bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management einer persistierenden Kolitis nach erfolgreicher Immuntherapie eines nicht-kleinzelligen Karzinoms der Lunge
Authors: Zellweger Matthias , Rogler Gerhard , Komminoth Paul , Werth Lucas , Breidert Matthias 
Published: January 2022

ZusammenfasssungImmuncheckpoint-Inhibitoren haben als neue Generation von Medikamenten in der Anti-Tumortherapie bemerkenswerte Wirksamkeit gezeigt. Die unspezifische Aktivierung des Immunsystems führt jedoch zu einer Reihe von unerwünschten Nebenwirkungen, sog. immune-related adverse events (irAEs), inklusive des Auftretens von Diarrhoe und Kolitis bei etwa einem Drittel der behandelten Patienten.Endoskopisch und histologisch gibt es weitreichende Überlappungen der immunvermittelten Kolitis mit der klassischen CED, was eine Unterscheidung erschwert.Therapeutisch kommen bei Grad-3- (schwere) bis Grad-4-Kolitiden (lebensbedrohlich) neben dem Abbruch der ICI-Therapie hochdosiert Glukokortikoide zum Einsatz. Steroidrefraktäre Fälle (bis 42%) profitieren vom TNF-Hemmer Infliximab. Vedolizumab stellt, analog bei chronisch entzündlichen Darmerkrankungen, die Zweitlinientherapie bei Infliximab-refraktären Fällen dar. Zur Wirksamkeit von Tofacitinib bei therapierefraktären Fällen existieren bislang nur wenige Daten.Wir beschreiben den Fall und das Therapiemanagement einer schweren und andauernden immunvermittelten Kolitis nach erfolgreicher Immunochemotherapie mit Pembrolizumab bei einem 80-jährigen Mann mit einem metastasierten, nicht kleinzelligen Karzinom der Lunge und vorbestehender Colitis indeterminata (colitis unclassified) sowie weiteren Komorbiditäten.
Contrast-enhanced ultrasonography (CEUS) reveals active bleeding into an abdominal hematoma in a patient with ongoing subcutaneous injections
Authors: Klenk Christopher , Clevert Dirk-André 
Published: January 2022

AbstractA 95-year-old woman with metastasizing bronchial carcinoma presents with left inguinal pain. The referring physician would like to exclude an inguinal hernia and a deep vein thrombosis due to her precondition of essential thrombocythemia. Conventional ultrasound excluded the presence of a deep vein thrombosis yet showed a 6 cm × 5 cm hematoma distal of the left m. rectus abdominis. The subsequently performed color Doppler examination excluded a pseudoaneurysm but could not preclude active bleeding. Eventually, CEUS showed contrast-pooling within the hematoma as a sign of active extravasation, suggesting ongoing bleeding.
Anticoagulation in Pediatric Patients
Authors: Male Christoph 
Published: January 2022

AbstractSpecial aspects of anticoagulation in children include the different epidemiology of thrombosis, developmental changes in the coagulation system, age-dependent pharmacokinetics of anticoagulants, risk of bleeding, and practical hurdles to anticoagulation. The classical anticoagulants so far used in children have several limitations, resulting in the need for regular monitoring. The pharmacological properties of direct oral anticoagulants (DOACs) and the special challenges of anticoagulation in children make the DOACs particularly attractive for children. All DOACs have pediatric development programs, targeting various indications for prevention and treatment of thrombosis. Child-appropriate formulations have been developed, age-specific dosing information generated, and safety and efficacy evaluated in ongoing phase 3 trials. Rivaroxaban and dabigatran have already been authorized for children for treatment of acute venous thrombosis and for extended secondary prevention. Their safety and efficacy have been demonstrated comparable to that of standard-of-care anticoagulants, without need for monitoring. Further studies are ongoing, which are expected to lead to pediatric authorizations of DOACs for primary venous thromboembolic event prevention in some high-risk settings. More real-life data will be necessary from postmarketing studies and registries to complement the evidence base for DOAC use in children, particularly in the youngest age groups and special disease populations.
In silico
Investigation of Lon Protease as a Promising
Therapeutic Target
Authors: Asadollahi Parisa , Pakzad Iraj , Ghafourian Sobhan , Kazemian Hossein , Fatahi Roohollah , Sadeghifard Nourkhoda , Kalani Behrooz Sadeghi 
Published: January 2022

