Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the safety of a novel peripheral vasopressor pilot program and the impact on central line placement in medical and surgical intensive care units

Abstract Purpose The purpose of this quality improvement project was to evaluate the safety and feasibility of peripheral vasopressor administration in an attempt to minimize the placement and improve early removal of unnecessary central lines to reduce central line–associated bloodstream infection (CLABSI) rates. Methods A retrospective chart review was conducted on patients who received vasopressors via peripheral infusion over 3 months, starting at the time of guideline implementation. Results We identified 129 vasopressor orders among 79 patients that were administered peripherally. Among these orders, 3 events were documented as possible extravasation events. Forty-five patients (57%) did not require central line placement due to increasing vasopressor requirements. Standard utilization ratio data suggest minimal central line impact of the protocol implementation. December 2020 to February 2021 was associated with a large second peak of coronavirus disease 2019 (COVID-19) in our region. Utilization of central lines was less than predicted in December 2020 to February 2021 in 2 of our 3 intensive care units (ICUs); however, the differences were statistically significant on only 3 occasions. In the third ICU, utilization was greater than predicted, but this unit housed a majority of the most critically ill patients with COVID-19. Conclusion This study suggests that short-term use of select vasopressors at conservative doses is safe for peripheral administration and points toward efficacy at preventing central line placement. Further analysis is required to confirm efficacy.
Microemulsion: a novel alternative technique for edible oil extraction_a mechanistic viewpoint

Abstract Microemulsions, as isotropic, transparent, nano size (<100 nm), and thermodynamically stable dispersions, are potentially capable of being used in food formulations, functional foods, pharmaceuticals, and in many other fields for various purposes, particularly for nano-encapsulation, extraction of bioactive compounds and oils, and as nano-reactors. However, their functionalities, and more importantly their oil extraction capability, strongly depend on, and are determined by, their formulation, molecular structures and the type, ratio and functionality of surfactants and co-surfactants. This review extensively describes microemulsions (definition, fabrication, thermodynamic aspects, and applications), and their various mechanisms of oil extraction (roll-up, snap-off, and solubilization including those by Winsor Types I, II, III, and IV systems). Applications of various food grade (natural or synthetic) and extended surfactants for edible oil extraction are then covered based on these concepts.
Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab

Kater and colleagues report on 5-year outcomes for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) when treated with fixed-duration venetoclax-rituximab (VenR) in a pivotal randomized trial. Over 50% of patients who completed a 3-year VenR treatment have not progressed, and median time to next treatment is 58 months. Of 43% of patients with no measurable residual disease (MRD) at completion of VenR, 39% remained MRD-negative 3 years later, emphasizing the durability of the benefits for many patients.
Effect of selective serotonin reuptake inhibitor discontinuation on anxiety-like behaviours in mice

Background: Abrupt cessation of therapy with a selective serotonin reuptake inhibitor (SSRI) is associated with a discontinuation syndrome, typified by numerous disabling symptoms, including anxiety. Surprisingly, little is known of the behavioural effect of SSRI discontinuation in animals. Aim: Here, the effect of SSRI discontinuation on anxiety-like behaviour was systematically investigated in mice. Methods: Experiments were based on a three-arm experimental design comprising saline, continued SSRI and discontinued SSRI. Mice were assessed 2 days after SSRI discontinuation over a 5-day period using the elevated plus maze (EPM) and other anxiety tests. Results: An exploratory experiment found cessation of paroxetine (12 days) was associated with decreased open-arm exploration and reduced total distance travelled, in male but not female mice. Follow-up studies confirmed a discontinuation effect on the EPM in male mice after paroxetine (12 days) and also citalopram (12 days). Mice receiving continued paroxetine (but not citalopram) also showed decreased open-arm exploration but this was dissociable from the effects of discontinuation. The discontinuation response to paroxetine did not strengthen after 28 days of treatment but was absent after 7 days of treatment. A discontinuation response was not discernible in other anxiety and fear-learning tests applied 3–5 days after treatment cessation. Finally, discontinuation effects on the EPM were typically associated with decreased locomotion on the test. However, separate locomotor testing implicated anxiety-provoked behavioural inhibition rather than a general reduction in motor activity. Conclusion: Overall, this study provides evidence for a short-lasting behavioural discontinuation response to cessation of SSRI treatment in mice.
Healthcare resource utilization and costs in individuals with Huntington’s disease by disease stage in a US population

