bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring signaling pathways with probabilistic programming
Authors: Merrell David , Gitter Anthony
Published: September 2020

Motivation

Cells regulate themselves via dizzyingly complex biochemical processes called signaling pathways. These are usually depicted as a network, where nodes represent proteins and edges indicate their influence on each other. In order to understand diseases and therapies at the cellular level, it is crucial to have an accurate understanding of the signaling pathways at work. Since signaling pathways can be modified by disease, the ability to infer signaling pathways from condition- or patient-specific data is highly valuable. A variety of techniques exist for inferring signaling pathways. We build on past works that formulate signaling pathway inference as a Dynamic Bayesian Network structure estimation problem on phosphoproteomic time course data. We take a Bayesian approach, using Markov Chain Monte Carlo to estimate a posterior distribution over possible Dynamic Bayesian Network structures. Our primary contributions are (i) a novel proposal distribution that efficiently samples sparse graphs and (ii) the relaxation of common restrictive modeling assumptions.

Results

We implement our method, named Sparse Signaling Pathway Sampling, in Julia using the Gen probabilistic programming language. Probabilistic programming is a powerful methodology for building statistical models. The resulting code is modular, extensible and legible. The Gen language, in particular, allows us to customize our inference procedure for biological graphs and ensure efficient sampling. We evaluate our algorithm on simulated data and the HPN-DREAM pathway reconstruction challenge, comparing our performance against a variety of baseline methods. Our results demonstrate the vast potential for probabilistic programming, and Gen specifically, for biological network inference.

Availability and implementation

Find the full codebase at https://github.com/gitter-lab/ssps.

Supplementary information

Supplementary data are available at Bioinformatics online.
Sex-biased parasitism and expression of a sexual signal
Authors: Rosso Adam A , Nicholson Daniel J , Logan Michael L , Chung Albert K , Curlis John David , Degon Zachariah M , Knell Robert J , Garner Trenton W J , McMillan W Owen , Cox Christian L
Published: September 2020

Given that sexual signals are often expressed more highly in one sex than the other, they can impose a sex-specific cost of reproduction through parasitism. The two primary paradigms regarding the relationship of parasites to sexual signals are the good genes hypothesis and the immunocompetence handicap hypothesis; however, there are other ecological, morphological and energetic factors that might influence parasite infections in a sex-specific fashion. We tested the relationship between expression of a sexual signal (the dewlap) and ecological, morphological and energetic factors mediating ectoparasite (mite) load between male and female Panamanian slender anoles (Anolis apletophallus). We found that males were more highly parasitized than females because of the preponderance of ectoparasites on the larger dewlap of males. Indeed, ectoparasite infection increased with both body size and dewlap size in males but not in females, and parasite infection was related to energy storage in a sex-specific fashion for the fat bodies, liver and gonads. Our work and previous work on testosterone in anoles suggests that this pattern did not arise solely from immunosuppression by testosterone, but that mites prefer the dewlap as an attachment site. Thus, the expression of this sexual signal could incur a fitness cost that might structure life-history trade-offs.
Optimal estimation of bacterial growth rates based on a permuted monotone matrix
Authors: Ma Rong , Cai T Tony , Li Hongzhe
Published: September 2020

Motivated by the problem of estimating bacterial growth rates for genome assemblies from shotgun metagenomic data, we consider the permuted monotone matrix model $Y=\Theta\Pi+Z$ where $Y\in \mathbb{R}^{n\times p}$ is observed, $\Theta\in \mathbb{R}^{n\times p}$ is an unknown approximately rank-one signal matrix with monotone rows, $\Pi \in \mathbb{R}^{p\times p}$ is an unknown permutation matrix, and $Z\in \mathbb{R}^{n\times p}$ is the noise matrix. In this article we study estimation of the extreme values associated with the signal matrix $\Theta$, including its first and last columns and their difference. Treating these estimation problems as compound decision problems, minimax rate-optimal estimators are constructed using the spectral column-sorting method. Numerical experiments on simulated and synthetic microbiome metagenomic data are conducted, demonstrating the superiority of the proposed methods over existing alternatives. The methods are illustrated by comparing the growth rates of gut bacteria in inflammatory bowel disease patients and control subjects.
The Impact of Hypertension and Use of Calcium Channel Blockers on Tuberculosis Treatment Outcomes
Authors: Chidambaram Vignesh , Gupte Akshay , Wang Jann-Yuan , Golub Jonathan E , Karakousis Petros C
Published: September 2020

Background

Hypertension induces systemic inflammation, but its impact on the outcome of infectious diseases like tuberculosis (TB) is unknown. Calcium channel blockers (CCB) improve TB treatment outcomes in preclinical models, but their effect in patients with TB remain unclear.

Methods

This retrospective cohort study, including all patients > 18 years receiving treatment for culture-confirmed, drug-sensitive TB from 2000 to 2016 at the National Taiwan University Hospital, assessed the association of hypertension and CCB use with all-cause and infection-related mortality during the first 9 months of TB treatment, as well as sputum smear microscopy and sputum culture positivity at 2 and 6 months.

