Miracle-dz/UniFAR-FTUs huggingface dataset:
Modified ultrafast Papanicolaou staining technique: A comparative study

Introduction: Ultrafast Papanicolaou stain (UFP) was introduced as a hybrid of Romanowsky and Papanicolaou (PAP) stain. It enhances the quality and reduces the time. In the present study, a modified staining technique was adapted where Gill's Hematoxylin was replaced by Harris Hematoxylin. Aims: The aim of the study was to assess the use of the modified ultrafast Papanicolaou (MUFP) stain for fine needle aspiration cytology (FNAC) of head and neck swellings in comparison with the routine PAP stain, hematoxylin and eosin (H and E), and Giemsa. Materials and Methods: Forty FNACs of head and neck swellings were collected. FNAC procedure was performed by standard method; two smears were fixed in 95% propanol and stained with PAP and H and E. Two smears were air dried, 1 was stained with Giemsa, and 1 was rehydrated with normal saline, fixed in alcoholic formalin, and stained with MUFP. Four parameters were considered and scored background, cell morphology, nuclear staining, and overall staining pattern). Results: The quality of MUFP smears were better when compared to routine PAP, H and E, and Giemsa, and was statistically significant by Wilcoxon matched pair test. Conclusions: MUFP stain in comparison to routine PAP, H and E, and Giemsa provides an excellent and suitable alterative in cytological staining for the study of various organs.
A Novel Method to Identify Routes of Hepatitis C Virus Transmission

Background We propose a new approach based on genetic distances among viral strains to infer about risk exposures and location of transmission at population level. Methods We re-analysed 133 viral sequences obtained during a cross-sectional survey of 4020 subjects living in a hepatitis C virus (HCV) endemic area in 2002. A permutation test was used to analyze the correlation between matrices of genetic distances in the NS5b region of all pairwise combinations of the 133 viral strains and exposure status (jointly exposed or not) to several potential HCV risk factors. Results Compared to subjects who did not share the same characteristics or iatrogenic exposures, the median Kimura genetic distances of viral strains were significantly smaller between brothers and sisters (0.031 versus 0.102, P<0.001), mother and child (0.044 versus 0.102, P<0.001), father and child (0.045 versus 0.102, P<0.001), or subjects exposed to periodontal treatment (0.084 versus 0.102, P = 0.02). Conversely, viral strains were more divergent between subjects exposed to blood transfusions (0.216 versus 0.102, P = 0.04) or tooth filling or extraction (0.108, versus 0.097, P = 0.05), suggesting acquisition of the virus outside of the village. Conclusion This method provided insights on where infection took place (household, village) for several socio-demographic characteristics or iatrogenic procedures, information of great relevance for targeting prevention interventions. This method may have interesting applications for virologists and epidemiologists studying transmission networks in health-care facilities or among intravenous drug users.
Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London Lung Cancer Group multicenter randomized clinical trial and meta-analysis.

PURPOSE To replicate an earlier National Cancer Institute of Canada (NCIC) trial that examined the effect on survival of the timing of thoracic radiotherapy (TRT) in patients with limited disease small-cell lung cancer (SCLC). PATIENTS AND METHODS Patients received three cycles of cyclophosphamide, doxorubicin, and vincristine alternating with three cycles of etoposide and cisplatin. Three hundred twenty five chemotherapy- and radiotherapy-naïve patients were randomly assigned to either early TRT administered concurrently in the second cycle or late TRT administered concurrently with the sixth cycle; the dose was 40 Gy in 15 fractions over 3 weeks. RESULTS TRT was received by 92% and 82% of patients in the early and late arms, respectively (P = .01). Sixty-nine percent of patients in the early arm received all six courses of chemotherapy compared with 80% in the late arm (P = .003). There was no evidence of a survival difference; median overall survival time was 13.7 and 15.1 months in the early and late arms, respectively (P = .23). In a meta-analysis of all eight trials that compared early and late TRT, there were three in which the proportion of patients who completed their planned chemotherapy was similar between the TRT arms (hazard ratio [HR] = 0.73; 95% CI, 0.62 to 0.86) and five in which proportionally fewer patients in the early TRT arm completed their chemotherapy (HR = 1.06; 95% CI, 0.97 to 1.17). CONCLUSION This study failed to show a survival advantage for early TRT with chemotherapy in limited-stage SCLC, unlike the NCIC trial. However, the results of a meta-analysis suggest that it is essential to ensure that the delivery of chemotherapy is optimal when administered with early TRT.
HIV pre-exposure prophylaxis for people who inject drugs: a review of current results and an agenda for future research

