bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Mendelian Randomization Studies in Deciphering the Effect of Obesity on Cancer
Authors: Fang Zhe , Song Mingyang , Lee Dong Hoon , Giovannucci Edward L 
Published: May 2021

Abstract
Associations of obesity have been established for at least 11 cancer sites in observational studies, though some questions remain as to causality, strength of associations, and timing of associations throughout the life course. In recent years, Mendelian randomization (MR) has provided complementary information to traditional approaches, but the validity requires that the genetic instrumental variables be causally related to cancers only mediated by the exposure. We summarize and evaluate existing evidence from MR studies in comparison with conventional observational studies to provide insights into the complex relationship between obesity and multiple cancers. MR studies further establish the causality of adult obesity with esophageal adenocarcinoma and cancers of the colorectum, endometrium, ovary, kidney, and pancreas, as well as the inverse association of early life obesity with breast cancer. MR studies, which might account for lifelong adiposity, suggest that the associations in observational studies typically based on single measurement may underestimate the magnitude of the association. For lung cancer, MR studies find a positive association with obesity, supporting that the inverse association observed in some conventional observational studies likely reflects reverse causality (loss of lean body mass before diagnosis) and confounding by smoking. However, MR studies have not had sufficient power for gallbladder cancer, gastric cardia cancer, and multiple myeloma. In addition, more MR studies are needed to explore the effect of obesity at different timepoints on postmenopausal breast cancer and aggressive prostate cancer.
Open stomata 1 exhibits dual serine/threonine and tyrosine kinase activity in regulating abscisic acid signaling
Authors: Shang Yun , Yang Dami , Ha Yunmi , Lee Ju Yeon , Kim Jin Young , Oh Man-Ho , Nam Kyoung Hee 
Published: May 2021

Abstract
Open Stomata 1 (OST1)/SnRK2.6 is a critical component connecting abscisic acid (ABA) receptor complexes and downstream components, including anion channels and transcription factors. Because OST1 is a serine/threonine kinase, several autophosphorylation sites have been identified, and S175 is known to be critical for its kinase activity. We previously reported that BAK1 interacts with and phosphorylates OST1 to regulate ABA signaling. Here, we mapped additional phosphosites of OST1 generated by autophosphorylation and BAK1-mediated transphosphorylation in Arabidopsis. Many phosphosites serve as both auto- and transphosphorylation sites, especially those clustered in the activation loop region. Phospho-mimetic transgenic plants containing quadruple changes in Y163, S164, S166, and S167 rescued ost1 mutant phenotypes, activating ABA signaling outputs. Moreover, we found that OST1 is an active tyrosine kinase, autophosphorylating the Y182 site. ABA induced tyrosine phosphorylation of Y182 in OST1; this event is catalytically important for OST1 activity in plants. ABA-Insensitive 1 (ABI1) and its homologs ABI2 and HAB1, PP2C serine/threonine phosphatases that are known to dephosphorylate OST1 at S175, function as tyrosine phosphatases acting on the phosphorylated Y182 site. Our results indicate that phosphorylation cycles between OST1 and ABI1, which have dual specificity for tyrosine and serine/threonine, coordinately control ABA signaling in Arabidopsis.
TOI-220 b: a warm sub-Neptune discovered byTESS
Authors: Hoyer S , Gandolfi D , Armstrong D J , Deleuil M , Acuña L , de Medeiros J R , Goffo E , Lillo-Box J , Delgado Mena E , Lopez T A , Santerne A , Sousa S , Fridlund M , Adibekyan V , Collins K A , Serrano L M , Cortés-Zuleta P , Howell S B , Deeg H , Aguichine A , Barragán O , Bryant E M , Canto Martins B L , Collins K I , Cooke B F , Díaz R F , Esposito M , Furlan E , Hojjatpanah S , Jackman J , Jenkins J M , Jensen E L N , Latham D W , Leão I C , Matson R A , Nielsen L D , Osborn A , Otegi J F , Rodler F , Sabotta S , Scott N J , Seager S , Stockdale C , Strøm P A , Vanderspek R , Van Eylen V , Wheatley P J , Winn J N , Almenara J M , Barrado D , Barros S C C , Bayliss D , Bouchy F , Boyd P T , Cabrera J , Cochran W D , Demangeon O , Doty J P , Dumusque X , Figueira P , Fong W , Grziwa S , Hatzes A P , Kabáth P , Knudstrup E , Korth J , Livingston J H , Luque R , Mousis O , Mullally S E , Osborn H P , Pallé E , Persson C M , Redfield S , Santos N C , Smith J , Šubjak J , Twicken J D , Udry S , Yahalomi D A 
Published: May 2021

