bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental enrichment prevents the late effect of acute stress-induced fear extinction deficit: the role of hippocampal AMPA-GluA1 phosphorylation
Authors: Novaes Leonardo Santana , Bueno-de-Camargo Letícia Morais , Munhoz Carolina Demarchi 
Published: January 2021

AbstractThe persistence of anxiety and the deficit of fear memory extinction are both phenomena related to the symptoms of a trauma-related disorder, such as post-traumatic stress disorder (PTSD). Recently we have shown that single acute restraint stress (2 h) in rats induces a late anxiety-related behavior (observed ten days after stress), whereas, in the present work, we found that the same stress impaired fear extinction in animals conditioned ten days after stress. Fourteen days of environmental enrichment (EE) prevented the deleterious effect of stress on fear memory extinction. Additionally, we observed that EE prevented the stress-induced increase in AMPA receptor GluA1 subunit phosphorylation in the hippocampus, but not in the basolateral amygdala complex and the frontal cortex, indicating a potential mechanism by which it exerts its protective effect against the stress-induced behavioral outcome.
Lenalidomide versus bortezomib maintenance after frontline autologous stem cell transplantation for multiple myeloma
Authors: Baertsch Marc-Andrea , Mai Elias K. , Hielscher Thomas , Bertsch Uta , Salwender Hans J. , Munder Markus , Fuhrmann Stephan , Dührsen Ulrich , Brossart Peter , Neben Kai , Schlenzka Jana , Kunz Christina , Raab Marc S. , Hillengaß Jens , Jauch Anna , Seckinger Anja , Hose Dirk , Luntz Steffen , Sonneveld Pieter , Lokhorst Henk , Martin Hans , Goerner Martin , Hoffmann Martin , Lindemann Hans-Walter , Bernhard Helga , Blau Igor W. , Scheid Christof , Besemer Britta , Weisel Katja C. , Hänel Mathias , Dürig Jan , Goldschmidt Hartmut ,   German-Speaking Myeloma Multicenter Group (GMMG)
Published: January 2021

AbstractLenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended (p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with <nCR after first ASCT were assigned tandem ASCT in both trials. In patients with <nCR and tandem ASCT (LEN: n = 54 vs. BTZ: n = 84), LEN MT significantly improved PFS (HR = 0.61, p = 0.04) but not OS (HR = 0.46, p = 0.09). In conclusion, the significant PFS benefit after eliminating the impact of different tandem ASCT rates supports the current standard of LEN MT after ASCT.
Effect of autologous hematopoietic stem cell transplant on the development of second primary malignancies in multiple myeloma patients
Authors: Rosenberg A. S. , Brunson A. , Tuscano J. , Jonas B. A. , Hoeg R. , Wun T. , Keegan T. H. M. 
Published: January 2021

AbstractAutologous stem cell transplant (aHSCT) is associated with improved survival for multiple myeloma (MM) patients but may be associated with second primary malignancy (SPM) development. Using the California Cancer Registry linked to statewide hospitalization data, we determined the cumulative incidence (CMI) of SPMs more than 1 year after MM diagnosis, accounting for the competing risk of death. AHSCT recipients were matched 1:2 to non-aHSCT patients. Adjusted hazard ratios (aHR) were estimated using the Fine and Gray method. Among 16,331 patients, 933 (5.7%) developed a SPM more than 1 year after diagnosis. The 10-year CMI of developing any SPM was 6.6%, 5.7% for solid tumor SPM and 0.9% for hematologic malignancies. The 10-year CMI of developing any SPM was similar among aHSCT [9.1% (7.7–10.7%)] and non-aHSCT [7.5% (6.5–8.6%)] (P = 0.26) recipients and there was no difference in solid-tumor SPMs (P = 0.98). The 10-year CMI of hematologic SPMs was higher among aHSCT recipients [2.1% (1.4–2.9%) vs. 0.8% (0.5–1.2%); P = 0.005], corresponding to a 1.3% absolute increase and an aHR of 1.51 (1.01–2.27). Ten-year myeloma-specific and non-cancer mortality rates were 59% (58.2–60.0%) and 18.1% (17.4–18.8%), respectively. Although aHSCT was associated with a small increase in hematologic SPMs, mortality was driven by MM and non-cancer causes.
STAT1-induced regulation of lncRNA ZFPM2-AS1 predicts poor prognosis and contributes to hepatocellular carcinoma progression via the miR-653/GOLM1 axis
Authors: Zhang Xi-wu , Li Qiu-han , Xu Zuo-di , Dou Jin-jin 
Published: January 2021

