Miracle-dz/UniFAR-FTUs huggingface dataset:
Sensitivity and reliability of zinc transporter and metallothionein gene expression in peripheral blood mononuclear cells as indicators of zinc status: responses to ex vivo zinc exposure and habitual zinc intake in humans

Abstract Zn is an essential nutrient for humans; however, a sensitive biomarker to assess Zn status has not been identified. The objective of this study was to determine the reliability and sensitivity of Zn transporter and metallothionein (MT) genes in peripheral blood mononuclear cells (PBMCs) to Zn exposure ex vivo and to habitual Zn intake in human subjects. In study 1, human PBMCs were cultured for 24 h with 0–50 µm ZnSO4 with or without 5 µm N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), and mRNA expression of SLC30A1-10, SLC39A1-14, MT1 subtypes (A, B, E, F, G, H, L, M and X), MT2A, MT3 and MT4 mRNA was determined. In study 2, fifty-four healthy male and female volunteers (31·9 (sd 13·8) years, BMI 25·7 (sd 2·9) kg/m2) completed a FFQ, blood was collected, PBMCs were isolated and mRNA expression of selected Zn transporters and MT isoforms was determined. Study 1: MT1E, MT1F, MT1G, MT1H, MT1L, MT1M, MT1X, MT2A and SLC30A1 increased with increasing concentrations of Zn and declined with the addition of TPEN. Study 2: Average daily Zn intake was 16·0 (sd 5·3) mg/d (range: 9–31 mg/d), and plasma Zn concentrations were 15·5 (SD 2·8) μmol/l (range 11–23 μmol/l). PBMC MT2A was positively correlated with dietary Zn intake (r 0·306, P = 0·03) and total Zn intake (r 0·382, P < 0·01), whereas plasma Zn was not (P > 0·05 for both). Findings suggest that MT2A mRNA in PBMCs reflects dietary Zn intake in healthy adults and may be a component in determining Zn status.
Anacroneuria (Plecoptera: Perlidae) from the Boracéia Biological Station, São Paulo State, Brazil

Seven species of Anacroneuria from the Boracéia Biological Station are studied; two — A. boraceiensis sp. n. and A. vanini sp. n. — are described as new. The others are A. paulina (Navás), A. petersi Froehlich, A. polita (Burmeister), A. subcostalis Klapálek and A. uyara Froehlich.
Which sample type is better for Xpert MTB/RIF to diagnose adult and pediatric pulmonary tuberculosis?

Abstract Objective: This review aimed to identify proper respiratory-related sample types for adult and pediatric pulmonary tuberculosis (PTB), respectively, by comparing performance of Xpert MTB/RIF when using bronchoalveolar lavage (BAL), induced sputum (IS), expectorated sputum (ES), nasopharyngeal aspirates (NPAs), and gastric aspiration (GA) as sample. Methods: Articles were searched in Web of Science, PubMed, and Ovid from inception up to 29 June 2020. Pooled sensitivity and specificity were calculated, each with a 95% confidence interval (CI). Quality assessment and heterogeneity evaluation across included studies were performed. Results: A total of 50 articles were included. The respective sensitivity and specificity were 87% (95% CI: 0.84–0.89), 91% (95% CI: 0.90–0.92) and 95% (95% CI: 0.93–0.97) in the adult BAL group; 90% (95% CI: 0.88–0.91), 98% (95% CI: 0.97–0.98) and 97% (95% CI: 0.95–0.99) in the adult ES group; 86% (95% CI: 0.84–0.89) and 97% (95% CI: 0.96–0.98) in the adult IS group. Xpert MTB/RIF showed the sensitivity and specificity of 14% (95% CI: 0.10–0.19) and 99% (95% CI: 0.97–1.00) in the pediatric ES group; 80% (95% CI: 0.72–0.87) and 94% (95% CI: 0.92–0.95) in the pediatric GA group; 67% (95% CI: 0.62–0.72) and 99% (95% CI: 0.98–0.99) in the pediatric IS group; and 54% (95% CI: 0.43–0.64) and 99% (95% CI: 0.97–0.99) in the pediatric NPA group. The heterogeneity across included studies was deemed acceptable. Conclusion: Considering diagnostic accuracy, cost and sampling process, ES was a better choice than other sample types for diagnosing adult PTB, especially HIV-associated PTB. GA might be more suitable than other sample types for diagnosing pediatric PTB. The actual choice of sample types should also consider the needs of specific situations.
Multiple vellus hair cysts of perianal skin

