bluuebunny/crossref_metadata_2025 huggingface dataset:
Molybdenum and Boron Isotopic Compositions of Porphyry Cu Mineralization‐Related Adakitic Rocks in Central‐Eastern China: New Insights Into their Petrogenesis and Crust‐Mantle Interaction
Authors: Fan Jing‐Jing , Wang Qiang , Li Jie , Wei Gang‐Jian , Wyman Derek , Zhao Zhen‐Hua , Liu Ying , Ma Jin‐Long , Zhang Le , Wang Zi‐Long
Published: November 2020

The voluminous Late Mesozoic porphyry ore‐related adakitic magmatism in central‐eastern China is crucial to understand the deep geodynamic process of the region and controls on porphyry deposit formation globally. Here, we present a novel study of whole‐rock Mo‐B isotopes on the mineralization‐related adakitic rocks from the Dexing (located in the interior of South China and associated with giant porphyry Cu deposits), and Middle‐Lower Yangtze River (MLYR) (host to one of the largest porphyry Cu‐Au deposit belts) areas in central‐eastern China. The Dexing adakitic rocks have δ98/95Mo ranging from −0.31‰ to −0.01‰ and δ11B from −17.65‰ to −11.49‰. The adakitic rocks from the MLYR area have δ98/95Mo values of −0.5‰ to 0.2‰ and δ11B values of −14.48‰ to −9.53‰. The δ98/95Mo values of both the Dexing and MLYR samples negatively correlate with the La/Yb and La/Sm ratios. Together with the high Mg#, Cr, and Ni contents, these results indicate a process of melt‐mantle interaction resulting in hybridization of initial adakitic melts with low δ98/95Mo and mantle‐derived melts/components with high δ98/95Mo. These adakitic rocks have distinct Mo isotope systematics compared with those of oceanic slab‐derived adakites and MORB‐type eclogites. Their relatively low δ11B values and the lack of correlation between δ11B and B contents support a mafic lower crust source for the initial adakitic melts. We thus suggest that these adakitic rocks were generated by partial melting of delaminated lower crust followed by interaction with the deep mantle, and that melt‐mantle interaction may facilitate Cu‐Mo‐Au mineralization.
Subgroup level differences of physiological activities in marine Lokiarchaeota
Authors: Yin Xiuran , Cai Mingwei , Liu Yang , Zhou Guowei , Richter-Heitmann Tim , Aromokeye David A , Kulkarni Ajinkya C , Nimzyk Rolf , Cullhed Henrik , Zhou Zhichao , Pan Jie , Yang Yuchun , Gu Ji-Dong , Elvert Marcus , Li Meng , Friedrich Michael W
Published: November 2020

Asgard is a recently discovered archaeal superphylum, closely linked to the emergence of eukaryotes. Among Asgard archaea, Lokiarchaeota are abundant in marine sediments, but their in situ activities are largely unknown except for Candidatus ‘Prometheoarchaeum syntrophicum’. Here, we tracked the activity of Lokiarchaeota in incubations with Helgoland mud area sediments (North Sea) by stable isotope probing (SIP) with organic polymers, 13C-labelled inorganic carbon, fermentation intermediates and proteins. Within the active archaea, we detected members of the Lokiarchaeota class Loki-3, which appeared to mixotrophically participate in the degradation of lignin and humic acids while assimilating CO2, or heterotrophically used lactate. In contrast, members of the Lokiarchaeota class Loki-2 utilized protein and inorganic carbon, and degraded bacterial biomass formed in incubations. Metagenomic analysis revealed pathways for lactate degradation, and involvement in aromatic compound degradation in Loki-3, while the less globally distributed Loki-2 instead rely on protein degradation. We conclude that Lokiarchaeotal subgroups vary in their metabolic capabilities despite overlaps in their genomic equipment, and suggest that these subgroups occupy different ecologic niches in marine sediments.
Coexistence of perseveration and apathy in the TDP-43Q331K knock-in mouse model of ALS–FTD
Authors: Kim Eosu , White Matthew A. , Phillips Benjamin U. , Lopez-Cruz Laura , Kim Hyunjeong , Heath Christopher J. , Lee Jong Eun , Saksida Lisa M. , Sreedharan Jemeen , Bussey Timothy J.
Published: November 2020

Perseveration and apathy are two of the most common behavioural and psychological symptoms of dementia (BPSDs) in amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD). Availability of a validated and behaviourally characterised animal model is crucial for translational research into BPSD in the FTD context. We behaviourally evaluated the male TDP-43Q331K mouse, an ALS–FTD model with a human-equivalent mutation (TDP-43Q331K) knocked into the endogenous Tardbp gene. We utilised a panel of behavioural tasks delivered using the rodent touchscreen apparatus, including progressive ratio (PR), extinction and visual discrimination/reversal learning (VDR) assays to examine motivation, response inhibition and cognitive flexibility, respectively. Relative to WT littermates, TDP-43Q331K mice exhibited increased responding under a PR schedule. While elevated PR responding is typically an indication of increased motivation for reward, a trial-by-trial response rate analysis revealed that TDP-43Q331K mice exhibited decreased maximal response rate and slower response decay rate, suggestive of reduced motivation and a perseverative behavioural phenotype, respectively. In the extinction assay, TDP-43Q331K mice displayed increased omissions during the early phase of each session, consistent with a deficit in activational motivation. Finally, the VDR task revealed cognitive inflexibility, manifesting as stimulus-bound perseveration. Together, our data indicate that male TDP-43Q331K mice exhibit a perseverative phenotype with some evidence of apathy-like behaviour, similar to BPSDs observed in human ALS–FTD patients. The TDP-43Q331K knock-in mouse therefore has features that recommend it as a useful platform to facilitate translational research into behavioural symptoms in the context of ALS–FTD.
VIS832, a novel CD138-targeting monoclonal antibody, potently induces killing of human multiple myeloma and further synergizes with IMiDs or bortezomib in vitro and in vivo
Authors: Yu Tengteng , Chaganty Bharat , Lin Liang , Xing Lijie , Ramakrishnan Boopathy , Wen Kenneth , Hsieh Phillip A. , Wollacott Andrew , Viswanathan Karthik , Adari Hedy , Cho Shih-Feng , Li Yuyin , Chen Hailin , Yang Wenjuan , Xu Yan , An Gang , Qiu Lugui , Munshi Nikhil , Babcock Gregory , Shriver Zachary , Myette James R. , Anderson Kenneth C. , Tai Yu-Tzu
Published: November 2020