AbstractLong noncoding RNAs (lncRNAs) have drawn growing attention owing to their important effects in various tumors, including hepatocellular carcinoma (HCC). Recently, a newly identified lncRNA, ZFPM2 antisense RNA 1 (ZFPM2-AS1), was reported to serve as an oncogene in gastric cancer. However, its function in tumors remains largely unknown. In this study, we identified ZFPM2-AS1 as a novel HCC-related lncRNA, which was observed to be distinctly upregulated in HCC tissues and associated with shorter overall survival. Luciferase reporter and chromatin immunoprecipitation assays suggested that overexpression of ZFPM2-AS1 was induced by STAT1. Functional investigations suggested that the inhibition of ZFPM2-AS1 suppressed cell proliferation, metastasis, cell cycle progression while accelerated cell apoptosis. Mechanistic studies showed that there were two binding sites of miR-653 within the sequence of ZFPM2-AS1 and the levels of ZFPM2-AS1 were negatively correlated with miR-653. In addition, ZFPM2-AS1 could reverse the suppressor effects of miR-653 on the proliferation and metastasis of HCC cells by the modulation of GOLM1, a target gene of miR-653. To conclude, we provided a better understanding of the interaction mechanism between ZFPM2-AS-miR-653-GOLM1 axis, which may help develop prognostic biomarkers and therapeutic target for HCC.
Nrf2 overexpression increases risk of high tumor mutation burden in acute myeloid leukemia by inhibiting MSH2
Authors: Liu Ping , Ma Dan , Wang Ping , Pan Chengyun , Fang Qin , Wang Jishi 
Published: January 2021

AbstractNuclear factor erythroid 2-related factor 2 (Nrf2, also called NFE2L2) plays an important role in cancer chemoresistance. However, little is known about the role of Nrf2 in tumor mutation burden and the effect of Nrf2 in modulating DNA mismatch repair (MMR) gene in acute myeloid leukemia (AML). Here we show that Nrf2 expression is associated with tumor mutation burden in AML. Patients with Nrf2 overexpression had a higher frequency of gene mutation and drug resistance. Nrf2 overexpression protected the AML cells from apoptosis induced by cytarabine in vitro and increased the risk of drug resistance associated with a gene mutation in vivo. Furthermore, Nrf2 overexpression inhibited MutS Homolog 2 (MSH2) protein expression, which caused DNA MMR deficiency. Mechanistically, the inhibition of MSH2 by Nrf2 was in a ROS-independent manner. Further studies showed that an increased activation of JNK/c-Jun signaling in Nrf2 overexpression cells inhibited the expression of the MSH2 protein. Our findings provide evidence that high Nrf2 expression can induce gene instability-dependent drug resistance in AML. This study demonstrates the reason why the high Nrf2 expression leads to the increase of gene mutation frequency in AML, and provides a new strategy for clinical practice.
Corneal endothelial cell loss after trabeculectomy and phacoemulsification in one or two steps: a prospective study
Authors: Soro-Martínez María Isabel , Miralles de Imperial-Ollero Juan Antonio , Pastor-Montoro Miriam , Arcos-Villegas Gabriel , Sobrado-Calvo Paloma , Ruiz-Gómez José María , Miralles de Imperial-Mora-Figueroa Jaime , Villegas-Pérez María Paz 
Published: January 2021

Abstract
Objective
The objective of this study was to analyse the results of the surgical treatment of coexisting cataract and glaucoma and its effects on corneal endothelial cell density (CECD).

Methods
We include two longitudinal prospective studies: one randomised that included 40 eyes with open angle glaucoma that received one- (n = 20) or two-step (n = 20) phacotrabeculectomy and another that included 20 eyes that received phacoemulsification. We assess the impact of surgery on different clinical variables and in particular in CECD using Confoscan 4™ confocal microscopy and semiautomatic counting methods.

Results
Phacoemulsification and phacotrabeculectomy, but not trabeculectomy, increase significantly best-corrected visual acuity and anterior chamber depth and trabeculectomy and one- or two-step phacotrabeculectomy decreased similarly the intraocular pressure. We document percentages of endothelial cell loss of 3.1%, 17.9%, 31.6% and 42.6% after trabeculectomy, phacoemulsification and one- or two-step phacotrabeculectomy, respectively. The coefficient of variation did not increase significantly after surgery but the percentage of hexagonality decreased significantly after phacoemulsification and after two-step phacotrabeculectomy.

