Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating Alternate Methods of Determining the Antimicrobial Efficacy of Contact Lens Care Products against Acanthamoeba Trophozoites

Acanthamoeba keratitis (AK) is a serious ocular infection caused by a ubiquitous free-living amoeba, Acanthamoeba. This infection often results in extensive corneal damage and blindness, and is notoriously difficult to cure. While Acanthamoeba is an abundant organism, AK is most associated with contact lens hygiene noncompliance and inadequate contact lens care (CLC) disinfection regimens. Thus, accurate and timely antimicrobial efficacy testing of CLC solutions is paramount. Published methods for antimicrobial efficacy testing of Acanthamoeba trophozoites requires 14 days for results. Presently, alternate and/or rapid methods for evaluating CLC products rarely demonstrate equivalent results compared to commonly-reported methods. Propidium iodide is a cellular stain that can only bind to cells with damaged outer membranes. We evaluated propidium iodide staining as an alternative method for determining the relative antimicrobial efficacy of 11 different CLC products against Acanthamoeba trophozoites. Following exposure to a CLC product, the fluorescence intensity of propidium iodide in an Acanthamoeba population demonstrated a strong correlation to the log reduction determined by established, growth-based Acanthamoeba testing used to evaluate the antimicrobial efficacy of CLC products. Thus, propidium iodide was found to be an effective rapid tool for determining cell death in Acanthamoeba trophozoites following exposure to CLC solutions.
‘I miss being honest’: sex workers’ accounts of silence and disclosure with health care providers in Ireland

Abstract In this paper, female sex workers tell stories of their interactions with health care providers (HCP) in four cities in the Republic of Ireland. While Irish society has made great progress in listening to the sexual stories of women that were historically silenced (e.g. stories of abortion, sexual abuse), sex workers have not benefited from this new climate. Regularly silenced by parliamentarians and non-governmental organisations who speak upon their behalf, sex workers are consigned within a narrative of victimhood and coercion. This paper draws from a participant action research study conducted in 2019–20 and explores women’s motivations in whether to disclose their sex work, and the strategies deployed to conceal it while seeking access to sexual health care. These strategies included traveling beyond their own communities for health care and STI home testing. The paper identifies women, particularly, migrants who felt their precarious position made it impossible for them to be truthful about their sex work to health care providers, exposing them to greater health risk. The paper understands this marginality within a context of structural violence where sex worker health is shaped by institutional power relations creating unequal health outcomes but is also challenged by stories of solidarity.
Lack of clinical significance for molecular detection of respiratory viruses in bronchoalveolar lavage samples

The clinical significance of molecular detection of respiratory viruses in bronchoalveolar lavage (BAL) samples is poorly defined. We performed an observational retrospective study including all patients who underwent a BAL procedure in our institution, regardless of the reason for bronchoscopy, from January 2015 to December 2018. Respiratory viruses were detected by real‐time polymerase chain reaction with a commercial multiplex panel, and a cell culture was performed to detect cytomegalovirus and herpes simplex virus. Positive results were correlated with clinical symptoms and patients' characteristics. Of 540 BAL samples analyzed, 113 (20.9%) were positive for any respiratory virus. Viral detection was significantly associated with respiratory symptoms (83.2% vs. 68.9%, p = .004) and radiological infiltrates (67.3% vs. 52.2%, p = .006). The most frequent viruses detected were rhinovirus (42/113, 37.2%), influenza virus (20/113, 17.7%), and parainfluenza virus (PIV) (16/113, 14.2%). Respiratory pathogens codetections were found in 51/113 (45.1%) BAL samples, including more than one virus (16/51, 31.4%), fungi (8/51, 15.7%), and bacteria (9/51, 17.6%). Viral detection was significantly higher in immunocompromised patients (26.5% vs. 16.9%; p = .022). PIV and human metapneumovirus were mostly observed in lung (50.0%, 8/16) and hemopoietic transplant recipients (25%, 2/8), respectively, with clinical repercussions. Our data underline that molecular diagnosis allows identification of viral agents as the etiology of respiratory infections; however, the high frequency of codetections hinders identification of the agent responsible for the current respiratory symptomatology. Immunocompromised patients are the target population in whom to investigate the presence of respiratory viruses in their BAL samples.
A phase-1 trial of linsitinib (OSI-906) in combination with bortezomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma

Abstract We report results of a phase-1 study evaluating the safety and anti-cancer activity of the small molecule insulin-like growth factor-1 receptor (IGF-1R) inhibitor, linsitinib combined with bortezomib, and dexamethasone in relapsed/refractory multiple myeloma. Nineteen patients were enrolled across four dose-escalation cohorts (75–150 mg bid). The maximum tolerated dose of linsitinib was 125 mg. The most frequent Grade 3/4 AEs occurring in ≥10% of patients were thrombocytopenia (53%), bone pain (26%), neutropenia (21%), diarrhea (14%), anemia (14%), rash (10%), and lung infection (10%). Study discontinuation due to treatment-related AEs was low (16%). Across all cohorts the ORR was 61% (95% CI: 28.9–75.6%). Three partial response or greater and one stable disease were observed in proteasome inhibitor (PI) refractory patients (n = 5). Median PFS was 7.1 months (95% CI: 3.6–NA). Linsitinib plus bortezomib and dexamethasone demonstrate a manageable safety profile while the clinical benefit particularly in PI refractory patients warrants further exploration.
Propensity score analysis methods with balancing constraints: A Monte Carlo study

The inverse probability weighting is an important propensity score weighting method to estimate the average treatment effect. Recent literature shows that it can be easily combined with covariate balancing constraints to reduce the detrimental effects of excessively large weights and improve balance. Other methods are available to derive weights that balance covariate distributions between the treatment groups without the involvement of propensity scores. We conducted comprehensive Monte Carlo experiments to study whether the use of covariate balancing constraints circumvent the need for correct propensity score model specification, and whether the use of a propensity score model further improves the estimation performance among methods that use similar covariate balancing constraints. We compared simple inverse probability weighting, two propensity score weighting methods with balancing constraints (covariate balancing propensity score, covariate balancing scoring rule), and two weighting methods with balancing constraints but without using the propensity scores (entropy balancing and kernel balancing). We observed that correct specification of the propensity score model remains important even when the constraints effectively balance the covariates. We also observed evidence suggesting that, with similar covariate balance constraints, the use of a propensity score model improves the estimation performance when the dimension of covariates is large. These findings suggest that it is important to develop flexible data-driven propensity score models that satisfy covariate balancing conditions.
Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets

Key Points Question What genes and genomic processes underlie risk of sporadic Parkinson disease? Findings This genetic association study integrated Parkinson disease genome-wide association study data and brain-derived gene regulation data using various complementary bioinformatic tools and identified 11 candidate genes with evidence of disease-associated regulatory changes. Coexpression and protein level analyses of these genes demonstrated a significant functional association with known mendelian Parkinson disease genes. Meaning This study suggests that gene regulation data may be used to identify candidate genes and pathways involved in sporadic Parkinson disease.
The Modern and Digital Transformation of Oral Health Care: A Mini Review

Dentistry is a part of the field of medicine which is advocated in this digital revolution. The increasing trend in dentistry digitalization has led to the advancement in computer-derived data processing and manufacturing. This progress has been exponentially supported by the Internet of medical things (IoMT), big data and analytical algorithm, internet and communication technologies (ICT) including digital social media, augmented and virtual reality (AR and VR), and artificial intelligence (AI). The interplay between these sophisticated digital aspects has dramatically changed the healthcare and biomedical sectors, especially for dentistry. This myriad of applications of technologies will not only be able to streamline oral health care, facilitate workflow, increase oral health at a fraction of the current conventional cost, relieve dentist and dental auxiliary staff from routine and laborious tasks, but also ignite participatory in personalized oral health care. This narrative article review highlights recent dentistry digitalization encompassing technological advancement, limitations, challenges, and conceptual theoretical modern approaches in oral health prevention and care, particularly in ensuring the quality, efficiency, and strategic dental care in the modern era of dentistry.
Reassessment of the enigmatic ruminant Miocene genus Amphimoschus Bourgeois, 1873 (Mammalia, Artiodactyla, Pecora)