AbstractConsidering the widespread occurrence of antibiotic resistance, the need for new
therapeutic strategies is inevitable. Bacterial proteases are a broad set of
enzymes that play a vital role in cell survival, stress response, and
pathogenicity. This in silico study was aimed to focus on the crucial
role of Lon protease in the regulation of toxin-antitoxin systems in E.
coli and to design inhibitory peptides against the action of this
protease. With the help of relevant servers and softwares, the communication
network, the evolutionary history, and the interaction of Lon with the
corresponding antitoxins were examined, following which the inhibitory peptides
were designed against these interactions. The results showed that Lon protease
plays a central role in the control of these systems and is a conserved protein,
especially among the Enterobacteriaceae family. The docking results of the
designed peptides with the Lon protease were significant. This study showed that
Lon protease may have the characteristics of a new therapeutic target.
Evaluation of the Genotoxic Potential of the Selective COX-2
Inhibitor Enflicoxib in a Battery of in vitro and in vivo
Genotoxicity Assays
Authors: Guzmán Antonio , Homedes Josep , Salichs Marta 
Published: January 2022

Abstract
Aim Enflicoxib, a selective COX-2 inhibitor approved for the treatment of
pain and inflammation associated with osteoarthritis in dogs
(Daxocox® [Ecuphar/Animalcare Group]) was
assessed for its genotoxic potential in a battery of in vitro and in
vivo genotoxicity assays. These comprised a bacterial reverse mutation
assay (Ames test), an in vitro human lymphocyte chromosome aberration
assay and an in vivo mouse bone marrow micronucleus assay.
Methods Relevant vehicle and positive control cultures and animals were
included in all assays. In the Ames test, enflicoxib was tested at
concentrations of up to 5000 μg/plate. Signs of
cytotoxicity were observed at the highest tested concentrations for several of
the bacterial strains, both in absence and presence of S9. In human lymphocytes,
enflicoxib was assessed for the induction of chromosomal aberrations when
exposed at concentrations of up to 62.5 (3 hours) and
29.6 µg/mL (20 hours) in the absence of S9, and
up to 66.7 µg/mL (3 hours) in presence of S9.
Signs of cell toxicity, evidenced as a decrease in the mitotic index, were
observed at these concentrations. In the mouse micronucleus assay, enflicoxib
dose levels of up to 2000 mg/kg were administered (single dose)
to male and female animals, and bone marrow samples were taken 24 and
48 hours (high-dose animals only) after administration.
Results Enflicoxib was shown to lack genotoxic activity in the conducted
assays.
Conclusions The administration of enflicoxib as a therapeutic analgesic
agent would not pose a genotoxic risk to animals or humans.
Mechanochemical Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles Mediated by PPh3-TCCA
Authors: Pattarawarapan Mookda , Yamano Dolnapa , Wiriya Nittaya , Phakhodee Wong , Wet-osot Sirawit 
Published: January 2022

AbstractMechanochemical synthesis of 2,5-disubstituted 1,3,4-oxadiazoles was developed as an environmentally benign alternative to conventional solvent-based methods. In the presence of triphenylphosphine and trichloroisocyanuric acid, N-acylbenzotriazoles condense with acylhydrazides leading to oxadiazoles derivatives in good to excellent yields within minutes. The approach circumvents the need for strictly anhydrous conditions, external heating, long reaction times, as well as tedious multistep procedures. A range of substrates with reactive functionalities was also well tolerated.
New Insights into the Prevention of Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia Caused by Viruses
Authors: Klompas Michael 
Published: January 2022

