Miracle-dz/UniFAR-FTUs huggingface dataset:
How Cold Is Cold Enough? Refrigeration of the Next-Generation Impactor to Prevent Aerosol Undersizing

Background: Heat transfer from impactor to aqueous aerosols causes underestimation of droplet size due to evaporation. Hence, pharmacopeia suggests cooling the impactor to 5°C, which is well below aerosol temperature. In this study, we assessed the droplet size at four different impactor temperatures under controlled ambient conditions to compare the compendial 5°C method with our in-house method, where the impactor is cooled to aerosol temperature. Materials and Methods: A single nebulizer/compressor unit was used throughout. It produced an aerosol at 17°C when operated at 50% RH and 23°C RT ambient conditions. Thirty-six experiments were conducted with saline, 9 each at impactor temperatures of 5°C, 10°C, 17°C, and 23°C. NaCl stage deposition was determined by conductometry, mass on stages by weighing. Moreover, a simulation was carried out to track aerosol temperature when entering the impactor. Results: Measuring at 23°C yields a significantly smaller mass median aerodynamic diameter (MMAD) than at 5°C–17°C. Despite elevated water condensation in the impactor at 5°C and 10°C, there was no increase in MMAD compared with 17°C. Instead, droplet size determination at 5°C led to significantly smaller values than at 17°C, probably due to distorted volumetric impactor flow rates at different impactor temperatures. Reevaluation of data with flow rates adjusted for impactor temperature (14.1 L/min at 5°C vs. 15.0 L/min at 23°C) led to indistinguishable results at 5°C–17°C. A computational fluid dynamics (CFD) simulation confirmed rapid cooling of the incoming air within the inlet and stage 1 and, with it, the systematic droplet undersizing due to reduced volumetric airflow using a cooled impactor. Conclusions: As long as the impactor temperature is at or below aerosol temperature, no effects on droplet size can be observed. Measuring at aerosol temperature yields the same results as at 5°C, but prevents condensation. However, cooling the impactor well below ambient temperature can cause a systematic error in the volumetric flow rate through the impactor if not corrected accordingly.
Gestational Exposure to Organophosphate Pesticides and Longitudinally Assessed Behaviors Related to Attention-Deficit/Hyperactivity Disorder and Executive Function

Abstract The brain’s prefrontal cortex directs higher-order cognitive and behavioral processes that are important for attention, working memory, and inhibitory control. We investigated whether gestational exposure to organophosphate (OP) pesticides was associated with these abilities in childhood and early adolescence. Between 1999 and 2000, we enrolled pregnant women in a birth cohort drawn from an agricultural region of California. We measured dialkyl phosphate (DAP) metabolites of OP pesticides in maternal pregnancy urine samples (13 and 26 weeks) and estimated associations with behaviors related to attention-deficit/hyperactivity disorder and executive function, assessed longitudinally; 351 families provided neurodevelopmental outcome data at any point when the child was aged 7–12 years. We assessed function across multiple dimensions (e.g., working memory, attention), methods (e.g., behavior reports, child assessment), and reporters (e.g., mothers, teachers, child self-reports). Higher gestational DAP concentrations were consistently associated with behaviors related to attention-deficit/hyperactivity disorder and executive function. For example, a 10-fold increase in gestational DAP concentration was associated with poorer longitudinally assessed Behavior Rating Inventory of Executive Function scores, as reported by mothers (β = 4.0 (95% confidence interval: 2.1, 5.8); a higher score indicates more problems), and Weschler Intelligence Scale for Children—Fourth Edition Working Memory scores (a 3.8-point reduction; β = −3.8 (95% confidence interval: −6.2, −1.3)). Reducing gestational exposure to OP pesticides through public health policy is an important goal.
Internal fixation for osteochondritis dissecans lesions of the knee in patients with physeal closure

