bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridging heterogeneous mutation data to enhance disease gene discovery
Authors: Zhou Kaiyin , Wang Yuxing , Bretonnel Cohen Kevin , Kim Jin-Dong , Ma Xiaohang , Shen Zhixue , Meng Xiangyu , Xia Jingbo
Published: February 2021

Bridging heterogeneous mutation data fills in the gap between various data categories and propels discovery of disease-related genes. It is known that genome-wide association study (GWAS) infers significant mutation associations that link genotype and phenotype. However, due to the differences of size and quality between GWAS studies, not all de facto vital variations are able to pass the multiple testing. In the meantime, mutation events widely reported in literature unveil typical functional biological process, including mutation types like gain of function and loss of function. To bring together the heterogeneous mutation data, we propose a ‘Gene–Disease Association prediction by Mutation Data Bridging (GDAMDB)’ pipeline with a statistic generative model. The model learns the distribution parameters of mutation associations and mutation types and recovers false-negative GWAS mutations that fail to pass significant test but represent supportive evidences of functional biological process in literature. Eventually, we applied GDAMDB in Alzheimer’s disease (AD) and predicted 79 AD-associated genes. Besides, 12 of them from the original GWAS, 60 of them are supported to be AD-related by other GWAS or literature report, and rest of them are newly predicted genes. Our model is capable of enhancing the GWAS-based gene association discovery by well combining text mining results. The positive result indicates that bridging the heterogeneous mutation data is contributory for the novel disease-related gene discovery.
PICS2: next-generation fine mapping via probabilistic identification of causal SNPs
Authors: Taylor Kimberly E , Ansel K Mark , Marson Alexander , Criswell Lindsey A , Farh Kyle Kai-How
Published: February 2021

The Probabilistic Identification of Causal SNPs (PICS) algorithm and web application was developed as a fine-mapping tool to determine the likelihood that each single nucleotide polymorphism (SNP) in LD with a reported index SNP is a true causal polymorphism. PICS is notable for its ability to identify candidate causal SNPs within a locus using only the index SNP, which are widely available from published GWAS, whereas other methods require full summary statistics or full genotype data. However, the original PICS web application operates on a single SNP at a time, with slow performance, severely limiting its usability. We have developed a next-generation PICS tool, PICS2, which enables performance of PICS analyses of large batches of index SNPs with much faster performance. Additional updates and extensions include use of LD reference data generated from 1000 Genomes phase 3; annotation of variant consequences; annotation of GTEx eQTL genes and downloadable PICS SNPs from GTEx eQTLs; the option of generating PICS probabilities from experimental summary statistics; and generation of PICS SNPs from all SNPs of the GWAS catalog, automatically updated weekly. These free and easy-to-use resources will enable efficient determination of candidate loci for biological studies to investigate the true causal variants underlying disease processes.

Availability and implementation

PICS2 is available at https://pics2.ucsf.edu.

Supplementary information

Supplementary data are available at Bioinformatics online.
Reported Individual Costs and Benefits of Sharing Open Data among Canadian Academic Faculty in Ecology and Evolution
Authors: Soeharjono Sandrine , Roche Dominique G
Published: February 2021

Open data facilitate reproducibility and accelerate scientific discovery but are hindered by perceptions that researchers bear costs and gain few benefits from publicly sharing their data, with limited empirical evidence to the contrary. We surveyed 140 faculty members working in ecology and evolution across Canada's top 20 ranked universities and found that more researchers report benefits (47.9%) and neutral outcomes (43.6%) than costs (21.4%) from openly sharing data. The benefits were independent of career stage and gender, but men and early career researchers were more likely to report costs. We outline mechanisms proposed by the study participants to reduce the individual costs and increase the benefits of open data for faculty members.
Simultaneous differential network analysis and classification for matrix-variate data with application to brain connectivity
Authors: Chen Hao , Guo Ying , He Yong , Ji Jiadong , Liu Lei , Shi Yufeng , Wang Yikai , Yu Long , Zhang Xinsheng ,   The Alzheimers Disease Neuroimaging Initiative
Published: February 2021

Growing evidence has shown that the brain connectivity network experiences alterations for complex diseases such as Alzheimer’s disease (AD). Network comparison, also known as differential network analysis, is thus particularly powerful to reveal the disease pathologies and identify clinical biomarkers for medical diagnoses (classification). Data from neurophysiological measurements are multidimensional and in matrix-form. Naive vectorization method is not sufficient as it ignores the structural information within the matrix. In the article, we adopt the Kronecker product covariance matrices framework to capture both spatial and temporal correlations of the matrix-variate data while the temporal covariance matrix is treated as a nuisance parameter. By recognizing that the strengths of network connections may vary across subjects, we develop an ensemble-learning procedure, which identifies the differential interaction patterns of brain regions between the case group and the control group and conducts medical diagnosis (classification) of the disease simultaneously. Simulation studies are conducted to assess the performance of the proposed method. We apply the proposed procedure to the functional connectivity analysis of an functional magnetic resonance imaging study on AD. The hub nodes and differential interaction patterns identified are consistent with existing experimental studies, and satisfactory out-of-sample classification performance is achieved for medical diagnosis of AD.
Neural Correlates of Successful Memory Encoding in Kindergarten and Early Elementary School Children: Longitudinal Trends and Effects of Schooling
Authors: Nolden Sophie , Brod Garvin , Meyer Ann-Kristin , Fandakova Yana , Shing Yee Lee
Published: February 2021

