bluuebunny/crossref_metadata_2025 huggingface dataset:
GÖDEL ON MANY-VALUED LOGIC
Authors: LETHEN TIM
Published: February 2021

This paper collects and presents unpublished notes of Kurt Gödel concerning the field of many-valued logic. In order to get a picture as complete as possible, both formal and philosophical notes, transcribed from the Gabelsberger shorthand system, are included.
High isolation 4-element ACS-fed MIMO antenna with band notched feature for UWB communications
Authors: Ibrahim Ahmed A. , Ali Wael A. E.
Published: February 2021

In this paper, a compact 4-port band-notched multi-input-multi-output (MIMO) antenna with asymmetric coplanar strip (ACS) feed is presented for ultra-wide band (UWB) applications. The MIMO antenna is comprised of four semi-elliptical radiators with ACS feed for UWB applications and it is printed on inexpensive FR4 substrate of size 48 × 52 mm2 with ɛr = 4.4 and 1.6 mm height. The impedance characteristics of the suggested MIMO antenna ranges from 2.7 to 11 GHz with a band-notched behavior from 3 to 4 GHz to reduce the interception with WiMAX applications, and the isolation level over the achieved band is more than 20 dB between any two adjacent elements. Moreover, the radiation pattern of the proposed UWB antenna is almost omnidirectional with an average realized gain of 3.5 dBi over the entire achieved frequency band. The proposed ACS-fed antenna is confirmed by fabricating and measuring it's impedance and radiation characteristics. Finally, good consistency between simulation and measured outcomes is obtained confirming the validity of the MIMO antenna for real-life UWB wireless systems.
Krebs Screening
Authors: Aschmann Hélène Eloise , Puhan Milo Alan
Published: February 2021

Zusammenfassung. Nutzen und Schaden von Krebs-Screening müssen sorgfältig aufgrund von wissenschaftlicher Evidenz beurteilt, in Kontext gesetzt und gegeneinander abgewogen werden. Der Erfolg von Krebs-Screening-Programmen hängt aber von vielen weiteren Faktoren ab, wie von der Teilnahmerate, der Organisation und der Qualität des Programmes. Dieser Artikel erläutert die epidemiologischen Voraussetzungen, damit ein Krebs-Screening sinnvoll sein kann, und wie ein erfolgreiches Screening-Programm gestaltet sein muss.
Check-ups in der Praxis – was macht Sinn?
Authors: Chmiel Corinne
Published: February 2021

Zusammenfassung. Der Wunsch nach einem Check-up ist ein häufiger Konsultationsgrund in der Grundversorgung. Systematische (jährliche) Check-ups bei asymptomatischen Personen ausserhalb der regulären hausärztlichen Betreuung, wie zum Beispiel in dafür designierten Check-up-Zentren, können aufgrund der aktuellen Datenlage nicht empfohlen werden, da das Risiko falsch positiver Resultate erhöht ist und die Morbidität und Mortalität nicht beeinflusst wird. Der Check-up in der Hausarztpraxis bringt jedoch gemäss aktueller Datenlage einen Benefit, er kann zu einer signifikanten Verbesserung der kardiovaskulären Risikofaktoren führen. Zudem bietet der Check-up die Gelegenheit zur individualisierten evidenzbasierten Prävention und Beratung, für die in der normalen Sprechstunde keine Zeit bleibt. Das Erkennen der Motive für den Check-up (Hidden Agenda) und eine individualisierte Risikobeurteilung, sowie eine Beratung zu gesundem Lebensstil sind zentrale Elemente eines hausärztlichen Check-ups. Der Check-up bietet zudem eine Chance zur Stärkung der Arzt-Patientenbeziehung, was wiederum einen positiven Einfluss auf die Gesundheit hat. Dieser Artikel geht auf die verschiedenen Aktivitäten während einer Check-up-Konsultation ein und stellt dazu einige nützliche Instrumente vor, mit einem Schwerpunkt auf dem kardiovaskulären Screening.
Frequency and anatomic distribution of arterial obstructions in	patients with vasculogenic erectile dysfunction not responding to intracavernous	prostaglandin
Authors: Mohan Vignes , Sangiorgi Giuseppe , Knöchel Jonas , Keo Hak-Hong , Schönhofen Jan , Schumacher Martin C. , Schönhofen Heinz , Kalka Christoph , Diehm Nicolas
Published: February 2021