Abstract Aims To quantify healthcare resource utilization (HRU) and costs by disease stage in individuals with Huntington’s disease (HD) in a US population. Materials and methods This retrospective cohort study used administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases between 1 January 2009 and 31 December 2018. Individuals with an HD claim between 1 January 2010 and 31 December 2017 were selected. Index date was the date of first HD diagnosis. Individuals were required to have continuous enrollment for ≥ 12 months pre-index, 3 months post-index, and have no pre-index HD claims. All-cause HRU and costs per patient per month (PPPM) (overall and stratified by disease stage) were assessed for individuals with HD. Results A total of 2,669 individuals with HD were identified. Of these, 1,432 (53.7%), 689 (25.8%), and 548 (20.5%) had early-, middle-, and late-stage HD at baseline, respectively. Mean HRU PPPM by post-index HD stage increased with disease stage for outpatient visits, pharmacy claims, and HD-related pharmacy claims (p < 0.05 for all). Mean inpatient visits and emergency room visits PPPM were highest in individuals with middle-stage HD (p <0.05 for all). Mean total all-cause healthcare cost PPPM for individuals with HD was $2,889, and it was significantly higher in middle-stage individuals, at $7,988, compared with early- and late-stage individuals, at $3,726 and $5,125, respectively; p <0.0001. Limitations In the absence of disease staging information in administrative claims data, staging was based on the presence of clinical markers in claims. Our evaluations didn’t include the indirect costs of HD, which may be substantial as HD typically affects people at their peak earning potential. Conclusions HRU and costs of care are high among individuals with HD, particularly among those with middle- and late-stage disease. This indicates that the disease burden in HD increases with disease stage, highlighting the need for interventions that can slow or prevent disease progression.
miR-146a suppresses the expression of vascular endothelial growth factor and inflammatory responses in diabetic retinopathy

Abstract This study was designed to explore the role of miR-146a in diabetic retinopathy (DR). 30 healthy control (HC), 50 patients with type 2 diabetes mellitus, and 48 DR patients were enrolled. Blood was collected and levels of miR-146a expression, vascular endothelial growth factor (VEGF), and three inflammatory cytokines (NF-κB, IL-1β, and TNF-α) were detected. Moreover, ARPE-19 cells were treated with miR-146a mimic or inhibitor in the presence of high glucose to evaluate its effect in vitro. DR patients had the lowest level of miR-146a and the highest level of VEGF as well as the most severe inflammation among the three groups. In addition, the miR-146a level was negatively correlated with the expression of VEGF and three inflammatory cytokines, respectively in DR patients. Moreover, VEGF expression was positively correlated with these three inflammatory cytokines in DR patients. In summary, miR-146a could inhibit VEGF expression and inflammation in DR.
Oncological outcomes of retroperitoneal lymph node dissection during retroperitoneal laparoscopic radical nephroureterectomy for renal pelvic or upper ureteral tumors: Matched-pair analysis.

OBJECTIVES To investigate the oncological outcomes and recurrence patterns of clinically node-negative patients with renal pelvic and/or upper or middle ureteral tumors after a template-based retroperitoneal lymph node dissection (RPLND) in conjunction with retroperitoneal laparoscopic radical nephroureterectomy (LRNU). METHODS A total of 283 patients who received LRNU with and without RPLND at three Japanese institutions were enrolled. The template of RPLND included the renal hilar and paraaortic lymph nodes (LNs) (left side) and renal hilar, paracaval, retrocaval, and intra-aortocaval LNs (right side). The LNs and kidneys were removed en bloc. The primary endpoint was set as recurrence-free survival. All RPLND cases were matched one-to-one with no RPLND cases using a propensity score matching approach, and 47 matched pairs were included in analyses. RESULTS Compared to the control group, significant differences were not observed in the RPLND group in terms of operation time, blood loss, postoperative complication rate, and pathological findings. The estimated five-year recurrence-free survival was significantly higher in the RPLND group (86.8%) compared to the group without RPLND (64.2%) (p = 0.014). The estimated five-year cancer-specific survival showed a similar tendency; however, it did not reach a statistically significant difference (87.5% vs 71.3%, respectively; p = 0.168). As for the first recurrence site, the RPLND group showed a lower incidence of distant recurrence, while a significant difference was not observed in the rate of regional LN recurrence. CONCLUSION This study suggests that a template-based RPLND in conjunction with retroperitoneal LRNU efficiently improves the recurrence-free survival by reducing distant recurrences.
Associations of Clinical and Social Risk Factors With Racial Differences in Premature Cardiovascular Disease

