Deep Interactive Learning: An Efficient Labeling Approach for Deep Learning-Based Osteosarcoma Treatment Response Assessment

Osteosarcoma is the most common malignant primary bone tumor. Standard treatment includes pre-operative chemotherapy followed by surgical resection. The response to treatment as measured by ratio of necrotic tumor area to overall tumor area is a known prognostic factor for overall survival. This assessment is currently done manually by pathologists by looking at glass slides under the microscope which may not be reproducible due to its subjective nature. Convolutional neural networks (CNNs) can be used for automated segmentation of viable and necrotic tumor on osteosarcoma whole slide images. One bottleneck for supervised learning is that large amounts of accurate annotations are required for training which is a time-consuming and expensive process. In this paper, we describe Deep Interactive Learning (DIaL) as an efficient labeling approach for training CNNs. After an initial labeling step is done, annotators only need to correct mislabeled regions from previous segmentation predictions to improve the CNN model until the satisfactory predictions are achieved. Our experiments show that our CNN model trained by only 7 hours of annotation using DIaL can successfully estimate ratios of necrosis within expected inter-observer variation rate for non-standardized manual surgical pathology task.Comment: Accepted at MICCAI 202

Supersymmetric QCD: Exact Results and Strong Coupling

We revisit two longstanding puzzles in supersymmetric gauge theories. The first concerns the question of the holomorphy of the coupling, and related to this the possible definition of an exact (NSVZ) beta function. The second concerns instantons in pure gluodynamics, which appear to give sensible, exact results for certain correlation functions, which nonetheless differ from those obtained using systematic weak coupling expansions. For the first question, we extend an earlier proposal of Arkani-Hamed and Murayama, showing that if their regulated action is written suitably, the holomorphy of the couplings is manifest, and it is easy to determine the renormalization scheme for which the NSVZ formula holds. This scheme, however, is seen to be one of an infinite class of schemes, each leading to an exact beta function; the NSVZ scheme, while simple, is not selected by any compelling physical consideration. For the second question, we explain why the instanton computation in the pure supersymmetric gauge theory is not reliable, even at short distances. The semiclassical expansion about the instanton is purely formal; if infrared divergences appear, they spoil arguments based on holomorphy. We demonstrate that infrared divergences do not occur in the perturbation expansion about the instanton, but explain that there is no reason to think this captures all contributions from the sector with unit topological charge. That one expects additional contributions is illustrated by dilute gas corrections. These are infrared divergent, and so difficult to define, but if non-zero give order one, holomorphic, corrections to the leading result. Exploiting an earlier analysis of Davies et al, we demonstrate that in the theory compactified on a circle of radius beta, due to infrared effects, finite contributions indeed arise which are not visible in the formal limit that beta goes to infinity.Comment: 28 pages, two references added, one typo correcte

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

Fatal cerebral edema associated with serine deficiency in CSF

Two young girls without a notable medical history except for asthma presented with an acute toxic encephalopathy with very low serine concentrations both in plasma and cerebrospinal fluid (CSF) comparable to patients with 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency. Clinical symptoms and enzyme measurement (in one patient) excluded 3-PGDH deficiency. Deficiencies in other serine biosynthesis enzymes were highly unlikely on clinical grounds. On basis of the fasting state, ketone bodies and lactate in plasma, urine and CSF, we speculate that reduced serine levels were due to its use as gluconeogenic substrate, conversion to pyruvate by brain serine racemase or decreased L-serine production because of a lack of glucose. These are the first strikingly similar cases of patients with a clear secondary serine deficiency associated with a toxic encephalopathy

On the pathogenesis of penile venous leakage: role of the tunica albuginea

<p>Abstract</p> <p>Background</p> <p>Etiology of venogenic erectile dysfunction is not exactly known. Various pathologic processes were accused but none proved entirely satisfactory. These include presence of large venous channels draining corpora cavernosa, Peyronie's disease, diabetes and structural alterations in fibroblastic components of trabeculae and cavernous smooth muscles. We investigated hypothesis that tunica albuginea atrophy with a resulting subluxation and redundancy effects venous leakage during erection.</p> <p>Methods</p> <p>18 patients (mean age 33.6 ± 2.8 SD years) with venogenic erectile dysfunction and 17 volunteers for control (mean age 31.7 ± 2.2 SD years) were studied. Intracorporal pressure was recorded in all subjects; tunica albuginea biopsies were taken from 18 patients and 9 controls and stained with hematoxylin and eosin and Masson's trichrome stains.</p> <p>Results</p> <p>In flaccid phase intracorporal pressure recorded a mean of 11.8 ± 0.8 cm H₂O for control subjects and for patients of 5.2 ± 0.6 cm, while during induced erection recorded 98.4 ± 6.2 and 5.9 ± 0.7 cmH₂O, respectively. Microscopically, tunica albuginea of controls consisted of circularly-oriented collagen impregnated with elastic fibers. Tunica albuginea of patients showed degenerative and atrophic changes of collagen fibers; elastic fibers were scarce or absent.</p> <p>Conclusion</p> <p>Study has shown that during erection intracorporal pressure of patients with venogenic erectile dysfunction was significantly lower than that of controls. Tunica albuginea collagen fibers exhibited degenerative and atrophic changes which presumably lead to tunica albuginea subluxation and floppiness. These tunica albuginea changes seem to explain cause of lowered intracorporal pressure which apparently results from loss of tunica albuginea veno-occlusive mechanism. Causes of tunica albuginea atrophic changes and subluxation need to be studied.</p

