bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clues from Garnet-Spinel-Bearing Peridotite and Pyroxenite Xenoliths about the Formation of the Subcratonic Lithospheric Mantle—a Case Study from the Orapa Kimberlite Cluster
Authors: Kaekane Jarious B , Proyer Alexander 
Published: June 2022

Abstract
A series of 18 ultramafic mantle xenoliths from the Orapa and Letlhakane mines containing both garnet and spinel were investigated petrographically and by means of classical and multi-equilibrium geothermobarometry in order to understand their P–T evolution and infer tectonic processes consistent with that evolution, assuming that samples from the shallow subcontinental lithospheric mantle (SCLM), may have remained cool enough to preserve memory of its formation. Samples broadly classify into peridotites, mainly harzburgites, and pyroxenites, mainly (olivine-) websterites with less than 15 vol% olivine. The websterites all show thin garnet coronas around xenomorphic spinel clusters and often coarse garnet and very fine spinel exsolving from pyroxenes. Classical geothermobarometry results vary consistently between the 40 mW/m2 geotherm at high pressures and the 50 mW/m2 geotherm at lower pressures but partly fail the reliability test indicating some degree of disequilibrium, particularly, as may be expected, toward lower P and T. Eleven samples were analyzed in detail for mineral modes, and pseudosections were calculated for the four compositionally most extreme samples. All four samples show systematic divergence of the mode and composition isopleths indicating overall chemical disequilibrium, but partial isopleth convergence in two distinct P–T regions that were interpreted as the main equilibration stage and a stage of late ‘freeze-in’ of a few composition isopleths at lower temperature and higher pressure. Specifically, the P–T changes between stage 1 and stage 2 were from 900°C and 13 kbar to 750°C and 23 kbar for a websterite and from 850°C and 24 kbar to 730°C and 33 kbar for a harzburgite. For an olivine-orthopyroxenite and -clinopyroxenite the change was from 910°C, 17 kbar and 770°C, 17 kbar for stage 1, respectively, to less well-constrained conditions for stage 2 of 650°C, 36 kbar and 630°C, 20 kbar, respectively. This interpretation of a protracted or stepwise freeze-in along a P–T path holds even after considering thermodynamic, analytical and, as far as possible, geological uncertainties. The result is consistent with a ‘subcretion’ or ‘buoyant subduction’ model for the formation of the SCLM, specifically with the down-drag of an already subcreted lithospheric platelet by a subsequently arriving platelet. In the framework of the crust–mantle evolution in the Orapa region this most likely occurred in the Neoarchean, between 2.8 and 2.5 Ga.
How was apical growth regulated in the ancestral land plant? Insights from the development of non-seed plants
Authors: Fouracre Jim P , Harrison C Jill 
Published: June 2022

Abstract
Land plant life cycles are separated into distinct haploid gametophyte and diploid sporophyte stages. Indeterminate apical growth evolved independently in bryophyte (moss, liverwort, and hornwort) and fern gametophytes, and tracheophyte (vascular plant) sporophytes. The extent to which apical growth in tracheophytes co-opted conserved gametophytic gene networks, or exploited ancestral sporophytic networks, is a long-standing question in plant evolution. The recent phylogenetic confirmation of bryophytes and tracheophytes as sister groups has led to a reassessment of the nature of the ancestral land plant. Here, we review developmental genetic studies of apical regulators and speculate on their likely evolutionary history.
Risk factors of clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy: A systematic review and meta-analysis
Authors: Zhang Biao , Yuan Qihang , Li Shuang , Xu Zhaohui , Chen Xu , Li Lunxu , Shang Dong 
Published: June 2022

Background:
Clinically relevant postoperative pancreatic fistula (CR-POPF) is a common and troublesome complication after pancreatoduodenectomy (PD). We conducted a systematic review and meta-analysis to identify the risk factors of CR-POPF after PD.

Methods:
We searched PubMed, EMBASE, and Cochrane Library databases for studies related to risk factors of CR-POPF after PD. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were extracted from the included studies, then a meta-analysis was conducted. If necessary, sensitivity analysis would be performed by changing the effect model or excluding 1 study at a time. Publication bias was assessed by funnel plot and Begg test and Egger test.