Summary: Background: The extent of arterial disease in patients with erectile dysfunction (ED) non-responsive to intracavernosal injection of Alprostadil is of importance for therapeutic options. However, published evidence, in particular angiographically validated is scarce. Here we investigated arterial lesion patterns in this specific patient cohort by selective angiography. Patients and methods: A cohort of 239 patients received a clinical and duplex-sonographic workup for ED of suspected vascular origin. Duplex ultrasound of the cavernosal arteries was performed after intracavernosal injection of 10 μg Alprostadil. Consequently, standardized workup included grading of the erectile and determination of peak systolic velocity (PSV) and end-diastolic velocity (EDV) in both cavernosal arteries. PSV-values below 30 cm/sec indicated reduced arterial flow, whereas EDV-values above 15 cm/sec indicated a venous leak of the pudendal veins. All patients with suspected arterial ED based on duplex sonography underwent contrast-enhanced computed tomography. Endovascular therapy was carried out in ED patients not responsive or with significant side effects to PDE-5-inhibitors or Alprostadil by selective angiographic depiction of erection-related arteries. Results: 54 patients with a mean age of 61.2 (±9.8) years underwent angioplasty of erectionr elated arteries. Out of these 48/54 (89%) patients presented with an erection considered insufficient for penetration (E0-E3) subsequent to intracavernous application of 10 μg Alprostadil. 14/48 (29%) patients had bilateral arterial obstructions and 34/48 (71%) had unilateral disease. Commonly affected was the internal pudendal artery (n = 31, 65%), followed closely by the common penile artery (n = 30, 64%). The least affected arteries were the dorsal penile (n = 6, 13%), hypogastric (n = 4, 8%), common iliac (n = 4, 8%), cavernosal (n = 4, 8%), and inferior gluteal (n = 1, 2%) arteries. Conclusions: Arterial obstructions amenable to endovascular revascularization are frequent in patients non-responsive to intracavernosal prostaglandin administration. Therapeutic strategies in ED patients non-responsive to conservative measures should therefore consider endovascular treatment opportunities.
Testing the Recycled Gabbro Hypothesis for the Origin of “Ghost Plagioclase” Melt Signatures Using 87Sr/86Sr of Individual Olivine‐Hosted Melt Inclusions From Hawai'i
Authors: Anderson O. E. , Jackson M. G. , Rose‐Koga E. F. , Marske J. P. , Peterson M. E. , Price A. A. , Byerly B. L. , Reinhard A. A.
Published: February 2021

Melt inclusions with large, positive Sr anomalies have been described in multiple tectonic settings, and the origins of this unusual geochemical feature are debated. Three origins have been proposed, all involving plagioclase as the source of the elevated Sr: (i) direct assimilation of plagioclase‐rich lithologies, (ii) recycled lower oceanic gabbro in the mantle source, and (iii) shallow‐level diffusive interaction between present day lower oceanic crust (i.e., plagioclase‐bearing lithologies) and the percolating melt. A “ghost plagioclase” signature (i.e., a large, positive Sr anomaly without associated high Al2O3) is present in melt inclusions from Mauna Loa. We present new 87Sr/86Sr measurements of individual olivine‐hosted melt inclusions from three Hawaiian volcanoes, Mauna Loa, Loihi, and Koolau. The data set includes a Mauna Loa melt inclusion with the highest reported Sr anomaly (or highest (Sr/Ce)N, which is 7.2) for Hawai'i. All melt inclusions have 87Sr/86Sr values within the range reported previously for the lavas from each volcano. Critically, the 87Sr/86Sr of the high (Sr/Ce)N melt inclusion lies within the narrow range of 87Sr/86Sr for Mauna Loa melts that lack high (Sr/Ce)N signatures. Therefore, to explain the high (Sr/Ce)N ratio of the ghost plagioclase signature using an ancient recycled gabbro, the gabbro‐infused mantle source would have had to evolve, by chance, to have the same 87Sr/86Sr as the source of the Mauna Loa melts that lack a recycled gabbro (ghost plagioclase) signature. Alternatively, shallow‐level diffusive interactions between Mauna Loa plagioclase‐rich cumulates and a percolating mantle‐derived melt provides a simpler explanation for the presence of the high (Sr/Ce)N Mauna Loa melts.
Geologically Old but Freshly Exposed Rock Fragments Encountered by Yutu‐2 Rover
Authors: Gou Sheng , Yue Zongyu , Di Kaichang , Bugiolacchi Roberto , Wan Wenhui , Yang Meiping , Ye Lejia
Published: February 2021

During the exploration traverse of the Von Kármán crater on the lunar farside, the Yutu‐2 rover, part of China's Chang'e‐4 mission, come across rock fragments with higher albedo than the surrounding surface. This study investigates their origin, emplacement, and composition based on in situ spectral analysis and geological considerations. The spectral signatures of two fragments show a clear dominance of low‐calcium pyroxenes against the high‐calcium phases characteristic of the basalts infilling the Von Kármán crater. Based on spectral considerations, this suggests an allochthonous origin for the ejecta fragments, with the most likely source attributable to the Imbrian 73‐km Finsen crater. We propose that these rock fragments might have had a convoluted history, born as ejected target materials from the Imbrian Finsen impact, possibly buried and resurfaced several times within Von Kármán by the churning mechanisms that continuously reshape the lunar surface, and finally exhumed by a secondary impact from the Copernican 3.8‐km Zhinyu crater.
Tussocks Enduring or Shrubs Greening: Alternate Responses to Changing Fire Regimes in the Noatak River Valley, Alaska
Authors: Gaglioti B. V. , Berner L. T. , Jones B. M. , Orndahl K. M. , Williams A. P. , Andreu‐Hayles L. , D'Arrigo R. D. , Goetz S. J. , Mann D. H.
Published: February 2021

