bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer Antigen 15-3/Mucin 1 Levels in CCTG MA.32: A Breast Cancer Randomized Trial of Metformin vs Placebo
Authors: Goodwin Pamela J , Dowling Ryan J O , Ennis Marguerite , Chen Bingshu E , Parulekar Wendy R , Shepherd Lois E , Gelmon Karen A , Whelan Timothy J , Ligibel Jennifer A , Hershman Dawn L , Mayer Ingrid A , Hobday Timothy J , Rastogi Priya , Rabaglio-Poretti Manuela , Lemieux Julie , Thompson Alastair M , Rea Daniel W , Stambolic Vuk 
Published: July 2021

Abstract

Background
Circulating levels of cancer antigen (CA) 15–3, a tumor marker and regulator of cellular metabolism, were reduced by metformin in a nonrandomized neoadjuvant study. We examined the effects of metformin (vs placebo) on CA 15–3 in participants of MA.32, a phase III randomized trial in early-stage breast cancer.

Methods
A total of 3649 patients with T1-3, N0-3, M0 breast cancer were randomly assigned; pretreatment and 6-month on-treatment fasting plasma were centrally assayed for CA 15–3. Genomic DNA was analyzed for the rs11212617 single nucleotide polymorphism. Absolute and relative change of CA 15–3 (metformin vs placebo) were compared using Wilcoxon rank and t tests. Regression models adjusted for baseline differences and assessed key interactions. All statistical tests were 2-sided.

Results
Mean (SD) age was 52.4 (10.0) years. The majority of patients had T2/3, node-positive, hormone receptor–positive, HER2-negative breast cancer treated with (neo)adjuvant chemotherapy and hormone therapy. Mean (SD) baseline CA 15–3 was 17.7 (7.6) and 18.0 (8.1 U/mL). At 6 months, CA 15–3 was statistically significantly reduced in metformin vs placebo arms (absolute geometric mean reduction in CA 15–3 = 7.7% vs 2.0%, P &lt; .001; relative metformin: placebo level of CA 15–3 [adjusted for age, baseline body mass index, and baseline CA 15–3] = 0.94, 95% confidence interval = 0.92 to 0.96). This reduction was independent of tumor characteristics, perioperative systemic therapy, baseline body mass index, insulin, and the single nucleotide polymorphism status (all Ps &gt; .11).

Conclusions
Our observation that metformin reduces CA 15–3 by approximately 6% was corroborated in a large placebo-controlled randomized trial. The clinical implications of this reduction in CA 15–3 will be explored in upcoming efficacy analyses of breast cancer outcomes in MA.32.
Parents’ Self-Reported Psychological Impacts of COVID-19: Associations With Parental Burnout, Child Behavior, and Income
Authors: Kerr Margaret L , Fanning Kerrie A , Huynh Tuyen , Botto Inés , Kim Christina N 
Published: July 2021

Abstract

Objective
The current study investigates associations between parents’ perceived coronavirus disease 2019 (COVID-19) psychological impacts and experiences of parental burnout, children’s behaviors, and income.

Methods
Data were collected during an online survey of parents’ (N = 1000) pandemic experiences in April 2020. Parents (M = 36.5 years old, SD = 6.0; 82.1% White) with at least one child 12 years or younger reported on measures of mental health, perceived COVID-19 impacts, parental burnout, and perceived increases in children’s stress and positive behaviors.

Results
Path model analyses revealed that parents who perceived increased psychological impacts from COVID-19 reported higher levels of parental burnout, greater increases in children’s stress behaviors, and less positive behavior in children. Additionally, there were significant indirect effects of parental burnout on the link between COVID-19 psychological impacts and children’s behaviors. Finally, family income moderated associations between psychological impacts and children’s stress behaviors, such that the association was stronger for families with lower income.

Conclusions
These results suggest parents’ perceptions of how the COVID-19 pandemic has impacted their mental health has implications for parent and child well-being, with stronger associations for low-income families. Given the potential for spillover effects between parents and children, promoting family well-being through practice and policy initiatives is crucial, including providing financial and caregiving relief for parents, and mental and behavioral health support for families.
BUSCO Update: Novel and Streamlined Workflows along with Broader and Deeper Phylogenetic Coverage for Scoring of Eukaryotic, Prokaryotic, and Viral Genomes
Authors: Manni Mosè , Berkeley Matthew R , Seppey Mathieu , Simão Felipe A , Zdobnov Evgeny M 
Published: July 2021

Abstract
Methods for evaluating the quality of genomic and metagenomic data are essential to aid genome assembly procedures and to correctly interpret the results of subsequent analyses. BUSCO estimates the completeness and redundancy of processed genomic data based on universal single-copy orthologs. Here, we present new functionalities and major improvements of the BUSCO software, as well as the renewal and expansion of the underlying data sets in sync with the OrthoDB v10 release. Among the major novelties, BUSCO now enables phylogenetic placement of the input sequence to automatically select the most appropriate BUSCO data set for the assessment, allowing the analysis of metagenome-assembled genomes of unknown origin. A newly introduced genome workflow increases the efficiency and runtimes especially on large eukaryotic genomes. BUSCO is the only tool capable of assessing both eukaryotic and prokaryotic species, and can be applied to various data types, from genome assemblies and metagenomic bins, to transcriptomes and gene sets.
Validation of the hen’s egg test for micronucleus induction (HET-MN): detailed protocol including scoring atlas, historical control data and statistical analysis
Authors: Maul Katrin , Fieblinger Dagmar , Heppenheimer Andreas , Kreutz Juergen , Liebsch Manfred , Luch Andreas , Pirow Ralph , Poth Albrecht , Strauch Pamela , Dony Eva , Schulz Markus , Wolf Thorsten , Reisinger Kerstin 
Published: July 2021

