bluuebunny/crossref_metadata_2025 huggingface dataset:
Modal verbs of strong obligation in Scottish Standard English
Authors: SCHÜTZLER OLE , HERZKY JENNY
Published: July 2021

This article investigates differences between Scottish Standard English (SSE) and Southern British Standard English (SBSE) in the semantic domain of strong obligation. Focusing on the modal verbsmust,have to,need toand(have) got to, we use new corpus material from nineteen written and spoken genres in the Scottish component of theInternational Corpus of English(ICE-SCO) and corresponding texts from ICE-GB. Data are analysed using a mixed-effect multinomial regression model to predict the choice of verb. Language-internal factors include mode of production (written/spoken), grammatical subject (first/second/third person) and source of obligation (objective/subjective). Our results show that, as previous research suggests, SSE is much more likely to employneed tofor the expression of strong obligation, and less likely to employmustand(have) got to. This general pattern remains essentially unaffected by language-internal factors. To account for our findings, we draw on the sociologically motivated process of democratisation and the language-internal process of grammaticalisation.
Small-seeded false flax (Camelina microcarpa) management in Oklahoma winter wheat
Authors: Crose Jodie A. , Manuchehri Misha R. , Baughman Todd A.
Published: July 2021

Three herbicide premixes have recently been introduced for weed control in wheat: halauxifen + florasulam, thifensulfuron + fluroxypyr, and bromoxynil + bicyclopyrone. The objective of this study was to evaluate these herbicides along with older products for their control of small-seeded false flax in winter wheat in Oklahoma. Studies took place during the 2017, 2018, and 2020 winter wheat growing seasons. Weed control was visually estimated every 2 wk throughout the growing season, and wheat yield was collected in all 3 yr. Small-seeded false flax diameter was approximately 6 cm at the time of application in all years. Control ranged from 96% to 99% following all treatments with the exception of bicyclopyrone + bromoxynil and dicamba alone, which controlled false flax 90%. All treatments containing an acetolactate synthase (ALS)–inhibiting herbicide achieved adequate control; therefore, resistance is not suspected in this population. Halauxifen + florasulam and thifensulfuron + fluroxypyr effectively controlled small-seeded false flax similarly to other standards recommended for broadleaf weed control in wheat in Oklahoma. Rotational use of these products allows producers flexibility in controlling small-seeded false flax and reduces the potential for development of herbicide resistance in this species.
Autismus-Spektrum-Störungen in einer Spezialsprechstunde für Geschlechtsdysphorie: Wie häufig kommt eine Doppeldiagnose vor und was bedeutet die gemeinsame Prävalenz für eine Behandlung?
Authors: Herrmann Lena , Bindt Carola , Fahrenkrug Saskia , Schweitzer Julia , Schulte-Markwort Michael , Barkmann Claus , Becker-Hebly Inga
Published: July 2021

Zusammenfassung. Fragestellung: Aktuelle Studien weisen auf ein erhöhtes gemeinsames Auftreten von Geschlechtsdysphorie (GD) und Autismus-Spektrum-Störungen (ASS) hin. Diese Studie soll Aufschluss über die klinische Prävalenz von ASS bei Kindern und Jugendlichen in einer deutschen Spezialsprechstunde für GD sowie über personen- und behandlungsbezogene Merkmale bei vorliegender Doppeldiagnose (GD, ASS) geben. Methodik: Angaben zum Zuweisungsgeschlecht, Alter, Diagnosen (GD, ASS) und Behandlungsstatus von 680 Kindern und Jugendlichen (Zeitraum: 2013 bis 2018) wurden erfasst. Die Häufigkeit von ASS-Diagnosen (F84.0, F84.1, F84.5, F84.8 oder F84.9, gesichert und ASS-Verdacht) wurde innerhalb der Stichprobe mit GD-Diagnose (gesichert: F64.0, F64.2; Verdacht: F64.8, F64.9; n = 579) ausgewertet. Personen- und behandlungsbezogene Merkmale wurden vergleichend zwischen 18 Kindern und Jugendlichen mit Doppeldiagnose und 40 Kindern und Jugendlichen mit GD-, aber ohne ASS-Diagnose ausgewertet. Ergebnisse: Die klinische Prävalenz von ASS bei vorliegender GD-Diagnose lag unter Einschluss der Verdachtsfälle bei 3.1 %. Kinder und Jugendliche mit einer Doppeldiagnose erhielten signifikant häufiger eine GD-Verdachtsdiagnose und wurden signifikant seltener körpermedizinisch behandelt als Jugendliche ohne ASS-Diagnose. Schlussfolgerungen: Obwohl die gemeinsame Prävalenz von GD und ASS in dieser Untersuchung geringer als in anderen internationalen Sprechstunden ausfiel, sprechen die Zahlen für ein erhöhtes gemeinsames Auftreten der Phänomene. Die Behandlungsergebnisse verdeutlichen, dass eine ASS-Diagnose die Diagnostik bei GD sowie die Indikation somatischer, geschlechtsangleichender Maßnahmen erschweren kann.
Performance of the Taiwan Earth System Model in Simulating Climate Variability Compared With Observations and CMIP6 Model Simulations
Authors: Wang Yi‐Chi , Hsu Huang‐Hsiung , Chen Chao‐An , Tseng Wan‐Ling , Hsu Pei‐Chun , Lin Cheng‐Wei , Chen Yu‐Luen , Jiang Li‐Chiang , Lee Yu‐Chi , Liang Hsin‐Chien , Chang Wen‐Ming , Lee Wei‐Liang , Shiu Chein‐Jung
Published: July 2021