Results:
A total of 27 studies with 24,740 patients were included, and CR-POPF occurred in 3843 patients (incidence = 17%, 95% CI: 16%–19%). Male (OR = 1.56, 95% CI: 1.42–1.70), body mass index >25 kg/m2 (OR = 1.98, 95% CI: 1.23–3.18), pancreatic duct diameter <3 mm (OR = 1.87, 95% CI: 1.66–2.12), soft pancreatic texture (OR = 3.49, 95% CI: 2.61–4.67), and blood transfusion (OR = 3.10, 95% CI: 2.01–4.77) can significantly increase the risk of CR-POPF. Pancreatic adenocarcinoma (OR = 0.54, 95% CI: 0.47–0.61), vascular resection (OR = 0.57, 95% CI: 0.39–0.83), and preoperative chemoradiotherapy (OR = 0.68, 95% CI: 0.57–0.81) can significantly decrease the factor of CR-POPF. Diabetes mellitus was not statistically associated with CR-POPF (OR = 0.66, 95% CI: 0.40–1.08). However, the analysis of body mass index, pancreatic texture, and diabetes mellitus had a high heterogeneity, then sensitivity analysis was performed, and the result after sensitivity analysis showed diabetes mellitus can significantly decrease the risk of CR-POPF. There was no significant publication bias in this meta-analysis.

Conclusions:
The current review assessed the effects of different factors on CR-POPF. This can provide a basis for the prevention and management of CR-POPF. Effective interventions targeting the above risk factors should be investigated in future studies for decreasing the occurrence of CR-POPF.
A systematic literature review of real-world treatment outcomes of small cell lung cancer
Authors: Stokes Michael , Berfeld Noami , Gayle Alicia , Descoteaux Andrew , Rohrmoser Oscar , Franks April 
Published: June 2022

Background:
Robust evidence from real-world studies is needed to aid decision-makers and other stakeholders in choosing the best treatment options for patients. The objective of this work was to assess real-world outcomes of treatment strategies for limited- and extensive-stage small cell lung cancer (SCLC) prior to the global introduction of immunotherapies for this disease.

Methods:
Searches were conducted in MEDLINE and Embase to identify articles published in English from October 1, 2015, through May 20, 2020. Searches were designed using a combination of Medical Subject Heading (Medline), Emtree (Embase subject headings), and free-text terms such as SCLC. Observational studies reporting data on outcomes of initial treatment strategies in patients with limited- and extensive-stage SCLC were included. Studies with limited sample sizes (<100 patients), enrolled all patients prior to 2010, or did not report outcomes for limited- and extensive-stage SCLC separately were excluded. Data were extracted into a predesigned template by a single researcher. All extractions were validated by a second researcher, with disagreements resolved via consensus.

Results:
Forty articles were included in this review. Most enrolled patients from the United States (n = 18 articles) or China (n = 12 articles). Most examined limited-stage (n = 27 articles) SCLC. All studies examined overall survival as the primary outcome. Articles investigating limited-stage SCLC reported outcomes for surgery, chemotherapy and/or radiotherapy, and adjuvant prophylactic cranial irradiation. In studies examining multiple treatment strategies, chemoradiotherapy was the most commonly utilized therapy (56%–82%), with chemotherapy used in 18% to 44% of patients. Across studies, median overall survival was generally higher for chemoradiotherapy (15–45 months) compared with chemotherapy alone (6.0–15.6 months). Studies of extensive-stage SCLC primarily reported on chemotherapy alone, consolidative thoracic radiotherapy, and radiotherapy for patients presenting with brain metastases. Overall survival was generally lower for patients receiving chemotherapy alone (median: 6.4–16.5 months; 3 years, 5%–14.9%) compared with chemotherapy in combination with consolidative thoracic radiotherapy (median: 12.1–18.0 months; 3 years, 15.0%–18.1%). Studies examining whole-brain radiotherapy for brain metastases reported lower median overall survival (5.6–8.7 months) compared with stereotactic radiosurgery (10.0–14.5 months).

