Miracle-dz/UniFAR-FTUs huggingface dataset:
Klotho overexpression improves amyloid‐β clearance and cognition in the APP/PS1 mouse model of Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by the presence of amyloid‐β (Aβ) plaques. We previously reported that Klotho lowered Aβ levels in the brain and protected against cognitive deficits in amyloid precursor protein/presenilin 1(APP/PS1) mice. However, the underlying mechanism remains unclear. In this study, we induced intracerebral Klotho overexpression in 13‐month‐old APP/PS1 mice by injecting lentivirus that carried full‐length mouse Klotho cDNA in the lateral ventricle of the brain. We examined the effects of Klotho overexpression on cognition, Aβ burden, Aβ‐related neuropathology, microglia transformation, and Aβ transport systems in vivo. Additionally, we investigated the effects of Klotho on Aβ transport at the blood–cerebrospinal fluid barrier by knocking down Klotho in primary human choroid plexus epithelial cells (HCPEpiCs). The upregulation of Klotho levels in the brain and serum significantly ameliorated Aβ burden, neuronal and synaptic loss and cognitive deficits in aged APP/PS1 mice. Klotho treatment significantly inhibited NACHT, LRR, and PYD domain‐containing protein 3 (NLRP3) and the subsequent transformation of microglia to the M2 type that may enhance microglia‐mediated Aβ clearance. Meanwhile, Klotho overexpression also regulated Aβ transporter expression, which may promote Aβ transporter‐mediated Aβ clearance. Moreover, the ability of HCPEpiCs to transport Aβ in vitro was also significantly impaired by Klotho knockdown. Given the neuroprotective effect of Klotho overexpression, the present findings suggest that Klotho should be further investigated as a potential therapeutic target for AD.
TACE combined with microwave ablation therapy vs. TACE alone for treatment of early- and intermediate-stage hepatocellular carcinomas larger than 5 cm: a meta-analysis.

There are many therapeutic options for primary hepatocellular carcinoma (HCC), but very limited options for unresectable HCC with a single lesion larger than 5 cm (Barcelona Clinic Liver Cancer [BCLC] stage A) or with 2-3 nodules beyond 5 cm (BCLC stage B). Transcatheter arterial chemoembolization (TACE) is considered the first-line treatment for these patients, and combination therapy has also been tried. However, the efficacy of microwave ablation (MWA) combined with TACE in the treatment of the above tumors remains to be further confirmed. Therefore, this meta-analysis aimed to compare the efficacy of combination therapy and TACE monotherapy on these patients. PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and the Wan Fang electronic databases were retrieved to search for studies comparing combination therapy and TACE monotherapy, published between the earliest available date and August 20, 2019. A total of 20 articles (reporting 1736 patients) were included. Meta-analysis showed that, compared to TACE alone, TACE + MWA resulted in significantly higher 1-, 2-, and 3-year overall survival (OS) (1-year OS rate: RR = 1.36, 95% CI 1.28-1.44, P < 0.001; 2-year OS rate: RR = 1.56, 95% CI 1.40-1.74, P < 0.001 and 3-year OS rate: RR = 2.07, 95% CI: 1.67-2.57, P < 0.001). Complete response, partial response, and objective response rates were significantly higher in TACE + MWA than those in TACE alone (P < 0.001). Meanwhile, publication bias and sensitivity analysis were performed and did not show statistical significance.
Molar-incisor hypomineralization (MIH), dental fluorosis and caries in rural areas with different fluoride levels in the drinking water.

