Miracle-dz/UniFAR-FTUs huggingface dataset:
Circadian Regulator-Mediated Molecular Subtypes Depict the Features of Tumor Microenvironment and Indicate Prognosis in Head and Neck Squamous Cell Carcinoma

Introduction Circadian rhythm is involved in multiple biological activities and implicated in cancer development. However, the role of circadian rhythm in head and neck squamous cell carcinoma (HNSCC) has not been fully interpreted yet. Herein, the present study set out to explore the significance of circadian regulator genes (CRGs) in HNSCC. Materials and Methods The molecular landscape and clinical significance of 13 CRGs in HNSCC were explored based on The Cancer Genome Atlas (TCGA). The biological functions of PER3, a key CRG, were validated by cellular experiments. The correlation of CRGs with microenvironment, pathway activities, and prognosis was determined by bioinformatic algorithms. A novel circadian score was introduced to evaluate the circadian modification pattern of each patient and further validated in an independent cohort from the Gene Expression Omnibus (GEO) dataset. Results CRGs presented high heterogeneity in HNSCC at both genomic and transcriptomic levels. Specifically, PER3 indicated a better prognosis and inhibited HNSCC cell proliferation. Moreover, HNSCC tissues displayed three circadian regulator patterns with distinct clinical outcomes, transcriptomic characteristics, and microenvironment features. Circadian score was an independent risk factor and exhibited excellent predictive efficiency in both the training cohort from the TCGA database and the validation cohort from the GEO database. Conclusions CRGs played an indispensable role in HNSCC development. An in-depth exploration of circadian rhythm would improve the understanding of HNSCC carcinogenesis and confer novel insights for future clinical practices.
Physiologic effects of surgical masking in children versus adults

Background Surgical masks remain a focal part of the CDC guidelines to decrease COVID-19 transmission. Evidence refuting significant effects of masking on ventilation is mostly limited to small studies, with a paucity of studies on children, and none comparing children to adults. Methods A total of 119 subjects were enrolled (71 adults, 49 children) in a prospective interventional study with each subject serving as their own mask-free control. End tidal CO2 (ETCO2), inspired CO2 (ICO2), and respiratory rate were measured by nasal cannula attached to an anesthesia machine D-fend module. Pulse oximetry and heart rate were also followed. After the mask-free period, an ASTM Level 3 disposable surgical mask was donned and 15 min of mask-worn data were collected. Results A steady state was confirmed for ETCO2 and ICO2 over the masked period, and mean ICO2 levels rose significantly (p < 0.001) after masking in all age groups. The increase in ICO2 for the 2- to 7-year-old group of 4.11 mmHg (3.23–4.99), was significantly higher (p < 0.001) than the final ΔICO2 levels for both the 7- to 14-year-old group, 2.45 mmHg (1.79–3.12), and adults, 1.47 mmHg (1.18–1.76). For the pediatric group there was a negative, significant correlation between age and ΔICO2, r = −0.49, p < 0.001. Masking resulted in a statistically significant (p < 0.01) rise in ETCO2 levels of 1.30 mmHg in adults and 1.36 mmHg in children. The final respective ETCO2 levels, 34.35 (33.55–35.15) and 35.07 (34.13–36.01), remained within normal limits. Pulse oximetry, heart rate, and respiratory rate were not significantly affected. Discussion The physiology of mechanical dead space is discussed, including the inverse relationship of subject age vs ICO2. The methodology and results are compared to previously published studies which detracted from the physiologic safety of surgical masking. Conclusions The wearing of a surgical mask results in a statistically significant rise in ICO2 and a smaller rise in ETCO2. Because ETCO2 and other variables remain well within normal limits, these changes are clinically insignificant.
Oxide bipolar electronics: materials, devices and circuits