This study evaluates the performance of the Taiwan Earth System Model version 1 (TaiESM1) in simulating the observed climate variability in the historical simulation of the Coupled Model Intercomparison Phase 6 (CMIP6). TaiESM1 is developed on the basis of the Community Earth System Model version 1.2.2, with the inclusion of several new physical schemes and improvements in the atmosphere model. The new additions include an improved triggering function in the cumulus convection scheme, a revised distribution‐based formula in the cloud fraction scheme, a new aerosol scheme, and a unique scheme for three‐dimensional surface absorption of shortwave radiation that accounts for the influence of complex terrains. In contrast to the majority of model evaluation processes, which focus mainly on the climatological mean, this evaluation focuses on climate variability parameters, including the diurnal rainfall cycle, precipitation extremes, synoptic eddy activity, intraseasonal fluctuation, monsoon evolution, and interannual and multidecadal atmospheric and oceanic teleconnection patterns. A series of intercomparisons between the simulations of TaiESM1 and CMIP6 models and observations indicate that TaiESM1, a participating model in CMIP6, can realistically simulate the observed climate variability at various time scales and are among the leading CMIP6 models in terms of many key climate features.
A Graphical Interpretation of the Rescaled Complementary Relationship for Evapotranspiration
Authors: Crago Richard D. , Qualls Russell J.
Published: July 2021

Wet‐surface evaporation equations related to the Penman equation can be represented graphically on vapor pressure (e) versus temperature (T) graphs (Qualls & Crago, 2020, https://doi.org/10.1029/2019wr026766). Here, actual regional evaporation is represented graphically on (e, T) graphs using the Complementary Relationship (CR) between actual and apparent potential evaporation. The CR proposed by the authors can be represented in a simple and intuitive geometric form, in which lines representing the regional latent heat flux, LE, and the wet surface (Priestley & Taylor, 1972, https://doi.org/10.1175/1520-0493(1972)100<0081:otaosh>2.3.co;2) evaporation rate, LEPT, intersect at e = 0. This approach allows a graphical estimate of LE (or the corresponding mathematical formulation), provided available energy, wind speed, air temperature and humidity, and roughness lengths for momentum and sensible heat are available. The wet surface temperature is needed, and a calculation method for it is provided. The formulation works well using monthly data from seven sites in Australia, even when the same value of the Priestley & Taylor parameter α is used for all sites. Overall, compared to eddy covariance measurements, root mean square difference averaged 19 W m−2; this compares favorably with the CR formulation proposed by Brutsaert (2015, https://doi.org/10.1002/2015wr017720).
A Robust Drought Index Accounting Changing Precipitation Characteristics
Authors: Singh Gauranshi Raj , Dhanya C. T. , Chakravorty Aniket
Published: July 2021

A realistic evaluation of drought onset is inevitable for the effective implementation of mitigation strategies. Meteorological droughts indicating the onset of drought propagation are usually quantified through unbiased indices that consider the month‐wise magnitude variations in historical climatic variables, while completely ignoring their intramonthly distributions. However, the applicability of such indices under the present scenario of changing climate, where intense short wet spells are reportedly increasing, is questionable. Such changes in the wet spells could eventually lead to prolonged intramonthly dry spells, which in turn will pose many agricultural and socioeconomic risks. To monitor the changed scenario realistically, we propose a new drought index—the Standardized Net‐Precipitation Distribution Index (SNEPI), which incorporates the distribution characteristics of the daily net‐precipitation variable. The applicability of SNEPI is critically evaluated using synthetically generated and observed precipitation series over six diverse climatic locations of India, at 1‐, 3‐, 6‐, and 12‐month time scales. The utility of SNEPI is more profound for longer time scales, understandably due to the enhanced emphasis imparted on the distribution of rainfall spells by the longer periods. Standardized Net‐Precipitation Distribution Index proves to be efficient in capturing the present scenario of increasing dryness (wetness) in wet (dry) regions when compared with the traditional Standardized Precipitation Evapotranspiration Index. Hence, the proposed index, which incorporates the changing precipitation characteristics, may aid in better quantification and monitoring of meteorological drought under the scenario of changing climate.
Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis
Authors: Cho Hyun-U , Kim Sunpil , Sim Jeongeun , Yang Seulkee , An Heeyoung , Nam Min-Ho , Jang Dong-Pyo , Lee C. Justin
Published: July 2021

Monoamine oxidase (MAO) is believed to mediate the degradation of monoamine neurotransmitters, including dopamine, in the brain. Between the two types of MAO, MAO-B has been believed to be involved in dopamine degradation, which supports the idea that the therapeutic efficacy of MAO-B inhibitors in Parkinson’s disease can be attributed to an increase in extracellular dopamine concentration. However, this belief has been controversial. Here, by utilizing in vivo phasic and basal electrochemical monitoring of extracellular dopamine with fast-scan cyclic voltammetry and multiple-cyclic square wave voltammetry and ex vivo fluorescence imaging of dopamine with GRABDA2m, we demonstrate that MAO-A, but not MAO-B, mainly contributes to striatal dopamine degradation. In contrast, our whole-cell patch-clamp results demonstrated that MAO-B, but not MAO-A, was responsible for astrocytic GABA-mediated tonic inhibitory currents in the rat striatum. We conclude that, in contrast to the traditional belief, MAO-A and MAO-B have profoundly different roles: MAO-A regulates dopamine levels, whereas MAO-B controls tonic GABA levels.
DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy
Authors: Huang Ruixue , Zhou Ping-Kun
Published: July 2021