Objective The aim of this study was to present mid-term functional and radiological outcomes of patients with physeal closure who underwent arthroscopic or open internal fixation with headless cannulated compressive screws due to unstable Osteochondritis Dissecans (OCD) lesions of the knee. Methods With a diagnosis of unstable OCD of the knee, ten consecutive patients (seven male, three female) with physeal closure (mean age: 23 years; range: 17–40), underwent arthroscopic or open internal fixation with headless cannulated compressive screws. The patients were retrospectively reviewed based on functional and radiological data, with a mean follow-up of 42 months (range: 27–61). The average size of the defects was 4.2 cm2 with a range from 1.7 to 8 cm2. The study protocol consisted of the Range of Motion (ROM), Tegner–Lysholm Score, Modified Cincinnati Rating System Questionnaire, Short Form-12 (SF-12) in addition to the plain radiograph and Computed Tomography (CT). Any development of arthrosis was assessed at the final follow-up according to the Internation Knee Documention Committee score (IKDC). Results At the final follow-up, control plain radiographs and CT showed complete union of the fragments in nine patients; however, CT imaging illustrated nonunion of the fragment in one patient. The main Tegner–Lysholm Score increased from 59 (range: 11–63) preoperatively to 97 (range: 88–100) at the final follow-up. Modified Cincinnati Rating System Questionnaire and IKDC score were 97 (range: 93–100) and 96 (range: 92–100), respectively, at the final follow-up. In addition, in terms of SF-12, the mean physical component score was 47.5 (range: 42–49), and the mean mental component score was 57.25 (range: 48–63). Conclusion In patients with physeal closure, internal fixation using cannulated compressive screws may be an influential procedure for the OCD lesions of the knee ranging in size from medium to large. Level of Evidence Level IV, Therapeutic Study
Biomechanical evaluation of stress distributions at the implant-abutment complex and peri-implant bone around mandibular dental implants with different neck geometries and inclinations

This study aimed to investigate the effects of the different dental implant neck designs, diameters, and inclinations, on the stress distributions at the mandibular crestal bone and implant-abutment complex, using three-dimensional (3D) finite element stress analysis (FEA) method. Finite element models of three-unit fixed partial dentures supported with two same length implants (10 mm), placed on the second premolar and second molar regions, were designed. Eight different models were designed according to the implants’ neck designs (platform switching/traditional), diameters (4.1 mm/4.8 mm) and the tilting angles of the posterior implants (0°/15°). The anterior implants’ widths were 4.1 mm and the neck design of the anterior implants matched the posterior implants. Two types of 100-N loads in vertical and 30° oblique directions were applied separately onto each central fossae and functional cusps of the fixed partial dentures crowns. Algor Fempro Software was used for the simulation and evaluation of the stress levels at the implant-abutment complex and the crestal bone. Stress levels measured at the crestal bone were found to be lower for the platform switching models. However, the platform switching design generated higher stress magnitudes within the implant-abutment complex. Inclined placement of posterior implants increased the amount of stress at the crestal bone around both implants. Biomechanically, selection of the largest diameter possible when using tilted platform switched implants may be recommended at the posterior mandible.
Time-Driven Adaptive Control of Switched Systems With Application to Electro-Hydraulic Unit

This article focuses on the <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> adaptive tracking problem of uncertain switched systems. A key point of the study is to set up a multiple piecewise Lyapunov function framework which provides an effective tool for designing an adaptive switching controller consisting of a state-feedback and time-driven switching signal and a time-driven adaptive law. The proposed switching signal guarantees the solvability of the <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> adaptive tracking problem for uncertain switched systems. Significantly, it provides plenty of adjusting time for the adaptive tracking control strategy to damp the transient caused by switching and avoids frequent switching. A novel time-driven adaptive switching controller is established such that the tracking error asymptotically converges to zero and all the signals in the error dynamic system are bounded under an achieved disturbance attenuation level. The solvability criterion ensuring an <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> adaptive tracking performance is established for the uncertain switched systems, where the solvability of the <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> adaptive tracking problem for individual subsystems is not required. Finally, the proposed method is applied to the electro-hydraulic unit.
In Situ Study of Spinel Ferrite Nanocrystal Growth Using Liquid Cell Transmission Electron Microscopy

