bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Demographic History Inferred by High-Resolution Analysis of Linkage Disequilibrium
Authors: Santiago Enrique , Novo Irene , Pardiñas Antonio F , Saura María , Wang Jinliang , Caballero Armando 
Published: July 2020

AbstractInferring changes in effective population size (Ne) in the recent past is of special interest for conservation of endangered species and for human history research. Current methods for estimating the very recent historical Ne are unable to detect complex demographic trajectories involving multiple episodes of bottlenecks, drops, and expansions. We develop a theoretical and computational framework to infer the demographic history of a population within the past 100 generations from the observed spectrum of linkage disequilibrium (LD) of pairs of loci over a wide range of recombination rates in a sample of contemporary individuals. The cumulative contributions of all of the previous generations to the observed LD are included in our model, and a genetic algorithm is used to search for the sequence of historical Ne values that best explains the observed LD spectrum. The method can be applied from large samples to samples of fewer than ten individuals using a variety of genotyping and DNA sequencing data: haploid, diploid with phased or unphased genotypes and pseudohaploid data from low-coverage sequencing. The method was tested by computer simulation for sensitivity to genotyping errors, temporal heterogeneity of samples, population admixture, and structural division into subpopulations, showing high tolerance to deviations from the assumptions of the model. Computer simulations also show that the proposed method outperforms other leading approaches when the inference concerns recent timeframes. Analysis of data from a variety of human and animal populations gave results in agreement with previous estimations by other methods or with records of historical events.
Mimicking the temperature gradient between the sow’s oviduct and uterus improves in vitro embryo culture output
Authors: García-Martínez S , Latorre R , Sánchez-Hurtado M A , Sánchez-Margallo F M , Bernabò N , Romar R , López-Albors O , Coy P 
Published: July 2020

Abstract
This work was designed to determine temperature conditions within the reproductive tract of the female pig and study their impact on ARTs. Temperatures were recorded using a laparo-endoscopic single-site surgery assisted approach and a miniaturized probe. Sows and gilts were used to address natural cycle and ovarian stimulation treatments, respectively. According to in vivo values, IVF was performed at three temperature conditions (37.0°C, 38.5°C and 39.5°C) and presumptive zygotes were cultured in these conditions for 20 h, while further embryo culture (EC) (21–168 h post-insemination) was maintained at 38.5°C. After 20 h, different fertility parameters were assessed. During EC, cleavage and blastocyst stages were evaluated. Sperm membrane fluidity at the experimental temperatures was studied by using differential scanning calorimetry and fluorescence recovery after photobleaching techniques. An increasing temperature gradient of 1.5°C was found between the oviduct and uterus of sows (P &lt; 0.05) and when this gradient was transferred to pig in vitro culture, the number of poly-nuclear zygotes after IVF was reduced and the percentage of blastocysts was increased. Moreover, the temperature transition phase for the boar sperm membrane (37.0°C) coincided with the temperature registered in the sow oviduct, and sperm membranes were more fluid at 37.0°C compared with those of sperm incubated at higher temperatures (38.5°C and 39.5°C). These data suggest that there may be an impact of physiological temperature gradients on human embryo development.
The alarmin interleukin-1α causes preterm birth through the NLRP3 inflammasome
Authors: Motomura K , Romero R , Garcia-Flores V , Leng Y , Xu Y , Galaz J , Slutsky R , Levenson D , Gomez-Lopez N 
Published: July 2020

