bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-149 rs2292832 C/T Polymorphism Predicts the Prognosis of Hepatocellular Carcinoma Patients With Bone Metastasis
Authors: Feng Jian , Liu Zhen , Yu Long , Wu Chaoyu , Luo Xiao-bo
Published: April 2022

Objective

The prognostic markers of hepatocellular carcinoma (HCC) patients with bone metastasis are of great significance for the design of treatment strategy, the maintenance of life quality of the patients, and the improvement of cancer prognosis. MicroRNA-149 (miR-149) rs2292832 C/T polymorphism in HCC patients has been reported to be associated with the risk of HCC, but whether it can predict the prognosis of HCC patients with bone metastasis remains unclear. The goal of our study was to examine the prognostic impact of miR-149 rs2292832 C/T polymorphism on HCC patients with bone metastasis.

Methods

A total of 67 cases of HCC patients with bone metastasis (BC group) and 73 cases of HCC patients without bone metastasis (NC group) were included in this study. The miR-149 levels in blood leukocytes and tumor tissues were determined by qRT-PCR. Genotyping analysis of miR-149 rs2292832 was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism assay.

Results

The blood leukocyte miR-149 levels were significantly decreased in HCC patients, compared with the healthy controls, and they were significantly decreased in the BC patients, compared with the NC cases. BC patients carrying miR-149 rs2292832 CC+CT phenotype have a better overall survival (OS) rate, whereas no significant correlation was found between miR-149 rs2292832 CC+CT phenotype and the OS rate in NC group. The miR-149 rs2292832 CC+CT phenotype was correlated with certain bone turnover markers and bone metabolism markers but was not correlated with receptor activator of nuclear factor-kappaB ligand (RANKL) expression. Meanwhile, the combination of miR-149 rs2292832 CC+CT phenotype and RANKL expression could improve the prognosis assessment of HCC patients with bone metastasis.

Conclusion

miR-149 rs2292832 polymorphism might be a novel prognostic biomarker for HCC patients with bone metastasis. A follow-up study with a larger cohort from a multicenter should be performed to test our conclusions.
What makes a Parent? Challenging the Importance of a Genetic Link for Legal Parenthood in International Surrogacy Arrangements
Authors: Tesfaye Meiraf G
Published: April 2022

This article advocates for consistent application of the best interests of children in recognition of legal parenthood of children born out of international surrogacy arrangements (ISAs) and opposes its differential application to surrogate children who do not have a genetic link to their intending parents (IPs). Owing to the lack of European consensus and specialized legal instruments regulating recognition of legal parenthood in ISAs, the European Court of Human Rights (ECtHR/the Court) via interpretation of Article 8 obligates prohibitionist home states of IPs to recognize legal parenthood coming out of such international arrangements only in instances where there is genetic link with one or both IPs. This leaves surrogate children with no genetic link to their IPs with no benefits stemming out of recognition of legal parentage often leaving them parentless and stateless. This work challenges the necessity for such limitations through analysis of two ECtHR cases, the Mennesson v. France and the Paradiso and Campanelli v. Italy, where differential consideration of the best interests of children was based on presence or lack of genetic link respectively. It concludes that non-recognition of parenthood is a disproportionate measure to protect legitimate aims of prohibitionist home states and advocates for expansion of their implied positive obligations to protect the best interests of surrogate children with no genetic link to their IPs.
Oral and Written Transmission in the Early Jeu-Parti
Authors: Mason Joseph W
Published: April 2022

This article explores the contentious issue of oral and written transmission in thirteenth-century French song by looking at a selection of early jeux-partis that share their melodies with other songs. It argues that acts of contrafacture were sometimes carried out using written exemplars, or when written transmission was occurring. First, it is asserted that melodic variance could result from both written and oral transmission. Second, evidence for ephemeral written exemplars of jeux-partis and their models is discussed. Finally, it is shown that for one contrafact jeu-parti and its model, some of the melodic variants must have resulted from errors in the process of copying the songs. The melodic variants show that scribes and performers continually engaged with the two songs during their reception, indicating that knowledge of contrafacture persisted several decades after the songs were originally composed.
Dynamical state of galaxy clusters evaluated from X-ray images
Authors: Yuan Z S , Han J L , Wen Z L
Published: April 2022

X-ray images of galaxy clusters often show disturbed structures that are indications of cluster mergers. To complement our previous work on the dynamical state of 964 clusters observed by Chandra, we process the X-ray images for 1308 clusters from XMM–Newton archival data, together with the images of 22 clusters newly released by Chandra, and we evaluate their dynamical state from these X-ray images. The concentration index c, the centroid shift ω and the power ratio P3/P0 are calculated in circular regions with a certain radius of 500 kpc, and the morphology index δ is estimated within elliptical regions that can be adapted to the cluster size and shape. In addition, the dynamical parameters for 42 clusters previously estimated from Chandra images are upgraded based on the newly available redshifts. Good consistence is found between dynamical parameters derived from XMM–Newton and Chandra images for the overlapped sample of clusters in the two data sets. The dependence of mass scaling relations on the dynamical state is shown by using the data of 388 clusters. All data and related software are available at http://zmtt.bao.ac.cn/galaxy_clusters/dyXimages/.
Jet-cocoon geometry in the optically dark, very high energy gamma-ray burst 201216C
Authors: Rhodes L , van der Horst A J , Fender R , Aguilera-Dena D R , Bright J S , Vergani S , Williams D R A
Published: April 2022

