Miracle-dz/UniFAR-FTUs huggingface dataset:
Actin-ring segment switching drives nonadhesive gap closure

Significance Gap closure to eliminate physical discontinuities and restore tissue integrity is a fundamental process in normal development and repair of damaged tissues and organs. Here, we report a previously unexplored gap-closure mechanism by which cell proliferation, collective cell migration, large-scale intercellular actin-network remodeling, and purse-string contraction act in a highly coordinated manner to restore the gap. In distinct contrast to the classical purse-string contraction mechanism, this mechanism involves intercellular switching of actin-cable segments at the gap front, which effectively empowers the actin cable for gap closure. Our study highlights the principles of wound healing driven by the close reciprocity between mechanics and cellular remodeling and might inspire mechanobiological intervention strategies for embryogenesis, tissue repair, antimetastasis, and plastic surgery. Gap closure to eliminate physical discontinuities and restore tissue integrity is a fundamental process in normal development and repair of damaged tissues and organs. Here, we demonstrate a nonadhesive gap closure model in which collective cell migration, large-scale actin-network fusion, and purse-string contraction orchestrate to restore the gap. Proliferative pressure drives migrating cells to attach onto the gap front at which a pluricellular actin ring is already assembled. An actin-ring segment switching process then occurs by fusion of actin fibers from the newly attached cells into the actin cable and defusion from the previously lined cells, thereby narrowing the gap. Such actin-cable segment switching occurs favorably at high curvature edges of the gap, yielding size-dependent gap closure. Cellular force microscopies evidence that a persistent rise in the radial component of inward traction force signifies successful actin-cable segment switching. A kinetic model that integrates cell proliferation, actin fiber fusion, and purse-string contraction is formulated to quantitatively account for the gap-closure dynamics. Our data reveal a previously unexplored mechanism in which cells exploit multifaceted strategies in a highly cooperative manner to close nonadhesive gaps.
Thioridazine hydrochloride: an antipsychotic agent that inhibits tumor growth and lung metastasis in triple-negative breast cancer via inducing G0/G1 arrest and apoptosis

ABSTRACT Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer and still lacks available targeted therapy options. Thioridazine hydrochloride (Thi-hyd), a common phenothiazine antipsychotic drug, has shown great tumor-suppressive potential in several types of cancer cells. In this study, we explored the anti-tumor effects of Thi-hyd on TNBC. Thi-hyd significantly inhibited the viability and migration of TNBC cells in vitro. PI3K/AKT signaling pathway was verified to be related to Thi-hyd-induced tumor inhibition. G0/G1 cell cycle arrest and apoptosis were observed after treatment with Thi-hyd. The cell cycle arrest was accompanied by down-regulation of CDK4/cyclin D1 and up-regulation of p21 and p27. The apoptosis was accompanied by mitochondrial dysfunction. In vivo, Thi-hyd significantly suppressed the growth of tumors showing a 63.73% inhibition rate in tumor weight. Spontaneous lung metastasis was also efficiently prevented by Thi-hyd treatment, with a 72.58% inhibition rate. Immunohistological analysis showed increased Ki67 expression and reduced cleaved caspase-3 expression in Thi-hyd-treated mice. No apparent side effects were observed according to blood test and H&E staining results. Collectively, our results show that Thi-hyd can be used as a potential drug for TNBC treatment and set the basis for its clinical evaluation and investigation. Abbreviations CCK8: Cell Counting Kit-8; CDK: cyclin-dependent kinase; DRD2: dopamine D2 receptor; ERK1/2: extracellular signal-regulated kinase 1/2; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; H&E: hematoxylin and eosin; MMP: membrane potential; NAC: N-acetyl-L-cysteine; PI: Propidium iodide; Rh123: rhodamine-123; ROS: reactive oxygen species; TBST: tris-buffered saline containing 0.1% Tween 20 TNBC: Triple-negative breast cancer; Thi-hyd: Thioridazine hydrochloride.
Obesity and the Western Diet: How We Got Here.

