bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanisms of bifunctional vitamin D receptor agonist-histone deacetylase inhibitor hybrid molecules in triple-negative breast cancer
Authors: Barbier Camille , Mansour Ali , Ismailova Aiten , Sarmadi Fatemeh , Scarlata David A. , Bouttier Manuella , Zeitouni Camille , Wang Catherine , Gleason James L. , White John H. 
Published: April 2022

AbstractThe active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), and its analogues signal through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor, and have been extensively investigated as anticancer agents. 1,25D and its analogs have potential in combination therapies because they exhibit synergistic activities with other anticancer agents such as histone deacetylase inhibitors (HDACi). We have developed a series of hybrid molecules that combine HDACi within the backbone of a VDR agonist and thus represent fully integrated bifunctional molecules. They exhibit anti-tumor efficacy in reducing tumor growth and metastases in an aggressive model of triple-negative breast cancer. However, their solubility is limited by their hydrophobic diarylpentane cores. Our goals here were two-fold: (1) to improve the solubility of hybrids by introducing nitrogen into diarylpentane cores, and (2) to investigate the molecular mechanisms underlying their anti-tumor efficacy by performing comparative gene expression profiling studies with 1,25D and the potent HDACi suberoylanilide hydroxamic acid (SAHA). We found that substituting aryl with pyrydyl rings did not sacrifice bifunctionality and modestly improved solubility. Notably, one compound, AM-193, displayed enhanced potency as a VDR agonist and in cellular assays of cytotoxicity. RNAseq studies in triple negative breast cancer cells revealed that gene expression profiles of hybrids were very similar to that of 1,25D, as was that observed with 1,25D and SAHA combined. The effects of SAHA alone on gene expression were limited and distinct from those 1,25D or hybrids. The combined results suggest that efficacy of hybrids arises from targeting HDACs that do not have a direct role in gene regulation. Moreover, pathways analysis revealed that hybrids regulate numerous genes controlling immune cell infiltration into tumors and suppress the expression of several secreted molecules that promote breast cancer growth and metastasis.
No significant difference in intermediate key outcomes in men with low- and intermediate-risk prostate cancer managed by active surveillance
Authors: Cyll Karolina , Löffeler Sven , Carlsen Birgitte , Skogstad Karin , Plathan May Lisbeth , Landquist Martin , Haug Erik Skaaheim 
Published: April 2022

AbstractActive surveillance (AS) is standard of care for patients with low-risk prostate cancer (PCa), but its feasibility in intermediate-risk patients is controversial. We compared outcomes of low- and intermediate-risk patients managed with multiparametric magnetic resonance imaging (mpMRI)-supported AS in a community hospital. Of the 433 patients enrolled in AS between 2009 and 2016, 358 complied with AS inclusion criteria (Cancer of the Prostate Risk Assessment (CAPRA) score ≤ 5, Gleason grade group (GGG) ≤ 2, clinical stage ≤ cT2 and prostate-specific antigen (PSA) ≤ 20 ng/ml) and discontinuation criteria (histological-, PSA-, clinical- or radiological disease reclassification). Of the 358 patients, 177 (49%) were low-risk and 181 (51%) were intermediate-risk. Median follow-up was 4.2 years. The estimated 5-year treatment-free survival (TFS) was 56% (95% confidence interval [CI] 51–62%). Intermediate-risk patients had significantly shorter TFS compared with low-risk patients (hazard ratio 2.01, 95% CI 1.47–2.76, p < 0.001). There were no statistically significant differences in the rate of adverse pathology, biochemical recurrence-free survival and overall survival between low- and intermediate-risk patients. Two patients developed metastatic disease and three died of PCa. These results suggest that selected patients with intermediate-risk PCa may be safely managed by mpMRI-supported AS, but longer follow-up is necessary.
Transglutaminase 3 negatively regulates immune responses on the heart of the mosquito, Anopheles gambiae
Authors: Yan Yan , Ramakrishnan Abinaya , Estévez-Lao Tania Y. , Hillyer Julián F. 
Published: April 2022