We report transition metal oxide nanocrystal formation in a liquid cell using transmission electron microscopy (TEM). The growth of M–Fe–oxide (M = Ni, Mn, Co, or Zn) nanoparticles from a growth solution of metal acetylacetonates dissolved in oleylamine, oleic acid, and benzyl ether was studied. Nickel iron oxide nanocrystals with spinel structure were obtained under electron beam irradiation of the Ni–Fe growth solution, whereas iron oxide nanocrystals were achieved with Mn remaining in the Mn–Fe growth solution. Similarly, we achieved cobalt iron oxide nanocrystals in the Co–Fe precursor solution, while iron oxide nanoparticles were obtained in the Zn–Fe solution. By tracking nanoparticle size evolution as a function of time along the Ni–Fe–oxide nanoparticle growth trajectories, we found the growth kinetics follow a Lifshitz–Slyozov–Wagner (LSW) model suggesting surface reaction-limited growth. Ex situ characterization shows elemental distribution and structural and valence state of the different nanop.
Lon protease downregulates phenazine‐1‐carboxamide biosynthesis by degrading the quorum sensing signal synthase PhzI and exhibits negative feedback regulation of Lon itself in Pseudomonas chlororaphis HT66

Pseudomonas chlororaphis HT66 exhibits strong antagonistic activity against various phytopathogenic fungi due to its main antibiotic phenazine‐1‐carboxamide (PCN). PCN gene cluster consists of phzABCDEFG, phzH, phzI, and phzR operons. phzABCDEFG transcription is activated by the PhzI/R quorum sensing system. Deletion of the lon gene encoding an ATP‐dependent protease resulted in significant enhancement of PCN production in strain HT66. However, the regulatory pathway and mechanism of Lon on PCN biosynthesis remain unknown. Here, lon mutation was shown to significantly improve antimicrobial activity of strain HT66. The N‐acyl‐homoserine lactone synthase PhzI mediates the negative regulation of PCN biosynthesis and phzABCDEFG transcription by Lon. Western blot showed that PhzI protein abundance and stability were significantly enhanced by lon deletion. The in vitro degradation assay suggested that Lon could directly degrade PhzI protein. However, Lon with an amino acid replacement (S674‐A) could not degrade PhzI protein. Lon‐recognized region was located within the first 50 amino acids of PhzI. In addition, Lon formed a new autoregulatory feedback circuit to modulate its own degradation by other potential proteases. In summary, we elucidated the Lon‐regulated pathway mediated by PhzI during PCN biosynthesis and the molecular mechanism underlying the degradation of PhzI by Lon in P. chlororaphis HT66.
Identification of the GlialCAM interactome: the G protein-coupled receptors GPRC5B and GPR37L1 modulate megalencephalic leukoencephalopathy proteins

Abstract Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC) is a type of vacuolating leukodystrophy, which is mainly caused by mutations in MLC1 or GLIALCAM. The two MLC-causing genes encode for membrane proteins of yet unknown function that have been linked to the regulation of different chloride channels such as the ClC-2 and VRAC. To gain insight into the role of MLC proteins, we have determined the brain GlialCAM interacting proteome. The proteome includes different transporters and ion channels known to be involved in the regulation of brain homeostasis, proteins related to adhesion or signaling as several G protein-coupled receptors (GPCRs), including the orphan GPRC5B and the proposed prosaposin receptor GPR37L1. Focusing on these two GPCRs, we could validate that they interact directly with MLC proteins. The inactivation of Gpr37l1 in mice upregulated MLC proteins without altering their localization. Conversely, a reduction of GPRC5B levels in primary astrocytes downregulated MLC proteins, leading to an impaired activation of ClC-2 and VRAC. The interaction between the GPCRs and MLC1 was dynamically regulated upon changes in the osmolarity or potassium concentration. We propose that GlialCAM and MLC1 associate with different integral membrane proteins modulating their functions and acting as a recruitment site for various signaling components as the GPCRs identified here. We hypothesized that the GlialCAM/MLC1 complex is working as an adhesion molecule coupled to a tetraspanin-like molecule performing regulatory effects through direct binding or influencing signal transduction events.
Vascular depression in Black Americans: A systematic review of the construct and its cognitive, functional, and psychosocial correlates

