Miracle-dz/UniFAR-FTUs huggingface dataset:
Temporal Dynamics of Brain White Matter Plasticity in Sighted Subjects during Tactile Braille Learning: A Longitudinal Diffusion Tensor Imaging Study

The white matter (WM) architecture of the human brain changes in response to training, though fine-grained temporal characteristics of training-induced white matter plasticity remain unexplored. We investigated white matter microstructural changes using diffusion tensor imaging at five different time points in 26 sighted female adults during 8 months of training on tactile braille reading. Our results show that training-induced white matter plasticity occurs both within and beyond the trained sensory modality, as reflected by fractional anisotropy (FA) increases in somatosensory and visual cortex, respectively. The observed changes followed distinct time courses, with gradual linear FA increase along the training in the somatosensory cortex and sudden visual cortex cross-modal plasticity occurring after braille input became linguistically meaningful. WM changes observed in these areas returned to baseline after the cessation of learning in line with the supply–demand model of plasticity. These results also indicate that the temporal dynamics of microstructural plasticity in different cortical regions might be modulated by the nature of computational demands. We provide additional evidence that observed FA training-induced changes are behaviorally relevant to tactile reading. Together, these results demonstrate that WM plasticity is a highly dynamic process modulated by the introduction of novel experiences. SIGNIFICANCE STATEMENT Throughout the lifetime the human brain is shaped by various experiences. Training-induced reorganization in white matter (WM) microstructure has been reported, but we know little about its temporal dynamics. To fill this gap, we scanned sighted subjects five times during tactile braille reading training. We observed different dynamics of WM plasticity in the somatosensory and visual cortices implicated in braille reading. The former showed a continuous increase in WM tissue anisotropy along with tactile training, while microstructural changes in the latter were observed only after the participants learned to read braille words. Our results confirm the supply–demand model of brain plasticity and provide evidence that WM reorganization depends on distinct computational demands and functional roles of regions involved in the trained skill.
Assurance in vaccine efficacy clinical trial design based on immunological responses

The assurance of a future clinical trial is a key quantitative tool for decision‐making in drug development. It is derived from prior knowledge (Bayesian approach) about the clinical endpoint of interest, typically from previous clinical trials. In this paper, we examine assurance in the specific context of vaccine development, where early development (Phase 2) is often based on immunological endpoints (e.g., antibody levels), while the confirmatory trial (Phase 3) is based on the clinical endpoint (very large sample sizes and long follow‐up). Our proposal is to use the Phase 2 vaccine efficacy predicted by the immunological endpoint (using a model estimated from epidemiological studies) as prior information for the calculation of the assurance.
Older Adults’ Perceptions of Frailty Language: A Scoping Review

Abstract There is growing interest in conceptualizing and diagnosing frailty. Less is understood, however, about older adults’ perceptions of the term “frail”, and the implications of being classified as “frail”. The purpose of this scoping review was to map the breadth of primary studies; and describe the meaning, perceptions, and perceived implications of frailty language amongst community-dwelling older adults. Eight studies were included in the review and three core themes were identified: (1) understanding frailty as inevitable age-related decline in multiple domains, (2) perceiving frailty as a generalizing label, and (3) perceiving impacts of language on health and health care utilization. Clinical practice recommendations for health care professionals working with individuals with frailty include: (1) maintaining a holistic view of frailty that extends beyond physical function to include psychosocial and environmental constructs, (2) using person-first language, and (3) using a strengths-based approach to discuss aspects of frailty.
PCSK9 deficiency rewires heart metabolism and drives heart failure with preserved ejection fraction

