Miracle-dz/UniFAR-FTUs huggingface dataset:
THE ORIGIN OF WEST INDIAN AMPHIBIANS AND REPTILES

The known West Indian herpetofauna is comprised of 175 species of amphibians (99% endemic) and 457 species of reptiles (93% endemic). Infonnation on distributions, relationships, and times of origin, with empha­ sis on estimates of divergence time from albumin immunological data, are analyzed in an attempt to understand the origin of the herpetofauna. Seventy-seven independent lineages of West Indian amphibians and reptiles are identi­ fied and nearly all (95%) originated in the New World. Of those lineages for which a source area within the New World can be determined, most (79%) show a South American origin, with smaller contributions from Central America (15%) and North America (6%). One very old and diverse lineage, frogs of the genus Eleutherodactylus, originated by vicariance or dispersal in the late Cretaceous (70 mya). With one possible exception (the xantusiid lizard Cricosaura typica), all other lineages appear to have arrived by dispersal during the Cenozoic, and all but nine lineages in the last half of the Cenozoic (30-0 mya). Most West Indian lineages with multiple endemic species originated in the mid-Tertiary, whereas most lineages with a single endemic species arose in the late Tertiary. Qua­ ternary dispersal is postulated to explain the origin of West Indian populations of mainland species. The probable explanation for the predominately South American origin of the West Indian herpetofauna is the nearly unidirectional (towards the west-northwest) water current patterns in the Caribbean: waterreaching the Greater Antilles originates near the Lesser Antilles and South America. Wide variation in the times of origin for the West Indian lineages does not support the recent suggestion of a mid-Cenozoic landbridge between South America and the Greater Antilles. Dispersal, in most cases, is believed to have occurred by the discharge of organisms attached to flotsam from the mouths of major rivers on the continents and carried by currents to the West Indies. Proto-Antillean vicariance remains a geological possibility, but recent paleocoastline data suggest that a dry land connection be­ tween the proto-Antilles and neighboring continents in the late Mesozoic may not have occurred. The widespread invoking of vicariance to explain nearly any distribution of West Indian organism without infonnation on time of origin is seen as a popular trend but one that lacks support.
High Content Screening Using New U2OS Reporter Cell Models Identifies Harmol Hydrochloride as a Selective and Competitive Antagonist of the Androgen Receptor

Prostate cancer is the most commonly diagnosed malignancy in men. Its growth mainly relies on the activity of the androgen receptor (AR), justifying the use of androgen deprivation therapy as a gold standard treatment for the metastatic disease. Inhibition of the androgen axis using second generation antagonists has improved patients’ survival, but is systematically confronted to resistance mechanisms, leading to a median survival that does not exceed 5 years. Counteracting this resistance has been the object of a large number of investigations, with a particular emphasis towards the identification of new AR inhibitors, whether they antagonize the receptor by a competitive or a non-competitive binding. To this end, many high content screens have been performed, to identify new non-steroidal AR antagonists, using a variety of approaches, but reported somewhat controversial results, depending on the approach and on the cell model that was used for screening. In our study, we used the U2OS osteosarcoma cells stably transfected with AR or ARv7 and a luciferase reporter as a previously validated model to screen the Prestwick Phytochemical library. The results of our screen identified ellipticine, harmol, and harmine hydrochloride as confirmed hits. Surprisingly, we could demonstrate that harmol hydrochloride, previously identified as a non-competitive inhibitor of AR or a weak inhibitor of androgen signaling, was actually a competitive antagonist of AR, which inhibits the growth of VCaP prostate cancer line, at concentrations for which it did not affect the growth of the AR negative DU145 and PC3 cells. Interestingly, we also report for the first time that harmol hydrochloride was selective for AR, as it could not alter the activity of other nuclear receptors, such as the glucocorticoid receptor (GR), the progesterone receptor (PR), or the mineralocorticoid receptor (MR). Additionally, we demonstrate that, conversely to enzalutamide, harmol hydrochloride did not show any agonistic activity towards the pregnane X receptor (PXR), a master regulator of drug metabolism. Together, our results shed light on the importance of the cellular context for the screening of new AR antagonists. They further indicate that some of the potential hits that were previously identified may have been overlooked.
Eukaryotic phosphatase inhibitors enhance colistin efficacy in gram‐negative bacteria

