bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe herpes virus 6 interstitial pneumonia in an infant with three variants in genes predisposing to lung disease
Authors: De Rose Domenico Umberto , Auriti Cinzia , Lozzi Simona , Coltella Luana , Piccioni Livia , Rossi Sabrina , Novelli Antonio , Iannotta Rossella , Pianini Teresa , Picone Simonetta , Paolillo Piermichele , Savignoni Ferdinando , Capolupo Irma , Digilio Maria Cristina , Cutrera Renato , Dotta Andrea
Published: April 2021

Infections due to human herpesvirus 6 (HHV‐6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV‐6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV‐6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV‐6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late‐onset (15 days of life) severe interstitial pneumonia and heavy HHV‐6 genome load, persistently detected in its BAL fluid. The baby underwent high‐frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next‐generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a “probably pathogenetic” heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV‐6 infection should be considered in the differential diagnosis of late‐onset severe respiratory distress in neonates and the co‐occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV‐6 genome load in BAL fluid could be an indicator of the response to antiviral therapy.
Targeting the viral‐entry facilitators of SARS‐CoV‐2 as a therapeutic strategy in COVID‐19
Authors: Muralidar Shibi , Gopal Gayathri , Visaga Ambi Senthil
Published: April 2021

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is the causative agent of coronavirus disease 2019 (COVID‐19) infection, which has emerged as a global pandemic causing serious concerns. Lack of specific and effective therapeutics for the treatment of COVID‐19 is a major concern and the development of vaccines is another important aspect in managing the infection effectively. The first step in the SARS‐CoV‐2 pathogenesis is the viral entry and it is mediated by its densely glycosylated spike protein (S‐protein). Similar to the SARS‐CoV, SARS‐CoV‐2 also engages angiotensin‐converting enzyme 2 (ACE2) as the host cell entry receptor. In addition to ACE2, several recent studies have implicated the crucial role of cell surface heparan sulfate (HS) as a necessary assisting cofactor for ACE2‐mediated SARS‐CoV‐2 entry. Furthermore, SARS‐CoV‐2 was also identified to use both endosomal cysteine proteases cathepsin B and L (CatB/L) and the transmembrane serine protease 2 (TMPRSS2) for the pivotal role of S‐protein priming mediating viral entry. As the entry of SARS‐CoV‐2 into host cells is mandatory for viral infection, it becomes an extremely attractive therapeutic intervention point. In this regard, this review will focus on the therapeutic targeting of the crucial steps of SARS‐CoV‐2 viral entry like S‐protein/ACE2 interaction and S‐protein priming by host cell proteases. In addition, this review will also give insights to the readers on several therapeutic opportunities, pharmacological targeting of the viral‐entry facilitators like S‐Protein, ACE2, cell surface HS, TMPRSS2, and CatB/L and evidence for those drugs currently ongoing clinical studies.
Early Outcomes of Simultaneous Translabyrinthine Resection and Cochlear Implantation
Authors: Conway Robert M. , Tu Nathan C. , Sioshansi Pedrom C. , Porps Sandra L. , Schutt Christopher A. , Hong Robert S. , Jacob Jeffrey T. , Babu Seilesh C.
Published: April 2021

Objectives/Hypothesis

Hearing rehabilitation after translabyrinthine resection of a vestibular schwannoma (VS) has largely been based on the transfer of acoustic stimulus to the contralateral ear, typically through a contralateral routing of signal hearing aid or bone‐anchored hearing aid (BAHA). Cochlear implant, either as a subsequent surgery or simultaneously, has become a more common treatment option; however, there is still relatively limited data available on its success. The purpose of this study is to evaluate the early outcomes of simultaneous cochlear implantation in patients with sporadic VS undergoing translabyrinthine resection.

Study Design

Prospective, nonrandomized study.

Methods

A prospective study of nonrandomized patients was completed at a tertiary care neurotology center. Audiologic outcomes, primarily based on AzBIO in quiet and background noise, as well as consonant‐nucleus‐consonant (CNC) testing of the affected ears were utilized. Tinnitus, dizziness, and spatial hearing questionnaries were also completed. Audiologic outcomes and questionnaires were compared between the pre‐ and postoperative groups.

Results

Ten patients were included in the study with 3 month follow‐up data. There was statistically significant improvement in AzBO with +10 and +5 signal to noise ratio and in quiet, as well as in CNC testing (P < .05). There was a significant improvement in Tinnitus Handicap Inventory between the two groups.

Conclusions

Simultaneous cochlear implantation is a viable treatment for hearing loss after translabyrinthine approach to VS. These patients have improved hearing in background noise and tinnitus compared to their preoperative state. Further prognostic data are required to determine which patients are the best candidates.

Level of Evidence

4 Laryngoscope, 131:E2312–E2317, 2021
Perceived Financial Insecurity Impacts Healthcare Decision‐Making Among Patients With Sinusitis
Authors: Pandrangi Vivek C. , Farrell Nyssa Fox , Mace Jess C. , Detwiller Kara Y. , Smith Timothy L. , Geltzeiler Mathew
Published: April 2021

Objectives/Hypothesis

The economic burden of sinusitis is significant, and socioeconomic factors can impact patient decision‐making. The purpose of this study was to examine the impact of perceived financial insecurity on healthcare decision‐making and treatment compliance among sinusitis patients.