AbstractSterile intra-amniotic inflammation is a clinical condition frequently observed in women with preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Growing evidence suggests that alarmins found in amniotic fluid, such as interleukin (IL)-1α, are central initiators of sterile intra-amniotic inflammation. However, the causal link between elevated intra-amniotic concentrations of IL-1α and preterm birth has yet to be established. Herein, using an animal model of ultrasound-guided intra-amniotic injection of IL-1α, we show that elevated concentrations of IL-1α cause preterm birth and neonatal mortality. Additionally, using immunoblotting techniques and a specific immunoassay, we report that the intra-amniotic administration of IL-1α induces activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in the fetal membranes, but not in the decidua, as evidenced by a concomitant increase in the protein levels of NLRP3, active caspase-1, and IL-1β. Lastly, using Nlrp3−/− mice, we demonstrate that the deficiency of this inflammasome sensor molecule reduces the rates of preterm birth and neonatal mortality caused by the intra-amniotic injection of IL-1α. Collectively, these results demonstrate a causal link between elevated IL-1α concentrations in the amniotic cavity and preterm birth as well as adverse neonatal outcomes, a pathological process that is mediated by the NLRP3 inflammasome. These findings shed light on the mechanisms underlying sterile intra-amniotic inflammation and provide further evidence that this clinical condition can potentially be treated by targeting the NLRP3 inflammasome.
A point mutation in the nuclease domain of MLH3 eliminates repeat expansions in a mouse stem cell model of the Fragile X-related disorders
Authors: Hayward Bruce E , Steinbach Peter J , Usdin Karen 
Published: July 2020

Abstract
The Fragile X-related disorders (FXDs) are Repeat Expansion Diseases, genetic disorders that result from the expansion of a disease-specific microsatellite. In those Repeat Expansion Disease models where it has been examined, expansion is dependent on functional mismatch repair (MMR) factors, including MutLγ, a heterodimer of MLH1/MLH3, one of the three MutL complexes found in mammals and a minor player in MMR. In contrast, MutLα, a much more abundant MutL complex that is the major contributor to MMR, is either not required for expansion or plays a limited role in expansion in many model systems. How MutLγ acts to generate expansions is unclear given its normal role in protecting against microsatellite instability and while MLH3 does have an associated endonuclease activity, whether that contributes to repeat expansion is uncertain. We show here, using a gene-editing approach, that a point mutation that eliminates the endonuclease activity of MLH3 eliminates expansions in an FXD mouse embryonic stem cell model. This restricts the number of possible models for repeat expansion and supports the idea that MutLγ may be a useful druggable target to reduce somatic expansion in those disorders where it contributes to disease pathology.
Impact of 5-formylcytosine on the melting kinetics of DNA by 1H NMR chemical exchange
Authors: Dubini Romeo C A , Schön Alexander , Müller Markus , Carell Thomas , Rovó Petra 
Published: July 2020

Abstract
5-Formylcytosine (5fC) is a chemically edited, naturally occurring nucleobase which appears in the context of modified DNA strands. The understanding of the impact of 5fC on dsDNA physical properties is to date limited. In this work, we applied temperature-dependent 1H Chemical Exchange Saturation Transfer (CEST) NMR experiments to non-invasively and site-specifically measure the thermodynamic and kinetic influence of formylated cytosine nucleobase on the melting process involving dsDNA. Incorporation of 5fC within symmetrically positioned CpG sites destabilizes the whole dsDNA structure—as witnessed from the ∼2°C decrease in the melting temperature and 5–10 kJ mol−1 decrease in ΔG°—and affects the kinetic rates of association and dissociation. We observed an up to ∼5-fold enhancement of the dsDNA dissociation and an up to ∼3-fold reduction in ssDNA association rate constants, over multiple temperatures and for several proton reporters. Eyring and van’t Hoff analysis proved that the destabilization is not localized, instead all base-pairs are affected and the transition states resembles the single-stranded conformation. These results advance our knowledge about the role of 5fC as a semi-permanent epigenetic modification and assist in the understanding of its interactions with reader proteins.
PARP1 catalytic variants reveal branching and chain length-specific functions of poly(ADP-ribose) in cellular physiology and stress response
Authors: Aberle Lisa , Krüger Annika , Reber Julia M , Lippmann Michelle , Hufnagel Matthias , Schmalz Michael , Trussina Irmela R E A , Schlesiger Sarah , Zubel Tabea , Schütz Karina , Marx Andreas , Hartwig Andrea , Ferrando-May Elisa , Bürkle Alexander , Mangerich Aswin 
Published: July 2020

