Miracle-dz/UniFAR-FTUs huggingface dataset:
Overcoming antimicrobial resistance: profile of a new ketolide antibacterial, telithromycin.

Antimicrobial resistance amongst common respiratory pathogens has increased worldwide at an alarming rate and now threatens the clinical usefulness of a number of antibacterial agents. A major concern is the selection of resistance in the community, which tends to parallel the (often inappropriate) overuse of such agents. Such problems highlight the need for new antibacterial agents that retain activity against bacterial strains resistant to existing agents, and have a low potential to select for resistance or induce cross-resistance. Telithromycin is the first of a new family of antibacterials--the ketolides--and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs). Numerous in vitro studies confirm the potent activity of telithromycin against pathogens commonly implicated in community-acquired RTIs, irrespective of their beta-lactam, macrolide or fluoroquinolone susceptibility. Against pneumococci, for example, MICs were < or = 1 mg/L irrespective of penicillin susceptibility, with > or = 98% of macrolide-resistant strains inhibited at < or = 0.5 mg/L, regardless of the underlying mechanism of resistance (including erm, mef and ribosomal L4 mutations). Against Haemophilus influenzae and Moraxella catarrhalis, including beta-lactamase-positive strains, telithromycin is at least as potent as azithromycin. In addition, telithromycin has a very low potential for selection of resistant isolates or induction of cross-resistance. Importantly, and unlike existing macrolides, telithromycin does not induce MLS(B) resistance, a finding explained by the presence of the innovative 3-keto group in its chemical structure. Telithromycin therefore represents an important addition to the therapeutic armamentarium in an era of increasing antimicrobial resistance, with an expected low likelihood of the development of resistance in clinical use.
Five-node biopsy of the axilla: an alternative to axillary dissection of levels I-II in operable breast cancer.

BACKGROUND Axillary clearance of patients with early breast cancer is accompanied by a high risk of arm morbidity. Less invasive ways to establish the axillary nodal status are therefore of interest, especially in women with low risk of nodal metastases. METHODS Four hundred and fifteen breast cancer patients (clinical stage T(0-3) N(0-1) M(0)) were operated in the axilla with a five-node biopsy followed in the same operation by a further dissection of levels I-II of the axilla in order to evaluate the accuracy of the five-node node biopsy compared with level I-II dissection. RESULTS In all patients the sensitivity of the five-node biopsy was 97.3% with a negative predictive value of 98.5% and a negative likelihood ratio of 0.027. Among cases detected by screening (n=204) and those clinically detected (n=197) the sensitivity of the five-node biopsy was 95.8% and 97.9% respectively, with negative predictive values of 98.7% and 98.0% and negative likelihood ratios of 0.042 and 0.021 respectively. CONCLUSION Five-node biopsy of the axilla has good accuracy for correctly staging the axilla in both clinically and screening-detected cases. Five-node biopsy is an alternative to axillary clearance and sentinel node biopsy in patients with operable breast cancer.
Analysis of Magnetic Shielding Effects for Thin-Film Inductors

Issues related to magnetic shielding effects are discussed for inner-coil type thin-film inductors with closed magnetic circuits. The relationship between magnetic shielding effects, mutual inductance, and proximity effects are investigated using the finite integral equation method. The results show that obvious shielding effects occur in the inductors and that the mutual inductance is not influenced by the shielding effects.
Fuzzy hyperbolic H∞ filter design for a class of nonlinear discrete-time dynamic systems

This paper studies fuzzy hyperbolic H∞ filter for signal estimation of nonlinear discrete-time systems with state time delay. The fuzzy hyperbolic model (FHM) can be used to establish models for certain unknown complex systems. Furthermore, the main advantage of using the FHM over the Takagi-Sugeno fuzzy model are that no premise structure identification is needed and no completeness design of premise variables space is needed. Also an FHM is a kind of valid global description and nonlinear model in nature. First, FHM is proposed to represent the state-space model for nonlinear discrete-time systems. Next, we design a stable fuzzy H∞ filter based on the FHM, which assures asymptotic stability and a prescribed H∞ index for the filtering error system. A sufficient condition for the existence o such a filter is established through seeking the feasible solutions of a linear mat ix inequality (LMI). Simulation example is provided to illustrate the design procedure of the proposed method.
Insulin degludec/insulin aspart produces a dose‐proportional glucose‐lowering effect in subjects with type 1 diabetes mellitus