Study Design

Cross‐sectional study using the 2018 National Health Interview Survey.

Methods

Survey responses to nine questions regarding financial stressors and nine questions regarding cost‐saving healthcare actions were recorded, which included seeking lower cost medication, medication noncompliance, and avoiding care visits due to costs.

Results

There was a total weighted sample size of 28.9 million patients who self‐reported a diagnosis of sinusitis (12% of the U.S. population). Sinusitis patients who reported cost‐saving actions had an increased severity of perceived financial insecurity than those without cost‐saving actions (P < .001). Sinusitis patients with perceived financial insecurity had the highest odds of at least one cost‐saving action (odds ratio [OR] = 5.94, 95% CI = 5.911–5.970, P < .001), followed by lack of health insurance (OR = 5.13, 95% CI = 5.107–5.159, P < .001), and poor self‐reported health status (OR = 2.81, 95% CI = 2.792–2.822, P < .001). Increasing the number of financial stressors increased the odds of at least one cost‐saving action (P < .001). Across all financial stressors, the most commonly performed cost‐saving action was asking for lower cost medication.

Conclusions

Perceived financial insecurity is associated with cost‐saving healthcare actions among sinusitis patients, including treatment noncompliance. Interventions to assess financial insecurity among sinusitis patients may facilitate shared decision‐making for optimal, individualized treatment plans that may lead to improved outcomes and quality of life.

Level of Evidence

NA Laryngoscope, 131:2403–2412, 2021
Quantum characteristics and applications of multi‐pixel photon counter
Authors: Cai Yujie , Chen Yu , Chen Xiuliang , Wu Guang , Wu E
Published: April 2021

In this invited paper, we present an overview of the multi‐pixel photon counter (MPPC), which is a kind of spatial‐multiplexed photon‐number‐resolving detector. We review the operation principles of MPPC, its characterization via quantum detector tomography, and the applications of this detector in research fields such as quantum information, remote sensing and biological medicine. Finally, we discuss the current progress on the improvement of MPPC.
Eltrombopag in children with severe aplastic anemia
Authors: Lesmana Harry , Jacobs Timothy , Boals Michelle , Gray Nathan , Lewis Sara , Ding Juan , Kang Guolian , Hale Melvanique , Weiss Mitchell , Reiss Ulrike , Wang Winfred , Wlodarski Marcin
Published: April 2021

Background

Immunosuppressive therapy with horse antithymocyte globulin and cyclosporine currently remains the standard therapy for children with severe aplastic anemia (SAA) who lack human leukocyte antigen (HLA)‐identical sibling. The thrombopoietin receptor agonist eltrombopag has been recently approved for SAA patients 2 years and older. However, there are limited data on its safety and efficacy in pediatric cohorts.

Methods

We conducted a retrospective study of patients ≤18 years old consecutively diagnosed with SAA between 2000 and 2018. Patients received either standard immunosuppressive therapy (IST‐Std) or IST with eltrombopag (IST‐Epag). The primary outcome was the objective response (OR), including partial and complete response (CR), at 6 and 12 months after starting therapy.

Results

We identified 16 patients receiving IST‐Std and nine IST‐Epag treatment (seven of nine as upfront therapy and two of seven after previously failed IST). The OR at 6 and 12 months in IST‐Std arm was 71% and 100%, with CR in 29% and 58%, respectively. Seven patients receiving upfront IST‐Epag had OR at 6 and 12 months, with two of seven (29%) achieving CR at 6 and 12 months. Two patients who previously failed standard IST did not respond to eltrombopag. No significant differences were observed in both cohorts with regard to infections. One IST‐Epag‐treated patient developed transient grade 3 transaminitis. Finally, no changes in paroxysmal nocturnal hemoglobinuria (PNH) clone size and cytogenetic abnormalities were seen in either cohort.

Conclusion

The addition of eltrombopag to standard IST was well tolerated and resulted in satisfactory hematological response at 6 and 12 months in this single‐institution experience. A larger cohort with longer follow‐up is required to assess response durability.
Preparation of alginate–chitosan floating granules loaded with 2‐methyl‐4‐chlorophenoxy acetic acid (MCPA) and their bioactivity on water hyacinth
Authors: Hou Ruiquan , Wu Jiyingzi , Yang Liupeng , Zhao Kunyu , Huang Suqing , Kaziem Amir E , Zhang Zhixiang
Published: April 2021

BACKGROUND

Water hyacinth (Eichhornia crassipes) is considered the most damaging aquatic weed in many countries. Chemical methods are still the primary approach to control, although this directly exposes the natural enemy of water hyacinth (water hyacinth weevil) to herbicides. In addition, spray drift can easily damage non‐target plants. In this study, herbicides, natural polymer materials (chitosan and carboxymethyl chitosan), sodium alginate and natural oils (citronella oil) were used to prepare novel floating polysaccharide granules as a solution for controlling water hyacinth.

RESULTS

2‐Methyl‐4‐chlorophenoxy acetic acid (MCPA) floating granules with a spherical structure were prepared using a MCPA–chitosan–sodium alginate–oil cross‐linking and embedding method. The granules produced showed the required properties of floatation and slow controlled herbicide release. In addition, the polysaccharide granules collected around water hyacinth plants and enabled targeted release of the active herbicide ingredients onto the stems and roots of the weed, thereby stopping the herbicide from reaching non‐target plants and preventing regrowth of water hyacinth.