Dear Editor, Cutaneous cysts are classified according to the lining epithelium, the type of keratinization, and the presence of vellus or terminal hair. In the perianal region, epidermal cysts are uncommon, while multiple cysts are rare. We describe a 76-year-old male patient who presented with a cutaneous squamous cell carcinoma (SCC) of the helix for Mohs surgery. On clinical examination, we observed multiple yellow to brownish tiny cysts of the perianal skin (Figure 1). These cysts were asymptomatic with a smooth surface and a diameter of 1 to 3 mm. No trauma or rubbing was reported. The lesions lasted at least for 1 year. No treatment was used. We performed a diagnostic proctoscopy to exclude involvement of the rectal mucosa. We observed no pathologies up to 12 cm upwards the anal sphincter. A skin biopsy was performed. The histologic investigation revealed an epidermal cyst of the mid-dermis lined by stratified epithelium and containing laminated keratin and vellus hairs. The diagnosis of multiple vellus hair cysts of the perianal skin was confirmed (Figure 2). Laser ablation was suggested. However, no further treatment was warranted by the patient. 1 | FC DR DISCUSSION
Efficacy and Safety of Locoregional Radiotherapy With Chemotherapy vs Chemotherapy Alone in De Novo Metastatic Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial.

Importance The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear. Objective To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC. Design, Setting, and Participants Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months. Interventions The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. Main Outcomes and Measures The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. Results Overall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. Conclusions and Relevance In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC. Trial Registration ClinicalTrials.gov Identifier: NCT02111460.
The role of the renin‐angiotensin system in skin physiology and pathophysiology

Since its first description around the year 2000, the local renin‐angiotensin system (RAS) in skin has been subject of an increasing number of studies with many additions over the last two to three years. A focus of research has been investigations on the role of cutaneous angiotensin receptors and locally synthesised angiotensin II in wound healing, in dermatoses associated with skin fibrosis and in melanoma. This review will provide an introduction into the RAS with emphasis on information relevant for the cutaneous RAS. It will discuss the role of the RAS in skin physiology, followed by a detailed review of the existing literature addressing the role of local angiotensin II and angiotensin AT1 and AT2 receptors in wound healing and in various skin diseases such as hypertrophic scars/keloids, scleroderma, dystrophic epidermolysis bullosa, Dupuytren's disease, squamous cell carcinoma, melanoma and psoriasis. In a final section, the potential relevance of drugs, which interfere with the RAS, for future therapy of dermatological disorders is discussed. Collectively, research about the RAS in skin can currently be described as an area, which has gained increasing attention by basic researchers, thus resulting in a multitude of preclinical studies pointing to the potential relevance of components of the RAS as drug targets in dermatological diseases. With a few small clinical studies already performed successfully for indications such as hypertrophic scars and keloids, it can be said that the skin RAS is now in the critical phase of translation from preclinical evidence to clinical use.
Real-Time Traffic Light Detection with Frequency Patterns Using a High-Speed Camera

LEDs are widely employed as traffic lights. Because most LED traffic lights are driven by alternative power, they blink at high frequencies, even at twice their frequencies. We propose a method to detect a traffic light from images captured by a high-speed camera that can recognize a blinking traffic light. This technique is robust under various illuminations because it can detect traffic lights by extracting information from the blinking pixels at a specific frequency. The method is composed of six modules, which includes a band-pass filter and a Kalman filter. All the modules run simultaneously to achieve real-time processing and can run at 500 fps for images with a resolution of 800 × 600. This technique was verified on an original dataset captured by a high-speed camera under different illumination conditions such as a sunset or night scene. The recall and accuracy justify the generalization of the proposed detection system. In particular, it can detect traffic lights with a different appearance without tuning parameters and without datasets having to be learned.
Impacts of contour saliency map transformations

—In recent years, many algorithms based on hierarchical segmentation were proposed. However, there has a need to represent their obtained results. The saliency map approach is an example of algorithm which allows the visualization of the hierarchy by deﬁning a relevance to the contours found in the image. And, in order to visualize the segmentation result, a normalization is needed. Even though the classical approaches are satisfactory, there are two major problems: (i) the normalization does not prevent oversegmentation; (ii) it is not possible to alter the normalization to achieve better results. In this paper, we have studied a normalization by a sigmoid function, we analyzed its impacts as a ﬁltering step, and as a ﬁnal (visualization) one, and we also examined how the gradient impacts on the ﬁnal result in accordance with our proposal. Experimental results show that, for both gradient functions, the pre-ﬁltering step has better results than classical approaches.
M1hot tumor-associated macrophages boost tissue-resident memory T cells infiltration and survival in human lung cancer

