bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the Pbrm1 subunit and the PBAF complex in Schwann cell development
Authors: Polanetzki Vanessa , Fröb Franziska , Baroti Tina , Schimmel Margit , Tamm Ernst R. , Wegner Michael 
Published: February 2022

AbstractMyelin sheath formation in the peripheral nervous system and the ensuing saltatory conduction rely on differentiated Schwann cells. We have previously shown that transition of Schwann cells from an immature into a differentiated state requires Brg1 that serves as the central energy generating subunit in two related SWI/SNF-type chromatin remodelers, the BAF and the PBAF complex. Here we used conditional deletion of Pbrm1 to selectively interfere with the PBAF complex in Schwann cells. Despite efficient loss of Pbrm1 early during lineage progression, we failed to detect any substantial alterations in the number, proliferation or survival of immature Schwann cells as well as in their rate and timing of terminal differentiation. As a consequence, postnatal myelin formation in peripheral nerves appeared normal. There were no inflammatory alterations in the nerve or other signs of a peripheral neuropathy. We conclude from our study that Pbrm1 and very likely the PBAF complex are dispensable for proper Schwann cell development and that Schwann cell defects previously observed upon Brg1 deletion are mostly attributable to altered or absent function of the BAF complex.
Two-dimensional temperature-responsive chromatography using a poly(N-isopropylacrylamide) brush-modified stationary phase for effective therapeutic drug monitoring
Authors: Nagase Kenichi , Inoue So , Inoue Masakazu , Kanazawa Hideko 
Published: February 2022

AbstractTherapeutic drug monitoring (TDM) is an effective pharmacological approach for controlling drug concentration in a patient’s serum. Herein, a new two-dimensional chromatography system was developed using two poly(N-isopropylacrylamide) (PNIPAAm)-modified bead-packed columns for effective and safe drug monitoring. PNIPAAm-modified silica beads were prepared as packing materials using atom transfer radical polymerization of NIPAAm. The increase in the retention times of the drugs requiring TDM with increasing temperature, was attributed to enhanced hydrophobic interactions at elevated temperatures. The drugs and serum proteins were separated on the prepared column at 40 °C using an all-aqueous mobile phase. Differences in the hydrophobic interactions accounted for the elution of the serum proteins and drugs at short and long retention times, respectively, and a primary column was employed to separate the serum proteins and drugs. After eluting the serum proteins from the column, the drug was introduced into the secondary column, leading to a peak of its purified form and enabling determination of the drug concentration. Two-dimensional temperature-responsive chromatography can benefit TDM by allowing the drug concentration in the serum to be measured in all-aqueous mobile phases without sample preparation.
Dual targeting micelles loaded with paclitaxel and lapatinib for combinational therapy of brain metastases from breast cancer
Authors: Lu Heng , Chen Tianran , Wang Yiran , He Yuwei , Pang Zhiqing , Wang Yajie 
Published: February 2022

AbstractDue to the presence of the blood–brain barrier (BBB), the delivery of general drugs into the brain tissue remains to be a tricky problem. For patients with brain metastases from breast cancer, drug delivery systems must overcome this physical barrier. Targeted nano vehicles arise as a promising alternative to deliver drugs to brain tissues successively. Herein, a dual targeting micelle drug delivery system loaded with paclitaxel (PTX) and lapatinib (LPTN) was developed for combinational therapy of brain metastases. In our study, it was shown the micelles modified with Angiopep-2 had high loading efficiency of paclitaxel and lapatinib (Ang-MIC-PTX/LP). In addition, Ang-MIC-PTX/LP could transport across the in vitro BBB model and accumulate in breast cancer cells. After intravenous injection, Ang-MIC significantly accumulated in the brain metastasis. Ang-MIC-PTX/LP could also extend the life span of brain metastasis mouse models. Overall, this study provided a promising method for treatment of brain metastases from breast cancer.
Sympatric cleptobiotic stingless bees have species-specific cuticular profiles that resemble their hosts
Authors: Vázquez Manuel , Muñoz David , Medina Rubén , Paxton Robert J. , de Oliveira Favizia Freitas , Quezada-Euán José Javier G. 
Published: February 2022