Studies examining the use of pre‐exposure prophylaxis (PrEP) to prevent HIV transmission among people who inject drugs (PWIDs) have not been adequately summarized. Recently, the Bangkok Tenofovir Study has shown that PrEP may be effective at reducing new HIV infections among this high‐risk group. This randomized controlled trial was the first study to specifically examine the efficacy of PrEP among PWIDs. In this review, we present the current state of evidence regarding the use of PrEP to prevent HIV infection in PWID populations, and set an agenda for future research to inform the most effective implementation of PrEP in the context of existing evidence‐based HIV prevention strategies.
Modeling linguistic segment and turn boundaries for n-best rescoring of spontaneous speech

Language modeling, especially for spontaneous speech, often suffers from a mismatch of utterance segmentations between training and test conditions. In particular, training often uses linguistically-based segments, whereas testing occurs on acoustically determined segments, resulting in degraded performance. We present an N-best rescoring algorithm that removes the effect of segmentation mismatch. Furthermore, we show that explicit language modeling of hidden linguistic segment boundaries is improved by including turn-boundary events in the model. 1. THE SEGMENTATION PROBLEM IN LANGUAGE MODELING One of the problems encountered in speech recognition on continuous, spontaneous speech is the segmentation of long waveforms. Because current recognizers prefer short waveform segments for best performance and to limit computational resources, conversation-length waveforms are typically pre-segmented using simple acoustic criteria, such as locations of long pauses and turn switches. This creates several problems for language modeling: The segmentation algorithm used (including its parameters) influences the statistics embodied in the language model (LM), creating a potential mismatch between training and test set. Strictly speaking, one would have to resegment the training data, recreate the word-level transcriptions, and retrain the language model every time the segmentation process is modified. The acoustic segmentation typically yields units that are not linguistically coherent, and hence sub-optimal for language modeling. Language modeling research on spontaneous speech [10] shows that N-gram LMs based on complete utterance units give lower perplexity than those based only on acoustic segmentations. Furthermore, work reported in [12] showed that the word error rate on spontaneous speech can be reduced simply by resegmenting the speech at linguistic boundaries and using a language model based on the same segmentation. Explicit modeling of spontaneous speech phenomena such as disfluencies also requires modeling of linguistic (as opposed to acoustic) segment boundaries [15]. Similarly, sophisticated LMs modeling syntactic structure typically assume complete sentences as their input [12]. The following excerpt from the Switchboard corpus [2] illustrates the discrepancies between acoustic and linguistic segmentations. Linguistic segment boundaries are marked by , whereas acoustic boundaries are indicated by //. A subset of acoustic boundaries corresponds to turn boundaries, indicated by . B: Worried that they’re not going to get enough attention?
Approximate inference in latent Gaussian-Markov models from continuous time observations

We propose an approximate inference algorithm for continuous time Gaussian Markov process models with both discrete and continuous time likelihoods. We show that the continuous time limit of the expectation propagation algorithm exists and results in a hybrid fixed point iteration consisting of (1) expectation propagation updates for discrete time terms and (2) variational updates for the continuous time term. We introduce post-inference corrections methods that improve on the marginals of the approximation. This approach extends the classical Kalman-Bucy smoothing procedure to non-Gaussian observations, enabling continuous-time inference in a variety of models, including spiking neuronal models (state-space models with point process observations) and box likelihood models. Experimental results on real and simulated data demonstrate high distributional accuracy and significant computational savings compared to discrete-time approaches in a neural application.
Financial Distortions and the Distribution of Global Volatility

