Miracle-dz/UniFAR-FTUs huggingface dataset:
YC-1 Prevents Tumor-Associated Tissue Factor Expression and Procoagulant Activity in Hypoxic Conditions by Inhibiting p38/NF-κB Signaling Pathway

Tissue factor (TF) expressed in cancer cells has been linked to tumor-associated thrombosis, a major cause of mortality in malignancy. Hypoxia is a common feature of solid tumors and can upregulate TF. In this study, the effect of YC-1, a putative inhibitor of hypoxia-inducible factor-1α (HIF-1α), on hypoxia-induced TF expression was investigated in human lung cancer A549 cells. YC-1 selectively prevented hypoxia-induced TF expression and procoagulant activity without affecting the basal TF levels. Surprisingly, knockdown or pharmacological inhibition of HIF-1α failed to mimic YC-1′s effect on TF expression, suggesting other mechanisms are involved. NF-κB, a transcription factor for TF, and its upstream regulator p38, were activated by hypoxia exposure. Treatment of hypoxic A549 cells with YC-1 prevented the activation of both NF-κB and p38. Inhibition of p38 suppressed hypoxia-activated NF-κB, and inhibited TF expression and activity to similar levels as treatment with an NF-κB inhibitor. Furthermore, stimulation of p38 by anisomycin reversed the effects of YC-1. Taken together, our results suggest that YC-1 prevents hypoxia-induced TF in cancer cells by inhibiting the p38/NF-κB pathway, this is distinct from the conventional anticoagulants that systemically inhibit blood coagulation and may shed new light on approaches to treat tumor-associated thrombosis.
A comprehensive study of immunology repertoires in both preoperative stage and postoperative stage in patients with colorectal cancer

Colorectal cancer (CRC) is the 3rd most common cancer type in the world. The correlation between immune repertoire and prognosis of CRC has been well studied in the last decades. The diversity and stability of the immune cells can be measured by hypervariable complementarity‐determining region 3 (CDR3) segments of the T‐cell receptor (TCR).
A topological view of human CD34+ cell state trajectories from integrated single-cell output and proteomic data.

Recent advances in single-cell molecular analytical methods and clonal growth assays are enabling more refined models of human hematopoietic lineage restriction processes to be conceptualized. Here, we report the results of integrating single-cell proteome measurements with clonally determined lymphoid, neutrophilic/monocytic, and/or erythroid progeny outputs from >1000 index-sorted CD34+ human cord blood cells in short-term cultures with and without stromal cells. Surface phenotypes of functionally examined cells were individually mapped onto a molecular landscape of the entire CD34+ compartment constructed from single-cell mass cytometric measurements of 14 cell surface markers, 20 signaling/cell cycle proteins, and 6 transcription factors in ∼300 000 cells. This analysis showed that conventionally defined subsets of CD34+ cord blood cells are heterogeneous in their functional properties, transcription factor content, and signaling activities. Importantly, this molecular heterogeneity was reduced but not eliminated in phenotypes that were found to display highly restricted lineage outputs. Integration of the complete proteomic and functional data sets obtained revealed a continuous probabilistic topology of change that includes a multiplicity of lineage restriction trajectories. Each of these reflects progressive but variable changes in the levels of specific signaling intermediates and transcription factors but shared features of decreasing quiescence. Taken together, our results suggest a model in which increasingly narrowed hematopoietic output capabilities in neonatal CD34+ cord blood cells are determined by a history of external stimulation in combination with innately programmed cell state changes.
Exploring the Perceptions of Young People in Care and Care Leavers of their Health Needs

This paper presents findings from a research study into the health needs and concerns of young people in care and leaving care (aged 14 to 24 years) carried out in Glasgow during 2001 (Scottish Health Feedback 2001). The study was commissioned by Glasgow Alliance Care Leavers Social Inclusion Partnership (known as the big step), which was set up in 1999 as part of the Scottish Executive's Social Inclusion Strategy. The paper discusses the findings and draws implications for future policy and practice.
Small-sample performance and underlying assumptions of a bootstrap-based inference method for a general analysis of covariance model with possibly heteroskedastic and nonnormal errors