ABSTRACTIn this paper, we report the discovery of TOI-220 b, a new sub-Neptune detected by the Transiting Exoplanet Survey Satellite (TESS) and confirmed by radial velocity follow-up observations with the HARPS spectrograph. Based on the combined analysis of TESS transit photometry and high precision radial velocity measurements, we estimate a planetary mass of 13.8 ± 1.0 M⊕ and radius of 3.03 ± 0.15 R⊕, implying a bulk density of 2.73 ± 0.47 $\rm {g\,cm}^{-3}$. TOI-220 b orbits a relative bright (V= 10.4) and old (10.1 ± 1.4 Gyr) K dwarf star with a period of ∼10.69 d. Thus, TOI-220 b is a new warm sub-Neptune with very precise mass and radius determinations. A Bayesian analysis of the TOI-220 b internal structure indicates that due to the strong irradiation it receives, the low density of this planet could be explained with a steam atmosphere in radiative–convective equilibrium and a supercritical water layer on top of a differentiated interior made of a silicate mantle and a small iron core.
An ACA 1 mm survey of HzRGs in the ELAIS-S1: survey description and first results
Authors: Messias Hugo G , Hatziminaoglou Evanthia , Hibon Pascale , Mroczkowski Tony , Matute Israel , Lacy Mark , Mason Brian , Martín Sergio , Afonso José M , Fomalont Edward , Amarantidis Stergios , Antón Sonia , Cortés Paulo C , Demarco Ricardo , Gendron-Marsolais Marie-Lou , Hopkins Andrew M , Kneissl Rüdiger , Lopez Cristian , Rebolledo David , Yang Chentao 
Published: May 2021

ABSTRACT
Radio-emitting jets might be one of the main ingredients shaping the evolution of massive galaxies in the Universe since early cosmic times. However, identifying early radio active galactic nuclei (AGNs) and confirming this scenario have been hard to accomplish, with studies of samples of radio AGN hosts at z &gt; 2 becoming routinely possible only recently. With the above in mind, we have carried out a survey with the Atacama Compact Array (ACA or Morita Array) at 1.3 mm (rms = 0.15 mJy) of 36 high-redshift radio AGN candidates found within 3.9 deg2 in the ELAIS-S1 field. The work presented here describes the survey and showcases a preliminary set of results. The selection of the sample was based on three criteria making use of infrared (IR) and radio fluxes only. The criterion providing the highest selection rate of high-redshift sources (86 per cent at z &gt; 0.8) is one combining an IR colour cut and radio flux cut (S5.8μm/S3.6μm &gt; 1.3 and $S_{\rm 1.4\, GHz}\gt 1\,$ mJy). Among the sample of 36 sources, 16 show a millimetre (mm) detection. In eight of these cases, the emission has a non-thermal origin. A zsp = 1.58 object, with a mm detection of non-thermal origin, shows a clear spatial offset between the jet-dominated mm continuum emission and that of the host’s molecular gas, as traced by serendipitously detected CO(5-4) emission. Among the objects with serendipitous line detections there is a source with a narrow jet-like region, as revealed by CS(6-5) emission stretching 20 kpc out of the host galaxy.
The mass–size relation of galaxy clusters
Authors: Contigiani O , Bahé Y M , Hoekstra H 
Published: May 2021

ABSTRACTThe outskirts of accreting dark matter haloes exhibit a sudden drop in density delimiting their multistream region. Due to the dynamics of accretion, the location of this physically motivated edge strongly correlates with the halo growth rate. Using hydrodynamical zoom-in simulations of high-mass clusters, we explore this definition in realistic simulations and find an explicit connection between this feature in the dark matter and galaxy profiles. We also show that the depth of the splashback feature correlates well with the direction of filaments and, surprisingly, the orientation of the brightest cluster galaxy. Our findings suggest that galaxy profiles and weak-lensing masses can define an observationally viable mass-size scaling relation for galaxy clusters, which can be used to extract cosmological information.
Radio afterglows from compact binary coalescences: prospects for next-generation telescopes
Authors: Dobie Dougal , Murphy Tara , Kaplan David L , Hotokezaka Kenta , Bonilla Ataides Juan Pablo , Mahony Elizabeth K , Sadler Elaine M 
Published: May 2021