As the Arctic warms, tundra wildfires are expected to become more frequent and severe. Assessing how the most flammable regions of the tundra respond to burning can inform us about how the rest of the Arctic may be affected by climate change. Here we describe ecosystem responses to tundra fires in the Noatak River watershed of northwestern Alaska using shrub dendrochronology, active‐layer depth monitoring, and remotely sensed vegetation productivity. Results show that relatively productive tundra is more likely to experience fires and to burn more severely, suggesting that fuel loads currently limit tundra fire distribution in the Noatak Valley. Within three years of burning, most alder shrubs sampled had either germinated or resprouted, and vegetation productivity inside 60 burn perimeters had recovered to prefire values. Tundra fires resulted in two phases of increased primary productivity as manifested by increased landscape greening. Phase one occurred in most burned areas 3–10 years after fires, and phase two occurred 16–44 years after fire at sites where tundra fires triggered near‐surface permafrost thaw resulting in shrub proliferation. A fire‐shrub‐greening positive feedback is currently operating in the Noatak Valley and this feedback could expand northward as air temperatures, fire frequencies, and permafrost degradation increase. This feedback will not occur at all locations. In the Noatak Valley, the fire‐shrub‐greening process is relatively limited in tussock tundra communities, where low‐severity fires and shallow active layers exclude shrub proliferation. Climate warming and enhanced fire occurrence will likely shift fire‐poor landscapes into either the tussock tundra or erect‐shrub‐tundra ecological attractor states that now dominate the fire‐rich Noatak Valley.
Spatiotemporal Drivers of Hydrochemical Variability in a Tropical Glacierized Watershed in the Andes
Authors: Saberi Leila , Crystal Ng G.‐H. , Nelson Leah , Zhi Wei , Li Li , La Frenierre Jeff , Johnstone Morgan
Published: February 2021

There is a critical knowledge gap about how glacier retreat in remote and rapidly warming tropical montane watersheds will impact solute export, which has implications for downstream geochemical cycling and ecological function. Because tropical glacierized watersheds are often uniquely characterized by year‐round ablation, upslope vegetation migration, and significant groundwater flow, baseline understanding is needed of how spatiotemporal variables within these watersheds control outlet hydrochemistry. We implemented a recently developed reactive transport watershed model, BioRT‐Flux‐PIHM, for a sub‐humid glacierized watershed in the Ecuadorian Andes with young volcanic soils and fractured bedrock. We found a unique simulated concentration and discharge (C‐Q) pattern that was mostly chemostatic but superimposed by dilution episodes. The chemostatic background was attributed to large simulated contributions of groundwater (subsurface lateral flow) to streamflow, of which a notable fraction (37%) comprised infiltrated ice‐melt. Relatively constant concentrations were further maintained in the model because times and locations of lower mineral surface wetting and dissolution were offset by concentrating effects of greater evapotranspiration. Ice‐melt did not all infiltrate in simulations, especially during large precipitation events, when high surface runoff contributions to discharge triggered dilution episodes. In a model scenario without ice‐melt, major ion concentrations, including Na+, Ca2+, and Mg2+, became more strongly chemostatic and higher, but weathering rates decreased, attenuating export by 23%. We expect this reduction to be exacerbated by higher evapotranspiration and drier conditions with expanded vegetation. This work brings to light the importance of subsurface meltwater flow, ecohydrological variability, and interactions between melt and precipitation for controlling hydrochemical processes in tropical watersheds with rapidly retreating glaciers.
Antibody affinity maturation and plasma IgA associate with clinical outcome in hospitalized COVID-19 patients
Authors: Tang Juanjie , Ravichandran Supriya , Lee Youri , Grubbs Gabrielle , Coyle Elizabeth M. , Klenow Laura , Genser Hollie , Golding Hana , Khurana Surender
Published: February 2021

Hospitalized COVID-19 patients often present with a large spectrum of clinical symptoms. There is a critical need to better understand the immune responses to SARS-CoV-2 that lead to either resolution or exacerbation of the clinical disease. Here, we examine longitudinal plasma samples from hospitalized COVID-19 patients with differential clinical outcome. We perform immune-repertoire analysis including cytokine, hACE2-receptor inhibition, neutralization titers, antibody epitope repertoire, antibody kinetics, antibody isotype and antibody affinity maturation against the SARS-CoV-2 prefusion spike protein. Fatal cases demonstrate high plasma levels of IL-6, IL-8, TNFα, and MCP-1, and sustained high percentage of IgA-binding antibodies to prefusion spike compared with non-ICU survivors. Disease resolution in non-ICU and ICU patients associates with antibody binding to the receptor binding motif and fusion peptide, and antibody affinity maturation to SARS-CoV-2 prefusion spike protein. Here, we provide insight into the immune parameters associated with clinical disease severity and disease-resolution outcome in hospitalized patients that could inform development of vaccine/therapeutics against COVID-19.
The influence of spaceflight and simulated microgravity on bacterial motility and chemotaxis
Authors: Acres Jacqueline M. , Youngapelian Myka Jaap , Nadeau Jay
Published: February 2021

As interest in space exploration rises, there is a growing need to quantify the impact of microgravity on the growth, survival, and adaptation of microorganisms, including those responsible for astronaut illness. Motility is a key microbial behavior that plays important roles in nutrient assimilation, tissue localization and invasion, pathogenicity, biofilm formation, and ultimately survival. Very few studies have specifically looked at the effects of microgravity on the phenotypes of microbial motility. However, genomic and transcriptomic studies give a broad general picture of overall gene expression that can be used to predict motility phenotypes based upon selected genes, such as those responsible for flagellar synthesis and function and/or taxis. In this review, we focus on specific strains of Gram-negative bacteria that have been the most studied in this context. We begin with a discussion of Earth-based microgravity simulation systems and how they may affect the genes and phenotypes of interest. We then summarize results from both Earth- and space-based systems showing effects of microgravity on motility-related genes and phenotypes.
Global 1-km present and future hourly anthropogenic heat flux
Authors: Varquez Alvin Christopher Galang , Kiyomoto Shota , Khanh Do Ngoc , Kanda Manabu
Published: February 2021