Results

Of the 2894 patients, 1052 (36.4%) had hypertension. A multivariable analysis revealed that hypertension was associated with increased mortality due to all causes (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.23–1.99) and infections (HR, 1.87; 95% CI, 1.34–2.6), but there were no statistical differences in microbiological outcomes when stratified based on hypertensive group. Dihydropyridine-CCB (DHP-CCB) use was associated only with reduced all-cause mortality (HR, 0.67; 95% CI, .45–.98) by univariable Cox regression. There were no associations between DHP-CCB use and infection-related mortality (HR, 0.78; 95% CI, .46–1.34) or microbiological outcomes in univariable or multivariable regression analyses.

Conclusions

Patients with hypertension have increased all-cause mortality and infection-related mortality during the 9 months following TB treatment initiation. DHP-CCB use may lower all-cause mortality in TB patients with hypertension. The presence of hypertension or the use of CCB did not result in a significant change in microbiological outcomes.
Human Papillomavirus Vaccination Prior to Loop Electroexcision Procedure Does Not Prevent Recurrent Cervical High-grade Squamous Intraepithelial Lesions in Women Living With Human Immunodeficiency Virus: A Randomized, Double-blind, Placebo-controlled Trial
Authors: Firnhaber Cynthia , Swarts Avril , Jezile Vuyokazi , Mulongo Masango , Goeieman Bridgette , Williams Sophie , Faesen Mark , Michelow Pamela , Wilkin Timothy
Published: September 2020

Background

Women living with human immunodeficiency virus (HIV), especially in sub-Saharan Africa, are at high risk for cervical high-grade squamous intraepithelial lesions (HSIL) and cervical cancer. These women have high HSIL recurrence rates after loop electroexcision procedure (LEEP). Retrospective studies suggest that human papillomavirus (HPV) vaccination improves response to treatment of cervical HSIL.

Methods

We performed a double-blind, randomized clinical trial enrolling 180 women living with HIV in Johannesburg, South Africa, diagnosed with cervical HSIL by colposcopic biopsy. Women received quadrivalent HPV vaccine or placebo (1:1) at entry, week 4, and week 26. LEEP was performed at week 4. Colposcopic-directed biopsies and cervical cytology were performed at weeks 26 and 52. The primary endpoint, cervical HSIL by histology or cytology at either week 26 or 52, was compared between arms using χ 2 analysis.

Results

Participant characteristics included median age of 39 years and median CD4 count 489 cells/μL, and 94% had HIV suppression. One hundred seventy-four women completed the vaccine/placebo series and had evaluable results at week 26 or 52. The proportion experiencing the primary endpoint was similar in the vaccine and placebo groups (53% vs 45%; relative risk, 1.18 [95% confidence interval, .87–1.6]; P = .29). HSIL recurrence was associated with a LEEP biopsy result of HSIL and detection of HSIL at the margins of the LEEP sample.

Conclusions

This study did not support HPV vaccination to prevent recurrent HSIL after LEEP in women living with HIV. Recurrent HSIL was high despite virologic suppression. Improved treatments are needed for HSIL to reduce the burden of cervical cancer among women living with HIV.

Clinical Trials Registration

NCT01928225.
Diagnostic Delay Is Associated With Complicated Disease and Growth Impairment in Paediatric Crohn’s Disease
Authors: Ricciuto Amanda , Mack David R , Huynh Hien Q , Jacobson Kevan , Otley Anthony R , deBruyn Jennifer , El-Matary Wael , Deslandres Colette , Sherlock Mary E , Critch Jeffrey N , Bax Kevin , Jantchou Prevost , Seidman Ernest G , Carman Nicholas , Rashid Mohsin , Muise Aleixo , Wine Eytan , Carroll Matthew W , Lawrence Sally , Van Limbergen Johan , Benchimol Eric I , Walters Thomas D , Griffiths Anne M , Church Peter C
Published: September 2020

Background

Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay.

Methods

We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression.

Results

Overall (64% Crohn’s disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0–9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41–4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005–0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay.

Conclusions

Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD.

Podcast

This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast
Seeking the historical listener
Authors: Plank Steven
Published: September 2020

This article considers questions relating to the performance practice of listening to music in early modern contexts. The evidence of paintings by Pieter Lastman, Gerard ter Borch and Hendrik Sorgh, poetry by Robert Herrick, William Shakespeare and Edmund Waller, and accounts of performances by Francesco da Milano, Nicola Matteis and Queen Elizabeth I all help to bring into focus questions of attentiveness, affective response and analogical understanding. The source material also interestingly raises the possibility of occasionally understanding the act of listening within a frame of erotic relationship modelled on Laura Mulvey’s well-known concept of the ‘male gaze’.
The species evenness of “prey” bacteria correlated with Bdellovibrio-and-like-organisms (BALOs) in the microbial network supports the biomass of BALOs in a paddy soil
Authors: Qian Hang , Hou Chunli , Liao Hao , Wang Li , Han Shun , Peng Shaobing , Chen Wenli , Huang Qiaoyun , Luo Xuesong
Published: September 2020

