Miracle-dz/UniFAR-FTUs huggingface dataset:
Catalytic effect of dissolved humic acids on the chemical degradation of phenylurea herbicides.

BACKGROUND Although biodegradation seems to be the main cause of herbicide degradation, abiotic degradation can also be important for chemicals such as phenylureas, which are subject to catalysed soil reactions. The aim of this work is to investigate the effect of dissolved humic acids (HAs), normally present in natural waters, on the hydrolysis of phenylurea herbicides, and it presents a kinetic model that takes into account the role of adsorption. RESULTS The linearity of the adsorption isotherms indicates that phenylurea-humic acid interaction can be considered in terms of a repartition-like equilibrium of phenylurea between water and HAs. Kinetic experiments show that the degradation rates of phenylureas increase with HA concentration. CONCLUSION The kinetic equation adopted adequately describes the experimental data trend, allowing the evaluation of the catalytic effect of HAs on the chemical degradation of phenylureas. Carboxyl groups of HAs seem to play a leading role in the catalysis. The kinetic equation derived in this work could be helpful in predicting the persistence of phenylureas and of related compounds in natural water.
Auditory dysfunction in aging and senile dementia of the Alzheimer's type.

OBJECTIVE To determine the prevalence and type of auditory dysfunction in older volunteer subjects with mild probable Alzheimer's disease (pAD). METHODS Pure-tone thresholds, word recognition in quiet, Synthetic Sentence Identification with Ipsilateral Competing Message or Contralateral Competing Message, distortion-product otoacoustic emissions, and auditory brain-stem responses were done in 82 elderly volunteer subjects whose cognitive, psychologic, and neurologic status had been determined through annual testing in a research center. Based on clinical criteria and the Clinical Dementia Rating (CDR) scale, 40 subjects had been judged to be nondemented (CDR score, 0), and 42 had a clinical diagnosis of pAD, with 22 in the questionable (CDR score, 0.5) and 20 in the mild (CDR score, 1) categories. RESULTS The mean age-adjusted pure-tone average thresholds (0.5, 1.0, and 2.0 kHz) were poorer in the subjects with pAD by 5.1 dB in the right ears and 6.1 dB in the left ears; these differences were not statistically significant. Word recognition in quiet did not differ by CDR category. The age-adjusted scores on the Synthetic Sentence Identification with Ipsilateral Competing Message or Contralateral Competing Message were significantly reduced in the subjects with mild pAD. Distortion-product otoacoustic emission amplitudes and auditory brain-stem response thresholds and latencies paralleled the pure-tone threshold results and did not differ across the CDR groups. CONCLUSIONS Central auditory dysfunction was evident in subjects with even mild cases of pAD, whereas peripheral auditory function was not different from that in age-matched control subjects. Additional research is needed to delineate the mechanisms of central auditory dysfunction and to establish the sensitivity and specificity of auditory testing in subjects with Alzheimer's disease. We recommend auditory assessment, including Synthetic Sentence Identification with Ipsilateral Competing Message or Contralateral Competing Message, for older patients in general and in particular for those in whom dementia is suspected.
Prevalence of gastrointestinal and psychosomatic symptoms among Asian patients undergoing regular hemodialysis

Gastrointestinal (GI) symptoms are reported to be common among patients with chronic disorders including end‐stage renal disease (ESRD). This questionnaire study assessed the prevalence of GI symptoms among patients undergoing hemodialysis (HD) and to correlate with the presence of diabetes mellitus and psychosomatic symptoms in Asian patients with ESRD.
Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy

The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agent like atezolimumab for use in patients with advanced stage urothelial carcinoma. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems. There are new safety data accumulating on ICIs in patients with previously diagnosed autoimmune conditions. It is challenging for clinicians to continuously update their working knowledge to diagnose and manage these events successfully. If diagnosed timely, the majority of events are completely reversible, and temporary immunosuppression with glucocorticoids, infliximab or other agents is warranted only in the most severe grade illnesses. The same principles of management will possibly apply as newer anti- cytotoxic T lymphocytes-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1/PD-L1) antibodies are introduced. The current focus of research is for prophylaxis and for biomarkers to predict the onset of these toxicities. In this review we summarize the irAEs of ICIs and emphasize their growing spectrum and their management algorithms, to update oncology practitioners.
Molecular function of α7 nicotinic receptors as drug targets

