bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting children’s math skills from task-based and resting-state functional brain connectivity
Authors: Lynn Andrew , Wilkey Eric D , Price Gavin R 
Published: November 2021

Abstract
A critical goal of cognitive neuroscience is to predict behavior from neural structure and function, thereby providing crucial insights into who might benefit from clinical and/or educational interventions. Across development, the strength of functional connectivity among a distributed set of brain regions is associated with children’s math skills. Therefore, in the present study we use connectome-based predictive modeling to investigate whether functional connectivity during numerical processing and at rest “predicts” children’s math skills (N = 31, Mage = 9.21 years, 14 Female). Overall, we found that functional connectivity during symbolic number comparison and rest, but not during nonsymbolic number comparison, predicts children’s math skills. Each task revealed a largely distinct set of predictive connections distributed across canonical brain networks and major brain lobes. Most of these predictive connections were negatively correlated with children’s math skills so that weaker connectivity predicted better math skills. Notably, these predictive connections were largely nonoverlapping across task states, suggesting children’s math abilities may depend on state-dependent patterns of network segregation and/or regional specialization. Furthermore, the current predictive modeling approach moves beyond brain–behavior correlations and toward building models of brain connectivity that may eventually aid in predicting future math skills.
Hippocampal asymmetry of regional development and structural covariance in preterm neonates
Authors: Ge Xinting , Zheng Yuanjie , Qiao Yuchuan , Pan Ningning , Simon Julia Pia , Lee Mitchell , Jiang Wenjuan , Kim Hosung , Shi Yonggang , Liu Mengting 
Published: November 2021

AbstractPremature birth is associated with a high prevalence of neurodevelopmental impairments in surviving infants. The hippocampus is known to be critical for learning and memory, yet the putative effects of hippocampal dysfunction remain poorly understood in preterm neonates. In particular, while asymmetry of the hippocampus has been well noted both structurally and functionally, how preterm birth impairs hippocampal development and to what extent the hippocampus is asymmetrically impaired by preterm birth have not been well delineated. In this study, we compared volumetric growth and shape development in the hippocampal hemispheres and structural covariance (SC) between hippocampal vertices and cortical thickness in cerebral cortex regions between two groups. We found that premature infants had smaller volumes of the right hippocampi only. Lower thickness was observed in the hippocampal head in both hemispheres for preterm neonates compared with full-term peers, though preterm neonates exhibited an accelerated age-related change of hippocampal thickness in the left hippocampi. The SC between the left hippocampi and the limbic lobe of the premature infants was severely impaired compared with the term-born neonates. These findings suggested that the development of the hippocampus during the third trimester may be altered following early extrauterine exposure with a high degree of asymmetry.
Glycosylation site Asn168 is important for slow in vivo clearance of recombinant human diamine oxidase heparin-binding motif mutants
Authors: Gludovacz Elisabeth , Resch Marlene , Schuetzenberger Kornelia , Petroczi Karin , Maresch Daniel , Hofbauer Stefan , Jilma Bernd , Borth Nicole , Boehm Thomas 
Published: November 2021

