bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two decades of X-ray observations of the isolated neutron star RX J1856.5 − 3754: detection of thermal and non-thermal hard X-rays and refined spin-down measurement
Authors: De Grandis Davide , Rigoselli Michela , Mereghetti Sandro , Younes George , Pizzochero Pierre , Taverna Roberto , Tiengo Andrea , Turolla Roberto , Zane Silvia 
Published: September 2022

ABSTRACT
The soft X-ray pulsar RX J1856.5 − 3754 is the brightest member of a small class of thermally emitting, radio-silent, isolated neutron stars. Its X-ray spectrum is almost indistinguishable from a blackbody with $kT^\infty \approx {60}\, {\rm eV}$, but evidence of harder emission above $\sim {1}\, {\rm keV}$ has been recently found. We report on a spectral and timing analysis of RX J1856.5 − 3754 based on the large amount of data collected by XMM-Newton in 2002–2022, complemented by a dense monitoring campaign carried out by NICER in 2019. Through a phase-coherent timing analysis we obtained an improved value of the spin-down rate $\dot{\nu }=-6.042(4)\times 10^{-16}\, {\rm Hz\, s}^{-1}$, reducing by more than one order magnitude the uncertainty of the previous measurement, and yielding a characteristic spin-down field of $1.47\times 10^{13}\, {\rm G}$. We also detect two spectral components above $\sim 1\, {\rm keV}$: a blackbody-like one with $kT^\infty =138\pm 13\,$eV and emitting radius $31_{-16}^{+8}\,$m, and a power law with photon index $\Gamma =1.4_{-0.4}^{+0.5}$. The power-law 2–8 keV flux, $(2.5_{-0.6}^{+0.7})\times 10^{-15}\, {\rm erg}\, {\rm cm}^{-2}\, {\rm s}^{-1}$, corresponds to an efficiency of 10−3, in line with that seen in other pulsars. We also reveal a small difference between the 0.1–0.3 keV and 0.3–1.2 keV pulse profiles, as well as some evidence for a modulation above 1.2 keV. These results show that, notwithstanding its simple spectrum, RX J1856.5 − 3754 still has a non-trivial thermal surface distribution and features non-thermal emission as seen in other pulsars with higher spin-down power.
Epi-MEIF: detecting higher order epistatic interactions for complex traits using mixed effect conditional inference forests
Authors: Saha Saswati , Perrin Laurent , Röder Laurence , Brun Christine , Spinelli Lionel 
Published: September 2022

Abstract
Understanding the relationship between genetic variations and variations in complex and quantitative phenotypes remains an ongoing challenge. While Genome-wide association studies (GWAS) have become a vital tool for identifying single-locus associations, we lack methods for identifying epistatic interactions. In this article, we propose a novel method for higher-order epistasis detection using mixed effect conditional inference forest (epiMEIF). The proposed method is fitted on a group of single nucleotide polymorphisms (SNPs) potentially associated with the phenotype and the tree structure in the forest facilitates the identification of n-way interactions between the SNPs. Additional testing strategies further improve the robustness of the method. We demonstrate its ability to detect true n-way interactions via extensive simulations in both cross-sectional and longitudinal synthetic datasets. This is further illustrated in an application to reveal epistatic interactions from natural variations of cardiac traits in flies (Drosophila). Overall, the method provides a generalized way to identify higher-order interactions from any GWAS data, thereby greatly improving the detection of the genetic architecture underlying complex phenotypes.
Mitochondrial stress induces AREG expression and epigenomic remodeling through c-JUN and YAP-mediated enhancer activation
Authors: Hino Yuko , Nagaoka Katsuya , Oki Shinya , Etoh Kan , Hino Shinjiro , Nakao Mitsuyoshi 
Published: September 2022

