Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantifying the added value of BNP in suspected heart failure in general practice: an individual patient data meta-analysis

Background Diagnosing early stages of heart failure with mild symptoms is difficult. B-type natriuretic peptide (BNP) has promising biochemical test characteristics, but its diagnostic yield on top of readily available diagnostic knowledge has not been sufficiently quantified in early stages of heart failure. Objectives To quantify the added diagnostic value of BNP for the diagnosis of heart failure in a population relevant to GPs and validate the findings in an independent primary care patient population. Design Individual patient data meta-analysis followed by external validation. The additional diagnostic yield of BNP above standard clinical information was compared with ECG and chest x-ray results. Patients and methods Derivation was performed on two existing datasets from Hillingdon (n=127) and Rotterdam (n=149) while the UK Natriuretic Peptide Study (n=306) served as validation dataset. Included were patients with suspected heart failure referred to a rapid-access diagnostic outpatient clinic. Case definition was according to the ESC guideline. Logistic regression was used to assess discrimination (with the c-statistic) and calibration. Results Of the 276 patients in the derivation set, 30.8% had heart failure. The clinical model (encompassing age, gender, known coronary artery disease, diabetes, orthopnoea, elevated jugular venous pressure, crackles, pitting oedema and S3 gallop) had a c-statistic of 0.79. Adding, respectively, chest x-ray results, ECG results or BNP to the clinical model increased the c-statistic to 0.84, 0.85 and 0.92. Neither ECG nor chest x-ray added significantly to the ‘clinical plus BNP’ model. All models had adequate calibration. The ‘clinical plus BNP’ diagnostic model performed well in an independent cohort with comparable inclusion criteria (c-statistic=0.91 and adequate calibration). Using separate cut-off values for ‘ruling in’ (typically implying referral for echocardiography) and for ‘ruling out’ heart failure—creating a grey zone—resulted in insufficient proportions of patients with a correct diagnosis. Conclusion BNP has considerable diagnostic value in addition to signs and symptoms in patients suspected of heart failure in primary care. However, using BNP alone with the currently recommended cut-off levels is not sufficient to make a reliable diagnosis of heart failure.
The physics of Cu pillar bump interconnect under electromigration stress testing

The industry saw the transition of flip chip technology from lead free solder system to Cu pillar bump a few years ago. The risk of fail location under electromigration (EM) shifts from the solder/UBM interface of the standard solder bump to the solder joint of the Cu pillar solder joint. This study investigated the performance of the Cu pillar solder interconnect under current stress testing and temperature acceleration. The EM stress test of Cu pillar bumps interconnect was designed and implemented comparing the bump solder tips joined with OSP (organic solderability preservative)-Cu (the OSP-Cu bump) substrate and ENEPIG (electroless Ni(P)/electroless Pd/immersion Au)-Cu (the ENEPIG-Cu bump) substrate. The bumps with different solder volumes, 20 μm and 50 μm in height, were investigated for EM performance comparison. The EM testing was conducted at current density 7 kA/cm2 under various temperatures of 125 °C, 135 °C and 150 °C. The EM duration time of Cu pillar bump joints were estimated for testing up to 10000 hours. The joint with smaller solder volume tends to exhibit better EM life. The experimental results showed that the Cu pillar bumps on OSP-Cu performed superior to that on ENEPIG-Cu. The cross sectional microstructure analysis indicates that the intermetallic compound (IMC) formed are mainly Cu6Sn5 and Cu3Sn for the Cu pillar bump joint on OSP-Cu substrate, while (Au, Pd)Sn4 was also detected for the ENEPIG-Cu substrate. The failure analysis of the failed joints indicated that the failure behavior closely related to the volume of IMC formed and the IMC structure within the Cu pillar joint.
Interpersonal Psychotherapy as Augmentation Treatment in Depressed Elderly Responding Poorly to Antidepressant Drugs: A Case Series