AbstractStingless bees are the largest group of eusocial pollinators with diverse natural histories, including obligate cleptobionts (genus Lestrimelitta) that completely abandoned flower visitation to rely on other stingless bees for food and nest materials. Species of Lestrimeliita are thought to specialize upon different host species, and deception through chemical similarity has been proposed as a mechanism to explain this phenomenon. In the Yucatan Peninsula of Mexico, Scaptotrigona pectoralis is a species chemically distinct from, and not preferred as a host by, locally widespread Lestrimeliita niitkib; witnessing attacks on S. pectoralis colonies offered the opportunity to test the sensory deception hypothesis to cletoparasitism. Analysis of cuticular profiles revealed that the Lestrimelitta attacking S. pectoralis differed significantly in odour bouquet to L. niitkib and, in contrast, it resembled that of S. pectoralis. Further analyses, including morphometrics, mtDNA barcoding, and the examination of taxonomic features, confirmed the existence of two sympatric Lestrimelitta species. The results give support to the hypothesis of chemical deception as a cleptobiotic strategy in Lestrimelitta sp. This is the first evidence that sympatric cleptobionts of the same genus select hosts in accordance with species-specific cuticular profiles, with possible consequences for ecological adaptation and the evolution of these remarkable organisms and the community of stingless bee hosts.
Comparison of faecal protein biomarkers' diagnostic accuracy for colorectal advanced neoplasms: a systematic review and meta-analysis
Authors: Nasir Kansestani Atefeh , Zare Mohammad Erfan , Tong Qingchao , Zhang Jun 
Published: February 2022

AbstractEarly diagnosis of colorectal advanced neoplasms (ANs), including colorectal cancer (CRC) and advanced adenoma (AA), has a positive effect on the survival rate. As a first attempt, the aim of this meta-analysis was to compare the diagnostic accuracy of faecal protein biomarkers for the detection of colorectal neoplasms with consideration of a wide range of covariates. A systematic literature search was performed up to Jun 10, 2021 on Web of Sciences, Scopus and PubMed. The diagnostic accuracies were calculated using the bivariate/hierarchical random effect model. Biomarkers were determined to be clinically applicable (CA) if they had areas under the curve > 0.70 and positive and negative likelihood ratios > 2 and < 0.5, respectively. A total of 47,059 test results were extracted from 16 immunochemical faecal occult blood test (iFOBT), 26 pyruvate kinase-M2 (PK-M2) and 23 faecal calprotectin (FC) studies. Only iFOBT, PK-M2 and FC for CRC plus iFOBT and PK-M2 for AN were CA. iFOBT had significantly superior accuracy (P = 0.02 versus PK-M2 and P < 0.01 versus FC for CRC; P < 0.01 versus PK-M2 for AN). Regarding covariates, the lateral flow method of PK-M2 measurement increased its accuracy for CRC detection compared to the enzyme-linked immunosorbent assay (P < 0.01). iFOBT is recommended as the most accurate faecal biomarker for CRC and AN diagnosis.
Brains and algorithms partially converge in natural language processing
Authors: Caucheteux Charlotte , King Jean-Rémi 
Published: February 2022

AbstractDeep learning algorithms trained to predict masked words from large amount of text have recently been shown to generate activations similar to those of the human brain. However, what drives this similarity remains currently unknown. Here, we systematically compare a variety of deep language models to identify the computational principles that lead them to generate brain-like representations of sentences. Specifically, we analyze the brain responses to 400 isolated sentences in a large cohort of 102 subjects, each recorded for two hours with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). We then test where and when each of these algorithms maps onto the brain responses. Finally, we estimate how the architecture, training, and performance of these models independently account for the generation of brain-like representations. Our analyses reveal two main findings. First, the similarity between the algorithms and the brain primarily depends on their ability to predict words from context. Second, this similarity reveals the rise and maintenance of perceptual, lexical, and compositional representations within each cortical region. Overall, this study shows that modern language algorithms partially converge towards brain-like solutions, and thus delineates a promising path to unravel the foundations of natural language processing.
Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptors
Authors: Sooda Anuradha , Rwandamuriye Francois , Wanjalla Celestine N. , Jing Lichen , Koelle David M. , Peters Bjoern , Leary Shay , Chopra Abha , Calderwood Michael A. , Mallal Simon A. , Pavlos Rebecca , Watson Mark , Phillips Elizabeth J. , Redwood Alec J. 
Published: February 2022