We present the results of a radio observing campaign on GRB 201216C, combined with publicly available optical and X-ray data. The detection of very high energy (VHE, >100 GeV) emission by MAGIC makes this the fifth VHE GRB at the time of publication. Comparison between the optical and X-ray light curves show that GRB 201216C is a dark GRB, i.e. the optical emission is significantly absorbed and is fainter than expected from the X-ray detections. Our e-MERLIN data also shows evidence of diffractive interstellar scintillation. We can study the column density along the line of sight to the GRB in both the host galaxy, from the damped optical light curve, and the Milky Way, via scintillation studies. We find that the afterglow is best modelled using a jet-cocoon geometry within a stellar wind environment. Fitting the data with a multicomponent model, we estimate that the optical, X-ray, and higher frequency radio data before ∼25 d originates from an ultrarelativistic jet with an isotropic equivalent kinetic energy of (0.6–10) × 1052 erg and an opening angle of ∼1–9°. The lower frequency radio emission detected by MeerKAT, from day 28 onwards, is produced by the cocoon with a kinetic energy that is between two and seven orders of magnitude lower (0.02–50) × 1048 erg. The energies of the two components are comparable to those derived in simulations of such scenarios.
Modulation of pulse profile as a signal for phase transitions in a pulsar core
Authors: Bagchi Partha , Layek Biswanath , Sarkar Anjishnu , Srivastava Ajit M
Published: April 2022

We calculate detailed modification of pulses from a pulsar arising from the effects of phase transition induced density fluctuations on the pulsar moment of inertia. We represent general statistical density fluctuations using a simple model where the initial moment of inertia tensor of the pulsar (taken to be diagonal here) is assumed to get random additional contributions for each of its component which are taken to be Gaussian distributed with certain width characterized by the strength of density fluctuations ϵ. Using sample values of ϵ, (and the pulsar deformation parameter η) we numerically calculate detailed pulse modifications by solving Euler’s equations for the rotational dynamics of the pulsar. We also give analytical estimates which can be used for arbitrary values of ϵ and η. We show that there are very specific patterns in the perturbed pulses which are observable in terms of modulations of pulses over large time periods. In view of the fact that density fluctuations fade away eventually leading to a uniform phase in the interior of pulsar, the off-diagonal components of MI tensor also vanish eventually. Thus, the modification of pulses due to induced wobbling (from the off-diagonal MI components) will also die away eventually. This allows one to distinguish these transient pulse modulations from the effects of any wobbling originally present. Further, the decay of these modulations in time directly relates to relaxation of density fluctuations in the pulsar giving valuable information about the nature of phase transition occurring inside the pulsar.
Coincidence between morphology and star formation activity through cosmic time: the impact of the bulge growth
Authors: Dimauro Paola , Daddi Emanuele , Shankar Francesco , Cattaneo Andrea , Huertas-Company Marc , Bernardi Mariangela , Caro Fernando , Dupke Renato , Häußler Boris , Johnston Evelyn , Cortesi Arianna , Mei Simona , Peletier Reynier
Published: April 2022

The origin of the quenching in galaxies is still highly debated. Different scenarios and processes are proposed. We use multiband (400–1600 nm) bulge–disc decompositions of massive galaxies in the redshift range 0 < z < 2 to explore the distribution and the evolution of galaxies in the $\log \, {\rm SFR-log}\: M_{*}$ plane as a function of the stellar mass weighted bulge-to-total ratio ($B/T_{M_{*}}$) and also for internal galaxy components (bulge/disc) separately. We find evidence of a clear link between the presence of a bulge and the flattening of the main sequence in the high-mass end. All bulgeless galaxies ($B/T_{M_{*}}$ < 0.2) lie on the main sequence, and there is little evidence of a quenching channel without bulge growth. Galaxies with a significant bulge component ($B/T_{M_{*}}$ > 0.2) are equally distributed in number between star forming and passive regions. The vast majority of bulges in the main-sequence galaxies are quiescent, while star formation is localized in the disc component. Our current findings underline a strong correlation between the presence of the bulge and the star formation state of the galaxy. A bulge, if present, is often quiescent, independently of the morphology or the star formation activity of the host galaxy. Additionally, if a galaxy is quiescent, with a large probability, is hosting a bulge. Conversely, if the galaxy has a discy shape is highly probable to be star forming.
Magnetic fields and young stellar objects in cometary cloud L1616
Authors: Saha Piyali , Soam Archana , Baug Tapas , Gopinathan Maheswar , Mondal Soumen , Ghosh Tuhin
Published: April 2022

The Lynds’ Dark Nebula (LDN) 1615/1616 and CB 28 (hereafter L1616) together form a cometary globule located at an angular distance of about 8° west of the Orion OB1 association, aligned roughly along the east–west direction, and showing a distinct head–tail structure. The presence of massive stars in the Orion belt has been considered to be responsible for the radiation-driven implosion mode of star formation in L1616. Based on the latest Gaia Early Data Release 3 (EDR3) measurements of the previously known young stellar objects (YSOs) associated with L1616, we find the distance to this cloud to be 384 ± 5 pc. We present optical polarimetry towards L1616 that maps the plane-of-sky component of the ambient magnetic field (BPOS) geometry. Based on the proper motion of the YSOs associated with L1616, we investigate their plane-of-sky motion relative to the exciting star ϵ Ori. Using the Gaia EDR3 measurements of the distances and proper motions of the YSOs, we find two additional sources comoving with the known YSOs. One comoving source is HD 33056, a B9 star, and the other might be a young pre-main-sequence star not reported in previous studies. The mean direction of BPOS is found to follow the cloud structure. This could be the effect of dragging of the magnetic field lines by the impact of the ionizing radiation from ϵ Ori. Based on the pressure exerted on L1616, and the ages of the associated YSOs, we show that it could possibly be the main source of ionization in L1616, and thus the star formation in it.
Categorize radio interference using component and temporal analysis
Authors: Yuan Mao , Zhu Weiwei , Zhang Haiyan , Huang Shijie , Xue Mengyao , Li Di , Yue Youling , Wang Pei , Niu Jiarui , Hu Yuxuan , Li Chunjiang , Miao Chenchen , Wang Yu , Meng Lingqi , Peng Bo
Published: April 2022