Therapeutically targeting CD138, a define multiple myeloma (MM) antigen, is not yet approved for patients. We here developed and determined the preclinical efficacy of VIS832, a novel therapeutic monoclonal antibody (MoAb) with differentiated CD138 target binding to BB4 that is anti-CD138 MoAb scaffold for indatuximab ravtansine (BT062). VIS832 demonstrated enhanced CD138-binding avidity and significantly improved potency to kill MM cell lines and autologous patient MM cells regardless of resistance to current standard-of-care therapies, via robust antibody-dependent cellular cytotoxicity and phagocytosis mediated by NK and macrophage effector cells, respectively. Specifically, CD38-targeting daratumumab-resistant MM cells were highly susceptible to VIS832 which, unlike daratumumab, spares NK cells. Superior maximal cytolysis of VIS832 vs. daratumumab corresponded to higher CD138 vs. CD38 levels in MM cells. Furthermore, VIS832 acted synergistically with lenalidomide or bortezomib to deplete MM cells. Importantly, VIS832 at a sub-optimal dose inhibited disseminated MM1S tumors in vivo as monotherapy (P < 0.0001), and rapidly eradicated myeloma burden in all mice concomitantly receiving bortezomib, with 100% host survival. Taken together, these data strongly support clinical development of VIS832, alone and in combination, for the therapeutic treatment of MM in relapsed and refractory patients while pointing to its potential therapeutic use earlier in disease intervention.
An ambruticin-sensing complex modulates Myxococcus xanthus development and mediates myxobacterial interspecies communication
Authors: Marcos-Torres Francisco Javier , Volz Carsten , Müller Rolf
Published: November 2020

Starvation induces cell aggregation in the soil bacterium Myxococcus xanthus, followed by formation of fruiting bodies packed with myxospores. Sporulation in the absence of fruiting bodies can be artificially induced by high concentrations of glycerol through unclear mechanisms. Here, we show that a compound (ambruticin VS-3) produced by a different myxobacterium, Sorangium cellulosum, affects the development of M. xanthus in a similar manner. Both glycerol (at millimolar levels) and ambruticin VS-3 (at nanomolar concentrations) inhibit M. xanthus fruiting body formation under starvation, and induce sporulation in the presence of nutrients. The response is mediated in M. xanthus by three hybrid histidine kinases (AskA, AskB, AskC) that form complexes interacting with two major developmental regulators (MrpC, FruA). In addition, AskB binds directly to the mrpC promoter in vitro. Thus, our work indicates that the AskABC-dependent regulatory pathway mediates the responses to ambruticin VS-3 and glycerol. We hypothesize that production of ambruticin VS-3 may allow S. sorangium to outcompete M. xanthus under both starvation and growth conditions in soil.
Sigma-1 receptor chaperones rescue nucleocytoplasmic transport deficit seen in cellular and Drosophila ALS/FTD models
Authors: Lee Pin-Tse , Liévens Jean-Charles , Wang Shao-Ming , Chuang Jian-Ying , Khalil Bilal , Wu Hsiang-en , Chang Wen-Chang , Maurice Tangui , Su Tsung-Ping
Published: November 2020

In a subgroup of patients with amyotrophic lateral sclerosis (ALS)/Frontotemporal dementia (FTD), the (G4C2)-RNA repeat expansion from C9orf72 chromosome binds to the Ran-activating protein (RanGAP) at the nuclear pore, resulting in nucleocytoplasmic transport deficit and accumulation of Ran in the cytosol. Here, we found that the sigma-1 receptor (Sig-1R), a molecular chaperone, reverses the pathological effects of (G4C2)-RNA repeats in cell lines and in Drosophila. The Sig-1R colocalizes with RanGAP and nuclear pore proteins (Nups) and stabilizes the latter. Interestingly, Sig-1Rs directly bind (G4C2)-RNA repeats. Overexpression of Sig-1Rs rescues, whereas the Sig-1R knockout exacerbates, the (G4C2)-RNA repeats-induced aberrant cytoplasmic accumulation of Ran. In Drosophila, Sig-1R (but not the Sig-1R-E102Q mutant) overexpression reverses eye necrosis, climbing deficit, and firing discharge caused by (G4C2)-RNA repeats. These results on a molecular chaperone at the nuclear pore suggest that Sig-1Rs may benefit patients with C9orf72 ALS/FTD by chaperoning the nuclear pore assembly and sponging away deleterious (G4C2)-RNA repeats.
Perturbed structural dynamics underlie inhibition and altered efflux of the multidrug resistance pump AcrB
Authors: Reading Eamonn , Ahdash Zainab , Fais Chiara , Ricci Vito , Wang-Kan Xuan , Grimsey Elizabeth , Stone Jack , Malloci Giuliano , Lau Andy M. , Findlay Heather , Konijnenberg Albert , Booth Paula J. , Ruggerone Paolo , Vargiu Attilio V. , Piddock Laura J. V. , Politis Argyris
Published: November 2020