We present the history of, and the latest progress in, the field of bipolar oxide thin film devices. As such we consider primarily pn-junctions in which at least one of the materials is a metal oxide semiconductor. A wide range of n-type and p-type oxides has been explored for the formation of such bipolar diodes. Since most oxide semiconductors are unipolar, challenges and opportunities exist with regard to the formation of heterojunction diodes and band lineups. Recently, various approaches have led to devices with high rectification, namely p-type ZnCo2O4 and NiO on n-type ZnO and amorphous zinc-tin-oxide. Subsequent bipolar devices and applications such as photodetectors, solar cells, junction field-effect transistors and integrated circuits like inverters and ring oscillators are discussed. The tremendous progress shows that bipolar oxide electronics has evolved from the exploration of various materials and heterostructures to the demonstration of functioning integrated circuits. Therefore a viable, facile and high performance technology is ready for further exploitation and performance optimization.
The classical bi-Poisson process: An invertible quadratic harness $

We give an elementary construction of a time-invertible Markov process which is discrete except at one instance. The process is one of the quadratic harnesses studied in Bryc and Weso"owski [2005. Conditional moments of q-Meixner processes. Probab. Theory Related Fields 131, 415–441 harxiv.org/abs/math.PR/0403016i], Bryc et al. [2005b. Quadratic harnesses, q-commutations, and orthogonal martingale polynomials. Trans. Amer. Math. Soc. harxiv.org/abs/math.PR/ 0504194i, to appear], and Bryc et al. [2005a. The bi-Poisson process: a quadratic harness harxiv.org/abs/math.PR/ 0510208i]. It can be constructed from a pair of independent Poisson processes with the same gamma-distributed intensity. r 2006 Elsevier B.V. All rights reserved.
Long-term cardiovascular outcomes among immigrants and non-immigrants in cardiac resynchronization therapy: a nationwide study

Abstract Aims To date, potential differences in outcomes for immigrants and non-immigrants with a cardiac resynchronization therapy (CRT), in a European setting, remain underutilized and unknown. Hence, we examined the efficacy of CRT measured by heart failure (HF)-related hospitalizations and all-cause mortality among immigrants and non-immigrants. Methods and results All immigrants and non-immigrants who underwent first-time CRT implantation in Denmark (2000–2017) were identified from nationwide registries and followed for up to 5 years. Differences in HF related hospitalizations and all-cause mortality were evaluated by Cox regression analyses. From 2000 to 2017, 369 of 10 741 (3.4%) immigrants compared with 7855 of 223 509 (3.5%) non-immigrants with a HF diagnosis underwent CRT implantation. The origins of the immigrants were Europe (61.2%), Middle East (20.1%), Asia-Pacific (11.9%), Africa (3.5%), and America (3.3%). We found similar high uptake of HF guideline-directed pharmacotherapy before and after CRT and a consistent reduction in HF-related hospitalizations the year before vs. the year after CRT (61% vs. 39% for immigrants and 57% vs. 35% for non-immigrants). No overall difference in 5-year mortality among immigrants and non-immigrants was seen after CRT [24.1% and 25.8%, respectively, P-value = 0.50, hazard ratio (HR) = 1.2, 95% confidence interval (CI): 0.8–1.7]. However, immigrants of Middle Eastern origin had a higher mortality rate (HR = 2.2, 95% CI: 1.2–4.1) compared with non-immigrants. Cardiovascular causes were responsible for the majority of deaths irrespective of immigration status (56.7% and 63.9%, respectively). Conclusion No overall differences in efficacy of CRT in improving outcomes between immigrants and non-immigrants were identified. Although numbers were low, a higher mortality rate among immigrants of Middle Eastern origin was identified compared with non-immigrants.
The Engulfing Theorem for Topological Manifolds

THEOREM. Every locally tame closed set X, of dimension p ? n 3 in a p-connected topological n-manifold-without-boundary M, can be engulfed by any (p 1)-connected open set V, such that X\ V is compact. ' This means that there is a self-homeomorphism h, of M such that X ' h V. There is an isotopy of h to the identity composed of a finite number of small pushes, each of which moves the points of a subset of a euclidean neighbourhood along parallel lines and leaves all else fixed. The theorem is in fact proved for a somewhat larger class of sets X, the p-dominated sets (p < n 3) defined in ? 9. By an argument due to E. H. Connell, based on Stallings' stretching process between dual skeletons, the Poincare hypothesis for topological n-manifolds (n ? 5) is derived from this form of the engulfing theorem.
Pilot Testing of the MyCog Assessment: Rapid Detection of Cognitive Impairment in Everyday Clinical Settings