Numerical weather prediction models are progressively used to downscale future climate in cities at increasing spatial resolutions. Boundary conditions representing rapidly growing urban areas are imperative to more plausible future predictions. In this work, 1-km global anthropogenic heat emission (AHE) datasets of the present and future are constructed. To improve present AHE maps, 30 arc-second VIIRS satellite imagery outputs such as nighttime lights and night-fires were incorporated along with the LandScanTM population dataset. A futuristic scenario of AHE was also developed while considering pathways of radiative forcing (i.e. representative concentration pathways), pathways of social conditions (i.e. shared socio-economic pathways), a 1-km future urbanization probability map, and a model to estimate changes in population distribution. The new dataset highlights two distinct features; (1) a more spatially-heterogeneous representation of AHE is captured compared with other recent datasets, and (2) consideration of future urban sprawls and climate change in futuristic AHE maps. Significant increases in projected AHE for multiple cities under a worst-case scenario strengthen the need for further assessment of futuristic AHE.
Network analysis of the immune state of mice
Authors: Fonseca dos Reis Elohim , Viney Mark , Masuda Naoki
Published: February 2021

The mammalian immune system protects individuals from infection and disease. It is a complex system of interacting cells and molecules, which has been studied extensively to investigate its detailed function, principally using laboratory mice. Despite the complexity of the immune system, it is often analysed using a restricted set of immunological parameters. Here we have sought to generate a system-wide view of the murine immune response, which we have done by undertaking a network analysis of 120 immune measures. To date, there has only been limited network analyses of the immune system. Our network analysis identified a relatively low number of communities of immune measure nodes. Some of these communities recapitulate the well-known T helper 1 vs. T helper 2 cytokine polarisation (where ordination analyses failed to do so), which validates the utility of our approach. Other communities we detected show apparently novel juxtapositions of immune nodes. We suggest that the structure of these other communities might represent functional immunological units, which may require further empirical investigation. These results show the utility of network analysis in understanding the functioning of the mammalian immune system.
RNA-seq analysis reveals different drought tolerance mechanisms in two broadly adapted wheat cultivars ‘TAM 111’ and ‘TAM 112’
Authors: Chu Chenggen , Wang Shichen , Paetzold Li , Wang Zhen , Hui Kele , Rudd Jackie C. , Xue Qingwu , Ibrahim Amir M. H. , Metz Richard , Johnson Charles D. , Rush Charles M. , Liu Shuyu
Published: February 2021

Wheat cultivars ‘TAM 111’ and ‘TAM 112’ have been dominantly grown in the Southern U.S. Great Plains for many years due to their high yield and drought tolerance. To identify the molecular basis and genetic control of drought tolerance in these two landmark cultivars, RNA-seq analysis was conducted to compare gene expression difference in flag leaves under fully irrigated (wet) and water deficient (dry) conditions. A total of 2254 genes showed significantly altered expression patterns under dry and wet conditions in the two cultivars. TAM 111 had 593 and 1532 dry–wet differentially expressed genes (DEGs), and TAM 112 had 777 and 1670 at heading and grain-filling stages, respectively. The two cultivars have 1214 (53.9%) dry–wet DEGs in common, which agreed with their excellent adaption to drought, but 438 and 602 dry–wet DEGs were respectively shown only in TAM 111 and TAM 112 suggested that each has a specific mechanism to cope with drought. Annotations of all 2254 genes showed 1855 have functions related to biosynthesis, stress responses, defense responses, transcription factors and cellular components related to ion or protein transportation and signal transduction. Comparing hierarchical structure of biological processes, molecule functions and cellular components revealed the significant regulation differences between TAM 111 and TAM 112, particularly for genes of phosphorylation and adenyl ribonucleotide binding, and proteins located in nucleus and plasma membrane. TAM 112 showed more active than TAM 111 in response to drought and carried more specific genes with most of them were up-regulated in responses to stresses of water deprivation, heat and oxidative, ABA-induced signal pathway and transcription regulation. In addition, 258 genes encoding predicted uncharacterized proteins and 141 unannotated genes with no similar sequences identified in the databases may represent novel genes related to drought response in TAM 111 or TAM 112. This research thus revealed different drought-tolerance mechanisms in TAM 111 and TAM 112 and identified useful drought tolerance genes for wheat adaption. Data of gene sequence and expression regulation from this study also provided useful information of annotating novel genes associated with drought tolerance in the wheat genome.
BOOSTing patient mobility and function on a general medical unit by enhancing interprofessional care
Authors: Johnson A. M. , Kuperstein J. , Graham R. Hogg , Talari P. , Kelly A. , Dupont-Versteegden E. E.
Published: February 2021