AbstractPoly(ADP-ribosyl)ation regulates numerous cellular processes like genome maintenance and cell death, thus providing protective functions but also contributing to several pathological conditions. Poly(ADP-ribose) (PAR) molecules exhibit a remarkable heterogeneity in chain lengths and branching frequencies, but the biological significance of this is basically unknown. To unravel structure-specific functions of PAR, we used PARP1 mutants producing PAR of different qualities, i.e. short and hypobranched (PARP1\G972R), short and moderately hyperbranched (PARP1\Y986S), or strongly hyperbranched PAR (PARP1\Y986H). By reconstituting HeLa PARP1 knockout cells, we demonstrate that PARP1\G972R negatively affects cellular endpoints, such as viability, cell cycle progression and genotoxic stress resistance. In contrast, PARP1\Y986S elicits only mild effects, suggesting that PAR branching compensates for short polymer length. Interestingly, PARP1\Y986H exhibits moderate beneficial effects on cell physiology. Furthermore, different PARP1 mutants have distinct effects on molecular processes, such as gene expression and protein localization dynamics of PARP1 itself, and of its downstream factor XRCC1. Finally, the biological relevance of PAR branching is emphasized by the fact that branching frequencies vary considerably during different phases of the DNA damage-induced PARylation reaction and between different mouse tissues. Taken together, this study reveals that PAR branching and chain length essentially affect cellular functions, which further supports the notion of a ‘PAR code’.
Human GTPBP5 (MTG2) fuels mitoribosome large subunit maturation by facilitating 16S rRNA methylation
Authors: Maiti Priyanka , Antonicka Hana , Gingras Anne-Claude , Shoubridge Eric A , Barrientos Antoni 
Published: July 2020

AbstractBiogenesis of mammalian mitochondrial ribosomes (mitoribosomes) involves several conserved small GTPases. Here, we report that the Obg family protein GTPBP5 or MTG2 is a mitochondrial protein whose absence in a TALEN-induced HEK293T knockout (KO) cell line leads to severely decreased levels of the 55S monosome and attenuated mitochondrial protein synthesis. We show that a fraction of GTPBP5 co-sediments with the large mitoribosome subunit (mtLSU), and crosslinks specifically with the 16S rRNA, and several mtLSU proteins and assembly factors. Notably, the latter group includes MTERF4, involved in monosome assembly, and MRM2, the methyltransferase that catalyzes the modification of the 16S mt-rRNA A-loop U1369 residue. The GTPBP5 interaction with MRM2 was also detected using the proximity-dependent biotinylation (BioID) assay. In GTPBP5-KO mitochondria, the mtLSU lacks bL36m, accumulates an excess of the assembly factors MTG1, GTPBP10, MALSU1 and MTERF4, and contains hypomethylated 16S rRNA. We propose that GTPBP5 primarily fuels proper mtLSU maturation by securing efficient methylation of two 16S rRNA residues, and ultimately serves to coordinate subunit joining through the release of late-stage mtLSU assembly factors. In this way, GTPBP5 provides an ultimate quality control checkpoint function during mtLSU assembly that minimizes premature subunit joining to ensure the assembly of the mature 55S monosome.
Trajectories and Risk Factors for Pediatric Postconcussive Symptom Recovery
Authors: Truss Katie , Hearps Stephen J C , Babl Franz E , Takagi Michael , Davis Gavin A , Clarke Cathriona , Anderson Nicholas , Rausa Vanessa C , Bressan Silvia , Dunne Kevin , Anderson Vicki 
Published: July 2020

AbstractBACKGROUNDPersistent postconcussive symptoms (PCS) are poorly understood in children. Research has been limited by an assumption that children with concussion are a homogenous group.OBJECTIVETo identify (i) distinctive postconcussive recovery trajectories in children and (ii) injury-related and psychosocial factors associated with these trajectories.METHODSThis study is part of a larger prospective, longitudinal study. Parents of 169 children (5-18 yr) reported their child's PCS over 3 mo following concussion. PCS above baseline levels formed the primary outcome. Injury-related, demographic, and preinjury information, and child and parent mental health were assessed for association with trajectory groups. Data were analyzed using group-based trajectory modeling, multinomial logistic regression, and chi-squared tests.RESULTSWe identified 5 postconcussive recovery trajectories from acute to 3 mo postinjury. (1) Low Acute Recovered (26.6%): consistently low PCS; (2) Slow to Recover (13.6%): elevated symptoms gradually reducing; (3) High Acute Recovered (29.6%): initially elevated symptoms reducing quickly to baseline; (4) Moderate Persistent (18.3%): consistent, moderate levels of PCS; (5) Severe Persistent (11.8%): persisting high PCS. Higher levels of child internalizing behaviors and greater parental distress were associated with membership to the Severe Persistent group, relative to the Low Acute Recovered group.CONCLUSIONThis study indicates variability in postconcussive recovery according to 5 differential trajectories, with groups distinguished by the number of reported symptoms, levels of child internalizing behavior problems, and parental psychological distress. Identification of differential recovery trajectories may allow for targeted early intervention for children at risk of poorer outcomes.
Engineering biocompatible TeSex nano-alloys as a versatile theranostic nanoplatform
Authors: Ling Xiang , Jin Zhaokui , Jiang Qi , Wang Xiaotao , Wei Bin , Wang Zhongchang , Xu Yangsen , Cao Tianye , Engle Jonathan W , Cai Weibo , Su Chenliang , He Qianjun 
Published: July 2020