Why are emerging economies excessively vulnerable to shocks to external funding? What was the role of financial flows from emerging to developed economies in setting the stage for the subprime crisis? This paper addresses these questions in a simple general equilibrium framework that emphasizes the aggregate implications of the misallocation of funds on the micro level. The analysis shows that the misallocation of funds amplifies volatility even in a closed economy. Financial integration between relatively distorted emerging economies and relatively undistorted developed economies leads to a further divergence in volatility, thereby providing a new and simple explanation for the divergent trends in output volatility up to the recent crisis. In the integrated environment, cheap funding leads to an endogenous deterioration of the financial system in developed economies. These predictions are consistent with a wide variety of microfoundations, in which distortions cause productive projects to be relatively more sensitive to aggregate shocks. The paper provides some empirical evidence for these microfoundations.
Thrombospondin-1 promotes proliferative healing through stabilization of PDGF.

PURPOSE Thrombospondin-1 (TSP-1) mediates chemotaxis, cell proliferation, angiogenesis, and protease regulation in healing. TSP-1 also binds platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). This study confirms the role of TSP-1 and defines the relationship between TSP-1 and PDGF in proliferative tissue repair. METHODS Purified TSP-1 was analyzed for bound PDGF. Cultured fibroblast growth response to TSP-1 and recombinant PDGF was studied and the effects of antibodies against TSP-1, PDGF, and TGF-beta on this response were evaluated. Levels of TSP-1 and PDGF and relative proteolytic activity in fluid collected from 10 skin graft donor sites were then assessed by ELISA and a protease assay kit. The effect of proteolysis on TSP-bound PDGF and free recombinant PDGF was studied by adding trypsin and measuring the remaining PDGF by ELISA. RESULTS TSP-1 promoted dose-dependent fibroblast growth. While antibody to TGF-beta had no effect on promotion, antibody to both TSP-1 and PDGF eliminated this. Since a strong correlation of TSP-1 with PDGF levels was found and strong proteolysis was seen in all samples, we proposed that TSP-1 protected PDGF from proteolysis. Consistent with this, we found PDGF bound to TSP-1 was 33% less degraded than free PDGF upon trypsinization. CONCLUSIONS These results suggest that TSP-1 stabilizes PDGF, enhancing the biological effects of PDGF in proliferative tissue repair. This effect of TSP-1 along with its matrix-modulating activities may have important clinical utility regarding topical growth factor therapy in wound healing, since high proteolytic activity is believed to be partially responsible for limiting the efficacy of this treatment.
Laparoscopic Repair of Paraesophageal Hernia: Long-term Follow-up Reveals Good Clinical Outcome Despite High Radiological Recurrence Rate

OBJECTIVE The purpose of this report is to evaluate and compare the long-term objective and subjective outcome after laparoscopic paraesophageal hernia repair (LPHR). BACKGROUND Short-term symptomatic results of LPHR are often excellent. However, a high recurrence rate is detected at objective radiographic follow-up. METHODS Retrospective review of a prospectively gathered database of consecutive patients undergoing LPHR with and without reinforced crural repair at a single institution. Subjective and objective outcomes were assessed by using a structured symptoms questionnaire, Gastrointestinal Quality-of-Life Index, satisfaction score, and barium esophagogram. RESULTS From September 1991 to September 2005, LPHR was performed in 85 patients (median age, 66 years) with (25 patients) and without (60 patients) reinforced crural repair. Two patients (3%) underwent laparoscopic reoperation, for severe dysphagia and for symptomatic recurrence, respectively. Subjective outcome, available for 64 patients (75%), improved significantly at median follow-up of 118 months with a postoperative median Gastrointestinal Quality-of-Life Index score of 116. Radiographic recurrence (median follow-up, 99 months) occurred in 23 (66%) of the 35 patients, independently of age at operation, type of paresophageal hiatal hernias, and crural reinforcement, and showed no impact on quality of life. CONCLUSIONS Although providing excellent symptomatic results, long-term objective evaluation of LPHR reveals a high recurrence rate even with reinforced cruroplasty. A tailored, lengthening gastroplasty and reinforced cruroplasty based on objective intraoperative evaluation, and not only on surgeon's personal judgment, may be the answer to recurrences.
Methylene Blue Binding to DNA with Alternating GC Base Sequence: A Modeling Study