Cognitive impairment (CI) and dementia can have profound social and emotional effects on older adults. Early detection of CI is imperative both to the identification of potentially treatable conditions and to provide services to minimize the effects of CI in cases of dementia. While primary care settings are ideal for identifying CI, it frequently goes undetected. We tailored a brief, iPad-based, cognitive assessment (MyCog) for primary care settings and piloted it in a sample of older adults. Eighty participants were recruited from an existing cohort study and completed a brief, in-person interview. CI was determined based on a diagnosis of dementia or CI in their medical record or based on a comprehensive cognitive battery performed within the past 18 months. MyCog had a sensitivity of 79% and specificity of 82%, offering a practical, scalable, primary care assessment for the routine case finding of cognitive impairment and dementia.
Human prion disease: molecular pathogenesis, and possible therapeutic targets and strategies

ABSTRACT Introduction Human prion diseases are heterogeneous, and often rapidly progressive, transmissible neurodegenerative disorders associated with misfolded prion protein (PrP) aggregation and self-propagation. Despite their rarity, prion diseases comprise a broad spectrum of phenotypic variants determined at the molecular level by different conformers of misfolded PrP and host genotype variability. Moreover, they uniquely occur in idiopathic, genetically determined, and acquired forms with distinct etiologies. Area covered This review provides an up-to-date overview of potential therapeutic targets in prion diseases and the main results obtained in cell and animal models and human trials. The open issues and challenges associated with developing effective therapies and informative clinical trials are also discussed. Expert opinion Currently tested therapeutic strategies target the cellular PrP to prevent the formation of misfolded PrP or to favor its elimination. Among them, passive immunization and gene therapy with antisense oligonucleotides against prion protein mRNA are the most promising. However, the disease’s rarity, heterogeneity, and rapid progression profoundly frustrate the successful undertaking of well-powered therapeutic trials and patient identification in the asymptomatic or early stage before the development of significant brain damage. Thus, the most promising therapeutic goal to date is preventing or delaying phenoconversion in carriers of pathogenic mutations by lowering prion protein expression.
Clinical outcomes in patients with metastatic castrate‐resistant prostate cancer treated with abiraterone with or without ongoing androgen deprivation therapy: A retrospective case–control study

Abiraterone and concurrent androgen deprivation therapy (ADT) are used in the treatment of patients with metastatic castration‐resistant prostate cancer. Recently, it has been suggested that the use of abiraterone alone (without ADT) may have comparable efficacy to abiraterone with ongoing ADT. Here, we sought to assess the impact of ADT cessation in patients beginning abiraterone for castration‐resistant prostate cancer.
Real-world survival of Danish patients with HER2-positive metastatic breast cancer

Abstract Background The purpose was to investigate the treatment flow of patients with HER2-positive metastatic breast cancer (mBC), progression-free survival (PFS) and overall survival (OS) across treatment lines and adherence to guidelines (defined as trastuzumab, pertuzumab and chemotherapy first line, where 85% received vinorelbine as backbone and T-DM1 second line). Furthermore, we identified clinical markers to predict the risk of developing brain metastases. Material and Methods Patients with HER2-positive mBC, diagnosed between 01.01. 2014–31.12. 2019, registered in the database of the Danish Breast Cancer Group were included in this real-word study. Clinical follow-up was assessed until 01.10. 2020 and complete follow-up for overall survival until 01.10. 2021. Survival data were analyzed using the Kaplan-Meier method with guidelines adherence analyzed as a time-varying covariate, and the risk of CNS metastasis was estimated by the cumulative incidence function. Results 631 patients were included. 329 (52%) patients followed the guidelines. The median OS for all patients was 42.3 months (95% Cl, 38.2–48.4), and significantly higher for the patients who followed guidelines; NA (95% CI, 78.2–NA). The median PFS for all patients was 13.4 months (95% Cl, 12.1–14.8), 6.6 (95% Cl, 5.8–7.6) and 5.8 (95% Cl, 4.9–6.9) for first, second and third line of treatment, respectively. Patients with ER-negative mBC had a higher risk of developing brain metastases and patients with high tumor burden had a higher risk of developing brain metastases with an adjusted HR of 0.69 (95% CI, 0.49–0.98), p = 0.047 and 2.69 (95% CI, 1.45–5.00), p = 0.002, respectively. Conclusion We found that only half of the patients with HER2-positive mBC, received first and second-line treatment according to national guidelines. Patients receiving treatment according to guidelines had a significantly higher median OS compared to patients who did not. We also found that patients with ER-negative disease or high tumor burden had a significantly higher risk of developing brain metastases.
Susceptibility and disease modifier genes in amyotrophic lateral sclerosis: from genetic associations to therapeutic implications

