bluuebunny/crossref_metadata_2025 huggingface dataset:
Nodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer
Authors: Cascone Tina , Weissferdt Annikka , Godoy Myrna C. B. , William William N. , Leung Cheuk H. , Lin Heather Y. , Basu Sreyashi , Yadav Shalini S. , Pataer Apar , Mitchell Kyle G. , Khan Md Abdul Wadud , Shi Yushu , Haymaker Cara , Solis Luisa M. , Parra Edwin R. , Kadara Humam , Wistuba Ignacio I. , Sharma Padmanee , Allison James P. , Ajami Nadim J. , Wargo Jennifer A. , Jenq Robert R. , Gibbons Don L. , Lee J. Jack , Swisher Stephen G. , Vaporciyan Ara A. , Heymach John V. , Sepesi Boris
Published: August 2021

Radiographic imaging is the standard approach for evaluating the disease involvement of lymph nodes in patients with operable NSCLC although the impact of neoadjuvant immune checkpoint inhibitors (ICIs) on lymph nodes has not yet been characterized. Herein, we present an ad hoc analysis of the NEOSTAR trial (NCT03158129) where we observed a phenomenon we refer to as “nodal immune flare” (NIF) in which patients treated with neoadjuvant ICIs demonstrate radiologically abnormal nodes post-therapy that upon pathological evaluation are devoid of cancer and demonstrate de novo non-caseating granulomas. Abnormal lymph nodes are analyzed by computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computer tomography to evaluate the size and the maximum standard uptake value post- and pre-therapy in NEOSTAR and an independent neoadjuvant chemotherapy cohort. NIF occurs in 16% (7/44) of patients treated with ICIs but in 0% (0/28) of patients after neoadjuvant chemotherapy. NIF is associated with an inflamed nodal immune microenvironment and with fecal abundance of genera belonging to the family Coriobacteriaceae of phylum Actinobacteria, but not with tumor responses or treatment-related toxicity. Our findings suggest that this apparent radiological cancer progression in lymph nodes may occur due to an inflammatory response after neoadjuvant immunotherapy, and such cases should be evaluated by pathological examination to distinguish NIF from true nodal progression and to ensure appropriate clinical treatment planning.
Dynamics of moisture diffusion and adsorption in plant cuticles including the role of cellulose
Authors: Tredenick E. C. , Farquhar G. D.
Published: August 2021

Food production must increase significantly to sustain a growing global population. Reducing plant water loss may help achieve this goal and is especially relevant in a time of climate change. The plant cuticle defends leaves against drought, and so understanding water movement through the cuticle could help future proof our crops and better understand native ecology. Here, via mathematical modelling, we identify mechanistic properties of water movement in cuticles. We model water sorption in astomatous isolated cuticles, utilising three separate pathways of cellulose, aqueous pores and lipophilic. The model compares well to data both over time and humidity gradients. Sensitivity analysis shows that the grouping of parameters influencing plant species variations has the largest effect on sorption, those influencing cellulose are very influential, and aqueous pores less so but still relevant. Cellulose plays a significant role in diffusion and adsorption in the cuticle and the cuticle surfaces.
Methyl groups as widespread Lewis bases in noncovalent interactions
Authors: Loveday Oliver , Echeverría Jorge
Published: August 2021

It is well known that, under certain conditions, C(sp3) atoms behave, via their σ-hole, as Lewis acids in tetrel bonding. Here, we show that methyl groups, when bound to atoms less electronegative than carbon, can counterintuitively participate in noncovalent interactions as electron density donors. Thousands of experimental structures are found in which methyl groups behave as Lewis bases to establish alkaline, alkaline earth, triel, tetrel, pnictogen, chalcogen and halogen bonds. Theoretical calculations confirm the high directionality and significant strength of the interactions that arise from a common pattern based on the electron density holes model. Moreover, despite the absence of lone pairs, methyl groups are able to transfer charge from σ bonding orbitals into empty orbitals of the electrophile to reinforce the attractive interaction.
SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation
Authors: Steens Jurre A. , Zhu Yifan , Taylor David W. , Bravo Jack P. K. , Prinsen Stijn H. P. , Schoen Cor D. , Keijser Bart J. F. , Ossendrijver Michel , Hofstra L. Marije , Brouns Stan J. J. , Shinkai Akeo , van der Oost John , Staals Raymond H. J.
Published: August 2021

Characteristic properties of type III CRISPR-Cas systems include recognition of target RNA and the subsequent induction of a multifaceted immune response. This involves sequence-specific cleavage of the target RNA and production of cyclic oligoadenylate (cOA) molecules. Here we report that an exposed seed region at the 3′ end of the crRNA is essential for target RNA binding and cleavage, whereas cOA production requires base pairing at the 5′ end of the crRNA. Moreover, we uncover that the variation in the size and composition of type III complexes within a single host results in variable seed regions. This may prevent escape by invading genetic elements, while controlling cOA production tightly to prevent unnecessary damage to the host. Lastly, we use these findings to develop a new diagnostic tool, SCOPE, for the specific detection of SARS-CoV-2 from human nasal swab samples, revealing sensitivities in the atto-molar range.
Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America
Authors: Herzog Josef S. , Chavarri-Guerra Yanin , Castillo Danielle , Abugattas Julio , Villarreal-Garza Cynthia , Sand Sharon , Clague-Dehart Jessica , Alvarez-Gómez Rosa M. , Wegman-Ostrosky Talia , Mohar Alejandro , Mora Pamela , Del Toro-Valero Azucena , Daneri-Navarro Adrian , Rodriguez Yenni , Cruz-Correa Marcia , Ashton-Prolla Patricia , Alemar Bárbara , Mejia Rosa , Gallardo Lenny , Shaw Robin , Yang Kai , Cervantes Aleck , Tsang Kevin , Nehoray Bita , Barrera Saldana Hugo , Neuhausen Susan , Weitzel Jeffrey N.
Published: August 2021