It is well known that the standard F test is severely affected by heteroskedasticity in unbalanced analysis of covariance models. Currently available potential remedies for such a scenario are based on heteroskedasticity-consistent covariance matrix estimation (HCCME). However, the HCCME approach tends to be liberal in small samples. Therefore, in the present paper, we propose a combination of HCCME and a wild bootstrap technique, with the aim of improving the small-sample performance. We precisely state a set of assumptions for the general analysis of covariance model and discuss their practical interpretation in detail, since this issue may have been somewhat neglected in applied research so far. We prove that these assumptions are sufficient to ensure the asymptotic validity of the combined HCCME-wild bootstrap analysis of covariance. The results of our simulation study indicate that our proposed test remedies the problems of the analysis of covariance F test and its heteroskedasticity-consistent alternatives in small to moderate sample size scenarios. Our test only requires very mild conditions, thus being applicable in a broad range of real-life settings, as illustrated by the detailed discussion of a dataset from preclinical research on spinal cord injury. Our proposed method is ready-to-use and allows for valid hypothesis testing in frequently encountered settings (e.g., comparing group means while adjusting for baseline measurements in a randomized controlled clinical trial).
Proteomic Screening for Serum Biomarkers for Cervical Cancer and Their Clinical Significance

Background The present study aimed to determine serum markers for cervical cancer (CC) and to provide valuable references for clinical diagnosis and treatment. Material/Methods Serum samples were collected from age-matched healthy control women, and from female CC patients before and after surgery. Serum biomarkers were selected by comparing serum peptides profiles among the 3 groups by magnetic bead-based weak cation – exchange chromatography fractionation combined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Probable serum biomarkers for cervical cancer were then further identified by liquid chromatography-electrospray ionization-tandem mass spectrometry system and the identified proteins were verified by enzyme-linked immunosorbent assay (ELISA). Results Three peptide biomarkers were identified for distinguishing CC patients from normal individuals, and distinguishing preoperative CC patients from postoperative CC patients. Of these 3 identified protein peptide regions, 2 peptide regions – TKT (Peak 2, 2435.63 m/z, 499–524) and FGA (Peak 4, 2761.79 m/z, 603–629) – were identified as upregulated markers, and peptide region of APOA1 (Peak 9, 2575.3 m/z, 245–260) was identified as a downregulated biomarker in preoperative CC patients compared with healthy women. Conclusions The present study provides a new method for identifying potential serum biomarkers for CC patients.
Response bias, recollection, and familiarity in individuals with Highly Superior Autobiographical Memory (HSAM)

ABSTRACT The current study focused on individuals with Highly Superior Autobiographical Memory (HSAM) and had two main objectives: 1) investigate whether HSAMs have increased recollection performance compared to controls, and 2) investigate whether HSAMs have a reliably different response bias than controls. While previous lab-based recognition tests have shown that HSAMs have normal memory performance, these tests were based on a mixture of both recollection and familiarity. Here, we employed recognition tests specifically designed to separate recollected responses from those based on familiarity. Additionally, we were interested in how HSAMs make their memory decisions. Several studies have shown a great deal of variability between individuals in their response bias. Here, individuals with HSAM and age- matched controls completed a remember/know and a source memory test. HSAMs behaved like controls in both overall and recollection-based memory discrimination. However, HSAMs showed a significantly more liberal response bias, endorsing more items as “old” than controls. These findings contribute to our understanding of how memory processes – especially those related to decision-making – function in those with superior memory abilities and may help elucidate how other (non-HSAM) memory experts make decisions.
Development of 1H MRS biomarkers for tracking early predementia Alzheimer disease

