Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemical Flavorants in Vaping Products Alter Neurobiology in a Sex-Dependent Manner to Promote Vaping-Related Behaviors

Electronic nicotine delivery systems (ENDS) are distinctly different from combustible cigarettes because of the availability of flavor options. Subjective measures have been used to demonstrate that adults and adolescents prefer flavors for various reasons; (1) they are pleasing and (2) they mask the harshness of nicotine. Despite this, there have been few investigations into the molecular interactions that connect chemical flavorants to smoking or vaping-related behaviors. Here, we investigated the effects of three chemical flavorants (hexyl acetate, ethyl acetate, and methylbutyl acetate) that are found in green apple (GA) ENDS e-liquids but are also found in other flavor categories. We used a translationally relevant vapor self-administration mouse model and observed that adult male and female mice self-administered GA flavorants in the absence of nicotine. Using α4-mCherryα6-GFP nicotinic acetylcholine receptor (nAChR) mice, we observed that mice exposed to GA flavorants exhibited a sex-specific increase (upregulation) of nAChRs that was also brain-region specific. Electrophysiology revealed that mice exposed to GA flavorants exhibited enhanced firing of ventral tegmental area dopamine neurons. Fast-scan cyclic voltammetry revealed that electrically stimulated dopamine release in the nucleus accumbens core is increased in mice that are exposed to GA flavorants. These effects were similarly observed in the medial habenula. Overall, these findings demonstrate that ENDS flavors alone change neurobiology and may promote vaping-dependent behaviors in the absence of nicotine. Furthermore, the flavorant-induced changes in neurobiology parallel those caused by nicotine, which highlights the fact that nonmenthol flavorants may contribute to or enhance nicotine reward and reinforcement. SIGNIFICANCE STATEMENT The impact of flavors on vaping is a hotly debated topic; however, few investigations have examined this in a model that is relevant to vaping. Although a full understanding of the exact mechanism remains undetermined, our observations reveal that chemical flavorants in the absence of nicotine alter brain circuits relevant to vaping-related behavior. The fact that the flavorants investigated here exist in multiple flavor categories of vaping products highlights the fact that a multitude of flavored vaping products may pose a risk toward vaping-dependent behaviors even without the impact of nicotine. Furthermore, as the neurobiological changes have an impact on neurons of the reward system, there exists the possibility that nonmenthol flavorants may enhance nicotine reward and reinforcement.
Effect of culture conditions at lab‐scale on metabolite composition and antibacterial and antibiofilm activities of Dunaliella tertiolecta

Dunaliella tertiolecta RCC6 was cultivated indoors in glass bubble column photobioreactors operated under batch and semi‐continuous regimens and using two different conditions of light and temperature. Biomass was harvested by centrifugation, frozen, and then lyophilized. The soluble material was obtained by sequential extraction of the lyophilized biomass with solvents with a gradient of polarity (hexane, ethyl acetate, and methanol) and its metabolic composition was investigated through nuclear magnetic resonance (NMR) spectroscopy. The effect of light on chlorophyll biosynthesis was clearly shown through the relative intensities of the 1H NMR signals due to pheophytins. The highest signal intensity was observed for the biomasses obtained at lower light intensity, resulting in a lower light availability per cell. Under high temperature and light conditions, the 1H NMR spectra of the hexane extracts showed an incipient accumulation of triacylglycerols. In these conditions and under semi‐continuous regimen, an enhancement of β‐carotene and sterols production was observed. The antibacterial and antibiofilm activities of the extracts were also tested. Antibacterial activity was not detected, regardless of culture conditions. In contrast, the minimal biofilm inhibitory concentrations (MBICs) against Escherichia coli for the hexane extract obtained under semi‐continuous regimen using high temperature and irradiance conditions was promising.
Prolonged Opioid Use and Pain Outcome and Associated Factors after Surgery under General Anesthesia: A Prospective Cohort Association Multicenter Study

Background: There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery. Methods: Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed. Results: Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively. Conclusions: Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery. In these prospectively collected cohort data, preoperative opioid use was identified as the strongest risk factor for opioid use at 3 months postoperatively. No correlation was found between persistent opioid use at 3 months and surgical site pain at 3 months. No association was identified between preoperative anxiety, preoperative depression, or surgery type and opioid use at 3 months in multivariable models, although credible intervals were large for some variables.
Infant brain regional cerebral blood flow increases supporting emergence of the default-mode network