Conclusions:
Under current standard of care, which has remained relatively unchanged over the past few decades, prognosis remains poor for patients with SCLC.
MenDEL: automated search of BAC sets covering long DNA regions of interest
Authors: German Sergei , Pinglay Sudarshan , Camellato Brendan , Fenyö David , Boeke Jef D. 
Published: June 2022

AbstractMotivationSynthetic genomics as a field seeks to synthesize large regions of genomes from the ground up. Such large-scale projects, especially in complex genomes can rely on pre-existing BAC (Bacterial Artificial Chromosome) libraries as starting material to reduce cost. However, choosing BACs that cover long DNA regions, especially those that require many BACs, is a manual, idiosyncratic, time consuming, and error prone process. Automating this work would make the assembly of large DNA constructs more efficient.ResultsWe have developed MenDEL – a web-based DNA design application, that provides efficient tools for finding BACs that cover long regions of interest and allow for sorting results based on multiple user defined criteria - total length, number of BACs, longest BAC. etc. In addition, it enables the user to find a combination of BACs from pre-existing libraries that cover a region of interest not found in any single BAC.Availability and ImplementationMenDEL application is available to registered users at https://mendel-isg.nyumc.org, Java code used in the application to find BAC sets is available at https://github.com/MendelProject/BACFinder
The double-layered structure of amyloid-β assemblage on GM1-containing membranes catalytically promotes fibrillization
Authors: Yagi-Utsumi Maho , Itoh Satoru G. , Okumura Hisashi , Yanagisawa Katsuhiko , Kato Koichi , Nishimura Katsuyuki 
Published: June 2022

AbstractAlzheimer’s disease (AD) is associated with progressive accumulation of amyloid-β (Aβ) cross-β fibrils in the brain. Aβ species tightly associated with GM1 ganglioside, a glycosphingolipid abundant in neuronal membranes, promote amyloid fibril formation; therefore, they could be attractive clinical targets. However, the active conformational state of Aβ in GM1-containing lipid membranes is still unknown. The present solid-state nuclear magnetic resonance study revealed a nonfibrillar Aβ assemblage characterized by a double-layered antiparallel β-structure specifically formed on GM1 ganglioside clusters. Our data show that this unique assemblage was not transformed into fibrils on GM1-containing membranes, but could promote conversion of monomeric Aβ into fibrils, suggesting that a solvent-exposed hydrophobic layer provides a catalytic surface evoking Aβ fibril formation. Our findings will offer structural clues for designing drugs targeting catalytically active Aβ conformational species for the development of anti-AD therapeutics.
A Novel Selective ERK1/2 Inhibitor, Laxiflorin B, Targets EGFR Mutation Subtypes in Non-small-cell Lung Cancer
Authors: Chiang Chengyao , Zhang Min , Huang Junrong , Zeng Juan , Chen Chunlan , Pan Dongmei , Yang Heng , Yang Min , Han Qiangqiang , Zou Wang , Xiao Tian , Zou Yongdong , Yin Feng , Li Zigang , Zhu Lizhi , Zheng Duo 
Published: June 2022

AbstractExtracellular regulated protein kinases 1/2 (ERK1/2) are key members of multiple signaling pathways including the ErbB axis. ERK1/2 ectopic activation is responsible for various types of cancer, especially drug resistance to inhibitors of RTK, RAF and MEK, but specific ERK1/2 inhibitors are scarce. In this study, we identified a potential novel ERK covalent inhibitor, Laxiflorin B, a herbal compound with anticancer activity. However, Laxiflorin B is present at low levels in herbs; therefore, we adopted a semi-synthetic process for the efficient production of Laxiflorin B to improve the yield. Laxiflorin B induced mitochondria-mediated apoptosis via BAD activation in non-small-cell lung cancer (NSCLC) cells, especially in EGFR mutant subtypes. Transcriptomic analysis suggested that Laxiflorin B inhibits amphiregulin (AREG) and epiregulin (EREG) expression through ERK inhibition, and suppressed the activation of their receptors, ErbBs, via a positive feedback loop. More importantly, mass spectrometry combined with computer simulation analysis revealed that Laxiflorin B binds covalently to Cys-183 in the ATP-binding pocket of ERK1 through D-ring, and Cys-178 of ERK1 though non-inhibitory binding of A-ring, respectively. Laxiflorin B also exhibited strong tumor suppressive effects with low toxicity in a NSCLC tumor xenograft model in nude mice, and AREG and EREG were identified as biomarkers of Laxiflorin B efficacy. Finally, Laxiflorin B-4, a C-6 modification of Laxiflorin B, exhibited higher affinity for ERK1/2 and stronger tumor suppression. These findings provide a new approach to tumor inhibition using natural anticancer compounds.
Modelling vasopressin synthesis and storage dynamics during prolonged osmotic challenge and recovery based on activity dependent upregulation of mRNA transcription
Authors: MacGregor Duncan J. 
Published: June 2022