[. ]the Dietary Approaches to Stop Hypertension study found that a diet low in fat and rich in fruits, vegetables, and low-fat dairy resulted in lower systolic and diastolic blood pressures when compared to a standard western diet.6 What is the Western "American" Diet? The typical Western (American) diet is low in fruits and vegetables, and high in fat and sodium. [. ]this diet consists of large portions, high calories, and excess sugar.3 This excess sugar accounts for more than 13% of the daily caloric intake with beverages constituting 47% of these added sugars.4 Other sources include cookies, cakes, and candy. [. ]half of all Americans have a preventable chronic illness.3 According to the American Heart Association, 81 million American adults have cardiovascular disease which includes coronary artery disease or cerebrovascular disease. According to the CDC, 13.7 million children and adolescents are considered obese in the United States.8 Multiple studies have also shown that obesity during midlife increases the risk of developing dementia.
Equivocal evaluation of progressive disease in patients treated with immune checkpoint inhibitors: a challenge for clinical trials and biomarker research

ABSTRACT We present two patient cases (one with bladder carcinoma and one with renal cell carcinoma) who consulted our department of General Medical Oncology, after having been treated in other hospitals in two clinical trials with immune checkpoint inhibitors and having been dismissed from the trials after 5 months of therapy for progressive disease. They consulted to discuss consecutive treatment opportunities. However, longer follow-up has shown that both patients were dismissed equivocally from both trials. We are worried that equivocal response evaluation in the context of clinical trials with immune checkpoint inhibitors, due to pseudo-progression or delayed responses, can negatively impact trial outcomes as well as biomarker research.
The Role of Calcium Signaling in Regulation of Epithelial-Mesenchymal Transition

Despite substantial advances in the field of cancer therapeutics, metastasis is a significant challenge for a favorable clinical outcome. Epithelial to mesenchymal transition (EMT) is a process of acquiring increased motility, invasiveness, and therapeutic resistance by cancer cells for their sustained growth and survival. A plethora of intrinsic mechanisms and extrinsic microenvironmental factors drive the process of cancer metastasis. Calcium (Ca2+) signaling plays a critical role in dictating the adaptive metastatic cell behavior comprising of cell migration, invasion, angiogenesis, and intravasation. By modulating EMT, Ca2+ signaling can regulate the complexity and dynamics of events leading to metastasis. This review summarizes the role of Ca2+ signal remodeling in the regulation of EMT and metastasis in cancer.
We and herbivores eat endophytes

Health depends on the diet and a vegetal diet promotes health by providing fibres, vitamins and diverse metabolites. Remarkably, plants may also provide microbes. Fungi and bacteria that reside inside plant tissues (endophytes) seem better protected to survive digestion; thus, we investigated the reported evidence on the endophytic origin of some members of the gut microbiota in animals such as panda, koala, rabbits and tortoises and several herbivore insects. Data examined here showed that some members of the herbivore gut microbiota are common plant microbes, which derived to become stable microbiota in some cases. Endophytes may contribute to plant fibre or antimetabolite degradation and synthesis of metabolites with the plethora of enzymatic activities that they display; some may have practical applications, for example, Lactobacillus plantarum found in the intestinal tract, plants and in fermented food is used as a probiotic that may defend animals against bacterial and viral infections as other endophytic‐enteric bacteria do. Clostridium that is an endophyte and a gut bacterium has remarkable capabilities to degrade cellulose by having cellulosomes that may be considered the most efficient nanomachines. Cellulose degradation is a challenge in animal digestion and for biofuel production. Other endophytic‐enteric bacteria may have cellulases, pectinases, xylanases, tannases, proteases, nitrogenases and other enzymatic capabilities that may be attractive for biotechnological developments, indeed many endophytes are used to promote plant growth. Here, a cycle of endophytic‐enteric‐soil‐endophytic microbes is proposed which has relevance for health and comprises the fate of animal faeces as natural microbial inoculants for plants that constitute bacterial sources for animal guts.
Risk factors for abutment and implant fracture after loading.