CONCLUSION

We successfully prepared highly effective MCPA‐loaded floating granules, which compared with an MCPA solution, exerted greater control on water hyacinth. Concomitantly, these granules provide a solution to spray drift and ensure the safety of natural enemies of water hyacinth, which is of great significance in research on herbicide formulations.
Hydrothermal Synthesis of Mn3O4/CoS2 as a Promising Photocatalytic Material for Boosting Visible‐Light Photocatalytic Hydrogen Production
Authors: Xu Jing , Liu Ye , Li Xuanhao , Li Yanru
Published: April 2021

Photocatalytic hydrogen evolution has received extensive attention for energy conversion and storage of clean energy. Herein, the composite catalyst Mn3O4/CoS2 is successfully prepared by a hydrothermal method. Photocatalytic hydrogen evolution experiments are conducted by adjusting the amount of Mn3O4. The results show that the composite photocatalyst Mn3O4/CoS2 has higher photocatalytic hydrogen evolution performance. The hydrogen production of the 50 mg Mn3O4/CoS2 composite catalyst at 5 h is 14.95 times and 1.60 times that of pure Mn3O4 and CoS2, respectively, indicating that the 50 mg Mn3O4/CoS2 composite catalyst has good photocatalytic stability. In addition, the structure, morphology, and composition of the prepared catalysts are characterized by scanning electron microcopy (SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), Brunauer–Emmett–Teller (BET), electrochemical and PL techniques. Compared with Mn3O4 and CoS2, the photocatalytic response of the 50 mg Mn3O4/CoS2 composite catalyst is significantly enhanced, the current density is increased, the fluorescence quenching efficiency is accelerated, and the pore volume and pore size are increased. Therefore, the composite catalyst can accelerate the separation and transfer of photogenerated electrons and holes and improve the photocatalytic efficiency.
Simultaneous modeling of Alzheimer's disease progression via multiple cognitive scales
Authors: Kühnel Line , Berger Anna‐Karin , Markussen Bo , Raket Lars L.
Published: April 2021

Analyzing the progression of Alzheimer's disease (AD) is challenging due to lacking sensitivity in currently available measures. AD stages are typically defined based on cognitive cut‐offs, but this results in heterogeneous patient groups. More accurate modeling of the continuous progression of the disease would enable more accurate patient prognosis. To address these issues, we propose a new multivariate continuous‐time disease progression (MCDP) model. The model is formulated as a nonlinear mixed‐effects model that aligns patients based on their predicted disease progression along a continuous latent disease timeline. The model is evaluated using long‐term follow‐up data from 2152 participants in the Alzheimer's Disease Neuroimaging Initiative. The MCDP model was used to simultaneously model three cognitive scales; the Alzheimer's Disease Assessment Scale‐cognitive subscale, the Mini‐Mental State Examination, and the Clinical Dementia Rating scale—sum of boxes. Compared with univariate modeling and previously proposed multivariate disease progression models, the MCDP model showed superior ability to predict future patient trajectories. Finally, based on the multivariate disease timeline estimated using the MCDP model, the sensitivity of the individual items of the cognitive scales along the different stages of disease was analyzed. The analysis showed that delayed memory recall items had the highest sensitivity in the early stages of disease, whereas language and attention items were sensitive later in disease.
A Dual‐Responsive Platform Based on Antifouling Dendrimer–CuS Nanohybrids for Enhanced Tumor Delivery and Combination Therapy
Authors: Xiong Zhijuan , Wang Yue , Zhu Wei , Ouyang Zhijun , Zhu Yu , Shen Mingwu , Xia Jindong , Shi Xiangyang
Published: April 2021

Design of stimuli‐responsive nanomedicine with enhanced tumor delivery for combination therapy still remains a great challenge. Here, a unique design of an antifouling‐dendrimer‐based nanoplatform with dual pH‐ and redox‐responsiveness is reported to meet this challenge. First, generation 5 (G5) poly(amidoamine) dendrimers are modified with targeting ligand cyclic arginine–glycine–aspartic acid (RGD) peptide through a polyethylene glycol (PEG) spacer and zwitterion of thiolated N,N‐dimethyl‐cysteamine‐carboxybetaine (CBT) via pH‐responsive benzoicimine bond to form G5.NH2PEGRGDCBT conjugates. Then, doxorubicin (DOX) is linked to the functional G5 dendrimers through a redox‐responsive disulfide bond, followed by entrapment of CuS nanoparticles within the dendrimers. The created functional dendrimer–CuS nanohybrids with a CuS core size of 3.6 nm display a good antifouling property and excellent photothermal conversion property in the second near‐infrared window. In addition, the neutral surface charge of the nanohybrids is able to be switched to be positive in the tumor region with slightly acidic microenvironment due to the break of benzoicimine bond to promote their intracellular uptake, while the redox‐sensitive disulfide bond affords the fast release of the conjugated DOX within tumor cells to exert its therapeutic effect. Taken together with the CuS cores, the created dendrimer–CuS nanohybrids enable enhanced combination chemotherapy and photothermal therapy of tumors.
Highly Enhanced Efficiency of Planar Perovskite Solar Cells by an Electron Transport Layer Using Phytic Acid–Complexed SnO2 Colloids
Authors: Liu Congcong , Su Haijun , Xie Keyu , Wang Hongqiang , Zhai Peng , Chang Ninghui , Zhang Shan , Ban Qingfu , Guo Min , Zhang Jun , Liu Lin
Published: April 2021