AbstractHypothalamic vasopressin neurons are neuroendocrine cells which form part of the homeostatic systems that maintain osmotic pressure. In response to synaptic inputs encoding osmotic pressure and changes in plasma volume, they generate spike triggered secretion of peptide hormone vasopressin from axonal terminals in the posterior pituitary. The thousands of neurons’ secretory signals generate a summed plasma vasopressin signal acting at the kidneys to regulate water loss. Vasopressin is synthesised in cell bodies, packaged into vesicles, and transported to large stores in the pituitary terminals. Supported by activity-dependent upregulation of synthesis and transport, these stores can maintain a secretion response for several days of elevated osmotic pressure, tested by dehydration or salt loading. However, despite upregulated synthesis, stores gradually decline during sustained challenge, followed by a slow recovery. With no evidence of a store encoding feedback signal, previous modelling explained these synthesis dynamics based on activity-dependent upregulation of transcription and mRNA content. Here this model is adapted and integrated into our existing spiking and secretion model to generate a neuronal population model, able to simulate the secretion, store depletion, and replenishment, response to sustained osmotic challenge, matching the dynamics observed experimentally and making functional predictions for the cell body mechanisms.
FLOW: maximum flow framework for the identification of factors mediating the signaling convergence of multiple receptors
Authors: Sheinin Ron , Dulberg Shai , Kaminitz Ayelet , Sharan Roded , Madi Asaf 
Published: June 2022

AbstractMotivationCell-cell crosstalk involves simultaneous interactions of multiple receptors and ligands, followed by downstream signaling cascades working through receptors converging at dominant transcription factors which then integrate and propagate multiple signals into a cellular response. Single cell RNAseq of multiple cell subsets isolated from a defined microenvironment provides us with a unique opportunity to learn about such interactions reflected in their gene expression levels.ResultsWe developed the FLOW framework to map the potential ligand-receptor interactions between different cell subsets based on a maximum flow computation in a network of protein-protein interactions (PPIs). The maximum flow approach further allows characterization of the intracellular downstream signal transduction from differentially expressed receptors towards dominant transcription factors, therefore, enabling the association between a set of receptors and their downstream activated pathways. Importantly, we were able to identify key transcription factors toward which the convergence of multiple receptor signaling occurs. These identified factors have a unique role in the integration and propagation of signaling following specific cell-cell interactions.
Masks Do No More Than Prevent Transmission: Theory and Data Undermine the Variolation Hypothesis
Authors: Koelle Katia , Lin Jack , Zhu Huisheng , Antia Rustom , Lowen Anice C. , Weissman Daniel 
Published: June 2022