Low mobility during hospitalization remains prevalent despite associated negative consequences. The goal of this quality improvement (QI) project was to increase patient mobility and function by adding a physical therapist (PT) to an existing interprofessional care team. A mobility technician assisted treatment group patients with mobility during hospitalization based on physical therapist recommendations. Change in functional status and highest level of mobility achieved by treatment group patients was measured from admission to discharge. Observed hospital length of stay (LOS), LOS index, and 30-day all cause hospital readmission comparisons between treatment group and a comparison group on the same unit, and between cross-sectional comparison groups one year prior were used for Difference in Difference analysis. Bivariate comparisons between the treatment and a cross-sectional comparison group from one year prior showed a statistically significant change in LOS Index. No other bivariate comparisons were statistically significant. Difference in Difference methods showed no statistically significant change in observed LOS, LOS Index, or 30-day readmission. Patients in the treatment group had statistically significant improvements in functional status and highest level of mobility achieved. Physical function and mobility improved for patients who participated in mobility sessions. Mobility technicians may contribute to improved care quality and patient safety in the hospital.
The incidence and clinical analysis of non-melanoma skin cancer
Authors: Ciążyńska Magdalena , Kamińska-Winciorek Grażyna , Lange Dariusz , Lewandowski Bogumił , Reich Adam , Sławińska Martyna , Pabianek Marta , Szczepaniak Katarzyna , Hankiewicz Adam , Ułańska Małgorzata , Morawiec Jan , Błasińska-Morawiec Maria , Morawiec Zbigniew , Piekarski Janusz , Nejc Dariusz , Brodowski Robert , Zaryczańska Anna , Sobjanek Michał , Nowicki Roman J. , Owczarek Witold , Słowińska Monika , Wróbel Katarzyna , Bieniek Andrzej , Woźniacka Anna , Skibińska Małgorzata , Narbutt Joanna , Niemczyk Wojciech , Ciążyński Karol , Lesiak Aleksandra
Published: February 2021

Non-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations. Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC). Unfortunately, most European cancer registries do not record individual types of NMSC. To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers. Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019. We recorded 13,913 NMSCs occurring in 10,083 patients. BCC represented 85.2% of all cases. SCC patients were older than BCC patients (77.1 ± 11.3 years vs. 70.1 ± 12.3 years, p < 0.01). The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes. The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01). The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01). BCC and SCC are common malignancies developing at various ages and anatomical sites. These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.
Graphene oxide assisted light-up aptamer selection against Thioflavin T for label-free detection of microRNA
Authors: Islam Md Mamunul , Ghielmetti Victoria Michele , Allen Peter B.
Published: February 2021

We selected an aptamer against a fluorogenic dye called Thioflavin T (ThT). Aptamers are single-stranded DNA that can bind a specific target. We selected the ThT aptamer using graphene oxide assisted SELEX and a low-cost Open qPCR instrument. We optimized, minimized, and characterized the best aptamer candidate against ThT. The aptamer, ThT dye, and the enzymatic strand displacement amplification (SDA) were used in a label-free approach to detect the micro RNA miR-215 in saliva and serum. The aptamer confers higher specificity than intercalating dyes but without expensive covalently modified DNA probes. This isothermal, low-cost, simple method can detect both DNA and RNA. The target, miR-215, was detected with a limit of detection of 2.6 nM.
The effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study
Authors: Mapelli Jonathan , Gandolfi Daniela , Giuliani Enrico , Casali Stefano , Congi Luigi , Barbieri Alberto , D’Angelo Egidio , Bigiani Albertino
Published: February 2021

The brain functions can be reversibly modulated by the action of general anesthetics. Despite a wide number of pharmacological studies, an extensive analysis of the cellular determinants of anesthesia at the microcircuits level is still missing. Here, by combining patch-clamp recordings and mathematical modeling, we examined the impact of sevoflurane, a general anesthetic widely employed in the clinical practice, on neuronal communication. The cerebellar microcircuit was used as a benchmark to analyze the action mechanisms of sevoflurane while a biologically realistic mathematical model was employed to explore at fine grain the molecular targets of anesthetic analyzing its impact on neuronal activity. The sevoflurane altered neurotransmission by strongly increasing GABAergic inhibition while decreasing glutamatergic NMDA activity. These changes caused a notable reduction of spike discharge in cerebellar granule cells (GrCs) following repetitive activation by excitatory mossy fibers (mfs). Unexpectedly, sevoflurane altered GrCs intrinsic excitability promoting action potential generation. Computational modelling revealed that this effect was triggered by an acceleration of persistent sodium current kinetics and by an increase in voltage dependent potassium current conductance. The overall effect was a reduced variability of GrCs responses elicited by mfs supporting the idea that sevoflurane shapes neuronal communication without silencing neural circuits.
Brain network analysis reveals that amyloidopathy affects comorbid cognitive dysfunction in older adults with depression
Authors: Lee Suji , Kim Daegyeom , Youn HyunChul , Hyung Won Seok William , Suh Sangil , Kaiser Marcus , Han Cheol E. , Jeong Hyun-Ghang
Published: February 2021

Late-life depression (LLD) may increase the risk of Alzheimer’s dementia (AD). While amyloidopathy accelerates AD progression, its role in such patients has not yet been elucidated. We hypothesized that cerebral amyloidopathy distinctly affects the alteration of brain network topology and may be associated with distinct cognitive symptoms. We recruited 26 and 27 depressed mild cognitive impairment (MCI) patients with (LLD-MCI-A(+)) and without amyloid accumulation (LLD-MCI-A(−)), respectively, and 21 normal controls. We extracted structural brain networks using their diffusion-weighted images. We aimed to compare the distinct network deterioration in LLD-MCI with and without amyloid accumulation and the relationship with their distinct cognitive decline. Thus, we performed a group comparison of the network topological measures and investigated any correlations with neurocognitive testing scores. Topological features of brain networks were different according to the presence of amyloid accumulation. Disrupted network connectivity was highly associated with impaired recall and recognition in LLD-MCI-A(+) patients. Inattention and dysexecutive function were more influenced by the altered networks involved in fronto-limbic circuitry dysfunction in LLD-MCI-A(−) patients. Our results show that alterations in brain network topology may reflect different cognitive dysfunction depending on amyloid accumulation in depressed older adults with MCI.
First prospective data on breast cancer patients from the multicentre italian bone metastasis database
Authors: Bongiovanni Alberto , Foca Flavia , Fantini Manuela , Forcignanò Maria Rosachiara , Artioli Fabrizio , Berardi Rossana , Campadelli Enrico , Procopio Giuseppe , Silvestris Francesco , Riva Nada , Gurrieri Lorena , Debonis Silvia Angela , Di Menna Giandomenico , Fausti Valentina , Recine Federica , Vespignani Roberto , Ibrahim Toni
Published: February 2021