The prevalence and contribution ofBRCA1/2(BRCA) pathogenic variants (PVs) to the cancer burden in Latin America are not well understood. This study aims to address this disparity.BRCAanalyses were performed on prospectively enrolled Latin American Clinical Cancer Genomics Community Research Network participants via a combination of methods: a Hispanic Mutation Panel (HISPANEL) on MassARRAY; semiconductor sequencing; and copy number variant (CNV) detection.BRCAPV probability was calculated using BRCAPRO. Among 1,627 participants (95.2% with cancer), we detected 236 (14.5%) BRCA PVs; 160BRCA1(31% CNVs); 76BRCA2PV frequency varied by country: 26% Brazil, 9% Colombia, 13% Peru, and 17% Mexico. Recurrent PVs (seen ≥3 times), some region-specific, represented 42.8% (101/236) of PVs. There was no ClinVar entry for 14% (17/125) of unique PVs, and 57% (111/196) of unique VUS. The area under the ROC curve for BRCAPRO was 0.76. In summary, we implemented a low-costBRCAtesting strategy and documented a significant burden of non-ClinVar reportedBRCAPVs among Latin Americans. There are recurrent, population-specific PVs and CNVs, and we note that the BRCAPRO mutation probability model performs adequately. This study helps address the gap in our understanding ofBRCA-associated cancer in Latin America.
Common workflows for computing material properties using different quantum engines
Authors: Huber Sebastiaan P. , Bosoni Emanuele , Bercx Marnik , Bröder Jens , Degomme Augustin , Dikan Vladimir , Eimre Kristjan , Flage-Larsen Espen , Garcia Alberto , Genovese Luigi , Gresch Dominik , Johnston Conrad , Petretto Guido , Poncé Samuel , Rignanese Gian-Marco , Sewell Christopher J. , Smit Berend , Tseplyaev Vasily , Uhrin Martin , Wortmann Daniel , Yakutovich Aliaksandr V. , Zadoks Austin , Zarabadi-Poor Pezhman , Zhu Bonan , Marzari Nicola , Pizzi Giovanni
Published: August 2021

The prediction of material properties based on density-functional theory has become routinely common, thanks, in part, to the steady increase in the number and robustness of available simulation packages. This plurality of codes and methods is both a boon and a burden. While providing great opportunities for cross-verification, these packages adopt different methods, algorithms, and paradigms, making it challenging to choose, master, and efficiently use them. We demonstrate how developing common interfaces for workflows that automatically compute material properties greatly simplifies interoperability and cross-verification. We introduce design rules for reusable, code-agnostic, workflow interfaces to compute well-defined material properties, which we implement for eleven quantum engines and use to compute various material properties. Each implementation encodes carefully selected simulation parameters and workflow logic, making the implementer’s expertise of the quantum engine directly available to non-experts. All workflows are made available as open-source and full reproducibility of the workflows is guaranteed through the use of the AiiDA infrastructure.
Exploring human-genome gut-microbiome interaction in Parkinson’s disease
Authors: Wallen Zachary D. , Stone William J. , Factor Stewart A. , Molho Eric , Zabetian Cyrus P. , Standaert David G. , Payami Haydeh
Published: August 2021

The causes of complex diseases remain an enigma despite decades of epidemiologic research on environmental risks and genome-wide studies that have uncovered tens or hundreds of susceptibility loci for each disease. We hypothesize that the microbiome is the missing link. Genetic studies have shown that overexpression of alpha-synuclein, a key pathological protein in Parkinson’s disease (PD), can cause familial PD and variants at alpha-synuclein locus confer risk of idiopathic PD. Recently, dysbiosis of gut microbiome in PD was identified: altered abundances of three microbial clusters were found, one of which was composed of opportunistic pathogens. Using two large datasets, we found evidence that the overabundance of opportunistic pathogens in PD gut is influenced by the host genotype at the alpha-synuclein locus, and that the variants responsible modulate alpha-synuclein expression. Results put forth testable hypotheses on the role of gut microbiome in the pathogenesis of PD, the incomplete penetrance of PD susceptibility genes, and potential triggers of pathology in the gut.
Codominant IgG and IgA expression with minimal vaccine mRNA in milk of BNT162b2 vaccinees
Authors: Low Jia Ming , Gu Yue , Ng Melissa Shu Feng , Amin Zubair , Lee Le Ye , Ng Yvonne Peng Mei , Shunmuganathan Bhuvaneshwari D/O , Niu Yuxi , Gupta Rashi , Tambyah Paul Anantharajah , MacAry Paul A. , Wang Liang Wei , Zhong Youjia
Published: August 2021

