Miracle-dz/UniFAR-FTUs huggingface dataset:
INDICATIONS AND OUTCOMES OF REPEAT PENETRATING KERATOPLASTY

Purpose: To evaluate indications, risk factors and outcome of repeat penetrating keratoplasty (PKP) at a tertiary referral eye care center Methods: In this retrospective study, medical chart of patients who underwent repeat PKP at Labbafinejad Medical Center between January 2004 and December 2009 were reviewed. Results: A total of 1,859 corneal transplantations were performed on 1,624 eyes during study period. Of these, 82 cases were repeat PKP which performed on 72 eyes (6.2% of the total number of primary PKP). Seventy-two eyes had two grafts; 10 eyes had three grafts. Among major indications, keratoconus was the least common initial indication for regraft and bullous keratopathies were the most common initial indication. The percentage of graft/regraft ratio ranged from a high of 9.6% for eyes with pseudophakic bullous keratopathy (PBK) / aphakic bullous keratopathy (ABK) to a low of 1.4% for eyes with keratoconus. Eyes with PBK/ABK were significantly overrepresented as a relative contributing factor to repeat PKP compared to initial PKP (29.2% vs. 11.7%, P=0.001), while those with keratoconus were significantly under-represented (13.9% vs. 38.4%, P=0.001). Conclusion: Bullous keratopathies are the leading indication for repeat PKP in our center. It has the highest relative risk for repeat PKP in comparison to other conditions whereas, keratoconus has the least.
Recent Insights into Long Bone Development: Central Role of Hedgehog Signaling Pathway in Regulating Growth Plate

The longitudinal growth of long bone, regulated by an epiphyseal cartilaginous component known as the “growth plate”, is generated by epiphyseal chondrocytes. The growth plate provides a continuous supply of chondrocytes for endochondral ossification, a sequential bone replacement of cartilaginous tissue, and any failure in this process causes a wide range of skeletal disorders. Therefore, the cellular and molecular characteristics of the growth plate are of interest to many researchers. Hedgehog (Hh), well known as a mitogen and morphogen during development, is one of the best known regulatory signals in the developmental regulation of the growth plate. Numerous animal studies have revealed that signaling through the Hh pathway plays multiple roles in regulating the proliferation, differentiation, and maintenance of growth plate chondrocytes throughout the skeletal growth period. Furthermore, over the past few years, a growing body of evidence has emerged demonstrating that a limited number of growth plate chondrocytes transdifferentiate directly into the full osteogenic and multiple mesenchymal lineages during postnatal bone development and reside in the bone marrow until late adulthood. Current studies with the genetic fate mapping approach have shown that the commitment of growth plate chondrocytes into the skeletal lineage occurs under the influence of epiphyseal chondrocyte-derived Hh signals during endochondral bone formation. Here, we discuss the valuable observations on the role of the Hh signaling pathway in the growth plate based on mouse genetic studies, with some emphasis on recent advances.
Comparison of the Biological Impact of UVA and UVB upon the Skin with Functional Proteomics and Immunohistochemistry

The skin provides protection against external stimuli; however, solar radiation, including ultraviolet A (UVA) and ultraviolet B (UVB), can result in profound influences on skin structure and function, which eventually impairs its molecular characteristics and normal physiology. In the current study, we performed proteome tools combined with an immunohistological approach on nude mouse skin to evaluate the adverse responses elicited by UVA and UVB irradiation, respectively. Our findings indicated that UVA significantly promotes oxidative damage in DNA, the breakdown of collagen fiber in the dermis, and the apoptosis of fibroblasts, which leads to inflammation. Meanwhile, UVB administration was found to enhance the carbonylation of various proteins and the proliferation of keratinocyte. Particularly, raspberry extract, which has been confirmed to have antioxidative efficacy, could effectively attenuate ultraviolet (UV) radiation-caused cell death. Network analysis also implied that UVA and UVB induce quite different responses, and that UVA results in cell death as well as inflammation mediated by caspase-3 and activator protein 1/nuclear factor kappa-light-chain-enhancer of activated B cells (AP-1/NF-κB), while UVB predominantly increases the risk of skin carcinogenesis involved with oncogenes such as p53 and c-Myc. Taken together, functional proteomics coordinated with histological experiments could allow for a high-throughput study to explore the alterations of crucial proteins and molecules linked to skin impacts subjected to UVA and UVB exposure.
Psychometric properties of the SCREESCO questionnaire used in a colorectal cancer screening programme—A Rasch analysis