PURPOSE Implant component fractures are one of the most serious complications in implant treatment. With a better understanding of the risk factors for fracture in the preoperative, surgery, superstructure, and post-loading phases of implant treatment, low-risk treatment could reduce implant component fractures, leading to a better prognosis. The aim of this study was to clarify the risk factors for abutment and implant fractures that occur after loading, and to perform a retrospective, approximately 10-year follow-up study to explore the risk factors in each treatment phase. METHODS Subjects were fitted with an implant prosthesis between January 2008 and December 2009. In total, 1,126 Ankylos implants in 430 patients were included for analysis. Binary logistic regression analysis was performed to extract factors related to non-fracture and fracture of the abutment or implant as a dependent variable. RESULTS Gender (OR = 3.466, 95% CI 1.296-9.268, P = 0.013), gonial angle (OR = 3.420, 95% CI 1.308-8.945, P = 0.012), and splinting status of the superstructure (OR = 4.456, 95% CI 1.861-10.669, P = 0.001) were identified as significant risk factors. CONCLUSION The risk of fracture is increased in males, especially those with a mandibular angle of less than 120° on panoramic radiographs, and those with a non-splinted superstructure.
Effect of a novel animal milk oligosaccharide biosimilar on macronutrient digestibility and gastrointestinal tolerance, fecal metabolites, and fecal microbiota of healthy adult cats.

GNU100 is a novel animal milk oligosaccharide (AMO) biosimilar. In a recent in vitro fermentation study, GNU100 was shown to be fermentable by feline gastrointestinal microbiota and lead to increased short-chain fatty acid production. Our objectives herein were to evaluate the palatability, safety, and gastrointestinal tolerance of GNU100 in healthy adult cats. Exploratory end-points were measured to assess utility. In Study #1, 20 adult cats were used to test the palatability of diets containing 0% or 1% GNU100. In Study #2, 32 (mean age = 1.9 yr; mean BW = 4.6 kg) male (n=12) and female (n=20) adult cats were used in a completely randomized design. After a 2-wk baseline, cats were assigned to one of the following treatment groups and fed for 26 wk: control (CT, no GNU100), low dose (LD, 0.5% GNU100), medium dose (MD, 1.0% GNU100), and high dose (HD, 1.5% GNU100). On wk 2, 4, and 26, fresh fecal samples were collected for measurement of stool quality and immune and inflammatory markers, and on wk 2 and 4 for microbiota and metabolites. On wk 4, total feces were collected to measure apparent total tract macronutrient digestibility. On wk 2, 4, and 26, blood samples were collected for serum chemistry, hematology, and inflammatory marker measurement. The palatability test showed that 1% GNU100 was strongly preferred (P < 0.05), with GNU100 having a 17.6:1 consumption ratio compared to control. In the long-term study, all cats remained healthy, without any signs of gastrointestinal intolerance or illness. All diets were well accepted, resulting in similar (P > 0.05) food intake, fecal characteristics, IgA, and calprotectin, and dry matter, organic matter, fat, and crude protein digestibilities. Fecal butyrate was greater (P = 0.02) in cats fed HD than cats fed LD or MD. Fecal indole was lower (P = 0.02) in cats fed HD than cats fed LD. Cats fed CT had a higher (P = 0.003) relative abundance of Actinobacteria than cats fed LD. Relative abundance of Peptococcus was impacted by diet and time. At 4 wk, Campylobacter was lower in fecal samples of cats fed HD. Overall, the data suggest that dietary GNU100 supplementation was highly palatable, well-tolerated, did not cause detrimental effects on fecal quality or nutrient digestibility, increased fecal butyrate concentrations, and reduced fecal indole concentrations, supporting the safety of GNU100 for inclusion in feline diets and suggesting potential benefits on gastrointestinal health of cats.
Are changes in binge drinking among European adolescents driven by changes in computer gaming?

Abstract Introduction There is currently no good explanation for the decline in adolescent drinking reported for many Western countries in recent years. As modern computer gaming is highly exciting and socially rewarding, it may function as a substitute for adolescent binge drinking. We hypothesized a negative correlation between country‐level changes in computer gaming and binge drinking. Methods We analysed within‐country changes based on data from 15–16 year‐old pupils (n = 517 794) participating in the European School Survey Project on Alcohol and Drugs from 1995 to 2015. Binge drinking in the last 30 days (5+ units on one occasion) was regressed on frequency of computer gaming and three control variables measuring the frequency of engagement in other hobbies, reading books and going out (to a disco, cafe, etc.). Results Descriptive data showed no general decline in binge drinking across European countries. In contrast to our prediction, the association between binge drinking and computer gaming was not negative [b = 0.26, one‐sided 95% confidence interval (−∞, 0.47), P = 0.98, Bayes Factor = 0.21]. We found the same pattern of result in a secondary analysis on six Nordic countries that have experienced declines in adolescent drinking recent years. In analyses with covariates reflecting engagement in other activities, we only observed statistical evidence for an effect of going out. Discussion and Conclusions A substantial decline in adolescent binge drinking during the years 1995–2015 is only evident in some European countries, and it is likely not caused by increased computer gaming.
Combined analysis of spatially resolved electronic structure and composition on a cross‐section of a thin film Cu(In1–x Gax)S2 solar cell