ABSTRACT
The detection of gravitational waves from a neutron star merger, GW170817, marked the dawn of a new era in time-domain astronomy. Monitoring of the radio emission produced by the merger, including high-resolution radio imaging, enabled measurements of merger properties including the energetics and inclination angle. In this work, we compare the capabilities of current and future gravitational wave facilities to the sensitivity of radio facilities to quantify the prospects for detecting the radio afterglows of gravitational wave events. We consider three observing strategies to identify future mergers – wide field follow-up, targeting galaxies within the merger localization and deep monitoring of known counterparts. We find that while planned radio facilities like the Square Kilometre Array will be capable of detecting mergers at gigaparsec distances, no facilities are sufficiently sensitive to detect mergers at the range of proposed third-generation gravitational wave detectors that would operate starting in the 2030s.
The HST large programme on ω Centauri – IV. Catalogue of two external fields
Authors: Scalco M , Bellini A , Bedin L R , Anderson J , Rosati P , Libralato M , Salaris M , Vesperini E , Nardiello D , Apai D , Burgasser A J , Gerasimov R 
Published: May 2021

ABSTRACT
In the fourth paper of this series, we present – and publicly release – the state-of-the-art catalogue and atlases for the two remaining parallel fields observed with the Hubble Space Telescope for the large programme on ω Centauri. These two fields are located at ∼12 arcmin from the centre of the globular cluster (in the west and south-west directions) and were imaged in filters from the ultraviolet to the infrared. Both fields were observed at two epochs separated by about 2 yr that were used to derive proper motions and to compute membership probabilities.
Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins
Authors: Lang Benjamin , Yang Jae-Seong , Garriga-Canut Mireia , Speroni Silvia , Aschern Moritz , Gili Maria , Hoffmann Tobias , Tartaglia Gian Gaetano , Maurer Sebastian P 
Published: May 2021

Abstract
RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H matrix screening to detect direct interactions between RBPs, sampling &gt; 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks. The dataset we provide will be a valuable resource for understanding the combinatorial interactions of RBPs with RNAs and the resulting regulatory outcomes.
Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study
Authors: Yamanouchi Masayuki , Furuichi Kengo , Shimizu Miho , Toyama Tadashi , Yamamura Yuta , Oshima Megumi , Kitajima Shinji , Hara Akinori , Iwata Yasunori , Sakai Norihiko , Oba Yuki , Matsuoka Shusaku , Ikuma Daisuke , Mizuno Hiroki , Suwabe Tatsuya , Hoshino Junichi , Sawa Naoki , Yuzawa Yukio , Kitamura Hiroshi , Suzuki Yoshiki , Sato Hiroshi , Uesugi Noriko , Ueda Yoshihiko , Nishi Shinichi , Yokoyama Hitoshi , Nishino Tomoya , Samejima Kenichi , Kohagura Kentaro , Shibagaki Yugo , Makino Hirofumi , Matsuo Seiichi , Ubara Yoshifumi , Wada Takashi 
Published: May 2021

Abstract

Background
Prognosticating disease progression in patients with diabetic kidney disease (DKD) is challenging, especially in the early stages of kidney disease. Anemia can occur in the early stages of kidney disease in diabetes. We therefore postulated that serum hemoglobin (Hb) concentration, as a reflection of incipient renal tubulointerstitial impairment, can be used as a marker to predict DKD progression.

Methods
Drawing on nationally representative data of patients with biopsy-proven DKD, 246 patients who had an estimated glomerular filtration rate (eGFR)  ≥60 mL/min/1.73 m2 at renal biopsy were identified: age 56 (45–63) years; 62.6% men; Hb 13.3 (12.0–14.5) g/dL; eGFR 76.2 (66.6–88.6) mL/min/1.73 m2; urine albumin-to-creatinine ratio 534 (100–1480) mg/g Crea. Serum Hb concentration was divided into quartiles: ≤12, 12.1–13.3, 13.4–14.5 and ≥14.6 g/dL. The association between serum Hb concentration and the severity of renal pathological lesions was explored. A multivariable Cox regression model was used to estimate the risk of DKD progression (new onset of end-stage kidney disease, 50% reduction of eGFR or doubling of serum creatinine). The incremental prognostic value of DKD progression by adding serum Hb concentration to the known risk factors of DKD was assessed.

Results
Serum Hb levels negatively correlated with all renal pathological features, especially with the severity of interstitial fibrosis (ρ = −0.52; P &lt; 0.001). During a median follow-up of 4.1 years, 95 developed DKD progression. Adjusting for known risk factors of DKD progression, the hazard ratio in the first, second and third quartile (the fourth quartile was reference) were 2.74 [95% confidence interval (CI) 1.26–5.97], 2.33 (95% CI 1.07–5.75) and 1.46 (95% CI 0.71–3.64), respectively. Addition of the serum Hb concentration to the known risk factors of DKD progression improved the prognostic value of DKD progression (the global Chi-statistics increased from 55.1 to 60.8; P &lt; 0.001).