Background: Medication is often the first choice in the treatment of depression, even though large numbers of depressed patients do not respond to antidepressant drugs or fail to achieve symptom remission or recovery. Generally, other drugs, rather than other therapeutic approaches such as psychotherapy, are used as augmentation treatment. This applies in particular to elderly patients. The aim of this work is to assess whether augmentation with interpersonal psychotherapy (IPT) can bring about symptom remission in depressed elderly responding poorly to medication. Method: Five cognitively intact patients aged over 60 and suffering from major depression were first treated for 6 weeks with a selective serotonin reuptake inhibitor compound. Owing to poor outcome, IPT was added to the treatment. IPT is a brief psychotherapy addressing the interpersonal problems linked to depression, and has been modified for use with elderly patients. Results: All patients achieved symptom remission after a cycle of psychotherapy lasting a minimum of 16 and a maximum of 20 weekly sessions. Conclusions: The methodological limitations of this open study do not allow us to generalize from the positive outcomes. Further studies might confirm these initial observations and establish whether an equally satisfactory therapeutic response can be attained if medication is discontinued after the start of psychotherapy.
Culture in whales and dolphins

Studies of animal culture have not normally included a consideration of cetaceans. However, with several long-term field studies now maturing, this situation should change. Animal culture is generally studied by either investigating transmission mechanisms experimentally, or observing patterns of behavioural variation in wild populations that cannot be explained by either genetic or environmental factors. Taking this second, ethnographic, approach, there is good evidence for cultural transmission in several cetacean species. However, only the bottlenose dolphin (Tursiops) has been shown experimentally to possess sophisticated social learning abilities, including vocal and motor imitation; other species have not been studied. There is observational evidence for imitation and teaching in killer whales. For cetaceans and other large, wide-ranging animals, excessive reliance on experimental data for evidence of culture is not productive; we favour the ethnographic approach. The complex and stable vocal and behavioural cultures of sympatric groups of killer whales (Orcinus orca) appear to have no parallel outside humans, and represent an independent evolution of cultural faculties. The wide movements of cetaceans, the greater variability of the marine environment over large temporal scales relative to that on land, and the stable matrilineal social groups of some species are potentially important factors in the evolution of cetacean culture. There have been suggestions of gene-culture coevolution in cetaceans, and culture may be implicated in some unusual behavioural and life-history traits of whales and dolphins. We hope to stimulate discussion and research on culture in these animals.
Molecular mechanisms and the conflict between courtship and aggression in three‐spined sticklebacks

In nature, animals often face conflicting demands. For example, breeding males must attract a mate but at the same time be ready to defend against rivals. The molecular mechanisms by which the brain resolves behavioural trade‐offs are largely unknown. In this study, we compared the brain transcriptional responses of territorial male three‐spined sticklebacks to a mating opportunity with a female and to a territorial challenge by a rival male. We focused on the diencephalon and the cerebellum, two regions of the brain implicated in courtship and aggression. There was a set of genes that were differentially expressed in response to both a courtship opportunity and a territorial challenge. Closer inspection of the direction of regulation revealed that genes that were downregulated in response to a courtship opportunity were upregulated in response to a territorial challenge and vice versa. Our study reveals some of the potential molecular mechanisms underlying behavioural trade‐offs between sex and aggression, along with a possible solution to the conflict via social context‐dependent gene regulation.
Community respiratory virus infections in bone marrow transplant recipients: the M.D. Anderson Cancer Center experience.

Community respiratory virus (CRV) infections are common among bone marrow transplant (BMT) recipients during community outbreaks. At M.D. Anderson Cancer Center (MDACC), experience with CRV infection in this population over the past decade suggests that BMT recipients in the preengraftment phase are at special risk of progression of upper respiratory tract infection (URTI) to pneumonia. After pneumonia is established, no currently available therapy substantially reduces mortality. For BMT recipients with respiratory syncytial virus URTIs, treatment with ribavirin and intravenous immunoglobulin may be helpful in preventing progression to pneumonia and thus in reducing mortality, but this approach requires confirmation in controlled clinical trials. Prevention of CRV infection in this vulnerable patient population is crucial to reducing morbidity and mortality. Aggressive infection control precautions, which have been in effect at MDACC since 1994, have reduced nosocomial transmission of these potentially lethal infections.
Graphene-supported silver nanoparticles for pH-neutral electrocatalytic oxygen reduction