In this work we present a combination of two spatially resolved experimental methods to analyse correlations between distributions of element concentrations and electronic structure of cross sections of thin film semiconductor devices. We applied these methods to a cross section of a thin film Cu(In1–x Gax)S2/CdS/ZnO solar cell. The electronic structure was analysed by measuring the work function of the cross section by Kelvin probe force microscopy. To determine the gallium concentration of the cross section of the Cu(In1–x Gax)S2 layer we performed energy dispersive X‐ray analysis (EDX). We were able to match the spatial coordinates of these measurements. By this we could observe a correlation between the gallium concentration of the Cu(In1–x Gax)S2 layer and its work function. The EDX measurements show that the Cu(In1–x Gax)S2 layer features a two‐layer structure – one layer with a low gallium concentration (x ≈ 0) and one (at the back of the solar cell) with a high gallium concentration (x ≈ 1). Furthermore we discuss the influence of the two‐layer structure of the Cu(In1–x Gax)S2 absorber layer on the photovoltaic properties of the solar cell. The spectral quantum efficiency was measured on the same sample before the depth resolved data were taken. We observe an improvement of short circuit current and overall efficiency of the Cu(In1–x Gax)S2/CdS/ZnO solar cell compared to a gallium‐free CuInS2/CdS/ZnO solar cell. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Peculiar Phenotypic and Cytotoxic Features of Pulmonary Mucosal CD8 T Cells in People Living with HIV Receiving Long-Term Antiretroviral Therapy

Key Points Pulmonary mucosal CD8 T cells are highly differentiated, activated, and exhausted. BAL versus blood CD8 T cells showed lower perforin/granzyme B expression. BAL CD8 T cells display reduced target killing ability compared to blood CD8 T cells. People living with HIV have high burdens of chronic lung disease, lung cancers, and pulmonary infections despite antiretroviral therapy (ART). The rates of tobacco smoking by people living with HIV vastly exceed that of the general population. Furthermore, we showed that HIV can persist within the lung mucosa despite long-term ART. As CD8 T cell cytotoxicity is pivotal for controlling viral infections and eliminating defective cells, we explored the phenotypic and functional features of pulmonary versus peripheral blood CD8 T cells in ART-treated HIV+ and uninfected controls. Bronchoalveolar lavage fluid and matched blood were obtained from asymptomatic ART-treated HIV+ smokers (n = 11) and nonsmokers (n = 15) and uninfected smokers (n = 7) and nonsmokers (n = 10). CD8 T cell subsets and phenotypes were assessed by flow cytometry. Perforin/granzyme B content, degranulation (CD107a expression), and cytotoxicity against autologous Gag peptide-pulsed CD4 T cells (Annexin V+) following in vitro stimulation were assessed. In all groups, pulmonary CD8 T cells were enriched in effector memory subsets compared with blood and displayed higher levels of activation (HLA-DR+) and exhaustion (PD1+) markers. Significant reductions in proportions of senescent pulmonary CD28−CD57+ CD8 T cells were observed only in HIV+ smokers. Pulmonary CD8 T cells showed lower perforin expression ex vivo compared with blood CD8 T cells, with reduced granzyme B expression only in HIV+ nonsmokers. Bronchoalveolar lavage CD8 T cells showed significantly less in vitro degranulation and CD4 killing capacity than blood CD8 T cells. Therefore, pulmonary mucosal CD8 T cells are more differentiated, activated, and exhausted, with reduced killing capacity in vitro than blood CD8 T cells, potentially contributing to a suboptimal anti-HIV immune response within the lungs.
UWB Low-Profile Boat-Radiator Antenna (BRA) with Dual C-Shape Co-Radiative Ground for Multi-Standard Communication Networks

