gebhart/patrepeval huggingface dataset:
<i>Nocardia</i>Infection in Solid Organ Transplant Recipients: A Multicenter European Case-control Study (2016)

We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.
Therapeutic Perspectives on Pancreatic Cancer (2013)

Pancreatic cancer has a poor prognosis, with only 10% survival one year following diagnosis. Despite significant advances in conventional therapies (chemotherapy and radiotherapy), little improvement in patient survival has occurred in the last decade. Therefore, there is a critical need for novel and effective therapeutic approaches for this cancer. This article reviews current concepts in the pathogenesis and treatment of pancreatic cancer, the latter including tumor resection approaches and the current standard of care. We further describe recent advances in new and combination therapies, which result only in modest increases in survival, and discuss challenges in drug delivery and limiting toxicity.
Olefin Epoxidation by Alkyl Hydroperoxide with a Novel Cross-Bridged Cyclam Manganese Complex:  Demonstration of Oxygenation by Two Distinct Reactive Intermediates (2007)

Olefin epoxidation provides an operative protocol to investigate the oxygen transfer process in nature. A novel manganese complex with a cross-bridged cyclam ligand, MnIV(Me2EBC)(OH)2(2+) (Me2EBC = 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane), was used to study the epoxidation mechanism with biologically important oxidants, alkyl hydroperoxides. Results from direct reaction of the freshly synthesized manganese(IV) complex, [Mn(Me2EBC)(OH)2](PF6)2, with various olefins in neutral or basic solution, and from catalytic epoxidation with oxygen-labeled solvent, H2 18O, eliminate the manganese oxo moiety, Mn(IV)=O, as the reactive intermediate and obviate an oxygen rebound mechanism. Epoxidations of norbornylene under different conditions indicate multiple mechanisms for epoxidation, and cis-stilbene epoxidation under atmospheric 18O2 reveals a product distribution indicating at least two distinctive intermediates serving as the reactive species for epoxidation. In addition to alkyl peroxide radicals as dominant intermediates, an alkyl hydroperoxide adduct of high oxidation state manganese(IV) is suggested as the third kind of active intermediate responsible for epoxidation. This third intermediate functions by the Lewis acid pathway, a process best known for hydrogen peroxide adducts. Furthermore, the tert-butyl peroxide adduct of this manganese(IV) complex was detected by mass spectroscopy under catalytic oxidation conditions.
Case of X‐linked hypohidrotic ectodermal dysplasia, along with facial bilateral reticular pigmentation (2020)

A novel phenotype of facial bilateral reticular pigmentation accompanied with severe xerotic dermatitis was found in a patient with X-linked hypohidrotic ectodermal dysplasia (XLHED). A novel point mutation p.C346R in EDA gene was identified without filaggrin mutations frequently observed in Japanese. A point mutation in EDA gene was considered to be responsible for these phenotype.
A distinct M2 macrophage infiltrate and transcriptomic profile decisively influence adipocyte differentiation in lipedema (2022)

Lipedema is a chronic and progressive adipose tissue disorder, characterized by the painful and disproportionate increase of the subcutaneous fat in the lower and/or upper extremities. While distinct immune cell infiltration is a known hallmark of the disease, its role in the onset and development of lipedema remains unclear. To analyze the macrophage composition and involved signaling pathways, anatomically matched lipedema and control tissue samples were collected intra-operatively from gender- and BMI-matched patients, and the Stromal Vascular Fraction (SVF) was used for Cytometry by Time-of-Flight (CyTOF) and RNA sequencing. The phenotypic characterization of the immune component of lipedema versus control SVF using CyTOF revealed significantly increased numbers of CD163 macrophages. To gain further insight into this macrophage composition and molecular pathways, RNA sequencing of isolated CD11b+ cells was performed. The analysis suggested a significant modification of distinct gene ontology clusters in lipedema, including cytokine-mediated signaling activity, interleukin-1 receptor activity, extracellular matrix organization, and regulation of androgen receptor signaling. As distinct macrophage populations are known to affect adipose tissue differentiation and metabolism, we evaluated the effect of M2 to M1 macrophage polarization in lipedema using the selective PI3Kγ inhibitor IPI-549. Surprisingly, the differentiation of adipose tissue-derived stem cells with conditioned medium from IPI-549 treated SVF resulted in a significant decreased accumulation of lipids in lipedema versus control SVF. In conclusion, our results indicate that CD163+ macrophages are a critical component in lipedema and re-polarization of lipedema macrophages can normalize the differentiation of adipose-derived stem cells <i>in vitro</i> evaluated by the cellular lipid accumulation. These data open a new chapter in understanding lipedema pathophysiology and may indicate potential treatment options.
Use of an Extracorporeal Membrane Oxygenation Circuit as a Bridge to Salvage a Major Upper-Extremity Replant in a Critically Ill Patient (2010)