Resistance–nodulation–division efflux pumps play a key role in inherent and evolved multidrug resistance in bacteria. AcrB, a prototypical member of this protein family, extrudes a wide range of antimicrobial agents out of bacteria. Although high-resolution structures exist for AcrB, its conformational fluctuations and their putative role in function are largely unknown. Here, we determine these structural dynamics in the presence of substrates using hydrogen/deuterium exchange mass spectrometry, complemented by molecular dynamics simulations, and bacterial susceptibility studies. We show that an efflux pump inhibitor potentiates antibiotic activity by restraining drug-binding pocket dynamics, rather than preventing antibiotic binding. We also reveal that a drug-binding pocket substitution discovered within a multidrug resistant clinical isolate modifies the plasticity of the transport pathway, which could explain its altered substrate efflux. Our results provide insight into the molecular mechanism of drug export and inhibition of a major multidrug efflux pump and the directive role of its dynamics.
Pan-cancer landscape of homologous recombination deficiency
Authors: Nguyen Luan , W. M. Martens John , Van Hoeck Arne , Cuppen Edwin
Published: November 2020

Homologous recombination deficiency (HRD) results in impaired double strand break repair and is a frequent driver of tumorigenesis. Here, we develop a genome-wide mutational scar-based pan-cancer Classifier of HOmologous Recombination Deficiency (CHORD) that can discriminate BRCA1- and BRCA2-subtypes. Analysis of a metastatic (n = 3,504) and primary (n = 1,854) pan-cancer cohort reveals that HRD is most frequent in ovarian and breast cancer, followed by pancreatic and prostate cancer. We identify biallelic inactivation of BRCA1, BRCA2, RAD51C or PALB2 as the most common genetic cause of HRD, with RAD51C and PALB2 inactivation resulting in BRCA2-type HRD. We find that while the specific genetic cause of HRD is cancer type specific, biallelic inactivation is predominantly associated with loss-of-heterozygosity (LOH), with increased contribution of deep deletions in prostate cancer. Our results demonstrate the value of pan-cancer genomics-based HRD testing and its potential diagnostic value for patient stratification towards treatment with e.g. poly ADP-ribose polymerase inhibitors (PARPi).
Geopositioning time series from offshore platforms in the Adriatic Sea
Authors: Palano Mimmo , Pezzo Giuseppe , Serpelloni Enrico , Devoti Roberto , D’Agostino Nicola , Gandolfi Stefano , Sparacino Federica , Anderlini Letizia , Poluzzi Luca , Tavasci Luca , Macini Paolo , Pietrantonio Grazia , Riguzzi Federica , Antoncecchi Ilaria , Ciccone Francesco , Rossi Giada , Avallone Antonio , Selvaggi Giulio
Published: November 2020

We provide a dataset of 3D coordinate time series of 37 continuous GNSS stations installed for stability monitoring purposes on onshore and offshore industrial settlements along a NW-SE-oriented and ~100-km-wide belt encompassing the eastern Italian coast and the Adriatic Sea. The dataset results from the analysis performed by using different geodetic software (Bernese, GAMIT/GLOBK and GIPSY) and consists of six raw position time series solutions, referred to IGb08 and IGS14 reference frames. Time series analyses and comparisons evidence that the different solutions are consistent between them, despite the use of different software, models, strategy processing and frame realizations. We observe that the offshore stations are subject to significant seasonal oscillations probably due to seasonal environmental loads, seasonal temperature-induced platform deformation and hydrostatic pressure variations. Many stations are characterized by non-linear time series, suggesting a complex interplay between regional (long-term tectonic stress) and local sources of deformation (e.g. reservoirs depletion, sediment compaction). Computed raw time series, logs files, phasor diagrams and time series comparison plots are distributed via PANGAEA (https://www.pangaea.de).
Inhaled corticosteroids in COPD and the risk for coronary heart disease: a nationwide cohort study
Authors: Shin Jiyoung , Yoon Hee-Young , Lee Yu Min , Ha Eunhee , Lee Jin Hwa
Published: November 2020

Inhaled corticosteroids (ICS) might lower the risk of coronary heart disease (CHD) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the association of ICS with the development of CHD in COPD patients by using data from the Korean Nationwide study. Patients who were newly diagnosed with COPD between 2004 and 2013 and who were not diagnosed with coronary heart disease before their diagnosis of COPD were included. Exposure of ICS was incorporated into multivariable Cox regression models using time-dependent methods. To accurately estimate ICS-exposure accumulation, a washout period of 2 years from 2002 to 2003 was applied. Among a total of 4,400 newly diagnosed COPD patients, 771 patients were diagnosed as CHD incident cases during a median follow-up of one year (interquartile range 0.1–2.9). The cumulative dose of ICS was associated with a reduced risk of CHD (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.52–0.89). When the cumulative exposure dose of ICS was divided into quartiles, the aHR for CHD incidence was 0.70 (95% CI, 0.55–0.88) in the highest quartile ICS dose use. The effect of ICS on reducing CHD incidence was pronounced in adults over 55 years, men under 55 years, and former smokers. Our findings demonstrate the role of ICS for the prevention of CHD in COPD patients without a history of CHD. Further research is needed to determine whether a certain amount of ICS exposure in COPD patients is protective against CHD.
Investigating the impact of captivity and domestication on limb bone cortical morphology: an experimental approach using a wild boar model
Authors: Harbers Hugo , Zanolli Clement , Cazenave Marine , Theil Jean-Christophe , Ortiz Katia , Blanc Barbara , Locatelli Yann , Schafberg Renate , Lecompte Francois , Baly Isabelle , Laurens Flavie , Callou Cécile , Herrel Anthony , Puymerail Laurent , Cucchi Thomas
Published: November 2020

