Miracle-dz/UniFAR-FTUs huggingface dataset:
Larotrectinib: A Targeted Therapy for Solid Tumors.

BACKGROUND Although neurotrophic tyrosine receptor kinase (NTRK) gene fusions are not common in most cancers, they are present in more than 90% of some rare tumors. The U.S. Food and Drug Administration has approved larotrectinib for patients with NTRK gene fusion-positive cancers that meet certain criteria. With ongoing advancements in tumor sequencing, it is anticipated that cancer treatment will be determined by genetic variants rather than by cancer type in the future. OBJECTIVES This article provides an overview of larotrectinib, a targeted therapy. METHODS This article reviews clinical trial results and highlights implications for oncology nurses caring for patients taking larotrectinib. FINDINGS Larotrectinib is an effective treatment option for some patients with NTRK gene fusion-positive cancers. Oncology nurses are key to educating patients on dosing, administration, side effects, and precautions.
Prevalence and factors associated with fertility desire among people living with HIV: A systematic review and meta-analysis

Background The fertility desire of people living with HIV (PLHIV) has been rising in the past decade. However, there are many studies among which the association remains controversial between the fertility desire of HIV-infected persons and antiretroviral therapy (ART), sex, marital status, and educational level. Methods We performed a literature search of these meta-analyses in PubMed, the Cochrane Library, Web of Science and ScienceDirect in November 2019. We also reviewed references of eligible studies to complement the search. We used pooled odds ratios (ORs) and 95% confidence intervals (CIs) with a random-effects model and a fixed-effects model to estimate the association between fertility desire among PLHIV and ART, sex, age, marital status, educational level, and number of children. Subgroups with I square values (I2) and sensitivity analyses were performed to assess the heterogeneity and the stability of the overall ORs, respectively. We evaluated publication bias using Egger’s test and a visual inspection of the symmetry in funnel plots. Results In these meta-analyses 50 articles were included with 22,367 subjects. The pooled prevalence of fertility desire among PLHIV was estimated to be 42.04%. The pooled analyses showed that the fertility desire of PLHIV is associated with ART (OR = 1.11, 95% CI:1.00–1.23, P = 0.043), sex (OR = 1.51, 95% CI:1.10–2.09), age (OR = 2.65, 95% CI:2.24–3.14), marital status (OR = 1.34, 95% CI:1.08–1.66), educational level (OR = 0.85, 95% CI:0.73–1.00, P = 0.047) and the number of children (OR = 3.99, 95% CI:3.06–5.20). PLHIV who are on ART, are male, are younger than 30, are married/cohabiting, have received a secondary education or above, and are childless have a higher prevalence of fertility desire. The two factors of age and the number of children, in particular demonstrated a strong significant association with fertility desire. We found moderate heterogeneity in the meta-analyses of age and educational level and high heterogeneity in the meta-analyses of sex, marital status and number of children. Publication bias was detected in the meta-analyses of the association of fertility with sex and educational level. Conclusion This study demonstrates that the prevalence of fertility desire among HIV-infected people is 42.04%, and the fertility desire among PLHIV is associated with ART experience, sex, age, marital status, the number of children, and educational level. Since a majority of PLHIV are of reproductive age, it is necessary to support PLHIV in terms of their needs regarding reproductive decision-making. Through counseling and reproductive health care, further measures to prevent the horizontal and vertical transmission of HIV should be taken.
Intravascular Ultrasound-Guided Contrast-Free Transcatheter Aortic Valve Implantation: A Porcine Feasibility Study