Multiple standard communication networks operate in the frequency band of 1.8–6 GHz, which makes lots of antennas available in the limited space. To solve the problem of interference and improve the performance of these antennas, an ultra-wideband (UWB) antenna is presented. It consists of a boat-radiator and a dual C-shape co-radiative ground (DCCRG). One half of the DCCRG plays a role of the ground of a co-planar waveguide fed to the proposed boat-radiator antenna (BRA), while the other half works as a multiple order L-resonant circuit to broaden the lower operating band. Uniform bidirectional radiation is presented with the size of 0.25 λ × 0.375 λ × 0.0063 λ over the frequency band of 1.7–6.3 GHz (115%). The proposed antenna achieves around twice the bandwidth (60%) of the same structured antenna without the structure acting as a multiple order L-resonant circuit. Moreover, the stable boresight gain of 3.6 dBi ± 1.25 dBi is realized over the operating band.
Sequencing platform shifts provide opportunities but pose challenges for combining genomic data sets

Technological advances in DNA sequencing over the last decade now permit the production and curation of large genomic data sets in an increasing number of nonmodel species. Additionally, these new data provide the opportunity for combining data sets, resulting in larger studies with a broader taxonomic range. Whilst the development of new sequencing platforms has been beneficial, resulting in a higher throughput of data at a lower per‐base cost, shifts in sequencing technology can also pose challenges for those wishing to combine new sequencing data with data sequenced on older platforms. Here, we outline the types of studies where the use of curated data might be beneficial, and highlight potential biases that might be introduced by combining data from different sequencing platforms. As an example of the challenges associated with combining data across sequencing platforms, we focus on the impact of the shift in Illumina's base calling technology from a four‐channel system to a two‐channel system. We caution that when data are combined from these two systems, erroneous guanine base calls that result from the two‐channel chemistry can make their way through a bioinformatic pipeline, eventually leading to inaccurate and potentially misleading conclusions. We also suggest solutions for dealing with such potential artefacts, which make samples sequenced on different sequencing platforms appear more differentiated from one another than they really are. Finally, we stress the importance of archiving tissue samples and the associated sequences for the continued reproducibility and reusability of sequencing data in the face of ever‐changing sequencing platform technology.
Downregulation of Lymphoid enhancer‐binding factor 1 (LEF‐1) expression (by immunohistochemistry and/ flow cytometry) in chronic Lymphocytic Leukemia with atypical immunophenotypic and cytologic features

Lymphoid enhancer‐binding factor 1 (LEF‐1) overexpression has been recently remarkably reported in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and has shown utility in distinguishing CLL/SLL from other B‐cell lymphomas. CLL has a well‐defined immunophenotype, yet, some cases of CLL demonstrate atypical morphology/ phenotype reflected by low Matutes score (atypical CLL). Till date, LEF1 expression has not been systematically studied in cases of CLL with atypical features.
Development of a device to measure adherence and pressure characteristics of positive expiratory pressure therapies used by adults with cystic fibrosis

ABSTRACT Introduction Positive expiratory pressure (PEP) and oscillating positive expiratory pressure (OscPEP) therapies are often used by people with cystic fibrosis (CF) to facilitate airway clearance. However, suboptimal adherence and poor technique may reduce their effectiveness. Objective To develop a device (PEPtrac) to accurately measure and provide preliminary clinical data of adherence and technique characteristics when airway clearance is performed using PEP/OscPEP devices. Methods This study comprised two distinct phases: 1) a benchtop validation study; and 2) clinical study. Benchtop study: Accuracy of PEPtrac was measured by comparing it to video analysis for five different PEP/OscPEP devices. Clinical study: Clinical data were then collected for 18 adults with CF using one of three PEP/OscPEP devices (PariPEP S®, Acapella DH® or Aerobika®) unsupervised. Results There was 100% agreement between PEPtrac and video analysis data. Clinical data revealed significant variability in expiratory duration and pressure properties between the three PEP/OscPEP devices and between participants. For example, expiratory duration with PariPEP S® (mean [SD] = 4.8 [1.2] sec) was longer (p < .001) than Acapella DH® (3.7 [0.8] sec) and Aerobika® (2.9 [1.1] sec) and Aerobika® had a higher oscillation amplitude than Acapella DH® (6.4 [1.7] vs 5.3 [1.5] cmH2O, p < .001). Discussion Accurate measurement of PEP/OscPEP adherence and technique using a device such as PEPtrac was possible. Further research is required to investigate the clinical importance of the variability in technique seen in our clinical data.