The lack of bone morphological markers associated with the human control of wild animals has prevented the documentation of incipient animal domestication in archaeology. Here, we assess whether direct environmental changes (i.e. mobility reduction) could immediately affect ontogenetic changes in long bone structure, providing a skeletal marker of early domestication. We relied on a wild boar experimental model, analysing 24 wild-born specimens raised in captivity from 6 months to 2 years old. The shaft cortical thickness of their humerus was measured using a 3D morphometric mapping approach and compared with 23 free-ranging wild boars and 22 pigs from different breeds, taking into account sex, mass and muscle force differences. In wild boars we found that captivity induced an increase in cortical bone volume and muscle force, and a topographic change of cortical thickness associated with muscular expression along a phenotypic trajectory that differed from the divergence induced by selective breeding. These results provide an experimental proof of concept that changes in locomotor behaviour and selective breeding might be inferred from long bones morphology in the fossil and archaeological record. These trends need to be explored in the archaeological record and further studies are required to explore the developmental changes behind these plastic responses.
Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency
Authors: Løchen Alessandra , Croucher Nicholas J. , Anderson Roy M.
Published: November 2020

Streptococcus pneumoniae is a significant cause of otitis media, pneumonia, and meningitis. Only seven of the approximately 100 serotypes were initially included in the pneumococcal polysaccharide conjugate vaccine (PCV) in 2000 before it was expanded in subsequent years. Although the invasive pneumococcal disease (IPD) incidence due to vaccine serotypes (VT) has declined, partial replacement by non-vaccine serotypes (NVT) was observed following widespread vaccine uptake. We conducted a trend analysis assembling the available evidence for PCV impact on European, North American and Australian national IPD. Significant effectiveness against VT IPD in infants was observed, although the impact on national IPD incidence varied internationally due to serotype replacement. Currently, NVT serotypes 8, 9N, 15A and 23B are increasing in the countries assessed, although a variety of other NVTs are affecting each country and age group. Despite these common emerging serotypes, there has not been a dominant IPD serotype post-vaccination as there was pre-vaccination (serotype 14) or post-PCV7 (serotype 19A), suggesting that future vaccines with additional serotypes will be less effective at targeting and reducing IPD in global populations than previous PCVs. The rise of diverse NVTs in all settings’ top-ranked IPD-causing serotypes emphasizes the urgent need for surveillance data on serotype distribution and serotype-specific invasiveness post-vaccination to facilitate decision making concerning both expanding current vaccination programmes and increasing vaccine valency.
Mirror replication of sexual facial expressions increases the success of sexual contacts in bonobos
Authors: Palagi Elisabetta , Bertini Marta , Annicchiarico Giulia , Cordoni Giada
Published: November 2020

Rapid Facial Mimicry (RFM), one of the possible predictors of emotional contagion, is defined as the rapid, involuntary and automatic replication of a facial expression. Up to now, RFM has been demonstrated in nonhuman animals exclusively during play. Since in bonobos, as in humans, socio-sexuality is a powerful tool for assessing/strengthening inter-individual relationships, we investigated RFM in this domain. Bonobos displayedsilent bared-teeth(sbt, the most common facial expression during sexual contacts) more frequently after thedetectionof ansbtemitted by the trigger than in theno-detectioncondition. This is the first demonstration of the presence of RFM during sex. The occurrence of RFM was positively affected by the sex of the partners with female homo-sexual contacts being punctuated by a higher presence of RFM. At an immediate level, RFM increased the duration of homo- and hetero-sexual contacts. This finding suggests that RFM can increase individuals’ potential fitness benefits. By prolonging their sexual contacts, females can strengthen their social relationships thus increasing the probability to obtain priority over resources (RFM indirect fitness benefits). Via longer copulations, males can increase the probability to make females pregnant (RFM direct fitness benefits). In conclusion, in bonobos the access to the partner’s face during sexual contacts (face-to-face, proximate factor) and the role of socio-sexuality in increasing the individual direct and indirect fitness (ultimate factor) could have favoured the evolution of specific sexual facial expressions and their rapid mirror replication. Our findings on bonobos expand the role of RFM well beyond the animal play domain thus opening new scenarios for future comparative studies exploring the evolution of socio-sexuality in humans.
Optimized and scalable synthesis of magnetic nanoparticles for RNA extraction in response to developing countries' needs in the detection and control of SARS-CoV-2
Authors: Chacón-Torres Julio C. , Reinoso C. , Navas-León Daniela G. , Briceño Sarah , González Gema
Published: November 2020