To seek how soil biotic and abiotic factors which might shape the Bdellovibrio-and-like-organisms community, we sampled paddy soils under different fertilization treatments including fertilization without nitrogen (Control), the nitrogen use treatment (N) and the nitrogen overuse one (HNK) at three rice growing stages. The abundances of BALOs were impacted by the rice-growing stages but not the fertilization treatments. The abundances of Bdellovibrionaceae-like were positively associated with soil moisture, which showed a negative relationship with Bacteriovoracaceae-like bacteria. High-throughput sequencing analysis of the whole bacterial community revealed that the α-diversity of BALOs was not correlated with any soil properties data. Network analysis detected eight families directly linked to BALOs, namely, Pseudomonadaceae, Peptostreptococcaceae, Flavobacteriaceae, Sediment-4, Verrucomicrobiaceae, OM27, Solirubrobacteraceae and Roseiflexaceae. The richness and composition of OTUs in the eight families were correlated with different soil properties, while the evenness of them had a positive effect on the predicted BALO biomass. These results highlighted that the bottom-up control of BALOs in paddy soil at least partially relied on the changes of soil water content and the diversity of bacteria directly linked to BALOs in the microbial network.
Back to the future: old methods for new estimation and test of the Gutenberg–Richter b-value for catalogues with variable completeness
Authors: Taroni Matteo
Published: September 2020

In this short paper we show how to use the classical maximum likelihood estimation procedure for the b-value of the Gutenberg–Richter law for catalogues with different levels of completeness. With a simple correction, that is subtracting the relative completeness level to each magnitude, it becomes possible to use the classical approach. Moreover, this correction allows to adopt the testing procedures, initially made for catalogues with a single level of completeness, for catalogues with different levels of completeness too.
Coenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated to one carbon metabolism
Authors: González-García Pilar , Hidalgo-Gutiérrez Agustín , Mascaraque Cristina , Barriocanal-Casado Eliana , Bakkali Mohammed , Ziosi Marcello , Abdihankyzy Ussipbek Botagoz , Sánchez-Hernández Sabina , Escames Germaine , Prokisch Holger , Martín Francisco , Quinzii Catarina M , López Luis C
Published: September 2020

Abnormalities of one carbon, glutathione and sulfide metabolisms have recently emerged as novel pathomechanisms in diseases with mitochondrial dysfunction. However, the mechanisms underlying these abnormalities are not clear. Also, we recently showed that sulfide oxidation is impaired in Coenzyme Q10 (CoQ10) deficiency. This finding leads us to hypothesize that the therapeutic effects of CoQ10, frequently administered to patients with primary or secondary mitochondrial dysfunction, might be due to its function as cofactor for sulfide:quinone oxidoreductase (SQOR), the first enzyme in the sulfide oxidation pathway. Here, using biased and unbiased approaches, we show that supraphysiological levels of CoQ10 induces an increase in the expression of SQOR in skin fibroblasts from control subjects and patients with mutations in Complex I subunits genes or CoQ biosynthetic genes. This increase of SQOR induces the downregulation of the cystathionine β-synthase and cystathionine γ-lyase, two enzymes of the transsulfuration pathway, the subsequent downregulation of serine biosynthesis and the adaptation of other sulfide linked pathways, such as folate cycle, nucleotides metabolism and glutathione system. These metabolic changes are independent of the presence of sulfur aminoacids, are confirmed in mouse models, and are recapitulated by overexpression of SQOR, further proving that the metabolic effects of CoQ10 supplementation are mediated by the overexpression of SQOR. Our results contribute to a better understanding of how sulfide metabolism is integrated in one carbon metabolism and may explain some of the benefits of CoQ10 supplementation observed in mitochondrial diseases.
The role of medicine donations in the global programme for the elimination of lymphatic filariasis
Authors: Williams Tijana , Taylor Rachel , Iwamoto Minne , Hida Takayuki , Gusovsky Fabian
Published: September 2020

World Health Assembly Resolution 50.29, adopted in 1997, committed the World Health Organization (WHO) and its member states to eliminate lymphatic filariasis (LF) as a public health problem. In 2000, to support this ambitious goal and the health ministries in the >70 LF-endemic countries, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) was created. The resulting WHO elimination strategy consists of two main components: to stop the spread of infection by interrupting transmission and to alleviate the suffering of affected populations (by controlling morbidity). The GPELF has brought together a broad global partnership of public and private actors, including three pharmaceutical companies with headquarters in three different continents. The medicine donations programmes from GlaxoSmithKline, MSD (trade name of Merck & Co. Inc., Kenilworth, NJ, USA) and Eisai have enabled significant achievements during the first 20 y of the GPELF and are positioned to provide essential contributions to the GPELF's goals for the next decade. As we celebrate the progress towards LF elimination during the GPELF's first 20 y, this article reflects on the factors that led to the creation of the three donation programmes, the contributions these programmes have made and some lessons learned along the way. We close by emphasizing our continued commitments to LF elimination and perspectives on the next decade.
Caring for patients in the global programme to eliminate lymphatic filariasis
Authors: Mackenzie Charles D , Mante Sunny
Published: September 2020