Abstract
Photothermal nanotheranostics, especially in the near infrared II (NIR-II) region, exhibits a great potential in precision and personalized medicine, owing to high tissue penetration of NIR-II light. NIR-II-photothermal nanoplatforms with high biocompatibility as well as high photothermal effect are urgently needed but rarely reported so far. Te nanomaterials possess high absorbance to NIR-II light but also exhibit high cytotoxicity, impeding their biomedical applications. In this work, the controllable incorporation of biocompatible Se into the lattice of Te nanostructures is proposed to intrinsically tune their inherent cytotoxicity and enhance their biocompatibility, developing TeSex nano-alloys as a new kind of theranostic nanoplatform. We have uncovered that the cytotoxicity of Te nanomaterials primarily derives from irreversible oxidation stress and intracellular imbalance of organization and energy, and can be eliminated by incorporating a moderate proportion of Se (x = 0.43). We have also discovered that the as-prepared TeSex nano-alloys have extraordinarily high NIR-II-photothermal conversion efficiency (77.2%), 64Cu coordination and computed tomography contrast capabilities, enabling high-efficacy multimodal photothermal/photoacoustic/positron emission tomography/computed tomography imaging-guided NIR-II-photothermal therapy of cancer. The proposed nano-alloying strategy provides a new route to improve the biocompatibility of biomedical nanoplatforms and endow them with versatile theranostic functions.
Religiosity and veteran mental health compared with non-veterans
Authors: Rogers R L 
Published: July 2020

Abstract

Background
While the potential buffering effects of spirituality are well established in the general population, how spirituality affects those in extremely high-stress occupations like the military and law enforcement is less clear.

Aims
This paper explores the possibility that spiritual influences may operate differently among military veterans than other people. It specifically proposes that attendance at religious services is an especially important buffer for combat veterans.

Methods
This study engaged in a secondary analysis of 74 480 respondents from the National Survey on Drug Use and Health for the years 2013–17. The respondents were split into four groups; veterans with combat experience before September 2001, veterans with combat experience since September 2001, veterans with no combat experience and non-veterans.

Results
The likelihood of mental illness decreased in the general population along three different measures of religion; the importance of religion, friendships that shared religious beliefs and attendance at religious services. The relationship was weak and disappeared when controls for non-religion variables were included. A major exception was combat veterans, for whom the religious effects were limited to attendance at services, and the effect survived with the addition of non-religion control variables.

Conclusions
Mental health professionals, chaplains, pastoral counsellors and clergy need to recognize that among the therapeutic benefits of religious attendance and recognize the value of the religious rituals as ends in themselves.
The Development of a Crosswalk for Functional Measures in Postacute Medicare Claims
Authors: McDonough Christine M , Carmichael Donald , Marino Molly E , Ni Pengsheng , Tosteson Anna N A , Bynum Julie P W 
Published: July 2020

Abstract

Objective
Although Medicare assessment files will include Standardized Patient Assessment Data Elements from 2016 forward, lack of uniformity of functional data prior to 2016 impedes longitudinal research. The purpose of this study was to create crosswalks for postacute care assessment measures and the basic mobility and daily activities scales of the Activity Measure for Post-Acute Care (AM-PAC) and to test their accuracy and validity in development and validation datasets.