To evaluate the pharmacodynamic dose–response relationship of insulin degludec/insulin aspart (IDegAsp), a novel, soluble co‐formulation of the ultra‐long‐acting basal insulin, insulin degludec (IDeg), with the rapid‐acting prandial insulin (IAsp), across different doses in patients with type 1 diabetes (T1DM).
Blood pressure control and risk of stroke in untreated and treated hypertensive patients screened from clinical practice: results of the ForLife study

Objectives Stroke has a high prevalence in Italy, and is the third cause of death worldwide. Hypertension is the most important risk factor contributing to the risk of stroke. The aims of this study were to assess the risk of stroke in a large cohort of hypertensive patients, and to determine the percentage with controlled blood pressure, to establish the contribution of this factor to the risk of stroke. Methods The study involved general practitioners to make it representative of clinical practice. They were asked to recruit 10 consecutive hypertensive patients, treated and untreated. Data collection included a full medical history and a physical examination. The 10-year absolute risk of stroke was calculated by an algorithm derived, with some modification, from the Framingham study. Results Most untreated hypertensive patients were grade 1 or 2. In treated hypertensive patients, controlled blood pressure values occurred in 18.4%, the percentage being less in patients with left ventricular hypertrophy and diabetes. In diabetic hypertensive patients the more stringent blood pressure control recommended by the guidelines was achieved in only 3.0% of cases. The average 10-year stroke risk was 17%, a greater risk being more common in elderly patients, diabetic individuals and in those with left ventricular hypertrophy. Conclusion Current antihypertensive treatment achieved blood pressure control in a limited fraction of hypertensive patients seen by general practitioners. The risk of stroke in hypertensive patients is by no means negligible, which emphasizes the need for more attention to be paid to the prevention of this disease.
The Frustrations and Benefits of Mobile Device Usage in the Home when Co-Present with Family Members

Mobile devices have begun to raise questions around the potential for overuse when in the presence of family or friends. As such, we conducted a diary and interview study to understand how people use mobile devices in the presence of others at home, and how this shapes their behavior and household dynamics. Results show that family members become frustrated when others do non-urgent activities on their phones in the presence of others. Yet people often guess at what others are doing because of the personal nature of mobile devices. In some cases, people developed strategies to provide a greater sense of activity awareness to combat the problem. Mobile phone usage was sometimes perceived as beneficial by providing a mechanism for needed disengagement from family members. These findings suggest several opportunities for redesigning mobile device software to mitigate emergent frustrations, and open up new opportunities for nurturing social interactions among family members.
Holmium laser enucleation versus transurethral resection of the prostate.

INTRODUCTION This was a prospective, randomized clinical trial to compare the safety, efficacy, and medium-term durability of holmium laser enucleation of the prostate (HoLEP) combined with mechanical morcellation versus standard transurethral resection of the prostate (TURP) for the surgical treatment of patients with bladder outlet obstruction due to benign prostatic hyperplasia (BPH). The patients had prostates that were greater than 30 g and less than 100 g and were followed for 1 year. PATIENTS AND METHODS From April 2008 to December 2009, 80 consecutive patients with lower urinary tract obstruction (LUTS) due to BPH were randomized to either surgical treatment with HoLEP (group 1, n = 40) or standard TURP (group 2, n = 40). Preoperative assessments included American Urological Association (AUA) symptom score, serum prostate-specific antigen (PSA), post-voiding residual (PVR) urine volume, transrectal ultrasound (TRUS), and urodynamic studies. Perioperative parameters included total operating time, resected tissue weight, hemoglobin loss, presence or absence of blood transfusion, time of catheter removal, and duration of hospital stay. Postoperative evaluations were conducted at 1, 6, and 12 months. RESULTS Patients in the HoLEP group had shorter catheterization times and hospital stays than patients in the TURP group. There was no significant difference in operating times between the two groups. Mean hemoglobin loss was lower in the HoLEP group (1.8 ± 1.3 g/dL versus 2.9 ± 1.5 g/dL). There was a significantly greater improvement from baseline AUA symptom scores and PVR urine volumes in the HoLEP group versus the TURP group, at all postoperative assessments. Postoperatively, 25% of patients in group 1 (HoLEP) and 20% of patients in group 2 (TURP) had irritative voiding symptoms. Urethral stricture occurred in three cases (one case in the HoLEP group and two cases in the TURP group). CONCLUSION HoLEP proved to be a safe and highly effective technique for surgical treatment of bladder outlet obstruction due to BPH.
Prevalence, Risk Factors and Diagnostic Accuracy of COPD Among Smokers in Primary Care