Abstract Aims PCSK9 is secreted into the circulation, mainly by the liver, and interacts with low-density lipoprotein receptor (LDLR) homologous and non-homologous receptors, including CD36, thus favouring their intracellular degradation. As PCSK9 deficiency increases the expression of lipids and lipoprotein receptors, thus contributing to cellular lipid accumulation, we investigated whether this could affect heart metabolism and function. Methods and results Wild-type (WT), Pcsk9 KO, Liver conditional Pcsk9 KO and Pcsk9/Ldlr double KO male mice were fed for 20 weeks with a standard fat diet and then exercise resistance, muscle strength, and heart characteristics were evaluated. Pcsk9 KO presented reduced running resistance coupled to echocardiographic abnormalities suggestive of heart failure with preserved ejection fraction (HFpEF). Heart mitochondrial activity, following maximal coupled and uncoupled respiration, was reduced in Pcsk9 KO mice compared to WT mice and was coupled to major changes in cardiac metabolism together with increased expression of LDLR and CD36 and with lipid accumulation. A similar phenotype was observed in Pcsk9/Ldlr DKO, thus excluding a contribution for LDLR to cardiac impairment observed in Pcsk9 KO mice. Heart function profiling of the liver selective Pcsk9 KO model further excluded the involvement of circulating PCSK9 in the development of HFpEF, pointing to a possible role locally produced PCSK9. Concordantly, carriers of the R46L loss-of-function variant for PCSK9 presented increased left ventricular mass but similar ejection fraction compared to matched control subjects. Conclusion PCSK9 deficiency impacts cardiac lipid metabolism in an LDLR independent manner and contributes to the development of HFpEF.
Diabetic eye: associated diseases, drugs in clinic, and role of self-assembled carriers in topical treatment

ABSTRACT Introduction: Diabetes is a pandemic disease that causes relevant ocular pathologies. Diabetic retinopathy, macular edema, cataracts, glaucoma, or keratopathy strongly impact the quality of life of the patients. In addition to glycemic control, intense research is devoted to finding more efficient ocular drugs and improved delivery systems that can overcome eye barriers. Areas covered: The aim of this review is to revisit first the role of diabetes in the development of chronic eye diseases. Then, commercially available drugs and new candidates in clinical trials are tackled together with the pros and cons of their administration routes. Subsequent sections deal with self-assembled drug carriers suitable for eye instillation combining patient-friendly administration with high ocular bioavailability. Performance of topically administered polymeric micelles, liposomes, and niosomes for the management of diabetic eye diseases is analyzed in the light of ex vivo and in vivo results and outcomes of clinical trials. Expert opinion: Self-assembled carriers are being shown useful for efficient delivery of not only a variety of small drugs but also macromolecules (e.g. antibodies) and genes. Successful design of drug carriers may offer alternatives to intraocular injections and improve the treatment of both anterior and posterior segments diabetic eye diseases.
Evaluating the Influence of Visual Attentional Tracking on Pointing Movement Precision

Abstract Multiple object tracking (MOT) and goal-directed movements are both based on attentional processes. This study focused on the instant effect of attentive tracking with respect to pointing performance. We measured the precision of pointing to the targets of an MOT task immediately after the tracking period when all the objects were still in motion, and to the precision of pointing to moving objects in the task without attentional tracking. The results demonstrated that an increase in the attentional tracking load was the primary factor that decreased pointing precision, although visual load may also contribute to this influence. We also manipulated the relationship between the number of targets and the density of the MOT display (the total number of objects displayed), which affected the MOT accuracy but not the pointing precision.
Phylogeographic reconstructions can be biased by ancestral shared alleles: The case of the polymorphic lichen Bryoria fuscescens in Europe and North Africa

Large phylogeographic studies on lichens are scarce, and none involves a single species within which different lineages show fixed alternative dispersal strategies. We investigated Bryoria fuscescens (including B. capillaris) in Europe and western North Africa by phenotypically characterizing 1400 specimens from 64 populations and genotyping them with 14 microsatellites. We studied population structure and genetic diversity at the local and continental scales, discussed the post‐glacial phylogeography, and compared dispersal capacities of phenotypes with and without soralia. Our main hypothesis is that the estimated phylogeography, migration routes, and dispersal capacities may be strongly biased by ancestral shared alleles. Scandinavia is genetically the richest area, followed by the Iberian Peninsula, the Carpathians, and the Alps. Three gene pools were detected: two partially linked to phenotypic characteristics, and the third one genetically related to the American sister species B. pseudofuscescens. The comparison of one gene pool producing soredia and one not, suggested both as panmictic, with similar levels of isolation by distance (IBD). The migration routes were estimated to span from north to south, in disagreement with the assessed glacial refugia. The presence of ancestral shared alleles in distant populations can explain the similar IBD levels found in both gene pools while producing a false signal of panmixia, and also biasing the phylogeographic reconstruction. The incomplete lineage sorting recorded for DNA sequence loci also supports this hypothesis. Consequently, the high diversity in Scandinavia may rather come from recent immigration into northern populations than from an in situ diversification. Similar patterns of ancestral shared polymorphism may bias the phylogeographical reconstruction of other lichen species.
Laryngeal Adductor Reflex Movement Latency Following Tactile Stimulation