AbstractThe immune and circulatory systems of insects are functionally integrated. Following infection, immune cells called hemocytes aggregate around the ostia (valves) of the heart. An earlier RNA sequencing project in the African malaria mosquito, Anopheles gambiae, revealed that the heart-associated hemocytes, called periostial hemocytes, express transglutaminases more highly than hemocytes elsewhere in the body. Here, we further queried the expression of these transglutaminase genes and examined whether they play a role in heart-associated immune responses. We found that, in the whole body, injury upregulates the expression of TGase2, whereas infection upregulates TGase1, TGase2 and TGase3. RNAi-based knockdown of TGase1 and TGase2 did not alter periostial hemocyte aggregation, but knockdown of TGase3 increased the number of periostial hemocytes during the early stages of infection and the sequestration of melanin by periostial hemocytes during the later stages of infection. In uninfected mosquitoes, knockdown of TGase3 also slightly reduced the number of sessile hemocytes outside of the periostial regions. Taken altogether, these data show that TGase3 negatively regulates periostial hemocyte aggregation, and we hypothesize that this occurs by negatively regulating the immune deficiency pathway and by altering hemocyte adhesion. In conclusion, TGase3 is involved in the functional integration between the immune and circulatory systems of mosquitoes.
Five nanometer size highly positive silver nanoparticles are bactericidal targeting cell wall and adherent fimbriae expression
Authors: Pokhrel Lok R. , Jacobs Zachary L. , Dikin Dmitriy , Akula Shaw M. 
Published: April 2022

AbstractTo tackle growing antibiotic resistance (AR) and hospital-acquired infections (HAIs), novel antimicrobials are warranted that are effective against HAIs and safer for human use. We hypothesize that small 5 nm size positively charged nanoparticles could specifically target bacterial cell wall and adherent fimbriae expression, serving as the next generation antibacterial agent. Herein we show highly positively charged, 5 nm amino-functionalized silver nanoparticles (NH2–AgNPs) were bactericidal; highly negatively charged, 45 nm citrate-functionalized AgNPs (Citrate–AgNPs) were nontoxic; and Ag+ ions were bacteriostatic forming honeycomb-like potentially resistant phenotype, at 10 µg Ag/mL in E. coli. Further, adherent fimbriae were expressed with Citrate–AgNPs (0.5–10 µg/mL), whereas NH2–AgNPs (0.5–10 µg/mL) or Ag+ ions (only at 10 µg/mL) inhibited fimbriae expression. Our results also showed no lipid peroxidation in human lung epithelial and dermal fibroblast cells upon NH2–AgNPs treatments, suggesting NH2–AgNPs as a biocompatible antibacterial candidate. Potent bactericidal effects demonstrated by biocompatible NH2–AgNPs and the lack of toxicity of Citrate–AgNPs lend credence to the hypothesis that small size, positively charged AgNPs may serve as a next-generation antibacterial agent, potentially addressing the rising HAIs and patient health and safety.
Using virtual global landmark to improve incidental spatial learning
Authors: Liu Jia , Singh Avinash Kumar , Lin Chin-Teng 
Published: April 2022

AbstractTo reduce the decline of spatial cognitive skills caused by the increasing use of automated GPS navigation, the virtual global landmark (VGL) system is proposed to help people naturally improve their sense of direction. Designed to accompany a heads-up navigation system, VGL system constantly displays silhouette of global landmarks in the navigator’s vision as a notable frame of reference. This study exams how VGL system impacts incidental spatial learning, i.e., subconscious spatial knowledge acquisition. We asked 55 participants to explore a virtual environment and then draw a map of what they had explored while capturing electroencephalogram (EEG) signals and eye activity. The results suggest that, with the VGL system, participants paid more attention during exploration and performed significantly better at the map drawing task—a result that indicates substantially improved incidental spatial learning. This finding might kickstart a redesigning navigation aids, to teach users to learn a route rather than simply showing them the way.
Short and long-term costs of inbreeding in the lifelong-partnership in a termite
Authors: Eyer Pierre-André , Vargo Edward L. 
Published: April 2022

AbstractSocial life and lifelong partner commitments are expected to favor thorough partner choice, as an ill-suited partnership may have long-term consequences, adversely affecting the parents and spanning several cohorts of offspring. Here, we used ~1400 termite incipient colonies to estimate the short- and long-term costs of inbreeding upon the survival of the parents over a 15-month period, their productivity, and the resistance of their offspring toward pathogen pressure. We observed that foundation success was not influenced by the relatedness of partners, but by their levels of microbial load. We showed faster growth in inbred colonies with low levels of microbial load, revealing a potential tradeoff between pathogen defense and offspring production. Yet, inbreeding takes its toll later in colony development when offspring from incipient colonies face pathogen pressure. Although the success of a lifetime partnership is initially determined by the partner’s health, the cost of inbreeding in incipient colonies favors outbred colonies reaching maturity.
Hidden Markov modeling for maximum probability neuron reconstruction
Authors: Athey Thomas L. , Tward Daniel J. , Mueller Ulrich , Vogelstein Joshua T. , Miller Michael I. 
Published: April 2022