Genomic instability is the hallmark of various cancers with the increasing accumulation of DNA damage. The application of radiotherapy and chemotherapy in cancer treatment is typically based on this property of cancers. However, the adverse effects including normal tissues injury are also accompanied by the radiotherapy and chemotherapy. Targeted cancer therapy has the potential to suppress cancer cells’ DNA damage response through tailoring therapy to cancer patients lacking specific DNA damage response functions. Obviously, understanding the broader role of DNA damage repair in cancers has became a basic and attractive strategy for targeted cancer therapy, in particular, raising novel hypothesis or theory in this field on the basis of previous scientists’ findings would be important for future promising druggable emerging targets. In this review, we first illustrate the timeline steps for the understanding the roles of DNA damage repair in the promotion of cancer and cancer therapy developed, then we summarize the mechanisms regarding DNA damage repair associated with targeted cancer therapy, highlighting the specific proteins behind targeting DNA damage repair that initiate functioning abnormally duo to extrinsic harm by environmental DNA damage factors, also, the DNA damage baseline drift leads to the harmful intrinsic targeted cancer therapy. In addition, clinical therapeutic drugs for DNA damage and repair including therapeutic effects, as well as the strategy and scheme of relative clinical trials were intensive discussed. Based on this background, we suggest two hypotheses, namely “environmental gear selection” to describe DNA damage repair pathway evolution, and “DNA damage baseline drift”, which may play a magnified role in mediating repair during cancer treatment. This two new hypothesis would shed new light on targeted cancer therapy, provide a much better or more comprehensive holistic view and also promote the development of new research direction and new overcoming strategies for patients.
Frequency comb ptychoscopy
Authors: Benirschke David J. , Han Ningren , Burghoff David
Published: July 2021

Multiheterodyne techniques using frequency combs—radiation sources whose lines are perfectly evenly-spaced—have revolutionized science. By beating sources with the many lines of a comb, their spectra are recovered. Even so, these approaches are fundamentally limited to probing coherent sources, such as lasers. They are unable to measure most spectra that occur in nature. Here we present frequency comb ptychoscopy, a technique that allows for the spectrum of any complex broadband source to be retrieved using a comb. In this approach, the spectrum is reconstructed by unfolding the simultaneous beating of a source with each comb line. We demonstrate this both theoretically and experimentally, at microwave frequencies. This approach can reconstruct the spectrum of nearly any complex source to high resolution, and the speed, resolution, and generality of this technique will allow chip-scale frequency combs to have an impact in a wide swath of new applications, such as remote sensing and passive spectral imaging.
Signaling of MK2 sustains robust AP1 activity for triple negative breast cancer tumorigenesis through direct phosphorylation of JAB1
Authors: Chen Haoming , Padia Ravi , Li Tao , Li Yue , Li Bin , Jin Lingtao , Huang Shuang
Published: July 2021

Triple negative breast cancer (TNBC) cells are generally more invasive than estrogen receptor-positive (ER + ) breast cancer cells. Consistent with the importance of activator protein 1 (AP1) transcription factors in invasion, AP1 activity is much higher in TNBC lines than ER + lines. In TNBC cells, robust AP1 activity is facilitated by both ERK and p38MAPK signaling pathways. While ERK signaling pathway regulates AP1 activity by controlling the abundance of AP1 transcription factors, p38MAPK signaling pathway does it by enhancing AP1 binding to AP1 sites without altering their abundance. Here, we show that p38MAPK regulation of AP1 activity involves both MAPKAPK2 (MK2) and JAB1, a known JUN-binding protein. MK2 not only interacts with JAB1 but also directly phosphorylates JAB1 at Ser177 in TNBC cells. Interestingly, Ser177 phosphorylation does not affect JAB1 and JUN interaction. Instead, interfering with p38MAPK signaling pathway or introducing an S to A point mutation at Ser177 of JAB1 reduces JUN recruitment to the AP1 sites in cyclin D1, urokinase plasminogen activator (uPA) and uPA receptor promoters. Moreover, knockdown of JAB1 diminishes >60% of AP1 transcriptional activity in TNBC cells. Taken together, these results indicate that MK2-mediated phosphorylation of JAB1 facilitates JUN recruitment to AP1 sites, thus augmenting AP1 activity. In line with the role of JAB1 in AP1 activity, silencing JAB1 leads to dramatic reduction in TNBC cell growth, in vitro invasion and in vivo tumor outgrowth. This study suggests that the p38MAPK-MK2 signaling pathway promotes TNBC tumorigenesis by sustaining robust AP1 activity.
Autonomous reinforcement learning agent for stretchable kirigami design of 2D materials
Authors: Rajak Pankaj , Wang Beibei , Nomura Ken-ichi , Luo Ye , Nakano Aiichiro , Kalia Rajiv , Vashishta Priya
Published: July 2021

Mechanical behavior of 2D materials such as MoS2 can be tuned by the ancient art of kirigami. Experiments and atomistic simulations show that 2D materials can be stretched more than 50% by strategic insertion of cuts. However, designing kirigami structures with desired mechanical properties is highly sensitive to the pattern and location of kirigami cuts. We use reinforcement learning (RL) to generate a wide range of highly stretchable MoS2 kirigami structures. The RL agent is trained by a small fraction (1.45%) of molecular dynamics simulation data, randomly sampled from a search space of over 4 million candidates for MoS2 kirigami structures with 6 cuts. After training, the RL agent not only proposes 6-cut kirigami structures that have stretchability above 45%, but also gains mechanistic insight to propose highly stretchable (above 40%) kirigami structures consisting of 8 and 10 cuts from a search space of billion candidates as zero-shot predictions.
Corrosion of ternary borosilicate glass in acidic solution studied in operando by fluid-cell Raman spectroscopy
Authors: Lenting Christoph , Geisler Thorsten
Published: July 2021