Conclusions
Trabeculectomy, phacoemulsification and phacotrabeculectomy are surgical techniques that cause morphological changes and decrease the densities of the corneal endothelial cells. Trabeculectomy produces lesser endothelial cell loss than phacoemulsification, and phacoemulsification lesser cell loss than phacotrabeculectomy. Two-step phacotrabeculectomy (trabeculectomy followed 3 months later by phacoemulsification) causes more cell loss than one-step phacotrabeculectomy, and this could be due to the cumulative effects of two separate surgical traumas or to a negative conditioning lesion effect of the first surgery. For the treatment of coexisting glaucoma and cataract, one-step phacotrabeculectomy is the treatment of choice.
Safety and efficacy of repeated crosslinking assisted by transepithelial double-cycle iontophoresis in keratoconus progression after primary corneal crosslinking
Authors: Wu Huping , Li Lan , Luo Shunrong , Fang Xie , Shang Xumin , Xie Zhiwen , Xiao Xianwen , He Huan , Lin Zhirong , Liu Zuguo 
Published: January 2021

AbstractObjectivesTo evaluate the safety and efficacy of repeated corneal collagen crosslinking assisted by transepithelial double-cycle iontophoresis (DI-CXL) in the management of keratoconus progression after primary CXL.MethodsA retrospective analysis was conducted in the patients who underwent repeated CXL between 2016 and 2018. These patients were treated with DI-CXL if keratoconus progression was confirmed after primary CXL. Scoring of ocular pain and corneal epithelial damage, visual acuity, corneal tomography, in vivo corneal confocal microscopy (IVCM) was performed before and at 3, 6, 12, and 24 months after DI-CXL.ResultsOverall, 21 eyes of 12 patients (mean age 17.3 ± 1.9 years) were included in this study. Before DI-CXL, an average increase of 4.26 D inKmaxwas detected in these patients with a mean follow-up interval of (23.0 ± 13.7) months. After DI-CXL, corneal epithelial damage rapidly recovered within days. Visual acuity remained unchanged with follow-up of 24 months. When compared to baseline, significant decreases were observed inKmax(at 3 months) and K2 (at 3 and 6 months) after DI-CXL. Corneal thickness of thinnest point significantly decreased at 3 months postoperatively. When compared to baseline, no significant differences were found in any of the refractive or tomographic parameters at 12 and 24 months. IVCM revealed trabecular patterned hyperdense tissues after DI-CXL in the anterior stroma at the depth of 200 μm or more. No corneal infiltration or persistent epithelial defect was recorded after DI-CXL.ConclusionDI-CXL is safe and effective as a good alternative in stabilizing keratoconus progression after primary CXL.
Excess protein enabled dog domestication during severe Ice Age winters
Authors: Lahtinen Maria , Clinnick David , Mannermaa Kristiina , Salonen J. Sakari , Viranta Suvi 
Published: January 2021

AbstractDogs (Canis familiaris) are the first animals to be domesticated by humans and the only ones domesticated by mobile hunter-gatherers. Wolves and humans were both persistent, pack hunters of large prey. They were species competing over resources in partially overlapping ecological niches and capable of killing each other. How could humans possibly have domesticated a competitive species? Here we present a new hypothesis based on food/resource partitioning between humans and incipient domesticated wolves/dogs. Humans are not fully adapted to a carnivorous diet; human consumption of meat is limited by the liver’s capacity to metabolize protein. Contrary to humans, wolves can thrive on lean meat for months. We present here data showing that all the Pleistocene archeological sites with dog or incipient dog remains are from areas that were analogous to subarctic and arctic environments. Our calculations show that during harsh winters, when game is lean and devoid of fat, Late Pleistocene hunters-gatherers in Eurasia would have a surplus of animal derived protein that could have been shared with incipient dogs. Our partitioning theory explains how competition may have been ameliorated during the initial phase of dog domestication. Following this initial period, incipient dogs would have become docile, being utilized in a multitude of ways such as hunting companions, beasts of burden and guards as well as going through many similar evolutionary changes as humans.
Angiotensin-converting enzyme 2 and COVID-19 in cardiorenal diseases
Authors: Sharma Ravindra K. , Li Jing , Krishnan Suraj , Richards Elaine M. , Raizada Mohan K. , Mohandas Rajesh 
Published: January 2021

