gebhart/patrepeval huggingface dataset:
Abstract A008: AI-driven image-based microbiome analysis reveals correlation of higher pre-treatment microbiome level with complete response in QUILT 3032 trial patients (2022)

Abstract The human microbiome, both systemic and tumor microenvironment (TME)-associated, exerts a profound influence on cancer development, progression, and response to treatment. To facilitate microbiome analysis in cancer, we developed an AI-driven computational pathology system that determines relative microbiome levels in H&amp;E-stained slides from formalin-fixed paraffin- embedded tissue specimens. We utilized available whole-genome and whole-transcriptome sequencing data for microbiome detection in TCGA bladder cancer [Poore et al. 2020; Nature 579], for which images were available, to define microbiome-low and -high labels. The TCGA bladder cancer cohort (n = 408) was distributed into training (66.7%, n = 272), validation (8.3%, n = 34) and test (25.0%, n = 102) sets; each with equal numbers of microbiome-low and -high patients. The cohort featured an average of 1.05 diagnostic (DX) images per patient, with 429 DX images in total. We trained a deep network using a total of 303,104 patches (of size 100 x 100 microns, equivalent to 400 x 400 pixels at 40X magnification) randomly selected from 296 DX images in the training set. Testing on untouched patient data (n = 102) gave area under the ROC curve of 0.74 and F1 score of 0.74. The developed system was then used to determine correlations between TCGA bladder cancer patient survival and microbiome level. Treatment-naïve bladder cancer patients identified as microbiome-low by our image-based system had higher survival rates, with hazard ratio of 1.45. Further, we assessed correlations between pathologic complete response (pCR) at 12 or 27 weeks and microbiome level in non-muscle invasive bladder cancer patients in ImmunityBio, Inc.’s QUILT-3.032 trial. Patients that achieved a pCR with treatment were found to have significantly higher probability of microbiome-high pre-treatment, as compared to those who did not achieve a pCR. Reductions in predicted microbiome levels after treatment were also observed in pCR patients. Conversely, 6 of 7 non-responders were found to have an increase in microbiome-high probability with treatment. These findings suggest our novel AI-driven image-based computational pathology system has the potential to provide data that may not only inform clinical decision-making, but also allow further investigation into the role of the TME microbiome in cancer. Citation Format: Mustafa I. Jaber, Kamil Wnuk, Patricia Spilman, Bing Song, David Trianni, Megan Huang, Paul Bhar, Patrick Soon-Shiong, Sandeep Reddy. AI-driven image-based microbiome analysis reveals correlation of higher pre-treatment microbiome level with complete response in QUILT 3032 trial patients [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A008.
Catheter Ablation and Device Therapy in Congenital Heart Disease (2013)

Arrhythmias in adult CHD patients represent the leading cause of morbidity and hospitalization, resulting in a major increase in ablation and device-related procedures in these patients. These procedures are often complex, not only because of underlying congenital anatomic variations but also because of the effects of prior surgical repair that can modify the arrhythmic substrate leading to an increased likelihood of multiple types of arrhythmias, even in the same patient. To optimize both success and safety with these procedures, the electrophysiologist must be thoroughly familiar with the underlying cardiac anatomy, prior cardiac surgical history, and known variants of both the pathology and surgical techniques. The purpose of this chapter is to outline the salient concepts and principles pertinent to arrhythmia and device management in patients with CHD.
Mobius: unified messaging and data serving for mobile apps (2012)

Mobile application development is challenging for several reasons: intermittent and limited network connectivity, tight power constraints, server-side scalability concerns, and a number of fault-tolerance issues. Developers handcraft complex solutions that include client-side caching, conflict resolution, disconnection tolerance, and backend database sharding. To simplify mobile app development, we present Mobius, a system that addresses the messaging and data management challenges of mobile application development. Mobius introduces MUD (Messaging Unified with Data). MUD presents the programming abstraction of a logical table of data that spans devices and clouds. Applications using Mobius can asynchronously read from/write to MUD tables, and also receive notifications when tables change via continuous queries on the tables. The system combines dynamic client-side caching (with intelligent policies chosen on the server-side, based on usage patterns across multiple applications), notification services, flexible query processing, and a scalable and highly available cloud storage system. We present an initial prototype to demonstrate the feasibility of our design. Even in our initial prototype, remote read and write latency overhead is less than 52 % when compared to a hand-tuned solution. Our dynamic caching reduces the number of messages by a factor of 4 to 8.5 when compared to fixed strategies, thus reducing latency, bandwidth, power, and server load costs, while also reducing data staleness.
Nonparametric Density Estimation With Region-Censored Data (2014)