AbstractRecent advances in brain clearing and imaging have made it possible to image entire mammalian brains at sub-micron resolution. These images offer the potential to assemble brain-wide atlases of neuron morphology, but manual neuron reconstruction remains a bottleneck. Several automatic reconstruction algorithms exist, but most focus on single neuron images. In this paper, we present a probabilistic reconstruction method, ViterBrain, which combines a hidden Markov state process that encodes neuron geometry with a random field appearance model of neuron fluorescence. ViterBrain utilizes dynamic programming to compute the global maximizer of what we call the most probable neuron path. We applied our algorithm to imperfect image segmentations, and showed that it can follow axons in the presence of noise or nearby neurons. We also provide an interactive framework where users can trace neurons by fixing start and endpoints. ViterBrain is available in our open-source Python package .
Acceleration of enzymatic catalysis by active hydrodynamic fluctuations
Authors: Tripathi Ashwani Kr. , Das Tamoghna , Paneru Govind , Pak Hyuk Kyu , Tlusty Tsvi 
Published: April 2022

AbstractThe cellular milieu is teeming with biochemical nano-machines whose activity is a strong source of correlated non-thermal fluctuations termed active noise. Essential elements of this circuitry are enzymes, catalysts that speed up the rate of metabolic reactions by orders of magnitude, thereby making life possible. Here, we examine the possibility that active noise in the cell, or in vitro, affects enzymatic catalytic rate by accelerating or decelerating the crossing rate of energy barriers during the reaction. Considering hydrodynamic perturbations induced by biochemical activity as a source of active noise, we evaluate their impact on the enzymatic cycle using a combination of analytic and numerical methods. Our estimates show that the fast component of the active noise spectrum may significantly enhance the turnover rate of enzymes, while reactions remain practically unaffected by the slow noise spectrum. Revisiting the physics of barrier crossing under the influence of active hydrodynamic fluctuations suggests that the biochemical activity of macromolecules such as enzymes is coupled to active noise. Thus, we propose that enzymatic catalysis is a collective, many-body process in which enzymes may affect each other’s activity via long-range hydrodynamic interaction, with potential impact on biochemical networks in living and artificial systems alike.
Machine learning‐assisted direction‐of‐arrival accuracy enhancement technique using oversized lens‐loaded cavity
Authors: Abbasi Muhammad Ali Babar , Yurduseven Okan , Akinsolu Mobayode O. , Fusco Vincent F. , Liu Bo , Khalily Mohsen , Cotton Simon L. , Imran Muhammad Ali 
Published: April 2022

AbstractThis paper presents a framework for achieving machine learning (ML)‐assisted direction‐of‐arrival (DoA) accuracy enhancement using a millimetre‐wave (mmWave) dynamic aperture. The technique used for the enhanced DoA estimation accuracy leverages an over‐sized lens‐loaded cavity antenna connected to a single RF chain in the physical layer and a computational method in the computational layer of the framework. It is shown for the first time that by introducing a reconfigurable mode‐mixing mechanism inside the over‐sized lens‐loaded cavity hardware, a greater number of spatially orthogonal radiation modes can be achieved giving rise to many cavity states. If the best cavity state is determined and selected by means of design exploration using a contemporary ML‐assisted antenna optimisation method, the computational DoA estimation accuracy can be improved. The mode‐mixing mechanism in this work is a randomly oriented metallic scatterer located inside an over‐sized constant−ϵr lens‐loaded cavity, connected to a stepper motor that is electronically controlled by inputs from the computational layer of the presented framework. Measurement results in terms of near‐field radiation mode scans are included in this study to verify and validate that the proposed ML‐assisted framework enhances the DoA estimation accuracy. Moreover, this investigation simultaneously provides a simplification in the physical layer implementation of mmWave radio hardware, and DoA accuracy enhancement, which in turn lends itself favourably to the adoption of the proposed framework for channel sounding in mmWave communication systems.
Transient obscuration event captured in NGC 3227
Authors: Mao J. , Kaastra J. S. , Mehdipour M. , Kriss G. A. , Wang Y. , Grafton-Waters S. , Branduardi-Raymont G. , Pinto C. , Landt H. , Walton D. J. , Costantini E. , Di Gesu L. , Bianchi S. , Petrucci P.-O. , De Marco B. , Ponti G. , Fukazawa Y. , Ebrero J. , Behar E. 
Published: April 2022