Background: Racial differences in cardiovascular disease (CVD) are likely related to differences in clinical and social factors. The relative contributions of these factors to Black-White differences in premature CVD have not been investigated. Methods: In Black and White adults aged 18 to 30 years at baseline in the CARDIA study (Coronary Artery Risk Development in Young Adults), the associations of clinical, lifestyle, depression, socioeconomic, and neighborhood factors across young adulthood with racial differences in incident premature CVD were evaluated in sex-stratified, multivariable-adjusted Cox proportional hazards models using multiply imputed data assuming missing at random. Percent reduction in the β estimate (log-hazard ratio [HR]) for race quantified the contribution of each factor group to racial differences in incident CVD. Results: Among 2785 Black and 2327 White participants followed for a median 33.9 years (25th–75th percentile, 33.7–34.0), Black (versus White) adults had a higher risk of incident premature CVD (Black women: HR, 2.44 [95% CI, 1.71–3.49], Black men: HR, 1.59 [1.20–2.10] adjusted for age and center). Racial differences were not statistically significant after full adjustment (Black women: HR, 0.91 [0.55–1.52], Black men: HR 1.02 [0.70–1.49]). In women, the largest magnitude percent reduction in the β estimate for race occurred with adjustment for clinical (87%), neighborhood (32%), and socioeconomic (23%) factors. In men, the largest magnitude percent reduction in the β estimate for race occurred with an adjustment for clinical (64%), socioeconomic (50%), and lifestyle (34%) factors. Conclusions: In CARDIA, the significantly higher risk for premature CVD in Black versus White adults was statistically explained by adjustment for antecedent multilevel factors. The largest contributions to racial differences were from clinical and neighborhood factors in women, and clinical and socioeconomic factors in men.
Ciliate research: From myth to trendsetting science

This special issue of the Journal of Eukaryotic Microbiology (JEM) summarizes achievements obtained by generations of researchers with ciliates in widely different disciplines. In fact, ciliates range among the first cells seen under the microscope centuries ago. Their beauty made them an object of scientia amabilis, and their manifold reactions made them attractive for college experiments and finally challenged causal analyses at the cellular level. Some of this work was honored by a Nobel Prize. Some observations yielded a baseline for additional novel discoveries, occasionally facilitated by specific properties of some ciliates. This also offers some advantages in the exploration of closely related parasites (malaria). Articles contributed here by colleagues from all over the world encompass a broad spectrum of ciliate life, from genetics to evolution, from molecular cell biology to ecology, from intercellular signaling to epigenetics, etc. This introductory chapter, largely based on my personal perception, aims at integrating work presented in this special issue of JEM into a broader historical context up to current research.
On Consistent Entropy-Regularized k-Means Clustering With Feature Weight Learning: Algorithm and Statistical Analyses

Clusters in real data are often restricted to low-dimensional subspaces rather than the entire feature space. Recent approaches to circumvent this difficulty are often computationally inefficient and lack theoretical justification in terms of their large-sample behavior. This article deals with the problem by introducing an entropy incentive term to efficiently learn the feature importance within the framework of center-based clustering. A scalable block-coordinate descent algorithm, with closed-form updates, is incorporated to minimize the proposed objective function. We establish theoretical guarantees on our method by Vapnik–Chervonenkis (VC) theory to establish strong consistency along with uniform concentration bounds. The merits of our method are showcased through detailed experimental analysis on toy examples as well as real data clustering benchmarks.
Investigating metacarpi of Hamdani sheep via different measurement and modelling methods: A methodological study

The aim of the study was to perform the morphometric analyses on metacarpi of Hamdani sheep via different measurement methods and to compare the methods. Thus, metacarpal bones of 15 females and 15 males were used in the study. Measurements were taken from the measurement points determined on metacarpus via four methods, and their statistical analyses were performed. When both male and female metacarpal bones were examined in the De parameter in the comparison with the methods, it was observed that the four measurement methods were different from one another (p < 0.01). When DEM and DEL measurement parameters were examined in male metacarpus, the highest value was measured in ImageJ and the smallest value was measured in 3D Slicer software; however, it was found that the statistical difference was not significant when compared numerically (p > 0.05). As a result, while it was observed that the measurements made by using digital calliper measurements, photometric analysis, and 3D software were similar in some of the parameters but there was no statistically significant difference; whereas, Statistical difference was detected in some parameters.
Factors Associated With Low Procedural Pain Scores Among 1- to 5-Year-Old Patients Undergoing Facial Laceration Repair

Objectives Our objectives were to quantify pain experienced by young children undergoing facial laceration repair and identify factors associated with low procedural pain scores. Methods We conducted a prospective cohort study of children’s distress among a convenience sample of children aged 1 to 5 years undergoing facial or scalp laceration repair in 2 pediatric emergency departments. We reviewed video recordings and documented pain scores at 15-second intervals using the Face, Leg, Activity, Cry, Consolability—Revised (FLACC-r) scale. We dichotomized FLACC-r into low/high scores (≤3 and >3) to evaluate practice variables. Results We included 11,474 FLACC-r observations from 258 procedures in the analysis. Two-thirds of 3- to 5-year-olds completed their laceration repair without the use of restraint, sedation, or anxiolytics. Mean distress scores were low (≤2.5 out of 10) across all procedure phases for 2- to 5-year-old patients. One-year-old patients experienced significantly more distress than their older counterparts (mean ≤4.2 out of 10). Odds of having low FLACC scores (≤3) were greater for patients with an expert clinician (adjusted odds ratio [aOR]: 1.72; 95% confidence interval [CI], 1.05–2.84). Wound infiltration (aOR, 0.35; 95% CI, 0.13–0.93), patient observation of a needle (aOR, 0.21; 95% CI, 0.14–0.33), and restraint (aOR, 0.04; 95% CI, 0.02–0.06) were negatively associated with low FLACC score. Conclusion The majority of 3- to 5-year-old patients were able to undergo facial laceration repair without restraint, sedation, or anxiolytics and with low mean distress scores. Our findings suggest that children’s risk of experiencing moderate and severe distress during facial and scalp laceration repair may be reduced by prioritizing wound closure by expert-level clinicians, ensuring effective lidocaine-epinephrine-tetracaine application, avoiding restraint, and concealing needles from patient view.
Cerebrovascular reactivity and deep white matter hyperintensities in migraine: A prospective CO2 targeting study