AIM This study determined the prevalence of molar-incisor hypomineralization (MIH), and its association with dental fluorosis and caries in children living in rural areas in northeastern Brazil who are exposed to residual fluoride (F) levels in the drinking water. DESIGN A census was carried out with 610 schoolchildren aged 6 to 12 years. The European Academy of Paediatric Dentistry criteria, Thysltrup and Fejerskov index, World Health Organization index were used for diagnosis of MIH, dental fluorosis and caries detection, respectively. The association between the outcome and exposure variables was determined by Robust Poisson regression (p < 0.05). RESULTS Water F-levels varied from 0.06 to 1.98 ppm. MIH was not related to fluoride levels in the drinking water, but it showed an inverse and direct correlation with dental caries and fluorosis, respectively. Children with MIH had a higher DMFT, and severe MIH cases were most frequent in children with dental fluorosis. CONCLUSION Drinking water F-levels were not directly related with the occurrence of MIH in schoolchildren. However, the severity of MIH was likely to be associated with dental fluorosis in areas with moderate to high fluoride levels in the drinking water.
Evolution of Systemic Sclerosis–Associated Interstitial Lung Disease One Year After Hematopoietic Stem Cell Transplantation or Cyclophosphamide

Hematopoietic stem cell transplantation (HSCT) and cyclophosphamide (CYC) are treatment options for progressive systemic sclerosis associated with interstitial lung disease (SSc‐ILD). The aims of our retrospective observational study were to evaluate: 1) the evolution of SSc‐ILD in SSc patients treated with HSCT (assessed by high‐resolution computed tomography [HRCT]; a group of patients treated with CYC was included as frame of reference); 2) how results of pulmonary function tests (PFTs) are associated with HRCT findings; and 3) which factors predict ILD reduction.
The Promotion of Physical Activity from Digital Services: Influence of E-Lifestyles on Intention to Use Fitness Apps

E-Lifestyles are individual forms of behavior in the digital environment that reflect the values, activities, interests, and opinions of consumers. Likewise, fitness Apps are considered technological tools for promoting physical activity online. Although there are studies related to sports lifestyles, it has not been analyzed yet how e-lifestyles are related to the use of fitness Apps. Based on this, this study represents a step to clarify how e-lifestyles influence different relationships with perceived ease of use, perceived usefulness, attitude, and intentions to use Fitness Apps. Therefore, the objective of the study was to analyze the relationship between the e-lifestyles of consumers of Boutique fitness centers and their relationship with the perceived ease of use, the perceived usefulness, the attitude, and the intention to use Fitness Apps. The sample was 591 customers (378 women and 213 men) of 25 Boutique fitness centers. An online questionnaire was used for data collection. Data was analyzed with confirmatory factor analysis and structural equation model. Findings provide an insight into the importance of e-lifestyles in the intention of using fitness Apps and therefore in promoting physical activity through online fitness services. The results showed positive relationships between e-lifestyles, perceived ease of use, perceived usefulness and attitude toward fitness Apps. Finally, the attitude toward fitness Apps offered a very high predictive value on use intention. This study provides a better understanding of consumer´s intention to use fitness Apps. The conclusions and recommendations for sports managers of fitness centers highlight the importance of e-lifestyles as a predecessor for the use of fitness Apps.
Could ferritin level be an indicator of COVID‐19 disease mortality?

While the number of coronavirus disease‐2019 (COVID‐19) cases is increasing day by day, there is limited information known about the hematological and laboratory findings of the disease. We aimed to investigate whether serum ferritin level predicts mortality is a marker for rapid progression for inpatients. Our study included 56 patients who were died due to COVID‐19 as the study group, and 245 patients who were hospitalized and recovered as the control group. The laboratory data of the patients were evaluated from the first blood tests (pre) taken from the first moment of admission to the hospital and the blood tests taken from before the patient's discharge or exitus (post) were evaluated retrospectively. The mean age of the nonsurvivor group was 62.0 ± 15.7 and the mean age of the control group was 54.34 ± 13.03. Age and length of stay are significantly higher in the nonsurvivor group. When comparing the pre‐ and postvalues of ferritin, according to the two groups separately, there was no significant difference in the control group and a high level of significance was observed in the nonsurvivor group (p < .01). COVID‐19 disease caused by severe acute respiratory syndrome coronavirus‐2 causes high mortality with widespread inflammation and cytokine storm. Ferritin is a cheap and widespread available marker, ferritin, which can be used for its predictivity of the mortality and hope it would be a useful marker for clinicians for the management of the disease.
ROS-producing immature neutrophils in giant cell arteritis are linked to vascular pathologies

Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/–CD64– band neutrophils and CD66bhiCD15+CD10lo/–CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged period of time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro coculture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a clinical cellular signature of GCA and suggesting different therapeutic approaches in systemic vascular inflammation.
Hypotension Prediction Index for Prevention of Hypotension during Moderate- to High-risk Noncardiac Surgery

Background: The Hypotension Prediction Index is a commercially available algorithm, based on arterial waveform features, that predicts hypotension defined as mean arterial pressure less than 65 mmHg for at least 1 min. We therefore tested the primary hypothesis that index guidance reduces the duration and severity of hypotension during noncardiac surgery. Methods: We enrolled adults having moderate- or high-risk noncardiac surgery with invasive arterial pressure monitoring. Participating patients were randomized to hemodynamic management with or without index guidance. Clinicians caring for patients assigned to guidance were alerted when the index exceeded 85 (range, 0 to 100) and a treatment algorithm based on advanced hemodynamic parameters suggested vasopressor administration, fluid administration, inotrope administration, or observation. Primary outcome was the amount of hypotension, defined as time-weighted average mean arterial pressure less than 65 mmHg. Secondary outcomes were time-weighted mean pressures less than 60 and 55 mmHg. Results: Among 214 enrolled patients, guidance was provided for 105 (49%) patients randomly assigned to the index guidance group. The median (first quartile, third quartile) time-weighted average mean arterial pressure less than 65 mmHg was 0.14 (0.03, 0.37) in guided patients versus 0.14 (0.03, 0.39) mmHg in unguided patients: median difference (95% CI) of 0 (–0.03 to 0.04), P = 0.757. Index guidance therefore did not reduce amount of hypotension less than 65 mmHg, nor did it reduce hypotension less than 60 or 55 mmHg. Post hoc, guidance was associated with less hypotension when analysis was restricted to episodes during which clinicians intervened. Conclusions: In this pilot trial, index guidance did not reduce the amount of intraoperative hypotension. Half of the alerts were not followed by treatment, presumably due to short warning time, complex treatment algorithm, or clinicians ignoring the alert. In the future we plan to use a lower index alert threshold and a simpler treatment algorithm that emphasizes prompt treatment. Of 214 noncardiac surgical patients, 105 (49%) patients randomized to management with a hypotension prediction algorithm, intraoperative hypotension was not reduced compared with controls. A lower alert threshold enabling adequate warning time and a simpler treatment algorithm that emphasizes prompt treatment after alert may help. Supplemental Digital Content is available in the text.
From statistical regularities in multisensory inputs to peripersonal space representation and body ownership: Insights from a neural network model

Peripersonal space (PPS), the interface between the self and the environment, is represented by a network of multisensory neurons with visual (or auditory) receptive fields anchored to specific body parts, and tactile receptive fields covering the same body parts. Neurophysiological and behavioural features of hand PPS representation have been previously modelled through a neural network constituted by one multisensory population integrating tactile inputs with visual/auditory external stimuli. Reference frame transformations were not explicitly modelled, as stimuli were encoded in pre‐computed hand‐centred coordinates. Here we present a novel model, aiming to overcome this limitation by including a proprioceptive population encoding hand position. We confirmed behaviourally the plausibility of the proposed architecture, showing that visuo‐proprioceptive information is integrated to enhance tactile processing on the hand. Moreover, the network's connectivity was spontaneously tuned through a Hebbian‐like mechanism, under two minimal assumptions. First, the plasticity rule was designed to learn the statistical regularities of visual, proprioceptive and tactile inputs. Second, such statistical regularities were simply those imposed by the body structure. The network learned to integrate proprioceptive and visual stimuli, and to compute their hand‐centred coordinates to predict tactile stimulation. Through the same mechanism, the network reproduced behavioural correlates of manipulations implicated in subjective body ownership: the invisible and the rubber hand illusion. We thus propose that PPS representation and body ownership may emerge through a unified neurocomputational process; the integration of multisensory information consistently with a model of the body in the environment, learned from the natural statistics of sensory inputs.
Physical Activity, Sport and Physical Education in Northern Ireland School Children: A Cross-Sectional Study