Objective Patients undergoing transcatheter aortic valve implantation (TAVI) frequently present with chronic kidney disease and are therefore particularly susceptible to nephrotoxic influences like iodinated contrast media. Acute kidney injury after TAVI is a severe complication that independently predicts short- and long-term mortality. The present study investigates the feasibility of a contrast-free approach by using intravascular ultrasound (IVUS) in conjunction with fluoroscopy. Methods Six domestic pigs (60 ± 5 kg) were anesthetized and underwent transapical implantation of a balloon-expandable transcatheter heart valve. In the control group (n = 3), the procedures were guided by fluoroscopy/angiography. In the study group (n = 3), the procedures were guided by IVUS for preimplantation evaluation, intra-procedural guidance, and post-implantation evaluation, in conjunction with fluoroscopy without contrast. The procedures were evaluated by IVUS, fluoroscopy, aortic root angiography, and explantation and dissection of the hearts. Results Relevant anatomical landmarks for correct implantation were assessed by IVUS. The following annulus measurements were obtained: area (359.67 ± 29.58 mm2), perimeter (68.28 ± 2.63 mm), maximum diameter (22.20 ± 1.22 mm), minimum diameter (20.43 ± 1.12 mm), mean diameter (21.32 ± 0.70 mm), ellipticity index (1.09 ± 0.10), and area-derived diameter (21.39 ± 0.87 mm). IVUS-guided valve deployment resulted in correct expansion within the aortic annulus without signs of paravalvular leak, compromised mitral valve, or coronary obstruction. IVUS-guided post-implantation assessment confirmed circular expansion (25.88 ± 0.30 mm) of the valves. Conclusions IVUS-guided, contrast-free transapical TAVI is feasible in a porcine model.
ACK1 is dispensable for development, skin tumor formation, and breast cancer cell proliferation

Activated Cdc42‐associated kinase 1 (ACK1), a widely expressed nonreceptor tyrosine kinase, is often amplified in cancer and has been shown to interact with Cell division cycle 42 (Cdc42), Epidermal growth factor receptor (EGFR), and several other cancer‐relevant molecules, suggesting a possible role for ACK1 in development and tumor formation. To directly address this scenario, we generated mice lacking a functional ACK1 gene (ACK1 ko) using CRISPR genome editing. ACK1 ko mice developed normally, displayed no obvious defect in tissue maintenance, and were fertile. Primary ACK1‐null keratinocytes showed normal phosphorylation of EGFR, but a tendency toward reduced activation of AKT serine/threonine kinase 1 (Akt) and Mitogen‐activated protein kinase 1 (Erk). DMBA/TPA‐induced skin tumor formation did not reveal significant differences between ACK1 ko and control mice. Deletion of the ACK1 gene in the breast cancer cell lines MDA‐MB‐231, 67NR, MCF7, 4T1, and T47D caused no differences in growth. Furthermore, EGF‐induced phosphorylation kinetics of Erk, Akt, and p130Cas were not detectably altered in T47D cells by the loss of ACK1. Finally, loss of ACK1 in MDA‐MB‐231 and T47D breast cancer cells had a very limited or no effect on directed cell migration. These data do not support a major role for ACK1 in Cdc42 and EGFR signaling, development, or tumor formation.
Closed genome sequences of Staphylococcus lloydii sp. nov. and Staphylococcus durrellii sp. nov. isolated from captive fruit bats (Pteropus livingstonii)

The increasing availability of whole genome sequencing of bacteria has accelerated the discovery of novel species which may not have been easy to discriminate using standard phenotypic or single gene methods. Phylogenomic analysis of genome sequences from a collection of coagulase-negative staphylococcal species isolated from captive fruit bats revealed two clusters which were close to Staphylococcus kloosii. To assess the relatedness of the strains we used digital DNA–DNA hybridization (dDDH) and two methods for average nucleotide identity (ANI) computation which predicted two novel species having dDDH less than 70 % and ANI less than 95%. We propose these species as Staphylococcus lloydii sp. nov. (type strain 23_2_7_LYT=NCTC 14453T=DSM 111639T) and Staphylococcus durrellii sp. nov (type strain 27_4_6_LYT=NCTC 14454T=DSM 111640T).
Revisiting Dust and Soil Ingestion Rates Based on Hand-to-Mouth Transfer

ABSTRACT Soil ingestion rates calculated using a tracer-based mass balance approach may carry considerable study errors, insensitivities, and “artefacts” of analysis that result in significant uncertainty. These same soil ingestion rates are often used as surrogates for dust ingestion rates. Therefore, a more direct and mechanistic method was developed to estimate soil and dust ingestion rates. The soil and dust ingestion rates were calculated using measures of: particle loading to indoor surfaces; fraction transferred to the hands; hand surface area; fraction of hand surface area that may be mouthed or contact food; frequency of hand-to-mouth events, amount dissolved by saliva; and exposure time. Adapted specifically for the Canadian context, estimated mean indoor dust ingestion rates range from 2.2 mg/d for teenagers to 41 mg/d for toddlers; mean soil ingestion rates range from 1.2 mg/d for seniors to 23 mg/d for children. Combined soil and dust ingestion rates ranged from 3.8 mg/d for seniors to 61 mg/d for toddlers. These ingestion rates are lower than values adopted by most agencies. These ingestion rates are mechanistic, can be adjusted on a site-specific basis, can be modified into an hourly rate and are presented as a more realistic alternative to traditional mass balance approaches. [Supplementary materials are available for this article. Go to the publisher's online edition of Human and Ecological Risk Assessment to view the free supplementary files. ]
Circular RNAs: new biomarkers of chemoresistance in cancer