Major replantation of the upper extremity is defined as replantation at or above the level of the wrist. Selection of appropriate candidates is complex and requires consideration of many patient- and injury-associated factors including patient age, associated injuries, patient desire, mechanism of injury, ischemia time, wound condition, and presence of multiple-level injury. With respect to age, younger patients, especially children, are deemed to have a distinct advantage over more elderly patients due to improved nerve regeneration, and many advocate making every effort to replant this population. The risks of major upper-extremity replantation are significant and include bleeding, depletion of coagulation factors, secondary infection, and sepsis. As a result, major systemic illness and significant associated injuries are accepted as contraindications to limb salvage in this patient population. Herein we describe the use of an extracorporeal membrane oxygenation (ECMO) circuit as a potential bridge for short-term preservation of the extremity in a young patient with an acute, concomitant systemic illness. In the authors' opinion, use of ECMO perfusion is a viable means of maintaining extremity perfusion over hours or even days and may lead to broadened replant criteria in patients with associated injuries.
Explaining Impossible High-Level Robot Behaviors (2012)

A key challenge in robotics is the generation of controllers for autonomous, high-level robot behaviors comprising nontrivial sequences of actions, including reactive and repeated tasks. When constructing controllers to fulfill such tasks, it is often not known a priori whether the intended behavior is even feasible; plans are modified on the fly to deal with failures that occur during execution, often still without guaranteeing correct behavior. Recently, formal methods have emerged as a powerful tool to automatically generate autonomous robot controllers that guarantee desired behaviors expressed by a class of temporal logic specifications. However, when the specification cannot be fulfilled, these approaches do not provide the user with a source of failure, making the troubleshooting of specifications an unstructured and time-consuming process. This paper describes an algorithm to automatically analyze an unsynthesizable specification in order to identify causes of failure. It also introduces an interactive game to explore possible causes of unsynthesizability, in which the user attempts to fulfill the robot specification against an adversarial environment. The proposed algorithm and game are implemented as features within the LTLMoP toolkit for robot mission planning.
Passivity of a class of sampled-data systems: application to haptic interfaces (2005)

Passivity of systems comprising a continuous time plant and discrete time controller is considered. This topic is motivated by stability considerations arising in the control of robots and force-reflecting human interfaces ("haptic interfaces"). A necessary and sufficient condition for the passivity of a class of sampled-data systems is derived. An example-implementation of a "virtual wall" via a one degree-of-freedom haptic interface-is presented.
Crosstalk Tolerance of Spatially Multiplexed MIMO Systems (2012)

We assess the tolerance of an optical MIMO system to crosstalk from other, nominally isolated MIMO systems to trade optical component crosstalk specifications with MIMO digital signal processing complexity in spatially multiplexed transmission.
GENDER DIFFERENCES IN SMALL INTESTINAL ENDOTHELIAL FUNCTION: ANDROGEN PLAYS AN INHIBITORY ROLE. (2003)

Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294
A scanning SQUID microscope for imaging high-frequency magnetic fields (2009)