Single-voxel 1H magnetic resonance spectroscopy (1H MRS) is a magnetic resonance technique for quantifying certain metabolites in the brain that are differentially associated with cellular, molecular, and clinical alterations characteristic of the pathophysiologic development and progression of Alzheimer disease (AD). 1,2 Specifically, lower N-acetylaspartate to creatine ratios (NAA/Cr) have been associated with increased levels of phosphorylated tau seen in pretangle, early neuritic, and mature state neurofibrillary tangle pathology but not with the extracellular neurofibrillary “ghost” tangle tau pathology that occurs later in the disease course.1,2 Lower NAA/Cr has also been associated with a loss of synaptic integrity measured with SV2A synaptic vesicle protein.2 In addition, higher myo-inositol to Cr ratios (mI/Cr) are associated with increased densities of diffuse, neuritic, and cored β-amyloid plaques.1,2 The accumulation of early tau and β-amyloid pathology, as well as loss of synaptic function, precede the onset of cognitive symptoms and dementia in older individuals across the AD continuum; and their association with NAA/Cr and NAA/mI ratios on 1H MRS imaging supports their use as biomarkers able to detect the earliest stages of AD pathophysiology.2
Ultrasonic Tethering to Enable Side-by-Side Following for Powered Wheelchairs

In social situations, people who use a powered wheelchair must divide their attention between navigating the chair and conversing with people. These conversations could lead to increased mental stress when navigating and distraction from maneuvering the chair. As a solution that maintains a good conversation distance between the wheelchair and the accompanying person (Social Following), a wheelchair control system was developed to provide automated side-by-side following by wirelessly connecting the wheelchair to the person. Two ultrasonic range sensors and three piezoelectric ultrasonic transducers were used to identify the accompanying person and determine their position and heading. Identification involved an ultrasonic beacon worn on the person’s side, at hip level, and receivers on the wheelchair. A drive control algorithm maintained a constant conversation distance along the person’s trajectory. A plug-and-play prototype was developed and connected to a Permobil F5 Corpus wheelchair with a modified Eightfold Technologies SmartChair Remote. Results demonstrated that the system can navigate a wheelchair based on the accompanying person’s trajectory, which is advantageous for users who require hands-free wheelchair control during social activities.
CKAP4, a DKK1 Receptor, Is a Biomarker in Exosomes Derived from Pancreatic Cancer and a Molecular Target for Therapy

Purpose: The survival rate of pancreatic ductal adenocarcinoma (PDAC) is poor; thus, novel molecularly targeted therapy and companion diagnostics are required. We asked whether cytoskeleton-associated protein 4 (CKAP4), a novel Dickkopf1 (DKK1) receptor, is a candidate for PDAC diagnosis and therapy. Experimental Design: Whether CKAP4 can be secreted with small extracellular vesicles (SEV) from PDAC cells was examined. It was also investigated whether CKAP4 can be detected in sera from patients with PDAC by ELISA using newly generated anti-CKAP4 mAbs and whether anti-CKAP4 mAbs can show antitumor activity in vivo. Results: CKAP4 was secreted with SEVs from PDAC cells, and the SEVs exhibited the characteristics of exosomes. The secretion of CKAP4-containing exosomes was mediated by DKK1-dependent endocytosis routes and required exosome biogenesis molecules. Two ELISAs capable of detecting tumor-secreted CKAP4 were developed. The serum CKAP4 levels were higher in patients with PDAC than healthy control individuals. CKAP4 was highly detected in the sera of pancreatic tumor-bearing xenografted mice and patients with PDAC, whereas CKAP4 was barely detectable in sera from normal mice and postoperative patients. Anti-CKAP4 mAbs with different epitopes demonstrated the inhibitory activities for the binding of DKK1 and CKAP4, AKT activity, and proliferation and migration of PDAC cells. Anti-CKAP4 mAbs also suppressed xenograft tumor formation in immunodeficient mice and extended the survival of mice receiving intraperitoneal or orthotopic injection of PDAC cells. Conclusions: CKAP4 secreted in exosomes may represent a biomarker for PDAC. Anti-CKAP4 mAbs can contribute to the development of novel diagnostic methods and therapeutics.
Photoswitching FRET to monitor protein–protein interactions