Lactating women can produce protective antibodies in their milk after vaccination, which has informed antenatal vaccination programs for diseases such as influenza and pertussis. However, whether SARS-CoV-2-specific antibodies are produced in human milk as a result of COVID-19 vaccination is still unclear. In this study, we show that lactating mothers who received the BNT162b2 vaccine secreted SARS-CoV-2-specific IgA and IgG antibodies into milk, with the most significant increase at 3–7 days post-dose 2. Virus-specific IgG titers were stable out to 4–6 weeks after dose 2. In contrast, SARS-CoV-2-specific IgA levels showed substantial decay. Vaccine mRNA was detected in few milk samples (maximum of 2 ng/ml), indicative of minimal transfer. Additionally, infants who consumed post-vaccination human milk had no reported adverse effects up to 28 days post-ingestion. Our results define the safety and efficacy profiles of the vaccine in this demographic and provide initial evidence for protective immunity conferred by milk-borne SARS-CoV-2-specific antibodies. Taken together, our study supports recommendations for uninterrupted breastfeeding subsequent to mRNA vaccination against COVID-19.
Lenghu on the Tibetan Plateau as an astronomical observing site
Authors: Deng Licai , Yang Fan , Chen Xiaodian , He Fei , Liu Qili , Zhang Bo , Zhang Chunguang , Wang Kun , Liu Nian , Ren Anbing , Luo Zhiquan , Yan Zhengzhou , Tian Jianfeng , Pan Jun
Published: August 2021

On Earth’s surface, there are only a handful of high-quality astronomical sites that meet the requirements for very large next-generation facilities. In the context of scientific opportunities in time-domain astronomy, a good site on the Tibetan Plateau will bridge the longitudinal gap between the known best sites1,2 (all in the Western Hemisphere). The Tibetan Plateau is the highest plateau on Earth, with an average elevation of over 4,000 metres, and thus potentially provides very good opportunities for astronomy and particle astrophysics3–5. Here we report the results of three years of monitoring of testing an area at a local summit on Saishiteng Mountain near Lenghu Town in Qinghai Province. The altitudes of the potential locations are between 4,200 and 4,500 metres. An area of over 100,000 square kilometres surrounding Lenghu Town has a lower altitude of below 3,000 metres, with an extremely arid climate and unusually clear local sky (day and night)6. Of the nights at the site, 70 per cent have clear, photometric conditions, with a median seeing of 0.75 arcseconds. The median night temperature variation is only 2.4 degrees Celsius, indicating very stable local surface air. The precipitable water vapour is lower than 2 millimetres for 55 per cent of the night.
Separating microparticles by material and size using dielectrophoretic chromatography with frequency modulation
Authors: Giesler Jasper , Weirauch Laura , Thöming Jorg , Baune Michael , Pesch Georg R.
Published: August 2021

Separation of (biological) particles ($$\ll {10}~{\upmu }\text {m}$$

≪
10

μ
m

) according to size or other properties is an ongoing challenge in a variety of technical relevant fields. Dielectrophoresis is one method to separate particles according to a diversity of properties, and within the last decades a pool of dielectrophoretic separation techniques has been developed. However, many of them either suffer selectivity or throughput. We use simulation and experiments to investigate retention mechanisms in a novel DEP scheme, namely, frequency-modulated DEP. Results from experiments and simulation show a good agreement for the separation of binary PS particles mixtures with respect to size and more importantly, for the challenging task of separating equally sized microparticles according to surface functionalization alone. The separation with respect to size was performed using 2 $${\upmu }$$
μ
m and 3 $${\upmu }$$
μ
m sized particles, whereas separation with respect to surface functionalization was performed with 2 $${\upmu }$$
μ
m particles. The results from this study can be used to solve challenging separation tasks, for example to separate particles with distributed properties.
Elevated temperature and browning increase dietary methylmercury, but decrease essential fatty acids at the base of lake food webs
Authors: Wu Pianpian , Kainz Martin J. , Valdés Fernando , Zheng Siwen , Winter Katharina , Wang Rui , Branfireun Brian , Chen Celia Y. , Bishop Kevin
Published: August 2021

Climate change scenarios predict increases in temperature and organic matter supply from land to water, which affect trophic transfer of nutrients and contaminants in aquatic food webs. How essential nutrients, such as polyunsaturated fatty acids (PUFA), and potentially toxic contaminants, such as methylmercury (MeHg), at the base of aquatic food webs will be affected under climate change scenarios, remains unclear. The objective of this outdoor mesocosm study was to examine how increased water temperature and terrestrially-derived dissolved organic matter supply (tDOM; i.e., lake browning), and the interaction of both, will influence MeHg and PUFA in organisms at the base of food webs (i.e. seston; the most edible plankton size for zooplankton) in subalpine lake ecosystems. The interaction of higher temperature and tDOM increased the burden of MeHg in seston (< 40 μm) and larger sized plankton (microplankton; 40–200 μm), while the MeHg content per unit biomass remained stable. However, PUFA decreased in seston, but increased in microplankton, consisting mainly of filamentous algae, which are less readily bioavailable to zooplankton. We revealed elevated dietary exposure to MeHg, yet decreased supply of dietary PUFA to aquatic consumers with increasing temperature and tDOM supply. This experimental study provides evidence that the overall food quality at the base of aquatic food webs deteriorates during ongoing climate change scenarios by increasing the supply of toxic MeHg and lowering the dietary access to essential nutrients of consumers at higher trophic levels.
Distribution of pathogens and antimicrobial resistance in ICU-bloodstream infections during hospitalization: a nationwide surveillance study
Authors: Sommerstein Rami , Damonti Lauro , Marschall Jonas , Harbarth Stephan , Gasser Michael , Kronenberg Andreas , Buetti Niccolò
Published: August 2021