From age 5 to 7, there are remarkable improvements in children’s cognitive abilities (“5–7 shift”). In many countries, including Germany, formal schooling begins in this age range. It is, thus, unclear to what extent exposure to formal schooling contributes to the “5–7 shift.” In this longitudinal study, we investigated if schooling acts as a catalyst of maturation. We tested 5-year-old children who were born close to the official cutoff date for school entry and who were still attending a play-oriented kindergarten. One year later, the children were tested again. Some of the children had experienced their first year of schooling whereas the others had remained in kindergarten. Using 2 functional magnetic resonance imaging tasks that assessed episodic memory formation (i.e., subsequent memory effect), we found that children relied strongly on the medial temporal lobe (MTL) at both time points but not on the prefrontal cortex (PFC). In contrast, older children and adults typically show subsequent memory effects in both MTL and PFC. Both children groups improved in their memory performance, but there were no longitudinal changes nor group differences in neural activation. We conclude that successful memory formation in this age group relies more heavily on the MTL than in older age groups.
Urine Lipoarabinomannan Testing in Adults With Advanced Human Immunodeficiency Virus in a Trial of Empiric Tuberculosis Therapy
Authors: Matoga Mitch M , Bisson Gregory P , Gupta Amita , Miyahara Sachiko , Sun Xin , Fry Carrie , Manabe Yukari C , Kumwenda Johnstone , Cecilia Kanyama , Nyirenda Mulinda , Ngongondo McNeil , Mbewe Abineli , Lagat David , Wallis Carole , Mugerwa Henry , Hosseinipour Mina C
Published: February 2021

Background

The urine lipoarabinomannan (LAM) antigen test is a tuberculosis (TB) diagnostic test with highest sensitivity in individuals with advanced human immunodeficiency virus (HIV). Its role in TB diagnostic algorithms for HIV-positive outpatients remains unclear.

Methods

The AIDS Clinical Trials Group (ACTG) A5274 trial demonstrated that empiric TB therapy did not improve 24-week survival compared to isoniazid preventive therapy (IPT) in TB screen–negative HIV-positive adults initiating antiretroviral therapy with CD4 counts <50 cells/µL. Retrospective LAM testing was performed on stored urine obtained at baseline. We determined the proportion of LAM-positive participants and conducted modified intent-to-treat analysis excluding LAM-positive participants to determine the effect on 24-week survival, TB incidence, and time to TB using Kaplan-Meier method.

Results

A5274 enrolled 850 participants; 53% were male and the median CD4 count was 18 (interquartile range, 9–32) cells/µL. Of the 850, 566 (67%) had LAM testing (283 per arm); 28 (5%) were positive (21 [7%] and 7 [2%] in the empiric and IPT arms, respectively). Of those LAM-positive, 1 participant in each arm died and 5 of 21 and 0 of 7 in empiric and IPT arms, respectively, developed TB. After excluding these 28 cases, there were 19 and 21 deaths in the empiric and IPT arms, respectively (P = .88). TB incidence remained higher (4.6% vs 2%, P = .04) and time to TB remained faster in the empiric arm (P = .04).

Conclusions

Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy, and Xpert testing, LAM testing identified an additional 5% of individuals with TB. Positive LAM results did not change mortality or TB incidence.
The Great Debate With IBD Biosimilars
Authors: Limdi Jimmy K , Farraye Francis A
Published: February 2021

The relatively high cost of anti-TNF agents and looming or actual expiry of patents for several biologics have led to the development of “highly similar” versions of the “originator” drugs called “biosimilars.” The approval of biosimilars has been based on “extrapolation,” whereby approval is granted in licensed indications for the reference product without the need for clinical trials. We discuss efficacy and safety data in support of biosimilar use from prospective studies, switching from originator biologic, impact on immunogenicity, pharmaco-economic, and practical considerations for clinicians.
An evolutionary mismatch narrative to improve lifestyle medicine: a patient education hypothesis
Authors: Basile Anthony J , Renner Michael W , Hidaka Brandon H , Sweazea Karen L
Published: February 2021

