Miracle-dz/UniFAR-FTUs huggingface dataset:
IMMUNOBIOLOGY Loss of the Rap 1 effector RIAM results in leukocyte adhesion de fi ciency due to impaired b 2 integrin function in mice

Integrins are a/b heterodimeric transmembrane receptors that are expressed on all cells. They provide stable adhesion of cells to the extracellular matrix or to other cell counter receptors by forming complex adhesion sites, which serve as signaling platforms (outside-in signaling) that induce cell polarity, migration, survival, and proliferation. Because integrins reside in an inactive state, integrin-ligand binding requires an integrin activation step (inside-out signaling), which switches the heterodimer from a lowto a high-affinity state. The majority of studies that defined integrin affinity regulation were performed on aIIbb3 and b2-class integrins expressed by platelets and leukocytes, respectively. These cells circulate in the blood and keep their integrins in an inactive state until they encounter soluble or membrane-bound agonists, which activate talin-1 and the hematopoietic cell-specific kindlin-3, which in turn cooperate to induce integrin activation and clustering. Consequently, loss of kindlin-3 or talin-1 expression in platelets and leukocytes abolishes activation of aIIbb3 and b2 integrins leading to severe bleeding and leukocyte adhesion defects. Talin, which consists of an N-terminal band 4.1, ezrin, radixin, moesin (FERM)andaC-terminal roddomain, exists inan autoinhibited globular and active extended conformation that binds and activates integrins. In the autoinhibited state, the rod domain interacts with the FERMdomain, whichmasks the integrin-binding site. This inhibition is released by binding of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) to the talin head, which disrupts the autoinhibitory interaction between the rod domain and integrin binding region on the talin head and orients talin on the plasma membrane enabling b integrin tail binding. Talin activity has been shown to be regulated by activation of the small GTPase Ras-related protein 1 (Rap1), a known regulator of cell adhesion. Rap1-guanosine triphosphate (GTP)–interacting adapter molecule (RIAM) is a Rap1 effector molecule, which localizes to the leading edge of spreading cells and is expressed in many tissues. It belongs to the Mig-10/RIAM/lamellipodin (MRL) protein family, a group of multidomain adapter proteins involved in the regulation of actin dynamics, cell adhesion and migration, and cell growth. Knockdown of RIAM abrogated Rap1-induced adhesion to integrin ligands, whereas RIAM overexpression increased cell spreading and adhesion to b1 and b2 integrin ligands. RIAM was identified in signaling complexes downstreamof the T-cell receptor andCCchemokine receptor 7, suggesting a role in integrin aLb2 inside-out signaling. The molecular mechanism that underlies RIAM-mediated
Optimization of the Production Process of Clinical-Grade Human Salivary Gland Organoid-Derived Cell Therapy for the Treatment of Radiation-Induced Xerostomia in Head and Neck Cancer

Head and neck cancer is a common cancer worldwide. Radiotherapy has an essential role in the treatment of head and neck cancers. After irradiation, early effects of reduced saliva flow and hampered water secretion are seen, along with cell loss and a decline in amylase production. Currently, there is no curative treatment for radiation-induced hyposalivation/xerostomia. This study aimed to develop and optimize a validated manufacturing process for salivary gland organoid cells containing stem/progenitor cells using salivary gland patient biopsies as a starting material. The manufacturing process should comply with GMP requirements to ensure clinical applicability. A laboratory-scale process was further developed into a good manufacturing practice (GMP) process. Clinical-grade batches complying with set acceptance and stability criteria were manufactured. The results showed that the manufactured salivary gland-derived cells were able to self-renew, differentiate, and show functionality. This study describes the optimization of an innovative and promising novel cell-based therapy.
Quality of Care and Patient Outcome in Stroke Units: Is Medical Specialty of Importance?