Amphimoschus is an extinct Eurasian ruminant genus, mostly recorded in Europe, without a close living relative and, hence, an unknown systematic position. This genus is known from around 50 localities from the late early to the middle Miocene. Two species were described during 180 years, but since their first description during the late 19th century and early 20th century, hardly any detailed taxonomic work has been done on the genus. Over the years, extensive collecting and excavating activities have enriched collections with more and more complete material of this still rare and enigmatic animal. Most interestingly, a number of skull remains have been unearthed and are promising in terms of providing phylogenetic information. In the present paper, we describe cranial material, the bony labyrinth, the dentition through 780 teeth and five skulls from different ontogenetic stages. We cannot find a clear morphometric distinction between the supposedly smaller and older species Amphimoschus artenensis and the supposedly younger and larger species A. ponteleviensis. Accordingly, we have no reason to retain the two species and propose, following the principle of priority (ICZN chapter 6 article 23), that only A. ponteleviensis Bourgeois, 1873 is valid. Our studies on the ontogenetic variation of Amphimoschus does reveal that the sagittal crest may increase in size and a supraorbital ridge may appear with age. Despite the abundant material, the family affiliation is still uncertain.
Medication adherence in community-dwelling older people exposed to chronic polypharmacy

Background To evaluate medication adherence and associated factors of seven of the most common drug classes prescribed to community-dwelling older people. Methods This is a retrospective cohort study on medication adherence in community-dwelling older people (65–94 years old) on chronic polypharmacy and recorded from 2013 to 2015 in the administrative database of the Lombardy region (Northern Italy). Adherence was assessed for diabetic drugs, antithrombotic agents, drugs acting on the renin–angiotensin system, statins, bisphosphonates, antidepressants and drugs for obstructive airway diseases by calculating the medication possession ratio (MPR). Patients were then divided in fully (MPR ≥80%), partially (40%≤MPR<80%) and poorly adherent (10%<MPR<40%). Results Among 140 537 patients included in the study, only 19.3% was fully adherent to all the therapies considered. Almost 40% of them were poorly adherent to at least one drug class, becoming 50% when patients exposed to four or more drug classes were considered. In adjusted regression model, being women (OR=1.14, 95% CI 1.13 to 1.16) and aged ≥80 years old (OR=1.22, 95% CI 1.20 to 1.24) were associated with an overall lower adherence. Instead, the participation to an experimental healthcare programme was associated with higher adherence (OR=0.92, 95% CI 0.87 to 0.96). Furthermore, being coprescribed with ≥10 drugs was associated with lower adherence to all the drug classes, with different effects (ORs from 0.42 to 0.73). Conclusion This study overall shows a low medication adherence in community-dwelling older people on chronic polypharmacy, especially in women and oldest old. The implementation and promotion of healthcare programmes for these patients could help improve overall adherence to chronic drug therapies.
Experimentally elevated testosterone shortens telomeres across years in a free‐living songbird

Reproductive investment often comes at a cost to longevity, but the mechanisms that underlie these long‐term effects are not well understood. In male vertebrates, elevated testosterone has been shown to increase reproductive success, but simultaneously to decrease survival. One factor that may contribute to or serve as a biomarker of these long‐term effects of testosterone on longevity is telomeres, which are often positively related to lifespan and have been shown to shorten in response to reproduction. In this longitudinal study, we measured the effects of experimentally elevated testosterone on telomere shortening in free‐living, male dark‐eyed juncos (Junco hyemalis carolinensis), a system in which the experimental elevation of testosterone has previously been shown to increase reproductive success and reduce survival. We found a small, significant effect of testosterone treatment on telomeres, with testosterone‐treated males exhibiting significantly greater telomere shortening with age than controls. These results are consistent with the hypothesis that increased telomere shortening may be a long‐term cost of elevated testosterone exposure. As both testosterone and telomeres are conserved physiological mechanisms, our results suggest that their interaction may apply broadly to the long‐term costs of reproduction in male vertebrates.
Enhanced In Vivo Absorption of Itraconazole via Stabilization of Supersaturation Following Acidic-to-Neutral pH Transition