Publication in the conference proceedings of EUSIPCO, Lisbon, Portugal, 2014
Kuntien väliset erot sairastavuudessa : THL:n sairastavuusindeksin tuloksia (2014)

Kuntien välillä oli merkittäviä eroja sairastavuudessa jaksolla 2009–2011. Myös perinteinen itä-länsijako sairaamman Itä-Suomen ja terveemmän Länsi-Suomen välillä oli edelleen näkyvissä. Yli 50 000 asukkaan kaupunkien vertailussa suurinta sairastavuus oli Kotkassa, Kuopiossa, Oulussa, Turussa ja Joensuussa, ja korkein indeksiarvo oli yli puolet suurempi kuin matalin (Kotka 124 – Espoo 76). Suurimmat sairausryhmittäiset alue-erot havaittiin sydän- ja verisuonisairauksissa, tuki- ja liikuntaelinsairauksissa, vakavissa mielenterveyden häiriöissä sekä dementiassa. Vaikka suurimman sairastavuuden kaupunkien tilanne näyttää johtuvan osittain eri sairauksista, yhteistä niille on se, että mielenterveyden häiriöt ovat niissä keskimääräistä yleisempiä.&#13;\n&#13;\nTHL:n sairastavuusindeksi soveltuu hyvin kuntien sairastavuuserojen arviointiin ja terveystyön kehittämistarpeiden tunnistamiseen. Ikävakioimaton indeksi kuvaa kuntien todellista sairaustaakkaa, johon myös ikärakenne vaikuttaa, kun taas ikävakioitu luku soveltuu kuntien väliseen vertailuun.
Inactivation of RAS association domain family 1A gene in cervical carcinomas and the role of human papillomavirus infection. (2003)

Recently, we have identified a new putative tumor suppressor gene, RASSF1A (Ras association domain family 1A gene), located at human chromosome 3p21.3, the segment that is often lost in many types of human cancers. The RASSF1A promoter was shown to be frequently hypermethylated in various epithelial tumors, including small cell lung, breast, bladder, prostate, gastric, and renal cell carcinomas. In this study, we have analyzed the methylation status of the RASSF1A gene in primary human cervical cancers and in eight cervical cancer cell lines. The RASSF1A promoter is hypermethylated in 4 of 42 (= 10%) of squamous cell carcinomas, in 4 of 19 (= 21%) of adenosquamous carcinomas, and in 8 of 34 (= 24%) of cervical adenocarcinomas. Although in adenocarcinomas, methylation of RASSF1A and presence of human papillomavirus (HPV) type 16 or 18 sometimes coexisted, not a single case of HPV-16/18-positive squamous cell carcinomas had RASSF1A methylation. Similarly, in all eight analyzed cervical cell lines, RASSF1A inactivation and HPV infection were mutually exclusive (Fisher's exact test; P = 0.0357): two HPV-negative cervical cancer cell lines had a methylated and silenced RASSF1A promoter (C-33A and HT-3), whereas the other six HPV-positive lines expressed RASSF1A mRNA (ME 180, MS751, SiHa, C-4I, HeLa, and CaSki). For cervical tumors and cell lines combined, the Pearson's chi(2) test (chi(2) = 3.99; P <or= 0.05) indicates a borderline-significant reverse correlation between inactivation of RASSF1A and the presence of high-risk HPVs. Our data imply that the presence of HPVs in cervical carcinomas alleviates the requirement for RASSF1A inactivation and suggests that these two events may engage the same tumorigenic pathway.
Direct Patterning of CdSe Quantum Dots into Sub-100 nm Structures (2010)