Objective To measure the latency of laryngeal adductor reflex (LAR) motion onset at 2 laryngopharyngeal subsites using calibrated aesthesiometers. Study Design Cross-sectional. Setting Academic institution. Methods Twenty-one asymptomatic, healthy subjects (11 male, 10 female) underwent laryngopharyngeal sensory testing with tactile stimuli delivered to the aryepiglottic fold and medial pyriform sinus using 30-mm Cheung-Bearelly monofilaments (4-0 and 5-0 nylon sutures) via channeled flexible laryngoscope. The LAR onset latency, defined as the first visual detection of ipsilateral vocal fold adduction following tactile stimulation, was measured with frame-by-frame analysis of video recordings. Results The overall mean LAR latency across both subsites and stimulation forces was 176.6 (95% CI, 170.3-183.0) ms, without significant difference between subsites or forces. The critical value for LAR response latency prolongation at the . 01 significance level was 244 ms. At 30 frames/s video capture resolution, LAR response latency ≥8 frame intervals would indicate abnormal prolongation. Conclusion Aesthesiometer-triggered LAR latency appears to be invariant over an 8.7-dB force range and between the aryepiglottic fold and medial pyriform sinus subsites in controls. Laryngeal adductor reflex latency incongruences between stimulation forces or laryngopharyngeal subsites may serve as pathophysiological features to dissect mechanisms of upper aerodigestive tract disorders. Level of Evidence Level 3B.
Primary central nervous system lymphomas with massive intratumoral hemorrhage: Clinical, radiological, pathological, and molecular features of six cases

Primary central nervous system lymphomas (PCNSLs) rarely exhibit intratumoral hemorrhage. The differential diagnosis of hemorrhagic neoplasms of the central nervous system (CNS) currently includes metastatic carcinomas, melanomas, choriocarcinomas, oligodendrogliomas, and glioblastomas. Here we present the clinical, radiological, pathological, and molecular genetic features of six cases of PCNSL associated with intratumoral hemorrhage. The median age of patients was 75 years, with male predominance. While conventional PCNSLs were associated with low cerebral blood volume (CBV), perfusion magnetic resonance imaging (MRI) revealed elevated CBV in three cases, consistent with vascular proliferation. All six cases were diagnosed pathologically as having diffuse large B‐cell lymphoma (DLBCL) with a non‐germinal center B‐cell‐like (non‐GCB) phenotype; marked histiocytic infiltrates and abundant non‐neoplastic T‐cells were observed in most cases. Expression of vascular endothelial growth factor and CD105 in the lymphoma cells and the small vessels, respectively, suggested angiogenesis within the neoplasms. Neoplastic cells were immunohistochemically negative for programmed cell death ligand 1 (PD‐L1), while immune cells in the microenvironment were positive for PD‐L1. Mutations in the MYD88 gene (MYD88) (L265P) and the CD79B gene (CD79B) were detected in five and one case, respectively. As therapeutic modalities used for PCNSLs differ from those that target conventional hemorrhagic neoplasms, full tissue diagnoses of all hemorrhagic CNS tumors are clearly warranted.
The phase diagram of K0.5Na0.5NbO3–Bi1/2Na1/2TiO3