SnO2 aqueous colloids as electron transport layers (ETLs) have been widely employed in planar perovskite solar cells (PSCs). However, the surface defects and energy level mismatch at the SnO2 ETL/perovskite interface are still great challenges for the power conversion efficiency (PCE) improvement. Herein, a natural and nontoxic phytic acid (PA) compound is introduced into the SnO2 aqueous colloids to prepare the ETL to depress its defects, and systematically study the influence of different PA complexation on the photovoltaic performance of PSCs. The results demonstrate that PA complexation can assemble unique coordination complexes between PA and SnO2 nanocrystals (NCs) in a new bonding of SnOP, which can passivate SnO2 inherent surface defects and tune the electronic properties of SnO2 ETLs. PA complexation can significantly disaggregate the SnO2 oligomers and reduce the cluster size distribution from 98.37 to 15.87 nm. Meanwhile, the reduction of surface trap states inhibits the potential barriers, thus the electrical conductivity is about two times as high as compared with the pristine SnO2 ETLs. Consequently, a high PCE of 21.43% in PA‐SnO2‐based PSCs is obtained, which presents an improvement of 10.9% over that of the pristine SnO2‐based PSCs.
The WNT/β‐catenin dependent transcription: A tissue‐specific business
Authors: Söderholm Simon , Cantù Claudio
Published: April 2021

β‐catenin‐mediated Wnt signaling is an ancient cell‐communication pathway in which β‐catenin drives the expression of certain genes as a consequence of the trigger given by extracellular WNT molecules. The events occurring from signal to transcription are evolutionarily conserved, and their final output orchestrates countless processes during embryonic development and tissue homeostasis. Importantly, a dysfunctional Wnt/β‐catenin pathway causes developmental malformations, and its aberrant activation is the root of several types of cancer. A rich literature describes the multitude of nuclear players that cooperate with β‐catenin to generate a transcriptional program. However, a unified theory of how β‐catenin drives target gene expression is still missing. We will discuss two types of β‐catenin interactors: transcription factors that allow β‐catenin to localize at target regions on the DNA, and transcriptional co‐factors that ultimately activate gene expression. In contrast to the presumed universality of β‐catenin's action, the ensemble of available evidence suggests a view in which β‐catenin drives a complex system of responses in different cells and tissues. A malleable armamentarium of players might interact with β‐catenin in order to activate the right “canonical” targets in each tissue, developmental stage, or disease context. Discovering the mechanism by which each tissue‐specific β‐catenin response is executed will be crucial to comprehend how a seemingly universal pathway fosters a wide spectrum of processes during development and homeostasis. Perhaps more importantly, this could ultimately inform us about which are the tumor‐specific components that need to be targeted to dampen the activity of oncogenic β‐catenin.

This article is categorized under:

Cancer > Molecular and Cellular Physiology

Cancer > Genetics/Genomics/Epigenetics

Cancer > Stem Cells and Development
The Effect of Measurement Preprocessing intheGravity-Aided Navigation
Authors: Stepanov Oleg Andreevich , Nosov Aleksei Sergeevich
Published: April 2021

The paper analyzes the effect of preliminary processing of gravity measurements on the accuracy of the marine gravity-aided navigation. The preliminary processing of the measurements is implemented in the filtering and smoothing modes. Obtained results are illustrated by a one-dimensional example of gravity-aided navigation problem.
Correction to: Gender, Protests and Political Change in Africa
Authors: Olonisakin Funmi
Published: April 2021

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Disentangling mass spectra of multiple fields in cosmological collider
Authors: Aoki Shuntaro , Yamaguchi Masahide
Published: April 2021

Abstract

We study effects of multiple scalar fields (scalar isocurvatons) with the Hubble scale masses on the inflationary bispectrum in the squeezed limit, particular paying attention to the question how to disentangle mass spectra of such fields. We consider two isocurvatons with almost degenerate masses and the coupling of an inflaton to both isocurvatons as an example. We find that the characteristic feature associated with nearly degenerate masses appears in the oscillating part of the bispectrum, which is dominated by a waveform with a specific wavelength roughly given by an inverse of the mass difference. Such a waveform with a relatively longer wavelength can be easily identified and useful for disentangling almost degenerate mass spectra. This situation is in sharp contrast with the case of collider experiments on earth, where the very precise energy resolution corresponding to the mass difference is required to disentangle almost degenerate mass spectra. Therefore, if future observations could detect this kind of a characteristic feature in bispectrum of the primordial curvature perturbations, it can prove the existence of degenerate multiple particles around the Hubble scale and resolve their mass degeneracies.
Real-life assessment of standardized contrast-enhanced ultrasound (CEUS) and CEUS algorithms (CEUS LI-RADS®/ESCULAP) in hepatic nodules in cirrhotic patients—a prospective multicenter study
Authors: Strobel D. , Jung E.-M. , Ziesch M. , Praktiknjo M. , Link A. , Dietrich C. F. , Klinger C. , Schultheiß M. , Jesper D. , Schellhaas B.
Published: April 2021

Objectives

Hepatocellular carcinoma (HCC) can be diagnosed non-invasively with contrast-enhanced ultrasound (CEUS) in cirrhosis if the characteristic pattern of arterial phase hyperenhancement followed by hypoenhancement is present. Recent studies suggest that diagnosis based on this “hyper-hypo” pattern needs further refinement. This study compares the diagnostic accuracies of standardized CEUS for HCC according to the current guideline definition and following the newly developed CEUS algorithms (CEUS LI-RADS®, ESCULAP) in a prospective multicenter real-life setting.