The mounting threat of multi‐drug‐resistant (MDR) bacteria places a tremendous strain on the antimicrobial clinical arsenal, forcing physicians to revert to near‐obsolete antibiotics to treat otherwise intractable infections. Antibiotic adjuvant therapy has emerged as a viable alternative to the development of novel antimicrobial agents. This method uses combinations of an existing antibiotic and a non‐antimicrobial small molecule, where the combination either breaks drug resistance or further potentiates antibiotic activity. Through a high‐content screen of eukaryotic kinase inhibitors, our group previously identified two highly potent adjuvants that synergize with colistin, a cyclic, polycationic antimicrobial peptide that serves as a drug of last resort for the treatment of MDR Gram‐negative bacterial infections. Cell signaling proteins implicated in colistin resistance mechanisms display both kinase and phosphatase activities. Herein, we explore the potential for eukaryotic phosphatase inhibitors to be repurposed as colistin adjuvants. From a panel of 48 unique structures, we discovered that the natural product kuwanon G breaks colistin resistance, while the non‐antimicrobial macrolide ascomycin potentiates colistin in polymyxin‐susceptible bacteria.
Real-World Setting Cost-Effectiveness Analysis Comparing Three Therapeutic Schemes of One-Year Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer from the Cyprus NHS Payer Perspective

Introduction: This study is one of the first real-world cost-effectiveness analyses of one-year adjuvant trastuzumab used in HER2-positive early female breast cancer in comparison to chemotherapy alone. It is just the second one in Europe, the first one in Cyprus, and the fourth one worldwide ever carried out using real-world data. Methods: Using a Markov model (four health states), a cost-effectiveness analysis was carried out both over 20 years and for a lifetime horizon. The sampling method used in this study was the randomized sampling of 900 women. Results: The findings for the 20-year horizon showed that all trastuzumab arms were more cost-effective, with a willingness-to-pay threshold of only €60,000 per quality-adjusted life year (QALY) [incremental cost-effectiveness ratios (ICER): €40,436.10/QALY]. For the lifetime horizon, with thresholds of €20,000, €40,000, and €60,000/QALY, all trastuzumab arms were found to be more cost-effective (ICER: €17,753.85/QALY). Moreover, for the 20-year and the lifetime horizons, with thresholds of €20,000/QALY, €40,000/QALY, and €60,000/QALY, the most cost-effective of the three subgroups (anthracyclines and then trastuzumab, no anthracyclines and then trastuzumab, and anthracyclines, taxanes, and trastuzumab) was that of anthracyclines and then trastuzumab (ICER: €18,301.55/QALY and €8954.97/QALY, respectively). Conclusions: The study revealed that adjuvant trastuzumab for one year in female HER2-positive early breast cancer can be considered cost-effective.
Frontline Blinatumomab in Older Adults with Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia

Outcomes of acute lymphoblastic leukemia (ALL) in older adults treated with chemotherapy are poor. The CD19/CD3 bispecific T-cell engager (BiTE) antibody blinatumomab is approved for refractory, relapsed or minimal/measurable residual disease (MRD)-positive B-cell ALL, but there is little experience in the upfront setting, including in older patients. We retrospectively analyzed outcomes of blinatumomab monotherapy in five newly diagnosed Philadelphia chromosome-negative B-cell ALL patients over 70 years. Three had cytokine release syndrome, treated with dexamethasone and/or tocilizumab, and four patients had neurotoxicity, treated with dexamethasone, without blinatumomab interruption. All five achieved complete remission (CR) after cycle one, three with undetectable MRD. All five were alive at 8 to 15 months. Three remained in MRD-negative CR. Two relapsed after cycle 3, one with extramedullary disease. In our small cohort of patients over 70 years, blinatumomab was safe initial therapy and produced a high response rate.
Behavioral and Autonomic Responses in Treating Children with High-Functioning Autism Spectrum Disorder: Clinical and Phenomenological Insights from Two Case Reports