Human infancy is characterized by most rapid regional cerebral blood flow (rCBF) increases across lifespan and emergence of a fundamental brain system default-mode network (DMN). However, how infant rCBF changes spatiotemporally across the brain and how the rCBF increase supports emergence of functional networks such as DMN remains unknown. Here, by acquiring cutting-edge multi-modal MRI including pseudo-continuous arterial-spin-labeled perfusion MRI and resting-state functional MRI of 48 infants cross-sectionally, we elucidated unprecedented 4D spatiotemporal infant rCBF framework and region-specific physiology–function coupling across infancy. We found that faster rCBF increases in the DMN than visual and sensorimotor networks. We also found strongly coupled increases of rCBF and network strength specifically in the DMN, suggesting faster local blood flow increase to meet extraneuronal metabolic demands in the DMN maturation. These results offer insights into the physiological mechanism of brain functional network emergence and have important implications in altered network maturation in brain disorders.
Laboratory indicators of hypothyroidism and TgAA-positivity in the Eurasian dog breed

Background Hereditary hypothyroidism represents a concern for dog breeders; thus, surveillance programs have been established for several dog breeds. Methods Thyroid profiles (total thyroxine (TT4), thyrotropin (thyroid stimulating hormone (TSH)), and thyroglobulin autoantibodies (TgAA)) collected as part of a breed surveillance program in Eurasians (2009–2017) were retrospectively analyzed. The study included data from 1,501 Eurasians from a German breeding club. Classification was exclusively based on laboratory data. Hypothyroidism was defined as a combined decrease in TT4 and increase in TSH in serum and was classified as TgAA-positive and TgAA-negative hypothyroidism. Thyroglobulin autoantibodies (TgAA) independent of the concentrations of TT4 and TSH were determined. The overall prevalence of hypothyroidism, TgAA-positive hypothyroidism, TgAA-negative hypothyroidism and TgAA-positivity was assessed when the dogs entered the program. Follow-up laboratory data was available for 324 dogs without hypothyroidism on initial examination. Results The initial screening was performed at a median age of 18 months (interquartile range (IQR): 15–29). The overall prevalence of hypothyroidism was 3.9% (n = 58; 95% CI: 2.9–4.8%) and the prevalence of a positive TgAA status was 7.9% (n = 118; 95% CI: 6.6–9.3%). The prevalence of TgAA-positive and TgAA-negative hypothyroidism was 1.7% (n = 26; 95% CI: 1.1–2.4%) and 2.1% (n = 32; 95% CI: 1.4–2.9%), respectively. 22.0% of dogs with positive TgAA status (26/118) were already hypothyroid on initial examination. Overall, 42.5% (17/40) of TgAA-positive dogs on initial examination developed hypothyroidism on follow-up. Conclusion The results of this study demonstrate that the Eurasian dog breed exhibits a relevant risk for hypothyroidism and presence of TgAA. The predictive value of TgAA for hypothyroidism or developing hypothyroidism was high in this breed. Further investigations with longitudinal studies in individual dogs are warranted.
LoveYourBrain Mindset: Feasibility, Acceptability, Usability, and Effectiveness of an Online Yoga, Mindfulness, and Psychoeducation Intervention for People with Traumatic Brain Injury

ABSTRACT Objective Despite the benefits of yoga, mindfulness, and psychoeducation after traumatic brain injury (TBI), no online programming exists. This study investigated the feasibility, acceptability, usability, and effectiveness of the LoveYourBrain Mindset online program for people with TBI. Research Design Pre-post, retrospective intervention. Methods LoveYourBrain Mindset is a six-week online yoga, mindfulness, and psychoeducation program with weekly interactive Zoom classes and prerecorded mindfulness tools. Two interactive class types (45-minute group discussion, 75-minute group discussion and gentle yoga) are offered to enhance accessibility. People were eligible if they experienced TBI, were a caregiver, or clinician; ≥15 years old; and capable of gentle exercise and group discussion. We analyzed attendance, program ratings, mindfulness tools utilization, and pre/post-intervention differences in QOL, resilience, emotional/behavioral dysregulation, cognition, and positive affect/well-being. Results Overall, 1539 individuals signed up for LoveYourBrain Mindset with 1093 (71.02%) participating in one/more classes. The mean program rating was 9.09 (SD=1.28). Majority (62.99%) used the mindfulness tools each week. Multiple linear regression models controlling for age, TBI severity, and gender indicated significant improvements in QOL, resilience, emotional/behavioral dysregulation, cognition, and positive affect/well-being (p<0.001). Conclusion LoveYourBrain Mindset is feasible, acceptable, usable, and may improve outcomes among people with TBI.
High-resolution Bayesian chronology of the earliest evidence of domesticated animals in the Dutch wetlands (Hardinxveld-Giessendam archaeological sites)

