Miracle-dz/UniFAR-FTUs huggingface dataset:
Initiating pancreatic neuroendocrine tumour (pNET) screening in young MEN1 patients: results from the DutchMEN Study Group.

CONTEXT Non-functioning pancreatic neuroendocrine tumours (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate. OBJECTIVE To assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients. PATIENTS AND SETTING Pancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. DESIGN Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. INTERVENTION(S) Not applicable. MAIN OUTCOME MEASURE(S) The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease. RESULTS Five of 350 patients developed clinically relevant NF-pNETs before age 18, two of which subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET-free survival were found for sex, timeframe, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5% and 5% risk of having developed a clinically relevant tumour are 9.5 (6.5 - 12.7), 13.5 (10.2 - 16.9) and 17.8 years (14.3 - 21.4) respectively. CONCLUSION Analyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13-14 is justified. The psychological and medical burden of screening at a young age should be considered.
Directed movement toward, translocation along, penetration into and exit from vascular networks by breast cancer cells in 3D

ABSTRACT We developed a computer-assisted platform using laser scanning confocal microscopy to 3D reconstruct in real-time interactions between metastatic breast cancer cells and human umbilical vein endothelial cells (HUVECs). We demonstrate that MB-231 cancer cells migrate toward HUVEC networks, facilitated by filopodia, migrate along the network surfaces, penetrate into and migrate within the HUVEC networks, exit and continue migrating along network surfaces. The system is highly amenable to 3D reconstruction and computational analyses, and assessments of the effects of potential anti-metastasis monoclonal antibodies and other drugs. We demonstrate that an anti-RHAMM antibody blocks filopodium formation and all of the behaviors that we found take place between MB-231 cells and HUVEC networks.
Physical Activity and Total Daily Energy Expenditure in Older US Adults: Constrained versus Additive Models

Supplemental digital content is available in the text. ABSTRACT Purpose This study aimed to examine the shape of the relationship between physical activity (PA) and total energy expenditure (TEE) and to explore the role of energy balance status (negative, stable, positive) in influencing this association. Methods Cross-sectional. Participants were 584 older adults (50–74 yr) participating in the Interactive Diet and Activity Tracking in AARP study. TEE was assessed by doubly labeled water and PA by accelerometer. The relationship between PA and TEE was assessed visually and using nonlinear methods (restricted cubic splines). Percent weight change (>3%) over a 6-month period was used as a proxy measurement of energy balance status. Results TEE generally increased with increasing deciles of PA averaging 2354 (SD, 351) kcal·d−1 in the bottom decile to 2693 (SD, 480) kcal·d−1 in the top decile. Cubic spline models showed an approximate linear association between PA and TEE (linear relation, P < 0.0001; curvature, P = 0.920). Results were similar in subgroup analyses for individuals classified as stable or positive energy balance. For those in negative energy balance, TEE was generally flat with increasing deciles of PA averaging 2428 (SD, 285) kcal·d−1 in the bottom decile to 2372 (SD, 560) kcal·d−1 in the top decile. Conclusions Energy balance status seems to play an important role in the relationship between PA and TEE. When in a positive energy balance, the relationship between TEE and PA was consistent with an additive model; however, when energy balance was negative, TEE seems to be consistent with a constrained model. These findings support PA for weight gain prevention by increasing TEE; however, the effect of PA on TEE during periods of weight loss may be limited. An adequately powered, prospective study is warranted to confirm these exploratory findings.
Effect of H2O2 Antiseptic on Dispersal of Cavitation-Induced Microdroplets