Changing microorganism distributions and decreasing antibiotic susceptibility over the duration of hospitalization have been described for the colonization or infection of selected organ systems. Few data are available on bacteremias in the intensive care unit (ICU) setting. We conducted a nationwide study on bloodstream infection (BSI) using data from the Swiss Centre for Antibiotic Resistance (ANRESIS). We analyzed data on BSI detected in the ICU from hospitals that sent information on a regular basis during the entire study period (2008–2017). We described specific trends of pathogen distribution and resistance during hospitalization duration. We included 6505 ICU- BSI isolates from 35 Swiss hospitals. We observed 2587 possible skin contaminants, 3788 bacteremias and 130 fungemias. The most common microorganism was Escherichia coli (23.2%, 910), followed by Staphylococcus aureus (18.7%, 734) and enterococci (13.1%, 515). Enterococcus spp (p < 0.0001) and Candida spp (p < 0.0001) increased in proportion, whereas E. coli (p < 0.0001) and S. aureus (p < 0.0001) proportions decreased during hospitalization. Resistances against first- and second-line antibiotics increased linearly during hospitalization. Pathogen distribution and antimicrobial resistance in ICU-BSI depends on the duration of the hospitalization. The proportion of enterococcal BSI, candidemia and resistant microorganisms against first- and second-line antibiotics increased during hospitalization.
Fine-grained data reveal segregated mobility networks and opportunities for local containment of COVID-19
Authors: Fan Chao , Lee Ronald , Yang Yang , Mostafavi Ali
Published: August 2021

Deriving effective mobility control measures is critical for the control of COVID-19 spreading. In response to the COVID-19 pandemic, many countries and regions implemented travel restrictions and quarantines to reduce human mobility and thus reduce virus transmission. But since human mobility decreased heterogeneously, we lack empirical evidence of the extent to which the reductions in mobility alter the way people from different regions of cities are connected, and what containment policies could complement mobility reductions to conquer the pandemic. Here, we examined individual movements in 21 of the most affected counties in the United States, showing that mobility reduction leads to a segregated place network and alters its relationship with pandemic spread. Our findings suggest localized area-specific policies, such as geo-fencing, as viable alternatives to city-wide lockdown for conquering the pandemic after mobility was reduced.
A randomized-controlled neurofeedback trial in adult attention-deficit/hyperactivity disorder
Authors: Barth Beatrix , Mayer-Carius Kerstin , Strehl Ute , Wyckoff Sarah N. , Haeussinger Florian B. , Fallgatter Andreas J. , Ehlis Ann-Christine
Published: August 2021

Attention-deficit/hyperactivity disorder (ADHD) is a childhood onset disorder persisting into adulthood for a large proportion of cases. Neurofeedback (NF) has shown promising results in children with ADHD, but randomized controlled trials in adults with ADHD are scarce. We aimed to compare slow cortical potential (SCP)- and functional near-infrared spectroscopy (fNIRS) NF to a semi-active electromyography biofeedback (EMG-BF) control condition regarding changes in symptoms and the impact of learning success, as well as changes in neurophysiological parameters in an adult ADHD population. Patients were randomly assigned to SCP-NF (n = 26), fNIRS-NF (n = 21) or EMG-BF (n = 20). Outcome parameters were assessed over 30 training sessions (pre, intermediate, post) and at 6-months follow-up (FU) including 3 booster sessions. EEG was recorded during two auditory Go/NoGo paradigms assessing the P300 and contingent negative variation (CNV). fNIRS measurements were conducted during an n-back- as well as a Go/NoGo task. All three groups showed equally significant symptom improvements suggesting placebo- or non-specific effects on the primary outcome measure. Only when differentiating between learners and non-learners, fNIRS learners displayed stronger reduction of ADHD global scores compared to SCP non-learners at FU, and fNIRS learners showed specifically low impulsivity ratings. 30.8% in the SCP-NF and 61.9% of participants in the fNIRS-NF learned to regulate the respective NF target parameter. We conclude that some adults with ADHD learn to regulate SCP amplitudes and especially prefrontal hemodynamic activity during NF. We did not find any significant differences in outcome between groups when looking at the whole sample. When evaluating learners only, they demonstrate superior effects as compared to non-learners, which suggests specific effects in addition to non-specific effects of NF when learning occurs.
Crag Martin neontology complements taphonomy at the Gorham's Cave Complex
Authors: Bensusan Keith , Holmes Tyson Lee , Perez Charles , Finlayson Geraldine , Finlayson Stewart , Guillem Rhian , Finlayson Clive
Published: August 2021

Species present in the fossil record may continue to exist at an archaeological site, allowing study that fine-tunes our picture of the ecological past. A large wintering population of Eurasian Crag MartinsPtyonoprogne rupestris(ECM) roosts at the ‘Gorham’s Cave Complex’ UNESCO World Heritage site in Gibraltar, which is best known for its occupation by Neanderthals at times when ECMs were also present. Its complex geomorphology allows the study of use of different micro-sites (caves) within the roost. We used mark-recapture to test whether birds showed fidelity to micro-sites for roosting, and for differences in condition of birds across micro-sites. ECM showed very high fidelity towards micro-sites, within and between years, with > 90% chance of recapture at caves where they were first caught. Condition of birds differed between micro-sites, suggesting differences in roost quality between caves; birds were more likely to be recaptured at the micro-site where birds were in best condition, indicating higher survivorship. Our results demonstrate extremely fine-scale fidelity at the largest roosting site documented for ECM globally. Implications for conservation are discussed. The study provides current knowledge of a bird that has been using these caves since the Pleistocene and more generally on these caves as refuges.
Predicting pediatric anxiety from the temporal pole using neural responses to emotional faces
Authors: Sawalha Jeffrey , Yousefnezhad Muhammad , Selvitella Alessandro M. , Cao Bo , Greenshaw Andrew J. , Greiner Russell
Published: August 2021