Abstract The prevalence of COPD is high, and most cases remain undiagnosed. In contrast, some patients labeled and treated as COPD do not have spirometric confirmation. Our objective was to determine the prevalence of COPD among smokers aged 45 years or older and investigate the accuracy of diagnosis of COPD in primary care. A population-based, epidemiological study was conducted in a primary care centre among subjects older than 45 years with a history of smoking. The participants underwent a clinical questionnaire and spirometry with bronchodilator test. Additionally, participants with newly diagnosed COPD, defined as postbronchodilator FEV1/FVC<0.7, underwent 4-week treatment with formoterol and budesonide to rule out reversible airflow obstruction. A total of 1,738 individuals (84.4% male) with a mean age of 59.9 years were included. The prevalence of COPD was 24.3% (95%, CI 22.3–26.4), with an overall underdiagnosis of 56.7%. Patients with COPD were older, more frequently male, with a lower body mass index, a longer history of smoking, lower educational level, previous occupational exposure, and more cardiovascular co-morbidity (all p < 0.001). After 4 weeks of treatment, 16% of initially obstructed patients had normal spirometry; in addition, 15.6% of individuals with a diagnosis of COPD did not have airflow obstruction. One out of four smokers 45 years or older presenting in primary care have airflow obstruction, mostly undiagnosed. However, among those with an initial diagnosis of COPD up to 16% will normalise spirometry after 4 weeks of treatment. There is also a significant number of individuals misdiagnosed with COPD.
Lipoprotein[a] as a risk factor for preclinical atherosclerosis.

Elevated mean levels of lipoprotein[a] (Lp[a]) have been associated with symptomatic cardiovascular diseases such as clinically manifest myocardial infarction (MI), coronary artery disease, restenosis of coronary artery vein grafts after bypass, and a family history of MI. Associations of Lp[a] with arterial wall thickening in asymptomatic individuals previously have not been addressed and are evaluated in this report among participants of the Atherosclerosis Risk in Communities (ARIC) Study. Intima-media wall thickening in the extracranial carotid arteries was assessed noninvasively with B-mode ultrasonography; Lp[a] was measured as its total protein component. Individuals with wall thickening > or = 90th percentile of the population maximum far-wall thickness were pair matched to participants < 75th percentile of wall thickness by race, gender, center, 10-year age group, and time of examination. These selection criteria yielded 492 matched pairs, with 395 white pairs and 97 black pairs. The mean Lp[a] protein level for all black participants was 174.6 micrograms/mL compared with 77.8 micrograms/mL for whites. Conditional logistic regression analysis for the association of Lp[a] with case-control status yielded a statistically significant prevalence odds ratio (OR) estimate of 1.49, based on a 1-SD difference in Lp[a] protein, after adjusting for age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fibrinogen, hypertension, and cigarette smoking. None of these risk factors significantly altered the OR, in agreement with reports that Lp[a] is unaffected by environmental influences. In addition, no differential effect of Lp[a] protein on case-control status (effect modification) was observed by race, gender, low-density lipoprotein cholesterol, or fibrinogen in this population. (ABSTRACT TRUNCATED AT 250 WORDS)
The Vehicle Routing Problem with Stochastic Travel Times

This paper considers vehicle routing problems (VRPs) with stochastic service and travel times, in which vehicles incur a penalty proportional to the duration of their route in excess of a preset constant. Three mathematical programming models are presented: a chance constrained model, a three-index simple recourse model and a two-index recourse model. A general branch and cut algorithm for the three models is described. Computational results indicate that moderate size problems can be solved to optimality.
Differential Roles of T‐cell Subsets in Regulation of Ultraviolet Radiation Induced Cutaneous Photocarcinogenesis