Abstract Objective: Vascular burden is associated with cognitive deficits and a form of late-life depression, vascular depression (VaDep), which is marked by decreased white matter integrity, executive dysfunction, poor treatment response, and functional disability. Older Black Americans represent a vulnerable population at risk of developing VaDep, but the literature in this group is limited. Thus, the goal of this systematic review is to summarize the existing literature that informs our understanding of VaDep in older Black Americans, including cognitive, functional, and psychosocial outcomes. Method: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, studies were identified that examined the relationship between vascular disease or vascular risk factors and that either had a sample of at least 75% Black participants or conducted race-specific analyses. Thirty studies met all inclusion criterion based on review of both authors. Results: Overall, studies support the construct of VaDep in older Black Americans. There is preliminary support for VaDep-related cognitive and functional deficits, and mixed findings regarding racial disparities in prevalence of VaDep. Conclusion: This review underscores the need for further neuroimaging and neuropsychological research in Black older adults with comorbid depression and vascular disease. Findings also highlight the importance of screening for depressive symptoms in Black individuals with multiple vascular risk factors.
Additive and non‐additive effects of day and night temperatures on thermally plastic traits in a model for adaptive seasonal plasticity

Developmental plasticity can match organismal phenotypes to ecological conditions, helping populations to deal with the environmental heterogeneity of alternating seasons. In contrast to natural situations, experimental studies of plasticity often use environmental conditions that are held constant during development. To explore potential interactions between day and night temperatures, we tested effects of circadian temperature fluctuations on thermally plastic traits in a seasonally plastic butterfly, Bicyclus anynana. Comparing phenotypes for four treatments corresponding to a full‐factorial analysis of cooler and warmer temperatures, we found evidence of significant interaction effects between day and night temperatures. We then focused on comparing phenotypes between individuals reared under two types of temperature fluctuations (warmer days with cooler nights, and cooler days with warmer nights) and individuals reared under a constant temperature of the same daily mean. We found evidence of additive‐like effects (for body size), and different types of dominance‐like effects, with one particular period of the light cycle (for development time) or one particular extreme temperature (for eyespot size) having a larger impact on phenotype. Differences between thermally plastic traits, which together underlie alternative seasonal strategies for survival and reproduction, revealed their independent responses to temperature. This study underscores the value of studying how organisms integrate complex environmental information toward a complete understanding of natural phenotypic variation and of the impact of environmental change thereon.
Valosin-Containing Protein Stabilizes Mutant p53 to Promote Pancreatic Cancer Growth

These findings identify valosin-containing protein (VCP) as a novel regulator of p53-R273H stability and suggest VCP as a potential target for development of pancreatic cancer therapy. Approximately 80% of human pancreatic ductal adenocarcinomas (PDAC) harbor TP53 mutations, among which, R273H is the most frequent. Although p53-R273H is known to possess gain-of-function properties, how it is regulated in PDAC has not been extensively explored. Here we identify valosin-containing protein (VCP) as a regulator of p53-R273H by conducting immunoprecipitation-tandem mass spectrometry analysis. VCP bound p53-R273H at its DNA binding domain. Ectopic or endogenous VCP stabilized p53-R273H by binding to MDM2 and disrupting its association with mutant p53. Inhibition of VCP either by genetic depletion or the pharmacologic inhibitor CB-5083 increased ubiquitination and degradation of p53-R273H, leading to cell death. Consistently, ablation of VCP markedly retarded growth of cultured PDAC cells and xenograft PDAC tumors. Together, these results unveil VCP as a novel partner of p53-R273H in promoting PDAC growth and as a potential target for developing anti-PDAC therapy. Significance: These findings identify valosin-containing protein (VCP) as a novel regulator of p53-R273H stability and suggest VCP as a potential target for development of pancreatic cancer therapy.
MRI findings of ischiofemoral impingement after total hip arthroplasty are associated with increased femoral antetorsion