AbstractPre-existing pathogen-specific memory T cell responses can contribute to multiple adverse outcomes including autoimmunity and drug hypersensitivity. How the specificity of the T cell receptor (TCR) is subverted or seconded in many of these diseases remains unclear. Here, we apply abacavir hypersensitivity (AHS) as a model to address this question because the disease is linked to memory T cell responses and the HLA risk allele, HLA-B*57:01, and the initiating insult, abacavir, are known. To investigate the role of pathogen-specific TCR specificity in mediating AHS we performed a genome-wide screen for HLA-B*57:01 restricted T cell responses to Epstein-Barr virus (EBV), one of the most prevalent human pathogens. T cell epitope mapping revealed HLA-B*57:01 restricted responses to 17 EBV open reading frames and identified an epitope encoded by EBNA3C. Using these data, we cloned the dominant TCR for EBNA3C and a previously defined epitope within EBNA3B. TCR specificity to each epitope was confirmed, however, cloned TCRs did not cross-react with abacavir plus self-peptide. Nevertheless, abacavir inhibited TCR interactions with their cognate ligands, demonstrating that TCR specificity may be subverted by a drug molecule. These results provide an experimental road map for future studies addressing the heterologous immune responses of TCRs including T cell mediated adverse drug reactions.
Engineering eukaryote-like regulatory circuits to expand artificial control mechanisms for metabolic engineering in Saccharomyces cerevisiae
Authors: Peng Bingyin , Bandari Naga Chandra , Lu Zeyu , Howard Christopher B. , Scott Colin , Trau Matt , Dumsday Geoff , Vickers Claudia E. 
Published: February 2022

AbstractTemporal control of heterologous pathway expression is critical to achieve optimal efficiency in microbial metabolic engineering. The broadly-used GAL promoter system for engineered yeast (Saccharomyces cerevisiae) suffers from several drawbacks; specifically, unintended induction during laboratory development, and unintended repression in industrial production applications, which decreases overall production capacity. Eukaryotic synthetic circuits have not been well examined to address these problems. Here, we explore a modularised engineering method to deploy new genetic circuits applicable for expanding the control of GAL promoter-driven heterologous pathways in S. cerevisiae. Trans- and cis- modules, including eukaryotic trans-activating-and-repressing mechanisms, were characterised to provide new and better tools for circuit design. A eukaryote-like tetracycline-mediated circuit that delivers stringent repression was engineered to minimise metabolic burden during strain development and maintenance. This was combined with a novel 37 °C induction circuit to relief glucose-mediated repression on the GAL promoter during the bioprocess. This delivered a 44% increase in production of the terpenoid nerolidol, to 2.54 g L−1 in flask cultivation. These negative/positive transcriptional regulatory circuits expand global strategies of metabolic control to facilitate laboratory maintenance and for industry applications.
Regulation of HTLV-1 transformation
Authors: Ernzen Kyle J. , Panfil Amanda R. 
Published: February 2022

AbstractHuman T-cell leukemia virus type 1 (HTLV-1) is the only identified oncogenic human retrovirus. HTLV-1 infects approximately 5–10 million people worldwide and is the infectious cause of adult T-cell leukemia/lymphoma (ATL) and several chronic inflammatory diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), dermatitis, and uveitis. Unlike other oncogenic retroviruses, HTLV-1 does not capture a cellular proto-oncogene or induce proviral insertional mutagenesis. HTLV-1 is a trans-activating retrovirus and encodes accessory proteins that induce cellular transformation over an extended period of time, upwards of several years to decades. Inarguably the most important viral accessory protein involved in transformation is Tax. Tax is a multifunctional protein that regulates several different pathways and cellular processes. This single viral protein is able to modulate viral gene expression, activate NF-κB signaling pathways, deregulate the cell cycle, disrupt apoptosis, and induce genomic instability. The summation of these processes results in cellular transformation and virus-mediated oncogenesis. Interestingly, HTLV-1 also encodes a protein called Hbz from the antisense strand of the proviral genome that counters many Tax functions in the infected cell, such as Tax-mediated viral transcription and NF-κB activation. However, Hbz also promotes cellular proliferation, inhibits apoptosis, and disrupts genomic integrity. In addition to viral proteins, there are other cellular factors such as MEF-2, superoxide-generating NAPDH oxidase 5-α (Nox5α), and PDLIM2 which have been shown to be critical for HTLV-1-mediated T-cell transformation. This review will highlight the important viral and cellular factors involved in HTLV-1 transformation and the available in vitro and in vivo tools used to study this complex process.
Single-cell transcriptomics analysis reveals intratumoral heterogeneity and identifies a gene signature associated with prognosis of hepatocellular carcinoma
Authors: Liang Jialu , Chen Wenhui , Ye Jianwen , Ni Chen , Zhai Wenlong 
Published: February 2022