Abstract Introduction Colorectal cancer (CRC) is one of the most common cancer diagnoses among both sexes. Sweden has not yet implemented any CRC screening programme, but a study, Screening of Swedish Colons (SCREESCO), is ongoing. The movement within the health care sector towards a more participatory perspective has led to the increased importance of shared decision making (SDM), and this is suggestively applied when deciding upon screening participation. There is no Swedish questionnaire for assessing the level of SDM in relation to CRC screening. Therefore, the CRC screening module of the National Survey of Medical Decisions was translated and culturally adapted into a Swedish context: the SCREESCO questionnaire. Aim The SCREESCO questionnaire requires further evaluation, and therefore, the aim, by using the Rasch approach, was to evaluate the psychometric properties of the SCREESCO questionnaire. Methods A Rasch partial credit model was chosen to investigate the psychometric properties. The sample consisted of individuals invited to the SCREESCO programme, who have answered the SCREESCO questionnaire. Results Rating scale structures indicated stability for the response structure used. Satisfactory evidence for validity of internal structure was also shown for the whole questionnaire and two of three concepts/subscales, after deletion of a few items. Validity in response processes indicated acceptable, or close to acceptable, findings, while the results for unidimensionality and differential item functioning (DIF) were somewhat mixed. Separation index revealed less satisfactory results, both for the whole questionnaire and the concepts/subscales. Conclusion This Rasch analysis of the SCREESCO questionnaire revealed that the questionnaire in its current form has difficulties to assess the level of SDM in relation to CRC screening. The achieved results will guide further evaluation and development with the long‐term goal of having a Swedish questionnaire, to be used in the health care sector, assessing the level of SDM in relation to CRC screening.
Ecosystem functioning in urban grasslands: The role of biodiversity, plant invasions and urbanization

Urbanization is driving the transformation of natural and rural ecosystems worldwide by affecting both the abiotic environment and the biota. This raises the question whether urban ecosystems are able to provide services in a comparable way to their non-urban counterparts. In urban grasslands, the effects of urbanization-driven ecological novelty and the role of plant diversity in modulating ecosystem functioning have received little attention. In this study, we assessed the influence of biodiversity, abiotic and biotic novelty on ecosystem functioning based on in situ measurements in non-manipulated grasslands along an urbanization gradient in Berlin (Germany). We focused on plant aboveground biomass (AGB), intrinsic water-use efficiency (iWUE) and 15N enrichment factor (Δδ15N) as proxies for biomass production, water and N cycling, respectively, within grassland communities, and tested how they change with plant biogeographic status (native vs alien), functional group and species identity. Approximately one third of the forb species were alien to Berlin and they were responsible for 13.1% of community AGB. Community AGB was positively correlated with plant-species richness. In contrast, iWUE and Δδ15N were mostly determined by light availability (depicted by sky view factor) and urban parameters like the percentage of impervious surface or human population density. We found that abiotic novelty potentially favors aliens in Berlin, mainly by enhancing their dispersal and fitness under drought. Mainly urban parameters indicating abiotic novelty were significantly correlated to both alien and native Δδ15N, but to AGB and iWUE of alien plants only, pointing to a stronger impact of abiotic novelty on N cycling compared to C and water cycling. At the species level, sky view factor appeared to be the prevailing driver of photosynthetic performance and resource-use efficiency. Although we identified a significant impact of abiotic novelty on AGB, iWUE and Δδ15N at different levels, the relationship between species richness and community AGB found in the urban grasslands studied in Berlin was comparable to that described in non-urban experimental grasslands in Europe. Hence, our results indicate that conserving and enhancing biodiversity in urban ecosystems is essential to preserve ecosystem services related to AGB production. For ensuring the provision of ecosystem services associated to water and N use, however, changes in urban abiotic parameters seem necessary.
EWI-2 Inhibits Cell–Cell Fusion at the HIV-1 Virological Presynapse