AbstractThe rapid spread of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought into focus the key role of angiotensin-converting enzyme 2 (ACE2), which serves as a cell surface receptor required for the virus to enter cells. SARS-CoV-2 can decrease cell surface ACE2 directly by internalization of ACE2 bound to the virus and indirectly by increased ADAM17 (a disintegrin and metalloproteinase 17)-mediated shedding of ACE2. ACE2 is widely expressed in the heart, lungs, vasculature, kidney and the gastrointestinal (GI) tract, where it counteracts the deleterious effects of angiotensin II (AngII) by catalyzing the conversion of AngII into the vasodilator peptide angiotensin-(1-7) (Ang-(1-7)). The down-regulation of ACE2 by SARS-CoV-2 can be detrimental to the cardiovascular system and kidneys. Further, decreased ACE2 can cause gut dysbiosis, inflammation and potentially worsen the systemic inflammatory response and coagulopathy associated with SARS-CoV-2. This review aims to elucidate the crucial role of ACE2 both as a regulator of the renin–angiotensin system and a receptor for SARS-CoV-2 as well as the implications for Coronavirus disease 19 and its associated cardiovascular and renal complications.
Unsupervised automated retinal vessel segmentation based on Radon line detector and morphological reconstruction
Authors: Tavakoli Meysam , Mehdizadeh Alireza , Pourreza Shahri Reza , Dehmeshki Jamshid 
Published: January 2021

AbstractRetinal blood vessel segmentation and analysis is critical for the computer‐aided diagnosis of different diseases such as diabetic retinopathy. This study presents an automated unsupervised method for segmenting the retinal vasculature based on hybrid methods. The algorithm initially applies a preprocessing step using morphological operators to enhance the vessel tree structure against a non‐uniform image background. The main processing applies the Radon transform to overlapping windows, followed by vessel validation, vessel refinement and vessel reconstruction to achieve the final segmentation. The method was tested on three publicly available datasets and a local database comprising a total of 188 images. Segmentation performance was evaluated using three measures: accuracy, receiver operating characteristic (ROC) analysis, and the structural similarity index. ROC analysis resulted in area under curve values of 97.39%, 97.01%, and 97.12%, for the DRIVE, STARE, and CHASE‐DB1, respectively. Also, the results of accuracy were 0.9688, 0.9646, and 0.9475 for the same datasets. Finally, the average values of structural similarity index were computed for all four datasets, with average values of 0.9650 (DRIVE), 0.9641 (STARE), and 0.9625 (CHASE‐DB1). These results compare with the best published results to date, exceeding their performance for several of the datasets; similar performance is found using accuracy.
Investigation on soil resistivity of two‐layer soil structures using finite element analysis method
Authors: Illias Hazlee Azil , Su Chuang Sheng , Bakar Ab Halim Abu 
Published: January 2021

AbstractEffective grounding is the most important aspect in every electrical installation because it can ensure efficient equipment operation in the event of electrical faults. Measurement data of soil resistivity is used to assess the suitability of the soil for grounding purpose and also to evaluate the structures of the soil. However, the limitation of soil resistivity measurement is various investigations on two‐layer soil structures cannot be performed due to the variation of natural soil structures is limited. Therefore, in this work, modelling of soil resistivity of two‐layer soil structures was proposed using finite element analysis method to estimate the depth of upper layer of non‐homogeneous soil based on the measurement results from Wenner and Schlumberger methods. Also, using the proposed method, the effect of soil resistivity of each layer on the overall two‐layer soil resistivity was investigated. To validate the results obtained from the proposed method, comparison between the FEA results and measured field data was made. It was found that the average error between both results is <3%. From the model that has been developed, the soil properties can be varied, which enhances the information that can be obtained from two‐layer soil structures.
Blended-Learning-Konzepte in der Intensivmedizin am Beispiel des ERIC-Trainings
Authors: Paul Nicolas , Dähnert Enrico , Grunow Julius J. , Landgraf Philipp , Schröder Torsten , Weiss Björn , Spies Claudia D. ,   und das ERIC-Konsortium
Published: January 2021

ZusamenfassungDie Implementierung der wachsenden medizinischen Evidenz und neuer Innovationen in dem dynamischen Umfeld der Intensivmedizin stellt hohe Anforderungen an die berufsbegleitende Weiterbildung des Personals. Die neue Versorgungsform Enhanced Recovery after Intensive Care (ERIC) kombiniert daher ein modernes Blended-Learning-Konzept mit einer telemedizinischen Versorgung im Rahmen einer komplexen Intervention zur Verbesserung der Behandlungsqualität.
Entwicklung der Ergebnisse des zweiten und dritten Abschnitts der
Ärztlichen Prüfung („M2“ Und
„M3“) In Deutschland
Authors: Palmowski Andriko 
Published: January 2021