Clinical lymphatic filariasis (LF) is a debilitating, disfiguring medical condition with severe psychosocial consequences for patients and their families. Addressing these patients’ medical needs is a major component of the global programme to eliminate lymphatic filariasis (GPELF). In the 20 y of providing a minimal package of care many thousands of surgical operations to correct LF hydrocoeles been performed and national programmes in >90% of LF endemic countries have received the training needed to care for their patients. The creation of educational materials detailing appropriate patient care, together with increased funding, have been key catalysts in increasing awareness of clinical LF in recent years. Nevertheless, the implementation of care for these patients has often faced challenges that have led to delays in fully implementing the patient care component of GPELF; these include locating these often stigmatised individuals, maintaining provision of the necessary consumables (e.g. soaps and creams) and maintaining programme support within already overstretched national LF teams. As the LF global programme moves to achieve success by 2030 it will be vital to continue to focus efforts on the care and rehabilitation of those suffering from lymphoedema and hydrocoeles, learning from the experiences of the past 20 y.
Impact of the COVID-19 pandemic on stress and emotional reactions in Israel: a mixed-methods study
Authors: Levkovich Inbar , Shinan-Altman Shiri
Published: September 2020

Background

The COVID-19 pandemic has had a profound impact worldwide. This study sought to assess the pandemic's psychological impact on the Israeli public.

Methods

Using mixed methods we assessed Israeli adults during the COVID-19 outbreak. In the quantitative study, participants (N=1407) completed an online battery of measures assessing psychological variables and perceived threat related to COVID-19. Statistical analyses included tests for between-group differences and Pearson correlations. The qualitative study entailed in-depth, semistructured interviews conducted by telephone (N=38).

Results

The quantitative findings indicate that about 48% of the public had negative emotional reactions and 20% perceived they were liable to contract the virus. Moreover, a positive correlation was found between these feelings and the degree of perceived threat. Three major themes emerged from the qualitative study: 1) a sense of shock and chaos; 2) gradual adjustment to the new reality; and 3) fears and concerns for self and family members. The study's results revealed the following sources of participants’ emotional responses and sense of threat: health concerns regarding themselves and their loved ones; employment concerns; problems with children and spouses caused by being together at home; and difficulties entailed in working at home.

Conclusions

The study reveals many of the psychological variables and perceived threats related to COVID-19 in Israel. While social distancing may make people feel safer, it can also increase their feelings of isolation, stress and frustration and cause difficulties in many life situations. The findings point to the necessity of addressing the public's perceived susceptibility and emotional reactions about COVID-19.
Optimizing the synthesis of clinical trial data using sequential trees
Authors: Emam Khaled El , Mosquera Lucy , Zheng Chaoyi
Published: September 2020

Objective

With the growing demand for sharing clinical trial data, scalable methods to enable privacy protective access to high-utility data are needed. Data synthesis is one such method. Sequential trees are commonly used to synthesize health data. It is hypothesized that the utility of the generated data is dependent on the variable order. No assessments of the impact of variable order on synthesized clinical trial data have been performed thus far. Through simulation, we aim to evaluate the variability in the utility of synthetic clinical trial data as variable order is randomly shuffled and implement an optimization algorithm to find a good order if variability is too high.

Materials and Methods

Six oncology clinical trial datasets were evaluated in a simulation. Three utility metrics were computed comparing real and synthetic data: univariate similarity, similarity in multivariate prediction accuracy, and a distinguishability metric. Particle swarm was implemented to optimize variable order, and was compared with a curriculum learning approach to ordering variables.

Results

As the number of variables in a clinical trial dataset increases, there is a pattern of a marked increase in variability of data utility with order. Particle swarm with a distinguishability hinge loss ensured adequate utility across all 6 datasets. The hinge threshold was selected to avoid overfitting which can create a privacy problem. This was superior to curriculum learning in terms of utility.

Conclusions

The optimization approach presented in this study gives a reliable way to synthesize high-utility clinical trial datasets.
Electoral Competition with Rationally Inattentive Voters
Authors: Matějka Filip , Tabellini Guido
Published: September 2020

This paper studies how voters’ selective ignorance interacts with policy design by political candidates. It shows that the selectivity empowers voters with extreme preferences and small groups, that divisive issues attract most attention, and that public goods are underfunded. Finer granularity of information increases these inefficiencies. Rational inattention can also explain why competing opportunistic candidates do not always converge on the same policy issues.
Opioid-induced constipation in patients with cancer pain in Japan (OIC-J study): a post hoc subgroup analysis of patients with lung cancer
Authors: Imai Hisao , Fumita Soichi , Harada Toshiyuki , Noriyuki Toshio , Gamoh Makio , Okamoto Masaharu , Akashi Yusaku , Kizawa Yoshiyuki , Tokoro Akihiro
Published: September 2020

Objective

To evaluate the opioid-induced constipation burden in the subgroup of patients with lung cancer who participated in the observational Opioid-Induced Constipation in Patients with Cancer Pain in Japan (OIC-J) study.