Chemotherapeutics are validated conventional treatments for patients with advanced cancer. However, with continual application of chemotherapeutics, chemoresistance, which is often predictive of poor prognosis, has gradually become a concern in recent years. Circular RNAs (circRNAs), a class of endogenous noncoding RNAs (ncRNAs) with a closed-loop structure, have been reported to be notable targets and markers for the prognosis, diagnosis, and treatment of many diseases, particularly cancer. Although dozens of studies have shown that circRNAs play major roles in drug-resistance activity in tumors, the mechanisms by which circRNAs affect chemoresistance have yet to be explored. In this review, we describe the detailed mechanisms of circRNAs and chemotherapeutics in various cancers and summarize potential therapeutic targets for drug-resistant tumors.
Effects of post-exercise sodium bicarbonate ingestion on acid-base balance recovery and time-to-exhaustion running performance: a randomised crossover trial in recreational athletes.

This study investigated the effect of post-exercise sodium bicarbonate (NaHCO3) ingestion on acid-base balance recovery and time-to-exhaustion (TTE) running performance. Eleven male runners (stature, 1.80 ± 0.05 m; body mass, 74.4 ± 6.5 kg; maximal oxygen consumption, 51.7 ± 5.4 ml.kg-1.min-1) participated in this randomised, single-blind, counterbalanced and crossover design study. Maximal running velocity (v-VO2max) was identified from a graded exercise test. During experimental trials, participants repeated 100% v-VO2max TTE protocols (TTE1, TTE2) separated by 40 min following the ingestion of either 0.3 g.kg-1 BM NaHCO3 (SB) or 0.03 g.kg-1 BM sodium chloride (PLA) at the start of TTE1 recovery. Acid-base balance (blood pH and bicarbonate, HCO3-) data were studied at baseline, post-TTE1, after 35 min recovery and post-TTE2. Blood pH and [HCO3-] were unchanged at 35 min recovery (p > 0.05), but [HCO3-] was elevated post-TTE2 for SB vs. PLA (+2.6 mmol.l-1; p = 0.005; g = 0.99). No significant differences were observed for TTE2 performance (p > 0.05), although a moderate effect size was present for SB vs. PLA (+14.3 s; g = 0.56). Post-exercise NaHCO3 ingestion is not an effective strategy for accelerating the restoration of acid-base balance or improving subsequent TTE performance when limited recovery is available. Novelty bullets: •Post-exercise sodium bicarbonate ingestion did not accelerate the restoration of blood pH or bicarbonate after 35 minutes •Performance enhancing effects of sodium bicarbonate ingestion may display a high degree of inter-individual variation •Small-to-moderate changes in performance were likely due to greater up-regulation of glycolytic activation during exercise.
Properties of nanometer-sized metal–semiconductor interfaces of GaAs and InP formed by an in situ electrochemical process

The properties of GaAs and InP Schottky diodes having nanometer-sized metal dots were investigated in order to clarify whether or not strong Fermi level pinning is an intrinsic property of the metal–semiconductor interface. Macroscopic Schottky diode samples having many nanometer-sized metal dots as well as single-dot Schottky diode samples were prepared by an in situ electrochemical process which consisted of pulsed anodic etching of the semiconductors followed by subsequent dc or pulsed cathodic deposition of the metal. Strong Fermi level pinning was not seen in the GaAs and InP macroscopic samples. The Schottky barrier height SBH values were strongly dependent on the metal work function and on the electrochemical processing conditions. Of particular interest, the difference in the dot size changed the SBH almost 340 meV in Pt/InP macroscopic Schottky diodes, indicating that Fermi level pinning disappears as the dot size is sufficiently reduced. X-ray photoelectron spectroscopy and Raman measurements in.
Isotropic and anisotropic Raman scattering from molecular liquids measured by spatially masked optical Kerr effect spectroscopy