Purpose of review Amyotrophic lateral sclerosis (ALS) is a severe disease characterized by the degeneration of motor neurons. Large-scale genetic studies have now identified over 60 genes that are associated with ALS, which in large part have also been functionally characterized. The purpose of this review is to outline how these advances are being translated into novel therapeutic strategies. Recent findings The emergence of techniques that allow the specific therapeutic targeting of a (mutant) gene, in particular antisense oligonucleotide therapy (ASOs), have led to the first successful gene therapy for SOD1-ALS and multiple other gene-targeted trials are underway. This includes genetic variants that modify the disease phenotype as well as causal mutations. Summary Technological and methodological advances are enabling researchers to unravel the genetics of ALS. Both causal mutations and genetic modifiers are viable therapeutic targets. By performing natural history studies, the phenotype-genotype correlations can be characterized. In conjunction with biomarkers for target engagement and international collaboration, this makes performing gene-targeted trials ALS feasible. The first effective treatment has now been developed for SOD1-ALS and, with multiple studies underway, it seems realistic that more therapies will follow.
Spin coating formation of self-assembled ferroelectric β-glycine films

ABSTRACT The formation of self-assembled ferroelectric glycine films of various morphologies by spin coating technique was investigated. The film morphology varied from dendritic feather-like structure to arrays of individual micro- and nanoislands and 15 nm-thick layers. It was confirmed by confocal Raman microscopy that most of the films belonged to ferroelectric beta phase. Piezoelectric properties and domain structure of the films were studied by piezoresponse force microscopy.
Differential risk of 23 site‐specific incident cancers and cancer‐related mortality among patients with metabolic dysfunction‐associated fatty liver disease: a population‐based cohort study with 9.7 million Korean subjects

Although an association between metabolic dysfunction‐associated fatty liver disease (MAFLD) and cardiovascular disease or overall mortality has been reported, it is unclear whether there is an association between MAFLD and cancer incidence or mortality. We aimed to investigate the differential risk of all‐ and site‐specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease.
Variational method for liquids moving on a substrate

A new variational method is proposed to calculate the evolution of liquid film and liquid droplet moving on a solid substrate. A simple time evolution equation is obtained for the contact angle of a liquid film that starts to move on a horizontal substrate. The equation indicates the dynamical transition at the receding side and the ridge formation at the advancing side. The same method is applied for the evolution of a droplet that starts to move on an inclined solid surface, and again the characteristic shape change of the droplet is obtained by solving a simple ordinary differential system. We will show that this method has a potential application to a wide class of problems of droplets moving on a substrate.
Deux méthodes d'apprentissage non supervisé : synthèse sur la méthode des centres mobiles et présentation des courbes principales * Title: Two methods in unsupervised learning : summary on k-means clustering and presentation of principal curves

This article proposes a review on unsupervised learning. After an introduction to quantization and to the related question of k-means clustering, the notion of principal curve, that may be seen as a generalization of these methods, is presented. We expound different definitions of principal curve and give an overview of its applications.
An open competition involving thousands of competitors failed to construct useful abstract classifiers for new diagnostic test accuracy systematic reviews