Radio frequency interference (RFI) is a significant challenge faced by today’s radio astronomers. While most past efforts were devoted to cleaning the RFI from the data, we develop a novel method for categorizing and cataloguing RFI for forensic purpose. We present a classifier that categorizes RFI into different types based on features extracted using Principal Component Analysis (PCA) and Fourier analysis. The classifier can identify narrowband non-periodic RFI above 2σ, narrowband periodic RFI above 3σ, and wideband impulsive RFI above 5σ with F1 scores [defined as F1 = (2 · recall × precision)/(recall + precision)] between 0.87 and 0.91 in simulation. This classifier could be used to identify the sources of RFI as well as to clean RFI contamination (particularly in pulsar search). In the long-term analysis of the categorized RFI, we found a special type of drifting periodic RFI that is detrimental to pulsar search. We also found pieces of evidence of an increased rate of impulsive RFI when the telescope is pointing towards the cities. These results demonstrate this classifier’s potential as a forensic tool for RFI environment monitoring of radio telescopes.
An asymmetrical model for high-energy radiation of Cassiopeia A
Authors: Zhan Shihong , Wang Wei , Mou Guobin , Li Zhuo
Published: April 2022

The supernova remnant Cassiopeia A (Cas A) shows strong radiation from radio to gamma-ray bands. The mechanism of gamma-ray radiation in Cas A and its possible contribution to PeV cosmic rays are still under debate. The X-ray imaging reveals an asymmetric profile of Cas A, suggesting the existence of a jet-like structure. In this paper, we propose an asymmetrical model for Cas A, consisting of a fast moving jet-like structure and a slowly expanding isotropic shell. This model can account for the multiwavelength spectra of Cas A, especially for the power-law hard X-ray spectrum from ∼60 to 220 keV. The GeV to TeV emission from Cas A should be contributed by both hadronic and leptonic processes. Moreover, the jet-like structure may produce a gamma-ray flux of $\sim 10^{-13}\rm erg\, cm^{-2}\, s^{-1}$ at ∼100 TeV, to be examined by the Large High Altitude Air Shower Observatory (LHAASO) and the Cherenkov Telescope Array (CTA).
A reliable workflow for improving nanoscale X-ray fluorescence tomographic analysis on nanoparticle-treated HeLa cells
Authors: Luo Yanqi , Paunesku Tatjana , Antipova Olga , Liu Yuzi , Zaluzec Nestor J , Di Zichao , Woloschak Gayle , Chen Si
Published: April 2022

Scanning X-ray fluorescence (XRF) tomography provides powerful characterization capabilities in evaluating elemental distribution and differentiating their inter- and intra-cellular interactions in a three-dimensional (3D) space. Scanning XRF tomography encounters practical challenges from the sample itself, where the range of rotation angles is limited by geometric constraints, involving sample substrates or nearby features either blocking or converging into the field of view. This study aims to develop a reliable and efficient workflow that can (1) expand the experimental window for nanoscale tomographic analysis of local areas of interest within a laterally extended specimen, and (2) bridge 3D analysis at micrometer and nanoscales on the same specimen. We demonstrate the workflow using a specimen of HeLa cells exposed to iron oxide core and titanium dioxide shell (Fe3O4/TiO2) nanocomposites. The workflow utilizes iterative and multiscale XRF data collection with intermediate sample processing by focused ion beam (FIB) sample preparation between measurements at different length scales. Initial assessment combined with precise sample manipulation via FIB allows direct removal of sample regions that are obstacles to both incident X-ray beam and outgoing XRF signals, which considerably improves the subsequent nanoscale tomography analysis. This multiscale analysis workflow has advanced bio-nanotechnology studies by providing deep insights into the interaction between nanocomposites and single cells at a subcellular level as well as statistical assessments from measuring a population of cells.
LoopGrafter: a web tool for transplanting dynamical loops for protein engineering
Authors: Planas-Iglesias Joan , Opaleny Filip , Ulbrich Pavol , Stourac Jan , Sanusi Zainab , Pinto Gaspar P , Schenkmayerova Andrea , Byska Jan , Damborsky Jiri , Kozlikova Barbora , Bednar David
Published: April 2022