Ordered, two-dimensional cadmium selenide (CdSe) arrays have been fabricated on indium-doped tin oxide (ITO) electrodes using the pattern replication in nonwetting templates (PRINT) process. CdSe quantum dots (QDs) with an average diameter of 2.7 nm and a pyridine surface ligand were used for patterning. The PRINT technique utilizes a perfluoropolyether (PFPE) elastomeric mold that is tolerant of most organic solvents, thus allowing solutions of CdSe QDs in 4-picoline to be used for patterning without significant deformation of the mold. Nanometer-scale diffraction gratings have been successfully replicated with CdSe QDs.
Luminescent iron clusters in solution (2013)

Metal clusters, composed of a few atoms at the core, exhibit unique properties and have potential applications. Although atomically precise clusters of noble metals have been synthesized, analogous systems of reactive metals, such as iron, have not been realized in solution due to high reactivity. Here we report the synthesis and characterization of novel iron clusters in the hemoglobin matrix that are highly luminescent (quantum yield 10% at 565 nm). The super-paramagnetic iron clusters, after successful ligand exchange from protein and phase transfer from water to chloroform using tri-octylphosphineoxide (TOPO), were detected as [Fe₁₀(TOPO)₃(H₂O)₃](+), [Fe₁₃(TOPO)₂(H₂O)](+) and [Fe₈(TOPO)(H₂O)₂](+) by mass spectrometry. This study lays the groundwork for exploiting unique properties of soluble iron clusters.
On the Ability of Coumarin Derivatives to Interact with Photoinitiators. (2000)

The interactions, in the excited states, between a coumarin and a ketocoumarin together with bisimidazole derivative, mercaptobenzoxazole, titanocene have been studied by laser absorption spectroscopy and by photoconductivity. The redox potentials of these different compounds have been measured and led to the calculation of free enthalpy change for a possible electron transfer reaction. The whole results show that the coumarin is able to demonstrate the formation of radicals through an electron transfer reaction with the additives. On the other hand, the ketocoumarin rather leads to an energy transfer reaction with bisimidazole and to a hydrogen abstraction reaction with the benzoxazole derivative. This study presumes that several coumarin or ketocoumarin/additives combinations should be able to initiate a radical polymerization reaction.
Accentuation of high susceptibility of hypertrophied myocardium to ischemia: Complementary assessment of Gadophrin‐enhancement and left ventricular function with MRI (2004)

The aim of the study was to compare infarction size and left ventricular (LV) function in normal and hypertrophied hearts after brief ischemia using Gadophrin-enhancement and functional assessment by MRI. Rats (n = 20) were assigned to aortic banding to induce LV hypertrophy or control. Eight weeks later, rats were subjected to 25 min of regional myocardial ischemia followed by 3 hr of reperfusion. The necrosis-specific agent Gadophrin-3 was injected to delineate infarcted myocardium on MRI. Effects of aortic banding and ischemia on LV mass and function were determined. At postmortem, areas at risk and infarction were measured. Close correlation was found between LV mass measured with MRI and at postmortem (r = 0.98). LV mass measured with MRI was significantly greater (0.81 +/- 0.02 g) in animals with aortic banding compared to control (0.62 +/- 0.02 g; P < 0.001). Infarction size was larger in hypertrophied hearts (19.0 +/- 1.4% / 18.3 +/- 1.5%) than in control (9.8 +/- 1.7% / 9.2 +/- 2.0%) on Gadophrin-enhanced MRI and at postmortem, respectively. Similarly, greater impairment in ejection fraction was observed in hypertrophied hearts with MRI (39 +/- 4% vs. 49 +/- 2%; P = 0.02). Gadophrin-3 provides accurate estimation of infarct size in hypertrophied hearts. Hypertrophied hearts are more sensitive to ischemia than nonhypertrophied hearts. The complementary assessment of Gadophrin-enhancement and LV function with MRI provides unique information about myocardium sensitivity to ischemia.
Paired tumor biopsy analysis and safety data from a pilot study evaluating Tremelimumab - a monoclonal antibody against CTLA-4 - in combination with ablative therapy in patients with hepatocellular carcinoma (HCC) (2014)

Meeting abstracts Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and results in inhibition of B7-CTLA-4-mediated down regulation of T cell activation. Both transcatheter arterial chemoembolization (TACE) and radiofrequency
Rod-shape theranostic nanoparticles facilitate antiretroviral drug biodistribution and activity in human immunodeficiency virus susceptible cells and tissues (2019)