Internationally, insufficient physical activity (PA) is a major health concern. Children in Northern Ireland (NI) are recorded as having the lowest levels of PA in the United Kingdom (UK). To date, validated and representative data on the PA levels of NI school children are limited. The aim of this study was to provide surveillance data on self-reported PA, sport and physical education (PE) participation of school children in NI. Differences between genders and factors associated with PA were also examined. A representative sample of primary (n = 446) and post-primary (n = 1508) children was surveyed in school using validated self-report measures. Findings suggest that PA levels are low, with a minority of children (13%) meeting the PA guidelines (primary pupils 20%, post-primary pupils 11%). NI school children have lower levels of PA, PE and sports participation than UK and European peers. A trend of age-related decline across all the domains of PA was apparent. The data presented highlighted that females are less likely to achieve PA guidelines, children from lower socio-economic background participate in school and community sport less often, and that enjoyment and social support are important variables in PA adherence. Policy solutions that would support implementation e.g., mandatory minimum PE time, whole school approaches to PA promotion and targeted investment in schools, particularly in areas of deprivation and for females, are suggested.
UhAVR1, an HR-Triggering Avirulence Effector of Ustilago hordei, Is Secreted via the ER–Golgi Pathway, Localizes to the Cytosol of Barley Cells during in Planta-Expression, and Contributes to Virulence Early in Infection

The basidiomycete Ustilago hordei causes covered smut disease of barley and oats. Virulence effectors promoting infection and supporting pathogen lifestyle have been described for this fungus. Genetically, six avirulence genes are known and one codes for UhAVR1, the only proven avirulence effector identified in smuts to date that triggers complete immunity in barley cultivars carrying resistance gene Ruh1. A prerequisite for resistance breeding is understanding the host targets and molecular function of UhAVR1. Analysis of this effector upon natural infection of barley coleoptiles using teliospores showed that UhAVR1 is expressed during the early stages of fungal infection where it leads to HR triggering in resistant cultivars or performs its virulence function in susceptible cultivars. Fungal secretion of UhAVR1 is directed by its signal peptide and occurs via the BrefeldinA-sensitive ER–Golgi pathway in cell culture away from its host. Transient in planta expression of UhAVR1 in barley and a nonhost, Nicotiana benthamiana, supports a cytosolic localization. Delivery of UhAVR1 via foxtail mosaic virus or Pseudomonas species in both barley and N. benthamiana reveals a role in suppressing components common to both plant systems of Effector- and Pattern-Triggered Immunity, including necrosis triggered by Agrobacterium-delivered cell death inducers.
Sprunggelenkschäden bei Milchkühen – eine Übersicht

Zusammenfassung Chronisch-traumatische Schädigungen des Sprunggelenks gehören zu den häufigsten Technopathien an den Gliedmaßen beim Rind. Die Prävalenz liegt heutzutage in vielen Betrieben zwischen 40 und 70%, was im Hinblick auf das Wohlergehen der Kühe bedenklich ist. Diese Schädigungen stellen vor allem Indikatoren für die unzureichende Tiergerechtheit der Liegeboxen und der Liegeflächen dar. Haarverlust und Dekubitalstellen an Sprunggelenken sind zudem mit Lahmheiten und weiteren Gliedmaßenkrankheiten, aber auch Eutererkrankungen und verringerter Milchleistung assoziiert. Deshalb haben sie nicht nur für das Wohlbefinden, sondern auch für die Leistung von Milchkühen Bedeutung. Epidemiologische Studien und Verhaltensuntersuchungen zeigen, dass – korrekte Abmessungen der Liegeboxen vorausgesetzt – unter den verschiedenen Liegeflächen die Stroh-Mist-Matratze sowie Sand hinsichtlich der Prävalenz von Liegeschäden am besten abschneiden.
Genetic Diversity of Bovine Hemoprotozoa in South Korea