AbstractElevated plasma and tissues histamine concentrations can cause severe symptoms in mast cell activation syndrome, mastocytosis or anaphylaxis. Endogenous and recombinant human diamine oxidase (rhDAO) can rapidly and completely degrade histamine, and administration of rhDAO represents a promising new treatment approach for diseases with excess histamine release from activated mast cells. We recently generated heparin-binding motif mutants of rhDAO with considerably increased in vivo half-lives in rodents compared with the rapidly cleared wildtype protein. Herein, we characterize the role of an evolutionary recently added glycosylation site asparagine 168 in the in vivo clearance and the influence of an unusually solvent accessible free cysteine 123 on the oligomerization of diamine oxidase (DAO). Mutation of the unpaired cysteine 123 strongly reduced oligomerization without influence on enzymatic DAO activity and in vivo clearance. Recombinant hDAO produced in ExpiCHO-S™ cells showed a 15-fold reduction in the percentage of glycans with terminal sialic acid at Asn168 compared with Chinese hamster ovary (CHO)-K1 cells. Capping with sialic acid was also strongly reduced at the other glycosylation sites. The high abundance of terminal mannose and N-acetylglucosamine residues in the four glycans expressed in ExpiCHO-S™ cells compared with CHO-K1 cells resulted in rapid in vivo clearance. Mutation of Asn168 or sialidase treatment also significantly increased clearance. Intact N-glycans at Asn168 seem to protect DAO from rapid clearance in rodents. Full processing of all glycoforms is critical for preserving the improved in vivo half-life characteristics of the rhDAO heparin-binding motif mutants.
The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer
Authors: Festari María Florencia , da Costa Valeria , Rodríguez-Zraquia Santiago A , Costa Monique , Landeira Mercedes , Lores Pablo , Solari-Saquieres Patricia , Kramer M Gabriela , Freire Teresa 
Published: November 2021

Abstract
Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although, TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors.
Pneumonectomy for primary lung cancer: contemporary outcomes, risk factors and model validation
Authors: Brunswicker Annemarie , Taylor Marcus , Grant Stuart W , Abah Udo , Smith Matthew , Shackcloth Michael , Granato Felice , Shah Rajesh , Rammohan Kandadai ,   the North West Thoracic Surgery Collaborative (NWTSC)†, Argus Leah , Michael Sarah , Mason Sabrina , Bhullar Dilraj , Obale Emmanuel , Fritsch NilsCristopher 
Published: November 2021

Abstract

OBJECTIVES
Despite the increased rate of adverse outcomes compared to lobectomy, for selected patients with lung cancer, pneumonectomy is considered the optimal treatment option. The objective of this study was to identify risk factors for mortality in patients undergoing pneumonectomy for primary lung cancer.

METHODS
Data from all patients undergoing pneumonectomy for primary lung cancer at 2 large thoracic surgical centres between 2012 and 2018 were analysed. Multivariable logistic and Cox regression analyses were used to identify risk factors associated with 90-day and 1-year mortality and reduced long-term survival, respectively.

RESULTS
The study included 256 patients. The mean age was 65.2 (standard deviation 9.4) years. In-hospital, 90-day and 1-year mortality were 6.3% (n = 16), 9.8% (n = 25) and 28.1% (n = 72), respectively. The median follow-up time was 31.5 months (interquartile range 9–58 months). Patients who underwent neoadjuvant therapy had a significantly increased risk of 90-day [odds ratio 6.451, 95% confidence interval (CI) 1.867–22.291, P = 0.003] and 1-year mortality (odds ratio 2.454, 95% CI 1.079–7.185, P = 0.044). Higher Performance Status score was associated with higher 1-year mortality (odds ratio 2.055, 95% CI 1.248–3.386, P = 0.005) and reduced overall survival (hazard ratio 1.449, 95% CI 1.086–1.934, P = 0.012). Advanced (stage III/IV) disease was associated with reduced overall survival (hazard ratio 1.433, 95% CI 1.019–2.016, P = 0.039). Validation of a pneumonectomy-specific risk model demonstrated inadequate model performance (area under the curve 0.54).

CONCLUSIONS
Pneumonectomy remains associated with a high rate of perioperative mortality. Neoadjuvant chemoradiotherapy, Performance Status score and advanced disease emerged as the key variables associated with adverse outcomes after pneumonectomy in our cohort.
Mortality among rough sleepers, squatters, residents of homeless shelters or hotels and sofa-surfers: a pooled analysis of UK birth cohorts
Authors: White James , Fluharty Meg , de Groot Rosa , Bell Steven , Batty G David 
Published: November 2021

Abstract

Background
Homelessness encompasses a wide spectrum of experience. Rough sleepers and people attending homeless shelters have been found to be at an increased risk of mortality. It is unclear whether risks are also elevated in those squatting, living temporarily in low-cost hotels or ‘sofa-surfing’ with friends or family members. This study examines mortality in a representative nationwide sample of people who have slept rough, squatted, lived in shelters or low-cost hotels and sofa-surfed.