Photoactive methylene blue is one of the most efficient singlet oxygen generating dyes. It binds to DNA and induces photosensitized reactions which can be used for sequence-specific cleavage of the DNA backbone. Photophysical data obtained for methylene blue in complexes with DNA indicate different binding modes of the dye depending on base sequences. In this study, the binding of methylene blue to a double-stranded decamer with an alternating GC sequence has been investigated by structural modeling and force field based energy calculations. Solvation and desolvation effects have been treated using an electrostatic continuum model. For each of the three possible binding modes (intercalation and minor and major groove binding), a search of the configurational space resulted in six model structures which were selected by the criterion of lowest total energies. The differences of estimated energies are only a few kilocalories per mole, but suggest a preference for symmetric intercalation at the 5‘-CpG-3‘ or .
Role of narK2X and narGHJI inHypoxic Upregulation of Nitrate Reduction byMycobacteriumtuberculosis

ABSTRACT Mycobacterium tuberculosis is one of the strongest reducers of nitrate in the genus Mycobacterium. Under microaerobic conditions, whole cells exhibit upregulation of activity, producing approximately eightfold more nitrite than those of aerobic cultures of the same age. Assays of cell extracts from aerobic cultures and hypoxic cultures yielded comparable nitrate reductase activities. Mycobacterium bovis produced only low levels of nitrite, and this activity was not induced by hypoxia. M. tuberculosis has two sets of genes, narGHJI and narX of the narK2X operon, that exhibit some degree of homology to prokaryotic dissimilatory nitrate reductases. Each of these were knocked out by insertional inactivation. The narG mutant showed no nitrate reductase activity in whole culture or in cell-free assays, while the narX mutant showed wild-type levels in both assays. A knockout of the putative nitrite transporter narK2 gene produced a strain that had aerobic levels of nitrate reductase activity but failed to show hypoxic upregulation. Insertion of the M. tuberculosis narGHJI into a nitrate reductase Escherichia coli mutant allowed anaerobic growth in the presence of nitrate. Under aerobic and hypoxic conditions, transcription of narGHJI was constitutive, while the narK2X operon was induced under hypoxia, as measured with a lacZ reporter system and by quantitative real-time reverse PCR. This indicates that nitrate reductase activity in M. tuberculosis is due to the narGHJI locus with no detectable contribution from narX and that the hypoxic upregulation of activity is associated with the induction of the nitrate and nitrite transport gene narK2.
Comparison of the Intracarotid Amobarbital Procedure and Interictal Cerebral 18‐Fluorodeoxyglucose Positron Emission Tomography Scans in Refractory Temporal Lobe Epilepsy

Summary: The relationship between interictal focal hypometabolism determined by 18‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scans and memory function with the intracarotid amobarbital procedure (IAP) was evaluated in 23 patients with temporal lobe epilepsy. All patients underwent prolonged EEG/video monitoring. The epileptogenic focus was defined by interictal epileptiform discharges and ictal onsets. All 23 patients had recorded seizures arising exclusively from one temporal lobe. PET showed temporal lobe hypometabolism ipsilateral to the epileptogenic focus in 86% (20 of 23) of patients; IAP showed impaired memory of the hemisphere of seizure onset in 65% (15 of 23). Sixty‐five percent (13 of 20) of patients with focal hypometabolism had ipsilateral memory impairment. Memory impairment contralateral to the hypometabolic zone was not observed. Ninety‐five percent (22 of 23) of patients demonstrated functional impairment by either PET or IAP (or both) on the epileptogenic side.
Myocardial Perfusion Reserve After a PET-Driven Revascularization Procedure: A Strong Prognostic Factor