The persisting outbreak of SARS-CoV-2 has posed an enormous threat to global health. The sustained human-to-human transmission of SARS-CoV-2 via respiratory droplets makes the medical procedures around the perioral area vulnerable to the spread of the disease. Such procedures include the ultrasonic dental cleaning method, which occurs within the oral cavity and involves cavitation-induced sprays, thus increasing the risk of pathogen transmission via advection. To understand the associated health and safety risks for patients and clinicians, it is critical to understand the flow pattern of the spray cloud around the operating region, the size and velocity distribution of the emitted droplets, and the extent of fluid dispersion until ultimate deposit on surfaces or escape through air vents. In this work, the droplet size and velocity distributions of the spray emerging from the tip of a free-standing common ultrasonic dental cleaning device were characterized via high-speed imaging. Deionized water and 1.5% and 3% aqueous hydrogen peroxide (H2O2) solutions were used as working fluids, with the H2O2—an established oxidizing agent—intended to curb the survival of virus released in aerosols generated from dental procedures. The measurements reveal that the presence of H2O2 in the working fluid increases the mean droplet size and ejection velocity. Detailed computational fluid dynamic simulations with multiphase flow models reveal benefits of adding small amounts of H2O2 in the feed stream of the ultrasonic cleaner; this practice causes larger droplets with shorter residence times inside the clinic before settling down or escaping through air vents. The results suggest optimal benefits (in terms of fluid spread) of adding 1.5% H2O2 in the feed stream during dental procedures involving ultrasonic tools. The present findings are not specific to the COVID-19 pandemic but should also apply to future outbreaks caused by airborne droplet transmission.
Quality-of-Care Implications of Antimicrobial Prescription Patterns for Acute Respiratory Tract Infections

ABSTRACT The Centers for Disease Control and Prevention estimates that half of the antibiotic prescriptions for acute respiratory tract infections (ARTIs) in ambulatory care settings are unnecessary. To better understand the quality-of-care implications of prescription patterns for ARTIs, we conducted a retrospective chart review of outpatient ARTI visits, across a large integrated health system, and examined the association of patient characteristics with receiving antimicrobials, as well as the association between receiving antimicrobials and healthcare utilization (outpatient and emergency department visits). We found that 55.4% of all ARTI outpatients were treated with antimicrobials. There was no association between patient demographics and antimicrobial prescriptions on either the first (p < .0771) or follow-up (p < .6316) visits. A lower comorbidity score was significantly associated with receiving antimicrobials (p < .0022). Patients who received antimicrobials at the first visit had significantly higher number of follow-up visits (p < .005) and more follow-up antimicrobial prescriptions (p < .0066) as compared with patients who did not receive antimicrobials at the first visit. Our results highlight the potential for clinicians to improve quality of care in ARTI management.
Association of systemic inflammation with survival in patients with cancer cachexia: results from a multicentre cohort study

Although systemic inflammation is an important feature of the cancer cachexia, studies on the association between systemic inflammation and prognostic of cancer cachexia are limited. The objective of this study is to evaluate whether the neutrophil‐to‐lymphocyte ratio (NLR) is associated with outcome and quality of life for patients with cancer cachexia and investigated any interaction between NLR and the clinical parameters.
Characterization of β-adrenergic receptors in bovine intramuscular and subcutaneous adipose tissue: comparison of lubabegron fumarate with β-adrenergic receptor agonists and antagonists