A prominent cognitive aspect of anxiety is dysregulation of emotional interpretation of facial expressions, associated with neural activity from the amygdala and prefrontal cortex. We report machine learning analysis of fMRI results supporting a key role for a third area, the temporal pole (TP) for childhood anxiety in this context. This finding is based on differential fMRI responses to emotional faces (angry versus fearful faces) in children with one or more of generalized anxiety, separation anxiety, and social phobia (n = 22) compared with matched controls (n = 23). In our machine learning (Adaptive Boosting) model, the right TP distinguished anxious from control children (accuracy = 81%). Involvement of the TP as significant for neurocognitive aspects of pediatric anxiety is a novel finding worthy of further investigation.
Hybrid nanofluid flow through a spinning Darcy–Forchheimer porous space with thermal radiation
Authors: Saeed Anwar , Jawad Muhammad , Alghamdi Wajdi , Nasir Saleem , Gul Taza , Kumam Poom
Published: August 2021

This work investigates numerically the solution of Darcy–Forchheimer flow for hybrid nanofluid by employing the slip conditions. Basically, the fluid flow is produced by a swirling disk and is exposed to thermal stratification along with non-linear thermal radiation for controlling the heat transfer of the flow system. In this investigation, the nanoparticles of titanium dioxide and aluminum oxide have been suspended in water as base fluid. Moreover, the Darcy–Forchheimer expression is used to characterize the porous spaces with variable porosity and permeability. The resulting expressions of motion, energy and mass transfer in dimensionless form have been solved by HAM (Homotopy analysis method). In addition, the influence of different emerging factors upon flow system has been disputed both theoretically in graphical form and numerically in the tabular form. During this effort, it has been recognized that velocities profiles augment with growing values of mixed convection parameter while thermal characteristics enhance with augmenting values of radiation parameters. According to the findings, heat is transmitted more quickly in hybrid nanofluid than in traditional nanofluid. Furthermore, it is estimated that the velocities of fluid $$f^{\prime}\left( \xi \right),g\left( \xi \right)$$

f
′

ξ

,
g

ξ

are decayed for high values of $$\phi_{1} ,\phi_{2} ,\,Fr$$

ϕ
1

,

ϕ
2

,

F
r

and $$k_{1}$$

k
1

factors.
Histology and μCT reveal the unique evolution and development of multiple tooth rows in the synapsid Endothiodon
Authors: Olroyd Savannah L. , LeBlanc Aaron R. H. , Araújo Ricardo , Angielczyk Kenneth D. , Duhamel Aliénor , Benoit Julien , Amaral Marisa
Published: August 2021

Several amniote lineages independently evolved multiple rows of marginal teeth in response to the challenge of processing high fiber plant matter. Multiple tooth rows develop via alterations to tooth replacement in captorhinid reptiles and ornithischian dinosaurs, but the specific changes that produce this morphology differ, reflecting differences in their modes of tooth attachment. To further understand the mechanisms by which multiple tooth rows can develop, we examined this feature in Endothiodon bathystoma, a member of the only synapsid clade (Anomodontia) to evolve a multi-rowed marginal dentition. We histologically sampled Endothiodon mandibles with and without multiple tooth rows as well as single-rowed maxillae. We also segmented functional and replacement teeth in µ-CT scanned mandibles and maxillae of Endothiodon and several other anomodonts with ‘postcanine’ teeth to characterize tooth replacement in the clade. All anomodonts in our sample displayed a space around the tooth roots for a soft tissue attachment between tooth and jaw in life. Trails of alveolar bone indicate varying degrees of labial migration of teeth through ontogeny, often altering the spatial relationships of functional and replacement teeth in the upper and lower jaws. We present a model of multiple tooth row development in E. bathystoma in which labial migration of functional teeth was extensive enough to prevent resorption and replacement by newer generations of teeth. This model represents another mechanism by which multiple tooth rows evolved in amniotes. The multiple tooth rows of E. bathystoma may have provided more extensive contact between the teeth and a triturating surface on the palatine during chewing.
Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
Authors: Thomas Chloe N. , Bernardo-Colón Alexandra , Courtie Ella , Essex Gareth , Rex Tonia S. , Blanch Richard J. , Ahmed Zubair
Published: August 2021

Ocular repeated air blast injuries occur from low overpressure blast wave exposure, which are often repeated and in quick succession. We have shown that caspase-2 caused the death of retinal ganglion cells (RGC) after blunt ocular trauma. Here, we investigated if caspase-2 also mediates RGC apoptosis in a mouse model of air blast induced indirect traumatic optic neuropathy (b-ITON). C57BL/6 mice were exposed to repeated blasts of overpressure air (3 × 2 × 15 psi) and intravitreal injections of siRNA against caspase-2 (siCASP2) or against a control enhanced green fluorescent protein (siEGFP) at either 5 h after the first 2 × 15 psi (“post-blast”) or 48 h before the first blast exposure (“pre-blast”) and repeated every 7 days. RGC counts were unaffected by the b-ITON or intravitreal injections, despite increased degenerating ON axons, even in siCASP2 “post-blast” injection groups. Degenerating ON axons remained at sham levels after b-ITON and intravitreal siCASP2 “pre-blast” injections, but with less degenerating axons in siCASP2 compared to siEGFP-treated eyes. Intravitreal injections “post-blast” caused greater vitreous inflammation, potentiated by siCASP2, with less in “pre-blast” injected eyes, which was abrogated by siCASP2. We conclude that intravitreal injection timing after ocular trauma induced variable retinal and ON pathology, undermining our candidate neuroprotective therapy, siCASP2.
A panel of DNA methylation biomarkers for detection and improving diagnostic efficiency of lung cancer
Authors: Wei Bing , Wu Fengxin , Xing Wenqun , Sun Haibo , Yan Chi , Zhao Chengzhi , Wang Dongqing , Chen Xiaobing , Chen Yanli , Li Mingming , Ma Jie
Published: August 2021