Human immunodeficiency virus theranostics facilitates the development of long acting (LA) antiretroviral drugs (ARVs) by defining drug-particle cell depots. Optimal drug formulations are made possible based on precise particle composition, structure, shape and size. Through the creation of rod-shaped particles of defined sizes reflective of native LA drugs, theranostic probes can be deployed to measure particle-cell and tissue biodistribution, antiretroviral activities and drug retention. <b>Methods</b>: Herein, we created multimodal rilpivirine (RPV) <sup>177</sup>lutetium labeled bismuth sulfide nanorods (<sup>177</sup>LuBSNRs) then evaluated their structure, morphology, configuration, chemical composition, biological responses and adverse reactions. Particle biodistribution was analyzed by single photon emission computed tomography (SPECT/CT) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging. <b>Results</b>: Nanoformulated RPV and BSNRs-RPV particles showed comparable physicochemical and cell biological properties. Drug-particle pharmacokinetics (PK) and biodistribution in lymphoid tissue macrophages proved equivalent, one with the other. Rapid particle uptake and tissue distribution were observed, without adverse reactions, in primary blood-derived and tissue macrophages. The latter was seen within the marginal zones of spleen. <b>Conclusions</b>: These data, taken together, support the use of <sup>177</sup>LuBSNRs as theranostic probes as a rapid assessment tool for PK LA ARV measurements.
Chemical Chaperones Mitigate Experimental Asthma by Attenuating Endoplasmic Reticulum Stress (2013)

Endoplasmic reticulum (ER) stress and consequent unfolded protein response (UPR) are important in inflammation but have been poorly explored in asthma. We used a mouse model of allergic airway inflammation (AAI) with features of asthma to understand the role of ER stress and to explore potential therapeutic effects of inhaled chemical chaperones, which are small molecules that can promote protein folding and diminish UPR. UPR markers were initially measured on alternate days during a 7-day daily allergen challenge model. UPR markers increased within 24 hours after the first allergen challenge and peaked by the third challenge, before AAI was fully established (from the fifth challenge onward). Three chemical chaperones-glycerol, trehalose, and trimethylamine-N-oxide (TMAO)-were initially administered during allergen challenge (preventive regimen). TMAO, the most effective of these chemical chaperones and 4-phenylbutyric acid, a chemical chaperone currently in clinical trials, were further tested for potential therapeutic activities after AAI was established (therapeutic regimen). Chemical chaperones showed a dose-dependent reduction in UPR markers, airway inflammation, and remodeling in both regimens. Our results indicate an early and important role of the ER stress pathway in asthma pathogenesis and show therapeutic potential for chemical chaperones.
Ultrafast broadband Fourier-transform CARS spectroscopy operating at 50,000 spectra/second (2017)

We present a coherent Raman scattering (CRS) spectroscopy technique achieving a CRS spectral acquisition rate of 50,000 spectra/second over a Raman spectral region of 200 - 1430 cm<sup>-1</sup> with a resolution of 4.2 cm<sup>-1</sup>. This ultrafast, broadband and high-resolution CRS spectroscopic performance is realized by a polygonal Fourier-domain delay line serving as an ultra-rapid optical-path-length scanner in a broadband Fourier-transform coherent anti-Stokes Raman scattering (CARS) spectroscopy platform. We present a theoretical description of the technique and demonstrate continuous, ultrafast, broadband, and high-resolution CARS spectroscopy on a liquid toluene sample using our proof-of-concept setup.
Aerosolization of Nanotherapeutics as a Newly Emerging Treatment Regimen for Peritoneal Carcinomatosis (2019)