In this study, we aimed to evaluate the process applied in subjects with Autism Spectrum Disorder (ASD) to elaborate and communicate their experiences of daily life activities, as well as to assess the autonomic nervous system response that subtend such a process. This procedure was evaluated for the first time in two eight-year-old girls with high-functioning ASDs. The subjects performed six months of training, based on the cognitive–motivational–individualized (c.m.i.®) approach, which mainly consisted in building domestic procedures and re-elaborating acquired experiences through drawing or the use of icons made by the children. Together with behavioral observations, the response of the autonomic nervous system during such re-elaboration was recorded. A change in communicative and interactive competences was observed, moving from a condition of spontaneity to one in which the girls were engaged in relating their experiences to a parent. Autonomic response highlighted how, in communicating their own experiences, they achieved a state of cognitive activation, which enabled a greater communicative and emotional connection with the interlocutor. This is a proof-of-concept study on the application of the c.m. i. ®, which needs to be extensively validated in the clinical setting.
Preliminary phylogeny of the thrips parasitoids of Turkey based on some morphological scales and 28S D2 rDNA, with description of a new species.

Species of the Ceranisus thrips-attacking genus are difficult to distinguish morphologically. The phylogenetic relationships within the Ceranisus species were explored using nucleotide sequences of the 28S D2 expansion region of the rDNA gene. Bayesian, maximum likelihood, and parsimony inference methods were employed to construct the phylogenetic relationships. Principal component analysis on the Turkish species of Ceranisus, namely antalyacus, menes, bozovaensis, hirsutus, planitianus (a new record for Turkey), pacuvius, and a new species, provided supporting evidence. All known data concerning hosts and geographical distribution are presented. A new species, C. onuri O. Doganlar, sp.n. , was described from Turkey.
Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor B in peripheral blood mononuclear cells

Background: Nuclear transcription factor B (NF-B) plays an important role in atherosclerosis by modulating gene expression. Postprandial lipemia has been correlated with an increase in NF-B activation in vascular cells and it is associated with an increase in postprandialtriacylglycerol-richlipoproteins,whichareinvolvedin the development of atherosclerotic plaque. Objective:Theobjectiveofthisstudywastodeterminetheeffectof theintakesof3differentfoodswithdifferentfatcompositionsonthe postprandial activation of monocyte NF-B. Design: Eight healthy men followed a 4-wk baseline diet and then consumed3fat-loadmealsconsistingof1gfat/kgbodywt(65%fat) according to a randomized crossover design. Each meal had a differentfattyacidcomposition,andtheconsumptionofeachmealwas separated by 1 wk. The compositions of the 3 test meals were as follows: olive oil meal [22% saturated fatty acids (SFAs), 38% monounsaturated fatty acids (MUFAs), 4% polyunsaturated fatty acids(PUFAs),and0.7%-linolenicacid],buttermeal(38%SFAs, 22% MUFAs, 4% PUFAs, and 0.7% -linolenic acid), and walnut meal (20% SFAs, 24% MUFAs, 16% PUFAs, and 4% -linolenic acid). Results: Ingestion of the olive oil meal did not elicit NF-B activation compared with ingestion of either the butter meal a t3h( P 0.05) or the walnut meal at 9 h (P 0.05). There was no significant differenceinthepostprandialtriacylglycerolresponsebetweenthe3 meals. Conclusions: Consumption of an olive oil–enriched meal does not activate NF-B in monocytes as do butter and walnut-enriched meals.Thiseffectcouldenhancethecardioprotectiveeffectofolive oil–enriched diets. Am J Clin Nutr 2004;80:1487–91.
Dental Anomalies in Rare, Genetic Ciliopathic Disorder—A Case Report and Review of Literature