BackgroundSpecialized stroke unit care improves outcome in stroke patients. However, it is uncertain whether the units should be placed in a neurological or non-neurological (eg, internal medicine or geriatric) setting. ObjectivesTo assess whether stroke unit setting (neurological/non-neurological) is associated with quality of care and outcome among patients with stroke, and whether these associations depend on the severity of comorbidity. MethodsIn a nationwide population-based follow-up study, we identified 45,521 patients admitted to stroke units in Denmark between 2003 and 2008. Outcomes were quality of care (whether patients received evidence-based processes of acute stroke care), mortality, length of stay, and readmission. Charlson comorbidity index was used to assess comorbidity, and comparisons were adjusted for patient and hospital characteristics. ResultsPatients admitted to stroke units in neurological settings had higher odds for early antiplatelet therapy (odds ratio, 1.68; 95% confidence interval, 1.10-2.56) and early computed tomographic scan or magnetic resonance imaging (odds ratio, 1.77; 95% confidence interval, 1.29-2.45) compared with patients in non-neurological settings. No other differences were found when studying quality of care and patient outcomes. However, patients with moderate comorbidity admitted to stroke units in neurological settings had higher odds for 1-year mortality, but comparisons across strata of comorbidity were not statistical significant. ConclusionsExcept for early antiplatelet therapy and early computed tomographic scan or magnetic resonance imaging, the medical setting was not associated with differences in processes of acute stroke care and patient outcome. No medical setting related differences were found according to comorbidity, although indications of a worse outcome in patients with moderate comorbidity in neurological settings warrant further investigation.
Biosynthesis of Cu-In-S Nanoparticles by a Yeast Isolated from Union Glacier, Antarctica: A Platform for Enhanced Quantum Dot-Sensitized Solar Cells

In recent years, the utilization of extremophile microorganisms for the synthesis of metal nanoparticles, featuring enhanced properties and diverse compositions, has emerged as a sustainable strategy to generate high-quality nanomaterials with unique characteristics. Our study focuses on the biosynthesis of Cu-In-S (CIS) nanoparticles, which has garnered considerable attention in the past decade due to their low toxicity and versatile applications in biomedicine and solar cells. Despite this interest, there is a notable absence of reports on biological methods for CIS nanoparticle synthesis. In this research, three yeast species were isolated from soil samples in an extreme Antarctic environment—Union Glacier, Ellsworth Mountains. Among these isolates, Filobasidium stepposum demonstrated the capability to biosynthesize CIS nanoparticles when exposed to copper sulfate, indium chloride, glutathione, and cysteine. Subsequent purification and spectroscopic characterization confirmed the presence of characteristic absorbance and fluorescence peaks for CIS nanoparticles at 500 and 650 nm, respectively. Transmission electron microscopy analysis revealed the synthesis of monodisperse nanoparticles with a size range of 3–5 nm. Energy dispersive X-ray spectroscopy confirmed the composition of the nanoparticles, revealing the presence of copper, indium, and sulfur. The copper/indium ratio ranged from 0.15 to 0.27, depending on the reaction time. The biosynthesized CIS nanoparticles showed higher photostability than biomimetic nanoparticles and demonstrated successful application as photosensitizers in quantum dot-sensitized solar cells (QDSSC), achieving a conversion efficiency of up to 0.0247%. In summary, this work presents a cost-effective, straightforward, and environmentally friendly method for CIS nanoparticle synthesis. Furthermore, it constitutes the first documented instance of a biological procedure for producing these nanoparticles, opening avenues for the development of environmentally sustainable solar cells.
[Transcervical tongue partial reduction combined with uvulopalatopharyngoplasty in treatment of obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE To treat severe obstructive sleep apnea-hypopnea syndrome (OSAHS) with transcervical tongue partial reduction and evaluate treating effect. METHODS Forty four patients of severe OSAHS were treated with transcervical tongue partial reduction + uvulopalatopharyngoplasty (UPPP). Apnea hypopnea index (AHI), minimal oxygen percent saturation, body mass index (BMI), area of retroglossal region were measured for diagnosis and evaluation. RESULTS AHI decreased from (67.5 ± 21.1) times/h to (10.5 ± 6.8) times/h (t = 2.1, P < 0.01). The lowest oxygen percent saturation increased from 0.694 ± 0.009 to 0.829 ± 0.008 (t = 4.3, P < 0.01). The area of retroglossal region increased from (291.7 ± 107.8) mm² to (398.1 ± 94.5) mm² (t = 3.318, P < 0.05). Four patients complained dysphagia half year after operation. One patient complained about pharyngeal fistula, which disappeared in 2 weeks. One patient appeared hypoglossis bleeding, which stopped after compression. CONCLUSION Transcervical tongue partial reduction is an effective attempt and supplement for OSAHS with retroglossal region narrow.
The Effects of Online Home-Based Pilates Combined with Diet on Body Composition in Women Affected by Obesity: A Preliminary Study