Recent advances in locoregional chemotherapy have opened the door to new approaches for the clinical management of peritoneal carcinomatosis (PC) by facilitating the delivery of anti-neoplastic agents directly to the tumor site, while mitigating adverse effects typically associated with systemic administration. In particular, an innovative intra-abdominal chemotherapeutic approach, known as Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC), was recently introduced to the intraperitoneal (IP) therapy regimens as a palliative therapeutic option in patients with PC, presumably providing a better drug distribution pattern together with deeper drug penetration into tumor nodules within the peritoneal space. Furthermore, the progress of nanotechnology in the past few decades has prompted the application of different nanomaterials in IP cancer therapy, offering new possibilities in this field ranging from an extended retention time to sustained drug release in the peritoneal cavity. This review highlights the progress, challenges, and opportunities in utilizing cancer nanotherapeutics for locoregional drug delivery, with a special emphasis on the aerosolization approach for intraperitoneal therapies.
Impact of BRCAness on the efficacy of oxaliplatin-based chemotherapy in patients with unresectable pancreatic cancer. (2017)

250 Background: Defects in individual genes that are involved in homologous recombination repair (HRR) is called “BRCAness” and several studies suggested that patients with BRCAness are more sensitive to platinum-based chemotherapy (Golan et al, 2014; Lowery et al, 2011; Vollebergh et al, 2014). We introduced the multiplex gene panel test into daily clinical practice since April 2015 at Kyoto University Hospital, in which we can monitor the entire coding region of 215 cancer-related genes and the rearrangement of 17 frequently rearranged genes. The purpose of this study was to evaluate the association between BRCAness status monitored by multiplex gene panel test and clinical outcome of patients with unresectable pancreatic ductal adenocarcinoma (PDAC) who received oxaliplatin-based chemotherapy. Methods: A total of consecutive 17 patients with histologically confirmed PDAC who underwent multiplex gene panel test were eligible. BRCAness status was determined according to the results of multiplex gene panel test. Oxaliplatin-based chemotherapy included FOLFIRINOX, GEMOX and SOX. We assessed the time to treatment failure (TTF) to evaluate the efficacy of oxaliplatin-based chemotherapy by log-rank test. Results: BRCAness-related mutations were detected in BRCA2 (n = 6), ATM (n = 4), ATR (n = 2), BRCA1 (n = 2), and PALB2 (n = 1). Based on these results, 11 patients were classified into non-BRCAness group and six patients were into BRCAness group. Seven and five patients received oxaliplatin-based chemotherapy in non-BRCAness and BRCAness group, respectively. Median TTF of oxaliplatin-based chemotherapy was 52 days (95% confidence interval [CI], 40–90 days) in non-BRCAness group and 294 days (95% CI, 56 days–NA) in BRCAness group. The difference was statistically significant (P = 0.027). Of note, two patients with BRCAness showed good response to FOLFIRINOX without disease progression &gt; 500 days. Conclusions: BRCAness-related mutations could be a promising predictive marker of the efficacy of oxaliplatin-based chemotherapy.
Fluctuating Thermal Field in the Near-Hole Region for Film Cooling Flows (1998)

The film cooling flow field is the result of a highly complex interaction between the film cooling jets and the mainstream. Understanding this interaction is important in order to explain the physical mechanisms involved in the rapid decrease of effectiveness, which occurs close to the hole exit. Not surprisingly, it is this region that is not modeled satisfactorily with current film cooling models. This study uses a high-frequency-response temperature sensor, which provides new information about the film cooling flow in terms of actual turbulence levels and probability density functions of the thermal field. Mean and rms temperature results are presented for 35 deg round holes at a momentum flux ratio of I = 0.16, at a density ratio of DR = 1.05. Probability density functions of the temperature indicate penetration of the mainstream into the coolant core, and ejection of coolant into the mainstream. Extreme excursions in the fluctuating temperature measurements suggest existence of strong intermittent flow structures responsible for dilution and dispersion of the coolant jets.
Phosphoproteomics revealed cellular signals immediately responding to disruption of cancer amino acid homeostasis induced by inhibition of l-type amino acid transporter 1 (2022)

This study provides new perspectives on LAT1-dependent cellular processes and a rationale for therapeutics targeting reprogrammed cancer metabolism.
92GHz 64QAM signal generation by optical frequency doubler (2016)

New communication system for high-speed train passengers is required to provide broadband services in the train. Radio over fiber in millimeter wave band is considered to provide a high throughput of the system. As a proof of concept, we generate 92 GHz 200 M symbol/sec 64QAM signals by optical frequency doubler. EVM of the signal is 7.14%. The result shows 1.2Gbps transmission is available in MMW band by radio over fiber.