AbstractA fifth or more of hospital-acquired pneumonias may be attributable to respiratory viruses. The SARS-CoV-2 pandemic has clearly demonstrated the potential morbidity and mortality of respiratory viruses and the constant threat of nosocomial transmission and hospital-based clusters. Data from before the pandemic suggest the same can be true of influenza, respiratory syncytial virus, and other respiratory viruses. The pandemic has also helped clarify the primary mechanisms and risk factors for viral transmission. Respiratory viruses are primarily transmitted by respiratory aerosols that are routinely emitted when people exhale, talk, and cough. Labored breathing and coughing increase aerosol generation to a much greater extent than intubation, extubation, positive pressure ventilation, and other so-called aerosol-generating procedures. Transmission risk is proportional to the amount of viral exposure. Most transmissions take place over short distances because respiratory emissions are densest immediately adjacent to the source but then rapidly dilute and diffuse with distance leading to less viral exposure. The primary risk factors for transmission then are high viral loads, proximity, sustained exposure, and poor ventilation as these all increase net viral exposure. Poor ventilation increases the risk of long-distance transmission by allowing aerosol-borne viruses to accumulate over time leading to higher levels of exposure throughout an enclosed space. Surgical and procedural masks reduce viral exposure but do not eradicate it and thus lower but do not eliminate transmission risk. Most hospital-based clusters have been attributed to delayed diagnoses, transmission between roommates, and staff-to-patient infections. Strategies to prevent nosocomial respiratory viral infections include testing all patients upon admission, preventing healthcare providers from working while sick, assuring adequate ventilation, universal masking, and vaccinating both patients and healthcare workers.
Combined EUS LAMS and Percutaneous Fully Covered SEMS-Guided Direct Endoscopic Necrosectomy (e-DEN + p-DEN) for Walled-Off Pancreatic Necrosis with Paracolic Extension
Authors: Gandhi Ashish , Borkar Mangesh , Bapaye Harsh , Pujari Rajendra , Bapaye Amol 
Published: January 2022

AbstractManagement of infected lesser sac walled-off pancreatic necrosis (WOPN) is technically challenging and involves endoscopic ultrasound (EUS)-guided transmural drainage using either lumen-apposing metal stent (LAMS) or multiple plastic stents as the standard approach. A step-up approach—drainage followed by additional direct endoscopic necrosectomy (DEN) whenever required—has been a standard recommendation. Collections extending to the paracolic gutter are difficult to manage endoscopically and often require additional surgical intervention. In this video case, we describe a combined approach using EUS-guided LAMS and percutaneous fully covered self-expandable metal stent-guided DEN (e-DEN + p-DEN) for successful management of an infected lesser sac WOPN with paracolic extension.
Composition of Piperine with Enteric-Coated Chitosan Microspheres Enhances the Transepithelial Permeation of Curcumin in Sheep Intestinal Mucosa and Caco-2 Cells
Authors: Thomas Githa , Koland Marina 
Published: January 2022

Abstract
Objectives The purpose of this study was to investigate the efficacy of enteric-coated chitosan microspheres with herbal bioenhancer, piperine, as a suitable composition for improving the permeation of curcumin through biological membranes using suitable ex vivo models.
Material and Methods Chitosan microspheres of curcumin and piperine were prepared by an emulsion cross-linking method using glutaraldehydes the cross-linking agent and characterized for size, shape, entrapment efficiency, mucoadhesion, and in vitro release. The effect of piperine on the permeation of curcumin through excised sheep intestinal mucosa and Caco-2-cell monolayer was investigated.
Statistical Analysis The data from permeation studies were analyzed by Student's t-test using Statistical Package for the Social Sciences (SPSS) software (SPSS, Chicago, IL, United States) with p-values <0.05 indicating statistical significance.
Results The formulations showed mucoadhesion for a period of more than 6 hours which was influenced by the chitosan content. The rate of drug release of uncoated formulation followed first-order kinetics, and the mechanism of release was non-Fickian transport. Optimized formulation was coated with a pH-sensitive polymer, Eudragit S-100, by a solvent evaporation technique in different concentrations and evaluated for ex vivo permeation through sheep intestinal mucosa and Caco-2-cell monolayer. Scanning electron microscopy images of the optimized coated formulation showed spherical particles with smooth surfaces. The calculated permeation flux and permeability coefficient of curcumin from microspheres were at least 20% greater in the presence of piperine through the intestinal mucosa and 30% through the Caco-2-cell monolayer model. The permeability coefficient of curcumin from microspheres with piperine was 1.93 × 10 to 5 cm/sec and significantly greater (p < 0.05) than that of microspheres devoid of piperine and from aqueous dispersion (p < 0.005).
Conclusion The study confirmed the contribution of piperine and mucoadhesive microspheres toward improved permeation of curcumin through biological membranes, thereby providing an approach that has the potential of increasing transport through intestinal epithelial cells and possibly enhancing the oral bioavailability of this drug.
Psychological Impact Assessment in Patients with Noncommunicable Diseases during COVID-19 Pandemic through Validated Fear of COVID-19 scale: A Cross-Sectional Online Survey
Authors: Ponnam Hima B. , Akondi Butchi R. , Jagadabhi Santosh K. , Koppula Divya T. , Konduru Shanmukha P. 
Published: January 2022