Background: Primary ciliary dyskinesia (PCD) is a rare, ciliopathic disorder. In many ciliopathies, dental anomalies are observed alongside other symptoms of the disease. To date, there are no published reports concerning the dental developmental problems that are associated with ciliary defects in PCD patients. Methods: Patients suffering from PCD underwent dental clinical examination, which included the assessment of developmental disorders regarding the number and morphological structure of the teeth (size and shape) as well as developmental disorders of mineralised dental tissues. Then, three-dimensional radiographic examination was performed utilising Cone Beam Computed Tomography (CBCT). Results: Four PCD patients, aged 31-54, agreed to enter the study. Dental examinations showed the presence of dental developmental disorders in three of them. Additionally, CBCT showed abnormalities in those patients. Conclusions: 1. The dental phenotype in PCD patients seems to be heterogeneous. Tooth developmental disorders resulting from abnormal odontogenesis may be a symptom of PCD that is concomitant with other developmental abnormalities resulting from malfunctioning primary cilia. 2. Patients with ciliopathies are likely to develop dental developmental defects. Therefore, beginning in early childhood, they should be included in a targeted specialised dental programme to enable early diagnosis and to ensure dedicated preventive and therapeutic measures.
Exopolysaccharides of Two Cyanobacterial Strains from Roman Hypogea

The cytomorphology and the exopolysaccharides of two heterocystous cyanobacteria, Scytonema ocellatum CP8-2 and Fischerella maior NAV 10 bis, isolated from biofilms collected in two Roman hypogea, were investigated from a cytochemical, ultrastructural and biochemical point of view. Cytochemical stains and observation using light and transmission electron microscopy showed a bi-layered sheath in both cyanobacteria, with a different composition in sulphated and carboxylic groups. RP-HPLC of the extracted polysaccharides forming the mucous matrix showed the neutral sugars glucose and arabinose and the charged galacturonic acid as the main monosaccharides. Circular dichroism spectra recorded at varying pH and temperature showed that these polymers followed a random coil model and did not present a structured organised conformation at ambient temperature. The outcomes of this study increase the understanding of colonization and biodeterioration of important archaeological and cultural sites by cyanobacterial biofilms and the role of the exopolymeric substances involved.
Host Utilization and Distribution of Nubenocephalid Gregarines (Eugregarinorida: Actinocephalidae) Parasitizing Argia spp. (Odonata: Zygoptera) in the Central United States

Abstract Gregarine host specificity has been the cornerstone of gregarine taxonomy for nearly a century. Several laboratory experiments have accepted strict host specificity by failure to cross-infect distantly related hosts with unrelated gregarine species. These empirical studies are not feasible for all gregarine hosts, especially nondomesticated groups. Additionally, studies of gregarine distributions have always focused on insect hosts of disparate groups, rather than targeting potential hosts species within a single genus and their congeneric gregarines. This study addresses host utilization of nubenocephalid gregarines parasitizing the odonate genus Argia (Odonata: Zygoptera: Coenagrionidae). Populations of 9 species of adult Argia were collected, dissected, and observed for gregarine infection during the April–September flight seasons in 2007 from 17 localities in the central United States. On average, 2.5 species of Argia were collected at each locality. A species of Nubenocephalus—Nubenocephalus nebraskensis, Nubenocephalus secundus, or Nubenocephalus spp. —was collected from every infected population of Argia except for the Argia vivida population at Prairie Dog Town Fork-Red River, Randall County (Co.), Texas, U.S.A. Nubenocephalus secundus utilizes at least 7 of the 9 argid hosts sampled whereas N. nebraskensis was collected from only 2 argid species. Only Argia translata was observed to host both N. secundus and N. nebraskensis. These patterns of host utilization by nubenocephalid gregarines represent an ecotypic gregarine assemblage rather than a vicariant assemblage, demonstrating that nubenocephalid gregarines do not differentiate between species of Argia as hosts.
Upper body motor function and swallowing impairments and its association in survivors of head and neck cancer: A cross-sectional study