Lung cancer remains the leading cause of cancer deaths worldwide. Although low-dose spiral computed tomography (LDCT) screening is used for the detection of lung cancer in a high-risk population, false-positive results of LDCT remain a clinical problem. Here, we developed a blood test of a novel panel of three established lung cancer methylation biomarkers for lung cancer detection. Short stature homeobox 2 gene (SHOX2), ras association domain family 1A gene (RASSF1A), and prostaglandin E receptor 4 gene (PTGER4) methylation was analyzed in a training cohort of 351 individuals (197 controls, 154 cases) and validated from an independent cohort of 149 subjects (89 controls, 60 cases). The novel panel biomarkers distinguished between malignant and benign lung disease at high sensitivity and specificity: 87.0% sensitivity [95% CI 80.2–91.5%], 98.0% specificity [95% CI 94.9–99.4%]. Sensitivity in adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and other lung cancer was 89.0%, 87.5%, 85.7%, and 77.8%, respectively. Notably, cancer patients in stage I and II showed high diagnostic sensitivity at 82.5% and 90.5%, respectively. Moreover, the diagnostic efficiency did not show bias toward age, gender, smoking, and the presence of other (nonlung) cancers. The performance of the panel in the validation cohort confirmed the diagnostic value. These findings clearly showed that this panel of DNA methylation biomarkers was effective in detecting lung cancer noninvasively and may provide clinical utility in stand-alone or in combination with current imaging techniques to improve the diagnosis of lung cancer.
Identities, concentrations, and sources of pesticide exposure in pollen collected by managed bees during blueberry pollination
Authors: Graham Kelsey K. , Milbrath Meghan O. , Zhang Yajun , Soehnlen Annuet , Baert Nicolas , McArt Scott , Isaacs Rufus
Published: August 2021

Bees are critical for crop pollination, but there is limited information on levels and sources of pesticide exposure in commercial agriculture. We collected pollen from foraging honey bees and bumble bees returning to colonies placed in blooming blueberry fields with different management approaches (conventional, organic, unmanaged) and located across different landscape settings to determine how these factors affect pesticide exposure. We also identified the pollen and analyzed whether pesticide exposure was correlated with corbicular load composition. Across 188 samples collected in 2 years, we detected 80 of the 259 pesticide active ingredients (AIs) screened for using a modified QuEChERS method. Detections included 28 fungicides, 26 insecticides, and 21 herbicides. All samples contained pesticides (mean = 22 AIs per pollen sample), with pollen collected from bees on conventional fields having significantly higher average concentrations (2019 mean = 882.0 ppb) than those on unmanaged fields (2019 mean = 279.6 ppb). Pollen collected by honey bees had more AIs than pollen collected by bumble bees (mean = 35 vs. 19 AIs detected at each farm, respectively), whereas samples from bumble bees had higher average concentrations, likely reflecting differences in foraging behavior. Blueberry pollen was more common in pollen samples collected by bumble bees (25.9% per sample) than honey bees (1.8%), though pesticide concentrations were only correlated with blueberry pollen for honey bees. Pollen collected at farms with more blueberry in the surrounding landscape had higher pesticide concentrations, mostly AIs applied for control of blueberry pathogens and pests during bloom. However, for honey bees, the majority of AIs detected at each farm are not registered for use on blueberry at any time (55.2% of AIs detected), including several highly toxic insecticides. These AIs therefore came from outside the fields and farms they are expected to pollinate. For bumble bees, the majority of AIs detected in their pollen are registered for use on blueberry during bloom (56.9% of AIs detected), though far fewer AIs were sprayed at the focal farm (16.7%). Our results highlight the need for integrated farm and landscape-scale stewardship of pesticides to reduce exposure to pollinators during crop pollination.
Intermediate ice scour disturbance is key to maintaining a peak in biodiversity within the shallows of the Western Antarctic Peninsula
Authors: Robinson B. J. O. , Barnes D. K. A. , Grange L. J. , Morley S. A.
Published: August 2021

Climate-related disturbance regimes are changing rapidly with profound consequences for ecosystems. Disturbance is often perceived as detrimental to biodiversity; however, the literature is divided on how they influence each other. Disturbance events in nature are diverse, occurring across numerous interacting trophic levels and multiple spatial and temporal scales, leading to divergence between empirical and theoretical studies. The shallow Antarctic seafloor has one of the largest disturbance gradients on earth, due to iceberg scouring. Scour rates are changing rapidly along the Western Antarctic Peninsula because of climate change and with further changes predicted, the Antarctic benthos will likely undergo dramatic shifts in diversity. We investigated benthic macro and megafaunal richness across 10–100 m depth range, much of which, 40–100 m, has rarely been sampled. Macro and megafauna species richness peaked at 50–60 m depth, a depth dominated by a diverse range of sessile suspension feeders, with an intermediate level of iceberg disturbance. Our results show that a broad range of disturbance values are required to detect the predicted peak in biodiversity that is consistent with the Intermediate Disturbance Hypothesis, suggesting ice scour is key to maintaining high biodiversity in Antarctica’s shallows.
Biomimetic reduced graphene oxide coated collagen scaffold for in situ bone regeneration
Authors: Bahrami Sajad , Baheiraei Nafiseh , Shahrezaee Mostafa
Published: August 2021