Bone metastases (BM) are still the main cause of morbidity in cancer patients because of skeletal-related events (SREs) that reduce quality of life. They have also led to increased social and healthcare costs. At present, data available on BM are insufficient. This was a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 months’ follow-up. Information on patients at the first diagnosis of BM, including demographics and characteristics of the primary tumor and BM. Data were periodically updated by participating centres and reviewed by the coordinator centre. From October 2014 to July 2019, 618 patients with BM from solid tumors were enrolled and 220 were eligible for the present study. Median age was 62 years (range 26–86). Median follow-up was 34 months (range 6–149). At the time of enrolment, 109 (50%) had only BM (BOM) and 109 (50%) had concomitant visceral lesions and BM (BVM). Median time-to-first BM was 47 months (range 0–312) in BOM and 78.6 months in BVM patients. Disease-free interval differed on the basis of BC molecular subtype and stage. Ninety-eight BM patients had at least on SRE. Zoledronate was used in 69.1% of cases and denosumab in 28.3%. First-line treatment was hormone-based (50.7%), chemotherapy-based (38.7%) or chemotherapy- + hormone therapy-based (9.7%). Median progression-free and overall survival were 15.1 months (95% CI 12.6–18.4) and 66.8 months (95% CI 52.1–79.2), respectively. Our prospective study could substantially help to better understand the natural history of BM from BC.
The occurrence of aflatoxins and human health risk estimations in randomly obtained maize from some markets in Ghana
Authors: Kortei Nii Korley , Annan Theophilus , Akonor Papa Toah , Richard Seidu A. , Annan Helen Ama , Kyei-Baffour Vincent , Akuamoa Felicia , Akpaloo Princess Golda , Esua-Amoafo Paul
Published: February 2021

Maize and its products are most often prone to fungal contamination especially during cultivation and storage by toxigenic fungi. Aflatoxicosis still persist in Ghana despite the numerous education on several ways of its prevention at the farm as well as its adverse health implications which are food safety concerns. A random assessment and human risk analysis was conducted on 90 maize (72 white and 18 colored) samples from markets across all the regions of Ghana. Total aflatoxins (AFtotal) and the constitutive aflatoxins (AFB1, AFB2, AFG1, and AFG2) were analyzed by High-Performance Liquid Chromatography (HPLC). Out of a total of ninety (90) samples investigated, 72 (80%) tested positive for AFB1 and the contamination levels ranged from 0.78 ± 0.04 to 339.3 ± 8.6 µg kg−1. Similarly, AFG2 was detected in only 14 (15.5%) samples, and their values ranged between 1.09 ± 0.03 and 5.51 ± 0.26 µg kg−1 while AF total ranged between 0.78 ± 0.04 and 445.01 ± 8.9 µg kg−1 constituting approximately 72 (80%). Limits of AFB1 and total aflatoxins (AFtotal) for the Ghana Standards Authority (GSA) (5 and 10 µg kg−1) and the European Food Safety Authority (EFSA) (2 and 4 µg kg−1), were used as checks. A total of 33 (41.25%) samples were above the limits for both. Risk assessments recorded for Estimated Daily Intake (EDI), Hazard Quotient (H.Q), Hazard Index (H.I), Margin of Exposure (MOE), av. Potency, and population risks ranged 0.087–0.38 μg kg−1 bw day−1, 1.5–6.9, 0.0087–0.38, 3.64–12.09, 0–0.0396 ng Aflatoxins kg−1 bw day−1 and, 3.5 × 10–1–0.015 respectively for total aflatoxins. While ranges for aflatoxins B1 (AFB1) recorded were 0.068–0.3 μg Kg bw−1 day−1, 2.43–10.64, 0.0068–0.030, 4.73–20.51, 0–0.0396 ng Aflatoxins kg−1 bw day−1 and, 2.69 × 10–3–0.012 for Estimated Daily Intake (EDI), Hazard Quotient (H.Q), Hazard Index (H.I), Margin of Exposure (MOE), Av. potency, and population risks respectively. It was deduced that although there was some observed contamination of maize across the different ecological zones, the consumption of maize (white and colored) posed no adverse health effects on the population of Ghana since computed H.I was less than 1 (< 1).
Serine 477 plays a crucial role in the interaction of the SARS-CoV-2 spike protein with the human receptor ACE2
Authors: Singh Amit , Steinkellner Georg , Köchl Katharina , Gruber Karl , Gruber Christian C.
Published: February 2021