Diet and exercise intervention are the first strategies to counteract obesity. An online home-based exercise program may be a feasible approach in an obese population. Therefore, this study aimed to investigate the effects of twelve weeks of online Pilates plus diet on body composition in individuals affected by obesity. Thirty-five females were randomly assigned to a home-based Pilates group (PG, n = 18) or a group without intervention (control group, CG, n = 17). All participants followed a Mediterranean diet. The PG followed a twelve-week online Pilates Matwork program (three times/week; 180 min/week), while the CG was not involved in any structured physical exercise program. Body composition and handgrip strength were evaluated at baseline (T0) and after the intervention (T1). A significant group × time interaction (p < 0.05) was found for the fat mass percentage (pFM). Specifically, the pFM was significantly lower at T1 than at T0 in the PG. Significant group × time interactions for fat-free mass (p < 0.05), appendicular skeletal muscle mass (p < 0.05), and skeletal muscle mass (p < 0.01) were found. All these variables were significantly higher at T1 than at T0 in the PG (p < 0.05). Home-based Pilates combined with diet intervention may represent an effective strategy to improve body composition in terms of fat mass reduction and muscle mass gain in adults affected by obesity.
Spontaneous Reactivation of Herpes Simplex Virus Type 1 in Latently Infected Murine Sensory Ganglia

ABSTRACT Careful studies of mouse trigeminal ganglia (TG) latently infected with herpes simplex virus type 1 (HSV-1) indicate the presence of productive cycle viral gene products and persistent immune response, suggesting ongoing spontaneous viral reactivation in these tissues. In the present study we set out to determine whether infectious virus is present in murine TG latently infected with HSV-1 (KOS). At 37 days after ocular inoculation we found a small amount of infectious virus in ca. 6% of latently infected murine TG. Furthermore, the amount of infectious virus that we detected (PFU per viral antigen-positive neuron) was similar to that detected in acutely infected ganglia. We conclude that spontaneous reactivation of infectious HSV-1 occurs in the mouse TG and is likely the principle cause of viral protein expression in these tissues. We next examined the role of latency-associated transcript (LAT) in spontaneous ganglionic reactivation by examining ganglia latently infected with KOS dlLAT1.8, a LAT deletion virus. Through the use of immunocytochemistry we found that KOS dlLAT1.8 had a rate of spontaneous ganglionic reactivation very similar to that of HSV-1 (KOS). Studying spontaneous ganglionic reactivation of HSV in the mouse TG allows a direct study of viral reactivation from latently infected neurons without the potential confounders and complicating downstream events that accompany the study of viral reactivation by explantation or peripheral viral shedding. Since most cases of human viral shedding and reactivation are not associated with a known trigger, spontaneous ganglionic reactivation of HSV-1 may be a better model of human disease than existing models.
A Reliable Parameter to Standardize the Scoring of Stem Cell Spheres

Sphere formation assay is widely used in selection and enrichment of normal stem cells or cancer stem cells (CSCs), also known as tumor initiating cells (TICs), based on their ability to grow in serum-free suspension culture for clonal proliferation. However, there is no standardized parameter to accurately score the spheres, which should be reflected by both the number and size of the spheres. Here we define a novel parameter, designated as Standardized Sphere Score (SSS), which is expressed by the total volume of selected spheres divided by the number of cells initially plated. SSS was validated in quantification of both tumor spheres from cancer cell lines and embryonic bodies (EB) from mouse embryonic stem cells with high sensitivity and reproducibility.
Characterization of T cell mutants with defects in capacitative calcium entry: genetic evidence for the physiological roles of CRAC channels