Methods

Cirrhotic patients with liver lesions on B-mode ultrasound were recruited prospectively from 04/2018 to 04/2019, and clinical and imaging data were collected. The CEUS standard included an additional examination point after 4–6 min in case of no washout after 3 min. The diagnostic accuracies of CEUS following the guidelines (“hyper-hypo” pattern), based on the examiner’s subjective interpretation (“CEUS subjective”), and based on the CEUS algorithms ESCULAP and CEUS LI-RADS® were compared.

Results

In total, 470 cirrhotic patients were recruited in 43 centers. The final diagnosis was HCC in 378 cases (80.4%) according to the reference standard (histology 77.4%, MRI 16.4%, CT 6.2%). The “hyper-hypo” pattern yielded 74.3% sensitivity and 63% specificity. “CEUS subjective” showed a higher diagnostic accuracy (sensitivity, 91.5%; specificity, 67.4%; positive predictive value, 92%; negative predictive value, 66%). Sensitivity was higher for ESCULAP (95%) and “CEUS subjective” (91.5%) versus CEUS LI-RADS® (65.2%; p < 0.001). Specificity was highest for CEUS LI-RADS® (78.6%; p < 0.001).

Conclusions

CEUS has an excellent diagnostic accuracy for the non-invasive diagnosis of HCC in cirrhosis. CEUS algorithms may be a helpful refinement of the “hyper-hypo” pattern defined by current HCC guidelines.

Key Points

• Contrast-enhanced ultrasound (CEUS) has a high diagnostic accuracy for the non-invasive diagnosis of hepatocellular carcinoma (HCC) in cirrhosis.

• The CEUS algorithm ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) showed the highest sensitivity, whereas the CEUS LI-RADS® (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System) algorithm yielded the highest specificity.

• A standardized CEUS examination procedure with an additional examination point in the late phase, after 4–6 min in lesions with no washout after 3 min, is vital.
Laparoscopic appendectomy versus antibiotic treatment for acute appendicitis—a systematic review
Authors: Köhler Franziska , Hendricks Anne , Kastner Carolin , Müller Sophie , Boerner Kevin , Wagner Johanna C. , Lock Johan F. , Wiegering Armin
Published: April 2021

Background

Over the last years, laparoscopic appendectomy has progressively replaced open appendectomy and become the current gold standard treatment for suspected, uncomplicated appendicitis. At the same time, though, it is an ongoing discussion that antibiotic therapy can be an equivalent treatment for patients with uncomplicated appendicitis. The aim of this systematic review was to determine the safety and efficacy of antibiotic therapy and compare it to the laparoscopic appendectomy for acute, uncomplicated appendicitis.

Methods

The PubMed database, Embase database, and Cochrane library were scanned for studies comparing laparoscopic appendectomy with antibiotic treatment. Two independent reviewers performed the study selection and data extraction. The primary endpoint was defined as successful treatment of appendicitis. Secondary endpoints were pain intensity, duration of hospitalization, absence from work, and incidence of complications.

Results

No studies were found that exclusively compared laparoscopic appendectomy with antibiotic treatment for acute, uncomplicated appendicitis.

Conclusions

To date, there are no studies comparing antibiotic treatment to laparoscopic appendectomy for patients with acute uncomplicated appendicitis, thus emphasizing the lack of evidence and need for further investigation.
Vascularisation of pluripotent stem cell–derived myocardium: biomechanical insights for physiological relevance in cardiac tissue engineering
Authors: King Oisín , Sunyovszki Ilona , Terracciano Cesare M.
Published: April 2021