Abstract
Nucleus–mitochondria crosstalk is essential for cellular and organismal homeostasis. Although anterograde (nucleus-to-mitochondria) pathways have been well characterized, retrograde (mitochondria-to-nucleus) pathways remain to be clarified. Here, we found that mitochondrial dysfunction triggered a retrograde signaling via unique transcriptional and chromatin factors in hepatic cells. Our transcriptomic analysis revealed that the loss of mitochondrial transcription factor A led to mitochondrial dysfunction and dramatically induced expression of amphiregulin (AREG) and other secretory protein genes. AREG expression was also induced by various mitochondria stressors and was upregulated in murine liver injury models, suggesting that AREG expression is a hallmark of mitochondrial damage. Using epigenomic and informatic approaches, we identified that mitochondrial dysfunction-responsive enhancers of AREG gene were activated by c-JUN/YAP1/TEAD axis and were repressed by chromatin remodeler BRG1. Furthermore, while mitochondrial dysfunction-activated enhancers were enriched with JUN and TEAD binding motifs, the repressed enhancers possessed the binding motifs for hepatocyte nuclear factor 4α, suggesting that both stress responsible and cell type-specific enhancers were reprogrammed. Our study revealed that c-JUN and YAP1-mediated enhancer activation shapes the mitochondrial stress-responsive phenotype, which may shift from metabolism to stress adaptation including protein secretion under such stressed conditions.
NMR determination of the 2:1 binding complex of naphthyridine carbamate dimer (NCD) and CGG/CGG triad in double-stranded DNA
Authors: Yamada Takeshi , Furuita Kyoko , Sakurabayashi Shuhei , Nomura Makoto , Kojima Chojiro , Nakatani Kazuhiko 
Published: September 2022

Abstract
Trinucleotide repeat (TNR) diseases are caused by the aberrant expansion of CXG (X = C, A, G and T) sequences in genomes. We have reported two small molecules binding to TNR, NCD, and NA, which strongly bind to CGG repeat (responsible sequence of fragile X syndrome) and CAG repeat (Huntington's disease). The NMR structure of NA binding to the CAG/CAG triad has been clarified, but the structure of NCD bound to the CGG/CGG triad remained to be addressed. We here report the structural determination of the NCD-CGG/CGG complex by NMR spectroscopy and the comparison with the NA-CAG/CAG complex. While the NCD-CGG/CGG structure shares the binding characteristics with that of the NA-CAG/CAG complex, a significant difference was found in the overall structure caused by the structural fluctuation at the ligand-bound site. The NCD-CGG/CGG complex was suggested in the equilibrium between stacked and kinked structures, although NA-CAG/CAG complex has only the stacked structures. The dynamic fluctuation of the NCD-CGG/CGG structure at the NCD-binding site suggested room for optimization in the linker structure of NCD to gain improved affinity to the CGG/CGG triad.
A spatiotemporal atlas of organogenesis in the development of orchid flowers
Authors: Liu Chang , Leng Jing , Li Yonglong , Ge Tingting , Li Jinglong , Chen Yamao , Guo Chunce , Qi Ji 
Published: September 2022

Abstract
Development of floral organs exhibits complex molecular mechanisms involving the co-regulation of many genes specialized and precisely functioning in various tissues and developing stages. Advance in spatial transcriptome technologies allows for quantitative measurement of spatially localized gene abundance making it possible to bridge complex scenario of flower organogenesis with genome-wide molecular phenotypes. Here, we apply the 10× Visium technology in the study of the formation of floral organs through development in an orchid plant, Phalaenopsis Big Chili. Cell-types of early floral development including inflorescence meristems, primordia of floral organs and identity determined tissues, are recognized based on spatial expression distribution of thousands of genes in high resolution. In addition, meristematic cells on the basal position of floral organs are found to continuously function in multiple developmental stages after organ initiation. Particularly, the development of anther, which primordium starts from a single spot to multiple differentiated cell-types in later stages including pollinium and other vegetative tissues, is revealed by well-known MADS-box genes and many other downstream regulators. The spatial transcriptome analyses provide comprehensive information of gene activity for understanding the molecular architecture of flower organogenesis and for future genomic and genetic studies of specific cell-types.
Protein intake and its effect on sleep outcomes: a systematic review and meta-analysis of randomized controlled trials
Authors: Wirth Janine , Hillesheim Elaine , Brennan Lorraine 
Published: September 2022

Abstract

Context
Poor sleep is increasingly seen as an issue of public health concern. In recent years, there has been growing interest in protein as a route to improve sleep outcomes; however, the evidence is limited and inconclusive.