Fluid-cell Raman spectroscopy is a space and time-resolving application allowing in operando studies of dynamic processes during solution–solid interactions. A currently heavily debated example is the corrosion mechanism of borosilicate glasses, which are the favoured material for the immobilization of high-level nuclear waste. With an upgraded fluid-cell lid design made entirely from the glass sample itself, we present the polymerization of the surface alteration layer over time in an initially acidic environment, including the differentiation between pore and surface-adsorbed water within it. Our results support an interface-coupled dissolution-precipitation model, which opposes traditional ion-exchange models for the corrosion mechanism. A sound description of the corrosion mechanism is essential for reliable numerical models to predict the corrosion rate of nuclear waste glasses during long-term storage in a geological repository.
Differential polarization and activation dynamics of systemic T helper cell subsets after aneurysmal subarachnoid hemorrhage (SAH) and during post-SAH complications
Authors: Chaudhry Shafqat Rasul , Kahlert Ulf Dietrich , Kinfe Thomas Mehari , Endl Elmar , Dolf Andreas , Niemelä Mika , Hänggi Daniel , Muhammad Sajjad
Published: July 2021

Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Devastating post-SAH complications, such as cerebral vasospasm (CVS), delayed cerebral ischemia or seizures to mention a few, are mainly responsible for the poor clinical outcome. Inflammation plays an indispensable role during early brain injury (EBI) and delayed brain injury (DBI) phases over which these complications arise. T helper cells are the major cytokine secreting cells of adaptive immunity that can polarize to multiple functionally unique sub-populations. Here, we investigate different CD4+ T cell subsets during EBI and DBI phases after SAH, and their dynamics during post-SAH complications. Peripheral venous blood from 15 SAH patients during EBI and DBI phases, was analyzed by multicolour flowcytometry. Different subsets of CD3+ CD4+ T cells were characterized by differential cell surface expression of CXCR3 and CCR6 into Th1, Th2, Th17, whereas Tregs were defined by CD25hiCD127lo. The analysis of activation states was done by the expression of stable activation markers CD38 and HLA-DR. Interestingly, compared to healthy controls, Tregs were significantly increased during both EBI and DBI phases. Different activation states of Tregs showed differential significant increase during EBI and DBI phases compared to controls. HLA-DR− CD38+ Tregs were significantly increased during DBI phase compared to EBI phase in SAH patients developing CVS, seizures and infections. However, HLA-DR− CD38− Tregs were significantly reduced during EBI phase in patients with cerebral ischemia (CI) compared to those without CI. HLA-DR− CD38− Th2 cells were significantly increased during EBI phase compared to controls. A significant reduction in Th17/Tregs and HLA-DR− CD38+ Th17/Tregs ratios was observed during both EBI and DBI phases compared to controls. While HLA-DR− CD38− Th17/Tregs and HLA-DR− CD38− Th1/Th2 ratios were impaired only during EBI phase compared to controls. In conclusion, CD4+ T cell subsets display dynamic and unique activation patterns after SAH and during the course of the manifestation of post-SAH complications, which may be helpful for the development of precision neurovascular care. However, to claim this, confirmatory studies with larger patient cohorts, ideally from different ethnic backgrounds, are required. Moreover, our descriptive study may be the grounds for subsequent lab endeavors to explore the underlying mechanisms of our observations.
Natal origin and age-specific egress of Pacific bluefin tuna from coastal nurseries revealed with geochemical markers
Authors: Rooker Jay R. , Wells R. J. David , Block Barbara A. , Liu Hui , Baumann Hannes , Chiang Wei-Chuan , Sluis Michelle Zapp , Miller Nathaniel R. , Mohan John A. , Ohshimo Seiji , Tanaka Yosuke , Dance Michael A. , Dewar Heidi , Snodgrass Owyn E. , Shiao Jen-Chieh
Published: July 2021

Geochemical chronologies were constructed from otoliths of adult Pacific bluefin tuna (PBT) to investigate the timing of age-specific egress of juveniles from coastal nurseries in the East China Sea or Sea of Japan to offshore waters of the Pacific Ocean. Element:Ca chronologies were developed for otolith Li, Mg, Mn, Zn, Sr, and Ba, and our assessment focused on the section of the otolith corresponding to the age-0 to age-1 + interval. Next, we applied a common time-series approach to geochemical profiles to identify divergences presumably linked to inshore-offshore migrations. Conspicuous geochemical shifts were detected during the juvenile interval for Mg:Ca, Mn:Ca, and Sr:Ca that were indicative of coastal-offshore transitions or egress generally occurring for individuals approximately 4–6 mo. old, with later departures (6 mo. or older) linked to overwintering being more limited. Changepoints in otolith Ba:Ca profiles were most common in the early age-1 period (ca. 12–16 mo.) and appear associated with entry into upwelling areas such as the California Current Large Marine Ecosystem following trans-Pacific migrations. Natal origin of PBT was also predicted using the early life portion of geochemical profile in relation to a baseline sample comprised of age-0 PBT from the two primary spawning areas in the East China Sea and Sea of Japan. Mixed-stock analysis indicated that the majority (66%) of adult PBT in our sample originated from the East China Sea, but individuals of Sea of Japan origin were also detected in the Ryukyu Archipelago.
In silico designing of vaccine candidate against Clostridium difficile
Authors: Basak Srijita , Deb Debashrito , Narsaria Utkarsh , Kar Tamalika , Castiglione Filippo , Sanyal Indraneel , Bade Pratap D. , Srivastava Anurag P.
Published: July 2021