The transplantation of loops between structurally related proteins is a compelling method to improve the activity, specificity and stability of enzymes. However, despite the interest of loop regions in protein engineering, the available methods of loop-based rational protein design are scarce. One particular difficulty related to loop engineering is the unique dynamism that enables them to exert allosteric control over the catalytic function of enzymes. Thus, when engaging in a transplantation effort, such dynamics in the context of protein structure need consideration. A second practical challenge is identifying successful excision points for the transplantation or grafting. Here, we present LoopGrafter (https://loschmidt.chemi.muni.cz/loopgrafter/), a web server that specifically guides in the loop grafting process between structurally related proteins. The server provides a step-by-step interactive procedure in which the user can successively identify loops in the two input proteins, calculate their geometries, assess their similarities and dynamics, and select a number of loops to be transplanted. All possible different chimeric proteins derived from any existing recombination point are calculated, and 3D models for each of them are constructed and energetically evaluated. The obtained results can be interactively visualized in a user-friendly graphical interface and downloaded for detailed structural analyses.
Histone H3.3 phosphorylation promotes heterochromatin formation by inhibiting H3K9/K36 histone demethylase
Authors: Udugama Maheshi , Vinod Benjamin , Chan F Lyn , Hii Linda , Garvie Andrew , Collas Philippe , Kalitsis Paul , Steer David , Das Partha P , Tripathi Pratibha , Mann Jeffrey R , Voon Hsiao P J , Wong Lee H
Published: April 2022

Histone H3.3 is an H3 variant which differs from the canonical H3.1/2 at four residues, including a serine residue at position 31 which is evolutionarily conserved. The H3.3 S31 residue is phosphorylated (H3.3 S31Ph) at heterochromatin regions including telomeres and pericentric repeats. However, the role of H3.3 S31Ph in these regions remains unknown. In this study, we find that H3.3 S31Ph regulates heterochromatin accessibility at telomeres during replication through regulation of H3K9/K36 histone demethylase KDM4B. In mouse embryonic stem (ES) cells, substitution of S31 with an alanine residue (H3.3 A31 –phosphorylation null mutant) results in increased KDM4B activity that removes H3K9me3 from telomeres. In contrast, substitution with a glutamic acid (H3.3 E31, mimics S31 phosphorylation) inhibits KDM4B, leading to increased H3K9me3 and DNA damage at telomeres. H3.3 E31 expression also increases damage at other heterochromatin regions including the pericentric heterochromatin and Y chromosome-specific satellite DNA repeats. We propose that H3.3 S31Ph regulation of KDM4B is required to control heterochromatin accessibility of repetitive DNA and preserve chromatin integrity.
Nearest neighbor rules for RNA helix folding thermodynamics: improved end effects
Authors: Zuber Jeffrey , Schroeder Susan J , Sun Hongying , Turner Douglas H , Mathews David H
Published: April 2022

Nearest neighbor parameters for estimating the folding stability of RNA secondary structures are in widespread use. For helices, current parameters penalize terminal AU base pairs relative to terminal GC base pairs. We curated an expanded database of helix stabilities determined by optical melting experiments. Analysis of the updated database shows that terminal penalties depend on the sequence identity of the adjacent penultimate base pair. New nearest neighbor parameters that include this additional sequence dependence accurately predict the measured values of 271 helices in an updated database with a correlation coefficient of 0.982. This refined understanding of helix ends facilitates fitting terms for base pair stacks with GU pairs. Prior parameter sets treated 5′GGUC3′ paired to 3′CUGG5′ separately from other 5′GU3′/3′UG5′ stacks. The improved understanding of helix end stability, however, makes the separate treatment unnecessary. Introduction of the additional terms was tested with three optical melting experiments. The average absolute difference between measured and predicted free energy changes at 37°C for these three duplexes containing terminal adjacent AU and GU pairs improved from 1.38 to 0.27 kcal/mol. This confirms the need for the additional sequence dependence in the model.
The tRNA discriminator base defines the mutual orthogonality of two distinct pyrrolysyl-tRNA synthetase/tRNAPyl pairs in the same organism
Authors: Zhang Haolin , Gong Xuemei , Zhao Qianqian , Mukai Takahito , Vargas-Rodriguez Oscar , Zhang Huiming , Zhang Yuxing , Wassel Paul , Amikura Kazuaki , Maupin-Furlow Julie , Ren Yan , Xu Xun , Wolf Yuri I , Makarova Kira S , Koonin Eugene V , Shen Yue , Söll Dieter , Fu Xian
Published: April 2022

Site-specific incorporation of distinct non-canonical amino acids into proteins via genetic code expansion requires mutually orthogonal aminoacyl-tRNA synthetase/tRNA pairs. Pyrrolysyl-tRNA synthetase (PylRS)/tRNAPyl pairs are ideal for genetic code expansion and have been extensively engineered for developing mutually orthogonal pairs. Here, we identify two novel wild-type PylRS/tRNAPyl pairs simultaneously present in the deep-rooted extremely halophilic euryarchaeal methanogen Candidatus Methanohalarchaeum thermophilum HMET1, and show that both pairs are functional in the model halophilic archaeon Haloferax volcanii. These pairs consist of two different PylRS enzymes and two distinct tRNAs with dissimilar discriminator bases. Surprisingly, these two PylRS/tRNAPyl pairs display mutual orthogonality enabled by two unique features, the A73 discriminator base of tRNAPyl2 and a shorter motif 2 loop in PylRS2. In vivo translation experiments show that tRNAPyl2 charging by PylRS2 is defined by the enzyme's shortened motif 2 loop. Finally, we demonstrate that the two HMET1 PylRS/tRNAPyl pairs can simultaneously decode UAG and UAA codons for incorporation of two distinct noncanonical amino acids into protein. This example of a single base change in a tRNA leading to additional coding capacity suggests that the growth of the genetic code is not yet limited by the number of identity elements fitting into the tRNA structure.
AutozygosityMapper: Identification of disease-mutations in consanguineous families
Authors: Steinhaus Robin , Boschann Felix , Vogel Melanie , Fischer-Zirnsak Björn , Seelow Dominik
Published: April 2022