AbstractBackgroundMasking serves an important role in reducing the transmission of respiratory viruses, including SARS-CoV-2. During the COVID-19 pandemic, several perspective and review articles have also argued that masking reduces the risk of developing severe disease by reducing the inoculum dose received by the contact. This hypothesis – known as the ‘variolation hypothesis’ – has gained considerable traction since its development.MethodsTo assess the plausibility of this hypothesis, we develop a quantitative framework for understanding the relationship between (i) inoculum dose and the risk of infection and (ii) inoculum dose and the risk of developing severe disease. We parameterize the mathematical models underlying this framework with parameters relevant for SARS-CoV-2 to quantify these relationships empirically and to gauge the range of inoculum doses in natural infections. We then identify and analyze relevant experimental studies of SARS-CoV-2 to ascertain the extent of empirical support for the proposed framework.ResultsMathematical models, when simulated under parameter values appropriate for SARS-CoV-2, indicate that the risk of infection and the risk of developing severe disease both increase with an increase in inoculum dose. However, the risk of infection increases from low to almost certain infection at low inoculum doses (with <1000 initially infected cells). In contrast, the risk of developing severe disease is only sensitive to dose at very high inoculum levels, above 106 initially infected cells. By drawing on studies that have estimated transmission bottleneck sizes of SARS-CoV-2, we find that inoculum doses are low in natural SARS-CoV-2 infections. As such, reductions in inoculum dose through masking or greater social distancing are expected to reduce the risk of infection but not the risk of developing severe disease conditional on infection. Our review of existing experimental studies support this finding.ConclusionsWe find that masking and other measures such as distancing that act to reduce inoculum doses in natural infections are highly unlikely to impact the contact’s risk of developing severe disease conditional on infection. However, in support of existing empirical studies, we find that masking and other mitigation measures that reduce inoculum dose are expected to reduce the risk of infection with SARS-CoV-2. Our findings therefore undermine the plausibility of the variolation hypothesis, underscoring the need to focus on other factors such as comorbidities and host age for understanding the heterogeneity in disease outcomes for SARS-CoV-2.
Assessing transmission risks and control strategy for monkeypox as an emerging zoonosis in a metropolitan area
Authors: Yuan Pei , Tan Yi , Yang Liu , Aruffo Elena , Ogden Nicholas H. , Bélair Jacques , Heffernan Jane , Arino Julien , Watmough James , Carabin Hélène , Zhu Huaiping 
Published: June 2022

AbstractObjectiveTo model the spread of Monkeypox (MPX) in a metropolitan area for assessing the risk of possible outbreaks, and identifying essential public health measures to contain the virus spread.MethodsThe animal reservoir is the key element in the modelling of a zoonotic disease. Using a one health approach, we model the spread of the MPX virus in humans considering animal hosts like rodents (e.g., rats, mice, squirrels, chipmunks, etc.) and emphasize their role and transmission of the virus in a high-risk group, including gay and bisexual men-who-have-sex-with-men (gbMSM). From model and sensitivity analysis, we identify key public health factors and present scenarios under different transmission assumptions.FindingsWe find that the MPX virus may spill over from gbMSM high-risk groups to broader populations if efficiency of transmission increases in the higher-risk group. However, the risk of outbreak can be greatly reduced if at least 65% of symptomatic cases can be isolated and their contacts traced and quarantined. In addition, infections in an animal reservoir will exacerbate MPX transmission risk in the human population.ConclusionRegions or communities with a higher proportion of gbMSM individuals need greater public health attention. Tracing and quarantine (or “effective quarantine” by post-exposure vaccination) of contacts with MPX cases in high-risk groups would have a significant effect on controlling the spreading. Also, surveillance for animal infections would be prudent.
Genome-wide gene by environment study of time spent in daylight and chronotype identifies emerging genetic architecture underlying light sensitivity
Authors: Burns Angus C. , Phillips Andrew J. K. , Rutter Martin K. , Saxena Richa , Cain Sean W. , Lane Jacqueline M. 
Published: June 2022

AbstractLight is the primary stimulus for synchronizing the circadian clock in humans. There are very large interindividual differences in the sensitivity of the circadian clock to light. Little is currently known about the genetic basis for these interindividual differences. We performed a genome-wide gene-by-environment interaction study (GWIS) in 280,897 individuals from the UK Biobank cohort to identify genetic variants that moderate the effect of daytime light exposure on chronotype (individual time of day preference), acting as ‘light sensitivity’ variants for the impact of daylight on the circadian system. We identified a genome-wide significant SNP mapped to the ARL14EP gene (rs3847634; p < 5×10−8), where additional minor alleles were found to enhance the morningness effect of daytime light exposure (βGxE = -.03, SE = 0.005) and were associated with increased gene ARL14EP expression in brain and retinal tissues. Gene-property analysis showed light sensitivity loci were enriched for genes in the G protein-coupled glutamate receptor signaling pathway and in Per2+ hypothalamic neurons. Linkage disequilibrium score regression identified significant genetic correlations of the light sensitivity GWIS with chronotype and sleep duration, such that greater light sensitivity was associated with later chronotype, greater insomnia symptoms and shorter sleep duration. Greater light sensitivity was also genetically correlated with greater risk for PTSD. This study is the first to assess light as an important exposure in the genomics of chronotype and is a critical first step in uncovering the genetic architecture of human circadian light sensitivity and its links to sleep and mental health.