Methods

The prospective, observational study, OIC-J, included 212 patients with various tumour types, 33% of whom had lung cancer. The incidence of opioid-induced constipation was evaluated using several diagnostic criteria, as well as the physician’s diagnosis and patient’s subjective assessment. Following initiation of opioids, patients recorded details of bowel movements (i.e. date/time, Bristol Stool Scale form, sensations of incomplete evacuation or anorectal obstruction/blockage and degree of straining) in a diary for 2 weeks. Relationships between patient characteristics and opioid-induced constipation onset and effects of opioid-induced constipation on quality of life were explored.

Results

In total, 69 patients were included in this post hoc analysis. The incidence of opioid-induced constipation varied (39.1–59.1%) depending on which diagnostic criteria was used. Diagnostic criteria that included a quality component or a patient’s feeling of bowel movement as an evaluation item (i.e. Rome IV, physician’s diagnosis, Bowel Function Index, patient’s assessment) showed higher incidences of opioid-induced constipation than recording the number of spontaneous bowel movements alone. Opioid-induced constipation occurred rapidly after initiating opioids and had a significant impact on Patient Assessment of Constipation Symptoms total score (P = 0.0031). Patient baseline characteristics did not appear to be predictive of opioid-induced constipation onset.

Conclusions

In patients with lung cancer, opioid-induced constipation can occur quickly after initiating opioids and can negatively impact quality of life. Early management of opioid-induced constipation, with a focus on quality-of-life improvement and patient’s assessments of bowel movements, is important for these patients.
Deriving Dual Dimensions of Bias: Preposed Negation Questions with EVEN
Authors: Jeong Sunwoo
Published: September 2020

Polar interrogatives with preposed negation (e.g., Didn’t Cam help?) convey positive epistemic bias. Polar interrogatives with even-type expressions, including prosodically stressed NPIs and minimizer NPIs (e.g., Did Cam lift a finger to help?), convey negative epistemic bias and often have a rhetorical flavor. This paper examines hybrid PQ constructions with both preposed negations and even-type expressions (e.g., Didn’t Cam lift a finger to help?; henceforth even-PNQs). It first presents a series of experimental studies which reveal that even-PNQs are characterized by complex, dual dimensions of bias contributed compositionally by both the preposed negation on the one hand and the even-type expression on the other. It then explores the theoretical implications of these results. The emerging data are shown to impose certain constraints on and generate additional desiderata for both the analyses of preposed negation questions and the analyses of even-type questions. Building on this discussion, a compositional analysis of even-PNQs is proposed. The analysis supports the presence of inner vs. outer negation ambiguity in PNQs, and identifies even-PNQs as inner-negation PNQs. It also adopts an informativity-based approach to the meaning contribution of even, formulated around the settledness of alternative issues.
Communicating with residents about 10 years of scientific progress in understanding thyroid cancer risk in children after the Fukushima Dai-ichi Nuclear Power Station accident
Authors: Suzuki Gen
Published: September 2020

After the Fukushima Dai-ichi Nuclear Power Station (FDNPS) accident in 2011, radiation-related risk of childhood thyroid cancer remains a matter of concern among residents living in areas affected by radioactive plumes. As a countermeasure to that, the Fukushima Prefectural Government—in conjunction with Fukushima Medical University—began the Fukushima Thyroid Examination (FTE) campaign in 2011. As 116 definite or suspected thyroid cancer cases were found after the first round of FTE and the total number of cases was >240 as of June 2020, residents’ concerns have deepened. Some researchers claim that these cases are radiation-induced, while others claim a screening effect (because FTE uses high-resolution ultrasound equipment) and express concern about over-diagnosis. Researchers therefore must address two conflicting issues: one is to elucidate radiation effects on thyroid cancer, which requires continuation of FTE; the other is to solve ethical problems associated with FTE. As to over-diagnosis, surgeons claim that early diagnosis benefits children by reducing the side-effects of treatment and prolonging disease-free survival, while cancer epidemiologists claim that early diagnosis will result in overtreatment without reducing the death rate. ‘To receive FTE or not’ and ‘to stop FTE or not’ are ongoing dilemmas for children (and their parents) and other stakeholders, respectively. To facilitate building a consensus among stakeholders, I overview recent findings about dose reconstruction, the dose–response relationship of thyroid cancer, over-diagnosis, and the natural history of thyroid cancer, all of which contribute to judging the risk–benefit balance of thyroid screening.
Hebrew In The Incantation Bowls and In The Babylonian Vocalization Tradition1
Authors: Frim Daniel J
Published: September 2020