The archaeological sites of Hardinxveld-Giessendam de Bruin and Polderweg, situated in the Rhine-Meuse delta, are the best-preserved Mesolithic sites in the Netherlands. Due to the early appearance of domesticated animals in their faunal assemblage, they are also integral to the research of the emergence of animal husbandry in the region. This study focuses on the precise chronology of the sites, using radiocarbon dating and Bayesian modelling of both newly acquired and legacy radiocarbon dates. To mitigate the risk of erroneous dates, we dated the bone collagen of 26 herbivorous and one aquatic mammals from clear archaeological contexts and discovered that the most recent occupational phases at both sites are several centuries younger than previously thought. This is consistent with material evidence of lifestyle changes in the final phase at Hardinxveld-Giessendam de Bruin, which is now, according to our chronology, contemporaneous with the similar patterns produced in the region.
Comment on the article on ‘Within‐field wheat yield prediction from IKONOS data, a new matrix approach’ by E. A. Enclona, P. S. Thenkabail, D. Celis and J. Diekmann, International Journal of Remote Sensing, 25, 377–388 (2004)

This article comments on a method of within‐field yield prediction from IKONOS data published in this Journal (International Journal of Remote Sensing, 25, 377–388). The authors propose what they call a new matrix approach, which solves a system of linear equations relating actual yield to expected yield in four classes defined based on spectral characteristics and the relative areas for these classes as measured by remote sensing. The authors use five observations to estimate four unknown parameters, and they propose that generally p+1 observations could be used to estimate p parameters. This article shows that this approach will lead to very unreliable predictions of class yield. The problem is shown to be a standard multiple regression problem. It is argued that sample size must be considerably larger than the number of classes in order to obtain reliable yield estimates for the classes. Due to the very nature of the regressor variables, the relative areas of the classes, multicollinearity is expected to be a severe problem. Therefore, it may be useful to reduce the number of regressor variables using standard model selection procedures.
Cultural differences, intergenerational contacts, and the spread of Covid-19: Evidence from Swiss language regions

The Covid-19 pandemic displayed large variations between and within countries in the speed of contagion and in observed fatality rates. This work sheds light on the role of social ties in old age, exploiting the high cultural variation between German-speaking and Latin- (French- and Italian-) speaking regions in Switzerland. We show that older adults in Latin-speaking regions exhibit a larger social network and more intergenerational contacts than their German-speaking counterparts. These differences are consistent with the heterogeneous incidence of the disease across language regions. Even controlling for several determinants of the contagion, we find large differences in the incidence of Covid-19 among older adults, in both the first and second waves of the pandemic. These findings also hold when exploiting language variations within the three Swiss bilingual cantons. We rule out the possibility that our results are driven by differences in canton-specific policies or in citizens’ compliance with containment measures.
Therapeutic non-ectasia applications of cornea cross-linking

ABSTRACT Corneal cross-linking is a photopolymerization technique traditionally used to strengthen corneal tissue. Corneal cross-linking utilizes riboflavin (vitamin B2) as a photosensitizer and ultraviolet-A light (UVA) to create strong covalent bonds within the corneal stroma, increasing tissue stiffness. Multiple studies have demonstrated corneal cross-linking’s effectiveness in treating corneal ectasia, a progressive, degenerative, and non-inflammatory thinning disorder, as quantified by key tomographic, refractive, and visual parameters. Since its introduction two decades ago, corneal cross-linking has surpassed its original application in halting corneal ectatic disease and its application has expanded into several other areas. Corneal cross-linking also possesses antibacterial, antienzymolytic and antioedematous properties, and has since become a tool in treating microbial keratitis, correcting refractive error, preventing iatrogenic ectasia, stabilising bullous keratopathy and controlling post keratoplasty ametropia. This review provides an overview of the current evidence base for the therapeutic non-ectasia applications of cornea cross-linking and looks at future developments in the field.
Cell and cell-derivative-based therapy for liver diseases: current approaches and future promises