With the shift from SNP arrays to high-throughput sequencing, most researchers studying diseases in consanguineous families do not rely on linkage analysis any longer, but simply search for deleterious variants which are homozygous in all patients. AutozygosityMapper allows the fast and convenient identification of disease mutations in patients from consanguineous pedigrees by focussing on homozygous segments shared by all patients. Users can upload multi-sample VCF files, including WGS data, without any pre-processing. Genome-wide runs of homozygosity and the underlying genotypes are presented in graphical interfaces. AutozygosityMapper extends the functions of its predecessor, HomozygosityMapper, to the search for autozygous regions, in which all patients share the same homozygous genotype. We provide export of VCF files containing only the variants found in homozygous regions, this usually reduces the number of variants by two orders of magnitude. These regions can also directly be analysed with our disease mutation identification tool MutationDistiller. The application comes with simple and intuitive graphical interfaces for data upload, analysis, and results. We kept the structure of HomozygosityMapper so that previous users will find it easy to switch. With AutozygosityMapper, we provide a fast web-based way to identify disease mutations in consanguineous families. AutozygosityMapper is freely available at https://www.genecascade.org/AutozygosityMapper/.
Eukaryotic initiation factor 4F promotes a reorientation of eukaryotic initiation factor 3 binding on the 5′ and the 3′ UTRs of barley yellow dwarf virus mRNA
Authors: Powell Paul , Bhardwaj Usha , Goss Dixie
Published: April 2022

Viral mRNAs that lack a 5′ m7GTP cap and a 3′ poly-A tail rely on structural elements in their untranslated regions (UTRs) to form unique RNA-protein complexes that regulate viral translation. Recent studies of the barley yellow dwarf virus (BYDV) have revealed eukaryotic initiation factor 3 (eIF3) plays a significant role in facilitating communication between its 5′ and 3′ UTRs by binding both UTRs simultaneously. This report uses in vitro translation assays, fluorescence anisotropy binding assays, and selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) footprinting to identify secondary structures that are selectively interacting with eIF3. SHAPE data also show that eIF3 alters its interaction with BYDV structures when another factor crucial for BYDV translation, eIF4F, is introduced by the 3′ BYDV translational enhancer (BTE). The observed BTE and eIF4F-induced shift of eIF3 position on the 5’ UTR and the translational effects of altering eIF3-binding structures (SLC and SLII) support a new model for BYDV translation initiation that requires the reorientation of eIF3 on BYDV UTRs. This eIF3 function in BYDV translation initiation is both reminiscent of and distinct from eIF3–RNA interactions found in other non-canonically translating mRNAs (e.g. HCV). This characterization of a new role in translation initiation expands the known functionality of eIF3 and may be broadly applicable to other non-canonically translating mRNAs.
The role of renal resistive index as a prognostic tool in kidney transplantation: a systematic review
Authors: Azzouz Safaa , Chen Anjellica , Ekmekjian Taline , Cantarovich Marcelo , Baran Dana , Sandal Shaifali
Published: April 2022

Background

In kidney transplant recipients (KTRs), observational data have reported conflicting findings about the utility of renal resistive index (RRI) in determining outcomes. This study aimed to synthesize the current literature and determine the prognostic role of RRI in KTRs.

Methods

The authors conducted a systematic review to assess the role of RRI in predicting death, graft failure, graft function and proteinuria. Of the 934 titles/abstracts reviewed, 26 studies were included. There was significant heterogeneity in RRI measurements and thresholds as well as in analytical methods, and a meta-analysis could not be performed.

Results

All included studies were observational and included 7049 KTRs. Eight studies analyzed death, of which five reported a significant association with higher RRI. In the remaining three, small sample sizes and lower/multiple RRI thresholds may have limited detection of a statistically significant difference. Three studies investigated all-cause graft failure, and an association with RRI was reported but varied by time of RRI measurement. Three out of five studies that analyzed a composite of patient and graft outcomes reported an association with RRI. Evidence analyzing death-censored graft failure, graft failure (unclear whether death-censored or all-cause), measures of graft function and proteinuria was conflicting. Most studies had a moderate to high risk of bias.

Conclusions

RRI likely has a prognostic role in predicting patient outcomes, reflecting patient systemic vascular disease burden rather than graft hemodynamics. Since cardiovascular diseases are a major cause of death and graft loss, RRI may be explored as a noninvasive tool to risk-stratify KTRs.
Glioma and the gut–brain axis: opportunities and future perspectives
Authors: Dono Antonio , Nickles Jack , Rodriguez-Armendariz Ana G , McFarland Braden C , Ajami Nadim J , Ballester Leomar Y , Wargo Jennifer A , Esquenazi Yoshua
Published: April 2022