This thesis examines the design and operation of a large-bandwidth scanning SQUID microscope for spatially imaging high frequency magnetic fields. Towards this end, I present results on a cryo-cooled 4.2 K scanning SQUID microscope with a bandwidth of dc to 2 GHz and a sensitivity of about 52.4 nT per sample. By using a thin-film hysteretic Nb dc-SQUID and a pulsed sampling technique, rather than a non-hysteretic SQUID and a flux-locked loop, the bandwidth limitation of existing scanning SQUID microscopes is overcome. The microscope allows for non-contact images of time-varying magnetic field to be taken of room-temperature samples with time steps down to 50 ps and spatial resolution ultimately limited by the size of the SQUID to about 10 micrometers. The new readout scheme involves repeatedly pulsing the bias current to the dc SQUID while the voltage across the SQUID is monitored. Using a fixed pulse amplitude and applying a fixed dc magnetic flux allows the SQUID to measure the applied magnetic flux with a sampling time set by the pulse length of about 400 ps. To demonstrate the capabilities of the microscope, I imaged magnetic fields from 0 Hz (static fields) up to 4 GHz. Samples included a magnetic loop, microstrip transmission lines, and microstrip lines with a break in order to identify and isolate electrical opens in circuits. Finally, I discuss the operation and modeling of the SQUID and how to further increase the bandwidth of the microscope to allow bandwidth of upwards of 10 GHz.
Supplementary Data (for Review only) from STING Signaling in Melanoma Cells Shapes Antigenicity and Can Promote Antitumor T-cell Activity (2023)

&lt;p&gt;Figure S1-S6&lt;/p&gt;
Synthesis of Functionalized <i>trans</i>‐A<sub>2</sub>B<sub>2</sub>‐Porphyrins Using Donor–Acceptor Cyclopropane‐Derived Dipyrromethanes (2013)

Abstract meso ‐Substituted trans ‐A 2 B 2 ‐porphyrins bearing specific patterns of substituents are crucial building blocks in porphyrin‐based biomimetic systems and molecular materials and can be used for the construction of well‐defined porphyrin‐based architectures. A new stepwise and rational synthesis of functionalized trans ‐A 2 B 2 ‐porphyrins is reported in which for the first time donor–acceptor‐substituted cyclopropane precursors (d–a cyclopropanes) are exploited. The three presented d–a cyclopropanes are readily accessible in a multi‐gram scale and serve as aldehyde equivalents in the reaction with an excess of pyrrole to afford the corresponding dipyrromethanes (DPMs). The three DPMs were synthesized in yields of 60–74%. They are stable in purified form in the absence of light and air and were subsequently condensed with a wide range of aliphatic and aromatic aldehydes bearing electron‐donating or electron‐withdrawing substituents followed by oxidation to form the corresponding trans ‐A 2 B 2 ‐porphyrins. Fourteen functionalized porphyrins were synthesized in yields of 14–31%, indicating the broad scope of the synthetic procedure. The possibility to introduce key functional groups is emphasized, which enables subsequent modification of these porphyrins with moieties inducing biological activity. Modification of the tetrapyrroles may occur by addition to one of the porphyrin peripheral double bonds, the use of substituents of the aryl groups or via the methoxycarbonyl group at two of the meso ‐substituents. Three examples of porphyrins were converted into the corresponding 7,8‐dihydroxychlorins by osmium‐mediated dihydroxylation and one of the resulting chlorins was subjected to saponification to give a highly polar chlorin dicarboxylic acid. A 4‐bromophenyl‐substituted d–a cyclopropane was prepared by rhodium‐catalyzed cyclopropanation and then transformed into a DPM which was subsequently condensed to a porphyrin. Its Zn complex allowed a Heck reaction to afford the functionalized bis(alkenyl)‐substituted trans ‐A 2 B 2 ‐Zn‐porphyrin.
Real-time handheld multispectral optoacoustic imaging (2013)

Multispectral optoacoustic tomography (MSOT) of functional and molecular contrast has the potential to find broad deployment in clinical practice. We have developed the first handheld MSOT imaging device with fast wavelength tuning achieving a frame rate of 50 Hz. In this Letter, we demonstrate its clinical potential by dynamically resolving multiple disease-relevant tissue chromophores, including oxy-/deoxyhemoglobin, and melanin, in human volunteers.
Lost in Transition: Start-Up of Glycolysis Yields Subpopulations of Nongrowing Cells (2014)

Cells need to adapt to dynamic environments. Yeast that fail to cope with dynamic changes in the abundance of glucose can undergo growth arrest. We show that this failure is caused by imbalanced reactions in glycolysis, the essential pathway in energy metabolism in most organisms. The imbalance arises largely from the fundamental design of glycolysis, making this state of glycolysis a generic risk. Cells with unbalanced glycolysis coexisted with vital cells. Spontaneous, nongenetic metabolic variability among individual cells determines which state is reached and, consequently, which cells survive. Transient ATP (adenosine 5'-triphosphate) hydrolysis through futile cycling reduces the probability of reaching the imbalanced state. Our results reveal dynamic behavior of glycolysis and indicate that cell fate can be determined by heterogeneity purely at the metabolic level.
Experimental and Computational Hydrate Screening: Cytosine, 5-Flucytosine, and Their Solid Solution (2017)