Clostridium difficile is a spore-forming gram-positive bacterium, recognized as the primary cause of antibiotic-associated nosocomial diarrhoea. Clostridium difficile infection (CDI) has emerged as a major health-associated infection with increased incidence and hospitalization over the years with high mortality rates. Contamination and infection occur after ingestion of vegetative spores, which germinate in the gastro-intestinal tract. The surface layer protein and flagellar proteins are responsible for the bacterial colonization while the spore coat protein, is associated with spore colonization. Both these factors are the main concern of the recurrence of CDI in hospitalized patients. In this study, the CotE, SlpA and FliC proteins are chosen to form a multivalent, multi-epitopic, chimeric vaccine candidate using the immunoinformatics approach. The overall reliability of the candidate vaccine was validated in silico and the molecular dynamics simulation verified the stability of the vaccine designed. Docking studies showed stable vaccine interactions with Toll‐Like Receptors of innate immune cells and MHC receptors. In silico codon optimization of the vaccine and its insertion in the cloning vector indicates a competent expression of the modelled vaccine in E. coli expression system. An in silico immune simulation system evaluated the effectiveness of the candidate vaccine to trigger a protective immune response.
Direct RT-PCR amplification of SARS-CoV-2 from clinical samples using a concentrated viral lysis-amplification buffer prepared with IGEPAL-630
Authors: Castellanos-Gonzalez Alejandro , Shelite Thomas R. , Lloyd Nicole , Sadiqova Aygul , Ping Ren , Williams-Bouyer Natalie , Melby Peter C. , Travi Bruno L.
Published: July 2021

The pandemic of 2019 caused by the novel coronavirus (SARS-CoV-2) is still rapidly spreading worldwide. Nucleic acid amplification serves as the gold standard method for confirmation of COVID-19 infection. However, challenges faced for diagnostic laboratories from undeveloped countries includes shortage of kits and supplies to purify viral RNA. Therefore, it is urgent to validate alternative nucleic acid isolation methods for SARS-CoV-2. Our results demonstrate that a concentrated viral lysis amplification buffer (vLAB) prepared with the nonionic detergent IGEPAL enables qualitative detection of SARS-CoV-2 by direct Reverse Transcriptase-Polymerase Chain Reaction (dRT-PCR). Furthermore, vLAB was effective in inactivating SARS-CoV-2. Since this method is inexpensive and no RNA purification equipment or additional cDNA synthesis is required, this dRT-PCR with vLAB should be considered as an alternative method for qualitative detection of SARS-CoV-2.
Metallomic profile in non-cirrhotic hepatocellular carcinoma supports a phenomenon of metal metabolism adaptation in tumor cells
Authors: Cano Luis , Bertani Stéphane , Island Marie-Laure , Cerapio Juan Pablo , Ruiz Eloy , Pineau Pascal , Monbet Valérie , Boudjema Karim , Taxa Luis , Casavilca-Zambrano Sandro , Ropert Martine , Turlin Bruno , Loréal Olivier
Published: July 2021

We have previously described a form of hepatocellular carcinoma (HCC) in non-cirrhotic liver (HCC-NC) developed by Peruvian patients. We analyzed the metallomic profile in hepatic tissues from two independent cohorts exhibiting HCC-NC. Clinical, histopathological data, and HCC and non-tumoral liver (NTL) samples of 38 Peruvian and 38 French HCC-NC patients, were studied. Twelve metals were quantified using ICP/MS: Mn, Fe, Cu, Co, Zn, As, Se, Rb, Mo, Cd, Pb, and Sn. Associations between metals and survival were assessed. Our data showed significant differences between cohorts. Mean ages were 40.6 ± 20, 67.5 ± 9 years old for Peruvians and French, respectively. Fifty percent of the Peruvian patients were positive for the HBsAg, versus 3% in French patients. Mn, Cu, Zn, As, Se, Rb, Mo, Cd, Sn metal concentrations were higher in NTL of Peruvians. Importantly, metal concentrations were lower in HCC areas compared to NTL tissues in both cohorts, except for Cu for which mean concentration was higher in HCC (p < 0.05). Se concentration in HCC was associated with extended survival only in Peruvians. Our data, obtained in Peruvian and French HCC-NC cohorts, highlights similarity in the metallomic profile of HCC compared to NTL during the hepatic tumorigenesis in these specific groups of patients.
A pilot study to assess the healing of meniscal tears in young adult goats
Authors: Fedje-Johnston William , Johnson Casey P. , Tóth Ferenc , Carlson Cathy S. , Ellingson Arin M. , Albersheim Melissa , Lewis Jack , Bechtold Joan , Ellermann Jutta , Rendahl Aaron , Tompkins Marc
Published: July 2021

Meniscal tears are a common orthopedic injury, yet their healing is difficult to assess post-operatively. This impedes clinical decisions as the healing status of the meniscus cannot be accurately determined non-invasively. Thus, the objectives of this study were to explore the utility of a goat model and to use quantitative magnetic resonance imaging (MRI) techniques, histology, and biomechanical testing to assess the healing status of surgically induced meniscal tears. Adiabatic T1ρ, T2, and T2* relaxation times were quantified for both operated and control menisci ex vivo. Histology was used to assign healing status, assess compositional elements, and associate healing status with compositional elements. Biomechanical testing determined the failure load of healing lesions. Adiabatic T1ρ, T2, and T2* were able to quantitatively identify different healing states. Histology showed evidence of diminished proteoglycans and increased vascularity in both healed and non-healed menisci with surgically induced tears. Biomechanical results revealed that increased healing (as assessed histologically and on MRI) was associated with greater failure load. Our findings indicate increased healing is associated with greater meniscal strength and decreased signal differences (relative to contralateral controls) on MRI. This indicates that quantitative MRI may be a viable method to assess meniscal tears post-operatively.
Recent expansion of marine protected areas matches with home range of grey reef sharks
Authors: Bonnin Lucas , Mouillot David , Boussarie Germain , Robbins William D. , Kiszka Jeremy J. , Dagorn Laurent , Vigliola Laurent
Published: July 2021