Tick-borne pathogens cause economically significant diseases in cattle. Theileria spp. are parasitic protozoa and the causative agent of bovine theileriosis. Here we report the distribution and risk factors of bovine Theileria using blood samples taken between 2018 and 2019. Of 737 tested cattle, nine animals (1.2%) were positive for Theileria orientalis infection by 18S rRNA gene amplification. Further analysis of the infected samples using the T. orientalis major piroplasm surface protein (MPSP) gene revealed five different genotypes circulating in the population: Types 1, 2, 3, 7, and N3. To the best of our knowledge, this is the first research to describe the existence of the T. orientalis MPSP genotype N3 in South Korea. Although the prevalence of bovine T. orientalis was low, our study offers data on the geographical distribution and prevalence of bovine Theileria spp. in South Korea. Further studies are warranted to determine the correlation of clinical symptoms with parasite MPSP genotypes. Our data provide epidemiological information to help control bovine theileriosis in South Korea.
Heart–brain interactions during social and cognitive stress in hypertensive disease: A multidimensional approach

Hypertensive disease (HTD), a prominent risk factor for cardiovascular and cerebrovascular diseases, is characterized by elevated stress‐proneness. Since stress levels are underpinned by both cardiac and neural factors, multidimensional insights are required to robustly understand their disruption in HTD. Yet, despite their crucial relevance, heart rate variability (HRV) and multimodal neurocognitive markers of stress in HTD remain controversial and unexplored respectively. To bridge this gap, we studied cardiodynamic as well as electrophysiological and neuroanatomical measures of stress in HTD patients and healthy controls. Both groups performed the Trier Social Stress Test (TSST), a validated stress‐inducing task comprising a baseline and a mental stress period. During both stages, we assessed a sensitive HRV parameter (the low frequency/high frequency [LF/HF ratio]) and an online neurophysiological measure (the heartbeat‐evoked potential [HEP]). Also, we obtained neuroanatomical data via voxel‐based morphometry (VBM) for correlation with online markers. Relative to controls, HTD patients exhibited increased LF/HF ratio and greater HEP modulations during baseline, reduced changes between baseline and stress periods, and lack of significant stress‐related HRV modulations associated with the grey matter volume of putative frontrostriatal regions. Briefly, HTD patients presented signs of stress‐related autonomic imbalance, reflected in a potential basal stress overload and a lack of responsiveness to acute psychosocial stress, accompanied by neurophysiological and neuroanatomical alterations. These multimodal insights underscore the relevance of neurocognitive data for developing innovations in the characterization, prognosis and treatment of HTD and other conditions with autonomic imbalance. More generally, these findings may offer new insights into heart–brain interactions.
Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations

Outdoor air pollution is a major contributor to the burden of disease worldwide. Most of the global population resides in places where air pollution levels, because of emissions from industry, power generation, transportation, and domestic burning, considerably exceed the World Health Organization's health‐based air‐quality guidelines. Outdoor air pollution poses an urgent worldwide public health challenge because it is ubiquitous and has numerous serious adverse human health effects, including cancer. Currently, there is substantial evidence from studies of humans and experimental animals as well as mechanistic evidence to support a causal link between outdoor (ambient) air pollution, and especially particulate matter (PM) in outdoor air, with lung cancer incidence and mortality. It is estimated that hundreds of thousands of lung cancer deaths annually worldwide are attributable to PM air pollution. Epidemiological evidence on outdoor air pollution and the risk of other types of cancer, such as bladder cancer or breast cancer, is more limited. Outdoor air pollution may also be associated with poorer cancer survival, although further research is needed. This report presents an overview of outdoor air pollutants, sources, and global levels, as well as a description of epidemiological evidence linking outdoor air pollution with cancer incidence and mortality. Biological mechanisms of air pollution‐derived carcinogenesis are also described. This report concludes by summarizing public health/policy recommendations, including multilevel interventions aimed at individual, community, and regional scales. Specific roles for medical and health care communities with regard to prevention and advocacy and recommendations for further research are also described.