Since the worldwide outbreak of the infectious disease COVID-19, several studies have been published to understand the structural mechanism of the novel coronavirus SARS-CoV-2. During the infection process, the SARS-CoV-2 spike (S) protein plays a crucial role in the receptor recognition and cell membrane fusion process by interacting with the human angiotensin-converting enzyme 2 (hACE2) receptor. However, new variants of these spike proteins emerge as the virus passes through the disease reservoir. This poses a major challenge for designing a potent antigen for an effective immune response against the spike protein. Through a normal mode analysis (NMA) we identified the highly flexible region in the receptor binding domain (RBD) of SARS-CoV-2, starting from residue 475 up to residue 485. Structurally, the position S477 shows the highest flexibility among them. At the same time, S477 is hitherto the most frequently exchanged amino acid residue in the RBDs of SARS-CoV-2 mutants. Therefore, using MD simulations, we have investigated the role of S477 and its two frequent mutations (S477G and S477N) at the RBD during the binding to hACE2. We found that the amino acid exchanges S477G and S477N strengthen the binding of the SARS-COV-2 spike with the hACE2 receptor.
Immune classification of clear cell renal cell carcinoma
Authors: Su Sumeyye , Akbarinejad Shaya , Shahriyari Leili
Published: February 2021

Since the outcome of treatments, particularly immunotherapeutic interventions, depends on the tumor immune micro-environment (TIM), several experimental and computational tools such as flow cytometry, immunohistochemistry, and digital cytometry have been developed and utilized to classify TIM variations. In this project, we identify immune pattern of clear cell renal cell carcinomas (ccRCC) by estimating the percentage of each immune cell type in 526 renal tumors using the new powerful technique of digital cytometry. The results, which are in agreement with the results of a large-scale mass cytometry analysis, show that the most frequent immune cell types in ccRCC tumors are CD8+ T-cells, macrophages, and CD4+ T-cells. Saliently, unsupervised clustering of ccRCC primary tumors based on their relative number of immune cells indicates the existence of four distinct groups of ccRCC tumors. Tumors in the first group consist of approximately the same numbers of macrophages and CD8+ T-cells and and a slightly smaller number of CD4+ T cells than CD8+ T cells, while tumors in the second group have a significantly high number of macrophages compared to any other immune cell type (P-value $$<0.01$$

<
0.01

). The third group of ccRCC tumors have a significantly higher number of CD8+ T-cells than any other immune cell type (P-value $$<0.01$$

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0.01

), while tumors in the group 4 have approximately the same numbers of macrophages and CD4+ T-cells and a significantly smaller number of CD8+ T-cells than CD4+ T-cells (P-value $$<0.01$$

<
0.01

). Moreover, there is a high positive correlation between the expression levels of IFNG and PDCD1 and the percentage of CD8+ T-cells, and higher stage and grade of tumors have a substantially higher percentage of CD8+ T-cells. Furthermore, the primary tumors of patients, who are tumor free at the last time of follow up, have a significantly higher percentage of mast cells (P-value $$<0.01$$

<
0.01

) compared to the patients with tumors for all groups of tumors except group 3.
Genetically predicted education attainment in relation to somatic and mental health
Authors: Yuan Shuai , Xiong Ying , Michaëlsson Madeleine , Michaëlsson Karl , Larsson Susanna C.
Published: February 2021

A deeper understanding of the causal links from education level to health outcomes may shed a light for disease prevention. In the present Mendelian randomization study, we found that genetically higher education level was associated with lower risk of major mental disorders and most somatic diseases, independent of intelligence. Higher education level adjusted for intelligence was associated with lower risk of suicide attempts, insomnia, major depressive disorder, heart failure, stroke, coronary artery disease, lung cancer, breast cancer, type 2 diabetes and rheumatoid arthritis but with higher risk of obsessive–compulsive disorder, anorexia nervosa, anxiety, bipolar disorder and prostate cancer. Higher education level was associated with reduced obesity and smoking, which mediated quite an extent of the associations between education level and health outcomes. These findings emphasize the importance of education to reduce the burden of common diseases.
Asymptomatic secondary hyperparathyroidism can mimic sacroiliitis on computed tomography
Authors: Kreutzinger Virginie , Diekhoff Torsten , Liefeldt Lutz , Poddubnyy Denis , Hermann Kay Geert A. , Ziegeler Katharina
Published: February 2021

Secondary hyperparathyroidism (sHPT) as a result of chronic kidney disease (CKD) is a common health problem and has been reported to manifest at the sacroiliac joints (SIJ). The aim of this investigation was to systematically assess sacroiliac joint changes in asymptomatic sHPT as detected by high-resolution CT. Included in this IRB-approved retrospective case–control study were 56 patients with asymptomatic sHPT as well as 259 matched controls without SIJ disease. Demographic data were retrieved from electronic patient records. High-resolution computed tomography datasets of all patients were subjected to a structured scoring, including erosions, sclerosis, osteophytes, joint space alterations and intraarticular calcifications. Chi2 tests were used to compare frequencies of lesions. Erosions were significantly more prevalent in patients with sHPT, and were found mainly in the ventral (28.6% vs. 13.9%; p = 0.016) and middle (17.9% vs. 7.7%; p = 0.040) iliac portions of the SIJ. Partial ankylosis was rare in both cohorts (3.6% vs. 5.0%; p > 0.999); complete ankylosis was not observed. Neither extent not prevalence of sclerosis or calcifications differed significantly between groups. Joint lesions reminiscent of sacroiliitis can be found in a substantial portion of asymptomatic patients with secondary hyperparathyroidism. Further investigations into the clinical significance of these findings are warranted.
The impacts of the atmospheric boundary layer on regional haze in North China
Authors: Li Qianhui , Zhang Hongsheng , Cai Xuhui , Song Yu , Zhu Tong
Published: February 2021