Background The role of tumor-associated macrophages (TAMs) in determining the outcome between the antitumor effects of the adaptive immune system and the tumor’s anti-immunity stratagems, is controversial. Macrophages modulate their activities and phenotypes by integration of signals in the tumor microenvironment. Depending on how macrophages are activated, they may adopt so-called M1-like, antitumor or M2-like, protumor profiles. In many solid tumors, a dominance of M2-like macrophages is associated with poor outcomes but in some tumor types, strong M1-like profiles are linked to better outcomes. We aimed to investigate the interrelationship of these TAM populations to establish how they modulate the efficacy of the adaptive immune system in early lung cancer. Methods Macrophages from matched lung (non-tumor-associated macrophages (NTAMs)) and tumor samples (TAMs) from resected lung cancers were assessed by bulk and single-cell transcriptomic analysis. Protein expression of genes characteristic of M1-like (chemokine (C-X-C motif) ligand 9) or M2-like (matrix metallopeptidase 12) functions was confirmed by confocal microscopy. Immunohistochemistry related the distribution of TAM transcriptomic signatures to density of CD8+ tissue-resident memory T cells (TRM) in tumors and survival data from an independent cohort of 393 patients with lung cancer. Results TAMs have significantly different transcriptomic profiles from NTAMs with >1000 differentially expressed genes. TAMs displayed a strong M2-like signature with no significant variation between patients. However, single-cell RNA-sequencing supported by immuno-stained cells revealed that additionally, in 25% of patients the M2-like TAMs also co-expressed a strong/hot M1-like signature (M1hot). Importantly, there was a strong association between the density of M1hot TAMs and TRM cells in tumors that was in turn linked to better survival. Our data suggest a mechanism by which M1hot TAMs may recruit TRM cells via CXCL9 expression and sustain them by making available more of the essential fatty acids on which TRM depend. Conclusions We showed that in early lung cancer, expression of M1-like and M2-like gene signatures are not mutually exclusive since the same TAMs can simultaneously display both gene-expression profiles. The presence of M1hot TAMs was associated with a strong TRM tumor-infiltrate and better outcomes. Thus, therapeutic approaches to re-program TAMs to an M1hot phenotype are likely to augment the adaptive antitumor responses.
The acyl lipid composition of wheat leaves and moss protonemata using a new, non‐carcinogenic extraction solvent system

As chloroform has proved to be carcinogenic we were looking for an alternative solvent system for chloroform:methanol widely used in plant lipid investigations. The lipids from leaves of wheat (Triticum aestivum L. cv. Vakka) and from protonemata of the moss Ceratodon purpureus (Hedw.) Brid. were extracted with two petroleum ether:methanol solvent systems. The polar lipids were separated by two-dimensional thin-layer chromatography and the amounts of each lipid class were compared with those obtained from chloroform:methanol (2:1, v/v) extractions. The significantly higher amounts of phosphatidylinositol observed in petroleum ether:methanol (1:1, v/v) extraction suggest that the small amounts reported earlier in plants may be an artefact relating to the solvent system used. As petroleum ether:methanol (1:1, v/v) proved to be at least as good a solvent system as chloroform:methanol (2:1, v/v) we propose it as an alternative extractant for plant polar lipids.
Coordinated variation in ecophysiological properties among life stages and tissue types in an invasive perennial forb of semiarid shrub steppe

Semiarid lands of North America are vulnerable to invasion by exotic forbs that frequently have an extended phenology compared with native herbaceous species. We hypothesized that photosynthetic stems, rosette leaves, and cauline leaves of Centaurea maculosa Lam. (knapweed) would differ in ecophysiological specialization and that these differences would enhance plant carbon uptake across seasonal variations in microclimate. Photosynthesis, water relations, and morphological features of C. maculosa were measured under natural variations in temperature and soil water, and under manipulated light environments, in adults compared with seedlings having only rosette leaves. Carbon gain was greater in adults than in seedlings owing to high photosynthesis in cauline and rosette leaves when water was abundant. Otherwise, photosynthesis was relatively lower but persistent through drought in all tissues and ages until senescence. Photosynthesis decreased with water stress in all tissues except stems. Stems comprised.
The long-lived neutrophil : a new functional entity in osteoimmunology