In order to improve the electrocatalysis of oxygen reduction and reduce the captive cost of microbial fuel cell (MFC), graphene-supported catalyst of silver nanoparticles (Ag/RG) was prepared and its activity toward oxygen reduction reaction (ORR) in pH-neutral condition was examined. The Ag/RG catalyst was prepared by chemical reduction of aqueous silver ions to silver nanoparticles on the surface of reduced graphene (RG), which was obtained from graphene oxide (GO) precursor synthesized via classic Hummer's method using graphite as starting material. The results demonstrated that aqueous co-reduction method could yield high-quality Ag/RG catalyst, in which Ag nanoparticles were dispersed on the graphene surface with average diameter of 13 nm as revealed by XRD and TEM examination. The XPS results suggested the presence of polar oxygen-containing functional groups on the graphene sheets could provide the nuclei to form Ag nano-structure. The CV results showed that Ag/RG was active of catalyzing ORR electrochemically in pH-neutral electrolyte. Since Ag costs much less than Pt, Ag/RG is expected to hold remarkable potential as a promising alternative to promote the commercialization of MFC for practical application.
Single cell analysis of intracellular osteopontin in osteogenic cultures of fetal rat calvarial cells

Osteopontin (OPN), a major component of the bone matrix, is expressed at different stages of bone formation. To determine possible relationships between OPN expression and stages of osteogenic cell differentiation, we have performed single cell analyses of intracellular OPN in early (proliferating), subconfluent (differentiating), and mature (mineralizing) cultures of fetal rat calvarial cells (FRCC) using a combination of flow cytometry and confocal microscopy. At each culture stage, a high proportion (60–98%) of cells were immunoreactive for OPN (OPN+ve). Each of these populations also included a small proportion of OPN‐ve cells which were characterized by their small size, low granularity, high proliferative capacity, and enhanced osteogenic potential. The OPN+ve cells displayed two distinct patterns of intracellular immunostaining: a perinuclear distribution typical of secreted proteins and a perimembrane distribution in which patches of OPN were concentrated at the cell surface. Perimembranous staining predominated in migrant cells, which contained greater than tenfold higher levels of OPN than nonmigrant cells as separated in a Boyden chamber. When cell proliferation was high (day 2), most cells were OPN+ve. At all culture stages the intensity of OPN staining was increased as cells progressed through the cell cycle. As cells differentiated and started to form matrix (days 4 and 6), the mean cell expression of OPN was also increased (fourfold), independent of changes in total cell protein. However, despite the association of OPN with osteogenic cells, we were surprised to find that a high proportion (60%) of fetal skin fibroblasts were also immunoreactive for OPN. The expression of OPN by these cell populations was confirmed by RT‐PCR, and a strong correlation was observed between the quantitative flow cytometry data and Western blot analysis of cell extracts in which the high and low phosphorylated isoforms of OPN were observed. These studies, therefore, have identified several phenotypes in FRCC cultures that are based on OPN expression: small OPN‐ve cell populations enriched in osteogenic precursors, differentiating osteogenic cells that synthesize and secrete OPN, and migrating stromal cells characterized by a perimembranous OPN staining pattern. J Cell Physiol 170:88–100, 1997 © 1997 Wiley‐Liss, Inc.
Efficient calibration of real-time model-based controllers for diesel engines — Part I: Approach and drive cycle results

Controlling a diesel engine air path to achieve optimal engine performance is a challenging problem, given its multivariable nature and high degree of nonlinearity. Modelbased control approaches like MPC have the potential for providing effective controller design, in the presence of operating constraints. However, conventional MPC formulations have too many tuning parameters for efficient calibration to meet transient performance specifications. Furthermore, they generally involve the solution of an online optimisation problem, making real-time implementation difficult for all but extremely short prediction horizons. These challenges may be addressed by introducing an MPC formulation suitable for real-time control of a diesel-engine air path, incorporating an appropriate cost-function parameterisation to aid calibration. In this paper, data-driven prediction models identified from engine bench tests are used within the proposed MPC formulation, and implemented on a production automotive diesel. Preliminary experiments show the efficacy of the implementation in tracking desired air path reference trajectories over the UDC and EUDC drive cycles.
Geometric validation of MV topograms for patient localization on TomoTherapy