Significance Since protein–protein interactions are extremely important in understanding normal and abnormal cell behavior, cell biologists have often relied on fluorescence techniques, such FRET, as a way to monitor interactions. FRET occurs when donor fluorescent molecules tagged to a protein of interest transfer their excited-state energy to acceptor molecules tagged to another protein of interest. The need to accurately and easily measure FRET led to our development of photoswitching FRET (psFRET). It provides advantages normally associated with advanced methods, like fluorescence lifetime imaging microscopy, with the ease and accessibility of other widely used methods, such as sensitized emission or acceptor photobleaching. The psFRET approach will greatly enhance the ability of cell biologists to utilize FRET in their studies. FRET is a powerful approach to study the interactions of fluorescent molecules, and numerous methods have been developed to measure FRET in cells. Here, we present a method based on a donor molecule’s photoswitching properties, which are slower in the presence vs. the absence of an acceptor. The technique, photoswitching FRET (psFRET), is similar to an established but underutilized method called photobleaching FRET (pbFRET), with the major difference being that the molecules are switched “off” rather than photobleached. The psFRET technique has some of the FRET imaging advantages normally attributed to fluorescence lifetime imaging microscopy (FLIM), such as monitoring only donor fluorescence. However, it can be performed on a conventional widefield microscope, requires less illumination light to photoswitch off than photobleaching, and can be photoswitched “on” again to repeat the experiment. We present data testing the validity of the psFRET approach to quantify FRET in cells and demonstrate its use in imaging protein–protein interactions and fluorescent protein-based biosensors.
Migraine Progression: A Systematic Review

Migraine is a common and often debilitating neurological disease. It can be divided into episodic and chronic subforms based on the number of monthly headache days. Because only a subset of individuals with episodic migraine (EM) progress to chronic migraine (CM) over any given time period, understanding the factors that predict the new onset of CM or “migraine progression” may provide insights into the mechanisms, pathophysiology, prevention, and treatment of CM. In this review, we identify and summarize studies that report risk factors associated with the new onset of CM or related chronic headache diagnoses, group these risk factors and report the strength of evidence for the identified risk factors.
Astrocytic changes with aging and Alzheimer's disease‐type pathology in chimpanzees

Astrocytes are the main homeostatic cell of the central nervous system. In addition, astrocytes mediate an inflammatory response when reactive to injury or disease known as astrogliosis. Astrogliosis is marked by an increased expression of glial fibrillary acidic protein (GFAP) and cellular hypertrophy. Some degree of astrogliosis is associated with normal aging and degenerative conditions such as Alzheimer's disease (AD) and other dementing illnesses in humans. The recent observation of pathological markers of AD (amyloid plaques and neurofibrillary tangles) in aged chimpanzee brains provided an opportunity to examine the relationships among aging, AD‐type pathology, and astrocyte activation in our closest living relatives. Stereologic methods were used to quantify GFAP‐immunoreactive astrocyte density and soma volume in layers I, III, and V of the prefrontal and middle temporal cortex, as well as in hippocampal fields CA1 and CA3. We found that the patterns of astrocyte activation in the aged chimpanzee brain are distinct from humans. GFAP expression does not increase with age in chimpanzees, possibly indicative of lower oxidative stress loads. Similar to humans, chimpanzee layer I astrocytes in the prefrontal cortex are susceptible to AD‐like changes. Both prefrontal cortex layer I and hippocampal astrocytes exhibit a high degree of astrogliosis that is positively correlated with accumulation of amyloid beta and tau proteins. However, unlike humans, chimpanzees do not display astrogliosis in other cortical layers. These results demonstrate a unique pattern of cortical aging in chimpanzees and suggest that inflammatory processes may differ between humans and chimpanzees in response to pathology.
Strengthening the Interaction of the Virology Community with the International Committee on Taxonomy of Viruses (ICTV) by Linking Virus Names and Their Abbreviations to Virus Species.

