bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED ARTICLE: PIK3R3, part of the regulatory domain of PI3K, is upregulated in sarcoma stem-like cells and promotes invasion, migration, and chemotherapy resistance
Authors: Yoon Changhwan , Lu Jun , Ryeom Sandra W. , Simon M. Celeste , Yoon Sam S. 
Published: July 2021

AbstractTo identify drivers of sarcoma cancer stem-like cells (CSCs), we compared gene expression using RNA sequencing between HT1080 fibrosarcoma and SK-LMS-1 leiomyosarcoma spheroids (which are enriched for CSCs) compared with the parent populations. The most overexpressed survival signaling-related gene in spheroids was phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of PI3K, which functions in tumorigenesis and metastasis. In a human sarcoma microarray, PIK3R3 was also overexpressed by 4.1-fold compared with normal tissues. PIK3R3 inhibition using shRNA in the HT1080, SK-LMS-1, and DDLS8817 dedifferentiated liposarcoma in spheroids and in CD133+ cells (a CSC marker) reduced expression of CD133 and the stem cell factor Nanog and blocked spheroid formation by 61–71%. Mechanistic studies showed that in spheroid cells, PIK3R3 activated AKT and ERK signaling. Inhibition of PIK3R3, AKT, or ERK using shRNA or inhibitors decreased expression of Nanog, spheroid formation by 68–73%, and anchorage-independent growth by 76–91%. PIK3R3 or ERK1/2 inhibition similarly blocked sarcoma spheroid cell migration, invasion, secretion of MMP-2, xenograft invasion into adjacent normal tissue, and chemotherapy resistance. Together, these results show that signaling through the PIK3R3/ERK/Nanog axis promotes sarcoma CSC phenotypes such as migration, invasion, and chemotherapy resistance, and identify PIK3R3 as a potential therapeutic target in sarcoma.
Impact of indoor temperature instability on diurnal and day-by-day variability of home blood pressure in winter: a nationwide Smart Wellness Housing survey in Japan
Authors: Umishio Wataru , Ikaga Toshiharu , Kario Kazuomi , Fujino Yoshihisa , Suzuki Masaru , Ando Shintaro , Hoshi Tanji , Yoshimura Takesumi , Yoshino Hiroshi , Murakami Shuzo ,   on behalf of the SWH survey group
Published: July 2021

AbstractHome blood pressure (HBP) variability is an important factor for cardiovascular events. While several studies have examined the effects of individual attributes and lifestyle factors on reducing HBP variability, the effects of living environment remain unknown. We hypothesized that a stable home thermal environment contributes to reducing HBP variability. We conducted an epidemiological survey on HBP and indoor temperature in 3785 participants (2162 households) planning to have their houses retrofitted with insulation. HBP was measured twice in the morning and evening for 2 weeks in winter. Indoor temperature was recorded with each HBP observation. We calculated the morning-evening (ME) difference as an index of diurnal variability and the standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM) as indices of day-by-day variability. The association between BP variability and temperature instability was analyzed using multiple linear regression models. The mean ME difference in indoor/outdoor temperature (a decrease in temperature overnight) was 3.2/1.5 °C, and the mean SD of indoor/outdoor temperature was 1.6/2.5 °C. Linear regression analyses showed that the ME difference in indoor temperature was closely correlated with the ME difference in systolic BP (0.85 mmHg/°C, p < 0.001). The SD of indoor temperature was also associated with the SD of systolic BP (0.61 mmHg/°C, p < 0.001). The CV, ARV, and VIM showed similar trends as the SD of BP. In contrast, outdoor temperature instability was not associated with either diurnal or day-by-day HBP variability. Therefore, residents should keep the indoor temperature stable to reduce BP variability.
Antibody toolkit reveals N-terminally ubiquitinated substrates of UBE2W
Authors: Davies Christopher W. , Vidal Simon E. , Phu Lilian , Sudhamsu Jawahar , Hinkle Trent B. , Chan Rosenberg Scott , Schumacher Frances-Rose , Zeng Yi Jimmy , Schwerdtfeger Carsten , Peterson Andrew S. , Lill Jennie R. , Rose Christopher M. , Shaw Andrey S. , Wertz Ingrid E. , Kirkpatrick Donald S. , Koerber James T. 
Published: July 2021