Objective
To examine, using a systematic review and meta-analysis, the effect of increased protein intake (≥1 g/kg//d, ≥25% of total energy intake, or protein supplementation of ≥10 g/d/) on sleep outcomes in adults.

Methods
On November 30, 2021, 5 electronic databases were searched to identify relevant randomized controlled trials (PubMed, Cochrane, Embase, Web of Science, and CINAHL Plus). Risk of bias was assessed using the Cochrane Risk-of-Bias tool, version 2.0.

Data Extraction
Five sleep outcomes were included in this systematic review (sleep quality [SQ], sleep latency [SL], sleep efficiency [SEff], sleep time [ST], wake episodes, and other sleep outcomes) and 4 in the meta-analysis (SQ, SL, SEff, and ST). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Data Analysis
Twelve intervention studies reported on in 10 articles were included. The qualitative analyses showed that increased protein consumption has little influence on sleep outcomes. Only subjective SQ was positively associated with protein consumption in a few studies. Meta-analyses also showed no significant effect of increased protein intake on sleep outcomes (number of studies for SQ, ST, SL, and SEff: 8, 8, 7, and 6, respectively), with very low certainty of evidence. However, results from sensitivity analyses, excluding high-risk studies, suggest a small effect on SQ in favor of high protein intake (mean difference, –4.28; 95%CI, –7.77, –0.79; on a scale from 0 to 100).

Conclusion
This systematic review and meta-analysis indicate there is no clear relationship between increased protein intake and sleep. However, the strength of the evidence is low and more randomized controlled trials that focus on this specific research question are warranted.
Systematic Review Registration: PROSPERO registration no. CRD42020196021.
Hatching failure is greater in altricial bird species with cavity nests and large clutches
Authors: Di Giovanni Alexander J , Miller Michael J , Jones Todd M , Benson Thomas J , Ward Michael P 
Published: September 2022

AbstractMortality rates are high for most avian species during early life stages, forming a critical source of natural selection that helps shape the diversity of avian life-history traits. We investigated hatching failure (i.e., non-predatory embryonic mortality, excluding abandoned or damaged eggs) and found significant variation among passerine species. Failure rates ranged from 1.0% to 12.7%, and species with cavity nests and larger clutches experienced greater rates of hatching failure. While past research has focused on the direct effects of predation on the nestling and fledgling stages, little is known about how predation may indirectly influence other sources of mortality such as hatching failure. We investigated the influence of nest predation risk and other factors on variation in hatching failure among 14 free-living grassland and shrubland songbird species. Across all species, 7.7% of 1,667 eggs failed to hatch. We found little evidence that variation in nest temperature influenced rates of hatching failure within and among species, although species with larger clutch sizes had more variable nest temperatures. Dissection of failed eggs revealed that most hatching failures occurred before or shortly after the onset of development; however, there was no difference between cavity and open-cup nesters in the rate of early-stage mortality. Our findings suggest there may be tradeoffs to having a large clutch, with a benefit of rearing more young at the cost of greater hatching failure, possibly due to delayed onset of incubation, poor incubation behavior, or inability to incubate large clutches. Additionally, as larger clutches are often laid in cavity nests, which have a relatively low predation risk, this may outweigh the costs of increased hatching failure. More experimental approaches, such as clutch size manipulations and egg-specific incubation behavior are needed to provide greater insight into factors driving variation in hatching failure across species.
Ethics and CAT
Authors: Batchelor Henrietta 
Published: September 2022

Abstract
This chapter explores the dilemmas posed by many ethical problems and explores ways of thinking through decisions. Whilst in the end the clinician will need to think through a course of action, the attention to strong and often uncomfortable feelings elicited by ethical dilemmas is important. Often such feelings are at odds with one another but cognitive analytic therapy (CAT) provides a useful way of mapping out such dilemmas in particular by the use of sequential diagrammatic formulations (SDRs). Factors influencing moral disengagement are explored and this chapter notes that whilst most clinicians are not involved in the serious abuse of their clients, practitioners may behave unethically at times particularly if they are stressed, tired, or burnt out. Useful tools to guide ethical practice are professional codes of ethics and practice (which include information and instruction about confidentiality and boundaries), and the four pillars of medical ethics: autonomy, beneficence, non-maleficence, and justice. A number of case studies are explored to illustrate the use of these principles. Supervision has a key role in supporting and challenging practitioners to maintain ethical practice and, to this end, the cultivation of trusting and honest relationships in supervision are clearly important.
Corruption in Customs
Authors: Chalendard Cyril , Fernandes Ana M , Raballand Gael , Rijkers Bob 
Published: September 2022