Abstract Chinese hamster ovary cell constructs expressing either the β 1-, β 2- or β 3-adrenergic receptor (AR) were used to determine whether a novel β-AR modulator, lubabegron fumarate (LUB; Experior, Elanco Animal Health) might exert greater potency for a specific β-AR subtype. EC50 values calculated based on cAMP accumulation in dose response curves indicate that LUB is highly selective for the β 3-AR subtype, with an EC50 of 6 × 10–9 M, with no detectible agonistic activity at the β 2-AR. We hypothesized that the accumulation of lipolytic markers would reflect the agonist activity at each of the β-receptor subtypes of the specific ligand; additionally, there would be differences in receptor subtype expression in subcutaneous (s.c.) and intrmuscular (i.m.) adipose tissues. Total RNA was extracted from adipose tissue samples and relative mRNA levels for β 1-, β2-, and β 3-AR were measured using real-time quantitative polymerase chain reaction. Fresh s.c. and i.m. adipose tissue explants were incubated with isoproterenol hydrochloride (ISO; β-AR pan-agonist), dobutamine hydrochloride (DOB; specific β 1-AA), salbutamol sulfate (SAL; specific β 2-AA), ractopamine hydrochloride (RAC), zilpaterol hydrochloride (ZIL), BRL-37344 (specific β 3-agonist), or LUB for 30 min following preincubation with theophylline (inhibitor of phosphodiesterase). Relative mRNA amounts for β 1-, β 2-, and β 3-AR were greater (P < 0.05) in s.c. than in i.m. adipose tissue. The most abundant β-AR mRNA in both adipose tissues was the β 2-AR (P < 0.05), with the β 1- and β 3-AR subtypes being minimally expressed in i.m. adipose tissue. ISO, RH, and ZH stimulated the release of glycerol and nonesterified fatty acid (NEFA) from s.c. adipose tissue, but these β-AR ligands did not alter concentrations of these lipolytic markers in i.m. adipose tissue. LUB did not affect glycerol or NEFA concentrations in s.c. or i.m. adipose tissue, but attenuated (P < 0.05) the accumulation of cAMP mediated by the β 1- and β 2-AR ligands DOB and SAL in s.c. adipose tissue. Collectively, these data indicate that bovine i.m. adipose tissue is less responsive than s.c. adipose tissue to β-adrenergic ligands, especially those that are agonists at the β 1- and β3-receptor subtypes. The minimal mRNA expression of the β 1- and β 3 subtypes in i.m. adipose tissue likely limits the response potential to agonists for these β-AR subtypes.
Combined spectroscopy methods and molecular simulations for the binding properties of trametinib to human serum albumin

Trametinib is a novel anticancer drug for treating metastatic cutaneous melanoma. The present study probed into the binding of trametinib to human serum albumin (HSA) through spectroscopy methods and molecular simulations. Trametinib could quench the fluorescence of HSA through static quenching which could be probed via fluorescence spectroscopy and time-resolved fluorescence. Thermodynamic parameters and docking results indicated that hydrogen bonds and van der Waals forces play crucial roles in this binding process, which exerts almost no effect on the HSA conformation under synchronous fluorescence, three-dimensional fluorescence, circular dichroism spectra, and molecular dynamics simulations. Site marker displacement experiments and molecular docking reveal that trametinib primarily binds to Sudlow site I of HSA. In addition, the trametinib–HSA interaction was hardly influenced by varying amino acid (glutamine, alanine, glycine, and valine) concentrations. This study can provide useful information for the pharmacokinetic properties of trametinib.
Association of Field Position and Career Length With Risk of Neurodegenerative Disease in Male Former Professional Soccer Players

Key Points Question What is the association of field position, career length, and playing era with risk of neurodegenerative disease in male former professional soccer players? Findings In this cohort study of 7676 Scottish male former professional soccer players and 23 028 general population control individuals matched by sex, year of birth, and area socioeconomic status, risk of neurodegenerative disease among former soccer players varied by field position and career length but was similar across era of participation. Meaning In this study, risk of neurodegenerative disease was higher among former professional soccer players with longer careers and among those in nongoalkeeper positions, indicating that factors associated with nongoalkeeper positions should be scrutinized to mitigate risk; meanwhile, strategies to reduce head impact exposure may be advisable to reduce negative outcomes in this population.
Evaluating racial disparities in healthcare system utilization and caregiver burden among older adults with dementia

ABSTRACT Objective: To evaluate racial differences in healthcare utilization and caregiver burden in a culturally diverse population of older adults with dementia. Method: One hundred and thirty-three dyads (person with dementia, PWD and caregiver, CG), with at least one emergency department (ED) visit or hospitalization 12 months prior, were enrolled. Independent sample t-tests and chi-squared analyses were performed to compare racial groups on healthcare utilization and CG burden. Mann–Whitney U test was used for item-level analyses, principal component analysis was used to examine relationships among outcomes, and regressions were used to identify the relationship between race and potential covariates. Results: PWD sample mean age was 79 years, predominantly female, and with high school education. Racial distribution was 65% White and 35% Black. CG sample mean age was 64 years, predominantly female, with more than 12 years of education. No differences were found for age or dementia severity across racial groups. Black PWD experienced more ED and ambulance utilization when compared to White counterparts. Non-emergency hospitalization rates were higher for White PWD. No significant differences were found by race for CG burden total score; however, item-level analysis suggested more anger, reduced social life, uncertainty, and inadequacy in White CGs. Regressions demonstrated a positive relationship between Black race and adult-child CGs with increased ED visits, while dyad educational attainment was associated with hospitalizations independent of race. Conclusions: Healthcare utilization disparities extend to older adults with dementia diagnoses. Our findings suggest that culturally tailored interventions may be appropriate. Future research is encouraged to explore the effect of other covariates.
Avaliação de polpa de cagaita (eugenia dysenterica DC.) submetida ao congelamento e atomização