The structural, temperature- and moisture dependent stability features of cytosine and 5-flucytosine monohydrates, two pharmaceutically important compounds, were rationalized using complementary experimental and computational approaches. Moisture sorption/desorption, water activity, thermal analysis and calorimetry were applied to determine the stability ranges of hydrate ↔ anhydrate systems, while X-ray diffraction, IR spectroscopy and crystal structure prediction provided the molecular level understanding. At 25 °C, the critical water activity for the cytosine hydrate ↔ anhydrate system is ~0.43 and for 5-flucytosine ~0.41. In 5-flucytosine the water molecules are arranged in open channels, therefore the kinetic desorption data, dehydration < 40% relative humidity (RH), conform with the thermodynamic data, whereas for the cytosine isolated site hydrate dehydration was observed at RH < 15%. Peritectic dissociation temperatures of the hydrates were measured to be 97 °C and 84.2 °C for cytosine and 5-flucytosine, respectively, and the monohydrate to anhydrate transition enthalpies to be around 10 kJ mol<sup>-1</sup>. Computed crystal energy landscapes not only revealed that the substitution of C5 (H or F) controls the packing and properties of cytosine/5-flucytosine solid forms, but also have enabled the finding of a monohydrate solid solution of the two substances which shows increased thermal- and moisture-dependent stability compared to 5-flucytosine monohydrate.
Electrochemical <i>ipso</i>‐Thiocyanation of Arylboron Compounds (2019)

Abstract An operationally simple electrochemical method for the transition‐metal‐free ipso ‐thiocyanation of arylboronic acids and aryl trifluoroborates has been developed. The SCN electrophile is generated in situ by anodic oxidation of thiocyanate anions, which avoids formation of salt waste and prevents unwanted side reactions arising from chemical oxidants. The reaction proceeds regiospecifically, and the scope extends to non‐activated aromatic systems. magnified image
Achievement of Subchannel Frequency Spacing Less Than Symbol Rate and Improvement of Dispersion Tolerance in Optical OFDM Transmission (2009)

We propose a novel optical orthogonal frequency-division multiplexing (OFDM) transmission, where the frequency spacing of subchannels is less than the symbol rate. We show experimentally that the novel OFDM transmission achieves an optical SNR (OSNR) sensitivity level and dispersion tolerance roughly equivalent to those of the conventional OFDM. We also show the influence of chromatic dispersion from the transmission channel on the OFDM signal. The chromatic dispersion causes a desynchronization of the symbol timing between subchannels and breaks the frequency orthogonality in OFDM. We confirm experimentally that it is possible to mitigate the signal degradation due to the chromatic dispersion by optimizing the symbol timing and orthogonally polarizing the subchannels to the neighboring subchannels.
Deletion of the orphan nuclear receptor COUP-TFII in uterus leads to implantation failure and placental deficiency (2007)

National audience
Inhibiting Fatty Acid Synthase with Omeprazole to Improve Efficacy of Neoadjuvant Chemotherapy in Patients with Operable TNBC (2021)

FASN is commonly expressed in early TNBC. Omeprazole can be safely administered in doses that inhibit FASN. The addition of omeprazole to neoadjuvant AC-T yields a promising pCR rate that needs further confirmation in randomized studies.
Engineering high throughput screening platforms of cervical cancer (2023)