Dramatic declines in reef shark populations have been documented worldwide in response to human activities. Marine Protected Areas (MPAs) offer a useful mechanism to protect these species and their roles in coral reef ecosystems. The effectiveness of MPAs notably relies on compliance together with sufficient size to encompass animal home range. Here, we measured home range of 147 grey reef sharks,Carcharhinus amblyrhynchos, using acoustic telemetry in New Caledonia. The distribution of home range was then compared to local MPA sizes. We report a home range of 12 km2of reef for the species with strong differences between adult males (21 km2), adult females (4.4 km2) and juveniles (6.2 km2for males, 2.7 km2for females). Whereas local historic MPA size seemed adequate to protect reef shark home range in general, these were clearly too small when considering adult males only, which is consistent with the reported failure of MPAs to protect sharks in New Caledonia. Fortunately, the recent implementation of several orders of magnitude larger MPAs in New Caledonia and abroad show that recent Indo-Pacific MPAs are now sufficiently large to protect the home ranges of this species, including males, across its geographical range. However, protection efforts are concentrated in a few regions and cannot provide adequate protection at a global scale.
Differences in the level of physical fitness and mobility among older women with osteoporosis and healthy women—cross-sectional study
Authors: Babiuch Anna Szczygielska , Oestervemb Katarzyna , Lipińska Anna , Stańczak Magdalena Lipińska , Cholewa Magdalena , Makulec Kamila , Nowakowska Kinga , Derengowska Magdalena Hagner
Published: July 2021

The main aim of the study was to assess the risk of falls, and physical fitness in the group of women aged 60 to 65 years of age suffering from an identified osteoporosis in comparison to a similar group of healthy women. The main question was: What is the level of physical fitness and risk of fall among women with osteoporosis compared to healthy women? The research included 262 women aged 60 to 65 of age: 135 with osteoporosis and 127 healthy ones, living in the Małopolskie and the Świętokrzyskie Provinces of Poland. To assess the level of physical fitness, the Senior Fitness Test (SFT) was used, while the Tinetti POMA (Performance Oriented Mobility Assessment) and Timed Up&Go test (TUG) were used to asses the risk of fall. Significant statistical differences in average results of physical fitness assessment were noticed as regards the following aspects: flexibility of the lower body part p < 0.001; flexibility of the upper body part p < 0.001. Essential differences were demonstrated in assessing the risk of falling with p < 0.01. Women with osteoporosis are marked by a lower physical fitness than healthy women. A higher percentage of great and serious risk of fall was demonstrated among women with osteoporosis.
Stratigraphy of stable isotope ratios and leaf structure within an African rainforest canopy with implications for primate isotope ecology
Authors: Lowry B. E. , Wittig R. M. , Pittermann J. , Oelze V. M.
Published: July 2021

The canopy effect describes vertical variation in the isotope ratios of carbon (δ13C), oxygen (δ18O) and partially nitrogen (δ15N) within plants throughout a closed canopy forest, and may facilitate the study of canopy feeding niches in arboreal primates. However, the nuanced relationship between leaf height, sunlight exposure and the resulting variation in isotope ratios and leaf mass per area (LMA) has not been documented for an African rainforest. Here, we present δ13C, δ18O and δ15N values of leaves (n = 321) systematically collected from 58 primate food plants throughout the canopy (0.3 to 42 m) in Côte d’Ivoire, West Africa. Besides leaf sample height and light availability, we measured leaf nitrogen and carbon content (%N, %C), as well as LMA (n = 214) to address the plants’ vertical resource allocations. We found significant variation in δ13C, δ18O and δ15N, as well as LMA in response to height in combination with light availability and tree species, with low canopy leaves depleted in 13C, 18O and 15N and slightly higher in %N compared to higher canopy strata. While this vertical isotopic variation was not well reflected in the δ13C and δ15N of arboreal primates from this forest, it did correspond well to primate δ18O values.
Local stability of cooperation in a continuous model of indirect reciprocity
Authors: Lee Sanghun , Murase Yohsuke , Baek Seung Ki
Published: July 2021

Reputation is a powerful mechanism to enforce cooperation among unrelated individuals through indirect reciprocity, but it suffers from disagreement originating from private assessment, noise, and incomplete information. In this work, we investigate stability of cooperation in the donation game by regarding each player’s reputation and behaviour as continuous variables. Through perturbative calculation, we derive a condition that a social norm should satisfy to give penalties to its close variants, provided that everyone initially cooperates with a good reputation, and this result is supported by numerical simulation. A crucial factor of the condition is whether a well-reputed player’s donation to an ill-reputed co-player is appreciated by other members of the society, and the condition can be reduced to a threshold for the benefit-cost ratio of cooperation which depends on the reputational sensitivity to a donor’s behaviour as well as on the behavioural sensitivity to a recipient’s reputation. Our continuum formulation suggests how indirect reciprocity can work beyond the dichotomy between good and bad even in the presence of inhomogeneity, noise, and incomplete information.
18Fluorodeoxyglucose uptake in relation to fat fraction and R2* in atherosclerotic plaques, using PET/MRI: a pilot study
Authors: Good Elin , Ochoa-Figueroa Miguel , Ziegler Magnus , Ressner Marcus , Warntjes Marcel , Dyverfeldt Petter , Lubberink Mark , Ahlström Håkan , de Muinck Ebo
Published: July 2021