The phase diagram of the lead-free piezoelectric (1 − x)K0.5Na0. 5NbO3–xBi1/2Na1/2TiO3 system has been studied by high-resolution synchrotron powder diffraction, neutron powder diffraction and selected area electron diffraction. The two lead-free piezoelectric materials K0.5Na0. 5NbO3 and Bi1/2Na1/2TiO3 form an infinite substitution solid solution. The orthorhombic (O), monoclinic (M), tetragonal (T) and rhombohedral (R) phases and the phase coexistence of M (Pm) + T (P4mm) for 0.02 < x ≤ 0.14, T (P4bm) + pseudocubic (Pm{\overline 3}m) for 0.14 < x ≤ 0.87 and T (P4bm) + R (R3c) for 0.87 < x ≤ 0.96 have been investigated at room temperature, with a subtle change in the structure observed. The oxygen octahedral tilt system has been mapped as a function of composition and temperature. The results indicate that K0.5Na0. 5NbO3–Bi1/2Na1/2TiO3 does not display a morphotropic phase boundary like lead zirconate titanate, and that the most significant structural changes as a function of composition occur near x = 0.14 and x = 0.87 as a result of ionic disorder at the A and B sites in the perovskite ABO3 structure at room temperature.
Transient Phenomena of Double Pulsed High Speed Liquid Jet in Polyacrylamide Gels

Jet injectors employ high-velocity liquid jets that directly penetrate into human skin and deposit drugs in the dermal or subdermal region. It is sometimes called needle-free jet injector. Although, jet injectors have been marketed for years, little knowledge about the interactions of high-speed jets with soft materials such as skin has been revealed. Therefore in this study use the new jet injector device which is constructed by impact driven method (IDM) or call that “IDM jet injector”. It can generate jet as double pulsed high speed liquid jet. After that investigate the penetration mechanism by use polyacrylamide as tissue simulant which vary the Young’s modulus (E) by increasing of acrylamide percentage are 10%, 20% and 30% to give 0.06, 0.22 and 0.38 MPa of Young’s modulus, respectively. The results reveal that, when Young’s modulus is increased, average velocity and penetration depth decrease respectively. The stage detail of delivery can be clearly separated into two stages as penetration stage and ejection stage together with dispersion stage. Especially, the penetration stage is divided as two penetration jets pulsed. The jet introductory penetrated by first pulse and repetitive penetration follow by the second pulse.
tRNA-like leader-trailer interaction promotes 3′-end maturation of MALAT1

Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a nuclear long noncoding RNA (lncRNA) that is highly overexpressed in many cancer tissues and plays important roles in tumor progression and metastasis. The MALAT1 primary transcript contains evolutionarily conserved structural elements in its 3′-terminal region: a triple helix forming element called element for nuclear expression (ENE) and a downstream tRNA-like structure called mascRNA. Instead of being polyadenylated, mature MALAT1 is generated by recognition and processing of the mascRNA by RNase P. A genomically encoded A-rich tract at the new 3′ end of MALAT1, which is generated upon RNase P cleavage, forms a triple helical structure with the upstream ENE. Triplex formation is vital for stabilization of the mature transcript and for subsequent accumulation and oncogenic activity of MALAT1. Here, we demonstrate that efficient 3′-end maturation of MALAT1 is dependent on an interaction between the A-rich tract and the mascRNA 3′ trailer. Using mutational analyses of cell-based reporter accumulation, we show that an extended mascRNA acceptor stem and formation of a single bulged A 5′ to the RNase P cleavage site are required for efficient maturation of the nascent MALAT1 3′ end. Our results should benefit the development of therapeutic approaches to cancer through targeting MALAT1.
Azole-Resistant Aspergillus fumigatus Clinical Isolate Screening in Azole-Containing Agar Plates (EUCAST E.Def 10.1): Low Impact of Plastic Trays Used and Poor Performance in Cryptic Species