Conclusions
Serum Hb concentration, which reflects incipient renal fibrosis, can be useful for predicting DKD progression in the early stages of kidney disease.
Radiological assessment schedule for 1p/19q-codeleted gliomas during the surveillance period using parametric modeling
Authors: Kang Ho , Lee Jongjin , Ji So Young , Choi Seung Won , Kim Kyung-Min , Lee Joo Ho , Lee Soon-Tae , Won Jae Kyung , Kim Tae Min , Choi Seung Hong , Park Sung-Hye , Moon Kyung-Sub , Kim Chae-Yong , Yoo Heon , Nam Do-Hyun , Kim Jeong Hoon , Kim Yongdai , Park Chul-Kee 
Published: May 2021

Abstract

Background
There have been no evidence-based guidelines on the optimal schedule for the radiological assessment of 1p/19q-codeleted glioma. This study aimed to recommend an appropriate radiological evaluation schedule for 1p/19q-codeleted glioma during the surveillance period through parametric modeling of the progression-free survival (PFS) curve.

Methods
A total of 234 patients with 1p/19q-codeleted glioma (137 grade II and 97 grade III) who completed regular treatment were retrospectively reviewed. The patients were stratified into each layered progression risk group by recursive partitioning analysis. A piecewise exponential model was used to standardize the PFS curves. The cutoff value of the progression rate among the remaining progression-free patients was set to 10% at each scan.

Results
Progression risk stratification resulted in 3 groups. The optimal magnetic resonance imaging (MRI) interval for patients without a residual tumor was every 91.2 weeks until 720 weeks after the end of regular treatment following the latent period for 15 weeks. For patients with a residual tumor after the completion of adjuvant radiotherapy followed by chemotherapy, the optimal MRI interval was every 37.5 weeks until week 90 and every 132.8 weeks until week 361, while it was every 33.6 weeks until week 210 and every 14.4 weeks until week 495 for patients with a residual tumor after surgery only or surgery followed by radiotherapy only.

Conclusions
The optimal radiological follow-up schedule for each progression risk stratification of 1p/19q-codeleted glioma can be established from the parametric modeling of PFS.
Rose without prickle: genomic insights linked to moisture adaptation
Authors: Zhong Mi-Cai , Jiang Xiao-Dong , Yang Guo-Qian , Cui Wei-Hua , Suo Zhi-Quan , Wang Wei-Jia , Sun Yi-Bo , Wang Dan , Cheng Xin-Chao , Li Xu-Ming , Dong Xue , Tang Kai-Xue , Li De-Zhu , Hu Jin-Yong 
Published: May 2021

Abstract
Prickles act against herbivores, pathogens or mechanical injury, while also preventing water loss. However, whether prickles have new function and the molecular genetics of prickle patterning remain poorly explored. Here, we generated a high-quality reference genome assembly for ‘Basye's Thornless’ (BT), a prickle-free cultivar of Rosa wichuraiana, to identify genetic elements related to stem prickle development. The BT genome harbors a high level of sequence diversity in itself and with cultivar ‘Old Blush’ (R. chinensis), a founder genotype in rose domestication. Inheritance of stem prickle density was determined and two QTL were identified. Differentially expressed genes in QTL were involved in water-related functions, suggesting that prickle density may hitchhike with adaptations to moist environments. While the prickle-related gene-regulatory-network (GRN) was highly conserved, the expression variation of key candidate genes was associated with prickle density. Our study provides fundamental resources and insights for genome evolution in the Rosaceae. Ongoing efforts on identification of the molecular bases for key rose traits may lead to improvements for horticultural markets.
Protecting Children From Tobacco Smoke Exposure: A Randomized Controlled Trial of Project Zero Exposure
Authors: Rosen Laura , Zucker David , Guttman Nurit , Brown Nili , Bitan Michal , Rule Ana , Berkovitch Mati , Myers Vicki 
Published: May 2021

Abstract

Introduction
Young children are vulnerable to harm from tobacco smoke exposure (TSE). This study assessed the effect of Project Zero Exposure—an intervention program designed to help parents protect children from TSE—on children’s exposure.