O Cerrado brasileiro apresenta grande diversidade de especies nativas, mas a forma de expansao agricola tem ignorado o alto potencial desse bioma. Dentre os frutos do Cerrado, tem-se a cagaita (Eugenia dysenterica DC.), com grande potencial de consumo, principalmente, pelas possibilidades de utilizacao na culinaria. A alta perecibilidade da maioria dos frutos, aliado a sua sazonalidade, tem impulsionado o desenvolvimento de processos tecnologicos, com vistas ao melhor aproveitamento destes frutos, alem da extensao de sua vida pos-colheita. Diante desses fatores, este estudo teve como proposta, avaliar o efeito do congelamento e atomizacao sobre os compostos bioativos da cagaita, bem como avaliar a vida util da polpa de cagaita atomizada, armazenada durante 45 dias, a temperatura de 30 oC. O trabalho foi realizado com frutos de cagaita, coletados maduros, pela manha, na Universidade Federal de Goias, em Goiânia-GO, para a obtencao da polpa congelada, e, posteriormente, atomizada. As amostras foram avaliadas quanto ao teor de compostos fenolicos totais, flavonoides totais, taninos condensados, potencial antioxidante (por ABTS e DPPH), vitamina C, β-caroteno (por HPLC), teores de acucares (frutose, glicose, sacarose) (por HPLC), perfil de minerais, compostos volateis. Os resultados demonstraram influencia dos metodos de conservacao (congelamento e atomizacao), podendo-se considerar que o metodo de secagem por spray dryer apresentou melhor performance, quando comparado a tecnica de congelamento da polpa de cagaita, com maiores teores de compostos fenolicos totais, flavoinoides totais e taninos condensados, apos a secagem da polpa, contribuindo para aumento do potencial antioxidante (ABTS). Porem, os metodos de conservacao de alimentos estudados nao foram eficazes para a preservacao do teor da vitamina C da cagaita in natura. Os metodos de conservacao (congelamento e atomizacao) apresentaram teores de acucares diferentes (frutose, glicose), mas nao apresentaram teores de sacarose para nennhum metodo. Utilizando-se a tecnica de atomizacao, observou-se a possibilidade de extracao de diferentes compostos volateis, em menor percentual de area, em comparacao com a fruta in natura e tambem com a polpa congelada. Durante o tempo de armazenamento (45 dias) a 30 oC observou-se a mantencao e aumento dos compostos bioativos presentes na polpa de cagaita atomizada, indicando que a atomizacao pode ser uma tecnica para conservacao da fruta. O trabalho contribuiu para uma maior valorizacao e aproveita
Angiotensin II‐induced natriuresis is attenuated in knockout mice lacking the receptors for tumor necrosis factor‐α