Context. A growing number of transient X-ray obscuration events in type I active galactic nuclei suggest that our line of sight to the central engine is not always free. Multiple X-ray obscuration events were reported in the nearby Seyfert 1.5 galaxy NGC 3227 from 2000 to 2016. In late 2019, another X-ray obscuration event was identified with Swift. Two coordinated target-of-opportunity observations with XMM-Newton, NuSTAR, and the Hubble Space Telescope (HST) Cosmic Origins Spectrograph (COS) were triggered in November and December 2019 to study this obscuration event.
Aims. We aim to constrain the physical properties of the absorbing material (i.e., the obscurer) that caused the X-ray obscuration event in late 2019. We also aim to compare the handful of obscuration events in NGC 3227 and other Seyfert galaxies.
Methods. For each observation, we analyzed the time-averaged X-ray spectra collected with XMM-Newton and NuSTAR. We performed photoionization modeling with the SPEX code, which allows us to constrain the intrinsic continuum simultaneously with various photoionized absorption and emission components.
Results. Similar to previous transient X-ray obscuration events in NGC 3227, the one caught in late 2019 is short-lived (less than five months). If the obscurer has only one photoionized component, the two X-ray observations in late 2019 cannot be explained by the same obscurer that responds to the varying ionizing continuum. Due to the unknown geometry of the obscurer, its number density and distance to the black hole cannot be well constrained. The inferred distance covers at least two orders of magnitude, from the broad-line region to the dusty torus. Unlike some other X-ray obscuration events in Seyfert galaxies, such as NGC 5548 and NGC 3783, no prominent blueshifted, broad absorption troughs were found in the 2019 HST/COS spectra of NGC 3227 when compared with archival UV spectra. This might be explained if the X-ray obscurer does not intercept our line of sight to (a significant portion of) the UV-emitting region. Understanding the variety of observational differences in the X-ray obscuration events observed so far is not straightforward. Future observations with high-quality data are needed to unveil the nature of the X-ray obscuration events.
Une clinique de la déliaison, une reprise du rêve traumatique
Authors: Malfait Anne 
Published: April 2022

La clinique de l’exil dans la rencontre avec des sujets présentant des états déliés complexes, interroge le dispositif de nouage des registres Réel, Symbolique, Imaginaire pour ceux-ci. Parmi les phénomènes de répétition, le rêve traumatique surgit avec ses effets de rupture : un réel affleure.
À l’appui de l’hypothèse de la déliaison des registres, celle-ci contribue à désaffilier le sujet du champ de l’Autre fragilisant l’abri que constitue l’ordre symbolique. Cette clinique exemplifie et actualise la disjonction structurelle présente, entre le réel du corps d’une part, et l’image unifiée du corps, d’autre part, même si la prévalence du symbolique et le primat du langage ont introduit le sujet dans la fonction métaphorique et la médiation du fantasme. L’adresse à l’analyste dans le transfert peut venir constituer pour un sujet un lieu d’appui, afin d’y tenter un re-nouage subjectif, notamment par un travail sur l’affect, « vraie touche du réel ».
Physikalische Medizin
Rehabilitationsmedizin Kurortmedizin
Authors: Lieb Max Emanuel 
Published: April 2022

Physikalische und Rehabilitative Medizin als klinisch-praktisches
Fachgebiet im Kontext der rehabilitativen GesundheitsstrategieIm Rahmen der Entwicklungen der Aus- und Weiterbildung ergaben sich in den letzten
Jahren für unser Fachgebiet viele Veränderungen. Auch weiterhin ist
vieles im Fluss. Viele dieser Änderungen haben einen normativen Charakter
für die zukünftige Entwicklung. Selten zuvor ergibt sich dabei so
häufig die Frage nach der Einordnung der Physikalischen und Rehabilitativen
Medizin (PRM) in den gesamten Kontext der Rehabilitation.
Abklärung der Alzheimer-Demenz – akademische Spielerei oder sinnvolle klinische Maßnahme?
Authors: Tatò Maia , Perneczky Robert 
Published: April 2022