The myocardium is a diverse environment, requiring coordination between a variety of specialised cell types. Biochemical crosstalk between cardiomyocytes (CM) and microvascular endothelial cells (MVEC) is essential to maintain contractility and healthy tissue homeostasis. Yet, as myocytes beat, heterocellular communication occurs also through constantly fluctuating biomechanical stimuli, namely (1) compressive and tensile forces generated directly by the beating myocardium, and (2) pulsatile shear stress caused by intra-microvascular flow. Despite endothelial cells (EC) being highly mechanosensitive, the role of biomechanical stimuli from beating CM as a regulatory mode of myocardial-microvascular crosstalk is relatively unexplored. Given that cardiac biomechanics are dramatically altered during disease, and disruption of myocardial-microvascular communication is a known driver of pathological remodelling, understanding the biomechanical context necessary for healthy myocardial-microvascular interaction is of high importance. The current gap in understanding can largely be attributed to technical limitations associated with reproducing dynamic physiological biomechanics in multicellular in vitro platforms, coupled with limited in vitro viability of primary cardiac tissue. However, differentiation of CM from human pluripotent stem cells (hPSC) has provided an unlimited source of human myocytes suitable for designing in vitro models. This technology is now converging with the diverse field of tissue engineering, which utilises in vitro techniques designed to enhance physiological relevance, such as biomimetic extracellular matrix (ECM) as 3D scaffolds, microfluidic perfusion of vascularised networks, and complex multicellular architectures generated via 3D bioprinting. These strategies are now allowing researchers to design in vitro platforms which emulate the cell composition, architectures, and biomechanics specific to the myocardial-microvascular microenvironment. Inclusion of physiological multicellularity and biomechanics may also induce a more mature phenotype in stem cell–derived CM, further enhancing their value. This review aims to highlight the importance of biomechanical stimuli as determinants of CM-EC crosstalk in cardiac health and disease, and to explore emerging tissue engineering and hPSC technologies which can recapitulate physiological dynamics to enhance the value of in vitro cardiac experimentation.
Selinexor decreases HIF-1α via inhibition of CRM1 in human osteosarcoma and hepatoma cells associated with an increased radiosensitivity
Authors: von Fallois Moritz , Kosyna Friederike Katharina , Mandl Markus , Landesman Yosef , Dunst Jürgen , Depping Reinhard
Published: April 2021

Background

The nuclear pore complexes (NPCs) are built of about 30 different nucleoporins and act as key regulators of molecular traffic between the cytoplasm and the nucleus for sizeable proteins (> 40 kDa) which must enter the nucleus. Various nuclear transport receptors are involved in import and export processes of proteins through the nuclear pores. The most prominent nuclear export receptor is chromosome region maintenance 1 (CRM1), also known as exportin 1 (XPO1). One of its cargo proteins is the prolyl hydroxylase 2 (PHD2) which is involved in the initiation of the degradation of hypoxia-inducible factors (HIFs) under normoxia. HIFs are proteins that regulate the cellular adaptation under hypoxic conditions. They are involved in many aspects of cell viability and play an important role in the hypoxic microenvironment of cancer. In cancer, CRM1 is often overexpressed thus being a putative target for the development of new cancer therapies. The newly FDA-approved pharmaceutical Selinexor (KPT-330) selectively inhibits nuclear export via CRM1 and is currently tested in additional Phase-III clinical trials. In this study, we investigated the effect of CRM1 inhibition on the subcellular localization of HIF-1α and radiosensitivity.

Methods

Human hepatoma cells Hep3B and human osteosarcoma cells U2OS were treated with Selinexor. Intranuclear concentration of HIF-1α protein was measured using immunoblot analysis. Furthermore, cells were irradiated with 2–8 Gy after treatment with Selinexor compared to untreated controls.

Results

Selinexor significantly reduced the intranuclear level of HIF-1α protein in human hepatoma cells Hep3B and human osteosarcoma cells U2OS. Moreover, we demonstrated by clonogenic survival assays that Selinexor leads to dose-dependent radiosensitization in Hep3B-hepatoma and U2OS-osteosarcoma cells.

Conclusion

Targeting the HIF pathway by Selinexor might be an attractive tool to overcome hypoxia-induced radioresistance.
Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial
Authors: Öcal Osman , Schütte Kerstin , Kupčinskas Juozas , Morkunas Egidijus , Jurkeviciute Gabija , de Toni Enrico N. , Ben Khaled Najib , Berg Thomas , Malfertheiner Peter , Klümpen Heinz Josef , Sengel Christian , Basu Bristi , Valle Juan W. , Benckert Julia , Gasbarrini Antonio , Palmer Daniel , Seidensticker Ricarda , Wildgruber Moritz , Sangro Bruno , Pech Maciej , Ricke Jens , Seidensticker Max
Published: April 2021

Purpose

To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib.

Methods

A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response.

Results

Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9–8.9],p < 0.001) and IL-8 (HR, 2.4 [1.2–4.7],p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22–7.3],p = 0.017) and IL-8 (HR, 2.19 [1.02–4.7],p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%,p = 0.007; IL-8, 50.0% vs. 17.4%,p = 0.011).

Conclusion

IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.
Multi-agent deep reinforcement learning: a survey
Authors: Gronauer Sven , Diepold Klaus
Published: April 2021

The advances in reinforcement learning have recorded sublime success in various domains. Although the multi-agent domain has been overshadowed by its single-agent counterpart during this progress, multi-agent reinforcement learning gains rapid traction, and the latest accomplishments address problems with real-world complexity. This article provides an overview of the current developments in the field of multi-agent deep reinforcement learning. We focus primarily on literature from recent years that combines deep reinforcement learning methods with a multi-agent scenario. To survey the works that constitute the contemporary landscape, the main contents are divided into three parts. First, we analyze the structure of training schemes that are applied to train multiple agents. Second, we consider the emergent patterns of agent behavior in cooperative, competitive and mixed scenarios. Third, we systematically enumerate challenges that exclusively arise in the multi-agent domain and review methods that are leveraged to cope with these challenges. To conclude this survey, we discuss advances, identify trends, and outline possible directions for future work in this research area.
Human amniotic membrane: an improvement in the treatment of Medication-related osteonecrosis of the jaw (MRONJ)? A case–control study
Authors: Ragazzo Mirko , Val Matteo , Montagner Giulia , Trojan Diletta , Fusetti Stefano , Guarda Nardini Luca
Published: April 2021