Previous attempts to improve the dissolution and absorption properties of itraconazole (ITZ) through advanced formulation design have focused only on release in acidic media; however, recent reports indicate that absorption occurs primarily in the proximal small intestine. This suggests that enhancing supersaturation of ITZ in neutral aqueous environments is essential for improving absorption. The aim of this study was to evaluate different polymeric stabilizers with either immediate release (IR) (Methocel™ E5, Methocel™ E50, Kollidon® 12, and Kollidon® 90) or enteric release (EUDRAGIT® L 100-55, HP-55, and HP-55S) properties to determine the chemical and physical attributes of the polymeric stabilizers that promote supersaturation of ITZ in neutral media. Each amorphous composition was produced by hot-melt extrusion and characterized by differential scanning calorimetry. Dissolution testing by a supersaturated acidic-to-neutral pH change method was conducted on each composition. Testing of IR compositions revealed that Methocel™ was a superior stabilizer compared with Kollidon® owing to stronger intermolecular interaction with ITZ molecules in solution. Increasing the molecular weight of polymers was found to promote ITZ supersaturation and was most likely attributable to increased solution viscosity resulting in retention of ITZ molecules in an enthalpically favored association with the polymer for extended durations. Of the enteric polymeric stabilizers, EUDRAGIT® L 100-55 was found to be superior to both HP-55 grades because of its greater permeability to acid that allowed for improved hydration of ITZ in the acid phase as well as a greater number of free hydroxyl groups on the polymer backbone that presumably helped to stabilize ITZ in solution. The Methocel™ E50 and EUDRAGIT® L 100-55 formulations were evaluated for in vivo drug absorption in male Sprague–Dawley rats and were found to produce a threefold greater ITZ absorption over our previously reported IR formulations. The results of this study confirmed the hypothesis that supersaturation of ITZ following an acidic-to-neutral pH transition in vitro correlates directly to in vivo absorption.
Inferring pore radius and density from ultrasonic attenuation using physics-based modeling.

This work proposes the use of two physics-based models for wave attenuation to infer the microstructure of cortical bone-like structures. One model for ultrasound attenuation in porous media is based on the independent scattering approximation (ISA) and the other model is based on the Waterman Truell (WT) approximation. The microstructural parameters of interest are pore radius and pore density. Attenuation data are simulated for three-dimensional structures mimicking cortical bone using the finite-difference time domain package SimSonic. These simulated structures have fixed sized pores (monodisperse), allowing fine-tuned control of the microstructural parameters. Structures with pore radii ranging from 50 to 100 μm and densities ranging from 20 to 50 pores/mm3 are generated in which only the attenuation due to scattering is considered. From here, an inverse problem is formulated and solved, calibrating the models to the simulated data and producing estimates of pore radius and density. The estimated microstructural parameters closely match the values used to simulate the data, validating the use of both the ISA and WT approximations to model ultrasonic wave attenuation in heterogeneous structures mimicking cortical bone. Furthermore, this illustrates the effectiveness of both models in inferring pore radius and density solely from ultrasonic attenuation data.
The Brain-Gut Axis: Psychological Functioning and Inflammatory Bowel Diseases