ZusammenfassungImmer mehr Menschen leiden an einer Demenz, deren häufigste Ursache die Alzheimer-Krankheit ist. Die Abklärung der Alzheimer-Demenz ist aufwendig und ihre klinische Relevanz angesichts fehlender spezifischer Therapien unsicher. Vor diesem Hintergrund ist ein gestuftes Vorgehen sinnvoll. Besteht der Verdacht auf eine Alzheimer-Demenz, sollten Anamnese, körperliche und psychiatrische Untersuchung, neuropsychologische Testdiagnostik, Bluttests und zerebrale Bildgebung erfolgen. Diese Maßnahmen erlauben in vielen Fällen eine diagnostische Einordnung. In unklaren Fällen kommen heute Biomarker-Tests zunehmend zum Einsatz. Wissen über die Diagnose hilft den Betroffenen, die Prognose einzuschätzen, ihre Zukunft zu planen und Therapieangebote in Anspruch zu nehmen. Die Zulassung von Aducanumab in den USA, Phase-3-Studien weiterer Antikörperstrategien und die Entwicklung neuer Blutbiomarker machen zudem Hoffnung für die Zukunft.
Neutralisierende monoklonale Antikörper bei COVID-19: eine Fallserie aus der Hausarztpraxis
Authors: Böbel Markus , Joos Stefanie , Förster Christian 
Published: April 2022

Zusammenfassung
Hintergrund Neutralisierende monoklonale Antikörper (mAK) gegen SARS-CoV-2 reduzieren bei Patienten mit Risikofaktoren die Schwere des Verlaufs von COVID-19. Für ihre Wirksamkeit ist die frühzeitige Gabe zu Infektionsbeginn entscheidend. In diesem frühen Stadium der Erkrankung ist der Hausarzt/die Hausärztin erster Ansprechpartner und somit zentral für den weiteren Verlauf. Bisher kommen mAK jedoch nur selten im hausärztlichen Setting zum Einsatz. Diese Fallserie soll zeigen, dass die Gabe von mAK auch in der Hausarztpraxis sicher durchführbar ist.
Kasuistiken Es werden 7 Fälle mit Risiko für einen schweren Verlauf von COVID-19 berichtet. Zwei von ihnen waren ungeimpft, 5 unter medikamentöser Immunsuppression und ein Patient hatte ein erhöhtes Risiko durch Trisomie-21. Alle Patientinnen und Patienten wurden im Januar/Februar 2022 in der Hausarztpraxis erfolgreich mit dem mAK Sotrovimab behandelt, 2 von ihnen als Hausbesuch. Anhand der Fälle werden klinische Eckdaten und ein praxisnahes Handling dieser Therapieform geschildert.
Schlussfolgerung Neutralisierende mAK können sicher und mit überschaubarem Aufwand im ambulanten Sektor verabreicht werden und bei Patienten mit COVID-19 und Risikofaktoren dazu beitragen, schwere Verläufe und Krankenhausaufnahmen zu vermeiden.
WALANT na osteossíntese percutânea do escafoide
Authors: Folberg Celso Ricardo , Alves Jairo André de Oliveira , Pereira Fernando Maurente Sirena , Pedrozo Vitor Bernardes 
Published: April 2022

ResumoAs fraturas do escafoide representam entre 50 e 70% de todas as fraturas dos ossos do carpo. A osteossíntese percutânea do escafoide pode usar a abordagem dorsal ou volar, ambas com bons resultados. É mais comumente realizada sob anestesia geral ou bloqueio nervoso regional. A técnica de anestesia local com o paciente totalmente acordado e sem torniquete (WALANT, na sigla em inglês) já é considerada uma técnica segura e eficaz na cirurgia da mão. A anestesia local com epinefrina causa vasoconstrição, o que evita o uso de torniquete e, consequentemente, a necessidade de sedação do paciente. Assim, a possibilidade de testar a estabilidade da fixação sob forças fisiológicas é outra grande vantagem do uso da anestesia local. Na técnica descrita aqui, o movimento ativo do punho e da mão pode ser testado imediatamente após a fixação escafoide. A técnica WALANT tem sido cada vez mais utilizada na cirurgia da mão em partes moles e na fixação de fraturas de metacarpo e falanges. No entanto, até o momento, não há literatura publicada abordando o uso dessa técnica na osteossíntese percutânea do escafoide. O objetivo desta nota técnica é descrever o uso de WALANT tanto para a abordagem dorsal quanto volar na osteossíntese percutânea do escafoide.
Endoscopic Sponge Vacuum Therapy for Large Infected Esophagus Pleural Fistula
Authors: Bhaware Bhushan , Mukewar Shrikant , Daswani Ravi , Gawande Atul , Mukewar Saurabh 
Published: April 2022

AbstractA 50-year-old man with hypothyroidism was diagnosed with severe pneumonia secondary to the SARS-CoV-2 virus with an HRCT CORAD score of 18/25 in September 2020. From the records, the patient appeared to have developed spontaneous esophageal perforation. In view of his poor general condition, he was treated with endoscopic sponge vacuum therapy (EVT). EVT is a novel approach for treatment for a closed cavity. Also, very few studies exist in the literature in regard to this procedure.