Our goal was to geometrically validate the use of mega-voltage orthogonal scout images (MV topograms) as a fast and low-dose alternative to mega-voltage computed tomography (MVCT) for daily patient localization on the TomoTherapy system. To achieve this, anthropomorphic head and pelvis phantoms were imaged on a 16-slice kilo-voltage computed tomography (kVCT) scanner to synthesize kilo-voltage digitally reconstructed topograms (kV-DRT) in the Tomotherapy detector geometry. MV topograms were generated for couch speeds of 1–4 cm s−1 in 1 cm s−1 increments with static gantry angles in the anterior-posterior and left-lateral directions. Phantoms were rigidly translated in the anterior-posterior (AP), superior-inferior (SI), and lateral (LAT) directions to simulate potential setup errors. Image quality improvement was demonstrated by estimating the noise level in the unenhanced and enhanced MV topograms using a principle component analysis-based noise level estimation algorithm. Average noise levels for the head phantom were reduced by 2.53 HU (AP) and 0.18 HU (LAT). The pelvis phantom exhibited average noise level reduction of 1.98 HU (AP) and 0.48 HU (LAT). Mattes Mutual Information rigid registration was used to register enhanced MV topograms with corresponding kV-DRT. Registration results were compared to the known rigid displacements, which assessed the MV topogram localization’s sensitivity to daily positioning errors. Reduced noise levels in the MV topograms enhanced the registration results so that registration errors were <1 mm. The unenhanced head MV topograms had discrepancies <2.1 mm and the pelvis topograms had discrepancies <2.7 mm. Result were found to be consistent regardless of couch speed. In total, 64.7% of the head phantom MV topograms and 60.0% of the pelvis phantom MV topograms exactly measured the phantom offsets. These consistencies demonstrated the potential for daily patient positioning using MV topogram pairs in the context bony-anatomy based procedures such as total marrow irradiation, total body irradiation, and cranial spinal irradiation.
The Capacity to Act in Trans Varies Among Drosophila Enhancers

The interphase nucleus is organized such that genomic segments interact in cis, on the same chromosome, and in trans, between different chromosomes. In Drosophila and other Dipterans, extensive interactions are observed between homologous chromosomes, which can permit enhancers and promoters to communicate in trans. Enhancer action in trans has been observed for a handful of genes in Drosophila, but it is as yet unclear whether this is a general property of all enhancers or specific to a few. Here, we test a collection of well-characterized enhancers for the capacity to act in trans. Specifically, we tested 18 enhancers that are active in either the eye or wing disc of third instar Drosophila larvae and, using two different assays, found evidence that each enhancer can act in trans. However, the degree to which trans-action was supported varied greatly between enhancers. Quantitative analysis of enhancer activity supports a model wherein an enhancer’s strength of transcriptional activation is a major determinant of its ability to act in trans, but that additional factors may also contribute to an enhancer’s trans-activity. In sum, our data suggest that a capacity to activate a promoter on a paired chromosome is common among Drosophila enhancers.
Paramecium bursaria Chlorella Virus-1 Encodes an Unusual Arginine Decarboxylase That Is a Close Homolog of Eukaryotic Ornithine Decarboxylases*