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand‐gated ion channels involved in many physiological and pathological processes. In vertebrates, there are seventeen different nAChR subunits that combine to yield a variety of receptors with different pharmacology, function, and localization. The homomeric α7 receptor is one of the most abundant nAChRs in the nervous system and it is also present in non‐neuronal cells. It plays important roles in cognition, memory, pain, neuroprotection, and inflammation. Its diverse physiological actions and associated disorders have made of α7 an attractive novel target for drug modulation. Potentiation of the α7 receptor has emerged as a novel therapeutic strategy for several neurological diseases, such as Alzheimer's and Parkinson's diseases, and inflammatory disorders. In contrast, increased α7 activity has been associated with cancer cell proliferation. The presence of different drug target sites offers a great potential for α7 modulation in different pathological contexts. In particular, compounds that target allosteric sites offer significant advantages over orthosteric agonists due to higher selectivity and a broader spectrum of degrees and mechanisms of modulation. Heterologous expression of α7, together with chaperone proteins, combined with patch clamp recordings have provided important advances in our knowledge of the molecular basis of α7 responses and their potential modulation for pathological processes. This review gives a synthetic view of α7 and its molecular function, focusing on how its unique activation and desensitization features can be modified by pharmacological agents. This fundamental information offers insights into therapeutic strategies.
Utility and Applications of Orthotopic Models of Human Non‐Small Cell Lung Cancer (NSCLC) for the Evaluation of Novel and Emerging Cancer Therapeutics

Lung cancer is a leading cause of cancer deaths worldwide. Despite advances in chemotherapy, radiation therapy, and surgery, lung cancer continues to have a low 5‐year survival rate, highlighting a dire need for more effective means of prevention, diagnosis, prognosis, and treatment. Mouse models that recapitulate the clinical features of advanced human lung cancer are critical for testing novel therapeutic approaches. This unit describes a highly reproducible, easy‐to‐establish orthotopic murine model of lung cancer, provides methods for in vivo imaging and monitoring of tumor growth, and discusses the usefulness of this model for translational lung cancer research and the development of therapeutic strategies. Curr. Protoc. Pharmacol. 62:14.27. 1‐14.27. 17. © 2013 by John Wiley & Sons, Inc.
Preliminary validation of an observational pain checklist for persons with cognitive impairments and inability to communicate verbally

To obtain a preliminary validation of the Non‐Communicating Children's Pain Checklist for individuals with an inability to communicate verbally, 32 caregivers of individuals with cognitive impairments aged 3 to 44 years retrospectively completed the Non‐Communicating Children's Pain Checklist and rated item usefulness (0 to 10). In the second part of the study 33 caregivers completed the Checklist after two painful (e.g. burns, falls, surgery), one distressful (e.g. unwanted grooming, feared animal/noise), and one calm event (e.g. watching television). Checklist scores did not correlate with the age, sex, or physical limitations of individuals with an inability to communicate verbally. In the first part of the study Cronbach's alpha was 0.66; all mean usefulness ratings exceeded 5 out of 10. In the second part of the study after four items were removed, Cronbach's alpha was 0.79. Checklist scores during pain correlated with numerical ratings of pain intensity did not differ between the two pain events, and differed significantly from calm scores. Differences in Checklist scores during pain and distress were found for two subscales. The Checklist exhibits internal consistency, and preliminary evidence suggests it can detect pain and is reliable over time.
Confirmatory factor analysis of the Arthritis Impact Measurement Scales 2 short form in patients with rheumatoid arthritis.

OBJECTIVE To examine the factorial validity of the short form Arthritis Impact Measurement Scales 2 (AIMS2-SF) in patients with rheumatoid arthritis (RA). METHODS Data were from a sample of 279 patients with active RA who completed the long form AIMS2 before starting treatment with tumor necrosis factor alpha-blocking agents. Confirmatory factor analyses were conducted to test and compare the fit of the currently used theoretical measurement model of the AIMS2-SF, originally suggested for the long form AIMS2, and 2 alternative models based on previous exploratory research. RESULTS A model with the physical dimension divided into upper and lower body limitations was superior to the current model, and both models provided a clearly better fit than a model without a separate symptom dimension. Under the restrictive assumption of uncorrelated error terms, none of the models achieved a consistent and acceptable fit as judged by several goodness-of-fit indices. Allowing error covariances between 6 pairs of items within the same dimension resulted in an improved and acceptable fit of both the current model and the model with a separate upper and lower body component. CONCLUSION This study generally supports the factorial validity of the AIMS2-SF and suggests the use of separate scores for upper and lower body limitations. Further research is needed to resolve the issue of high error correlations associated with particular items.
Mass Spectrometric Analysis of Phosphoserine Residues Conserved in the Catalytic Domain of Membrane-Bound Guanylyl Cyclase from the Sea Urchin Spermatozoa