Inflammation inside Atherosclerotic plaques represents a major pathophysiological process driving plaques towards rupture. Pre-clinical studies suggest a relationship between lipid rich necrotic core, intraplaque hemorrhage and inflammation, not previously explored in patients. Therefore, we designed a pilot study to investigate the feasibility of assessing the relationship between these plaque features in a quantitative manner using PET/MRI. In 12 patients with high-grade carotid stenosis the extent of lipid rich necrotic core and intraplaque hemorrhage was quantified from fat and R2* maps acquired with a previously validated 4-point Dixon MRI sequence in a stand-alone MRI. PET/MRI was used to measure 18F-FDG uptake. T1-weighted images from both scanners were used for registration of the quantitative Dixon data with the PET images. The plaques were heterogenous with respect to their volumes and composition. The mean values for the group were as follows: fat fraction (FF) 0.17% (± 0.07), R2* 47.6 s−1 (± 10.9) and target-to-blood pool ratio (TBR) 1.49 (± 0.48). At group level the correlation between TBR and FFmean was − 0.406, p 0.19 and for TBR and R2*mean 0.259, p 0.42. The lack of correlation persisted when analysed on a patient-by-patient basis but the study was not powered to draw definitive conclusions. We show the feasibility of analysing the quantitative relationship between lipid rich necrotic cores, intraplaque haemorrhage and plaque inflammation. The 18F-FDG uptake for most patients was low. This may reflect the biological complexity of the plaques and technical aspects inherent to 18F-FDG measurements.

Trial registration: ISRCTN, ISRCTN30673005. Registered 05 January 2021, retrospectively registered.
Platelet-to-lymphocyte ratio is not a predictor of clinically significant prostate cancer at the prostate biopsy: A large cohort study
Authors: Lee Jeong Woo , Jeong Hyeon , Son Hwancheol , Cho Min Chul
Published: July 2021

Previous studies have reported conflicting results on the predictive role of the platelet-to-lymphocyte ratio (PLR) in detecting clinically significant prostate cancer (CSPCa) at the time of prostate biopsies. We explored the predictive value of pre-biopsy PLRs for CSPCa using our large-cohort database. Consecutive men with serum prostate-specific antigen (PSA) levels of ≥ 3.0 ng/mL or abnormal digital rectal examination (DRE) findings and who underwent prostate biopsies were included in the study. There was no significant difference in the pre-biopsy PLR between men with benign disease, clinically insignificant prostate cancer (CISPCa), and CSPCa. Only the subset of CSPCa patients with serum PSA levels of < 10 ng/mL showed lower PLRs than those with benign disease or CISPCa. In the entire patient cohort, multivariate analyses revealed that older age, diabetes mellitus, DRE abnormalities, higher serum PSA levels, and smaller prostate volume were predictors of CSPCa. However, the pre-biopsy PLR was not a significant predictor of CSPCa at the prostate biopsy in the entire patient cohort or the subset of patients with serum PSA levels of < 10 ng/mL. In summary, the pre-biopsy PLR is not an independent predictor of CSPCa at the prostate biopsy, regardless of the serum PSA level.
Perception of geometric sequences and numerosity both predict formal geometric competence in primary school children
Authors: Castaldi Elisa , Arrighi Roberto , Cicchini Guido M. , Andolfi Arianna , Maduli Giuseppe , Burr David C. , Anobile Giovanni
Published: July 2021

While most animals have a sense of number, only humans have developed symbolic systems to describe and organize mathematical knowledge. Some studies suggest that human arithmetical knowledge may be rooted in an ancient mechanism dedicated to perceiving numerosity, but it is not known if formal geometry also relies on basic, non-symbolic mechanisms. Here we show that primary-school children who spontaneously detect and predict geometrical sequences (non-symbolic geometry) perform better in school-based geometry tests indexing formal geometric knowledge. Interestingly, numerosity discrimination thresholds also predicted and explained a specific portion of variance of formal geometrical scores. The relation between these two non-symbolic systems and formal geometry was not explained by age or verbal reasoning skills. Overall, the results are in line with the hypothesis that some human-specific, symbolic systems are rooted in non-symbolic mechanisms.
Machine learning application for the prediction of SARS-CoV-2 infection using blood tests and chest radiograph
Authors: Du Richard , Tsougenis Efstratios D. , Ho Joshua W. K. , Chan Joyce K. Y. , Chiu Keith W. H. , Fang Benjamin X. H. , Ng Ming Yen , Leung Siu-Ting , Lo Christine S. Y. , Wong Ho-Yuen F. , Lam Hiu-Yin S. , Chiu Long-Fung J. , So Tiffany Y , Wong Ka Tak , Wong Yiu Chung I. , Yu Kevin , Yeung Yiu-Cheong , Chik Thomas , Pang Joanna W. K. , Wai Abraham Ka-chung , Kuo Michael D. , Lam Tina P. W. , Khong Pek-Lan , Cheung Ngai-Tseung , Vardhanabhuti Varut
Published: July 2021