The gut–brain axis has presented a valuable new dynamic in the treatment of cancer and central nervous system (CNS) diseases. However, little is known about the potential role of this axis in neuro-oncology. The goal of this review is to highlight potential implications of the gut–brain axis in neuro-oncology, in particular gliomas, and future areas of research. The gut–brain axis is a well-established biochemical signaling axis that has been associated with various CNS diseases. In neuro-oncology, recent studies have described gut microbiome differences in tumor-bearing mice and glioma patients compared to controls. These differences in the composition of the microbiome are expected to impact the metabolic functionality of each microbiome. The effects of antibiotics on the microbiome may affect tumor growth and modulate the immune system in tumor-bearing mice. Preliminary studies have shown that the gut microbiome might influence PD-L1 response in glioma-bearing mice, as previously observed in other non-CNS cancers. Groundbreaking studies have identified intratumoral bacterial DNA in several cancers including high-grade glioma. The gut microbiome and its manipulation represent a new and relatively unexplored area that could be utilized to enhance the effectiveness of therapy in glioma. Further mechanistic studies of this therapeutic strategy are needed to assess its clinical relevance.
Pediatric pineoblastoma: A pooled outcome study of North American and Australian therapeutic data
Authors: Hansford Jordan R , Huang Jie , Endersby Raelene , Dodgshun Andrew J , Li Bryan K , Hwang Eugene , Leary Sarah , Gajjar Amar , Von Hoff Katja , Wells Olivia , Wray Alison , Kotecha Rishi S , Raleigh David R , Stoller Schuyler , Mueller Sabine , Schild Steven E , Bandopadhayay Pratiti , Fouladi Maryam , Bouffet Eric , Huang Annie , Onar-Thomas Arzu , Gottardo Nicholas G
Published: April 2022

Background

Pineoblastoma is a rare brain tumor usually diagnosed in children. Given its rarity, no pineoblastoma-specific trials have been conducted. Studies have included pineoblastoma accruing for other embryonal tumors over the past 30 years. These included only occasional children with pineoblastoma, making clinical features difficult to interpret and determinants of outcome difficult to ascertain.

Patients and Methods

Centrally or independently reviewed series with treatment and survival data from North American and Australian cases were pooled. To investigate associations between variables, Fisher’s exact tests, Wilcoxon-Mann-Whitney tests, and Spearman correlations were used. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analyses.

Results

We describe a pooled cohort of 178 pineoblastoma cases from Children’s Oncology Group (n = 82) and institutional series (n = 96) over 30 years. Children <3 years of age have significantly worse survival compared to older children, with 5-year progression-free survival (PFS) and overall survival (OS) estimates of 13.5 ± 5.1% and 16.2 ± 5.3%, respectively, compared with 60.8 ± 5.6% and 67.3 ± 5.0% for ≥3 years old (both P < .0001). Multivariable analysis showed male sex was associated with worse PFS in children <3 years of age (hazard ratio [HR] 3.93, 95% CI 1.80-8.55; P = .0006), suggestive of sex-specific risks needing future validation. For children ≥3 years of age, disseminated disease at diagnosis was significantly associated with an inferior 5-year PFS of 39.2 ± 9.7% (HR 2.88, 95% CI 1.52-5.45; P = .0012) and 5-year OS of 49.8 ± 9.1% (HR 2.87, 95% CI 1.49-5.53; P = .0016).

Conclusion

Given the rarity of this tumor, prospective, collaborative international studies will be vital to improving the long-term survival of these patients.
Etiology-based dietary approach for managing hyperkalemia in people with chronic kidney disease
Authors: St-Jules David E , Fouque Denis
Published: April 2022

Diet therapy for hyperkalemia in chronic kidney disease (CKD) is at a crossroads: many researchers and clinicians are no longer recommending the low-potassium diet, which has defined practice for the last half century, and instead are favoring a high-potassium, plant-rich diet. Central to this shift is the observation that reported dietary potassium intake is not associated with plasma potassium concentrations. However, kinetic studies using potassium salts indicate that people with CKD have impaired potassium tolerance that may make them susceptible to transient increases in plasma potassium levels from dietary potassium (postprandial hyperkalemia). Observational studies generally measure plasma potassium in the fasting state and before hemodialysis treatment, and therefore may not detect the acute effects of dietary potassium on plasma potassium concentrations. Differences between the acute and chronic effects of dietary potassium on plasma potassium levels may help explain clinical experiences and case studies attributing hyperkalemic episodes in patients with CKD to intakes of high-potassium foods despite their apparent lack of association. To reconcile these findings, an etiology-based approach to managing hyperkalemia is proposed in this review. The approach combines key elements of the low-potassium and plant-rich diets, and adds new features of meal planning to lower the risk of postprandial hyperkalemia.
Estimates of resting energy expenditure and total energy expenditure using predictive equations in adults with overweight and obesity: a systematic review with meta-analysis
Authors: Macena Mateus de Lima , Paula Déborah Tenório da Costa , da Silva Júnior André Eduardo , Praxedes Dafiny Rodrigues Silva , Pureza Isabele Rejane de Oliveira Maranhão , de Melo Ingrid Sofia Vieira , Bueno Nassib Bezerra
Published: April 2022

Context

Energy expenditure predictive equations can generate inaccurate estimates for overweight or obese individuals.

Objective

The objective of this review was to determine which predictive equations for resting energy expenditure (REE) and total energy expenditure (TEE) have the lowest bias and the highest precision in adults with overweight and obesity.

Data Sources

Searches were performed in January 2022 in MEDLINE, Web of Science, Scopus, CENTRAL, and the gray literature databases.

Data Extraction

Meta-analyses were performed with equations included in more than 1 study. The DerSimonian and Laird random-effects model and the I2 statistic were used to quantify heterogeneity in the quantitative analyses. The Egger test was performed to assess potential publication biases, and metaregressions were conducted to explore the heterogeneity. Findings were presented separated by participants’ body mass index classification (overweight and obesity).