Abstract We have developed a large-scale purification method of the phosphorylated form (131 kDa) of membrane-bound guanylyl cyclase (mGC) from Hemicentrotus pulcherrimus spermatozoa. The purified mGC contained 26.0 ± 1.3 moles of phosphate/mol enzyme (mean ± S.D., n = 6). Phosphorylated peptides were isolated from the trypsin digest of the carboxymethylated H. pulcherrimus sperm mGC by affinity chromatography on a Chelating Sepharose Fast Flow column, and the peptides were then subjected to mass spectrometric analysis and determination of phosphoserines, after the conversion of phosphoserines to Sethylcysteines by amino acid analysis. Based on the observed mass number and the content of phosphoserine, serine residues at positions 561, 565, 652, 722, 740, 755, 894, 897, 914, 918, 927, 930, 951, and 985, in addition to two residues among those at positions 666, 670, and 671, were shown to be phosphorylated. They are all located in the intracellular region (kinase-like and catalytic domains). Notably, serine residues at positions 894, 918, 927, and 930, that are conserved in the sequence of mammalian mGCs and medaka fish-eye-specific mGCs, are phosphorylated in the sea urchin sperm mGC.
Modulation of Cell Death Pathways by Hepatitis C Virus Proteins in Huh7.5 Hepatoma Cells

The hepatitis C virus (HCV) causes chronic liver disease leading to fibrosis, cirrhosis, and hepatocellular carcinoma. HCV infection triggers various types of cell death which contribute to hepatitis C pathogenesis. However, much is still unknown about the impact of viral proteins on them. Here we present the results of simultaneous immunocytochemical analysis of markers of apoptosis, autophagy, and necrosis in Huh7.5 cells expressing individual HCV proteins or their combinations, or harboring the virus replicon. Stable replication of the full-length HCV genome or transient expression of its core, Е1/Е2, NS3 and NS5B led to the death of 20–47% cells, 72 h posttransfection, whereas the expression of the NS4A/B, NS5A or NS3-NS5B polyprotein did not affect cell viability. HCV proteins caused different impacts on the activation of caspases-3, -8 and -9 and on DNA fragmentation. The structural core and E1/E2 proteins promoted apoptosis, whereas non-structural NS4A/B, NS5A, NS5B suppressed apoptosis by blocking various members of the caspase cascade. The majority of HCV proteins also enhanced autophagy, while NS5A also induced necrosis. As a result, the death of Huh7.5 cells expressing the HCV core was induced via apoptosis, the cells expressing NS3 and NS5B via autophagy-associated death, and the cells expressing E1/E2 glycoproteins or harboring HCV the replicon via both apoptosis and autophagy.
Outcomes of Cochlear Implantation in Adults with Asymmetric Hearing Loss

Objective To analyze speech recognition outcomes in adult cochlear implant recipients who have asymmetric sensorineural hearing loss between the two ears. Study Design Retrospective cohort study of 35 adults with asymmetric hearing loss. Preoperative unaided pure-tone averages (PTA), and pre- and post-op (6 and 12 mo) aided Consonant Nucleus Consonant (CNC) words and sentence recognition scores were obtained for ears in isolation (opposite ear plugged). Patients were categorized according to the PTA of the implanted and contralateral ears as (a) moderate-severe, (b) moderate-profound, and (c) severe-profound. Setting A single tertiary care center. Patients Adults with asymmetric PTA implanted unilaterally at our institution. Intervention Cochlear implantation with devices approved by the U.S. Food and Drug Administration. Main Outcome Measure(s) Post-implantation word, phoneme, and sentence recognition in the cochlear implant alone testing condition. Results Patients who were implanted in the worse-hearing ear (n = 21) performed significantly better on CNC words and phonemes at 6 and 12 months than patients who were implanted in the better-hearing ear (n = 14). Patients with the worse ear implanted also obtained 6 to 12% higher sentence recognition scores than the group received an implant in their better ear, although this difference is not statistically significant (p = 0.06 at 6 mo; p = 0.1 at 12 mo). Conclusion Patients with asymmetrical hearing loss who were implanted in the worse-hearing ear achieved 15% greater CNC word scores and 6 to 12% greater sentence scores than patients implanted in the better-hearing ear in the first year after surgery. Our results provide further support for clinicians to use caution if considering implanting the better-hearing ear in patients with asymmetric hearing loss.
Methylprednisolone injection via the portal vein suppresses inflammation in acute liver failure induced in rats by lipopolysaccharide and d‐galactosamine

Background: We have reported that hepatic arterial steroid injection is an effective therapy to rescue patients from fulminant or severe acute hepatic failure. We speculate that a high concentration of steroid suppresses inflammatory processes in the liver directly by restraining activated inflammatory cells, including macrophages. To analyse the detailed mechanism, steroid injection via the portal vein was performed in an experimental model of liver damage.
Comparison of an Industry-Derived LCx Chlamydia pneumoniae PCR Research Kit to In-House Assays Performed in Five Laboratories