Cell-to-cell transfer of virus particles at the Env-dependent virological synapse (VS) is a highly efficient mode of HIV-1 transmission. While cell-cell fusion could be triggered at the VS, leading to the formation of syncytia and preventing exponential growth of the infected cell population, this is strongly inhibited by both viral (Gag) and host (ezrin and tetraspanins) proteins. Here, we identify EWI-2, a protein that was previously shown to associate with ezrin and tetraspanins, as a host factor that contributes to the inhibition of Env-mediated cell-cell fusion. Using quantitative fluorescence microscopy, shRNA knockdowns, and cell-cell fusion assays, we show that EWI-2 accumulates at the presynaptic terminal (i.e. the producer cell side of the VS), where it contributes to the fusion-preventing activities of the other viral and cellular components. We also find that EWI-2, like tetraspanins, is downregulated upon HIV-1 infection, mostly by Vpu. Despite strong inhibition of fusion at the VS, T cell-based syncytia do form in vivo and in physiologically relevant culture systems, but they remain small. In regard to that, we demonstrate that EWI-2 and CD81 levels are restored on the surface of syncytia, where they (presumably) continue to act as fusion inhibitors. This study documents a new role for EWI-2 as an inhibitor of HIV-1-induced cell-cell fusion, and provides novel insight into how syncytia are prevented from fusing indefinitely.
Human Cytochrome P450 1A1 Adapts Active Site for Atypical Nonplanar Substrate

The human cytochrome P450 1A1 (CYP1A1) is well known for chemical activation of procarcinogens and often has a substrate scope of small and highly planar compounds. Substrates deviating from these characteristics are certainly known, but how these larger and nonplanar substrates are accommodated and oriented within the CYP1A1 active site is not understood. Herein a new X-ray structure of CYP1A1 bound to the pan-Pim kinase inhibitor GDC-0339 reveals how the CYP1A1 active site cavity is reconfigured to bind larger and nonplanar compounds. The shape and size of the cavity are controlled by structural elements in the active site roof, with major changes in the conformation of the F helix break and relocation of Phe224 from the active site to the protein surface. This altered CYP1A1 active site architecture is consistent with the proposed mechanism for CYP1A1 generation of an unusual aminoazepane-rearranged metabolite for this substrate. SIGNIFICANCE STATEMENT Cytochrome P450 1A1 metabolizes drugs, procarcinogens, and toxins and although previous structures have revealed how its stereotypical planar, aromatic compounds are accommodated in the CYP1A1 active site, this is not the case for flexible and nonplanar compounds. The current work determines the X-ray structure of CYP1A1 with such a flexible, nonplanar Pim kinase inhibitor, revealing significant modification of the CYP1A1 roof that accommodate this preclinical candidate and support an unusual intramolecular rearrangement reaction.
Effectiveness of warm compress and cold compress to reduce laceration perineum pain on primiparous at Candimulyo Magelang 2015

Background: The problem that most felt the presence of perineal laceration was pain. In the postpartum mothers experience pain because of perineal lacerations cause unpleasant effects such as pain and fear to move, so it can cause many problems. The solve of this problem can be administered with pharmacologic therapy and nonpharmacologic therapy. Non-pharmacologic therapy can be given to reduce pain include stimulation of the skin, giving warm and cold compresses. Warm compress is the act of giving a sense of warmth to the client specific parts of the body and a cold compress is provide a sense of cold on the client by using ice water on the body that feels pain. Objective of the study was to determine the effectiveness of warm compress and cold compress against the perineal laceration primiparous. Methods: This study using Quasi Experiments with two group pretest and posttest with Mann Whitney test. Total sample is 36 people, 18 people warm compresses and 18 people cold compresses, by using accidental sampling technique. Techniques warm compresses and cold compresses performed three times during one day. Results: This study shows that there is a difference between therapeutic warm compresses and cold compresses. Conclusions: Cold compress more effective in reducing laceration perineum pain on primiparous.
The Response of UV/Blue Light and Ozone Sensing Using Ag-TiO2 Planar Nanocomposite Thin Film