The neutrophil, the most abundant circulating leukocyte, is a major player in the inflammatory reaction. Indispensable for host defence, deregulated release of neutrophil-derived substances also has the potential to cause substantial tissue damage. We hypothesized that long-term exposure to inflammatory mediators could change the functional profile of the neutrophil. To this end, we incubated circulating human neutrophils with survival enhancing cytokines and found a subpopulation of these cells to persist for more than 72 hours. In comparison to freshly-isolated neutrophils, these long lived neutrophils had a markedly different phénotype with altered cell surface characteristics, and modified effector functions including chemotaxis, superoxide and leukotriene production, degranulation and cytokine synthesis. Since neutrophil-derived mediators have been implicated in the propogation of RA inflammation, we next attempted to place the 'reprogrammed' neutrophil in this specific context. We found rheumatoid synovial fluid neutrophils and neutrophil stimulated with lipopolysaccharide to upregulate surface expression of receptor activator of NF-KB ligand (RANKL), a molecule crucial for activation of bone resorption. Indeed, we showed neutrophil RANKL to interact with the RANK expressing osteoclast, and induce osteoclast differentiation and resorption. Furthermore, membrane associated RANKL was active within the neutrophil itself, activating Src-homology 2 domain-containing tyrosine phosphatase -1 and inhibiting neutrophil functions. Further, we performed co-incubations of neutrophils with rheumatoid fibroblast-like synoviocytes (RA-FLS). RA-FLS induced RANK expression in the neutrophil. Membrane RANK when activated by its biological ligand enhanced neutrophil survival, granule release and cytokine synthesis. In conclusion, we present evidence for the inflammatory neutrophil to acquire novel functions beyond those associated with its classical circulating counterpart. Furthermore, expression of osteotropic molecules of the RANKL-RANK-OPG axis places the neutrophil as a new cellular link between the skeletal and immune systems.
Landscape of T Follicular Helper Cell Dynamics in Human Germinal Centers

Key Points Confocal imaging microscopy uncovers Tfh cell dynamics in human lymphoid tissues. Tfh cells show a heterogeneous distribution and migration in GC light zones. In outer zones, Tfh cells move fast, forming brief homotypic interactions. Visual Abstract T follicular helper (Tfh) cells play a very important role in mounting a humoral response. Studies conducted in mouse models have revealed with good kinetic and spatial resolution the dynamics of these cells in germinal centers (GC) and their cross-talk with B cells upon an immune response. However, whether a similar migratory behavior is performed by human Tfh cells is unclear, as technology to track them in situ has been lacking. In this study, we combined traditional immunohistochemistry and real-time fluorescent imaging approaches on fresh human adenoid slices to provide static and dynamic information on Tfh cells. Our data indicate that GC light zones are composed of two distinct areas in terms of Tfh cell distribution and migration. In the outer GC light zones, Tfh cells migrate actively and with a high ability to form dynamic clusters showing intense and rapid reorganization. In these outer regions, Tfh cells demonstrate multiple interactions between each other. Conversely, in central regions of GC light zones, Tfh cells are much more static, forming long-lasting conjugates. These findings reveal for the first time, to our knowledge, the dynamic behavior whereby Tfh cells migrate in human GC and highlight the heterogeneity of GC for Tfh cell motility.
Physiological Response of Escherichia coli W3110 and BL21 to the Aerobic Expression of Vitreoscilla Hemoglobin

The aerobic growth and metabolic performance of Escherichia coli strains BL21 and W3110 were studied when the Vitreoscilla hemoglobin (VHb) was constitutively expressed in the chromosome. When VHb was expressed, acetate production decreased in both strains and was nearly eliminated in BL21. Transcriptional levels of the glyoxylate shunt genes decreased in both strains when VHb was expressed. However, higher transcription of the α-ketoglutarate dehydrogenase genes were observed for W3110, while for BL21 transcription levels decreased. VHb expression reduced the transcription of the cytochrome bo3 genes only in BL21. These results are useful for better selecting a production host.
Exploring how harming and helping behaviors drive prediction and explanation during anthropomorphism

ABSTRACT Cacioppo and colleagues advanced the study of anthropomorphism by positing three motives that moderated the occurrence of this phenomenon; belonging, effectance, and explanation. Here, we further this literature by exploring the extent to which the valence of a target’s behavior influences its anthropomorphism when perceivers attempt to explain and predict that target’s behavior, and the involvement of brain regions associated with explanation and prediction in such anthropomorphism. Participants viewed videos of varying visually complex agents - geometric shapes, computer generated (CG) faces, and greebles - in nonrandom motion performing harming and helping behaviors. Across two studies, participants reported a narrative that explained the observed behavior (both studies) while we recorded brain activity (study one), and participants predicted future behavior of the protagonist shapes (study two). Brain regions implicated in prediction error (striatum), not language generation (inferior frontal gyrus; IFG) engaged more to harming than helping behaviors during the anthropomorphism of such stimuli. Behaviorally, we found greater anthropomorphism in explanations of harming rather than helping behaviors, but the opposite pattern when participants predicted the agents’ behavior. Together, these studies build upon the anthropomorphism literature by exploring how the valence of behavior drives explanation and prediction.