AbstractThe ubiquitin conjugating enzyme UBE2W catalyzes non-canonical ubiquitination on the N-termini of proteins, although its substrate repertoire remains unclear. To identify endogenous N-terminally-ubiquitinated substrates, we discover four monoclonal antibodies that selectively recognize tryptic peptides with an N-terminal diglycine remnant, corresponding to sites of N-terminal ubiquitination. Importantly, these antibodies do not recognize isopeptide-linked diglycine (ubiquitin) modifications on lysine. We solve the structure of one such antibody bound to a Gly-Gly-Met peptide to reveal the molecular basis for its selective recognition. We use these antibodies in conjunction with mass spectrometry proteomics to map N-terminal ubiquitination sites on endogenous substrates of UBE2W. These substrates include UCHL1 and UCHL5, where N-terminal ubiquitination distinctly alters deubiquitinase (DUB) activity. This work describes an antibody toolkit for enrichment and global profiling of endogenous N-terminal ubiquitination sites, while revealing functionally relevant substrates of UBE2W.
Atomic-scale unveiling of multiphase evolution during hydrated Zn-ion insertion in vanadium oxide
Authors: Byeon Pilgyu , Hong Youngjae , Bae Hyung Bin , Shin Jaeho , Choi Jang Wook , Chung Sung-Yoon 
Published: July 2021

AbstractAn initial crystalline phase can transform into another phases as cations are electrochemically inserted into its lattice. Precise identification of phase evolution at an atomic level during transformation is thus the very first step to comprehensively understand the cation insertion behavior and subsequently achieve much higher storage capacity in rechargeable cells, although it is sometimes challenging. By intensively using atomic-column-resolved scanning transmission electron microscopy, we directly visualize the simultaneous intercalation of both H2O and Zn during discharge of Zn ions into a V2O5 cathode with an aqueous electrolyte. In particular, when further Zn insertion proceeds, multiple intermediate phases, which are not identified by a macroscopic powder diffraction method, are clearly imaged at an atomic scale, showing structurally topotactic correlation between the phases. The findings in this work suggest that smooth multiphase evolution with a low transition barrier is significantly related to the high capacity of oxide cathodes for aqueous rechargeable cells, where the crystal structure of cathode materials after discharge differs from the initial crystalline state in general.
The genomic landscape of 85 advanced neuroendocrine neoplasms reveals subtype-heterogeneity and potential therapeutic targets
Authors: van Riet Job , van de Werken Harmen J. G. , Cuppen Edwin , Eskens Ferry A. L. M. , Tesselaar Margot , van Veenendaal Linde M. , Klümpen Heinz-Josef , Dercksen Marcus W. , Valk Gerlof D. , Lolkema Martijn P. , Sleijfer Stefan , Mostert Bianca 
Published: July 2021

AbstractMetastatic and locally-advanced neuroendocrine neoplasms (aNEN) form clinically and genetically heterogeneous malignancies, characterized by distinct prognoses based upon primary tumor localization, functionality, grade, proliferation index and diverse outcomes to treatment. Here, we report the mutational landscape of 85 whole-genome sequenced aNEN. This landscape reveals distinct genomic subpopulations of aNEN based on primary localization and differentiation grade; we observe relatively high tumor mutational burdens (TMB) in neuroendocrine carcinoma (average 5.45 somatic mutations per megabase) withTP53,KRAS,RB1,CSMD3,APC,CSMD1,LRATD2,TRRAP and MYCas major drivers versus an overall low TMB in neuroendocrine tumors (1.09). Furthermore, we observe distinct drivers which are enriched in somatic aberrations in pancreatic (MEN1,ATRX,DAXX,DMDandCREBBP) and midgut-derived neuroendocrine tumors (CDKN1B). Finally, 49% of aNEN patients reveal potential therapeutic targets based upon actionable (and responsive) somatic aberrations within their genome; potentially directing improvements in aNEN treatment strategies.
Evading strength-corrosion tradeoff in Mg alloys via dense ultrafine twins
Authors: Yan Changjian , Xin Yunchang , Chen Xiao-Bo , Xu Daokui , Chu Paul K. , Liu Chaoqiang , Guan Bo , Huang Xiaoxu , Liu Qing 
Published: July 2021

AbstractConventional ultrafine-grains can generate high strength in Mg alloys, but significant tradeoff of corrosion resistance due to inclusion of a large number of non-equilibrium grain boundaries. Herein, an ultrafine-grain structure consisting of dense ultrafine twins is prepared, yielding a high strength up to 469 MPa and decreasing the corrosion rate by one order of magnitude. Generally, the formation of dense ultrafine twins in Mg alloys is rather difficult, but a carefully designed multi-directional compression treatment effectively stimulates twinning nucleation within twins and refines grain size down to 300 nm after 12-passes compressions. Grain-refinement by low-energy twins not only circumvents the detrimental effects of non-equilibrium grain boundaries on corrosion resistance, but also alters both the morphology and distribution of precipitates. Consequently, micro-galvanic corrosion tendency decreases, and severe localized corrosion is suppressed completely. This technique has a high commercial viability as it can be readily implemented in industrial production.
Adaptive ecological niche migration does not negate extinction susceptibility
Authors: Woodhouse A. , Jackson S. L. , Jamieson R. A. , Newton R. J. , Sexton P. F. , Aze T. 
Published: July 2021