Ultraviolet (UV) radiation, in particular the midwavelength range (UVB; 290–320 nm), is one of the most significant risk factors for the development of nonmelanoma skin cancer. UVB radiation‐induced immunosuppression, which occurs in both humans and laboratory animals, contributes to their pathogenesis. However, there are conflicting reports on the relative role of CD4+ and CD8+ T cells in UVB induced skin cancer. The purpose of this study was to delineate the contribution of these two cell subpopulations to UVB induced immunosuppression and tumor development using C3H/HeN (WT), CD4 knockout (CD4−/−) and CD8 knockout (CD8−/−) mice. We observed that UVB induced skin carcinogenesis was retarded in terms of number of tumors per group, tumor volume and percentage of mice with tumors, in mice deficient in CD4+ T cells compared with wild‐type mice, whereas significantly greater (P < 0.05) numbers of tumors occurred in CD8−/− mice. These results indicate that, CD4+ T cells promote tumor development while CD8+ T cells have the opposite effect. Further, we found that CD4+ T cells from tumor‐bearing mice produced interleukin (IL)‐4, IL‐10, and IL‐17 whereas CD8+ T cells produced interferon‐γ. Manipulation of T‐cell subpopulations that are induced by UVB radiation could be a means of preventing skin cancers caused by this agent.
Body location and tail regeneration effects on osteoderms morphology—are they useful tools for systematic, paleontology, and skeletochronology in diploglossine lizards (squamata, anguidae)?

Although diploglossine osteoderms were mentioned in several systematic and paleontological studies, their morphological variability in single specimens or within species remains paradoxically undescribed. This is mainly the effect of the lack of attention paid hitherto to the morphological and histological characteristics of the tail osteoderms. This study demonstrated that a previously undescribed morphological variability exists in these osteoderms, especially in those resulting from tail regeneration. Indeed, regenerated osteoderms display a plesiomorphic anguid morphology that was previously considered to be absent in Diploglossinae. We also provide the first histological description of diploglossine osteoderms and new information about the obvious differences in growth dynamic between regenerated and nonregenerated osteoderms. These new data raise questions about the usefulness of diploglossine osteoderms in systematic, paleontological, and skeletochronological studies. Our study shows that the exact position on the trunk or on a regenerated or nonregenerated tail of each studied osteoderm must be known in order to avoid mistakes related to their important interspecies and intraspecies variability. J. Morphol. 276:1333–1344, 2015. © 2015 Wiley Periodicals, Inc.
Interleukin‐13 in the skin and interferon‐γ in the liver are key players in immune protection in human schistosomiasis

Summary: Immunity against schistosomes includes anti‐infection immunity, which is mainly active against invading larvae in the skin, and anti‐disease immunity, which controls abnormal fibrosis in tissues invaded by schistosome eggs. Anti‐infection immunity is T‐helper 2 (Th2) cell‐dependent and is controlled by a major genetic locus that is located near the Th2 cytokine locus on chromosome 5q31‐q33. Mutations in the gene encoding interleukin (IL)‐13 that decrease or increase IL‐13 production account, at least in part, for that genetic control. In contrast, protection against hepatic fibrosis is dependent on interferon (IFN)‐γ and is controlled by a major genetic locus that is located on 6q23, near the gene encoding the IFN‐γ receptor β chain. Mutations that modulate IFN‐γ gene transcription are associated with different susceptibility to disease. These data indicate that IL‐13 in the skin and IFN‐γ in the liver are key players in protective immunity against schistosomes. These roles relate to the high anti‐fibrogenic activities of IFN‐γ and to the unique ability of IL‐13 in Th2 priming in the skin and in the mobilization of eosinophils in tissues. The coexistence of strong IFN‐γ and IL‐13‐mediated immune responses in the same subject may involve the compartmentalization of the anti‐schistosome immune response between the skin and the liver.
Investigations of monolayers by fluorescence microscopy