The brain-gut axis represents a complex bi-directional system comprising multiple interconnections between the neuroendocrine pathways, the autonomous nervous system and the gastrointestinal tract. Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a chronic, relapsing-remitting inflammatory disorder of the gastrointestinal tract with a multifactorial etiology. Depression and anxiety are prevalent among patients with chronic disorders characterized by a strong immune component, such as diabetes mellitus, cancer, multiple sclerosis, rheumatoid arthritis and IBD. Although psychological problems are an important aspect of morbidity and of impaired quality of life in patients with IBD, depression and anxiety continue to be under-diagnosed. There is lack of evidence regarding the exact mechanisms by which depression, anxiety and cognitive dysfunction may occur in these patients, and whether psychological disorders are the result of disease activity or determinants of the IBD occurrence. In this comprehensive review, we summarize the role of the brain-gut axis in the psychological functioning of patients with IBD, and discuss current preclinical and clinical data on the topic and therapeutic strategies potentially useful for the clinical management of these patients. Personalized pathways of psychological supports are needed to improve the quality of life in patients with IBD.
Free P-Cresyl Sulfate Shows The Highest Association With Cardiovascular Outcome In Chronic Kidney Disease.

BACKGROUND Several protein-bound uremic toxins (PBUT) have been associated with cardiovascular (CV) and all-cause mortality in chronic kidney disease (CKD) but the degree to which this is the case per individual PBUT and the pathophysiological mechanism had only partially been unraveled. METHODS We compared the prognostic value of both total and free concentrations of 5 PBUT [p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG); indoxyl sulfate (IxS); indole acetic acid (IAA) and hippuric acid (HA)] in a cohort of 523 patients with non-dialysis CKD stage G1-G5. Patients were followed prospectively for the occurrence of a fatal or non-fatal CV event as the primary endpoint and a number of other major complications as secondary endpoints. In addition, association with and the prognostic value of 9 markers of endothelial activation/damage was compared. RESULTS After a median follow-up of 5.5 years, 149 patients developed the primary endpoint. In multivariate Cox-regression models adjusted for age, sex, systolic blood pressure, diabetes mellitus, and eGFR, and corrected for multiple testing, only free p-cresyl sulfate (pCS) was associated with the primary endpoint (1.39[1.14-1.71]; p = 0.0014). Free pCS also correlated with ADAMST13 (r=-0.114; p < 0.05), ANGPT2 (r = 0.194; p < 0.001), MMP-7 (r = 0.238; p < 0.001) and syndecan 1 (r = 0.235; p < 0.001). Of these markers of endothelial activation/damage, ANGPT2 (1.46[1.25-1.70]; p < 0.0001) and MMP-7 (1.31[1.08-1.59]; p = 0.0056) were also predictive of the primary outcome. CONCLUSIONS Among PBUTs, free pCS shows the highest association with cardiovascular outcome in non-dialysed patients with CKD. Two markers of endothelial activation/damage that were significantly correlated to free pCS, ANGPT2 and MMP-7, were also associated with CV outcome. The hypothesis that free pCS exerts its cardiovascular toxic effects by an adverse effect on endothelial function deserves further exploration.
Effects of Acute Visual Stimulation Exercise on Attention Processes: An ERP Study

Backgrounds: It remains to be determined whether visual stimuli during exercise differentially influence the attention process. The purpose of the present study was to examine if different color stimuli during aerobic exercise are associated with different attention processes. Methods: 22 college students completed a four 30-min running session during the presentation of different color stimuli (blue, green, red, and yellow) and without color stimulus on separate visits. The Kanizsa triangle task was administrated before and immediately after exercise to assess the attention process. Behavioral performance (accuracy and response time (RT)) and event-related potential (P2, N2b and P3a) were recorded during the test. Results: Valid/invalid cue RT during the Kaniza test performance was significantly faster following the presentation of color stimuli during treadmill exercise compared to the seated rest. During exercise, these changes were larger after green and yellow stimuli than red in invalid cue RT. P2, N2b and P3a amplitudes of green were significantly larger than the other colors for both valid and invalid cues. Red color showed the lowest P2 and P3a amplitudes for both valid and invalid cues among colors. Conclusion: The distinctive neurocognitive changes during aerobic exercise suggest different effects of color stimuli on visual search attention, attention capture, attentional orienting and processing speed. This study will be a first step to understand the optimal environmental setting during exercise for subsequent improvements in the attention process.