A variety of bone-related diseases and injures and limitations of traditional regeneration methods require new tissue substitutes. Tissue engineering and regeneration combined with nanomedicine can provide different natural or synthetic and combined scaffolds with bone mimicking properties for implantation in the injured area. In this study, we synthesized collagen (Col) and reduced graphene oxide coated collagen (Col-rGO) scaffolds, and we evaluated their in vitro and in vivo effects on bone tissue repair. Col and Col-rGO scaffolds were synthesized by chemical crosslinking and freeze-drying methods. The surface topography, and the mechanical and chemical properties of scaffolds were characterized, showing three-dimensional (3D) porous scaffolds and successful coating of rGO on Col. The rGO coating enhanced the mechanical strength of Col-rGO scaffolds to a greater extent than Col scaffolds by 2.8 times. Furthermore, Col-rGO scaffolds confirmed that graphene addition induced no cytotoxic effects and enhanced the viability and proliferation of human bone marrow-derived mesenchymal stem cells (hBMSCs) with 3D adherence and expansion. Finally, scaffold implantation into rabbit cranial bone defects for 12 weeks showed increased bone formation, confirmed by Hematoxylin–Eosin (H&E) and alizarin red staining. Overall, the study showed that rGO coating improves Col scaffold properties and could be a promising implant for bone injuries.
Nutrient-related metabolite profiles explain differences in body composition and size in Nile tilapia (Oreochromis niloticus) from different lakes
Authors: Bayissa Tokuma Negisho , Geerardyn Michelle , Vanhauteghem Donna , Wakjira Mulugeta , Janssens Geert Paul Jules
Published: August 2021

This study investigated how metabolite analysis can explain differences in tissue composition and size in fish from different habitats. We, therefore, studied Nile tilapia (Oreochromis niloticus) from three Ethiopian lakes (Gilgel Gibe, Ziway, and Langano) using dried bloodspot (DBS) analysis of carnitine esters and free amino acids. A total of sixty (N = 60) Nile tilapia samples were collected comprising twenty (n = 20) fish from each lake. The proximate composition of the targeted tissues (muscle, skin, gill, gut, and liver) were analyzed. The DBS samples were analyzed for acylcarnitine and free amino acid profiles using quantitative electrospray tandem mass spectrometry. Metabolite ratios were calculated from relevant biochemical pathways that could identify relative changes in nutrient metabolism. The mean weight of Nile tilapia sampled from each lake showed weight variation among the lakes, fish from Lake Ziway were largest (178 g), followed by Gilgel Gibe reservoir (134 g) and Lake Langano (118 g). Fish from Gilgel Gibe showed significantly higher fat composition in all tissues (P < 0.05) except the liver in which no significant variation was observed. The source of fish affected the tissue fat composition. Marked differences were observed in Nile tilapia metabolic activity between the lakes. For instance, the lower body weight and condition of the fish in Lake Langano coincided with several metabolite ratios pointing to a low flow of glucogenic substrate to the citric acid cycle. The low propionyl to acetylcarnitine ratio (C3:C2) in Gilgel Gibe fish is indicating that more of the available acetyl CoA is not led into the citric acid cycle, but instead will be used for fat synthesis. The metabolic markers for lipogenesis and metabolic rate could explain the high-fat concentration in several parts of the body composition of fish from Gilgel Gibe. Our results show that nutrition-related blood metabolite ratios are useful to understand the underlying metabolic events leading to the habitat-dependent differences in the growth of Nile tilapia, and by extension, other species.
A machine learning approach for the factorization of psychometric data with application to the Delis Kaplan Executive Function System
Authors: Camilleri J. A. , Eickhoff S. B. , Weis S. , Chen J. , Amunts J. , Sotiras A. , Genon S.
Published: August 2021

While a replicability crisis has shaken psychological sciences, the replicability of multivariate approaches for psychometric data factorization has received little attention. In particular, Exploratory Factor Analysis (EFA) is frequently promoted as the gold standard in psychological sciences. However, the application of EFA to executive functioning, a core concept in psychology and cognitive neuroscience, has led to divergent conceptual models. This heterogeneity severely limits the generalizability and replicability of findings. To tackle this issue, in this study, we propose to capitalize on a machine learning approach, OPNMF (Orthonormal Projective Non-Negative Factorization), and leverage internal cross-validation to promote generalizability to an independent dataset. We examined its application on the scores of 334 adults at the Delis–Kaplan Executive Function System (D-KEFS), while comparing to standard EFA and Principal Component Analysis (PCA). We further evaluated the replicability of the derived factorization across specific gender and age subsamples. Overall, OPNMF and PCA both converge towards a two-factor model as the best data-fit model. The derived factorization suggests a division betweenlow-levelandhigh-levelexecutive functioning measures, a model further supported in subsamples. In contrast, EFA, highlighted a five-factor model which reflects the segregation of the D-KEFS battery into its main tasks while still clustering higher-level tasks together. However, this model was poorly supported in the subsamples. Thus, the parsimonious two-factors model revealed by OPNMF encompasses the more complex factorization yielded by EFA while enjoying higher generalizability. Hence, OPNMF provides a conceptually meaningful, technically robust, and generalizable factorization for psychometric tools.
Plasma fibrinogen, d-dimer, and fibrin degradation product as biomarkers of rheumatoid arthritis
Authors: Xue Li , Tao Li , Li Xueyi , Wang Yan , Wang Biao , Zhang Yanping , Gao Ning , Dong Yanying , Xu Nan , Xiong Chaoliang , Zhou Ting , Liu Zeshi , Liu Hailong , He Juntao , Li Ke , Geng Yan , Li Ming
Published: August 2021