Data Analysis

Sixty-one studies were included. The FAO/WHO/UNU (1985) equation, which uses only body weight in its formula, showed the lowest bias in estimating REE (mean difference [MD] = 8.97 kcal; 95% CI = –26.99; 44.94). In the subgroup analysis for individuals with obesity, the Lazzer (2007) equation showed the lowest bias (MD = 4.70 kcal; 95% CI = –95.45; 104.86). The Harris–Benedict equation (1919) showed the highest precision values for individuals with overweight (60.65%) and for individuals with obesity (62.54%). Equations with body composition data showed the highest biases. The equation proposed by the Institute of Medicine (2005) showed the lowest bias (MD = –2.52 kcal; 95% CI = –125.94; 120.90) in estimating the TEE. Most analyses showed high heterogeneity (I2 > 90%). There was no evidence of publication bias.

Conclusion

For individuals with overweight, the FAO/WHO/UNU (1985) and the Harris–Benedict equations (1919) showed the lowest bias and the highest precision in predicting the REE, respectively. For individuals with obesity, the Harris–Benedict equation (1919) showed the highest precision and the Lazzer equation (2007) showed the lowest bias. More studies are needed on predictive equations to estimate the TEE.

Systematic Review Registration

PROSPERO registration no. CRD42021262969.
Can wishful thinking explain evidence for overconfidence? An experiment on belief updating
Authors: Gneezy Uri , Hoffman Moshe , Lane Mark A , List John A , Livingston Jeffrey A , Seiler Michael J
Published: April 2022

Recent theoretical work shows that the better-than-average effect, where a majority believes their ability to be better than average, can be perfectly consistent with Bayesian updating. However, later experiments that account for this theoretical advance still find behavior consistent with overconfidence. The literature notes that overoptimism can be caused by either overconfidence (optimism about performance), wishful thinking (optimism about outcomes), or both. To test whether the better-than-average effect might be explained by wishful thinking instead of overconfidence, we conduct an experiment that is similar to those used in the overconfidence literature, but removes performance as a potential channel. We find evidence that wishful thinking might explain overconfidence only among the most optimistic subjects and that conservatism is possibly more of a worry; if unaccounted for, overconfidence might be underestimated.
Longitudinal Improvements in Viral Suppression for Persons With New HIV Diagnosis Receiving Care in the Ryan White Program: A 10-Year Experience in New Haven, CT (2009–2018)
Authors: Zhao Alice , Rizk Christina , Zhao Xiwen , Esu Arit , Deng Yanhong , Barakat Lydia , Villanueva Merceditas
Published: April 2022

Background

The Ryan White (RW) program funds medical and other support services for low-income persons with HIV, significantly improving progress along the HIV care continuum. Although the program has shown overall improvements in achievement of viral suppression, the relative contributions of changes in clinical practice and RW service components to the optimization of the HIV care continuum, particularly for those with new HIV diagnoses, remain unknown.

Methods

The target population was patients with recent HIV diagnoses who received care at RW-funded clinics in the greater New Haven area between 2009 and 2018. Client data were extracted from the RW-funded database, CAREWare, and the electronic medical record. Primary outcomes included time between HIV diagnosis and first HIV primary care (PC) visit, antiretroviral therapy (ART) initiation, and viral suppression (VS).

Results

There were 386 eligible patients. Between 2009 and 2018, the median number of days from HIV diagnosis to first PC visit decreased from 58.5 to 8.5 days, and ART initiation decreased from 155 to 9 days. In 2018, 86% of participants achieved viral suppression within 1 year, compared with 2.5% in 2009. Patients who initiated single-tablet ART and integrase inhibitor–containing regimens were more likely to reach viral suppression within 1 year (P < .001). Receipt of medical case management services was also associated with achieving viral suppression (P < .001).

Conclusions

Longitudinal improvements over 10 years in ART initiation and viral suppression were observed due to clinical advances and their effective implementation through the RW comprehensive care model. Further study of the essential components promoting these outcomes is needed.
Health Care Workers’ Sick Leave due to COVID-19 Vaccination in Context With SARS-CoV-2 Infection and Quarantine—A Multicenter Cross-Sectional Survey
Authors: Bauernfeind Stilla , Huppertz Gunnar , Mueller Karolina , Hitzenbichler Florian , Hardmann Loredana , Pemmerl Sylvia , Hollnberger Harald , Sieber Wolfgang , Wettstein Matthias , Seeliger Stephan , Kienle Klaus , Paetzel Christian , Kutz Norbert , Daller Dionys , Zorger Niels , Mohr Arno , Lampl Benedikt M J , Salzberger Bernd
Published: April 2022

Background

Reactogenicity of coronavirus disease 2019 (COVID-19) vaccines can result in inability to work. The object of this study was to evaluate health care workers’ sick leave after COVID-19 vaccination and to compare it with sick leave due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and quarantine leave.

Methods

A multicenter cross-sectional survey was conducted at Regensburg University Medical Center and 10 teaching hospitals in South-East Germany from July 28 to October 15, 2021.