An evolutionary perspective provides a unifying explanation for the modifiable risk factors and lifestyle-based interventions for the leading causes of morbidity and mortality globally. Non-communicable diseases develop from an evolutionary mismatch between the prior environment and modern patterns of behavior; however, it is unclear whether an evolutionary mismatch narrative could promote positive behavior change in patients. We hypothesize that educating patients about evolutionary mismatch could augment efforts to improve healthful behavior. Specifically, explaining the ‘why’ behind what is being recommended could promote health literacy and adherence. Furthermore, we offer suggestions of how clinicians could educate patients about evolutionary mismatch for key-lifestyle factors, diet and physical activity, as well as several specific modern diseases. We also consider how to sidestep patients’ skepticism of evolutionary theory. Here, we lay the groundwork for research on how educating patients with an evolutionary mismatch narrative could impact health behaviors and improve outcomes.
Growth and adhesion inhibition of pathogenic bacteria by live and heat-killed food-origin Lactobacillus strains or their supernatants
Authors: Zielińska Dorota , Łepecka Anna , Ołdak Aleksandra , Długosz Ewa , Kołożyn-Krajewska Danuta
Published: February 2021

The study aimed to evaluate qualitatively and quantitatively the antimicrobial capacity of 10 potential probiotic Lactobacillus strains against model enteropathogens and spoilage microorganisms. The probiotic strains (live and heat-killed forms) were also assessed for their ability to inhibit adhesion of selected pathogens to Caco-2 cells. The largest inhibition zones (the diffusion method) were connected with the usage of whole bacteria cultures (WBC), also high and moderate with cell-free supernatant (CFS) and the lowest with cell-free neutralized supernatant (CNS). The highest antagonistic activity of Lactobacillus strains was observed against L. monocytogenes strains, moderate activity against Salmonella, Shigella, Escherichia coli, Pseudomonas and, the lowest against S.aureus, Bacillus and Enterococcus. The inhibition of adhesion to Caco-2 cells was very high in the case of E. coli, Salmonella and L. monocytogenes, and moderate in the case of S.aureus. On average, the inhibition effect was higher when pathogenic bacteria were treated by WBC, than heat-killed Lactobacillus. Although, in most samples, the effect was not significantly different (P> 0.05). The strains Lb. brevis O24 and Lb. rhamnosus K3 showed the biggest overall antimicrobial properties, and were most effective in adherence inhibition of investigated indicator strains. These bacteria or their metabolites can be used for the production of various foods or pharmaceutical products.
Is the Machecoul fault the source of the ∼M6 1799 Vendée earthquake (France)?
Authors: Kaub C , Geoffroy L , Bollinger L , Perrot J , Le Roy P , Authemayou C
Published: February 2021

The ∼M6 1799 Bouin earthquake is considered as one of the largest earthquakes to have struck Western France. However, the seismogenic source potentially responsible for this event remain marginally documented. We present results from a focused offshore-onshore multidisciplinary survey in its meizoseismal area in order to identify the fault segments that potentially ruptured during this earthquake. Based on macroseismic data and the geology, we focused our study on the so-called Machecoul Fault as a potential source of the 1799 Bouin event. Our survey includes extensive high-resolution seismic reflection, high resolution bathymetry and a 1-yr seismological survey. These data were combined with existing topography, onshore gravity data and drill data to document the geometry of the Marais Breton/Baie de Bourgneuf basin, the past tectonic activity and the current local microearthquakes at depth along its bounding faults. Offshore and onshore observations suggest a recent activity of the segmented Machecoul Fault bounding the basin to the North. Offshore, the planar contact between the Plio-Quaternary sediments and the basement along the fault trace as well as the thickening of these sedimentary units near this contact suggests tectonic control rather than erosion. Onshore, the recent incision of the footwall of the fault suggests a recent tectonic activity. The temporary local seismological experiment deployed between 2016 and 2017 recorded a diffuse microseismicity down to the depth of 22 ± 5 km along the southward dipping Machecoul Fault, associated with predominantly normal fault mechanisms. Altogether, these results suggest that the Machecoul Fault is a serious candidate for being the source of the historical Bouin 1799 earthquake.
Building evidence on what works (and what does not): practical guidance from the World Health Organization on post-project evaluation of adolescent sexual and reproductive health projects
Authors: Igras Susan , Plesons Marina , Chandra-Mouli Venkatraman
Published: February 2021

Over the past 25 years, there has been significant progress in increasing the recognition of, resources for, and action on adolescent health, and adolescent sexual and reproductive health (ASRH) in particular. As with numerous other health areas, however, many of the projects that aim to improve ASRH are implemented without well-thought-out plans for evaluation. As a result, the lessons that projects learn as they encounter and address policy and programmatic challenges are often not extracted and placed in the public arena. In such cases, post-project evaluation (PPE) offers the possibility to generate learnings about what works (and does not work), to complement prospective studies of new or follow-on projects. To fill the gap in the literature and guidance on PPE, the World Health Organization developed The project has ended, but we can still learn from it! Practical guidance for conducting post-project evaluations of adolescent sexual and reproductive health projects. This article provides an overview of the guidance by outlining key methodological and contextual challenges in conducting PPE, as well as illustrative solutions for responding to them.
Mapping 3D structure of aSargassumforest with high-resolution sounding data obtained by multibeam echosounder
Authors: Hamana Masahiro , Komatsu Teruhisa
Published: February 2021