Several studies suggested the association of migraine with deep white matter hyperintensities (WMHs). We aimed to explore the cerebrovascular reactivity (CVR), deep WMH burden, and their association in patients with migraine using a state-of-the-art methodology. A total of 31 patients with migraine without aura and 31 age/sex-matched controls underwent 3T MRI with prospective end-tidal carbon dioxide (CO2) targeting. We quantified deep WMH clusters using an automated segmentation tool and measured voxel-wise CVR by changes in blood oxygen level-dependent signal fitted to subjects’ end-tidal CO2. The association of migraine and CVR with the presence of WMH in each voxel and interaction of migraine and CVR on WMH were analysed. Patients had a higher number of deep WMHs than controls (p = 0.015). Migraine and reduced CVR were associated with increased probability of having WMHs in each voxel (adjusted OR 30.78 [95% CI 1.89–500.53], p = 0.016 and adjusted OR 0.30 [0.29–0.32], p < 0.001, respectively). Migraine had an effect modification on CVR on deep WMHs (p for interaction <0.001): i.e. the association between CVR and WMH was greater in patients than in controls. We suggest that the migraine-WMH association can be explained by the effect modification on the CVR.
Component analysis of nucleolar protein compartments using Xenopus laevis oocytes

The nucleolus is a multi‐compartment, non‐membrane‐bound organelle within the nucleus. Nucleolar assembly is influenced by proteins capable of phase separation. Xenopus laevis oocytes contain hundreds of large nucleoli that provide experimental access for nucleoli that is unavailable in other systems. Here we detail methods to streamline the in vivo analysis of the compartmentalization of nucleolar proteins that are suspected of phase separation. The nucleolus is the main hub of ribosome biogenesis and here we present data supporting the division of proteins into nucleolar domains based on their function in ribosome biogenesis. We also describe the use of vital dyes such as Hoechst 33342 and Thioflavin T in nucleolar staining. Additionally, we quantify nucleolar morphology changes induced by heat shock and actinomycin D treatments. We suggest these approaches will be valuable in a variety of studies that seek to better understand the nucleolus, particularly those regarding phase separation. These approaches may also be instructive for other studies on phase separation, especially in the nucleus.
Collectively learning to talk about personal concerns in a peer‐led youth program: A field study of a community of practice

Abstract Youth peer‐support is an increasingly established approach to youth work. Drawing on Wenger's theory of a ‘community of practice’, this study explored social learning processes in an Australian community‐based and peer‐led youth program for young people from disadvantaged backgrounds. Social learning was conceptualised as arising from processes of ‘negotiated meaning’, which Wenger described as a duality of ‘participation’ and ‘reification’. The study was designed as a qualitative field study drawing on participant observation data from weekend workshops and 16 semi‐structured interviews with young program participants. Results indicate that the program was highly conventionalised with repeated practices reifying the meaning negotiated by the participants. However, it was also open for participatory negotiation of meaning through which participants learned to recognise and share their own and others' vulnerabilities, which created a strong sense of belonging to a community of equals. The study's conception of social learning offers a novel explanation of how the youth program created and sustained alternative transformative spaces. This was done through simple, repetitive and highly conventionalised practices, brokered by peers, that allowed participants to recognise and address their own and others' vulnerabilities in new ways.
Self-Care of Chronic Illness Inventory: An Initial Psychometric Evaluation in People Living With HIV in Italy

Abstract Self-care is essential to achieve positive clinical outcomes in patients with chronic diseases; however, self-care behaviors of people living with HIV (PLWH) have not been extensively studied due to the lack of validated measurements. We performed preliminary psychometric analyses of the structural validity and internal consistency of the Self-Care of Chronic Illness Inventory among 108 PLWH living in Italy and assessed self-care levels. Our findings largely replicate the instrument's original factor structure and indicated high internal consistency and reliability. Additionally, we found that PLWH performed self-care behaviors at suboptimal levels. Recommendations for clinical care and future investigations are advanced.