The technique of fluorescence microscopy enables imaging of coexisting domains in Langmuir monolayers which have been doped with a small amount of a fluorescent probe. It is also possible to image surface aggregates formed by labeled proteins interacting with phosholipid monolayers. The method has provided information concerning phase behavior and structure of monolayers and proven useful in the study of monolayers as model systems of membrance processes. © 1994 Wiley‐Liss, Inc.
TGF-β Signal Transduction in Corneal Wound Healing as a Therapeutic Target

Abstract This article reviews recent progress in research on the role of Smad signaling in corneal wound healing. Smad2 and Smad3 are key signaling molecules downstream of the cell surface receptor of transforming growth factor-β (TGF-β) or activin. On ligand binding to the receptor, Smads2/3 undergo phosphorylation, form complexes with Smad4, and thence convey signaling. TGF-β isoforms have been detected in corneal epithelium and are also deposited in wounded stroma, suggesting their participation in the wound-healing process in corneal tissue. Human or mouse uninjured healthy corneal epithelium shows nuclear accumulation of Smads3/4, indicating active Smad signaling in this tissue. Migrating corneal epithelium lacks nuclear Smad accumulation with up-regulation of Smad7, but p38MAPK is activated. Organ-culture experiments show that p38MAPK activation depends on endogenous TGF-β and that activation of p38MAPK results in cell proliferation cessation with a reduction of Erk activation and acceleration of cell migration in healing corneal epithelium. These findings indicate that during healing of corneal epithelial defects, endogenous TGF-β activates p38MAPK for cell migration and suppression of cell proliferation and up-regulates Smad7 for inhibition of Smad2 and Smad3 signaling, resulting in rapid initial resurfacing of the epithelium. Such involvement of p38MAPK in cell migration has been reported in many cell types and observed in keratocyte culture. Possible benefits of preserving non-Smad cascades in treating problems in corneal wound healing by manipulating TGF-β signals have been suggested.
Ensemble of convolutional neural networks for classification of breast microcalcification from mammograms

Human level recall performance in detecting breast cancer considering microcalcifications from mammograms has a recall value between 74.5% and 92.3%. In this research, we approach to breast microcalcification classification problem using convolutional neural networks along with various preprocessing methods such as contrast scaling, dilation, cropping etc. and decision fusion using ensemble of networks. Various experiments on Digital Database for Screening Mammography dataset showed that preprocessing poses great importance on the classification performance. The stand-alone models using the dilation and cropping preprocessing techniques achieved the highest recall value of 91.3%. The ensembles of the stand-alone models surpass this recall value and a 97.3% value of recall is achieved. The ensemble having the highest F1 Score (harmonic mean of precision and recall), which is 94.5%, has a recall value of 94.0% and a precision value of 95.0%. This recall is still above human level performance and the models achieve competitive results in terms of accuracy, precision, recall and F1 score measures.
A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5

The yeast ABC transporter Pdr5 plays a major role in drug resistance against a large number of structurally unrelated compounds. Although Pdr5 has been extensively studied, many important aspects regarding its molecular mechanisms remain unresolved. For example, a striking degeneration of conserved amino acid residues exists in the nucleotide binding domains (NBDs), but their functional relevance is unknown. Here, we performed in vivo and in vitro experiments to address the functional asymmetry of NBDs. It became evident by ATPase activity and drug transport studies that catalysis at only one of the two NBD composite sites is crucial for protein function. Furthermore, mutations of the proposed “catalytic carboxylate” (E1036) and the “catalytic dyad histidine” (H1068) were characterized. Although a mutation of the glutamate abolished ATPase activity and substrate transport, mutation of H1068 had no influence on ATP consumption. However, the H1068A mutation abolished rhodamine transport in vivo and in vitro, while leaving the transport of other substrates unaffected. By contrast to mammalian P-glycoprotein (P-gp), the ATPase activity of yeast Pdr5 is not stimulated by the addition of substrates, indicating that Pdr5 is an uncoupled ABC transporter that constantly hydrolyses ATP to ensure active substrate transport. Taken together, our data provide important insights into the molecular mechanism of Pdr5 and suggest that not solely the transmembrane domains dictate substrate selection.