Paramecium bursaria chlorella virus (PBCV-1) is a large double-stranded DNA virus that infects chlorella-like green algae. The virus encodes a homolog of eukaryotic ornithine decarboxylase (ODC) that was previously demonstrated to be capable of decarboxylating l-ornithine. However, the active site of this enzyme contains a key amino acid substitution (Glu for Asp) of a residue that interacts with the δ-amino group of ornithine analogs in the x-ray structures of ODC. To determine whether this active-site change affects substrate specificity, kinetic analysis of the PBCV-1 decarboxylase (PBCV-1 DC) on three basic amino acids was undertaken. The kcat/Km for l-arginine is 550-fold higher than for either l-ornithine or l-lysine, which were decarboxylated with similar efficiency. In addition, α-difluoromethylarginine was a more potent inhibitor of the enzyme than α-difluoromethylornithine. Mass spectrometric analysis demonstrated that inactivation was consistent with the formation of a covalent adduct at Cys347. These data demonstrate that PBCV-1 DC should be reclassified as an arginine decarboxylase. The eukaryotic ODCs, as well as PBCV-1 DC, are only distantly related to the bacterial and plant arginine decarboxylases from their common β/α-fold class; thus, the finding that PBCV-1 DC prefers l-arginine to l-ornithine was unexpected based on evolutionary analysis. Mutational analysis was carried out to determine whether the Asp-to-Glu substitution at position 296 (position 332 in Trypanosoma brucei ODC) conferred the change in substrate specificity. This residue was found to be an important determinant of substrate binding for both l-arginine and l-ornithine, but it is not sufficient to encode the change in substrate preference.
Precision measurements of quantum hall resistance plateau in doping-controlled graphene device

We report preliminary results of precision measurements of the graphene quantum Hall resistance plateau value with respect to magnetic field, temperature and applied current. Resistance value of SiC graphene Hall device was modulated by chemical doping, heating, and UV irradiation at the ambient condition. Precision measurements for Rh (filing factor v = 2) were then performed with a cryogenic current comparator resistance bridge. Relative deviation from RH (v = 2) less than 30 parts in 109 can be achieved down to 7 T of magnetic field and up to 6 K of temperature with driving current of 19. 37 μA.
Photoacoustic-guided focused ultrasound for accurate visualization of brachytherapy seeds with the photoacoustic needle.

An important problem in minimally invasive photoacoustic (PA) imaging of brachytherapy seeds is reflection artifacts caused by the high signal from the optical fiber/needle tip reflecting off the seed. The presence of these artifacts confounds interpretation of images. In this letter, we demonstrate a recently developed concept called photoacoustic-guided focused ultrasound (PAFUSion) for the first time in the context of interstitial illumination PA imaging to identify and remove reflection artifacts. In this method, ultrasound (US) from the transducer is focused on the region of the optical fiber/needle tip identified in a first step using PA imaging. The image developed from the US diverging from the focus zone at the tip region visualizes only the reflections from seeds and other acoustic inhomogeneities, allowing identification of the reflection artifacts of the first step. These artifacts can then be removed from the PA image. Using PAFUSion, we demonstrate reduction of reflection artifacts and thereby improved interstitial PA visualization of brachytherapy seeds in phantom and
Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer

ABSTRACT Tumor-associated macrophages (TAMs) play a role in tumor development and progression. We hypothesized that abundance of TAMs might modify efficacy of 5-fluorouracil chemotherapy in colorectal cancer. We measured the density of CD68+ TAMs at the invasive front of primary tumor of colorectal carcinoma (PT-TAMs; n = 208), at available matched metastatic lymph node (LN-TAMs; n = 149), and in an independent set of primary colorectal cancers (PT-TAMs, n = 111). The hazard ratios for disease-free survival were computed by Cox proportional-hazards model. In exploratory analysis, the interaction between TAMs and 5-fluorouracil adjuvant therapy was significant (PT-TAMs, p = 0.02; LN-TAMs, p = 0.005). High TAMs were independently associated with better disease-free survival only in 5-fluorouracil-treated patients (PT-TAMs, HR 0.23; 95%CI, 0.08–0.65; p = 0.005; LN-TAMs, HR 0.13; 95%CI, 0.04–0.43; p = 0.001). The independent predictive value of PT-TAMs was replicated in the external set (HR, 0.14; 95%CI 0.02–1.00; p = 0.05). In an in vitro experiment, 5-fluorouracil and macrophages showed a synergistic effect and increased colorectal cancer cell death. High densities of TAMs, particularly in metastatic lymph-nodes, identify stage III colorectal cancer patients benefitting from 5-fluorouracil adjuvant therapy.