We successfully fabricated a planar nanocomposite film that uses a composite of silver nanoparticles and titanium dioxide film (Ag-TiO2) for ultraviolet (UV) and blue light detection and application in ozone gas sensor. Ultraviolet-visible spectra revealed that silver nanoparticles have a strong surface plasmon resonance (SPR) effect. A strong redshift of the plasmonic peak when the silver nanoparticles covered the TiO2 thin film was observed. The value of conductivity change for the Ag-TiO2 composite is 4–8 times greater than that of TiO2 film under UV and blue light irradiation. The Ag-TiO2 nanocomposite film successfully sensed 100 ppb ozone. The gas response of the composite film increased by roughly six and four times under UV and blue light irradiation, respectively. We demonstrated that a Ag-TiO2 composite gas sensor can be used with visible light (blue). The planar composite significantly enhances photo catalysis. The composite films have practical application potential for wearable devices.
Suberin deposition in potato periderm: a novel resistance mechanism against tuber greening.

Light-induced tuber greening is one of the most important quality defects of potato. Although varietal and maturity factors are known to affect greening resistance, physiological mechanisms of resistance are poorly understood. We proposed that physiological and biochemical factors within the tuber periderm provide resistance and hypothesised that resistance is primarily related to suberin content. We investigated differences in the tuber periderm between genotypes and tuber maturities that varied in greening propensity. We examined suberin and light-induced pigment accumulation, and phellem cell development, and studied greening propensity in mutant and chemically-treated tubers with enhanced suberisation. Resistance to greening was strongly linked to increased suberin in the periderm, which varied with variety and tuber maturity. Furthermore, greening was reduced in mutant and chemically-treated tubers with enhanced suberisation. Increases in phellem cell layers and light-induced carotenoids and anthocyanins were identified as secondary resistance factors. Our work represents the first physiological mechanism of varietal and tuber maturity resistance to greening, expanding the known functionality of suberin and providing for the first time a biomarker that will aid producers and breeders in selection and improvement of potato varieties for greening resistance.
Pathogenesis of neurotoxicity and role of signaling in the efficacy of anticancer agents

Neurotoxicity is a burdensome side effect of platinum-based chemotherapy that prevents administration of the full efficacious dosage and often leads to treatment withdrawal. Peripheral sensory neurotoxicity varies from paresthesia in fingers to ataxic gait, which might be transient or irreversible. Because the number of patients being treated with these neurotoxic agents is still increasing, the need for understanding the pathogenesis of this dramatic side effect is critical. Platinum derivatives, such as cisplatin and carboplatin, harm mainly peripheral nerves and dorsal root ganglia neurons, possibly because of progressive DNA-adduct accumulation and inhibition of DNA repair pathways (e.g., extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 mitogen-activated protein kinass), which finally mediate apoptosis. Oxaliplatin, with a completely different pharmacokinetic profile, may also alter calcium-sensitive voltage-gated sodium channel kinetics through a calcium ion immobilization by oxalate residue as a calcium chelator and cause acute neurotoxicity. Polymorphisms in several genes, such as voltage-gated sodium channel genes or genes affecting the activity of pivotal metal transporters (e.g., organic cation transporters, organic cation/carnitine transporters, and some metal transporters, such as the copper transporters, and multidrug resistance-associated proteins), can also influence drug neurotoxicity and treatment response. However, most pharmacogenetics studies need to be elucidated by robust evidence. There are supportive reports about the effectiveness of several neuroprotective agents (e.g., vitamin E, glutathione, amifostine, xaliproden, and venlafaxine), but dose adjustment and/or drug withdrawal seem to be the most frequently used methods in the management of platinum-induced peripheral neurotoxicity.To develop alternative options in the treatment of platinum-induced neuropathy, studies on in vitro models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution. The Oncologist 2015;20:411–432 Implications for Practice: Neurotoxicity is a burdensome side effect of platinum-based chemotherapy that prevents administration of the full efficacious dosage and often leads to treatment withdrawal. This review summarizes preclinical and clinical evidence of pathogenesis and pathophysiology of platinum-induced peripheral neurotoxicity, as well as available evidence of neuroprotective and therapeutic strategies. These data may help to develop alternative options in the treatment of platinum-induced neuropathy, studies on in vitro models, and appropriate trials planning to find the best patient-oriented solution.
Reassessing the role of chemoimmunotherapy in chronic lymphocytic leukemia