AbstractThis article presents a new methodology to detect corruption in customs and applies it to Madagascar’s main port. Manipulation of assignment of import declarations to inspectors is identified by measuring deviations from random assignment prescribed by official rules. Deviant declarations are more at risk of tax evasion, yet less likely to be deemed fraudulent by inspectors, who also clear them faster. An intervention in which inspector assignment was delegated to a third party validates our approach, but also triggered a novel manifestation of manipulation that rejuvenated systemic corruption. Tax revenue losses associated with the corruption scheme are approximately 3% of total taxes collected and are highly concentrated among a select few inspectors and brokers.
METABOLISMS OF 13C IN CATTLE SEMITENDINOSUS MUSCLE AFTER ADMINISTRATION OF 13C LABELED ORCHARD GRASS
Authors: Masuda Tsuyoshi , Tani Takashi , Arai Ryuji , Tako Yasuhiro 
Published: September 2022

Abstract
14C released from nuclear facilities is transferred to cattle through their consumption of 14C contaminated grasses. To estimate the concentrations of 14C in their meat, we conducted two sets of experiments. In the first experiment, 230 mg of 13C per day was administered to cattle aged 10 months for 28 days in the form of 13C-labeled grass. The 13C concentration in the semitendinosus muscle decreased exponentially after reaching its peak value. The mean half-life was 76 ± 13 days. In the second experiment, 550 mg of 13C per day was administered to 24-month-old cattle. The change in the semitendinosus muscle was smaller than that recorded in the first experiment, even though the amount of 13C administered per body weight was slightly higher than that in the first experiment. Consequently, the half-life was not determined. Therefore, further studies are required to clarify the metabolism of carbon in 2-year-old cattle.
ON RADIATION-INDUCED AGING: ACCELERATED OR PREMATURE AGING
Authors: Wada Takahiro , Kinugawa Tetsuhiro , Tanaka Satoshi 
Published: September 2022

Abstract
The concept of radiation-induced aging is revisited from the viewpoint of a mathematical model. The effect of radiation on carcinogenesis is treated based on the Armitage–Doll multi-stage theory. The formula obtained for cancer incidence rate indicates that radiation dose can be explained in terms of time. Radiation-induced aging for acute and chronic exposures is described using age-specific cancer incidence rates as a measure of aging. It shows that accelerated aging is related to the dose rate, whereas premature aging is related to the cumulative dose, providing a simple and natural interpretation of radiation-induced aging. The usefulness of this approach is demonstrated by applying the formula to cancer prevalence data from mice chronically exposed to low dose-rate radiation.
Measuring sleep health in primary school-aged children: A systematic review of instruments and their content validity
Authors: Inhulsen Maj-Britt M R , van Stralen Maartje M , Terwee Caroline B , Ujcic-Voortman Joanne K , Seidell Jacob C , Busch Vincent 
Published: September 2022

Abstract

Study Objectives
This review aimed to summarize instruments that measure one or more domains of sleep health (i.e. duration, quality, efficiency, timing, daytime sleepiness and sleep-related behaviors) in a general population of 4–12-year old children, and to assess these instruments’ content validity. Other measurement properties were evaluated for instruments with indications of sufficient content validity.

Methods
A systematic literature search was performed in PubMed, PsycINFO, Web of Science, and EmBase. Methodological quality, content validity, and other measurement properties were assessed via the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Instruments with indications of sufficient content validity (i.e. relevance, comprehensiveness and comprehensibility) were further evaluated on other measurement properties (i.e. other aspects of validity, reliability, responsiveness). A modified GRADE approach was applied to determine the quality of evidence.

Results
Twenty instruments, containing 36 subscales, were included. None of the instruments measured all sleep health domains. For five (subscales of) instruments sufficient relevance and comprehensibility was found. The quality of evidence ranged from very low to moderate. For these five instruments all additional measurement properties were assessed. Sufficient results were found for structural validity (n = 1), internal consistency (n = 1), and construct validity (n = 1), with quality of evidence ranging from very low to high.