AbstractExtinction rates in the modern world are currently at their highest in 66 million years and are likely to increase with projections of future climate change. Our knowledge of modern-day extinction risk is largely limited to decadal-centennial terrestrial records, while data from the marine realm is typically applied to high-order (> 1 million year) timescales. At present, it is unclear whether fossil organisms with common ancestry and ecological niche exhibit consistent indicators of ecological stress prior to extinction. The marine microfossil record, specifically that of the planktonic foraminifera, allows for high-resolution analyses of large numbers of fossil individuals with incredibly well-established ecological and phylogenetic history. Here, analysis of the isochronous extinction of two members of the planktonic foraminiferal genusDentoglobigerinashows disruptive selection differentially compounded by permanent ecological niche migration, “pre-extinction gigantism”, and photosymbiont bleaching prior to extinction. Despite shared ecological and phylogenetic affinity, and timing of extinction, the marked discrepancies observed within the pre-extinction phenotypic responses are species-specific. These behaviours may provide insights into the nature of evolution and extinction in the open ocean and can potentially assist in the recognition and understanding of marine extinction risk in response to global climate change.
Mathematical model of the feedback between global supply chain disruption and COVID-19 dynamics
Authors: Li Xingyu , Ghadami Amin , Drake John M. , Rohani Pejman , Epureanu Bogdan I. 
Published: July 2021

AbstractThe pandemic of COVID-19 has become one of the greatest threats to human health, causing severe disruptions in the global supply chain, and compromising health care delivery worldwide. Although government authorities sought to contain the spread of SARS-CoV-2, by restricting travel and in-person activities, failure to deploy time-sensitive strategies in ramping-up of critical resource production exacerbated the outbreak. Here, we developed a mathematical model to analyze the effects of the interaction between supply chain disruption and infectious disease dynamics using coupled production and disease networks built on global data. Analysis of the supply chain model suggests that time-sensitive containment strategies could be created to balance objectives in pandemic control and economic losses, leading to a spatiotemporal separation of infection peaks that alleviates the societal impact of the disease. A lean resource allocation strategy can reduce the impact of supply chain shortages from 11.91 to 1.11% in North America. Our model highlights the importance of cross-sectoral coordination and region-wise collaboration to optimally contain a pandemic and provides a framework that could advance the containment and model-based decision making for future pandemics.
Zooarchaeology through the lens of collagen fingerprinting at Denisova Cave
Authors: Brown Samantha , Wang Naihui , Oertle Annette , Kozlikin Maxim B. , Shunkov Michael V. , Derevianko Anatoly P. , Comeskey Daniel , Jope-Street Blair , Harvey Virginia L. , Chowdhury Manasij Pal , Buckley Michael , Higham Thomas , Douka Katerina 
Published: July 2021

AbstractDenisova Cave, a Pleistocene site in the Altai Mountains of Russian Siberia, has yielded significant fossil and lithic evidence for the Pleistocene in Northern Asia. Abundant animal and human bones have been discovered at the site, however, these tend to be highly fragmented, necessitating new approaches to identifying important hominin and faunal fossils. Here we report the results for 8253 bone fragments using ZooMS. Through the integration of this new ZooMS-based data with the previously published macroscopically-identified fauna we aim to create a holistic picture of the zooarchaeological record of the site. We identify trends associated with climate variability throughout the Middle and Upper Pleistocene as well as patterns explaining the process of bone fragmentation. Where morphological analysis of bones from the site have identified a high proportion of carnivore bones (30.2%), we find that these account for only 7.6% of the ZooMS assemblage, with large mammals between 3 and 5 more abundant overall. Our analysis suggests a cyclical pattern in fragmentation of bones which sees initial fragmentation by hominins using percussive tools and secondary carnivore action, such as gnawing and digestion, likely furthering the initial human-induced fragmentation.
Pumping infusions with a syringe may cause contamination of the fluid in the syringe
Authors: Kawakami Yutaka , Tagami Takashi 
Published: July 2021