Ecuador is one of the most affected countries, with the coronavirus disease 2019 (COVID-19) infection, in Latin America derived from an ongoing economic crisis. One of the most important methods for COVID-19 detection is the use of techniques such as real time RT-PCR based on a previous extraction/purification of RNA procedure from nasopharyngeal cells using functionalized magnetic nanoparticles (MNP). This technique allows the processing of ~ 10,000 tests per day in private companies and around hundreds per day at local Universities guaranteeing to reach a wide range of the population. However, the main drawback of this method is the need for specialized MNP with a strong negative charge for the viral RNA extraction to detect the existence of the SARS-CoV-2 virus. Here we present a simplified low cost method to produce 10 g of nanoparticles in 100 mL of solution that was scaled to one litter by parallelizing the process 10 times in just two days and allowing for the possibility of making ~ 50,000 COVID-19 tests. This communication helps in reducing the cost of acquiring MNP for diverse biomolecular applications supporting developing country budgets constraints and chemical availability specially during the COVID-19 International Health Emergency.
Genetic diversity and inter-relationships of fruit bio-chemicals and antioxidant activity in Iranian wild blackberry species
Authors: Garazhian Mehdi , Gharaghani Ali , Eshghi Saeid
Published: November 2020

Blackberries are a rich source of bio-chemicals such as anthocyanins and polyphenolic antioxidants. The evaluation of the extent of variation among wild genetic resources can provide useful information for the establishment of effective conservation strategies and future breeding programs. In this study, variations and inter-relationship of berry weight, total phenol (TP), total soluble solids (TSS), titratable acidity (TA), ascorbic acid (AA), anthocyanin and antioxidant activity were estimated in their values among 57 accessions belonging to 4 different Rubus spp. native to Iran. The experiments were performed during two consecutive years (2014 and 2015). Combine analysis showed that there is no significant difference between the data of 2 years in all measured traits. High or very high levels of variations were detected in berry weight (0.14–1.30 g), antioxidant activity (40.21–88.08%), anthocyanin (80.74–145.09 mg/100 g), TSS (7.9–17.8 °Brix), TA (0.36–0.83%) and AA (9.56–20.92 mg/100 g). This is while TP showed very low levels of variation (109.5–129.1 mg/100 g). Correlation analysis showed that antioxidant activity correlated highly and positively with all of the measured characteristics including ascorbic acid (r = 0.927), anthocyanin (r = 0.752), total phenol (r = 0.681), TSS (r = 0.473) and berry weight (r = 0.541) except for TA. Cluster analysis based on all measured characteristics showed a partial differentiation between the accessions based on their species and, to lesser extent, according to their origin within the main clusters. Based on the bi-plot of the first two PCAs, genotypes and traits classified into four quadrants. This grouping was in agreement with that of cluster analysis, considering the fact that almost all of accessions in quadrants II and III (with a few exceptions) were same to those in the first clade of cluster analysis and the genotypes grouped in quadrants I and IV, represents the accessions of clade 2 in cluster analysis. The projection of the traits vectors in PCA were also fully in accordance to that of correlation analysis in almost all of studied traits. Results showed that a rich source of variations is available considering berry weight, fruit bio-chemical and antioxidant activity in the Iranian wild Rubus species, which needs immediate conservation and worth to be utilized in commercial breeding programs.
An artificial intelligence-based first-line defence against COVID-19: digitally screening citizens for risks via a chatbot
Authors: Martin Alistair , Nateqi Jama , Gruarin Stefanie , Munsch Nicolas , Abdarahmane Isselmou , Zobel Marc , Knapp Bernhard
Published: November 2020

To combat the pandemic of the coronavirus disease 2019 (COVID-19), numerous governments have established phone hotlines to prescreen potential cases. These hotlines have struggled with the volume of callers, leading to wait times of hours or, even, an inability to contact health authorities. Symptoma is a symptom-to-disease digital health assistant that can differentiate more than 20,000 diseases with an accuracy of more than 90%. We tested the accuracy of Symptoma to identify COVID-19 using a set of diverse clinical cases combined with case reports of COVID-19. We showed that Symptoma can accurately distinguish COVID-19 in 96.32% of clinical cases. When considering only COVID-19 symptoms and risk factors, Symptoma identified 100% of those infected when presented with only three signs. Lastly, we showed that Symptoma’s accuracy far exceeds that of simple “yes–no” questionnaires widely available online. In summary, Symptoma provides unparalleled accuracy in systematically identifying cases of COVID-19 while also considering over 20,000 other diseases. Furthermore, Symptoma allows free text input, furthered with disease-specific follow up questions, in 36 languages. Combined, these results and accessibility give Symptoma the potential to be a key tool in the global fight against COVID-19. The Symptoma predictor is freely available online at https://www.symptoma.com.
Statistics of dislocation avalanches in FCC and BCC metals: dislocation mechanisms and mean swept distances across microsample sizes and temperatures
Authors: Alcalá Jorge , Očenášek Jan , Varillas Javier , A. El-Awady Jaafar , Wheeler Jeffrey M. , Michler Johann
Published: November 2020