Sargassum forests play an important role in coastal waters as habitats for marine organisms, including commercial species. However, human activities have negatively affected their distribution causing a worldwide decline of Sargassum forests. Mapping and monitoring the distribution and biomass of these habitats using acoustic remote sensing techniques is key for their conservation. Nonetheless, most researches based on acoustic remote sensing methods focus on estimations of macrophyte area and its canopy height, and less researches reporting 3D visualization of these habitats. This study demonstrates the use of high-resolution multibeam echosounder (MBES) bathymetric data to visualize the 3D structure of Sargassum forests. Comparing acoustic data and underwater camera photos collected in field surveys, we identified Sargassum individuals as vertical clusters of contiguous sounding points with a base close to the sea bottom in the sounding data of the MBES. Using this criterion, we could distinguish Sargassum echoes, visualize the 3D structure of Sargassum forests and estimate the number of Sargassum individuals in the survey area. Using the relation between thallus length and dry weight of sampled Sargassum plants, standing stock and biomass could be estimated assuming the thallus length was the height of Sargassum plants identified with the MBES.
Linking of Lagrangian Tori and Embedding Obstructions in Symplectic 4-Manifolds
Authors: Ĉoté Laurent , Dimitroglou Rizell Georgios
Published: February 2021

We classify weakly exact, rational Lagrangian tori in $T^* \mathbb{T}^2- 0_{\mathbb{T}^2}$ up to Hamiltonian isotopy. This result is related to the classification theory of closed $1$-forms on $\mathbb{T}^n$ and also has applications to symplectic topology. As a 1st corollary, we strengthen a result due independently to Eliashberg–Polterovich and to Giroux describing Lagrangian tori in $T^* \mathbb{T}^2-0_{\mathbb{T}^2}$, which are homologous to the zero section. As a 2nd corollary, we exhibit pairs of disjoint totally real tori $K_1, K_2 \subset T^*\mathbb{T}^2$, each of which is isotopic through totally real tori to the zero section, but such that the union $K_1 \cup K_2$ is not even smoothly isotopic to a Lagrangian. In the 2nd part of the paper, we study linking of Lagrangian tori in $({\mathbb{R}}^4, \omega )$ and in rational symplectic $4$-manifolds. We prove that the linking properties of such tori are determined by purely algebro-topological data, which can often be deduced from enumerative disk counts in the monotone case. We also use this result to describe certain Lagrangian embedding obstructions.
Stable Pair Invariants of Local Calabi–Yau 4-folds
Authors: Cao Yalong , Kool Martijn , Monavari Sergej
Published: February 2021

In 2008, Klemm–Pandharipande defined Gopakumar–Vafa type invariants of a Calabi–Yau 4-folds $X$ using Gromov–Witten theory. Recently, Cao–Maulik–Toda proposed a conjectural description of these invariants in terms of stable pair theory. When $X$ is the total space of the sum of two line bundles over a surface $S$, and all stable pairs are scheme theoretically supported on the zero section, we express stable pair invariants in terms of intersection numbers on Hilbert schemes of points on $S$. As an application, we obtain new verifications of the Cao–Maulik–Toda conjectures for low-degree curve classes and find connections to Carlsson–Okounkov numbers. Some of our verifications involve genus zero Gopakumar–Vafa type invariants recently determined in the context of the log-local principle by Bousseau–Brini–van Garrel. Finally, using the vertex formalism, we provide a few more verifications of the Cao–Maulik–Toda conjectures when thickened curves contribute and also for the case of local $\mathbb{P}^3$.
Characterization of the MurT/GatD complex in Mycobacterium tuberculosis towards validating a novel anti-tubercular drug target
Authors: Maitra Arundhati , Nukala Syamasundari , Dickman Rachael , Martin Liam T , Munshi Tulika , Gupta Antima , Shepherd Adrian J , Arnvig Kristine B , Tabor Alethea B , Keep Nicholas H , Bhakta Sanjib
Published: February 2021

Objectives

Identification and validation of novel therapeutic targets is imperative to tackle the rise of drug resistance in tuberculosis. An essential Mur ligase-like gene (Rv3712), expected to be involved in cell-wall peptidoglycan (PG) biogenesis and conserved across mycobacteria, including the genetically depleted Mycobacterium leprae, was the primary focus of this study.

Methods

Biochemical analysis of Rv3712 was performed using inorganic phosphate release assays. The operon structure was identified using reverse-transcriptase PCR and a transcription/translation fusion vector. In vivo mycobacterial protein fragment complementation assays helped generate the interactome.