Cervical cancer is the second leading cause of cancer-related death in women under 40 and is one of the few cancers to have an increased incidence rate and decreased survival rate over the last 10 years. One in five patients will have recurrent and/or distant metastatic disease and these patients face a 5-year survival rate of less than 17%. Thus, there is a pressing need to develop new anticancer therapeutics for this underserved patient population. However, the development of new anticancer drugs remains a challenge, as only 7% of novel anticancer drugs are approved for clinical use. To facilitate identification of novel and effective anticancer drugs for cervical cancer, we developed a multilayer multicellular platform of human cervical cancer cell lines and primary human microvascular endothelial cells that interfaces with high throughput drug screening methods to evaluate the anti-metastatic and anti-angiogenic drug efficacy simultaneously. Through the use of design of experiments statistical optimization, we identified the specific concentrations of collagen I, fibrinogen, fibronectin, GelMA, and PEGDA in each hydrogel layer that maximized both cervical cancer invasion and endothelial microvessel length. We then validated the optimized platform and assessed its viscoelastic properties. Finally, using this optimized platform, we conducted a targeted drug screen of four clinically relevant drugs on two cervical cancer cell lines. Overall, this work provides a valuable platform that can be used to screen large compound libraries for mechanistic studies, drug discovery, and precision oncology for cervical cancer patients.
Comparing metastatic (M) young onset (YO) colorectal cancer (CRC) with average onset (AO): Do they differ clinically and genetically? (2018)

Background: The incidence of colorectal cancer in patients(pts) under the age of 50 has been steadily on rising over the last two decades. This is in sharp contrast to average onset CRC where there has been a decline. Little is known about clinical behavior and biology of metastatic CRC in the growing YO population. Methods: We defined YO as < 45 yo and AO as > 50 yo. To better understand the differences in biology of early onset rectal tumors, we tabulated the clinical characteristics, genomics using next generation sequencing(MSK-IMPACT), treatments and outcomes in 175 metastatic pts with EO CRC, treated at Memorial Sloan Kettering Cancer Center between 2014 and 2017 and compared these cases to a cohort of AO M CRC cases (n = 413) with CRC related hereditary syndromes such as Lynch Syndrome and inflammatory bowel disease were excluded. Results: We analyzed 175 in the YO cohort. Age at diagnosis was between 17-35yo in 46 and between 36-45 in 129 pts. Among YO patients, there were 50.2% males, 27.7% smokers and the median BMI was 25.5. Comparing to AO, YO pts have significantly less right sided tumors (22.8% vs 33%; p = 0.01). Treatment choices did not differ among YO vs AO groups; systemic chemotherapy (46.7% vs 42.6%; p = 0.40) and metastasectomy (54.6 vs 49.4; p = 0.33). Overall survival was 59months in the YO vs 63.9 for the AO (p = 0.194). Among genetic characteristics mutational burden and copy number comparison showed no significant differences between the groups. Conclusions: Our series describes a comprehensive clinical and genomic profile of EO mCRC. In contrast to prior reports YO does not appear to be associated with more aggressive disease and there was no difference in treatment modalities. Detailed genomic and clinical characteristics will be presented. Legal entity responsible for the study: Andrea Cercek. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Phenotypic Spectrum of Simpson–<scp>G</scp>olabi–<scp>B</scp>ehmel Syndrome in a Series of 42 Cases With a Mutation in <scp><i>GPC</i></scp><i>3</i> and Review of the Literature (2013)

Simpson-Golabi-Behmel syndrome (SGBS) is a rare X-linked multiple congenital abnormality/intellectual disability syndrome characterized by pre- and post-natal overgrowth, distinctive craniofacial features, macrocephaly, variable congenital malformations, organomegaly, increased risk of tumor and mild/moderate intellectual deficiency. In 1996, Glypican 3 (GPC3) was identified as the major gene causing SGBS but the mutation detection rate was only 28-70%, suggesting either genetic heterogeneity or that some patients could have alternative diagnoses. This was particularly suggested by some reports of atypical cases with more severe prognoses. In the family reported by Golabi and Rosen, a duplication of GPC4 was recently identified, suggesting that GPC4 could be the second gene for SGBS but no point mutations within GPC4 have yet been reported. In the genetics laboratory in Tours Hospital, GPC3 molecular testing over more than a decade has detected pathogenic mutations in only 8.7% of individuals with SGBS. In addition, GPC4 mutations have not been identified thus raising the question of frequent misdiagnosis. In order to better delineate the phenotypic spectrum of SGBS caused by GPC3 mutations, and to try to define specific clinical criteria for GPC3 molecular testing, we reviewed the clinical features of all male cases with a GPC3 mutation identified in the two molecular laboratories providing this test in France (Tours and Paris). We present here the results of the analysis of 42 patients belonging to 31 families and including five fetuses and three deceased neonates.