Triaging and prioritising patients for RT-PCR test had been essential in the management of COVID-19 in resource-scarce countries. In this study, we applied machine learning (ML) to the task of detection of SARS-CoV-2 infection using basic laboratory markers. We performed the statistical analysis and trained an ML model on a retrospective cohort of 5148 patients from 24 hospitals in Hong Kong to classify COVID-19 and other aetiology of pneumonia. We validated the model on three temporal validation sets from different waves of infection in Hong Kong. For predicting SARS-CoV-2 infection, the ML model achieved high AUCs and specificity but low sensitivity in all three validation sets (AUC: 89.9–95.8%; Sensitivity: 55.5–77.8%; Specificity: 91.5–98.3%). When used in adjunction with radiologist interpretations of chest radiographs, the sensitivity was over 90% while keeping moderate specificity. Our study showed that machine learning model based on readily available laboratory markers could achieve high accuracy in predicting SARS-CoV-2 infection.
Kondo effect and superconductivity in niobium with iron impurities
Authors: Zeng Hansong , Zhou Dan , Liang Guoqing , Tang Rujun , Hang Zhi H. , Hu Zhiwei , Pei Zixi , Ling X. S.
Published: July 2021

Kondo effect is an interesting phenomenon in quantum many-body physics. Niobium (Nb) is a conventional superconductor important for many superconducting device applications. It was long thought that the Kondo effect cannot be observed in Nb because the magnetic moment of a magnetic impurity, e.g. iron (Fe), would have been quenched in Nb. Here we report an observation of the Kondo effect in a Nb thin film structure. We found that by co-annealing Nb films with Fe in Argon gas at above 400 $$^{\circ }$$

∘

C for an hour, one can induce a Kondo effect in Nb. The Kondo effect is more pronounced at higher annealing temperature. The temperature dependence of the resistance suggests existence of remnant superconductivity at low temperatures even though the system never becomes superconducting. We find that the Hamann theory for the Kondo resistivity gives a satisfactory fitting to the result. The Hamann analysis gives a Kondo temperature for this Nb–Fe system at $$\sim $$
∼
16 K, well above the superconducting transition onset temperature 9 K of the starting Nb film, suggesting that the screening of the impurity spins is effective to allow Cooper pairs to form at low temperatures. We suggest that the mechanism by which the Fe impurities retain partially their magnetic moment is that they are located at the grain boundaries, not fully dissolved into the bcc lattice of Nb.
Detection of PD-L1 in the urine of patients with urothelial carcinoma of the bladder
Authors: Tosev Georgi , Wahafu Wasilijiang , Reimold Philipp , Damgov Ivan , Schwab Constantin , Aksoy Cem , Kaczorowski Adam , Stenzinger Albrecht , Nyarangi-Dix Joanne , Hohenfellner Markus , Duensing Stefan
Published: July 2021

There are currently five programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors approved for the treatment of locally advanced or metastatic urothelial carcinoma (UC) of the bladder. For platinum-ineligible patients, testing of tumor specimens for PD-L1 expression is required. However, scoring of PD-L1 immunohistochemistry is complex due to different antibodies used, the requirement to score expression in different cellular compartments and intratumoral heterogeneity. It can also be difficult to obtain and test longitudinal tumor samples, which would be desirable to monitor treatment responses and tumor evolution under treatment-induced selective pressure. In the present proof-of concept study, we provide evidence that PD-L1 can be detected in the urine of patients with non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Urine PD-L1 levels were significantly higher in NMIBC and MIBC patients when compared to patients with various non-malignant urological diseases. Further prospective and independent studies are required to assess the value of PD-L1 in the urine as a novel biomarker with potential for the early detection, prediction and therapeutic monitoring of patients with UC of the bladder.
Head-nodding: a driving force for the circulation of cerebrospinal fluid
Authors: Xu Qiang , Shao Chang-Xi , Zhang Ying , Zhang Yu , Liu Cong , Chen Yu-Xiao , Wang Xue-Mei , Chi Yan-Yan , Yu Sheng-Bo , Sui Hong-Jin
Published: July 2021

The myodural bridge (MDB) is a dense connective tissue bridge connecting the suboccipital muscles to the spinal dura mater, and it has been proven to be a normal common existing structure in humans and mammals. Some scholars believe that the suboccipital muscles can serve as a dynamic cerebrospinal fluid (CSF) pump via the MDB, and they found head rotations promote the CSF flow in human body, which provided evidence for this hypothesis. Head movement is a complex motion, but the effects of other forms of head movement on CSF circulation are less known. The present study explored the effects of head-nodding on CSF circulation. The CSF flow of 60 healthy volunteers was analyzed via cine phase-contrast magnetic resonance imaging at the level of the occipitocervical junction before and after one-minute-head-nodding period. Furthermore, the CSF pressures of 100 volunteers were measured via lumbar puncture before and after 5 times head-nodding during their anesthetizing for surgical preparation. As a result, it was found that the maximum and average CSF flow rates at the level of the upper border of atlas during ventricular diastole were significantly decreased from 1.965 ± 0.531 to 1.839 ± 0.460 ml/s and from 0.702 ± 0.253 to 0.606 ± 0.228 ml/s respectively. In the meantime, the changes in the ratio of cranial and caudal orientation of the net flow volume were found differed significantly after the one-minute-head-nodding period (p = 0.017). And on the other hand, the CSF pressures at the L3–L4 level were markedly increased 116.03 ± 26.13 to 124.64 ± 26.18 mmH2O. In conclusion, the head-nodding has obvious effects on CSF circulation and head movement is one of the important drivers of cerebrospinal fluid circulation. We propose that the suboccipital muscles, participating in various head movements, might pull the dura sac via the myodural bridge, and thus, head movement provides power for the CSF circulation.