An intensive atmospheric boundary layer (ABL) experiment was conducted simultaneously at six stations arranged in a cross shape on the North China Plain (NCP) from 26 November to 26 December 2019. The impacts of the regional ABL structure on heavy haze pollution and the relationship between the ABL height and aerosol accumulation layer (AAL) depth were discussed. Bouts of downdrafts generate a persistent descending elevated inversion layer, helping the maintenance and exacerbation of haze pollution. Continuous weak wind layers contribute to the pollutants accumulation, and low-level jets promote the removal of air pollutants. The unique landform conditions of the NCP are reflected in its regional ABL structure and further affect the spatial distribution of haze pollution. Due to the drainage flow and strong downdrafts, the western stations near the mountains have a colder surface and warmer upper air masses, resulting in a more stable stratification and worse diffusion conditions; these stations also experience a thicker weak wind layer caused by increased friction. Thus, the spatial distribution of haze is heavier in the west and lighter in the east. The convective boundary layer (CBL) height declines evidently during haze episodes, usually lower than 560 m. Furthermore, as the vertical distribution of aerosols is mainly influenced by daytime thermal turbulence and maintained at night, it is appropriate to determine the CBL height using the AAL depth. However, the AAL depth is not consistent with the stable boundary layer height due to the influence of the residual layer at night.
Multiplexed neurochemical transmission emulated using a dual-excitatory synaptic transistor
Authors: Ma Mingxue , Ni Yao , Chi Zirong , Meng Wanqing , Yu Haiyang , Gong Jiangdong , Wei Huanhuan , Han Hong , Wang Xinran , Xu Wentao
Published: February 2021

The ability to emulate multiplexed neurochemical transmission is an important step toward mimicking complex brain activities. Glutamate and dopamine are neurotransmitters that regulate thinking and impulse signals independently or synergistically. However, emulation of such simultaneous neurotransmission is still challenging. Here we report design and fabrication of synaptic transistor that emulates multiplexed neurochemical transmission of glutamate and dopamine. The device can perform glutamate-induced long-term potentiation, dopamine-induced short-term potentiation, or co-release-induced depression under particular stimulus patterns. More importantly, a balanced ternary system that uses our ambipolar synaptic device backtrack input ‘true’, ‘false’ and ‘unknown’ logic signals; this process is more similar to the information processing in human brains than a traditional binary neural network. This work provides new insight for neuromorphic systems to establish new principles to reproduce the complexity of a mammalian central nervous system from simple basic units.
Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation
Authors: Sims Travis T. , El Alam Molly B. , Karpinets Tatiana V. , Dorta-Estremera Stephanie , Hegde Venkatesh L. , Nookala Sita , Yoshida-Court Kyoko , Wu Xiaogang , Biegert Greyson W. G. , Delgado Medrano Andrea Y. , Solley Travis , Ahmed-Kaddar Mustapha , Chapman Bhavana V. , Sastry K. Jagannadha , Mezzari Melissa P. , Petrosino Joseph F. , Lin Lilie L. , Ramondetta Lois , Jhingran Anuja , Schmeler Kathleen M. , Ajami Nadim J. , Wargo Jennifer , Colbert Lauren E. , Klopp Ann H.
Published: February 2021

Diversity of the gut microbiome is associated with higher response rates for cancer patients receiving immunotherapy but has not been investigated in patients receiving radiation therapy. Additionally, current studies investigating the gut microbiome and outcomes in cancer patients may not have adjusted for established risk factors. Here, we sought to determine if diversity and composition of the gut microbiome was independently associated with survival in cervical cancer patients receiving chemoradiation. Our study demonstrates that the diversity of gut microbiota is associated with a favorable response to chemoradiation. Additionally, compositional variation among patients correlated with short term and long-term survival. Short term survivor fecal samples were significantly enriched in Porphyromonas, Porphyromonadaceae, and Dialister, whereas long term survivor samples were significantly enriched in Escherichia Shigella, Enterobacteriaceae, and Enterobacteriales. Moreover, analysis of immune cells from cervical tumor brush samples by flow cytometry revealed that patients with a high microbiome diversity had increased tumor infiltration of CD4+ lymphocytes as well as activated subsets of CD4 cells expressing ki67+ and CD69+ over the course of radiation therapy. Modulation of the gut microbiota before chemoradiation might provide an alternative way to enhance treatment efficacy and improve treatment outcomes in cervical cancer patients.
High-throughput screening and validation of antibodies against synaptic proteins to explore opioid signaling dynamics
Authors: Lemos Duarte Mariana , Trimbake Nikita A. , Gupta Achla , Tumanut Christine , Fan Xiaomin , Woods Catherine , Ram Akila , Gomes Ivone , Bobeck Erin N. , Schechtman Deborah , Devi Lakshmi A.
Published: February 2021

Antibodies represent powerful tools to examine signal transduction pathways. Here, we present a strategy integrating multiple state-of-the-art methods to produce, validate, and utilize antibodies. Focusing on understudied synaptic proteins, we generated 137 recombinant antibodies. We used yeast display antibody libraries from the B cells of immunized rabbits, followed by FACS sorting under stringent conditions to identify high affinity antibodies. The antibodies were validated by high-throughput functional screening, and genome editing. Next, we explored the temporal dynamics of signaling in single cells. A subset of antibodies targeting opioid receptors were used to examine the effect of treatment with opiates that have played central roles in the worsening of the ‘opioid epidemic.’ We show that morphine and fentanyl exhibit differential temporal dynamics of receptor phosphorylation. In summary, high-throughput approaches can lead to the identification of antibody-based tools required for an in-depth understanding of the temporal dynamics of opioid signaling.