The aim of this article is to report the results obtained by the use of HAM in surgical wound healing and the reduction of relapse in patients affected by Medication-related osteonecrosis of the jaw (MRONJ).The study involved patients with the diagnosis of MRONJ, surgically treated between October 2016 and April 2019, in a case–control setting. Enrolled patients were randomly divided into 2 groups. One group will be treated with resective surgery and with the insertion of HAM patch (Group A), while the second group had been treated exclusively with resective surgery (Group B).The patients underwent MRONJ surgical treatment with the placement of amniotic membrane patches at the wound site. Data regarding the long-term complications/functions were evaluated at 3, 6, 12, and 24 months after surgery. Pain measurements were performed before the intervention (T0), 7(T1) and 30(T2) days after surgery. 49 patients were included in the study. 2 patients of GROUP A after 30 days since they were surgically treated showed persistent bone exposure. 5 patients of group B demonstrated a lack of healing of the surgical wound with the persistence of bone exposed to 30 days after surgery. Statistical analysis ruled out any difference in OUTCOME (relapse) between GROUP A and B (p = 0.23). However, the Fisher test highlighted a significant difference between the use of HAM and only surgical treatment in pain at rest (p = 0.032). The use of amniotic membrane implement the patient's quality of life and reduce pain perception. has a learning curve that is fast enough to justify its routine use.
Interaction of pig manure-derived dissolved organic matter with soil affects sorption of sulfadiazine, caffeine and atenolol pharmaceuticals
Authors: Zhang Wei , Tang Xiangyu , Thiele-Bruhn Sören
Published: April 2021

Pharmaceutically active compounds (PhACs) released into the environment have an adverse impact on the soil and water ecosystem as well as human health. Sorption of PhACs by soils and its potential modification through introduced DOM in the applied animal manure or treated wastewater (TWW) determines the mobility and environmental relevance of PhACs. Sulfadiazine, caffeine and atenolol were selected as target PhACs to investigate their sorption behaviors by five selected arable soils in the absence and presence of pig manure DOM. Sulfadiazine was least sorbed, followed by caffeine and atenolol according to the Freundlich sorption isotherm fit (soil average Kf [μg(1−n) mLn g−1] 4.07, 9.06, 18.92, respectively). The addition of manure DOM (31.34 mg C L−1) decreased the sorption of sulfadiazine and especially of caffeine and atenolol (average Kf 3.04, 6.17, 5.79, respectively). Freundlich sorption isotherms of the PhACs became more nonlinear in the presence of manure DOM (Freundlich exponent n changed from 0.74–1.40 to 0.62–1.12), implying more heterogeneous sorption of PhACs in soil–DOM binary systems. Sorption competition of DOM molecules with sulfadiazine and caffeine mostly contributed to their decreased soil sorption when DOM was present. In contrast, the formation of DOM–atenolol associates in the solution phase caused the largely decreased soil sorption of atenolol in the presence of DOM. It is suggested that DOM concentration (e.g., ≥ 60 mg C L−1) and its interaction with PhACs should be taken into consideration when assessing the environmental impact of land application of animal manure or irrigation with TWW.
Water and Carbon Dioxide Adsorption on CaO(001) Studied via Single Crystal Adsorption Calorimetry
Authors: Seifert J. , Carey S. J. , Schauermann S. , Shaikhutdinov S. , Freund H.-J.
Published: April 2021

A new method to analyze microcalorimetry data was employed to study the adsorption energies and sticking probabilities of D2O and CO2 on CaO(001) at several temperatures. This method deconvolutes the line shapes of the heat detector response into an instrument response function and exponential decay functions, which correspond to the desorption of distinct surface species. This allows for a thorough analysis of the adsorption, dissociation, and desorption processes that occur during our microcalorimetry experiments. Our microcalorimetry results, show that D2O adsorbs initially with an adsorption energy of 85–90 kJ/mol at temperatures ranging from 120 to 300 K, consistent with prior spectroscopic studies that indicate dissociation. This adsorption energy decreases with increasing coverage until either D2O multilayers are formed at low temperatures (120 K) or the surface is saturated (> 150 K). Artificially producing defects on the surface by sputtering prior to dosing D2O sharply increases this adsorption energy, but these defects may be healed after annealing the surface to 1300 K. CO2 adsorbs on CaO(001) with an initial adsorption energy of ~ 125 kJ/mol, and decreases until the saturation coverage is reached, which is a function of surface temperature. The results showed that pre-adsorbed water blocks adsorption sites, lowers the saturation coverage, and lowers the measured adsorption energy of CO2. The calorimetry data further adds to our understanding of D2O and CO2 adsorption on oxide surfaces.
Prädiktoren von prozessbezogener und strukturierender elterlicher Unterstützung während des (coronabedingten) Distanzunterrichts
Authors: Sander Andreas , Schäfer Laura , van Ophuysen Stefanie
Published: April 2021