This study aimed to assess the association of coagulation-related indicators such as plasma fibrinogen (FIB), d-dimer, and fibrin degradation product (FDP) in rheumatoid arthritis (RA) with the disease activity. Data from 105 RA patients and 102 age- and gender-matched healthy controls were collected in the retrospective study. Disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) was used to divide RA patients into low activity group (DAS28-CRP ≤ 2.7) and active group (DAS28-CRP > 2.7). Receiver operating characteristic (ROC) curve was applied to determine area under the curve (AUC). The association between plasma FIB, d-dimer, and FDP and DAS28-CRP was evaluated by spearman correlation. Logistical regression analysis was used to identify the independent variables associated with RA disease activity. RA patients showed higher levels of plasma FIB, d-dimer, and FDP than the controls (P < 0.01). Plasma FIB, d-dimer, and FDP were also increased in active groups of RA patients than those in inactive groups (P < 0.001). ROC curve analyses revealed that the AUC of d-dimer was higher than erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF), and that of FDP was higher than RF in RA patients. In addition, the optimal cut-off value of plasma FIB, d-dimer, and FDP for RA diagnosis was 286 mg/dL, 470 μg/L, and 1.45 mg/L, respectively. Spearman analysis showed that plasma FIB, d-dimer, and FDP were positively related with DAS28-CRP (P < 0.001) in RA patients. Logistical regression analysis showed that d-dimer (odds ratio 2.862, 95% confidence interval 1.851–5.426, P < 0.001) was an independent variable associated with RA disease activity. FIB, d-dimer, and FDP were increased in RA patients and positively correlated with the disease activity of RA. d-dimer may act as a novel inflammatory indice for indicating disease activity in RA patients.
Trace proteinuria as a risk factor for cancer death in a general population
Authors: Matsui Masaru , Tsuruya Kazuhiko , Yoshida Hisako , Iseki Kunitoshi , Fujimoto Shouichi , Konta Tsuneo , Moriyama Toshiki , Yamagata Kunihiro , Narita Ichiei , Kasahara Masato , Shibagaki Yugo , Kondo Masahide , Asahi Koichi , Watanabe Tsuyoshi
Published: August 2021

Growing evidence has demonstrated an association between nondialysis chronic kidney disease and cancer incidence, although the association between trace proteinuria and cancer death remains unclear. The aim of this study was to investigate the association between trace proteinuria and cancer death in a community-based population in Japan. This was a prospective cohort study of 377,202 adults who participated in the Japanese Specific Health Check and Guidance System from 2008 to 2011. Exposure was dipstick proteinuria categorized as − (negative), ± (trace), 1 + (mild), or ≥ 2 + (moderate to heavy). Outcome was cancer death based on information from the national database of death certificates. Adjusted Cox hazard regression model was used to evaluate the associations between trace proteinuria and cancer death. During median follow-up of 3.7 years, 3056 cancer deaths occurred, corresponding to overall cancer death rate of 21.7/10,000 person-years. In the fully adjusted model, risk of cancer death increased significantly in each successive category of proteinuria: hazard ratio (HR) (95% confidence interval [95% CI]) for risk of cancer death was 1.16 (1.03–1.31), 1.47 (1.27–1.70), and 1.61 (1.33–1.96) for trace, mild, and moderate to heavy proteinuria, respectively. Sensitivity analyses revealed a similar association between trace proteinuria and cancer death, and participants with trace proteinuria had greater risk of mortality from hematological cancers (HR: 1.59 [95% CI: 1.09–2.31]). Both mild to heavy and trace proteinuria were significantly associated with risk of mortality from cancer in a general population.
Tightly linked Rps12 and Rps13 genes provide broad-spectrum Phytophthora resistance in soybean
Authors: Sahoo Dipak K. , Das Anindya , Huang Xiaoqiu , Cianzio Silvia , Bhattacharyya Madan K.
Published: August 2021

The Phytophtora root and stem rot is a serious disease in soybean. It is caused by the oomycete pathogen Phytophthora sojae. Growing Phytophthora resistant cultivars is the major method of controlling this disease. Resistance is race- or gene-specific; a single gene confers immunity against only a subset of the P. sojae isolates. Unfortunately, rapid evolution of new Phytophthora sojae virulent pathotypes limits the effectiveness of an Rps (“resistance to Phytophthora sojae”) gene to 8–15 years. The current study was designed to investigate the effectiveness of Rps12 against a set of P. sojae isolates using recombinant inbred lines (RILs) that contain recombination break points in the Rps12 region. Our study revealed a unique Rps gene linked to the Rps12 locus. We named this novel gene as Rps13 that confers resistance against P. sojae isolate V13, which is virulent to recombinants that contains Rps12 but lack Rps13. The genetic distance between the two Rps genes is 4 cM. Our study revealed that two tightly linked functional Rps genes with distinct race-specificity provide broad-spectrum resistance in soybean. We report here the molecular markers for incorporating the broad-spectrum Phytophthora resistance conferred by the two Rps genes in commercial soybean cultivars.