Abstract
Background The novel coronavirus disease 2019 (COVID-19) pandemic has created immense panic globally with its advent in December 2019 and now showing readvent with its camouflage of different dangerous mutant strains. Its psychological repercussions on the community are very disastrous and immeasurable. At this juncture, the most vulnerable group are the patients of Noncommunicable diseases (NCDs) who are the most sufferers due to the impact caused by the anxiety and fear of COVID-19 apart from its high rate of infectivity. In this context, an online survey to assess the levels of anxiety and fear of COVID-19 in patients with lifestyle diseases has been taken up.
Methods This was an online cross-sectional survey using the Fear of COVID-19 Scale (FCV-19S) to assess the levels of anxiety and fear in patients with NCDs. The survey was made available for both genders and an age group of 30 years and above in India.
Results and Discussion A total of 627 participants participated in this online survey. The Indian residents with NCDS )Noncommunicable diseases) were found to suffer from significantly increased levels of anxiety and fear of COVID-19 and almost 60.4% of the participants were found to acquire these lifestyle diseases as diabetes and hypertension during this recent COVID-19 times.
Conclusion This survey shows the real-time psychological impact of COVID-19 which has a disastrous effect upon the community especially on the patients with NCDs who are the most vulnerable group. The study findings corroborate with the recent studies conducted on NCDs.
A Study of Clinical and Serological Correlation of Positive Direct Antiglobulin Test in Blood Bank at a Tertiary Care Center
Authors: Kerkar Alisha Suresh , Bhagwat Swarupa Nikhil , Sharma Jayashree Harihara 
Published: January 2022

Abstract
Objectives Detection of red cell bound immunoglobulins and/or complement by direct antiglobulin test (DAT) is a crucial serological assay in the diagnosis of autoimmune hemolytic anemia (AIHA). However, DAT may be positive in a variety of clinical conditions with or without hemolysis. We aimed at evaluating the clinical and serological correlation of positive DAT by categorizing the clinical conditions associated with positive DAT, estimating the presence of in vivo hemolysis in case of positive DAT with polyspecific and monospecific antisera and correlating the strength of positive DAT with the presence of hemolysis.
Materials and Methods The prospective observational study was performed on 200 samples that were positive for DAT with polyspecific antiglobulin reagent as the baseline investigation. These samples were further tested with anti-immunoglobulin G and anti-C3 monospecific DAT reagents to evaluate the type of protein responsible for positive DAT. The antiglobulin tests were performed by tube technique. DAT positivity was graded (1+ to 4 + ) in each patient. Autocontrol test was included. The patients with positive polyspecific DAT were categorized into different clinical conditions. The presence or absence of in vivo hemolysis was evaluated in all clinical categories and also for each grade of positivity with polyspecific and monospecific antiglobulin reagents.
Statistical Analysis Binomial logistic regression and Mann–Whitney U test were applied to between the group analyses. For categorical variables, Fisher's exact test and relative risk were used. The qualitative data were expressed in numbers and percentages.
Results The highest number of patients (75/200, 37.5%) belonged to the autoimmune diseases group. Tuberculosis and hepatitis C were the main infectious diseases associated with positive DAT. Out of 200 DAT-positive patients, 98 (49%) had in vivo hemolysis and 102 (51%) did not have hemolysis. AIHA (22) and systemic lupus erythematosus (18) were the commonest clinical conditions associated with in vivo hemolysis. All the 11 samples that showed positivity with only anti-C3 reagent did not show any hemolysis. There was statistically significant increase in the incidence of in vivo hemolysis with increasing grades of DAT positivity with all the three antihuman globulin reagents.
Conclusion There are different disease conditions which show positive DAT with or without hemolysis. So, it is important to clinically and serologically correlate positive DAT results.
Passive near-field imaging via grating-based spectroscopy
Authors: Sakuma R. , Lin K.-T. , Kim S. , Kimura F. , Kajihara Y. 
Published: January 2022