Background Upper body motor function and swallowing may be affected after curative treatment for head and neck cancer. The aims of this study are to compare maximum mouth opening (MMO), temporomandibular dysfunction (TMD), cervical and shoulder active range of motion (AROM) and strength, and swallowing difficulty between survivors of head and neck cancer (sHNC) and healthy matched controls (HMC) and to examine the correlations between these outcomes in sHNC. Methods Thirty-two sHNC and 32 HMC participated on the study. MMO, TMD, cervical and shoulder AROM, cervical and shoulder strength, the SPADI shoulder pain and disability indices, the Eating Assessment Tool (EAT-10) score, swallowing difficulty as determined using a visual analogue scale (VAS), and the location of disturbances in swallowing, were recorded. Results MMO and cervical and shoulder AROM and strength were significantly lower in sHNC, whereas FAI, SPADI score, EAT-10 and VAS were higher. The MMO, TMD, cervical and shoulder AROM, and cervical shoulder strength values showed significant correlations (some direct, others inverse) with one another. Swallowing difficulty was inversely associated with the MMO, cervical AROM and shoulder strength. Conclusion Compared with controls, sHNC present smaller MMO, lower cervical and shoulder AROM, lower cervical and shoulder strength and higher perception of TMD, shoulder pain and disability and swallowing difficulty. sHNC suffer impaired swallowing related to lower MMO, presence of TMD, cervical AROM and shoulder strength values. Improving these variables via physiotherapy may reduce the difficulty in swallowing experienced by some sHNC.
A Graphene/Polycrystalline Silicon Photodiode and Its Integration in a Photodiode–Oxide–Semiconductor Field Effect Transistor

In recent years, the characteristics of the graphene/crystalline silicon junction have been frequently discussed in the literature, but study of the graphene/polycrystalline silicon junction and its potential applications is hardly found. The present work reports the observation of the electrical and optoelectronic characteristics of a graphene/polycrystalline silicon junction and explores one possible usage of the junction. The current–voltage curve of the junction was measured to show the typical exponential behavior that can be seen in a forward biased diode, and the photovoltage of the junction showed a logarithmic dependence on light intensity. A new phototransistor named the “photodiode–oxide–semiconductor field effect transistor (PDOSFET)” was further proposed and verified in this work. In the PDOSFET, a graphene/polycrystalline silicon photodiode was directly merged on top of the gate oxide of a conventional metal–oxide–semiconductor field effect transistor (MOSFET). The magnitude of the channel current of this phototransistor showed a logarithmic dependence on the illumination level. It is shown in this work that the PDOSFET facilitates a better pixel design in a complementary metal–oxide–semiconductor (CMOS) image sensor, especially beneficial for high dynamic range (HDR) image detection.
Heparin affects the induction of regulatory T cells independent of anti‐coagulant activity and suppresses allogeneic immune responses

Heparin is a widely used anti‐coagulant that enhances anti‐thrombin (AT) activity. However, heparin also suppresses immune and inflammatory responses in various rodent models and clinical trials, respectively. The mechanism by which heparin suppresses immune responses is unclear. The effect of heparin on regulatory T cells (Tregs) in allogeneic immune responses was analysed using an acute graft‐versus‐host disease (aGVHD) mouse model and mixed lymphocyte reactions (MLRs). In‐vitro culture systems were utilized to study the effects of heparin on Tregs. Heparin administration reduced mortality rates and increased the proportion of Tregs in the early post‐transplantation period of aGVHD mice. In both murine and human MLRs, heparin increased Tregs and inhibited responder T cell proliferation. Heparin promoted functional CD4+CD25+forkhead box protein 3 (FoxP3)+ Treg generation from naive CD4+ T cells, increased interleukin (IL)‐2 production and enhanced the activation of pre‐existing Tregs with IL‐2. Heparin‐induced Treg increases were not associated with anti‐coagulant activity through AT, but required negatively charged sulphation of heparin. Importantly, N‐acetyl heparin, a chemically modified heparin without anti‐coagulant activity, induced Tregs and decreased mortality in aGVHD mice. Our results indicate that heparin contributes to Treg‐mediated immunosuppression through IL‐2 production and suggest that heparin derivatives may be useful for immunopathological control by efficient Treg induction.