Methods
Using unpublished data from two national birth cohorts, namely the National Child Development Study and the 1970 British Birth Cohort study, Cox proportional-hazards models and random-effects meta-analyses were used to analyse associations between homelessness and different types of homeless experience (rough sleeping, squatting, staying in a homeless shelter or low-cost hotel, and sofa-surfing) and mortality.

Results
Out of the 23 678 participants, 1444 (6.1%) reported having been homeless and 805 (3.4%) deaths occurred. Homelessness was associated with an increased risk of mortality [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.24–2.26]. Mortality risk was raised across the spectrum of homeless experience, from sleeping rough (HR 4.71, 95% CI 2.38–9.30), to squatting (HR 6.35, 95% CI 2.73–14.75), staying in a homeless shelter (HR 4.89, 95% CI 2.36–10.11), staying in a low-cost hotel (HR 3.38, 95% CI 1.30–8.79 through to sofa-surfing (HR 2.86, 95% CI 1.84–4.42). Associations remained after separate control for socio-economic status, mental health, substance use, accidents and assaults, and criminality.

Conclusions
Mortality rates were raised across all types of homeless experience. This included squatting and sofa-surfing that have not previously been reported. Studies that have omitted the less severe, but more prevalent, use of low-cost hotels and sofa-surfing may have underestimated the impacts of homelessness on mortality.
A scoping review of the use of e-learning and e-consultation for healthcare workers in low- and middle-income countries and their potential complementarity
Authors: Ionescu Alma , de Jong Peter G M , Drop Stenvert L S , van Kampen Sanne C 
Published: November 2021

Abstract

Objective
Although the provision of e-learning (EL) training for healthcare workers (HCWs) and provider-to-HCW e-consultation (EC) is considered useful for health outcomes, research on their joint use is limited. This scoping review aimed to create an overview of what is currently known in the literature about the use and implementation of EC and EL by HCWs in LMICs and to answer the question of whether there is evidence of complementarity.

Materials and Methods
Scientific databases were searched and peer-reviewed papers were reviewed systematically according to predefined inclusion/exclusion criteria. Data were extracted including the study focus (EC/EL), year of publication, geographical location, target population, target disease(s) under study, type(s) of study outcomes, and article type.

Results
A total of 3051 articles were retrieved and screened for eligibility, of which 96 were kept for analysis. Of these, only 3 addressed both EL and EC; 54 studies addressed EL; and 39 addressed EC. Most studies looked at gain in knowledge/skills usability, efficiency, competence, and satisfaction of HCW, or barriers/challenges to implementation. Descriptive studies focused on the application of EL or EC for targeting specific health conditions. Factors contributing to the success of EC or EL networks were institutional anchoring, multiple partnership, and capacity building of local experts.

Conclusions
Our review found an important gap in the literature in relation to the complementary role of EL and EC for HCWs in LMICs evidenced by outcome measures. There is an important role for national and international academic institutions, learned medical societies, and networks to support regional experts in providing EL and EC for added value that will help the clinical performance of HCWs and improve health outcomes.
Cosmology from clustering, cosmic shear, CMB lensing, and cross correlations: combining Rubin observatory and Simons Observatory
Authors: Fang Xiao , Eifler Tim , Schaan Emmanuel , Huang Hung-Jin , Krause Elisabeth , Ferraro Simone 
Published: November 2021