Background Ischiofemoral impingement (IFI) is a known complication after total hip arthroplasty (THA). Purpose To assess if increased postoperative (FA) is associated with magnetic resonance imaging (MRI) findings of IFI. Material and Methods In 221 patients with THA, two independent readers measured FA, ischiofemoral space (IFS), quadratus femoris space (QFS), edema, and fatty infiltration of quadratus femoris muscle. Three sets of IFI-imaging features were defined: acute IFI (set 1): IFS ≤15 mm or QFS ≤10 mm and edema in the quadratus femoris muscle; chronic IFI (set 2): IFS ≤15 mm or QFS ≤10 mm and fatty infiltration of quadratus femoris muscle Goutallier grade ≥2; acute and chronic IFI (set 3) with both criteria applicable. For each set, FA angles were compared between positive findings of IFI and negative findings of IFI. The t-test for independent samples tested statistical significance. Results In 7.2% (16/221) of patients, findings of IFI (IFS ≤15 mm or QFS ≤10 mm and edema, n = 1; fatty infiltration, n = 9; or both, n = 6) were observed. In women, 11.4% (14/123) exhibited findings of IFI compared to 2.0% (2/98) in men. Comparison in set 1 (n = 7): mean antetorsion of 23.9° ± 9.8° (findings of acute IFI) compared to 14.4° ± 9.7° (P = 0.01). Comparison in set 2 (n = 15): mean antetorsion of 16.2° ± 6.3° (findings of chronic IFI) compared to 14.5° ± 9.9° (P = 0.49). Comparison in set 3 (n = 6): mean antetorsion of 20.4° ± 3.8° (findings of acute and chronic IFI) compared to 14.5° ± 9.9° (P = 0.01). Conclusion After THA, high postoperative FA is associated with MRI findings of acute as well as acute and chronic IFI. Findings of IFI were commonly seen in women.
Population Pharmacokinetics of Meropenem and Vaborbactam Based on Data from Noninfected Subjects and Infected Patients

Meropenem-vaborbactam is a broad-spectrum carbapenem–beta-lactamase inhibitor combination approved in the United States and Europe to treat patients with complicated urinary tract infections and in Europe for other serious bacterial infections, including hospital-acquired and ventilator-associated pneumonia. Population pharmacokinetic (PK) models were developed to characterize the time course of meropenem and vaborbactam using pooled data from two phase 1 and two phase 3 studies. ABSTRACT Meropenem-vaborbactam is a broad-spectrum carbapenem–beta-lactamase inhibitor combination approved in the United States and Europe to treat patients with complicated urinary tract infections and in Europe for other serious bacterial infections, including hospital-acquired and ventilator-associated pneumonia. Population pharmacokinetic (PK) models were developed to characterize the time course of meropenem and vaborbactam using pooled data from two phase 1 and two phase 3 studies. Multicompartment disposition model structures with linear elimination processes were fit to the data using NONMEM 7.2. Since both drugs are cleared primarily by the kidneys, estimated glomerular filtration rate (eGFR) was evaluated as part of the base structural models. For both agents, a two-compartment model with zero-order input and first-order elimination best described the pharmacokinetic PK data, and a sigmoidal Hill-type equation best described the relationship between renal clearance and eGFR. For meropenem, the following significant covariate relationships were identified: clearance (CL) decreased with increasing age, CL was systematically different in subjects with end-stage renal disease, and all PK parameters increased with increasing weight. For vaborbactam, the following significant covariate relationships were identified: CL increased with increasing height, volume of the central compartment (Vc) increased with increasing body surface area, and CL, Vc, and volume of the peripheral compartment were systematically different between phase 1 noninfected subjects and phase 3 infected patients. Visual predictive checks demonstrated minimal bias, supporting the robustness of the final models. These models were useful for generating individual PK exposures for pharmacokinetic-pharmacodynamic (PK-PD) analyses for efficacy and Monte Carlo simulations to evaluate PK-PD target attainment.
Gender-dependent association of TYMS-TSER polymorphism with 5-fluorouracil or capecitabine based chemotherapy toxicity.

Aim: TYMS gene encodes for TS enzyme involved in 5-fluorouracil (5-FU) and capecitabine (CAP) metabolism. This study assessed the association of TYMS-TSER and 3RG>C polymorphisms with 5-FU/CAP adverse event (AE) incidence. Materials & methods: TYMS-TSER and 3RG>C polymorphisms were analyzed by use of PCR/PCR-RFLP in 313 5-FU/CAP-treated cancer patients. Results: Female TYMS-TSER 2R carriers were at increased risk for 5-FU/CAP AEs (odds ratio: 2.195; p = 0.032). 2R/2R genotype was the only factor that increased risk for delayed drug administration or therapy discontinuation (odds ratio: 5.049; p = 0.016). No other associations were found. Conclusion: TYMS-TSER 3R/2R polymorphism was associated with incidence of AEs in female cancer patients. This gender-driven association potentially implicates the ER that, in female patients, potentially regulates TS expression.