Results

Of 2662 participants, 2309 (91.8%) were fully vaccinated without a history of SARS-CoV-2 infection. Sick leave after first/second vaccination occurred in 239 (10.4%) and 539 (23.3%) participants. In multivariable logistic regression, the adjusted odds ratio for sick leave after first/second vaccination compared with BNT162b2 was 2.26/3.72 for mRNA-1237 (95% CI, 1.28–4.01/1.99–6.96) and 27.82/0.48 for ChAdOx1-S (95% CI, 19.12–40.48/0.24–0.96). The actual median sick leave (interquartile range [IQR]) was 1 (0–2) day after any vaccination. Two hundred fifty-one participants (9.4%) reported a history of SARS-CoV-2 infection (median sick leave [IQR] 14 [10–21] days), 353 (13.3%) were quarantined at least once (median quarantine leave [IQR], 14 [10–14] days). Sick leave due to SARS-CoV-2 infection (4642 days) and quarantine leave (4710 days) accounted for 7.7 times more loss of workforce than actual sick leave after first and second vaccination (1216 days) in all fully vaccinated participants.

Conclusions

Sick leave after COVID-19 vaccination is frequent and is associated with the vaccine applied. COVID-19 vaccination should reduce the much higher proportion of loss of workforce due to SARS-CoV-2 infection and quarantine.
Beyond Fair Labelling: Offence Differentiation in Criminal Law
Authors: Cornford Andrew
Published: April 2022

How should criminal conduct be divided among different offences? To date, this question has received only one serious answer: the fair labelling principle, which states that distinctions among offences should reflect distinctions in the nature and seriousness of the wrongdoing that they criminalise. This article argues that the fair labelling principle should not be the sole or main principle governing offence differentiation decisions. Its argument consists in three main claims. First, the only plausible foundation for the principle is a duty to ensure that the blame expressed through criminal conviction is allocated justly. Second, this duty cannot be absolute: if it were, the result would be an absurdly highly differentiated criminal law. Third, several other factors are relevant to how we should differentiate offences, and these will often count against the demands of just blaming. A complete normative account of offence differentiation must thus extend beyond fair labelling—or indeed, any single principle.
Recent FDA Approvals in the Treatment of Graft-Versus-Host Disease
Authors: Martini Dylan J , Chen Yi-Bin , DeFilipp Zachariah
Published: April 2022

Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic cell transplantation (HCT) and is associated with significant morbidity and mortality. For many years, there have been few effective treatment options for patients with GVHD. First-line systemic treatment remains corticosteroids, but up to 50% of patients will develop steroid-refractory GVHD and the prognosis for these patients is poor. Elucidation of the pathophysiological mechanisms of acute and chronic GVHD has laid a foundation for novel therapeutic approaches. Since 2017, there have now been 4 approvals by the US Food and Drug Administration (FDA) for GVHD. Ruxolitinib, an oral selective JAK1/2 inhibitor, received FDA approval for the treatment of steroid-refractory acute GVHD in 2019 and remains the only agent approved for acute GVHD. There are currently 3 FDA approvals for the treatment of chronic GVHD: (1) ibrutinib, a BTK inhibitor traditionally used for B-cell malignancies, was the first agent approved for chronic GVHD after failure of one or more lines of systemic therapy, (2) belumosudil, an oral selective inhibitor of ROCK2, for patients with chronic GVHD who received at least 2 prior lines of treatment, and (3) ruxolitinib for chronic GVHD after failure of one or two lines of systemic therapy. In this review, we highlight the clinical data which support these FDA approvals in acute and chronic GVHD with a focus on mechanism of actions, clinical efficacy, and toxicities associated with these agents.
Physical Function, Psychosocial Status, and Symptom Burden Among Adults with Plasma Cell Disorders and Associations with Quality of Life
Authors: Jensen Christopher E , Vohra Sanah N , Nyrop Kirsten A , Deal Allison M , LeBlanc Matthew R , Grant Shakira J , Muss Hyman B , Lichtman Eben I , Rubinstein Samuel M , Wood William A , Mangieri Nicholas J , Jamison Lee , Tuchman Sascha A
Published: April 2022

Background

The plasma cell disorders (PCDs), multiple myeloma (MM), and light-chain amyloidosis (AL) are disproportionately diseases of older adults, whose care may be complicated by frailty associated with advancing age. We sought to evaluate the prevalence of functional deficits and symptoms in a cohort of persons with PCDs and associations of demographic, disease-related, functional, and psychosocial measures with quality of life (QoL).

Patients and Methods

Adults with PCDs were recruited into an observational registry in 2018-2020. Patients completed a functional assessment and European Organization for Research and Treatment of Cancer QoL questionnaire (QLQ-C30). Associations of covariates of interest with QoL were evaluated via univariate linear regression.

Results

Among 121 adults, the mean age was 68.6. Diagnoses were 74% MM, 14% AL, 7% both MM and AL, and 5% other PCDs. The median time from diagnosis was 34.9 months. Median lines of therapy were 2, with 11% having received ≥4th-line therapy.

Patients with functional deficits had lower mean QoL scores: dependence in IADLs (66.3 vs. 79.9, P = .001) and recent falls (56.7 vs. 76.8, P = .001). Patients ≤6 months from diagnosis had lower QoL (66.7) than those ≥2 years from diagnosis (77.3, P = .03). However, patients on later lines of therapy (≥4th-line) had lower QoL (62.2) than those on 1st-line treatment (76.0, P = .04).

Conclusions

Patients with physical impairments and more advanced PCDs had lower QoL than those without deficits or earlier in their disease course. Early identification of physical impairments may facilitate interventions that mitigate these deficits and thereby improve QoL for patients with PCDs.