Spatially masked optical Kerr effect (SM-OKE) spectroscopy is a nonresonant femtosecond pump–probe technique capable of measuring isotropic contributions to the transient birefringence of molecular liquids. In conjunction with traditional optical-heterodyne-detected optical Kerr effect spectroscopy, polarization-selective SM-OKE measurements are used to experimentally measure the anisotropic and isotropic third-order nonlinear response of CS2, acetonitrile, methanol, and water. These two responses, which allow the intermolecular dynamics to be separated by symmetry, form a complete and independent basis for describing the polarization dependence of nonresonant third-order experiments. The Fourier transform spectral densities of these responses are presented for each liquid and are interpreted in terms of the molecular and interaction-induced contributions to the many-body polarizability. The molecular contributions are suppressed in the isotropic response for all liquids, while the line shape in the inter.
Dielectric spectroscopy and conductivity of polyelectrolyte solutions

The dielectric and conductometric properties of aqueous polyelectrolyte solutions present a very complex phenomenology, not yet completely understood, differing from the properties of both neutral macromolecular solutions and of simple electrolytes. Three relaxations are evident in dielectric spectroscopy of aqueous polyelectrolyte solutions. Near 17 GHz, water molecules relax and hence this highest frequency relaxation gives information on the state of water in the solution. At lower frequencies in the MHz range, free counterions respond to the applied field and polarize on the scale of the correlation length. This intermediate frequency relaxation thus provides information about the effective charge on the polyelectrolyte chains, and the fraction of condensed counterions. However, the presence of polar side chains adds a further polarization mechanism that also contributes in this intermediate frequency range. At still lower frequencies, the condensed counterions polarize in a non-uniform way along the polyelectrolyte chain backbone and dielectric spectroscopy in the kHz range may determine the effective friction coefficient of condensed counterions. In this review, we analyse in detail the dielectric and conductometric behaviour of aqueous polyelectrolyte solutions in the light of recent scaling theories for polyelectrolyte conformation and summarize the state-of-the-art in this field.
Transverse electric and transverse magnetic polarization active intersubband transitions in narrow InGaAs quantum wells

Polarization‐resolved infrared spectroscopy has been used to demonstrate the existence of transverse electric (TE) and transverse magnetic (TM) active intersubband transitions in lattice‐matched, unstrained In0.53Ga0. 47As/In0.52Al0. 48As and strained In0.7Ga0.3As/AlAs quantum wells grown by molecular beam epitaxy on Fe‐doped semi‐insulating InP (001) substrates. It is shown that a previously reported intersubband absorption peak at 0.3 eV in a 4.0‐nm wide, lattice‐matched InGaAs/InAlAs quantum well can be resolved into two peaks active for TE and TM polarizations, respectively, with a 10 meV splitting between them. Bound to quasibound state transition at 0.59 eV (2.1 μm) for a narrow, 2.8‐nm‐wide InGaAs quantum well has also been observed. Group symmetry analyses considering D2d symmetry, tetragonal perturbation of local crystal and strain deformation potential, and interface roughness of the ternary quantum‐well structure is proposed to explain the polarization selection rules, and the Stark splitting in .
Cross‐species transcriptomics uncovers genes underlying genetic accommodation of developmental plasticity in spadefoot toads

That hardcoded genomes can manifest as plastic phenotypes responding to environmental perturbations is a fascinating feature of living organisms. How such developmental plasticity is regulated at the molecular level is beginning to be uncovered aided by the development of ‐omic techniques. Here, we compare the transcriptome‐wide responses of two species of spadefoot toads with differing capacity for developmental acceleration of their larvae in the face of a shared environmental risk: pond drying. By comparing gene expression profiles over time and performing cross‐species network analyses, we identified orthologues and functional gene pathways whose environmental sensitivity in expression have diverged between species. Genes related to lipid, cholesterol and steroid biosynthesis and metabolism make up most of a module of genes environmentally responsive in one species, but canalized in the other. The evolutionary changes in the regulation of the genes identified through these analyses may have been key in the genetic accommodation of developmental plasticity in this system.
Upper limb movement profiles during spontaneous motion in acute stroke