Die Schulschließungen aufgrund der Corona-Pandemie verlagerten das schulische Lernen in die Familien. Schüler*innen standen vor der Aufgabe, ihr Lernen und ihre Lernzeit eigenständiger zu gestalten und wurden dabei vornehmlich von ihren Eltern sowohl organisatorisch als auch fachlich begleitet. Auf Basis bisheriger Forschung zur elterlichen Hausaufgabenunterstützung und zu Bildungspartnerschaften ist anzunehmen, dass sowohl die strukturierende als auch die prozessbezogene Lernbegleitung durch die Eltern von soziodemographischen Merkmalen der Familie abhängen, aber ebenfalls mit Merkmalen des Kindes (z. B. Alter, Lernverhalten) und der wahrgenommenen schulischen Lernbegleitung (Engagement der Lehrkraft, Anforderungsniveau) assoziiert sind. Diese postulierten Zusammenhänge wurden auf Basis von Daten einer standardisierten Onlinebefragung mitN = 6685 Eltern von Kindern an weiterführenden Schulen in Nordrhein-Westfalen regressionsanalytisch untersucht. Die Befunde sprechen für eine adaptive Lernbegleitung der Eltern, die für ältere, weibliche Kinder mit günstigem Lernverhalten weniger intensiv ausfällt als für jüngere, männliche Kinder mit ungünstigem Lernverhalten. Auch die Lernbegleitung durch die Schule trägt zur Vorhersage des elterlichen Verhaltens bei, wobei engagiertes Lehrkraftverhalten gerade bei Familien mit nicht-gymnasialer Schulbildung der Eltern zu verstärkter Unterstützung des Kindes beiträgt.
Deep Audio-visual Learning: A Survey
Authors: Zhu Hao , Luo Man-Di , Wang Rui , Zheng Ai-Hua , He Ran
Published: April 2021

Audio-visual learning, aimed at exploiting the relationship between audio and visual modalities, has drawn considerable attention since deep learning started to be used successfully. Researchers tend to leverage these two modalities to improve the performance of previously considered single-modality tasks or address new challenging problems. In this paper, we provide a comprehensive survey of recent audio-visual learning development. We divide the current audio-visual learning tasks into four different subfields: audio-visual separation and localization, audio-visual correspondence learning, audio-visual generation, and audio-visual representation learning. State-of-the-art methods, as well as the remaining challenges of each subfield, are further discussed. Finally, we summarize the commonly used datasets and challenges.
Joining of ultra-high-strength steels using resistance element welding on conventional resistance spot welding guns
Authors: Günter Heinrich , Meschut Gerson
Published: April 2021

Single-step joining of dissimilar material combinations between ultra-high-strength steels and high-strength aluminium alloys with sufficient mechanical joint properties by using conventional resistance spot welding equipment has not been reported yet. In this research paper, a novel single-step joining technology, so-called self-penetrating resistance element welding, is introduced. First, the motivation for this novel joining technology, the state of the art in joining, and the process characteristics are presented. In the results section, the welding rivet geometry is first determined using forming simulations and validated by head tensile tests. Followed by the description of the welding process and its characteristics, the mechanical joint properties are reported. The results show that a numerically optimised welding rivet geometry can guarantee sufficient joint strength. By this welding rivet geometry, a thermally assisted penetration of aluminium and therefore welding to steel is possible with and without adhesive. Furthermore, it is shown that the welding process can be designed by means of simulations. Finally, the shear tensile tests prove that an overall sufficient joint strength is ensured.
Population Modelling in Affective Disorders
Authors: Pulcu Erdem
Published: April 2021

Purpose of Review

The prevalence of affective disorders is on the rise. This upward trajectory leads to a substantial personal and societal cost. There is growing body of literature demonstrating decision-making impairments associated with affective disorders, and more studies are using computational modelling methods to infer underlying mechanisms of these impairments from participant choice behaviour. However, lack of population modelling suggests that data resources may still be underutilised.

Recent Findings

A number of recent studies associated major depression with abnormal risky decision-making as well as impairments in temporal discounting and social decision-making. These domains capture relevant aspects of real-life decision-making. Consequently, data from these studies can be used to define behavioural phenotypes for major depression.

The manuscript describes a detailed proposal for population modelling to capture changes in the prevalence rate of major depression. The population modelling approach can also identify which decision-making domains can account for a larger part of impairments in psychosocial functioning and how behavioural interventions built on computational principles can target these to improve real-life psychosocial functioning in patient groups.
Narratives Argumentieren in politischen Leserbriefen
Authors: Schröter Juliane
Published: April 2021

Wie und warum werden Erzählungen in zeitgenössischen politischen Leserbriefen zur Argumentation verwendet? Um Antworten auf diese Frage zu gewinnen, untersuche ich gut 50 Leserbriefe aus Schweizer und deutschen Tageszeitungen, die alle einen Bezug zu COVID-19 haben. In allen Briefen wird argumentiert, indem erzählt wird. Es zeigt sich, dass die Narration in der Regel als Prämisse eines Arguments durch Induktion in einer Argumentation mit evaluativem Standpunkt fungiert. Eine solche Prämisse zu erzählen, hat für die Schreibenden den Vorteil, dass sie mit dem beispielhaften Geschehen sukzessive auch dessen Bewertung vermitteln können. Ein gesellschaftlich-kultureller Mehrwert solch narrativer Argumente durch Induktion lässt sich darin erkennen, dass sie in politischen Diskussionen auf unkomplizierte Weise die soziale Mikroebene mit der gesellschaftlichen Makroebene verbinden können.