Prolonged Ca2+ influx is an essential signal for the activation of T lymphocytes by antigen. This influx is thought to occur through highly selective Ca2+ release-activated Ca2+ (CRAC) channels that are activated by the depletion of intracellular Ca2+ stores. We have isolated mutants of the Jurkat human T cell line NZdipA to explore the molecular mechanisms that underlie capacitative Ca2+ entry and to allow a genetic test of the functions of CRAC channels in T cells. Five mutant cell lines (CJ-1 through CJ-5) were selected based on their failure to express a lethal diphtheria toxin A chain gene and a lacZ reporter gene driven by NF-AT, a Ca(2+)- and protein kinase C-dependent transcription factor. The rate of Ca2+ influx evoked by thapsigargin was reduced to varying degrees in the mutant cells whereas the dependence of NF-AT/lacZ gene transcription on [Ca2+]i was unaltered, suggesting that the transcriptional defect in these cells is caused by a reduced level of capacitative Ca2+ entry. We examined several factors that determine the rate of Ca2+ entry, including CRAC channel activity, K(+)-channel activity, and Ca2+ clearance mechanisms. The only parameter found to be dramatically altered in most of the mutant lines was the amplitude of the Ca2+ current (ICRAC), which ranged from 1 to 41% of that seen in parental control cells. In each case, the severity of the ICRAC defect was closely correlated with deficits in Ca2+ influx rate and Ca(2-)-dependent gene transcription. Behavior of the mutant cells provides genetic evidence for several roles of ICRAC in T cells. First, mitogenic doses of ionomycin appear to elevate [Ca2+]i primarily by activating CRAC channels. Second, ICRAC promotes the refilling of empty Ca2+ stores. Finally, CRAC channels are solely responsible for the Ca2+ influx that underlies antigen-mediated T cell activation. These mutant cell lines may provide a useful system for isolating, expressing, and exploring the functions of genes involved in capacitative Ca2+ entry.
Common binding site for disialyllactose and tri‐peptide in C‐fragment of tetanus neurotoxin

Clostridial neurotoxins are comprised of botulinum (BoNT) and tetanus (TeNT), which share significant structural and functional similarity. Crystal structures of the binding domain of TeNT complexed with disialyllactose (DiSia) and a tri‐peptide Tyr‐Glu‐Trp (YEW) have been determined to 2.3 and 2.2 Å, respectively. Both DiSia and YEW bind in a shallow cleft region on the surface of the molecule in the β‐trefoil domain, interacting with a set of common residues, Asp1147, Asp1214, Asn1216, and Arg1226. DiSia and YEW binding at the same site in tetanus toxin provides a putative site that could be occupied either by a ganglioside moiety or a peptide. Soaking experiments with a mixture of YEW and DiSia show that YEW competes with DiSia, suggesting that YEW can be used to block ganglioside binding. A comparison with the TeNT binding domain in complex with small molecules, BoNT/A and /B, provides insight into the different modes of ganglioside binding. Proteins 2005. Published 2005 Wiley‐Liss, Inc.
Rheumatic and Musculoskeletal Immune‐Related Adverse Events Due to Immune Checkpoint Inhibitors: A Systematic Review of the Literature

Immune checkpoint inhibitors (ICIs) are improving prognoses in advanced stage cancers, but they also lead to immune‐related adverse events (IRAEs). IRAEs targeting many organ systems have been reported, but musculoskeletal and rheumatic IRAEs have not been well‐characterized. We systematically reviewed published literature on musculoskeletal and rheumatic IRAEs to better understand prevalence and clinical characteristics.
The putative l‐lactate dehydrogenase from Methanococcus jannaschii is an NADPH‐dependent l‐malate dehydrogenase