Results

Rv3712 was found to be an ATPase. Characterization of its operon revealed a mycobacteria-specific promoter driving the co-transcription of Rv3712 and Rv3713. The two gene products were found to interact with each other in vivo. Sequence-based functional assignments reveal that Rv3712 and Rv3713 are likely to be the mycobacterial PG precursor-modifying enzymes MurT and GatD, respectively. An in vivo network involving Mtb-MurT, regulatory proteins and cell division proteins was also identified.

Conclusions

Understanding the role of the enzyme complex in the context of PG metabolism and cell division, and the implications for antimicrobial resistance and host immune responses will facilitate the design of therapeutics that are targeted specifically to M. tuberculosis.
Comparative Study for the Assay of Plant Derived Chemicals in Pharmaceutical Formulation Using Methods Dependent on Factorized Spectra
Authors: Fahmy Nesma M , Michael Adel M
Published: February 2021

Background

Modern built-in spectrophotometer software supporting mathematical processes provided a solution for increasing selectivity for multicomponent mixtures.

Objective

Simultaneous spectrophotometric determination of the three naturally occurring antioxidants—rutin(RUT), hesperidin(HES), and ascorbic acid(ASC)—in bulk forms and combined pharmaceutical formulation.

Method

This was achieved by factorized zero order method (FZM), factorized derivative method (FD1M), and factorized derivative ratio method (FDRM), coupled with spectrum subtraction(SS).

Results

Mathematical filtration techniques allowed each component to be obtained separately in either its zero, first, or derivative ratio form, allowing the resolution of spectra typical to the pure components present in Vitamin C Forte® tablets. The proposed methods were applied over a concentration range of 2–50, 2–30, and 10–100 µg/mL for RUT, HES, and ASC, respectively.

Conclusions

Recent methods for the analysis of binary mixtures, FZM and FD1M, were successfully applied for the analysis of ternary mixtures and compared to the novel FDRM. All were revealed to be specific and sensitive with successful application on pharmaceutical formulations. Validation parameters were evaluated in accordance with the International Conference on Harmonization guidelines. Statistical results were satisfactory, revealing no significant difference regarding accuracy and precision.

Highlights

Factorized methods enabled the resolution of spectra identical to those of pure drugs present in mixtures. Overlapped spectra of ternary mixtures could be resolved by spectrum subtraction coupled FDRM (SS-FDRM) or by successive application of FZM and FD1M.
Police trust and domestic violence among immigrants: evidence from VAWA self-petitions
Authors: Amuedo-Dorantes Catalina , Arenas-Arroyo Esther
Published: February 2021

Domestic violence is a serious under-reported crime in the United States, especially among immigrant women. The Violence Against Women Act (VAWA) was an attempt to partially address this problem by allowing battered immigrants to petition for legal status without relying on the sponsorship of an abusive U.S. citizen or legal permanent resident spouse. The tougher immigration policy climate may have made immigrant women more vulnerable to domestic violence, as well as more reluctant to report domestic violence to law enforcement. Sanctuary policies, which limit local law enforcement’s cooperation with federal immigration authorities, may counteract these effects. After exploiting the temporal and geographic variation in the adoption of interior immigration enforcement and sanctuary policies, we can successfully identify the impact of sanctuary policies, which help boost the rate of VAWA self-petitions. Additionally, we provide suggestive evidence of the channel through which this impact is likely taking place—namely through victims’ increased willingness to report cases and leave their abusers. Understanding survivors’ responses to immigration policy is crucial given growing police mistrust and immigrants’ vulnerability to crime.
Pervasive Genomic Signatures of Local Adaptation to Altitude Across Highland Specialist Andean Hummingbird Populations
Authors: Lim Marisa C W , Bi Ke , Witt Christopher C , Graham Catherine H , Dávalos Liliana M
Published: February 2021

Populations along steep environmental gradients are subject to differentiating selection that can result in local adaptation, despite countervailing gene flow, and genetic drift. In montane systems, where species are often restricted to narrow ranges of elevation, it is unclear whether the selection is strong enough to influence functional differentiation of subpopulations differing by a few hundred meters in elevation. We used targeted capture of 12 501 exons from across the genome, including 271 genes previously implicated in altitude adaptation, to test for adaptation to local elevations for 2 highland hummingbird species, Coeligena violifer (n = 62) and Colibri coruscans (n = 101). For each species, we described population genetic structure across the complex geography of the Peruvian Andes and, while accounting for this structure, we tested whether elevational allele frequency clines in single nucleotide polymorphisms (SNPs) showed evidence for local adaptation to elevation. Although the 2 species exhibited contrasting population genetic structures, we found signatures of clinal genetic variation with shifts in elevation in both. The genes with SNP-elevation associations included candidate genes previously discovered for high-elevation adaptation as well as others not previously identified, with cellular functions related to hypoxia response, energy metabolism, and immune function, among others. Despite the homogenizing effects of gene flow and genetic drift, natural selection on parts of the genome evidently optimizes elevation-specific cellular function even within elevation range-restricted montane populations. Consequently, our results suggest local adaptation occurring in narrow elevation bands in tropical mountains, such as the Andes, may effectively make them “taller” biogeographic barriers.
Videos of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens
Authors: Kibel Adam S , Inman Brant A , Pachynski Russell K , Vu Tuyen , Sheikh Nadeem A , Petrylak Daniel P
Published: February 2021

Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and cocultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video recorded during coculture. Here, we present video recordings and analyses of T cells from sipuleucel-T–treated subjects showing—for the first time—direct lysis of cells that express prostate cancer target antigens, prostate acid phosphatase, or prostate-specific antigen.
The Path to Adulthood: A Mixed-Methods Approach to the Exploration of the Experiences of Unaccompanied Minors in Portugal
Authors: Moleiro Carla , Roberto Sandra
Published: February 2021

Unaccompanied minors who reach the age of majority often experience this transition as a complex stage. Insecurity and helplessness may arise and, in some cases, survival without the support of the institutions and services that previously protected them as minors in the host country may mean becoming at risk for social exclusion. The objective of the present study was to characterize unaccompanied minors in Portugal (N = 67) and understand the processes of transition into the age of majority, using a mixed-methods approach. Quantitative (survey) and qualitative (interviews on autobiographical narratives) methodologies were used as a means of acknowledging the voice of minors/young adults in their trajectories and experiences. Two groups were included, with minors (in residential care) and youths who had already reached adulthood (living independently). Results illustrate diverse reasons for arrival in Portugal and distinct strengths and struggles in the integration experiences, with both positive and negative aspects being identified in the transition to autonomy.
Amyand’s hernia complicated with appendicitis: an interval approach with transabdominal laparoscopic appendectomy and laparoscopic hernioplasty—a case report
Authors: Parekh Akshat T , Diamond Keith , Littlejohn Monty , Ehsani-Nia Hamid , Amro Chris
Published: February 2021

Amyand’s hernia is a rare classification of inguinal hernia where the vermiform appendix is located within the hernial sac. This case report discusses a patient presenting with abdominal and groin pain shown to be an Amyand’s hernia complicated by acute appendicitis on computed tomography. The patient was treated with a two-stage approach, involving transabdominal laparoscopic appendectomy and elective laparoscopic hernioplasty after recovery. As some controversy exists regarding the timing of appendectomy and hernioplasty, we examine the benefits of the interval approach in the reduction of postoperative infection risk compared with a concurrent approach in patients presenting with Amyand’s hernia complicated by appendiceal inflammation.
Effects of initial density profiles on massive star cluster formation in giant molecular clouds
Authors: Chen Yingtian , Li Hui , Vogelsberger Mark
Published: February 2021

We perform a suite of hydrodynamic simulations to investigate how initial density profiles of giant molecular clouds (GMCs) affect their subsequent evolution. We find that the star formation duration and integrated star formation efficiency of the whole clouds are not sensitive to the choice of different profiles but are mainly controlled by the interplay between gravitational collapse and stellar feedback. Despite this similarity, GMCs with different profiles show dramatically different modes of star formation. For shallower profiles, GMCs first fragment into many self-gravitation cores and form subclusters that distributed throughout the entire clouds. These subclusters are later assembled ‘hierarchically’ to central clusters. In contrast, for steeper profiles, a massive cluster is quickly formed at the centre of the cloud and then gradually grows its mass via gas accretion. Consequently, central clusters that emerged from clouds with shallower profiles are less massive and show less rotation than those with the steeper profiles. This is because (1) a significant fraction of mass and angular momentum in shallower profiles is stored in the orbital motion of the subclusters that are not able to merge into the central clusters, and (2) frequent hierarchical mergers in the shallower profiles lead to further losses of mass and angular momentum via violent relaxation and tidal disruption. Encouragingly, the degree of cluster rotations in steeper profiles is consistent with recent observations of young and intermediate-age clusters. We speculate that rotating globular clusters are likely formed via an ‘accretion’ mode from centrally concentrated clouds in the early Universe.
Possible evidence of a universal radio/X-ray correlation in a near-complete sample of hard X-ray selected seyfert galaxies
Authors: Chang N , Xie F G , Liu X , Ho L C , Dong A-J , Han Z H , Wang X
Published: February 2021