AbstractClinicians often perform pumping of infusions with a syringe (PIS) to quickly deliver fluid or blood transfusion to patients, especially during an emergency. Despite the efforts of the clinicians, critically ill patients are prone to acquire catheter-related bloodstream infections. Although clinicians have reported the possibility of PIS contamination, no group of researchers has studied nor confirmed this possibility. Here, we examined whether PIS can cause bacterial contamination of the fluid inside the syringes, using microbiological tests, including the analysis Escherichia coli DH-5 alpha growth by measuring the absorbance at OD600. We confirmed that contamination of fluid in the barrel was almost proportional to the applied volume of bacterial fluid. Aliquots of DH-5 alpha artificially applied on the surface of the gloved hand of an examiner, the plunger or the inner side of the barrel of a syringe could permeate inside the syringe. Furthermore, disinfection with ethanol before PIS almost successfully prevented bacterial multiplication. Our findings suggest that PIS can cause intraluminal contamination when performed with unsterilized hands, and that previous disinfection with ethanol can effectively prevent PIS-induced contamination. These results highlight the risk of PIS-induced contamination and the importance of disinfection in the daily clinical practice.
Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1
Authors: Roque Patricia Soriano , Hooshmandi Mehdi , Neagu-Lund Laura , Yin Shelly , Yousefpour Noosha , Sato Hiroaki , Sato Tamaki , Nakadate Yosuke , Kawakami Akiko , Tahmasebi Soroush , Ribeiro-da-Silva Alfredo , Gkogkas Christos G. , Prager-Khoutorsky Masha , Schricker Thomas , Wykes Linda , Khoutorsky Arkady 
Published: July 2021

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.
Configuration of flowsheet and reagent dosage for gilsonite flotation towards the ultra-low-ash concentrate
Authors: Bahrami Ataallah , Kazemi Fatemeh , Mirmohammadi Mirsaleh , Ghorbani Yousef , Farajzadeh Saghar 
Published: July 2021

AbstractGilsonite has a wide variety of applications in the industry, including the manufacture of electrodes, paints and resins, as well as the production of asphalt and roof-waterproofing material. Gilsonite ash is a determining parameter for its application in some industries (e.g., gilsonite with ash content < 5% used as an additive in drilling fluids, resins). Due to the shortage of high grade (low ash) gilsonite reserves, the aim of this study is to develop a processing flowsheet for the production of ultra-low-ash gilsonite (< 5%), based on process mineralogy studies and processing tests. For this purpose, mineralogical studies and flotation tests have been performed on a sample of gilsonite with an average ash content of 15%. According to mineralogical studies, carbonates and clay minerals are the main associated impurities (more than 90 vol.%). Furthermore, sulfur was observed in two forms of mineral (pyrite and marcasite) and organic in the structure of gilsonite. Most of these impurities are interlocked with gilsonite in size fractions smaller than 105 µm. The size fraction of + 105 − 420 µm has a higher pure gilsonite (approximately 90%) than other size fractions. By specifying the gangue minerals with gilsonite and the manner and extent of their interlocking with gilsonite, + 75 − 420 µm size fraction selected to perform flotation tests. Flotation tests were performed using different reagents including collector (Gas oil, Kerosene and Pine oil), frother (MIBC) and depressant (sodium silicate, tannic acid, sulfuric acid and sodium cyanide) in different dosages. Based on the results, the use of kerosene collector, MIBC frother and a mixture of sodium silicate, tannic acid, sulfuric acid and sodium cyanide depressant had the most favorable results in gilsonite flotation in the rougher stage. Cleaner and recleaner flotation stages for the rougher flotation concentrate resulted in a product with an ash content of 4.89%. Due to the interlocking of gilsonite with impurities in size fractions − 105 µm, it is better to re-grinding the concentrate of the rougher stage beforehand flotation in the cleaner and recleaner stages. Finally, based on the results of mineralogical studies and processing tests, a processing flowsheet including crushing and initial granulation of gilsonite, flotation in rougher, cleaner and recleaner stages has been proposed to produce gilsonite concentrate with < 5% ash content.
Ungewöhnliche Ursache einer PCT-Erhöhung
Authors: Vogelbacher Laura Clarissa , Thimme Robert 
Published: July 2021