The International Committee on Taxonomy of Viruses (ICTV) is tasked with classifying viruses into taxa (orders to species) and devising taxon names. Virus names and virus name abbreviations are currently not within the ICTV's official remit and are not regulated by an official entity. Many scientists, medical/veterinary professionals, and regulatory agencies do not address evolutionary questions nor are they concerned with the hierarchical organization of the viral world and therefore have limited use for ICTV-devised taxa. Instead, these professionals look to the ICTV as an expert point source that provides the most current taxonomic affiliations of viruses of interests to facilitate document writing. These needs are currently unmet as an ICTV-supported, easily-searchable database that includes all published virus names and abbreviations linked to their taxa is not available. In addition, in stark contrast to other biological taxonomic frameworks, virus taxonomy currently permits individual species to have several members. Consequently, confusion emerges among those who are not aware of the difference between taxa and viruses, and because certain well-known viruses cannot be located in ICTV publications or be linked to their species. In addition, the number of duplicate names and abbreviations has increased dramatically in the literature. To solve this conundrum, the ICTV could mandate listing all viruses of established species and all reported unclassified viruses in forthcoming online ICTV Reports and create a searchable webpage using this information. The International Union of Microbiology Societies could also consider changing the mandate of the ICTV to include the nomenclature of all viruses in addition to taxon considerations. With such a mandate expansion, official virus names and name abbreviations could be catalogued and virus nomenclature could be standardized. As a result, the ICTV would become an even more useful resource for all stakeholders in virology.
Relationship between primary open angle glaucoma and blood pressure

Abstract Background: Glaucoma is commonly defined as high intra ocular pressure (≥21 mmHg) with optic neuropathy characterised by progressive loss of retinal ganglion cells which is associated with characteristic structural damage to the optic nerve and visual field loss. There are several studies investigating relation between primary open angle glaucoma (POAG) and both systemic hypertension and especially night hypotension. Our aim was to compare 24-h ambulatory blood pressure variability of patients with glaucoma followed-up in the eye outpatient clinic with that of patients free of glaucoma. Methods: A total of 75 patients were included in the study, 35 in the patient group and 40 in the control group. Both groups were compared for daytime, night-time, and whole day mean systolic and diastolic blood pressure (BP) readings in the ambulatory blood pressure testing. Results: Mean daytime systolic BP of the glaucoma patients was 119.5 ± 11.6 mmHg, and 128.3 ± 15.5 mmHg for control group (p = 0.008). The night-time systolic blood pressure, whole day systolic BP, and mean diastolic BP were significantly lower in patients with glaucoma (p = 0.001, p = 0.001, p = 0.028, respectively). In multiple regression analysis, we identified daytime systolic BP, night-time systolic BP, and whole day systolic BP were independent risk factors for developing glaucoma. Conclusion: If the progression of the disease is noticeable in patients with glaucoma at follow-up, night-time hypotension should be ruled out with ambulatory blood pressure and if this is observed medical treatments used by the patients should be reviewed and necessary measures should be taken.
Switchable Photonic Nanojet by Electro-Switching Nematic Liquid Crystals

This paper first presents a switchable photonic nanojet (PNJ) generated by a polystyrene (PS) microsphere immersed in nematic liquid crystals (NLCs). The PNJ is switched by applying external voltage, which originates from the refractive index change in the surrounding medium caused by the field-induced realignment of liquid crystal molecules. By tuning the refractive index of NLCs larger or smaller than that of the PS microsphere, the PNJ can be switched off or on. Moreover, we present an optimization study to seek a better electric energy focusing property of the PNJ. Our results reveal that the switchability of PNJ can be optimized by applying a shorter incident wavelength, a double-layer microsphere, and a PS ellipsoid. The full width at half-maximum (FWHM) generated by the PS ellipsoid is narrower than that generated by the microsphere with a shorter incident wavelength. The intensity contrast of the PS ellipsoid is higher than that of the double-layer microsphere. As a whole, the switchability of PNJ can be best optimized by a PS ellipsoid. This should open the way for the development of integrated photonic devices.