Abstract
Hepatocellular carcinoma (HCC) tumors exhibit high heterogeneity. However, current understanding of tumor cell heterogeneity of HCC and the association with prognosis remains very limited. In the present study, we collected and examined tumor tissue from one HCC patient by single-cell RNA sequencing (scRNA-seq). We identified 5753 cells and 16 clusters including hepatocytes/cancer cells, T cells, macrophages, endothelial cells, fibroblasts, NK cells, neutrophils, and B cells. In six tumor cell subclusters, we identified a cluster of proliferative tumor cells associated with poor prognosis. We downloaded scRNA-seq data of GSE125449 from the NCBI-GEO as validation dataset, and found that a cluster of hepatocytes exhibited high proliferation activity in HCC. Furthermore, we identified a gene signature related to the proliferation of HCC cells. This gene signature is efficient to classify HCC patients into two groups with distinct prognosis in both TCGA and ICGC database cohorts. Our results reveal the intratumoral heterogeneity of HCC at single cell level and identify a gene signature associated with HCC prognosis.
Host galaxy properties of quasi-periodically erupting X-ray sources
Authors: Wevers T. , Pasham D. R. , Jalan P. , Rakshit S. , Arcodia R. 
Published: February 2022

Context.Quasi-periodic X-ray eruptions (QPEs) are a recently discovered phenomenon, the nature of which remains unclear. Based on their discovery in active galactic nuclei (AGNs), explanations related to an AGN accretion disk or potentially a stellar tidal disruption event (TDE) have been put forward. Alternatives, including highly unequal mass compact object binaries, have also been proposed to explain their properties.Aims.We perform a systematic study of the five known QPE host galaxies with the aim of providing new insights as to their nature.Methods.We analysed new and archival medium resolution optical spectroscopy of the QPE hosts. We measured emission (and absorption) line fluxes, their ratios, and equivalent widths (EWs) to locate the QPE hosts on diagnostic diagrams. We also measured the velocity dispersion of the stellar absorption lines to estimate their black hole masses.Results.All QPE host galaxies show emission lines in their optical spectra. Based on their ratios and EWs, we find evidence for the presence of an AGN in all sources, including those previously reported as passive. We measure velocity dispersions between 36 and 90 km s−1, implying the presence of low mass (105−6.7 M⊙) black holes, consistent with literature findings. Finally, we find a significant over-representation (two out of the five sources, or a factor of 13−10+13) of quiescent Balmer strong (post-starburst) galaxies among QPE hosts.Conclusions.The presence of a narrow line region consistent with an AGN in all QPE host galaxies implies that a long-lived accretion flow likely plays an integral part in the QPE phenomenon. The strong over-representation of quiescent Balmer strong galaxies among QPE hosts can be naturally explained in both the TDE and interacting extreme mass ratio inspiral hypotheses.
Optimierung der Depotführung für Erythrozytenkonzentrate in Krankenhäusern
Authors: Dietrich Gerald 
Published: February 2022