There are currently no abstract classifiers, which can be used for new diagnostic test accuracy (DTA) systematic reviews to select primary DTA study abstracts from database searches. Our goal was to develop machine‐learning‐based abstract classifiers for new DTA systematic reviews through an open competition. We prepared a dataset of abstracts obtained through database searches from 11 reviews in different clinical areas. As the reference standard, we used the abstract lists that required manual full‐text review. We randomly splitted the datasets into a train set, a public test set, and a private test set. Competition participants used the training set to develop classifiers and validated their classifiers using the public test set. The classifiers were refined based on the performance of the public test set. They could submit as many times as they wanted during the competition. Finally, we used the private test set to rank the submitted classifiers. To reduce false exclusions, we used the Fbeta measure with a beta set to seven for evaluating classifiers. After the competition, we conducted the external validation using a dataset from a cardiology DTA review. We received 13,774 submissions from 1429 teams or persons over 4 months. The top‐honored classifier achieved a Fbeta score of 0.4036 and a recall of 0.2352 in the external validation. In conclusion, we were unable to develop an abstract classifier with sufficient recall for immediate application to new DTA systematic reviews. Further studies are needed to update and validate classifiers with datasets from other clinical areas.
Children across cultures respond emotionally to the acoustic environment

ABSTRACT Among human and non-human animals, the ability to respond rapidly to biologically significant events in the environment is essential for survival and development. Research has confirmed that human adult listeners respond emotionally to environmental sounds by relying on the same acoustic cues that signal emotionality in speech prosody and music. However, it is unknown whether young children also respond emotionally to environmental sounds. Here, we report that changes in pitch, rate (i.e. playback speed), and intensity (i.e. amplitude) of environmental sounds trigger emotional responses in 3- to 6-year-old American and Chinese children, including four sound types: sounds of human actions, animal calls, machinery, and natural phenomena such as wind and waves. Children’s responses did not differ across the four types of sounds used but developed with age – a finding observed in both American and Chinese children. Thus, the ability to respond emotionally to non-linguistic, non-music environmental sounds is evident at three years of age – an age when the ability to decode emotional prosody in language and music emerges. We argue that general mechanisms that support emotional prosody decoding are engaged by all sounds, as reflected in emotional responses to non-linguistic acoustic input such as music and environmental sounds.
Low-Dose Ketamine-Induced Deficits in Arbitrary Visuomotor Mapping in Monkeys

Abstract Ketamine, an NMDA antagonist, is widely used in clinical settings. Recently, low-dose ketamine has gained attention because of its promising role as a rapid antidepressant. However, the effects of low-dose ketamine on brain function, particularly higher cognitive functions of primate brains, are not fully understood. In this study, we used two macaques as subjects and found that acute low-dose ketamine administration significantly impaired the ability for arbitrary visuomotor mapping (AVM), a form of associative learning (AL) essential for flexible behaviors, including executions of learned stimuli-response contingency or learning of new contingencies. We conducted in-depth analyses and identified intrinsic characteristics of these ketamine-induced functional deficits, including lowered accuracy, prolonged time for planning and movement execution, increased tendency to make errors when visual cues are changed from trial to trial, and stronger impact on combining associative learning and another key higher cognitive function, working memory (WM). Our results shed new light on how associative learning relies on the NMDA-mediated synaptic transmission of the brain and contribute to a better understanding of the potential acute side effects of low-dose ketamine on cognition, which can help facilitate its safe usage in medical practice.
Darwin's ‘mystery of mysteries’: the role of sexual selection in plant speciation

Sexual selection is considered one of the key processes that contribute to the emergence of new species. While the connection between sexual selection and speciation has been supported by comparative studies, the mechanisms that mediate this connection remain unresolved, especially in plants. Similarly, it is not clear how speciation processes within plant populations translate into large‐scale speciation dynamics. Here, we review the mechanisms through which sexual selection, pollination, and mate choice unfold and interact, and how they may ultimately produce reproductive isolation in plants. We also overview reproductive strategies that might influence sexual selection in plants and illustrate how functional traits might connect speciation at the population level (population differentiation, evolution of reproductive barriers; i.e. microevolution) with evolution above the species level (macroevolution). We also identify outstanding questions in the field, and suitable data and tools for their resolution. Altogether, this effort motivates further research focused on plants, which might potentially broaden our general understanding of speciation by sexual selection, a major concept in evolutionary biology.