Babylonian Jewish communities possessed a Hebrew vocalization tradition in parallel to the better-known Tiberian and Palestinian traditions. Most of the available evidence regarding Babylonian Hebrew comes from vocalized manuscripts, which were produced during a late period in the history of the dialect. This article examines Jewish Babylonian Aramaic incantation bowls as earlier sources of information regarding the Babylonian Hebrew vocalization tradition. Plene spellings of Hebrew words in these texts, along with other orthographic details, attest to characteristically Babylonian features, such as the preservation of short u, o, e, and i in phonological environments that trigger lowering to ɔ and ε in the Tiberian tradition; the correspondence between Babylonian a-vowels and Tiberian sĕgōl; and non- systematic differences between the Babylonian and Tiberian traditions.
Arabidopsis exoribonuclease USB1 interacts with the PPR-domain protein SOAR1 to negatively regulate abscisic acid signaling
Authors: Ma Yu , Zhang Shang , Bi Chao , Mei Chao , Jiang Shang-Chuan , Wang Xiao-Fang , Lu Zhi John , Zhang Da-Peng
Published: September 2020

Signaling by the phytohormone abscisic acid (ABA) involves pre-mRNA splicing, a key process of post-transcriptional regulation of gene expression. However, the regulatory mechanism of alternative pre-mRNA splicing in ABA signaling remains largely unknown. We previously identified a pentatricopeptide repeat protein SOAR1 (suppressor of the ABAR-overexpressor 1) as a crucial player downstream of ABAR (putative ABA receptor) in ABA signaling. In this study, we identified a SOAR1 interaction partner USB1, which is an exoribonuclease catalyzing U6 production for spliceosome assembly. We reveal that together USB1 and SOAR1 negatively regulate ABA signaling in early seedling development. USB1 and SOAR1 are both required for the splicing of transcripts of numerous genes, including those involved in ABA signaling pathways, suggesting that USB1 and SOAR1 collaborate to regulate ABA signaling by affecting spliceosome assembly. These findings provide important new insights into the mechanistic control of alternative pre-mRNA splicing in the regulation of ABA-mediated plant responses to environmental cues.
Multifaceted roles of RNA polymerase IV in plant growth and development
Authors: Zhang Shuai , Wu Xiao-Qing , Xie Hui-Ting , Zhao Shan-Shan , Wu Jian-Guo
Published: September 2020

We discuss the latest findings on RNA polymerase IV (Pol IV) in plant growth and development, providing new insights and expanding on new ideas for further, more in-depth research on Pol IV.
Delineating the future of iron biofortification studies in rice: challenges and future perspectives
Authors: Kawakami Yuta , Bhullar Navreet K
Published: September 2020

Iron (Fe) deficiency in humans is a widespread problem worldwide. Fe biofortification of rice (Oryza sativa) is a promising approach to address human Fe deficiency. Since its conceptualization, various biofortification strategies have been developed, some of which have resulted in significant increases in grain Fe concentration. However, there are still many aspects that have not yet been addressed in the studies to date. In this review, we first overview the important rice Fe biofortification strategies reported to date and the complications associated with them. Next, we highlight the key outstanding questions and hypotheses related to rice Fe biofortification. Finally, we make suggestions for the direction of future rice biofortification studies.
The Economic Consequences of Marital Separation for Parents in New Zealand: Insights from a Large Administrative Dataset
Authors: Fletcher Michael , Maré David C , Maloney Tim
Published: September 2020

Marital separation, especially when dependent children are involved, is a significant and disruptive event that often involves considerable changes in living standards. This article uses a newly available dataset to provide, for the first time, estimates of the short- to medium-term economic impacts of marital separation for parents of dependent-aged children in New Zealand. Unlike most similar studies, which are based on relatively small samples of separating individuals drawn from panel surveys, we exploit a large database of longitudinal tax and welfare records. This allows us to examine the economic consequences of separation for approximately 16,000 New Zealand parents and carers of dependent-aged children who separated in a 12-month period. The analysis applies propensity score matching, combined with difference-in-differences estimation, to estimate impacts. We find an average 29 per cent first-year decline in equivalised incomes for separating women and a 15 per cent average rise for men. In both cases, the effects persist to the end of the study period three years after separation. Our results also show a significant rise in poverty rates for both men and women, relatively small changes in employment and earnings, and a large increase in welfare receipts among the women.
Understanding the origin of white dwarf atmospheric pollution by dynamical simulations based on detected three-planet systems
Authors: Maldonado R F , Villaver E , Mustill A J , Chavez M , Bertone E
Published: September 2020