Routine Laboratory Results and Thirty Day and One-Year Mortality Risk Following Hospitalization with Acute Decompensated Heart Failure

INTRODUCTION: Several blood tests are performed uniformly in patients hospitalized with acute decompensated heart failure and are predictive of the outcomes: complete blood count, electrolytes, renal function, glucose, albumin and uric acid. We sought to evaluate the relationship between routine admission laboratory tests results, patient characteristics and 30-day and one-year mortality of patients admitted for decompensated heart failure and to construct a simple mortality prediction tool. METHODS: A retrospective population based study. Data from seven tertiary hospitals on all admissions with a principal diagnosis of heart failure during the years 2002-2005 throughout Israel were captured. RESULTS: 8,246 patients were included in the study cohort. Thirty day mortality rate was 8.5% (701 patients) and one-year mortality rate was 28.7% (2,365 patients). Addition of five routine laboratory tests results (albumin, sodium, blood urea, uric acid and WBC) to a set of clinical and demographic characteristics improved c-statistics from 0.76 to 0.81 for 30-days and from 0.72 to 0.76 for one-year mortality prediction (both p-values <0.0001). Three dichotomized abnormal laboratory results with highest odds ratio for one-year mortality (hypoalbuminaemia, hyponatremia and elevated blood urea) were used to construct a simple prediction score, capable of discriminating from 1.1% to 21.4% in 30-day and from 11.6% to 55.6% in one-year mortality rates between patients with a score of 0 (1,477 patients) vs. score of 3 (544 patients). DISCUSSION: A small set of abnormal routine laboratory results upon admission can risk-stratify and independently predict 30-day and one-year mortality in patients hospitalized with acute decompensated heart failure

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57&nbsp;keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9})  eV^{2}. From this, we derive an upper limit of 1.1&nbsp;eV (90%&nbsp;confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation

Estimating alcohol-related premature mortality in san francisco: use of population-attributable fractions from the global burden of disease study

<p>Abstract</p> <p>Background</p> <p>In recent years, national and global mortality data have been characterized in terms of well-established risk factors. In this regard, alcohol consumption has been called the third leading "actual cause of death" (modifiable behavioral risk factor) in the United States, after tobacco use and the combination of poor diet and physical inactivity. Globally and in various regions of the world, alcohol use has been established as a leading contributor to the overall burden of disease and as a major determinant of health disparities, but, to our knowledge, no one has characterized alcohol-related harm in such broad terms at the local level. We asked how alcohol-related premature mortality in San Francisco, measured in years of life lost (YLLs), compares with other well-known causes of premature mortality, such as ischemic heart disease or HIV/AIDS.</p> <p>Methods</p> <p>We applied sex- and cause-specific population-attributable fractions (PAFs) of years of life lost (YLLs) from the Global Burden of Disease Study to 17 comparable outcomes among San Francisco males and females during 2004-2007. We did this in three ways: Method 1 assumed that all San Franciscans drink like populations in developed economies. These estimates were limited to alcohol-related harm. Method 2 modified these estimates by including several beneficial effects. Method 3 assumed that Latino and Asian San Franciscans drink alcohol like populations in the global regions related to their ethnicity.</p> <p>Results</p> <p>By any of these three methods, alcohol-related premature mortality accounts for roughly a tenth of all YLLs among males. Alcohol-related YLLs among males are comparable to YLLs for leading causes such as ischemic heart disease and HIV/AIDS, in some instances exceeding them. Latino and black males bear a disproportionate burden of harm. Among females, for whom estimates differed more by method and were smaller than those for males, alcohol-related YLLs are comparable to leading causes which rank somewhere between fifth and fourteenth.</p> <p>Conclusions</p> <p>Alcohol consumption is a major contributor to premature mortality in San Francisco, especially among males. Interventions to avert alcohol-related harm in San Francisco should be taken at the population level and deserve the same attention that is given to other major risk factors, such as smoking or obesity.</p

Photodynamic and Antibiotic Therapy Impair the Pathogenesis of Enterococcus faecium in a Whole Animal Insect Model

Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT) is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS). PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth) caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics). In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively). In the study of antimicrobial PDT, we verified that methylene blue (MB) injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192). Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095) or vancomycin treatment alone (P = 0.0025), suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to study the antimicrobial PDT and to explore combinatorial aPDT-based treatments