Because the disc–jet coupling likely depends on various properties of sources probed, the sample control is always an important but challenging task. In this work, we re-analysed the INTEGRAL hard X-ray-selected sample of Seyfert galaxies. We only consider sources that have measurements in black hole (BH) mass, and luminosities in radio and X-rays. Our final sample includes 64 (out of the original 79) sources, consists of both bright active galactic nucleus and low-luminosity ones. The 2–10 keV X-ray Eddington ratio LX/LEdd locates in the range between ∼10−4.5 and ∼10−0.5. We first find that, because of the similarity in the LHX/LX distribution, the X-ray origin of radio-loud Seyferts may be the same to that of radio-quiet (RQ) ones, where we attribute to the hot accretion flow (or similarly, the corona). We then investigate the connections between luminosities in radio and X-rays. Since our sample suffers a selection bias of a BH mass MBH dependence on LX/LEdd, we focus on the correlation slope ξX between the radio (at 1.4 GHz) and X-ray luminosities in Eddington unit, i.e. $({L_{\rm R}}/{L_{\rm Edd}}) \propto ({L_{\rm X}}/{L_{\rm Edd}})^{\xi _{\rm X}}$. We classify the sources according to various properties, i.e. 1) Seyfert classification, 2) radio loudness, and 3) radio morphology. We find that, despite these differences in classification, all the sources in our sample are consistent with a universal correlation slope ξX (note that the normalization may be different), with ξX = 0.77 ± 0.10. This is unexpected, considering various possible radio emitters in RQ systems. For the jet (either relativistic and well collimated, or sub-relativistic and weakly collimated) interpretation, our result may suggest a common/universal but to be identified jet launching mechanism among all the Seyfert galaxies, while properties like BH spin and magnetic field strength only play secondary roles. We further estimate the jet production efficiency ηjet of Seyfert galaxies, which is $\eta _{\rm jet}\approx 1.9^{+0.9}_{-1.5}\times 10^{-4}$ on average. We also find that ηjet increases as the system goes fainter. Alternative scenarios for the radio emission in RQ systems are also discussed.
Blending and obscuration in weak-lensing magnification
Authors: Gaztanaga E , Schmidt S J , Schneider M D , Tyson J A
Published: February 2021

We test the impact of some systematic errors in weak-lensing (WL) magnification measurements with the COSMOS 30-band photo-z Survey flux limited to Iauto < 25.0 using correlations of both source galaxy counts and magnitudes. Systematic obscuration effects are measured by comparing counts and magnification correlations. We use the Advanced Camera for Survey-Hubble Space Telescope catalogues to identify potential blending objects (close pairs) and perform the magnification analyses with and without blended objects. We find that blending effects start to be important (∼0.04-mag obscuration) at angular scales smaller than 0.1 arcmin. Extinction and other systematic obscuration effects can be as large as 0.10 mag (U band) but are typically smaller than 0.02 mag depending on the band. After applying these corrections, we measure a 3.9σ magnification signal that is consistent for both counts and magnitudes. The corresponding projected mass profiles of galaxies at redshift z ≃ 0.6 (MI ≃ −21) is Σ = 25 ± 6 M⊙ h3 pc–2 at 0.1 Mpc h–1, consistent with NFW type profile with M200 ≃ 2 × 1012 M⊙h pc–2. Tangential shear and flux-size magnification over the same lenses show similar mass profiles. We conclude that magnification from counts and fluxes using photometric redshifts has the potential to provide complementary WL information in future wide-field surveys once we carefully take into account systematic effects, such as obscuration and blending.
Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity
Authors: Burgess Joshua T , Cheong Chee Man , Suraweera Amila , Sobanski Thais , Beard Sam , Dave Keyur , Rose Maddison , Boucher Didier , Croft Laura V , Adams Mark N , O’Byrne Kenneth , Richard Derek J , Bolderson Emma
Published: February 2021

DNA repair pathways are essential to maintain the integrity of the genome and prevent cell death and tumourigenesis. Here, we show that the Barrier-to-Autointegration Factor (Banf1) protein has a role in the repair of DNA double-strand breaks. Banf1 is characterized as a nuclear envelope protein and mutations in Banf1 are associated with the severe premature aging syndrome, Néstor–Guillermo Progeria Syndrome. We have previously shown that Banf1 directly regulates the activity of PARP1 in the repair of oxidative DNA lesions. Here, we show that Banf1 also has a role in modulating DNA double-strand break repair through regulation of the DNA-dependent Protein Kinase catalytic subunit, DNA-PKcs. Specifically, we demonstrate that Banf1 relocalizes from the nuclear envelope to sites of DNA double-strand breaks. We also show that Banf1 can bind to and directly inhibit the activity of DNA-PKcs. Supporting this, cellular depletion of Banf1 leads to an increase in non-homologous end-joining and a decrease in homologous recombination, which our data suggest is likely due to unrestrained DNA-PKcs activity. Overall, this study identifies how Banf1 regulates double-strand break repair pathway choice by modulating DNA-PKcs activity to control genome stability within the cell.
A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study
Authors: Fangusaro Jason , Onar-Thomas Arzu , Poussaint Tina Young , Wu Shengjie , Ligon Azra H , Lindeman Neal , Campagne Olivia , Banerjee Anu , Gururangan Sridharan , Kilburn Lindsay B , Goldman Stewart , Qaddoumi Ibrahim , Baxter Patricia , Vezina Gilbert , Bregman Corey , Patay Zoltan , Jones Jeremy Y , Stewart Clinton F , Fisher Michael J , Doyle Laurence Austin , Smith Malcolm , Dunkel Ira J , Fouladi Maryam
Published: February 2021

Background

Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type 1) optic pathway and hypothalamic gliomas (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes.