ZusammenfassungBlutdepots ohne eigene Herstellung müssen Versorgungssicherheit garantieren, dabei aber auch eine möglichst geringe Verfallsrate sicherstellen. Für die Anzahl der zu bevorratenden
Erythrozytenkonzentrate (EK) der verschiedenen Blutgruppen wird folgendes Berechnungsmodell gefunden: 1. Die örtliche Verteilung der AB0-Blutgruppen im Patientenkollektiv kann mit dem
Hardy-Weinberg-Gesetz auf Plausibilität überprüft werden. 2. Der Beobachtungszeitraum ist die durchschnittliche Restlaufzeit von der Lieferung bis zum Ende der Haltbarkeit. 3. Der
Erwartungswert für die Fallzahl transfundierter Patienten einer bestimmten Blutgruppe gehorcht einer Binomialverteilung. 4. Die Anzahl transfundierter Erythrozytenkonzentrate pro Patient ist
geometrisch verteilt. 5. Eine Matrix wird gebildet, deren Zellen das Produkt aus Fallzahl (3.) und EK pro Fall (4.) und somit die Anzahl der benötigten EK enthalten. Nur letztgenannte sind
für die Führung des Blutdepots interessant. Subtrahiert man die Zahl der im Beobachtungszeitraum (2.) benötigten EK von der Depotgröße, erhält man den Verfall. Der Vorrat von EK der
Blutgruppe 0 bemisst sich an der maximal zu erwartenden Zahl benötigter Konserven für einen Fall bis zur nächstmöglichen Lieferung, wenn der durchschnittliche Depotumsatz diesen Wert nicht
übersteigt. Er kann somit insbesondere in peripheren Krankenhäusern mit Akutversorgung die oben beschriebene Kalkulation deutlich überschreiten. Für Blutgruppe A gilt dieser Grundsatz nicht,
wenn auch kompatible (0 auf A) Transfusionen stattfinden sollen. Binomial ist bei kleiner Anzahl nach links – das heißt gegen Null – schief verteilt. Dies betrifft in jedem Fall AB, bei
jährlichem Depotumsatz unter ungefähr 1000 EK aber auch Blutgruppe B. Möchte man den Verfall vermeiden, darf man die betroffenen Blutgruppen nicht – zumindest nicht in dem notwendigen Umfang
– bevorraten und muss dann majorkompatibel transfundieren. Die Unterschiede der einzelnen AB0-Blutgruppen in Herstellung (Blutgruppenverteilung in der Spenderpopulation) und der Bevorratung
in Krankenhaus-Blutdepots sind hierin begründet. Entsprechende Überlegungen gelten gleichermaßen für den Rhesusfaktor D. Die oft emotional geführte Debatte über die zu bevorratende Anzahl an
EK kann mittels dieses mathematischen Modells auf eine rationale Grundlage zurückgeführt werden. Das Rechenmodell ist mit einem einfachen Tabellenkalkulationsprogramm möglich. Das Blutdepot
bestimmt damit den optimalen Bestand. Für die Blutspendedienste ergibt sich hieraus die Möglichkeit, die Kunden individuell, das heißt umsatzabhängig, zu beraten und gegebenenfalls den Preis
entsprechend zu gestalten. Im Rahmen der Qualitätssicherung können abteilungs- oder krankenhausspezifische Besonderheiten im Transfusionsverhalten dargestellt werden.
Dexamethason für die postoperative Schmerztherapie in der Bandscheibenchirurgie
Authors: Schreiber Nikolaus , Gebauer David , Schittek Gregor , Sandner-Kiesling Andreas 
Published: February 2022

ZusammenfassungBandscheibenoperationen gehören in Deutschland zu den häufigen Operationen und eine effektive perioperative Schmerztherapie ist entscheidend für die rasche Genesung der Patient*innen. In
diesem Beitrag präsentieren wir die aktuelle Studienlage zum Einfluss einer perioperativen Dexamethason-Gabe auf den postoperativen Opioidbedarf sowie das Schmerzempfinden nach
Bandscheibenoperationen.
Gangtraining nach Amputation der unteren Extremität –
Ein systematisches Pyramiden-Review
Authors: Einfeldt Ann-Kathrin , Brinck Ann-Kathrina , Schiller Sandra , Borgetto Bernhard Maria 
Published: February 2022

Zusammenfassung
Hintergrund Menschen mit einer Amputation der unteren Extremität
haben ein asymmetrisches Gangbild, welches durch Fortbestehen konsekutiv zu
Beschwerden in anderen Körperregionen führen kann.
Methode Im Rahmen einer systematischen Recherche wurde in fünf
Datenbanken nach Publikationen zu Gangtrainingsmethoden bei Menschen mit einer
transtibialen oder transfemoralen Amputation gesucht. Die acht eingeschlossenen
Studien wurden bezüglich ihrer methodischen Strenge sowie ihrer
Durchführungs- und Ergebnisqualität kritisch bewertet und einer
Evidenzklasse der Forschungspyramide zugeordnet, um anschließend
Empfehlungen zu Behandlungsmöglichkeiten dieser
Patient*innengruppe geben zu können.
Ergebnisse Alle betrachteten Gangtrainingsmethoden führen zu einer
Verbesserung des Gangbildes. In sieben Studien werden in einer Trainingsmethode
mindestens vier verschiedene Trainingsformen verwendet. Eine Kombination aus
verschiedenen Trainingsformen scheint daher vielversprechend. Inwieweit die
Methoden langfristige Erfolge mit sich bringen, wird in den Studien nicht
überprüft. Aufgrund der unterschiedlichen Interventionen und
Outcome-Parameter, konnte keine Metaanalyse durchgeführt werden.
Schlussfolgerung Das Evidence-Based Amputee Rehabilitation Programm bietet
eine gute Grundlage für ein standardisiertes Trainingsprogramm
für Amputationspatient*innen und sollte um funktionelle
Dual-Task Übungen und Aufklärungsinterventionen ergänzt
werden. Die genaue Dauer und Intensität eines solchen Programmes sollten
erforscht werden. Des Weiteren sollten in zukünftigen Untersuchungen
vermehrt beobachtende und qualitative Studiendesigns herangezogen werden, um das
Gangtraining im physiotherapeutischen Praxisalltag zu optimieren.