Methods
Randomized controlled trial of a home-based, theory-driven intervention. Parents of young children (&lt;8 y) in families with a smoking parent were eligible. The intervention included feedback on child TSE (hair nicotine), and home air quality (PM2.5), with motivational interviewing. Families were randomized to: intervention group (IG, N = 69), regular control group (RCG, N = 70), or to a secondary enhanced control group, (ECG, N = 20). Child hair samples were taken at baseline and follow-up. We report on child TSE in the IG versus RCG at six months.

Results
Most enrolled families completed the trial (IG: 98.6%[68/69], RCG: 97.1%[68/70]). Log hair nicotine (LHN [ng/mg]) decreased in both the IG (Baseline: –1.78 ± 1.91, Follow-up: –2.82 ± 1.87, p = .003) and RCG (Baseline: –1.79 ± 1.54, Follow-up: –2.85 ± 1.73, p = .002), but did not differ between groups at study end (p = .635). Three of five parentally-reported outcomes showed improvement over time in the IG, and one in the RCG. Among IG participants, 90% found hair nicotine feedback useful.

Conclusions
No difference between the intervention and control groups was found on the objective biomarker, LHN. Child TSE decreased during the trial in intervention and control groups. Trial participation, which included hair nicotine monitoring, may have contributed to decreasing exposure in both groups. Concurrent control group improvements may partially explain lack of proven intervention benefit. Biomarker monitoring warrants further investigation for reduction of child TSE.

Implications
Project Zero Exposure is an intervention program designed to help parents protect their children from TSE. Results from the randomized controlled trial of the program showed no difference between groups at study end, but a clear and substantial reduction in child exposure to tobacco smoke from beginning to end of the trial, in both intervention and control groups. Biomarker monitoring, a key element of the trial, was used with all participants. Biomarker monitoring of child exposure to tobacco smoke may help parents become aware of their child’s exposure and better protect them, and should be explored as a means to reduce child TSE.
Clinical Trial Registration: NCT02867241
Unburned Tobacco Cigarette Smoke Alters Rat Ultrastructural Lung Airways and DNA
Authors: Vivarelli Fabio , Canistro Donatella , Cirillo Silvia , Elias Ryan J , Granata Silvia , Mussoni Matilde , Burattini Sabrina , Falcieri Elisabetta , Turrini Eleonora , Fimognari Carmela , Buschini Annamaria , Lazzaretti Mirca , Beghi Sofia , Girotti Stefano , Sangiorgi Stefano , Bolelli Luca , Ghini Severino , Ferri Elida Nora , Fagiolino Ivan , Franchi Paola , Lucarini Marco , Mercatante Dario , Rodriguez-Estrada Maria Teresa , Lorenzini Antonello , Marchionni Silvia , Gabriele Morena , Longo Vincenzo , Paolini Moreno 
Published: May 2021

Abstract

Introduction
Recently, the Food and Drug Administration authorized the marketing of IQOS Tobacco Heating System as a Modified Risk Tobacco Product based on an electronic heat-not-burn technology that purports to reduce the risk.

Methods
Sprague-Dawley rats were exposed in a whole-body mode to IQOS aerosol for 4 weeks. We performed the chemical characterization of IQOS mainstream and we studied the ultrastructural changes in trachea and lung parenchyma of rats exposed to IQOS stick mainstream and tissue pro-inflammatory markers. We investigated the reactive oxygen species amount along with the markers of tissue and DNA oxidative damage. Moreover, we tested the putative genotoxicity of IQOS mainstream through Ames and alkaline Comet mutagenicity assays.

Results
Here, we identified irritating and carcinogenic compounds including aldehydes and polycyclic aromatic hydrocarbons in the IQOS mainstream as sign of incomplete combustion and degradation of tobacco, that lead to severe remodelling of smaller and largest rat airways. We demonstrated that IQOS mainstream induces lung enzymes that activate carcinogens, increases tissue reactive radical concentration; promotes oxidative DNA breaks and gene level DNA damage; and stimulates mitogen activated protein kinase pathway which is involved in the conventional tobacco smoke-induced cancer progression.

Conclusions
Collectively, our findings reveal that IQOS causes grave lung damage and promotes factors that increase cancer risk.

Implications
IQOS has been proposed as a safer alternative to conventional cigarettes, due to depressed concentration of various harmful constituents typical of traditional tobacco smoke. However, its lower health risks to consumers have yet to be determined. Our findings confirm that IQOS mainstream contains pyrolysis and thermogenic degradation by-products, the same harmful constituents of traditional cigarette smoke, and, for the first time, we show that it causes grave lung damage and promotes factors that increase cancer risk in the animal model.