Not all patients treated on the basis of PET-proven viability benefit from revascularization. Myocardial perfusion reserve (MPR) predicts survival in patients not undergoing revascularization. In the present study, we investigated whether MPR is related to survival in ischemic heart disease (IHD) patients after a PET-driven intervention. Methods: Between 1995 and 2003, 119 consecutive patients with chronic IHD underwent a PET-driven revascularization procedure based on ischemia–viability assessment with PET. Patients were followed for all-cause mortality and major cardiovascular events. Results: One hundred nineteen patients underwent a PET-driven revascularization procedure (67 percutaneous coronary interventions, 52 coronary artery bypass grafts) because of angina complaints. The mean age was 67 ± 11 y (96 men, 23 women); global left ventricle MPR was 1.54 ± 0.43. MPR intertertile boundaries were 1.34 and 1.67. Significantly more cardiac deaths were observed in the lowest and middle MPR tertiles than in the highest tertile. The age- and sex-corrected hazard ratio for the middle tertile was 8.3 (95% confidence interval, 1.02–68.3) and for the lowest tertile 23.6 (95% confidence interval, 3.1–179) (P = 0.002). After left ventricular ejection fraction (LVEF) and viability were added to the model, MPR remained significant, with hazard ratios of 6.5 (0.8–54.4) and 18.5 (2.3−145.5) (P = 0.004), whereas neither LVEF nor viability reached significance in this model. Comparable results were found for major adverse cardiac events, with hazard ratios of 3.15 (0.82–12.0) and 8.24 (2.36–28.8) (P = 0.002). Conclusion: Patients with IHD revascularized on the basis of PET viability assessment who have a low MPR are at risk for cardiac death and subsequent cardiac events. MPR is a more sensitive predictor for cardiac death than LVEF and extent of viability.
Therapeutic activities of 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine and -thymine alone and in combination with acyclovir and vidarabine in mice infected intracerebrally with herpes simplex virus

The therapeutic effectiveness of two new antiviral agents, 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine and 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine, was compared with that of acyclovir and vidarabine. In mice inoculated intracerebrally with high 50% lethal doses of herpes simplex virus type 2, nontoxic intraperitoneal or oral treatments with the two new fluorinated antiviral agents were highly effective in reducing mortality. The two drugs were also effective when treatment was begun as late as 48 h after virus inoculation. The relative order of potencies of the drugs when compared on a molar basis or in terms of therapeutic index was 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine much greater than 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine greater than vidarabine approximately to acyclovir. The new pyrimidine analogs were also found to lack immunosuppressive activity in mice. The combination of 1-(2-fluoro-2-deoxy-beta-=D-arabinofuranosyl)-5-iodocytosine and vidarabine was the most effective; significantly greater reduction in mortality was achieved with this combination than with either drug alone. Thirty minutes after intraperitoneal treatment with the fluorinated analogs, the drugs (or their metabolites) were transported to the brains of virus-inoculated and normal mice at levels about one-third to two thirds those in the blood. The levels of 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine in the blood or brain were consistently higher than those found with equivalent intraperitoneal doses of the 5-iodocytosine analog.
Direct Innervation of GnRH Neurons by Metabolic- and Sexual Odorant-Sensing Leptin Receptor Neurons in the Hypothalamic Ventral Premammillary Nucleus

Leptin acts via its receptor (LepRb) on specific CNS neurons to signal the adequacy of long-term energy stores, thereby permitting the expenditure of resources on energy-intensive processes such as reproduction. The ventral premammillary nucleus of the hypothalamus (PMv), which has been implicated in the stimulation of gonadotropin release by olfactory cues, contains numerous LepRb neurons, suggesting a potential role for LepRb PMv neurons in transmitting both metabolic and odorant signals to the neuroendocrine reproductive system. Indeed, Fos immunoreactivity and electrophysiologic recordings revealed the direct activation of LepRb PMv neurons by leptin, and exposure to odors from mice of the opposite sex promoted Fos immunoreactivity (Fos-IR) in many LepRb PMv neurons. To determine the regions innervated by the LepRb PMv neurons, we used two novel cre-activated tract-tracing systems in Leprcre animals; data from these systems and from standard tracing techniques revealed that LepRb PMv neurons project to a subset of the regions, including the preoptic area, that are innervated by the PMv as a whole. Furthermore, the retrograde accumulation in LepRb PMv neurons of a trans-synaptic tracer from GnRH neurons revealed the direct innervation of GnRH neurons by many LepRb PMv neurons. Thus, LepRb PMv neurons sense metabolic and sexual odorant cues and project to the rostral hypothalamus to directly innervate GnRH neurons. These results are consistent with a role for LepRb PMv neurons in regulating the reproductive axis in response to metabolic and odorant stimuli.