ABSTRACT In a multicenter comparison of PCR assays utilizing 120 quantitated samples of 16 Chlamydia pneumoniae isolates, an LCx research-use-only (RUO) PCR developed by Abbott Laboratories demonstrated 100% sensitivity on 48 samples with >1 copy of DNA per μl of specimen. The sensitivities of five in-house PCR assays ranged from 54 to 94% for the same samples. All six assays showed decreased sensitivities as the DNA copy numbers of the samples decreased. Overall, sensitivities ranged from 68% for the LCx PCR assay to 29% for one of the in-house tests. The LCx RUO PCR and three of the five in-house PCR tests reported no false positives with the 24 negative samples. Increasing the number of replicates tested increased the sensitivities of all of the assays, including the LCx PCR. The LCx RUO assay showed high reproducibility for a single technologist and between technologists, with a kappa agreement of 0.77. The within-center agreements of the five in-house PCR tests varied from 0.19 to 0.74 on two challenges of 60 specimens 1 month apart. The LCx C. pneumoniae RUO PCR shows excellent potential for use in clinical studies, which could enable standardization of results in the field.
Spontaneous testicular atrophy occurs despite normal spermatogonial proliferation in a Tp53 knockout rat

The tumor suppressor protein p53 (TP53) has many functions in cell cycle regulation, apoptosis, and DNA damage repair and is also involved in spermatogenesis in the mouse. To evaluate the role of p53 in spermatogenesis in the rat, we characterized testis biology in adult males of a novel p53 knockout rat (SD‐Tp53tm1sage). p53 knockout rats exhibited variable levels of testicular atrophy, including significantly decreased testis weights, atrophic seminiferous tubules, decreased seminiferous tubule diameter, and elevated spermatocyte TUNEL labeling rates, indicating a dysfunction in spermatogenesis. Phosphorylated histone H2AX protein levels and distribution were similar in the non‐atrophic seminiferous tubules of both genotypes, showing evidence of pre‐synaptic DNA double‐strand breaks in leptotene and zygotene spermatocytes, preceding cell death in p53 knockout rat testes. Quantification of the spermatogonial stem cell (SSC) proliferation rate with bromodeoxyuridine (BrdU) labeling, in addition to staining with the undifferentiated type A spermatogonial marker GDNF family receptor alpha‐1 (GFRA1), indicated that the undifferentiated spermatogonial population was normal in p53 knockout rats. Following exposure to 0.5 or 5 Gy X‐ray, p53 knockout rats exhibited no germ cell apoptotic response beyond their unirradiated phenotype, while germ cell death in wild‐type rat testes was elevated to a level similar to the unexposed p53 knockout rats. This study indicates that seminiferous tubule atrophy occurs following spontaneous, elevated levels of spermatocyte death in the p53 knockout rat. This phenomenon is variable across individual rats. These results indicate a critical role for p53 in rat germ cell survival and spermatogenesis.
Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC.

Hepatitis A virus (HAV) is distinguished from other picornaviruses by its slow and relatively poor, noncytopathic growth in cultures of mammalian cells. The 2C and 2BC proteins of HAV have been implicated in the determination of virus growth in cultured cells. The homologous proteins from other picornaviruses, such as poliovirus, have been demonstrated to exhibit multiple activities, such as RNA binding, nucleotide binding and NTPase, and membrane binding and reorganization. At least some of these activities are required for viral RNA replication. We report here that HAV 2C and 2BC proteins, like their poliovirus counterparts, can induce rearrangement of intracellular membranes and directly or indirectly interact with membranes. Therefore, the inefficient replication properties of HAV are not consequences of the inherent ability of 2C (2BC) to interact with membranes. The effect of 2C (2BC) protein sequences derived from a cell culture-adapted (cc) strain of HAV was compared with that of corresponding protein sequences from either a wild-type (wt) strain of HAV or a faster replicating cytopathic (cp) strain. The analysis demonstrated that mutations acquired in wt virus during adaptation to cell culture do not change dramatically either the ability of these proteins to associate with membranes and induce membrane alterations or the specific architecture of the induced membrane structures. On the other hand, 2C, but not 2BC, protein from the cp strain of HAV induced different membrane structures.
A long period grating liquid level sensor

Liquid level sensing is a requirement in many applications in which knowledge of the volume of a liquid is necessary, for example, in fuel storage systems and chemical processing. A wide range of liquid level sensing techniques have been reported based around mechanical, electrical, and optical methods. Electrical liquid level sensors are widely employed, but their applicability is compromised if the liquid to be monitored is conductive or if the environment is potentially explosive. Optical fibre sensors offer well-established advantages under these conditions. The optical fibre is a dielectric, and thus is non-conducting, and the sensor may be configured such the light is confined within the fibre, reducing the likelihood of ignition of a flammable environment. In this paper a liquid level sensor is demonstrated by exploiting the refractive index sensitivity of long period gratings (LPGs) to measure the length of the fibre immersed in a liquid.