Zusammenfassung
Zusammenfassung Procalcitonin (PCT) ist ein etablierter Marker für bakterielle Infektionen. Erhöhungen des PCT können jedoch aufgrund vielfältiger Ursachen auftreten und sind nicht spezifisch, wie wir in dem vorliegenden Fall kurz skizzieren möchten.
Anamnese Wir berichten über eine 29-jährige Patientin, die bei unklaren abdominellen Schmerzen sowie seit 2 Tagen bestehender Übelkeit und Erbrechen von der psychiatrischen Klinik vorgestellt wurde. Die Anamnese war zunächst nicht zielführend.
Untersuchung und Diagnose Klinisch ergaben sich keine wegweisenden Befunde. Die Patientin war afebril. Laborchemisch zeigten sich deutlich erhöhte Transaminasen sowie ein massiv erhöhtes PCT. Sonografisch stellten sich keine Auffälligkeiten dar, die Hepatitis-Serologie fiel negativ aus. Entnommene Blutkulturen blieben steril, die weitere Infektfokussuche war blande.
Therapie und Verlauf Im Verlauf des stationären Aufenthalts berichtete die Patientin, 2 Tage zuvor kumulativ ca. 40 g Paracetamol in suizidaler Absicht eingenommen zu haben. Eine Therapie mit N-Acetylcystein (NAC) wurde eingeleitet. Die Transaminasen und das PCT zeigten sich in den Folgetagen fallend. Auf eine antibiotische Therapie wurde verzichtet.
Folgerung Der Fall zeigt, dass eine PCT-Erhöhung keinesfalls spezifisch für bakterielle Infektionen ist und der Laborwert immer in Korrelation mit der Anamnese und Klinik betrachtet werden muss.
68Ga-PSMA-11-PET/mpMRT zur Lokaldetektion des primären Prostatakarzinoms bei Männern mit negativer Vorbiopsie
Authors: Maurer Tobias , Gesterkamp Hannah , Nguyen Noemi , Westenfelder Kay , Gschwend Jürgen E. , Budäus Lars , Rauscher Isabel , Vag Tibor , Weber Wolfgang , Eiber Matthias 
Published: July 2021

Zusammenfassung
Hintergrund Die multiparametrische MRT (mpMRT) stellt den Goldstandard der bildgebenden Diagnostik zur Detektion eines primären Prostatakarzinoms (PC) nach negativer Biopsie dar. Die PSMA-PET weist eine hohe Genauigkeit auf, wird aber derzeit vor allem in der Rezidivsituation eingesetzt. Das Ziel der vorliegenden Arbeit war nun, die Effektivität einer kombinierten 68Ga-PSMA-11-PET/mpMRT-Bildgebung zur Detektion eines PC nach vorheriger negativer Prostatabiopsie zu untersuchen.
Material und Methoden Es wurden 57 Patienten in die retrospektive Analyse eingeschlossen, bei denen zuvor mindestens eine negative Prostatabiopsie erfolgt war. Alle Patienten erhielten eine 68Ga-PSMA-11-PET/mpMRT-Bildgebung der Prostata. Die mpMRT wurde anhand der PI-RADS-Klassifikation, die 68Ga-PSMA-11-PET durch eine 5-stufige Likert-Skala ausgewertet (1: PC sehr unwahrscheinlich; 2: PC unwahrscheinlich; 3: unklarer Befund; 4: PC wahrscheinlich; 5: PC sehr wahrscheinlich). Alle Patienten erhielten sowohl eine systematische randomisierte als auch eine gezielte transrektale Biopsie auffälliger Läsionen in der Bildgebung. Ergebnisse der Bildgebung und der histologischen Untersuchung der Prostatabiopsate wurden auf Patientenebene korreliert.
Ergebnisse In der histologischen Untersuchung zeigten sich bei 35/57 (61,4 %) der Patienten Prostatakarzinominfiltrate. Bei Patienten mit histologisch gesichertem PC zeigte sich bei 21/35 (60,0 %) eine PI-RADS-4- oder -5-Läsion im mpMRT bzw. bei 28/35 (80,0 %) ein PET-Rating von 4 oder 5. Die kombinierte 68Ga-PSMA-11-PET/mpMRT übersah nur einen Patienten mit PC-Gleason-Score (GS) 7a (Beurteilung mit 1 oder 2 in sowohl PET als auch mpMRT). Als Limitationen sind sowohl die retrospektive Analyse als auch negative Resultate trotz gezielter Biopsieentnahme anzuführen.
Schlussfolgerung In dieser ersten Analyse zeigte sich die kombinierte 68Ga-PSMA-11-PET/mpMRT als zuverlässige bildgebende Diagnostik für die Prostatabiopsie zur Detektion eines PC bei Patienten nach vorheriger negativer Biopsie. Dabei lieferten die 68Ga-PSMA-11-PET und die mpMRT teilweise komplementäre Ergebnisse, die die Detektion eines PC erhöhten.