ABSTRACT Introduction: The treatment paradigm of chronic lymphocytic leukemia (CLL) has changed significantly in the last few years. There are multiple front-line therapy options for the treatment of CLL, including chemoimmunotherapy (CIT), ibrutinib, and most recently venetoclax with obinutuzumab. The role of CIT has declined significantly for patients with CLL and novel agents are now being used more frequently in the front-line setting. Areas covered: Authors reviewed the latest data examining the role of CIT versus ibrutinib and ibrutinib combined with CIT for the treatment of CLL. Data reviewed here include: preliminary results from CLL12, long-term results of CLL8 and MD Anderson Cancer Center (MDACC) data with FCR, 7-year follow-up of PCYC-1102/1103 (phase 2 data) with ibrutinib, results of two-phase 3 randomized trials comparing CIT to ibrutinib, E1912 and A041202, and results of HELIOS and other phase 2 trials evaluating CIT combined with ibrutinib. Expert opinion: Treatment approaches for patients with CLL should be individualized and that there is still a role, albeit diminished, for CIT in the treatment of CLL, predominately in the front-line setting. Clinicians should focus on prognostic factors, patient preference, and evaluate short and long-term effects of CIT versus novel agents. Newly diagnosed patients should be encouraged to enroll in clinical trials.
High-Mobility Hydrogenated Fluorine-Doped Indium Oxide Film for Passivating Contacts c-Si Solar Cells

Broadband transparent conductive oxide layers with high electron mobility (μe) are essential to further enhance crystalline silicon (c-Si) solar cell performances. Although metallic cation-doped In2O3 thin films with high μe (>60 cm2 V–1 s–1) have been extensively investigated, the research regarding anion doping is still under development. In particular, fluorine-doped indium oxide (IFO) shows promising optoelectrical properties; however, they have not been tested on c-Si solar cells with passivating contacts. Here, we investigate the properties of hydrogenated IFO (IFO:H) films processed at low substrate temperature and power density by varying the water vapor pressure during deposition. The optimized IFO:H shows a remarkably high μe of 87 cm2 V–1 s–1, a carrier density of 1.2 × 1020 cm–3, and resistivity of 6.2 × 10–4 Ω cm. Then, we analyzed the compositional, structural, and optoelectrical properties of the optimal IFO:H film. The high quality of the layer was confirmed by the low Urbach energy of 197 meV, compared to 444 meV obtained on the reference indium tin oxide. We implemented IFO:H into different front/back-contacted solar cells with passivating contacts processed at high and low temperatures, obtaining a significant short-circuit current gain of 1.53 mA cm–2. The best solar cell shows a conversion efficiency of 21.1%.
Effects of Pioglitazone on Glucose-Dependent Insulinotropic Polypeptide–Mediated Insulin Secretion and Adipocyte Receptor Expression in Patients With Type 2 Diabetes

Incretin hormone dysregulation contributes to reduced insulin secretion and hyperglycemia in patients with type 2 diabetes mellitus (T2DM). Resistance to glucose-dependent insulinotropic polypeptide (GIP) action may occur through desensitization or downregulation of β-cell GIP receptors (GIP-R). Studies in rodents and cell lines show GIP-R expression can be regulated through peroxisome proliferator–activated receptor γ (PPARγ) response elements (PPREs). Whether this occurs in humans is unknown. To test this, we conducted a randomized, double-blind, placebo-controlled trial of pioglitazone therapy on GIP-mediated insulin secretion and adipocyte GIP-R expression in subjects with well-controlled T2DM. Insulin sensitivity improved, but the insulinotropic effect of infused GIP was unchanged following 12 weeks of pioglitazone treatment. In parallel, we observed increased GIP-R mRNA expression in subcutaneous abdominal adipocytes from subjects treated with pioglitazone. Treatment of cultured human adipocytes with troglitazone increased PPARγ binding to GIP-R PPREs. These results show PPARγ agonists regulate GIP-R expression through PPREs in human adipocytes, but suggest this mechanism is not important for regulation of the insulinotropic effect of GIP in subjects with T2DM. Because GIP has antilipolytic and lipogenic effects in adipocytes, the increased GIP-R expression may mediate accretion of fat in patients with T2DM treated with PPARγ agonists.