The enyme encoded by Methanococcus jannaschii open reading frame (ORF) 0490 was purified and characterized. It was shown to be an NADPH‐dependent [lactate dehydrogenase (LDH)‐like]l‐malate dehydrogenase (MalDH) and not an l‐lactate dehydrogenase, as had been suggested previously on the basis of amino acid sequence similarity. The results show the importance of biochemical data in the assignment of ORF function in genomic sequences and have implications for the phylogenetic distribution of members of the MalDH/LDH enzyme superfamilies within the prokaryotic kingdom.
Thrombomodulin Ala455Val Polymorphism and Risk of Coronary Heart Disease

Background —Thrombomodulin (TM) is expressed on the endothelial surface and plays an important role in vasoprotection. A common polymorphism of TM at amino acid position 455 with an alanine (A) to valine (V) transition was previously reported to be associated cross-sectionally with acute myocardial infarction. Whether this single nucleotide polymorphism predicts risk of developing coronary heart disease (CHD) is unclear. Methods and Results —Within a large cohort study, we identified 467 incident CHD cases during an average of 5 years of follow-up. We determined TM-455 genotypes on 376 CHD cases (23% black, 77% white) and a reference sample of 461. The AA genotype was significantly more prevalent in noncases than in cases (P =0.016). The prevalences of the AA genotype in noncase blacks and whites were 93% and 67%, respectively. The AA genotype frequency was significantly reduced in black cases versus noncases (P =0.018). It was also lower in white cases than in noncases, but the difference was not statistically significant (P =0.066). Weighted proportional hazards regression analysis after adjustment for age, sex, and other CHD risk factors showed that having the V allele increased risk of CHD by 6.1-fold (risk ratio 6.1, 95% CI 1.7 to 22.9) in blacks but did not significantly increase the risk in whites. Conclusions —The TM A455V polymorphism predicts risk of developing CHD in blacks.
Molecular Signature of Early Hepatocellular Carcinoma

The advances in imaging techniques and establishment of screening and surveillance protocols for high-risk populations for hepatocellular carcinoma (HCC) have led to the detection of small hepatic nodules in patients with chronic liver diseases, but in general the prognosis for HCC remains poor. Early detection of HCC or detection of small/early HCC followed by appropriate treatment is the key to significantly alter the prognosis and significantly decrease tumor-related deaths. Recent advances in gene profiling have led to a better understanding in early hepatocarcinogenesis and have suggested several possible molecular signatures which are able to separate early HCCs from their precursors, the dysplastic nodules. The continued search for new and more accurate molecular signatures must be translated into the clinical setting, where they can advance screening and surveillance of high-risk patients in the detection of early HCC.
An Information Theoretic Framework for Multi-view Learning

In the multi-view learning paradigm, the input variable is partitioned into two different views X1 and X2 and there is a target variable Y of interest. The underlying assumption is that either view alone is sufficient to predict the target Y accurately. This provides a natural semi-supervised learning setting in which unlabeled data can be used to eliminate hypothesis from either view, whose predictions tend to disagree with predictions based on the other view. This work explicitly formalizes an information theoretic, multi-view assumption and studies the multi-view paradigm in the PAC style semisupervised framework of Balcan and Blum [2006]. Underlying the PAC style framework is that an incompatibility function is assumed to be known — roughly speaking, this incompatibility function is a means to score how good a function is based on the unlabeled data alone. Here, we show how to derive incompatibility functions for certain loss functions of interest, so that minimizing this incompatibility over unlabeled data helps reduce expected loss on future test cases. In particular, we show how the class of empirically successful coregularization algorithms fall into our framework and provide performance bounds (using the results in Rosenberg and Bartlett [2007], Farquhar et al. [2005]). We also provide a normative justification for canonical correlation analysis (CCA) as a dimensionality reduction technique. In particular, we show (for strictly convex loss functions of the form `(w·x, y)) that we can first use CCA as dimensionality reduction technique and (if the multi-view assumption is satisfied) this projection does not throw away much predictive information about the target Y — the benefit being that subsequent learning with a labeled set need only work in this lower dimensional space.