Plastic deformation in crystalline materials consists of an ensemble of collective dislocation glide processes, which lead to strain burst emissions in micro-scale samples. To unravel the combined role of crystalline structure, sample size and temperature on these processes, we performed a comprehensive set of strict displacement-controlled micropillar compression experiments in conjunction with large-scale molecular dynamics and physics-based discrete dislocation dynamics simulations. The results indicate that plastic strain bursts consist of numerous individual dislocation glide events, which span over minuscule time intervals. The size distributions of these events exhibit a gradual transition from an incipient power-law slip regime (spanning $$\approx$$
≈
2.5 decades of slip sizes) to a large avalanche domain (spanning $$\approx$$
≈
4 decades of emission probability) at a cut-off slip magnitude $${s}_{\mathrm{c}}$$

s
c

. This cut-off slip provides a statistical measure to the characteristic mean dislocation swept distance, which allows for the scaling of the avalanche distributions vis-à-vis the archetypal dislocation mechanisms in face-centered cubic (FCC) and body-centered cubic (BCC) metals. Our statistical findings provide a new pathway to characterizing metal plasticity and towards comprehension of the sample size effects that limit the mechanical reliability in small-scale structures.
Driven progressive evolution of genome sequence complexity in Cyanobacteria
Authors: Moya Andrés , Oliver José L. , Verdú Miguel , Delaye Luis , Arnau Vicente , Bernaola-Galván Pedro , de la Fuente Rebeca , Díaz Wladimiro , Gómez-Martín Cristina , González Francisco M. , Latorre Amparo , Lebrón Ricardo , Román-Roldán Ramón
Published: November 2020

Progressive evolution, or the tendency towards increasing complexity, is a controversial issue in biology, which resolution entails a proper measurement of complexity. Genomes are the best entities to address this challenge, as they encode the historical information of a species’ biotic and environmental interactions. As a case study, we have measured genome sequence complexity in the ancient phylum Cyanobacteria. To arrive at an appropriate measure of genome sequence complexity, we have chosen metrics that do not decipher biological functionality but that show strong phylogenetic signal. Using a ridge regression of those metrics against root-to-tip distance, we detected positive trends towards higher complexity in three of them. Lastly, we applied three standard tests to detect if progressive evolution is passive or driven—the minimum, ancestor–descendant, and sub-clade tests. These results provide evidence for driven progressive evolution at the genome-level in the phylum Cyanobacteria.
Spatial distribution of stygobitic crustacean harpacticoids at the boundaries of groundwater habitat types in Europe
Authors: Iannella Mattia , Fiasca Barbara , Di Lorenzo Tiziana , Biondi Maurizio , Di Cicco Mattia , Galassi Diana M. P.
Published: November 2020

The distribution patterns of stygobitic crustacean harpacticoids at the boundaries of three different groundwater habitat types in Europe were analysed through a GIS proximity analysis and fitted to exponential models. The results showed that the highest frequency of occurrences was recorded in aquifers in consolidated rocks, followed by the aquifers in unconsolidated sediments and, finally, by the practically non-aquiferous rocks. The majority of the stygobitic harpacticoid species were not able to disperse across the boundaries between two adjacent habitats, with 66% of the species occurring in a single habitat type. The species were not evenly distributed, and 35–69% of them occurred from 2 to 6 km to the boundaries, depending on the adjacent habitat types. The distribution patterns were shaped by features extrinsic to the species, such as the hydrogeological properties of the aquifers, and by species’ intrinsic characteristics such as the preference for a given habitat type and dispersal abilities. Most boundaries between adjacent habitat types resulted to be “breaches”, that is transmissive borders for stygobitic harpacticoids, while others were “impermeable walls”, that is absorptive borders. Our results suggest that conservation measures of groundwater harpacticoids should consider how species are distributed within the different groundwater habitat types and at their boundaries to ensure the preservation of species metapopulations within habitat patches and beyond them.
On the correlation between material-induced cell shape and phenotypical response of human mesenchymal stem cells
Authors: Vasilevich Aliaksei S. , Vermeulen Steven , Kamphuis Marloes , Roumans Nadia , Eroumé Said , Hebels Dennie G. A. J. , van de Peppel Jeroen , Reihs Rika , Beijer Nick R. M. , Carlier Aurélie , Carpenter Anne E. , Singh Shantanu , de Boer Jan
Published: November 2020

Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. In this paper we were aiming to identify a universal set of genes that regulate the material-induced phenotypical response of human mesenchymal stem cells. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.
Description of neurotoxicity in a series of patients treated with CAR T-cell therapy
Authors: Belin Catherine , Devic Perrine , Ayrignac Xavier , Dos Santos Amélie , Paix Adrien , Sirven-Villaros Lila , Simard Claire , Lamure Sylvain , Gastinne Thomas , Ursu Renata , Berger Colette , Platon Laura , Tessoulin Benoît , Azoulay Elie , Wallet Florent , Thieblemont Catherine , Bachy Emmanuel , Cartron Guillaume , Laplaud David A. , Carpentier Antoine F.
Published: November 2020

Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine release syndrome and neurotoxicity. Between July 2018 and July 2019, all patients treated with CD19-targeted CAR T-cell therapy for relapsing lymphoma were followed-up longitudinally to describe neurological symptoms and their evolution over time. Four different French centres participated and 84 patients (median age 59 years, 31% females) were included. Neurotoxicity, defined as the presence of at least one neurological symptom appearing after treatment infusion, was reported in 43% of the patients. The median time to onset was 7 days after infusion with a median duration of 6 days. More than half of the patients (64%) had grade 1–2 severity and 34% had grade 3–4. CRS was observed in 80% of all patients. The most frequent neurological symptoms were cognitive signs, being severe in 36%, and were equally distributed between language disorders and cognitive disorders without language impairment. Non-pyramidal motor disorders, severe in 11%, were reported in 42% of the patients. Elevation of C-reactive protein (CRP) within 4 days after treatment was significantly correlated with the occurrence of grade 3–4 neurotoxicity. Although sometimes severe, neurotoxicity was almost always reversible. The efficacy of steroids and antiepileptic drugs remains unproven in the management of neurotoxicity. Neurotoxicity associated with CAR T-cell therapies occurs in more than 40% of patients. The clinical pattern is heterogeneous but cognitive disorders (not limited to language disorders) and, to a minor degree, non-pyramidal motor disorders, appeared as a signature of severe neurotoxicity.
Bone tissue morphology of rat offspring lactationally exposed to polychlorinated biphenyl 169 and 155
Authors: Brankovič Jana , Jan Janja , Fazarinc Gregor , Vrecl Milka
Published: November 2020