Zusammenfassung
Ziel der Studie Analyse der Entwicklung der Ergebnisse des Zweiten
(klinisch-schriftlichen, „M2“) und Dritten
(klinisch-mündlichen; „M3“) Abschnitts der
Ärztlichen Prüfung in Deutschland.
Methodik Es wurden öffentlich verfügbare Daten des
Zweiten und Dritten Abschnitts der Ärztlichen Prüfung
analysiert (Jahre 2014–2020). Meta-Regressions-Modelle
(mixed-effects) schätzten Zusammenhänge zwischen
Prüfungsergebnissen und dem Zeitpunkt der Prüfung ein.
Ergebnisse Im untersuchten Zeitraum nahmen insgesamt 63 811
bzw. 32 852 Teilnehmer an den untersuchten M2- bzw.
M3-Prüfungen teil. Der Prozentsatz durchschnittlich richtig
beantworteter Fragen aller M2-Examina lag bei 77,7% (Minimum:
73%; Maximum: 82,7%). Es zeigte sich über die Zeit
eine große Variation in den Ergebnissen: Der Anteil von Teilnehmern
mit „sehr gutem“ Ergebnis variierte zwischen 0,1%
(Frühjahr 2020) und 17% (Herbst 2015) und der Anteil von
Teilnehmern mit „gutem“ Ergebnis zwischen 21%
(Frühjahr 2020) und 52% (Herbst 2015). Insgesamt zeigte sich
bei Analyse der M2-Examina ein negativer Trend. Über die Zeit sanken
bspw. der Prozentsatz richtig beantworteter Fragen (Steigung
β=-0,82%; p < 0,01) und der Anteil von
Teilnehmern mit „sehr gutem“ (β=-1,17;
p=0,04) und „gutem“ (β=-2,58;
p=0,02) Ergebnis. In den Modellen konnte mit dem Zeitpunkt der
Prüfung zwischen 20 und 34% der Heterogenität
zwischen den Prüfungen erklärt werden. In den M3-Examina
zeigte sich nur eine sehr geringe Variation über die Zeit,
außerdem waren keine Trends zu erkennen
(p=0,08–0,60).
Schlussfolgerung Die Ergebnisse der M2-Examina variierten über
die letzten Jahre stark, außerdem zeigte sich ein deutlicher Trend
hin zu durchschnittlich schlechteren Ergebnissen. Die Ergebnisse der
M3-Examina blieben hingegen bei geringer Variation auf konstantem Niveau.
Mögliche Ursachen dieser Entwicklungen – etwa schlechter
werdende schriftliche Fähigkeiten der Studierenden oder ein
höherer Anforderungsgrad in den M2-Examina – sollten
untersucht werden. Die große Variation der durchschnittlichen
Ergebnisse stellt die Reliabilität und Vergleichbarkeit der
M2-Examina in Frage.
Lungenultraschall in der Neonatologie zur Diagnostik eines Pneumothorax (Teil 1): Eine Evidenzanalyse – Zeit für einen neuen Goldstandard
Authors: Sandig Jan , Bührer Christoph , Czernik Christoph 
Published: January 2021

ZusammenfassungDer Lungenultraschall ist eine in der Notfallmedizin gut erforschte Untersuchungsmethode. Der Pneumothoraxausschluss mithilfe des Lungenultraschalls ist in den letzten Jahren auch bei Neugeborenen intensiv erforscht worden. Es wurden standardisierte Untersuchungsalgorithmen und unstrittige pathognomonische Untersuchungsbefunde veröffentlicht. Im Vergleich zum etablierten diagnostischen Standardverfahren, der Röntgenthoraxaufnahme, bietet der Lungenultraschall eine Reihe von Vorteilen, wobei der Verzicht auf ionisierende Strahlung und die rasche Diagnosestellung bei exzellenter Sensitivität und vergleichbarer Spezifität herausstechen. Der Lungenultraschall leistet somit einen Beitrag zur Verbesserung der Versorgungsqualität in der neonatologischen Intensivmedizin. Wir sehen daher die Nutzung des Lungenultraschalls als neues Standardverfahren in der Pneumothoraxdiagnostik beim Neugeborenen an.