Methods
This cross-sectional study is a secondary analysis of AM-PAC, the Inpatient Rehabilitation Facility Patient Assessment Instrument, the Minimum Data Set, and the Outcome and Assessment Information Set data from 300 adults receiving rehabilitation recruited from 6 health care networks in 1 metropolitan area. Rasch analysis was used to co-calibrate items from the 3 measures onto the AM-PAC metric and to create look-up tables to create estimated AM-PAC (eAM-PAC) scores. Mean scores and correlation and agreement between actual and estimated scores were examined in the development dataset. Scores were estimated in a cohort of Medicare beneficiaries with hip, humerus and radius fractures. Correlations between eAM-PAC and Functional Independence Measure motor scores were examined. Differences in mean eAM-PAC scores were evaluated across groups of known differences (age, fracture type, dementia).

Results
Strong correlations were found between actual and eAM-PAC scores in the development dataset. Moderate to strong correlations were found between the eAM-PAC basic mobility and Functional Independence Measure motor scores in the validation dataset. Differences in basic mobility scores across known groups were statistically significant and appeared to be clinically important. Differences between mean daily activities scores were statistically significant but appeared not to be clinically important.

Conclusion
Although further testing is warranted, the basic mobility crosswalk appears to provide valid scores for aggregate analysis of Medicare postacute care data.

Impact
This study reports on a method to take data from different Medicare administrative data sources and estimate scores on 1 scale. This approach was applied separately for data related to basic mobility and to daily activities. This may allow researchers to overcome challenges with using Medicare administrative data from different sources.
The patient’s perspective: are quality of life and disease burden a possible treatment target in systemic lupus erythematosus?
Authors: Kernder Anna , Elefante Elena , Chehab Gamal , Tani Chiara , Mosca Marta , Schneider Matthias 
Published: July 2020

Abstract
A few decades ago, the therapy goal of patients with systemic lupus erythematosus (SLE) was survival and the prevention of organ failure. Today, clinical remission and low disease activity are believed to be the optimal therapeutic targets. These aims are difficult to reach for many patients, but they still do not address the health-related quality of life (QoL) that is significantly impaired in SLE patients. Even in the state of remission, QoL and fatigue are insufficient controlled. Thus, patient-oriented research is essential to design new strategies for the management of lupus patients. The INTEGRATE project analyses the patients’ and physicians’ perspectives to pave the way to design an innovative therapeutic strategy for lupus and focuses on the multifaceted dimensions of the disease burden. Shared decision making (SDM) could include the patient’s perspective of SLE to treatment strategy and consider QoL and the burden of lupus into the process of therapy decision.
Untargeted lipidomics reveals specific lipid abnormalities in Sjögren’s syndrome
Authors: Lu Jiawei , Guo Yunke , Lu Yan , Ji Wei , Lin Lili , Qian Wenjuan , Chen Wenjun  , Wang Jue , Lv Xiangyu , Ke Mengying , Kong Deshun , Shen Qiuxiang , Zhu Youjuan , Liu Ping , Su Jinfeng , Wang Lu , Li Yuhua , Gao Pan  , Shan Jinjun , Liu Shijia 
Published: July 2020

Abstract

Objective
The relationship between serum lipid variations in SS and healthy controls was investigated to identify potential predictive lipid biomarkers.

Methods
Serum samples from 230 SS patients and 240 healthy controls were collected. The samples were analysed by ultrahigh-performance liquid chromatography coupled with Q Exactive™ spectrometry. Potential lipid biomarkers were screened through orthogonal projection to latent structures discriminant analysis and further evaluated by receiver operating characteristic analysis.

Results
A panel of three metabolites [phosphatidylcholine (18:0/22:5), triglyceride (16:0/18:0/18:1) and acylcarnitine (12:0)] was identified as a specific biomarker of SS. The receiver operating characteristic analysis showed that the panel had a sensitivity of 84.3% with a specificity of 74.8% in discriminating patients with SS from healthy controls.

Conclusion
Our approach successfully identified serum biomarkers associated with SS patients. The potential lipid biomarkers indicated that SS metabolic disturbance might be associated with oxidized lipids, fatty acid oxidation and energy metabolism.