Objective. The clinical assessment of upper limb hemiparesis in acute stroke involves repeated manual examination of hand movements during instructed tasks. This process is labour-intensive and prone to human error as well as being strenuous for the patient. Wearable motion sensors can automate the process by measuring characteristics of hand activity. Existing work in this direction either uses multiple sensors or complex instructed movements, or analyzes only the quantity of upper limb motion. These methods are obtrusive and strenuous for acute stroke patients and are also sensitive to noise. In this work, we propose to use only two wrist-worn accelerometer sensors to study the quality of completely spontaneous upper limb motion and investigate correlation with clinical scores for acute stroke care. Approach. The velocity time series estimated from acquired acceleration data during spontaneous motion is decomposed into smaller movement elements. Measures of density, duration and smoothness of these component elements are extracted and their disparity is studied across the two hands. Main results. Spontaneous upper limb motion in acute stroke can be decomposed into movement elements that resemble point-to-point reaching tasks. These elements are smoother and sparser in the normal hand than in the hemiparetic hand, and the amount of smoothness correlates with hemiparetic severity. Features characterizing the disparity of these movement elements between the two hands show statistical significance in differentiating mild-to-moderate and severe hemiparesis. Using data from 67 acute stroke patients, the proposed method can classify the two levels of hemiparetic severity with 85% accuracy. Additionally, compared to activity-based features, the proposed method is robust to the presence of noise in acquired data. Significance. This work demonstrates that the quality of upper limb motion can characterize and identify hemiparesis in stroke survivors. This is clinically significant towards the continuous automated assessment of hemiparesis in acute stroke using minimally intrusive wearable sensors.
Recent advances in the ontogeny of drug disposition

Developmental changes that occur throughout childhood have long been known to impact drug disposition. However, pharmacokinetic studies in the paediatric population have historically been limited due to ethical concerns arising from incorporating children into clinical trials. As such, much of the early work in the field of developmental pharmacology was reliant on difficult‐to‐interpret in vitro and in vivo animal studies. Over the last 2 decades, our understanding of the mechanistic processes underlying age‐related changes in drug disposition has advanced considerably. Progress has largely been driven by technological advances in mass spectrometry‐based methods for quantifying proteins implicated in drug disposition, and in silico tools that leverage these data to predict age‐related changes in pharmacokinetics. This review summarizes our current understanding of the impact of childhood development on drug disposition, particularly focusing on research of the past 20 years, but also highlighting select examples of earlier foundational research. Equally important to the studies reviewed herein are the areas that we cannot currently describe due to the lack of research evidence; these gaps provide a map of drug disposition pathways for which developmental trends still need to be characterized.
Hepatic and renal expression of Oatp1 in obstructive uropathy. First detection of Oatp1 in urine, a potential biomarker

Obstructive renal diseases affect renal function and kidney integrity. Nevertheless, little is known about its systemic or extra‐renal effects. The organic anion transporting polypeptide 1 (Oatp1) is a carrier expressed in liver and kidneys. In this study, the hepatic and renal expression of Oatp1 was evaluated in rats with obstructive nephropathy. Moreover, the urinary excretion of Oatp1 (Oatp1u) was evaluated as a potential biomarker for this pathology. Male Wistar rats with bilateral ureteral obstruction for 5 hours (BUO5), 24 hours (BUO24) or sham operated were used. After 24 hours of ureteral releasing, liver and kidney functional parameters, histopathology, Oatp1 tissular expression and Oatp1u were evaluated. For Oatp1u evaluation two groups were added; BUO1 and BUO2 (1 and 2 hours of ureteral obstruction, respectively). Both liver and kidney functional parameters and histopathological studies showed alterations in BUO5 and BUO24. In hepatic homogenates, Oatp1 significantly decreased in BUO groups and in total liver membranes no modifications were observed. In renal homogenates, Oatp1 significantly decreased in BUO groups, but in apical kidney membranes, its expression was increased. Oatp1u was only detected in BUO groups, even in those (BUO1, BUO2) in which no alterations in the traditional parameters of renal function were observed. Modulations in liver and renal expression of Oatp1 could be an organism strategy to attenuate the effects of the disease and an attempt to maintain the complex organ cross‐talk between liver and kidneys. Oatp1u could be a new, early and specific biomarker of obstructive nephropathy.