ABSTRACT
In the near future, the overlap of the Rubin Observatory Legacy Survey of Space and Time (LSST) and the Simons Observatory (SO) will present an ideal opportunity for joint cosmological data set analyses. In this paper, we simulate the joint likelihood analysis of these two experiments using six two-point functions derived from galaxy position, galaxy shear, and CMB lensing convergence fields. Our analysis focuses on realistic noise and systematics models and we find that the dark energy Figure of merit (FoM) increases by 53 per cent (92 per cent) from LSST-only to LSST+SO in Year 1 (Year 6). We also investigate the benefits of using the same galaxy sample for both clustering and lensing analyses, and find the choice improves the overall signal to noise by ${\sim}30{-}40{{\ \rm per\ cent}}$, which significantly improves the photo-z calibration and mildly improves the cosmological constraints. Finally, we explore the effects of catastrophic photo-z outliers finding that they cause significant parameter biases when ignored. We develop a new mitigation approach termed ‘island model’, which corrects a large fraction of the biases with only a few parameters while preserving the constraining power.
The formation and early evolution of embedded star clusters in spiral galaxies
Authors: Rieder Steven , Dobbs Clare , Bending Thomas , Liow Kong You , Wurster James 
Published: November 2021

ABSTRACT
We present Ekster, a new method for simulating star clusters from birth in a live galaxy simulation that combines the smoothed-particle hydrodynamics (SPH) method Phantom with the N-body method PeTar. With Ekster, it becomes possible to simulate individual stars in a simulation with only moderately high resolution for the gas, allowing us to study whole sections of a galaxy rather than be restricted to individual clouds. We use this method to simulate star and star cluster formation in spiral arms, investigating massive giant molecular clouds (GMCs) and spiral arm regions with lower mass clouds, from two galaxy models with different spiral potentials. After selecting these regions from pre-run galaxy simulations, we re-sample the particles to obtain a higher resolution. We then re-simulate these regions for 3 Myr to study where and how star clusters form. We analyse the early evolution of the embedded star clusters in these regions. We find that the massive GMC regions, which are more common with stronger spiral arms, form more massive clusters than the sections of spiral arms containing lower mass clouds. Clusters form both by accreting gas and by merging with other proto-clusters, the latter happening more frequently in the denser GMC regions.
Inhibition mechanisms of CRISPR-Cas9 by AcrIIA17 and AcrIIA18
Authors: Wang Xiaoshen , Li Xuzichao , Ma Yongjian , He Jiaqi , Liu Xiang , Yu Guimei , Yin Hang , Zhang Heng 
Published: November 2021

Abstract
Mobile genetic elements such as phages and plasmids have evolved anti-CRISPR proteins (Acrs) to suppress CRISPR-Cas adaptive immune systems. Recently, several phage and non-phage derived Acrs including AcrIIA17 and AcrIIA18 have been reported to inhibit Cas9 through modulation of sgRNA. Here, we show that AcrIIA17 and AcrIIA18 inactivate Cas9 through distinct mechanisms. AcrIIA17 inhibits Cas9 activity through interference with Cas9-sgRNA binary complex formation. In contrast, AcrIIA18 induces the truncation of sgRNA in a Cas9-dependent manner, generating a shortened sgRNA incapable of triggering Cas9 activity. The crystal structure of AcrIIA18, combined with mutagenesis studies, reveals a crucial role of the N-terminal β-hairpin in AcrIIA18 for sgRNA cleavage. The enzymatic inhibition mechanism of AcrIIA18 is different from those of the other reported type II Acrs. Our results add new insights into the mechanistic understanding of CRISPR-Cas9 inhibition by Acrs, and also provide valuable information in the designs of tools for conditional manipulation of CRISPR-Cas9.
Grouped-seq for integrated phenotypic and transcriptomic screening of patient-derived tumor organoids
Authors: Wu Yushuai , Li Kaiyi , Li Yaqian , Sun Tao , Liu Chang , Dong Chunhui , Zhao Tian , Tang Decong , Chen Xiaojie , Chen Xiaofang , Liu Peng 
Published: November 2021