Passive scattering-type scanning near-field optical microscopy (s-SNOM) has recently been developed for studying long-wavelength infrared (LWIR) waves. It detects surface-localized waves without any external illumination or heating and enables the imaging of hot-electron energy dissipation and nanoscale Joule heating. However, the lack of a wavelength selection mechanism in the passive LWIR s-SNOM makes it difficult to perform a thorough analysis of the surface-localized waves. Here, we develop a novel passive scanning near-field optical spectroscopy with a diffraction grating. The spectroscopic optics are designed to exhibit a high signal efficiency and mechanical performance at the temperature of liquid helium (4.2 K). Using the developed passive LWIR near-field spectroscopy, the spectral information of thermally excited evanescent waves can be directly obtained without any influence from the external environment factors, including environmental heat. We have detected the thermally excited evanescent waves on a SiC/Au micropatterned sample at room temperature with a spatial resolution of 200 nm and a wavelength resolution of 500 nm at several wavelengths in the range of 14–15 µm. The obtained spectra are consistent with the electromagnetic local density of states calculated based on the fluctuation–dissipation theorem. The developed passive LWIR near-field spectroscopy enables the spectral analysis of ultrasmall surface-localized waves, making it a high-performance surface analysis tool.
Design and fabrication of a large-range graphene/hexagonal boron nitride heterostructure based pressure sensor with poly(methyl methacrylate) substrate
Authors: Zhang Guodong , Zhao Yulong , Sun Jing 
Published: January 2022

Aiming at overpressure measurement, this paper presents a large-range graphene/hexagonal boron nitride (h-BN) heterostructure-based pressure sensor with a poly(methyl methacrylate) (PMMA) substrate. Graphene and h-BN are chosen as sensitive materials because they both have large Young’s modulus, high intrinsic strength, high natural frequency, and atomic thickness at the same time. These characteristics provide favorable conditions for the application of the sensor in the high pressure and high frequency dynamic environment. Moreover, the photoresist-assisted transfer technology is proposed for transferring graphene from the growth substrate to the PMMA substrate and the lift-off method with exposure and development is developed to achieve metal patterning on the PMMA substrate. The sensor characterization results suggest that the graphene and h-BN films have good transfer qualities and the heterojunction possesses excellent electrical performance. The static pressure loading experiments confirm that the sensor has a pressure range of up to 85 MPa and its piezoresistive coefficient is 0.7 GPa−1, which indicates that the designed sensor is suitable for overpressure fields. This study provides a novel method for determining overpressure and lays a foundation for the fabrication of graphene-based electronic devices with an organic substrate.
Rapid radiation in a highly diverse marine environment
Authors: Hench Kosmas , Helmkampf Martin , McMillan W. Owen , Puebla Oscar 
Published: January 2022

SignificanceAdaptive radiation, the evolutionary process whereby a lineage diversifies over a short period of time, often occurs in geographically isolated or newly formed habitats where colonizing species encounter unoccupied niches and reduced selective pressures. Rapid radiations may also occur in diverse and complex environments, but these cases are less well documented. Here, we show that the hamlets, a group of Caribbean reef fishes, radiated within the last 10,000 generations in a burst of diversification that ranks among the fastest in fishes. Genomic analysis suggests that color pattern diversity is generated by different combinations of alleles at a few genes with large effect. Such a modular genomic architecture of diversification is emerging as a common denominator to a variety of radiations.
Surrogate gradients for analog neuromorphic computing
Authors: Cramer Benjamin , Billaudelle Sebastian , Kanya Simeon , Leibfried Aron , Grübl Andreas , Karasenko Vitali , Pehle Christian , Schreiber Korbinian , Stradmann Yannik , Weis Johannes , Schemmel Johannes , Zenke Friedemann 
Published: January 2022

SignificanceNeuromorphic systems aim to accomplish efficient computation in electronics by mirroring neurobiological principles. Taking advantage of neuromorphic technologies requires effective learning algorithms capable of instantiating high-performing neural networks, while also dealing with inevitable manufacturing variations of individual components, such as memristors or analog neurons. We present a learning framework resulting in bioinspired spiking neural networks with high performance, low inference latency, and sparse spike-coding schemes, which also self-corrects for device mismatch. We validate our approach on the BrainScaleS-2 analog spiking neuromorphic system, demonstrating state-of-the-art accuracy, low latency, and energy efficiency. Our work sketches a path for building powerful neuromorphic processors that take advantage of emerging analog technologies.