Polychlorinated biphenyls (PCBs) are ubiquitous, persistent, organic pollutants also considered endocrine-disrupting chemicals. Our study examined the effects of lactational exposure to nondioxin-like PCB-155 and/or dioxin-like PCB-169 on longitudinal femur growth at the distal epiphyseal growth plate (EGP) in young rats at three different ages [postnatal days (PNDs) 9, 22, and 42]. After delivery, lactating rats were divided into four groups (PCB-169, PCB-155, PCB-155 + 169, and control) and administered PCBs intraperitoneally. The femurs of offspring were used to estimate growth rate (µm/day), and histomorphometric analysis on the distal femur included the thickness of the EGP and zones of proliferation and hypertrophy with calcification. Stereometry was used to determine trabecular bone volume density. In the PCB-169 and PCB-155 + 169 groups, PCB-169 affected longitudinal bone growth in the early postnatal period by interfering with chondrocytes in the EGP zone of proliferation and, to a lesser extent, the zone of hypertrophy. Morphometric alterations in EGP structure diminished until puberty. A slow growth rate persisted in the PCB-169 group until PND 42, while in the PCB-155 group, a fast growth rate between PNDs 9 to 22 was significantly reduced between PNDs 22 to 42. Sterometric assessment showed decreased trabecular bone volume in the PCB-155 + 169 group compared with that in the control on PND 9 and increased in the PCB-169 group compared with that in the PCB-155 group on PND 42. To summarize, studied PCB congeners exerted congener- and age-dependent effects on femur growth rate and its histomorphometric characteristics.
Reproduction and signals regulating worker policing under identical hormonal control in social wasps
Authors: Oi Cintia Akemi , Brown Robert L. , da Silva Rafael Carvalho , Wenseleers Tom
Published: November 2020

In social Hymenoptera, fertility and fertility signalling are often under identical hormonal control, and it has been suggested that such hormonal pleiotropies can help to maintain signal honesty. In the common wasp Vespula vulgaris, for example, fertile queens have much higher juvenile hormone (JH) titers than workers, and JH also controls the production of chemical fertility cues present on the females’ cuticle. To regulate reproductive division of labour, queens use these fertility cues in two distinct ways: as queen pheromones that directly suppress the workers’ reproduction as well as to mark queen eggs and enable the workers to recognize and police eggs laid by other workers. Here, we investigated the hormonal pleiotropy hypothesis by testing if experimental treatment with the JH analogue methoprene could enable the workers to lay eggs that evade policing. In support of this hypothesis, we find that methoprene-treated workers laid more eggs, and that the chemical profiles of their eggs were more queen-like, thereby causing fewer of their eggs to be policed compared to in the control. Overall, our results identify JH as a key regulator of both reproduction and the production of egg marking pheromones that mediate policing behaviour in eusocial wasps.
A prospective observational prevalence study of elevated HbA1c among elective surgical patients
Authors: Teo L. M. , Lim W. Y. , Ke Y. , Sia I. K. L. , Gui C. H. , Abdullah H. R.
Published: November 2020

Type 2 Diabetes Mellitus (DM) is a chronic disease with high prevalence worldwide. Using glycated haemoglobin (HbA1c) as a surrogate for potential pre-DM and DM conditions, our primary objective was to determine the HbA1c epidemiology in non-cardiac elective surgical patients in Singapore. Our secondary aim was to identify risk factors associated with elevated HbA1c. We conducted a prospective, observational single-centre study in adult patients. HbA1c screening was performed. Patient demographics and comorbidities were recorded. Patients were divided into those with HbA1C ≤ 6.0% and HbA1C ≥ 6.1%. Regression analyses were performed to identify associated factors. Subgroup analysis was performed comparing patients with HbA1C ≥ 6.1% and HbA1C ≥ 8.0%. Of the 875 patients recruited, 182 (20.8%) had HbA1c ≥ 6.1%, of which 32 (3.7%) had HbA1c ≥ 8%. HbA1C ≥ 6.1% was associated with Indian ethnicity [1.07 (1.01–1.13), p = 0.023], BMI > 27.5 [1.07 (1.02–1.11), p = 0.002], higher preoperative random serum glucose [1.03 (1.02–1.04), p < 0.001], pre-existing diagnosis of DM [1.85 (1.75–1.96), p < 0.001] and prediabetes [1.44 (1.24–1.67), p < 0.001], and peripheral vascular disease [1.30 (1.10–1.54), p = 0.002]. HbA1c ≥ 8% had an additional association with age > 60 years [0.96 (0.93–0.99), p = 0.017]. The prevalence of elevated HbA1c is high among the surgical population. Targeted preoperative HbA1c screening for at-risk elective surgical patients reduces cost, allowing focused use of healthcare resources.
Efficacy of S-PRG filler containing varnishes on enamel demineralization prevention
Authors: Spinola Manuela da Silva , Moecke Sabrina Elise , Rossi Natália Rivoli , Nakatsuka Toshiyuki , Borges Alessandra Bühler , Torres Carlos Rocha Gomes
Published: November 2020