Methods

We present results from children with recurrent/progressive OPHGs treated on a PBTC (Pediatric Brain Tumor Consortium) phase II trial evaluating efficacy of selumetinib (AZD6244, ARRY-142886) a MEK-1/2 inhibitor. Stratum 4 of PBTC-029 included patients with sporadic recurrent/progressive OPHGs treated with selumetinib at the recommended phase II dose (25mg/m2/dose BID) for a maximum of 26 courses.

Results

Twenty-five eligible and evaluable patients were enrolled with a median of 4 (1-11) previous therapies. Six of 25 (24%) had partial response, 14/25 (56%) had stable disease, and 5 (20%) had progressive disease while on treatment. The median treatment courses were 26 (2-26); 14/25 patients completed all 26 courses. Two-year PFS was 78 ± 8.5%. Nineteen of 25 patients were evaluable for visual acuity which improved in 4/19 patients (21%), was stable in 13/19 (68%), and worsened in 2/19 (11%). Five of 19 patients (26%) had improved visual fields and 14/19 (74%) were stable. The most common toxicities were grade 1/2 CPK elevation, anemia, diarrhea, headache, nausea/emesis, fatigue, AST and ALT increase, hypoalbuminemia, and rash.

Conclusions

Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS, and visual outcomes.
Theater and Performance in the 19th Century
Authors: Jones Douglas , Ozier Amadi
Published: February 2021

Theater and performance of the long 19th century (1789–1914) is one of the most dynamic fields in African American studies today. Scholars have turned to these embodied practices to understand the achievements, hardships, and imaginaries of black life in this period because enslaved and free African Americans were often denied access to, or the wherewithal to use, the archivable materials we traditionally use for historical research. The field has devised innovative methodologies and reading practices to reimagine and theorize the aesthetics, affects, labor demands, and politics of African American theater and performance in this period. These critical strategies have helped to offset some of the challenges that hinder the study of all live performance. In spite of these limitations, generative observations of theatrical and performance cultures of the enslaved and free African Americans are available, albeit often beneath layers of condemnation, mockery, and scorn. This article focuses on primary works that document, and criticism that analyzes, the origins and evolution of African American theater culture from the late 18th century up to but not including the New Negro (or Harlem) Renaissance (c. 1920). It also offers representative studies of contemporaneous dance and music that help to contextualize black theatrical practice, but it leaves the bulk of that scholarship to other bibliographies. Major archival collections, canonical play texts, and a broad range of criticism clustered in major scholarly categories of African American theater and performance of the era are included here.
For-Profit Private Prisons and the Criminal Justice–Industrial Complex
Authors: Leighton Paul
Published: February 2021

Privatization refers to outsourcing government functions to a private, usually for-profit, business although the arrangement can be with a non-profit organization. Currently, the most privatized aspect of criminal justice is punishment in general and prisons in particular. Prisons have historically engaged in “nominal privatization,” which includes privatization of services such as the designing and construction of prisons, provision of food services, medical care, and commissary. During the 1980s, contracts expanded to include “operational privatization,” which meant contracting out the day-to-day management of prisons to private, for-profit companies. Operational privatization involves a private company operating a facility owned by the government or managing inmates in a prison that the company owns. In some countries, such arrangements may be called public private partnerships (PPP) or private finance initiatives (PFI). Operational privatization originated during the 1980s in the United States, which was undergoing an unprecedented prison expansion because of ongoing wars on crime and drugs. At the same time, politicians were promising tax cuts, so privatization allowed a resolution to the contradiction by allowing private capital to profit by taking on some traditional responsibilities of government. Despite objections that the privatization of punishment and prison were different in nature than, say, trash collection, the dominant political view was that government kept sentencing authority and business could do the other functions more efficiently. While operational privatization has spread to a handful of countries, the largest private prison corporations are US-based, multibillion-dollar multinational companies that are traded on stock exchanges. As such, private prisons are the tip of a much larger criminal justice (CJ)–industrial complex, which describes a range of business and financial interests whose profit motive can shape criminal justice policy, including in ways that perpetuate current injustices. The CJ-industrial complex, mirroring the military-industrial complex President Eisenhower warned of, is comprised of everyone who financially profits from the police, courts, and corrections system. In turn, it is part of a larger security-industrial complex, which includes private security, investigators, intelligence, and technology sold as a response to (real and exaggerated) fear of crime, hackers, terrorists, and youth. Even when considered on its own, though, the CJ-industrial complex is significant because it could also mirror the concerns Eisenhower had: that because of its size and lobbying power, the defense industry could start to make policy based too much on its own interest rather than for the public good.