Between 25 and 50 ${{\ \rm per\ cent}}$ of white dwarfs (WD) present atmospheric pollution by metals, mainly by rocky material, which has been detected as gas/dust discs, or in the form of photometric transits in some WDs. Planets might be responsible for scattering minor bodies that can reach stargazing orbits, where the tidal forces of the WD can disrupt them and enhance the chances of debris to fall on to the WD surface. The planet–planet scattering process can be triggered by the stellar mass-loss during the post main-sequence (MS) evolution of planetary systems. In this work, we continue the exploration of the dynamical instabilities that can lead to WD pollution. In a previous work, we explored two-planet systems found around MS stars and here we extend the study to three-planet system architectures. We evolved 135 detected three-planet systems orbiting MS stars to the WD phase by scaling their orbital architectures in a way that their dynamical properties are preserved using the N-body integrator package mercury. We find that 100 simulations (8.6 ${{\ \rm per\ cent}}$) are dynamically active (having planet losses, orbit crossing, and scattering) on the WD phase, where low-mass planets (1–100 M⊕) tend to have instabilities in Gyr time-scales, while high-mass planets (>100 M⊕) decrease the dynamical events more rapidly as the WD ages. Besides, 19 simulations (1.6 ${{\ \rm per\ cent}}$) were found to have planets crossing the Roche radius of the WD, where 9 of them had planet–star collisions. Our three-planet simulations have a slight increase in percentage of simulations that may contribute to the WD pollution than the previous study involving two-planet systems and have shown that planet–planet scattering is responsible of sending planets close to the WD, where they may collide directly to the WD, become tidally disrupted or circularize their orbits, hence producing pollution on the WD atmosphere.
The Completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: exploring the halo occupation distribution model for emission line galaxies
Authors: Avila S , Gonzalez-Perez V , Mohammad F G , de Mattia A , Zhao C , Raichoor A , Tamone A , Alam S , Bautista J , Bianchi D , Burtin E , Chapman M J , Chuang C-H , Comparat J , Dawson K , Divers T , du Mas des Bourboux H , Gil-Marin H , Mueller E M , Habib S , Heitmann K , Ruhlmann-Kleider V , Padilla N , Percival W J , Ross A J , Seo H J , Schneider D P , Zhao G
Published: September 2020

We study the modelling of the halo occupation distribution (HOD) for the eBOSS DR16 emission line galaxies (ELGs). Motivated by previous theoretical and observational studies, we consider different physical effects that can change how ELGs populate haloes. We explore the shape of the average HOD, the fraction of satellite galaxies, their probability distribution function (PDF), and their density and velocity profiles. Our baseline HOD shape was fitted to a semi-analytical model of galaxy formation and evolution, with a decaying occupation of central ELGs at high halo masses. We consider Poisson and sub/super-Poissonian PDFs for satellite assignment. We model both Navarro–Frenk–White and particle profiles for satellite positions, also allowing for decreased concentrations. We model velocities with the virial theorem and particle velocity distributions. Additionally, we introduce a velocity bias and a net infall velocity. We study how these choices impact the clustering statistics while keeping the number density and bias fixed to that from eBOSS ELGs. The projected correlation function, wp, captures most of the effects from the PDF and satellites profile. The quadrupole, ξ2, captures most of the effects coming from the velocity profile. We find that the impact of the mean HOD shape is subdominant relative to the rest of choices. We fit the clustering of the eBOSS DR16 ELG data under different combinations of the above assumptions. The catalogues presented here have been analysed in companion papers, showing that eBOSS RSD+BAO measurements are insensitive to the details of galaxy physics considered here. These catalogues are made publicly available.
Going back to basics: accelerating exoplanet transit modelling using Taylor-series expansion of the orbital motion
Authors: Parviainen H , Korth J
Published: September 2020

A significant fraction of an exoplanet transit model evaluation time is spent calculating projected distances between the planet and its host star. This is a relatively fast operation for a circular orbit, but slower for an eccentric one. However, because the planet’s position and its time derivatives are constant for any specific point in orbital phase, the projected distance can be calculated rapidly and accurately in the vicinity of the transit by expanding the planet’s x and y positions in the sky plane into a Taylor series at mid-transit. Calculating the projected distance for an elliptical orbit using the four first time derivatives of the position vector (velocity, acceleration, jerk, and snap) is ∼100 times faster than calculating it using the Newton’s method, and also significantly faster than calculating z for a circular orbit because the approach does not use numerically expensive trigonometric functions. The speed gain in the projected distance calculation leads to 2–25 times faster transit model evaluation speed, depending on the transit model complexity and orbital eccentricity. Calculation of the four position derivatives using numerical differentiation takes $\sim 1\, \mu$s with a modern laptop and needs to be done only once for a given orbit, and the maximum error the approximation introduces to a transit light curve is below 1 ppm for the major part of the physically plausible orbital parameter space.
SINEUP long non-coding RNA acts via PTBP1 and HNRNPK to promote translational initiation assemblies
Authors: Toki Naoko , Takahashi Hazuki , Sharma Harshita , Valentine Matthew N Z , Rahman Ferdous-Ur M , Zucchelli Silvia , Gustincich Stefano , Carninci Piero
Published: September 2020

SINEUPs are long non-coding RNAs (lncRNAs) that contain a SINE element, and which up-regulate the translation of target mRNA. They have been studied in a wide range of applications, as both biological and therapeutic tools, although the underpinning molecular mechanism is unclear. Here, we focused on the sub-cellular distribution of target mRNAs and SINEUP RNAs, performing co-transfection of expression vectors for these transcripts into human embryonic kidney cells (HEK293T/17), to investigate the network of translational regulation. The results showed that co-localization of target mRNAs and SINEUP RNAs in the cytoplasm was a key phenomenon. We identified PTBP1 and HNRNPK as essential RNA binding proteins. These proteins contributed to SINEUP RNA sub-cellular distribution and to assembly of translational initiation complexes, leading to enhanced target mRNA translation. These findings will promote a better understanding of the mechanisms employed by regulatory RNAs implicated in efficient protein translation.
METTL3 counteracts premature aging via m6A-dependent stabilization of MIS12 mRNA
Authors: Wu Zeming , Shi Yue , Lu Mingming , Song Moshi , Yu Zihui , Wang Jilu , Wang Si , Ren Jie , Yang Yun-Gui , Liu Guang-Hui , Zhang Weiqi , Ci Weimin , Qu Jing
Published: September 2020