Abstract
Patient-derived tumor organoids (PDOs) have emerged as a reliable in vitro model for drug discovery. However, RNA sequencing-based analysis of PDOs treated with drugs has not been realized in a high-throughput format due to the limited quantity of organoids. Here, we translated a newly developed pooled RNA-seq methodology onto a superhydrophobic microwell array chip to realize an assay of genome-wide RNA output unified with phenotypic data (Grouped-seq). Over 10-fold reduction of sample and reagent consumption together with a new ligation-based barcode synthesis method lowers the cost to ∼$2 per RNA-seq sample. Patient-derived colorectal cancer (CRC) organoids with a number of 10 organoids per microwell were treated with four anti-CRC drugs across eight doses and analyzed by the Grouped-seq. Using a phenotype-assisted pathway enrichment analysis (PAPEA) method, the mechanism of actions of the drugs were correctly derived, illustrating the great potential of Grouped-seq for pharmacological screening with tumor organoids.
The ASCEND-ND trial: study design and participant characteristics
Authors: Perkovic Vlado , Blackorby Allison , Cizman Borut , Carroll Kevin , Cobitz Alexander R , Davies Rich , DiMino Tara L , Jha Vivekanand , Johansen Kirsten L , Lopes Renato D , Kler Lata , Macdougall Iain C , McMurray John J V , Meadowcroft Amy M , Obrador Gregorio T , Solomon Scott , Taft Lin , Wanner Christoph , Waikar Sushrut S , Wheeler David C , Wiecek Andrzej , Singh Ajay K 
Published: November 2021

ABSTRACT

Background
Anaemia is common in chronic kidney disease (CKD) and assessment of the risks and benefits of new therapies is important.

Methods
The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3–5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8–10 g/dL or receiving ESAs with screening Hb of 8–12 g/dL. Participants were randomized to daprodustat or darbepoetin alfa (1:1) in an open-label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28–52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials.

Results
Overall, 3872 patients were randomized from 39 countries (median age 67 years, 56% female, 56% White, 27% Asian and 10% Black). The median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and estimated glomerular filtration rate was 18 mL/min/1.73 m2. Among randomized patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin–angiotensin system blockers, 55% were taking statins and 49% were taking oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials.

Conclusion
ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis.
Combined immunotherapy with controlled interleukin-12 gene therapy and immune checkpoint blockade in recurrent glioblastoma: An open-label, multi-institutional phase I trial
Authors: Chiocca E Antonio , Gelb Arnold B , Chen Clark C , Rao Ganesh , Reardon David A , Wen Patrick Y , Bi Wenya Linda , Peruzzi Pierpaolo , Amidei Christina , Triggs Dan , Seften Leah , Park Grace , Grant James , Truman Kyla , Buck Jill Y , Hadar Nira , Demars Nathan , Miao John , Estupinan Taylor , Loewy John , Chadha Kamal , Tringali Joseph , Cooper Laurence , Lukas Rimas V 
Published: November 2021

Abstract

Background
Veledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation of immune checkpoint signaling, providing the rationale for a combination trial with immune checkpoint inhibition.

Methods
An open-label, multi-institutional, dose-escalation phase I trial in rGBM subjects (NCT03636477) accrued 21 subjects in 3 dose-escalating cohorts: (1) neoadjuvant then ongoing nivolumab (1mg/kg) and VDX (10 mg) (n = 3); (2) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (10 mg) (n = 3); and (3) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (20 mg) (n = 15). Nivolumab was administered 7 (±3) days before resection of the rGBM followed by peritumoral injection of IL-12 gene therapy. VDX was administered 3 hours before and then for 14 days after surgery. Nivolumab was administered every two weeks after surgery.

Results
Toxicities of the combination were comparable to IL-12 gene monotherapy and were predictable, dose-related, and reversible upon withholding doses of VDX and/or nivolumab. VDX plasma pharmacokinetics demonstrate a dose-response relationship with effective brain tumor tissue VDX penetration and production of IL-12. IL-12 levels in serum peaked in all subjects at about Day 3 after surgery. Tumor IFNγ increased in post-treatment biopsies. Median overall survival (mOS) for VDX 10 mg with nivolumab was 16.9 months and for all subjects was 9.8 months.

Conclusion
The safety of this combination immunotherapy was established and has led to an ongoing phase II clinical trial of immune checkpoint blockade with controlled IL-12 gene therapy (NCT04006119).