Azole-containing agar is used in routine Aspergillus fumigatus azole resistance screening. We evaluated the impact of the type of plastic used to prepare in-house agar plates on the procedure’s performance against A. fumigatus sensu stricto and cryptic species. A. fumigatus sensu stricto (n = 91) and cryptic species (n = 52) were classified as susceptible or resistant (EUCAST E.Def 9.3.2; clinical breakpoints v10). ABSTRACT Azole-containing agar is used in routine Aspergillus fumigatus azole resistance screening. We evaluated the impact of the type of plastic used to prepare in-house agar plates on the procedure’s performance against A. fumigatus sensu stricto and cryptic species. A. fumigatus sensu stricto (n = 91) and cryptic species (n = 52) were classified as susceptible or resistant (EUCAST E.Def 9.3.2; clinical breakpoints v10). In-house azole-containing agar plates were prepared following EUCAST E.Def 10.1 on three types of multidish plates. We assessed the sensitivity, specificity, and agreement values of the agar plates to screen for azole resistance. Overall, sensitivity and specificity values of the agar screening method were 100% and 93.3%, respectively. The type of tray used did not affect these values. All isolates harboring TR34-L98H substitutions were classified as resistant to itraconazole and voriconazole by the agar method; however, false susceptibility (very major error) to posaconazole was not uncommon and happened in isolates with posaconazole MICs of 0.25 mg/liter. Isolates harboring G54R and TR46-Y121F-T289A substitutions were correctly classified by the agar method as itraconazole/posaconazole resistant and voriconazole resistant, respectively. False resistance (major error) occurred in isolates showing tiny fungal growth. Finally, agreements between both procedures against cryptic species were much lower. Azole-containing agar plates are a convenient and reliable tool to screen for resistance in A. fumigatus sensu stricto; the type of plastic tray used minimally affects the method. On the contrary, the performance against cryptic species is rather poor.
Recent advances in herbal combination nanomedicine for cancer: delivery technology and therapeutic outcomes

ABSTRACT Introduction: The use of herbal compounds in cancer therapy has great potential to promote the efficacy of current cancer therapeutic strategies. Herbal compounds were successfully reported to enhance tumor cells sensitization to the action of chemo-, hormonal- and gene-therapeutic agents via different mechanisms. Herbal ingredients can affect different signaling pathways, reduce the toxic side effects or inhibit the efflux of anticancer drugs. Areas covered: This review will discuss the delivery of herbal compounds with other cancer treatments such as hormonal, small molecule inhibitors and inorganic hybrids to tumor cells. An overview of physicochemical properties of herbal components that require intelligent design of combo-nanomedicines for efficient co-delivery of those herbal-derived and other anticancer agents was discussed. Nanocarriers provide various benefits to overcome the shortcomings of the encapsulated herbal compounds including improved solubility, increased stability and enhanced tumor targeting. Different nanocarrier systems were the focus of this review. Expert opinion: Multifunctional nanocarrier systems encapsulating herbal and different anticancer drugs showed to be a wonderful approach in the treatment of cancer enabling the co-delivery of anticancer drugs with versatile modes of action in an accurate manner in an attempt to enhance the efficacy, benefit from the synergism between the drugs as well as to minimize the development of multi-drug resistance. The main challenge point is the early detection and management of any developed adverse effect.
The association between internet usage and sleep problems among Japanese adolescents: three repeated cross-sectional studies.

STUDY OBJECTIVES Sleep problems and problematic internet use have important implications for adolescent health; however, there have been no large-scale surveys using comprehensive measures. We examined the association between internet use duration and sleep problems among Japanese adolescents. METHODS We used data from the Lifestyle Survey of Adolescents collected in 2012, 2014, and 2017. We calculated the change in sleep status (insomnia, sleep duration, bedtime, and sleep quality) and internet usage (screen time and services such as internet surfing, social media use, streaming such as YouTube, and online gaming). A binary logistic model was estimated for insomnia. Generalized ordered logit models were employed for the ordinal outcomes (sleep duration, bedtime, sleep quality, and multidimensional sleep health). Sampling weights were constructed based on participation rate on survey years and selection rates from population statistics. RESULTS We analyzed data from 248,983 adolescents. Sleep status was unchanged; however, many adolescents used more internet services and for longer durations. The odds ratio of internet screen time for all sleep problems (insomnia, shorter sleep duration, later bedtime, and worse sleep quality) gradually declined. Longer internet screen time (> 5 hours) was strongly associated with all sleep problems. Internet services were also associated with sleep problems; particularly, social media use and online gaming were linked to later bedtimes. CONCLUSIONS Despite the decreased strength in the association between internet usage and sleep problems, longer internet time was strongly associated with sleep problems. Public health interventions should consider internet use as an intervention target to improve adolescents' health.