mL melatonin for 36 h. The results suggested that melatonin inhibited testosterone synthesis in rooster Leydig cells, and silencing MEL1A and MEL1B relieved the inhibition of melatonin on testosterone synthesis. Additionally, melatonin reduced the intracellular cyclic adenosine monophosphate (cAMP) level and the phosphorylation level of cAMP-response element binding protein (CREB), and CREB overexpression alleviated the inhibition of melatonin on testosterone synthesis. Furthermore, pretreatment with cAMP activator forskolin or protein kinase A (PKA) activator 8-bromo-cAMP blocked the inhibition of melatonin on CREB phosphorylation and testosterone synthesis. These results indicated that prolonging photoperiod promoted testosterone synthesis associated with the decrease in melatonin production and membrane receptors and biosynthetic enzyme of melatonin in rooster testes, and melatonin inhibited testosterone synthesis of rooster Leydig cells by inhibiting the cAMP/PKA/CREB pathway via MEL1A and MEL1B. This may be evidence that prolonging photoperiod could promote testosterone synthesis through the inhibition of the local melatonin pathway in rooster testes. Summary sentence Prolonging photoperiod promotes testosterone synthesis through the inhibition of the local melatonin pathway in rooster testes. Graphical Abstract
Cholecystokinin octapeptide improves hippocampal glutamatergic synaptogenesis and postoperative cognition by inhibiting induction of A1 reactive astrocytes in aged mice

Delayed neurocognitive recovery (dNCR) is a common postoperative complication in geriatric surgical patients for which there is no efficacious therapy. Cholecystokinin octapeptide (CCK‐8), an immunomodulatory peptide, regulates memory and learning. Here, we explored the effects and mechanism of action of CCK‐8 on dNCR.
Failure of Urinary Beta-Glucuronidase Activity to Localize the Site of Urinary Tract Infection

The differentiation of renal from bladder bacteriuria is difficult on clinical grounds alone. To evaluate the correlation between site of infection and urinary beta-glucuronidase activity, 46 patients with well documented recurrent bacteriuria were studied by bilateral ureteral catheterization. Urinary beta-glucuronidase activity was also determined in 46 control subjects. In general, asymptomatic patients with renal bacteriuria, either unilateral or bilateral, had levels of enzyme activity in their urine comparable to patients with infection confined to the bladder and to normals. Only 4 of 25 patients with renal bacteriuria had significant elevations of urinary beta-glucuronidase. After localization of infection, 9 of 10 patients treated with kanamycin, a potentially nephrotoxic drug, developed significant elevations of urinary beta-glucuronidase. The results of these studies indicate that determination of beta-glucuronidase activity in urine is not useful in predicting the site of infection in patients with bacteriuria but may find a role in screening for early nephrotoxicity.