N6-Methyladenosine (m6A) messenger RNA methylation is a well-known epitranscriptional regulatory mechanism affecting central biological processes, but its function in human cellular senescence remains uninvestigated. Here, we found that levels of both m6A RNA methylation and the methyltransferase METTL3 were reduced in prematurely senescent human mesenchymal stem cell (hMSC) models of progeroid syndromes. Transcriptional profiling of m6A modifications further identified MIS12, for which m6A modifications were reduced in both prematurely senescent hMSCs and METTL3-deficient hMSCs. Knockout of METTL3 accelerated hMSC senescence whereas overexpression of METTL3 rescued the senescent phenotypes. Mechanistically, loss of m6A modifications accelerated the turnover and decreased the expression of MIS12 mRNA while knockout of MIS12 accelerated cellular senescence. Furthermore, m6A reader IGF2BP2 was identified as a key player in recognizing and stabilizing m6A-modified MIS12 mRNA. Taken together, we discovered that METTL3 alleviates hMSC senescence through m6A modification-dependent stabilization of the MIS12 transcript, representing a novel epitranscriptional mechanism in premature stem cell senescence.
Case Report: Overwhelming Babesia Parasitemia Successfully Treated Promptly With RBC Apheresis and Triple Therapy With Clindamycin, Azithromycin, and Atovaquone
Authors: Li Yijia , Stanley Susan , Villalba Julian A , Nelson Sandra , Gelfand Jeffrey
Published: September 2020

Babesiosis with high-grade parasitemia is life-threatening, especially in asplenic hosts. We report an asplenic patient with parasitemia >50% who was successfully treated with prompt red blood cell apheresis and triple therapy with clindamycin + azithromycin + atovaquone. This regimen may be an alternative to poorly tolerated clindamycin + quinine in severe cases.
Female Gender Is Associated with a Higher Prevalence of Chronic Neck Pain, Chronic Low Back Pain, and Migraine: Results of the Spanish National Health Survey, 2017
Authors: Palacios-Ceña Domingo , Albaladejo-Vicente Romana , Hernández-Barrera Valentin , Lima-Florencio Lidiane , Fernández-de-las-Peñas Cesar , Jimenez-Garcia Rodrigo , López-de-Andrés Ana , de Miguel-Diez Javier , Perez-Farinos Napoleon
Published: September 2020

Objectives

To assess the prevalence of chronic neck pain (CNP), chronic low back pain (CLBP), and migraine headache (MH) in the Spanish population and to identify sociodemographic and health-related variables associated with CNP, CLBP, and MH.

Design

Observational study.

Setting

Spain.

Subjects

A total of 22,511 persons 18 years of age or older (10,304 males and 12,207 females) who participated in the 2017 Spanish National Health Survey.

Methods

Stratified three-stage sampling was applied. CNP, CLBP, and MH were the dependent variables. The analysis was conducted separately by gender. Sociodemographic features, self-perceived health status, lifestyle habits, comorbidities, and pain features were analyzed by using logistic regression models.

Results

Females reported a higher prevalence of CNP, CLBP, and MH (P < 0.001) than males. For both sexes, anxiety and/or depression and poor self-rated health were associated with a significantly increased prevalence of CNP, CLBP, and MH. For CNP and CLBP, the identified associated factors were older age and limitations to usual activity. For CNP and MH, the most common associated factor was comorbid respiratory disease.

Conclusions

Our study identified several factors associated with CNP, CLBP, and MH in Spanish female and male adults, with potential implications for health care providers.
A cross-sectional population survey of physicians in Alberta, Canada about a novel provincial contact tracing smartphone app
Authors: Jerome D , Pietrosanu M , Dhillon K
Published: September 2020

Background

The Canadian province of Alberta released the ABTraceTogether smartphone app in May 2020 to assist in contact tracing during the SARS-CoV-2 pandemic. Public engagement with this public health tool has been low, limiting the effectiveness of the intervention. This study examines physician knowledge of the app and practice patterns in relation to the app.

Methods

We conducted a cross-sectional self-administered online English language survey of physicians and medical students in Alberta, Canada. The survey link was sent to all registered members of the College of Physicians and Surgeons of Alberta and was distributed by other provincial physician organizations and health zone leaders.

Results

The survey received 317 responses. 96% of participants were aware of the app but only 27% had recommended the app to patients. The most common reason provided for not downloading or recommending the app was that participants had security concerns about the app. 23% of participants indicated they did not believe they had a responsibility to recommend the app to others.

Conclusions

Our study provides insights into participants’ knowledge and beliefs about the ABTraceTogether app. This information may be valuable to public health officials who wish to engage physicians in future public health campaigns.