ABSTRACT Introduction According to the recent updates from World Health Organization, liver diseases are the 12th most common cause of mortality. Currently, orthotopic liver transplantation (OLT) is the most effective and the only treatment for end-stage liver diseases. Owing to several shortcomings like finite numbers of healthy organ donors, lifelong immunosuppression, and complexity of the procedure, cell and cell-derivatives therapies have emerged as a potential therapeutic alternative for liver diseases. Various cell types and therapies have been proposed and their therapeutic effects evaluated in preclinical or clinical studies, including hepatocytes, hepatocyte-like cells (HLCs) derived from stem cells, human liver stem cells (HLSCs), combination therapies with various types of cells, organoids, and implantable cell-biomaterial constructs with synthetic and natural polymers or even decellularized extracellular matrix (ECM). Areas covered In this review, we highlighted the current status of cell and cell-derivative-based therapies for liver diseases. Furthermore, we discussed future prospects of using HLCs, liver organoids, and their combination therapies. Expert opinion Promising application of stem cell-based techniques including iPSC technology has been integrated into novel techniques such as gene editing, directed differentiation, and organoid technology. iPSCs offer promising prospects to represent novel therapeutic strategies and modeling liver diseases.
Sequencing antigen‐targeting antibodies and cellular therapies in adults with relapsed/refractory B‐cell acute lymphoblastic leukemia

The recent approvals of four CD19‐or CD22‐targeted therapies for B‐cell acute lymphoblastic leukemia (B‐ALL) have transformed the treatment of relapsed/refractory (r/r) disease. Adults with r/r B‐ALL are usually eligible for all options, but there are no studies directly comparing these agents, and the treating physician must decide which to select. Each therapy has notable activity as a single agent but has limitations in particular settings, and the optimal choice varies. These therapies can be complementary and used either sequentially or concomitantly. Here, we review the current landscape of antigen‐targeted therapies for r/r B‐ALL and discuss considerations for their use.
Benchmarking the Compton coincidence technique for measuring electron response non-proportionality in inorganic scintillators

To study the light yield non-proportionality of inorganic scintillation materials, a Compton coincidence experiment has been designed and implemented. The coincidence technique is used to measure the nearly mono-energetic electron response by recording events only when energetic electrons are produced by gamma rays that are Compton scattered through a specific angle. This technique provides the ability to accurately determine the light yield non-proportionality of scintillation materials as a function electron energy while minimizing the potential effects of surface interaction and X-ray escape. To benchmark the Compton coincidence technique (CCT), the electron response for NaI(Tl) has been measured for electron energies from 2 keV to 450 keV and compared to previously-published analytical and measured light yield response data for electrons. The CCT data represent the most accurate electron response measurement to date on NaI(Tl) for energies below 20 keV. With the CCT benchmarked, the electron response non-proportionality of other scintillators can be analyzed.
ESSENTIAL SELF ADJOINTNESS OF LAPLACIANS ON RIEMANNIAN MANIFOLDS WITH FRACTAL BOUNDARY

We stutly the problem of the essential self-adjointness of Laplacians on Riemannian Manifolds. We show that a sufficient, condition is if the boundary of a manifold M. by which we mean M/M, where M is the metric completion of M, is almost polar set. Two other results concern special cases. when the boundary is some sort of fractal set or even a manifold. It is shown that the boundary is almost polar set in the cases under certain dimensional restrictions.
On Planar Elliptic Structures with Infinite Type Degeneracy

This paper studies global properties of a class of planar vector fields that are elliptic except along a simple and closed curve. With each such vector field, we associate a complex number. This complex number characterizes the structure and bears heavily on the solvability of the associated pde equations. Let L be a subbundle of the complexified tangent bundle CTR. Suppose that L is generated by a C vector field
The kinetic evolution and velocity distribution of gravitational galaxy clustering

The spatial statistical distribution function for quasi-equilibrium gravitational clustering in an expanding universe is derived from more general assumptions than before, without needing an earlier Ansatz. Then, it is shown how this statistical distribution is related to the kinetic development of the BBGKY hierarchy and how to obtain an analytic descriptioin for the time evolution of an initial Poisson distribution. From general principles, an analytic velocity distribution function for quasi-equilibrium gravitational clustering is also derived. It has no free parameters. Comparison with N-body experiments shows excellent agreement. 22 refs.