Intravenous infusion of relatively higher doses of angiotensin II (AngII) elicits natriuresis as opposed to its usual anti‐natruretic response. As AngII can induce tumor necrosis factor‐α (TNFα) production which elicits natriuresis via its action on TNFα receptor type 1 (TNFR1), we hypothesize that the concomitant release of TNFα contributes to the natriuretic response to AngII. Responses to AngII infusion (1 ng min−1 g−1 for 75 min, iv) were evaluated in anesthetized knockout (KO) mice lacking TNFR1 (n = 6) and TNFR2 (TNFα receptor type 2; n = 6) and compared these responses with those in wild type (WT; n = 6) mice. Arterial pressure (AP) was recorded from a cannula placed in the carotid artery. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by PAH and inulin clearances, respectively. Urine was collected from a catheter placed in the bladder. AngII caused similar increases (p < 0.05 vs basal values) in AP (WT, 37 ± 5%; TNFR1KO, 35 ± 4%; TNFR2KO, 30 ± 4%) and decreases (p < 0.05) in RBF (WT, −39 ± 5%; TNFR1KO, −28 ± 6%; TNFR2KO, −31 ± 4%) without significant changes in GFR (WT, −17 ± 7%; TNFR1KO, −18 ± 7%; TNFR2KO, −12 ± 7%). However, despite similar changes in AP and renal hemodynamics, AngII induced increases (p < 0.05) in urinary sodium excretion in WT (3916 ± 942%) were less in the KO strains, more or less in TNFR1KO (473 ± 170%) than in TNFR2KO (1176 ± 168%). These data indicate that TNF‐α receptors, particularly TNFR1 are involved in the natriuretic response that occur during acute infusion of AngII and thus, plays a protective role in preventing excessive salt retention at clinical conditions associated with elevated AngII level.
Identification of steroidal saponins from Tribulus terrestris and their in silico docking studies

Tribulus terrestris is known to possess many pharmacological properties, most notably its anticancer activities, owing to its rich steroidal saponin contents. Even though many reports are available elucidating the anticancer potential of the herb, we, for the very first time have attempted to isolate and identified the active compound present in seed crude saponin extract and confers its in silico docking ability with various cellular targets proteins. High performance thin layer chromatography confirms the presence of active saponins in leaf and seed saponin extracts which were further fractionated by silica gel column chromatography. Fractions collected were assessed for cytotoxicity on human breast cancer cells. High resolution liquid chromatography and mass spectroscopy was employ to identify the active components present in fraction with highest cytotoxicity. Intriguingly, Nautigenin type of steriodal saponin was identified to present in the active fraction of seed extract (SF11) and the identified compound was further analyzed for its in silico docking interaction using PyRx AutodockVina. Docking studies revealed the high binding affinity of Nuatigenin at significant sites with apoptotic proteins Bcl‐2, Bax, caspase‐3, caspase‐8, p53 and apoptosis inducing factor along with cell surface receptors estrogen receptor, projesterone receptor, epidermal growth factor receptor, and human epidermal growth factor receptor‐2. Thus, the conclusions were drawn that saponin fraction of Tribulus terrestis possesses active compounds having anticancer property and specifically, Nuatigenin saponin can be considered as an important therapeutic drug for the breast cancer treatment.
Effectiveness of Surgical Treatment in Traumatic Facial Paralysis

Introduction: In the etiology of facial nerve palsy, trauma is the most important. Our aim was to present our experience gained by evaluating the surgical approaches we have used in extratemporal and intratemporal facial nerve injuries and their long-term results, also to contribute to the consensus that will be formed on this subject. Materials and Methods: Thirteen patients among 24 patients who underwent surgery with a diagnosis of traumatic facial paralysis were evaluated in this study. The clinical response of these patients to treatment was examined by classifying them according to the House-Brackmann classification in the preoperative and postoperative periods. Results: Of the 13 patients, 9 had fractures due to temporal bone trauma, and 4 had nerve damage in the extratemporal part of the facial nerve. in the treatment, facial nerve decompression was performed using the middle fossa approach in 9 patients with temporal bone fractures. in the 4 patients with extratemporal facial nerve injury, graft repair or primary suturing was performed. in the postoperative period, the stages of the patients were III or below in 12 patients (92%), and only 1 (8%) patient remained in stage IV. Discussion: When the postop conditions of the patients were examined according to House-Brackmann staging, it was observed that surgical treatment caused a significant improvement in the functions of the facial nerve. Conclusions: Our results showed that surgery was an effective treatment method in patients with indications for traumatic facial paralysis.
Slow oscillations open susceptible time windows for epileptic discharges

In patients with epilepsy, interictal epileptic discharges are a diagnostic hallmark of epilepsy and represent abnormal, so‐called “irritative” activity that disrupts normal cognitive functions. Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients. We aim to study the period preceding these epileptic discharges, to extract potential proepileptogenic mechanisms supporting their expression.