Conclusions
Several (subscales of) instruments measuring domains of child sleep health showed good promise, demonstrating sufficient relevance, comprehensibility, and some also sufficient results on other measurement properties. However, more high quality studies on instrument development and the evaluation of measurement properties are required.
PROSPERO registration number: CRD42021224109
Looking back at a life in sleep research—and some thoughts for the future
Authors: Mendelson Wallace B 
Published: September 2022

AbstractIn reviewing my studies, some of which are nearing the half century mark, I’ve described work on sleep-related growth hormone, the effects of hypnotics on the perception of sleep, REM sleep induction in humans by cholinergic drugs, the benzodiazepine receptor, the anatomic sites of action of hypnotics, the endocannabinoid system and sleep, and the relation of anesthesia to sleep. Special mention along the way goes to cases in which drugs produced totally unexpected effects, including methysergide producing opposite effects on growth hormone secretion in sleep and a waking provocative test, the converse actions on sleep of the B-10 benzodiazepine enantiomers, and the promotion of wakefulness by microinjection of the hypnotic triazolam into the dorsal raphe nuclei. This work is placed in the context of what was known at the time, as well as what has been observed in subsequent years. Many of these studies indicate that the medial preoptic area may be a common site for the sleep-promoting action of a wide range of agents including traditional hypnotics, ethanol, propofol and melatonin. In the future it may be worthwhile looking at the beta-carbolines, and also the endocannabinoid system, when exploring drugs with new mechanisms of action for treating sleep/wake disorders. An Addendum to this paper describes memories of working with Frederick Snyder, J. Christian Gillin, Richard Jed Wyatt, and Floyd E. Bloom.
Immunobiologicals and ocular surface disease
Authors: Bielory Leonard 
Published: September 2022

Purpose of review
Immunobiologicals have surfaced to become a new cornerstone of treatment for a wide spectrum of inflammatory disorders with an immune basis. The targets have ranged from autoimmune conditions to transplantation, and now more into atopic inflammatory disorders with primary targets of asthma and atopic dermatitis.

Recent findings
The clinical information garnered from these studies have provided an initial snapshot on the potential adverse effects of the immunobiologicals on the ocular surface as well as providing a potential opening of their use in the treatment of various chronic ocular surface and intraocular inflammatory disorders that have previously been relegated to limited therapeutic options primarily to the broad anti-inflammatory use of glucocorticosteroids.

Summary
The use of immunobiologicals provides a more directed therapeutic approach to many of the ocular inflammatory disorders, as we continue to appreciate more of their underlying immunopathophysiology of ocular surface disorder,s including ocular allergy and tear film dysfunction.
Frequency and outcomes of periprocedural myocardial infarction in patients with chronic coronary syndromes undergoing percutaneous coronary intervention
Authors: Ueki Yasushi , Räber Lorenz 
Published: September 2022

Purpose of review
Various definitions of periprocedural myocardial infarction (MI) have been proposed by academic groups and professional societies differing in terms of biomarker thresholds and ancillary criteria for myocardial ischemia. The incidence and clinical significance of periprocedural MI substantially varies according to the definitions applied. In this review, we summarize available clinical data on the frequency and outcomes of periprocedural MI according to various MI definitions in patients undergoing percutaneous coronary intervention (PCI).

Recent findings
Numerous clinical studies and meta-analyses have investigated the incidence and prognostic relevance of periprocedural MI following PCI. The incidence of periprocedural MI was higher when defined by universal definition of myocardial infarction (UDMI), which applies a lower biomarker threshold with broader ancillary criteria compared with the Society for Cardiovascular Angiography and Intervention (SCAI) and academic research consortium (ARC)-2. The prognostic impact of periprocedural MI defined by SCAI and ARC-2 on mortality was consistently greater compared with the UDMI definition.

Summary
Among chronic coronary syndrome patients undergoing PCI, the frequency and prognostic value of periprocedural MI varies considerably based on definitions. Periprocedural MI defined by the ARC-2 and SCAI occurred 3–6 times less frequently and were prognostically more relevant as compared with the UDMI. Clinically relevant definitions should be used in daily practice and clinical trials.