This study evaluated the efficacy of S-PRG vanishes on preventing enamel demineralization. Bovine enamel specimens were obtained, polished and the baseline Knoop microhardness was evaluated. Specimens were stratified into six groups (n = 15), according to the varnish applied: S10—experimental varnish containing 10% of S-PRG fillers, S20—20% of S-PRG fillers, S30—30% of S-PRG fillers; S40—40% of S-PRG fillers; PC (positive control)—5% of NaF; NC (negative control)—no treatment was performed. Half of enamel surfaces were protected to work as a control and varnishes were applied over the unprotected area. A demineralizing pH-cycling was performed, and surface and cross-sectional microhardness were measured. The percentage of microhardness of the treated area was calculated comparing with the untreated area. Statistical analysis was performed by one-way ANOVA and Tukey’s test (p = 5%). All experimental S-PRG varnishes protected against demineralization in relation to no treatment, but S40 was the most effective on the surface. For all depths, S30 and S40 were superior in enamel demineralization prevention than other S-PRG filler concentrations and 5% NaF. It was concluded that S-RPG filler containing varnishes were effective to prevent enamel demineralization. The higher concentrated products were more effective than 5% sodium fluoride on surface demineralization prevention.
Deep learning classification of early normal-tension glaucoma and glaucoma suspects using Bruch’s membrane opening-minimum rim width and RNFL
Authors: Seo Sat byul , Cho Hyun-kyung
Published: November 2020

We aimed to classify early normal-tension glaucoma (NTG) and glaucoma suspect (GS) using Bruch’s membrane opening-minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer (RNFL), and the color classification of RNFL based on a deep-learning model. Discriminating early-stage glaucoma and GS is challenging and a deep-learning model may be helpful to clinicians. NTG accounts for an average 77% of open-angle glaucoma in Asians. BMO-MRW is a new structural parameter that has advantages in assessing neuroretinal rim tissue more accurately than conventional parameters. A dataset consisted of 229 eyes out of 277 GS and 168 eyes of 285 patients with early NTG. A deep-learning algorithm was developed to discriminate between GS and early NTG using a training set, and its accuracy was validated in the testing dataset using the area under the curve (AUC) of the receiver operating characteristic curve (ROC). The deep neural network model (DNN) achieved highest diagnostic performance, with an AUC of 0.966 (95%confidence interval 0.929–1.000) in classifying either GS or early NTG, while AUCs of 0.927–0.947 were obtained by other machine-learning models. The performance of the DNN model considering all three OCT-based parameters was the highest (AUC 0.966) compared to the combinations of just two parameters. As a single parameter, BMO-MRW (0.959) performed better than RNFL alone (0.914).
De novo necroptosis creates an inflammatory environment mediating tumor susceptibility to immune checkpoint inhibitors
Authors: Workenhe Samuel T. , Nguyen Andrew , Bakhshinyan David , Wei Jiarun , Hare David N. , MacNeill Kelly L. , Wan Yonghong , Oberst Andrew , Bramson Jonathan L. , Nasir Jalees A. , Vito Alyssa , El-Sayes Nader , Singh Sheila K. , McArthur Andrew G. , Mossman Karen L.
Published: November 2020

Cancer immunotherapies using monoclonal antibodies to block inhibitory checkpoints are showing durable remissions in many types of cancer patients, although the majority of breast cancer patients acquire little benefit. Human melanoma and lung cancer patient studies suggest that immune checkpoint inhibitors are often potent in patients that already have intratumoral T cell infiltrate; although it remains unknown what types of interventions can result in an intratumoral T cell infiltrate in breast cancer. Using non-T cell-inflamed mammary tumors, we assessed what biological processes and downstream inflammation can overcome the barriers to spontaneous T cell priming. Here we show a specific type of combination therapy, consisting of oncolytic virus and chemotherapy, activates necroptosis and limits tumor growth in autochthonous tumors. Combination therapy activates proinflammatory cytokines; intratumoral influx of myeloid cells and cytotoxic T cell infiltrate in locally treated and distant autochthonous tumors to render them susceptible to immune checkpoint inhibitors.
Hydrolysis of doped conducting polymers
Authors: Sethumadhavan Vithyasaahar , Zuber Kamil , Bassell Christopher , Teasdale Peter R. , Evans Drew
Published: November 2020

Conducting polymers display a range of interesting properties, from electrical conduction to tunable optical absorption and mechanical flexibility, to name but a few. Their properties arise from positive charges (carbocations) on their conjugated backbone that are stabilised by counterions doped in the polymer matrix. In this research we report hydrolysis of these carbocations when poly(3,4-ethylenedioxy thiophene) is exposed to 1 mM aqueous salt solutions. Remarkably, two classes of anion interactions are revealed; anions that oxidise PEDOT via a doping process, and those that facilitate the SN1 hydrolysis of the carbocation to create hydroxylated PEDOT. A pKa of 6.4 for the conjugate acid of the anion approximately marks the transition between chemical oxidation and hydrolysis. PEDOT can be cycled between hydrolysis and oxidation by alternating exposure to different salt solutions. This has ramifications for using doped conducting polymers in aqueous environments (such as sensing, energy storage and biomedical devices).