Abstract
A validation exercise of the hen’s egg test for micronucleus induction was finalised with a very good predictivity based on the analysis of micronuclei in peripheral erythrocytes of fertilised chicken eggs (Reisinger et al. The hen’s egg test for micronucleus-induction (HET-MN): validation data set. Mutagenesis, this issue). For transparency reasons this complementary publication provides further details on the assay especially as it was the first validation study in the field of genotoxicity testing involving the use of chicken eggs. Thus, the experimental protocol is described in detail and is complemented by a scoring atlas for microscopic analysis in blood cells. In addition, general characteristics of the test system, which is able to mirror the systemic availability of test compounds, are delineated: the test compound passes the egg membrane and is taken up by the blood vessels of the underlying chorioallantoic membrane. Subsequently, it is distributed by the circulating blood, metabolised by the developing liver and the yolk sac membrane and finally excreted into the allantois, a bladder equivalent. In specific, the suitability of the test system for genotoxicity testing is shown by, inter alia, a low background DNA damage in a comprehensive historical control database. In addition, the state-of-the-art statistical method used to evaluate obtained data is delineated. It combines laboratory-specific effect threshold with the Umbrella–Williams test, a statistical model also of interest for other genotoxicity test methods.
Mouse models of glioblastoma for the evaluation of novel therapeutic strategies
Authors: Haddad Alexander F , Young Jacob S , Amara Dominic , Berger Mitchel S , Raleigh David R , Aghi Manish K , Butowski Nicholas A 
Published: July 2021

AbstractGlioblastoma (GBM) is an incurable brain tumor with a median survival of approximately 15 months despite an aggressive standard of care that includes surgery, chemotherapy, and ionizing radiation. Mouse models have advanced our understanding of GBM biology and the development of novel therapeutic strategies for GBM patients. However, model selection is crucial when testing developmental therapeutics, and each mouse model of GBM has unique advantages and disadvantages that can influence the validity and translatability of experimental results. To shed light on this process, we discuss the strengths and limitations of 3 types of mouse GBM models in this review: syngeneic models, genetically engineered mouse models, and xenograft models, including traditional xenograft cell lines and patient-derived xenograft models.
Impact of the SnRK1 protein kinase on sucrose homeostasis and the transcriptome during the diel cycle
Authors: Peixoto Bruno , Moraes Thiago A , Mengin Virginie , Margalha Leonor , Vicente Rubén , Feil Regina , Höhne Melanie , Sousa António G G , Lilue Jingtao , Stitt Mark , Lunn John E , Baena-González Elena 
Published: July 2021

AbstractSNF1-related Kinase 1 (SnRK1) is an evolutionarily conserved protein kinase with key functions in energy management during stress responses in plants. To address a potential role of SnRK1 under favorable conditions, we performed a metabolomic and transcriptomic characterization of rosettes of 20-d-old Arabidopsis (Arabidopsis thaliana) plants of SnRK1 gain- and loss-of-function mutants during the regular diel cycle. Our results show that SnRK1 manipulation alters the sucrose and trehalose 6-phosphate (Tre6P) relationship, influencing how the sucrose content is translated into Tre6P accumulation and modulating the flux of carbon to the tricarboxylic acid cycle downstream of Tre6P signaling. On the other hand, daily cycles of Tre6P accumulation were accompanied by changes in SnRK1 signaling, leading to a maximum in the expression of SnRK1-induced genes at the end of the night, when Tre6P levels are lowest, and to a minimum at the end of the day, when Tre6P levels peak. The expression of SnRK1-induced genes was strongly reduced by transient Tre6P accumulation in an inducible Tre6P synthase (otsA) line, further suggesting the involvement of Tre6P in the diel oscillations in SnRK1 signaling. Transcriptional profiling of wild-type plants and SnRK1 mutants also uncovered defects that are suggestive of an iron sufficiency response and of a matching induction of sulfur acquisition and assimilation when SnRK1 is depleted. In conclusion, under favorable growth conditions, SnRK1 plays a role in sucrose homeostasis and transcriptome remodeling in autotrophic tissues and its activity is influenced by diel fluctuations in Tre6P levels.
Recent developments in German taxation of distributions of foreign trusts and foundations to their Germany-based beneficiaries
Authors: Haag Maximilian , Tischendorf Michael 
Published: July 2021

Abstract
Distributions of foreign trusts and foundations to their Germany-based beneficiaries may be subject to German income and gift tax. Fortunately, German tax authorities now have implemented a judgment of the German Federal Fiscal Court rendered on 3 July 2019 stating that distributions made by a foreign foundation to its Germany-based beneficiaries are not subject to German gift tax provided that (i) the distribution has been made in accordance with the foundation’s statutes and (ii) the beneficiary does not have a claim regarding the distribution received. However, there are still some cases in which gift tax may be levied on such distributions, so that the risk of potential double taxation with both income and gift tax is still not completely off the table.
New horizons in early drugs development in solid cancers
Authors: Kotecki Nuria , Kindt Nadège , Krayem Mohammad , Awada Ahmad 
Published: July 2021

Purpose of review
Drug development is the process of bringing new anticancer agents into clinical practice. From the basic research to clinical research each step is essential and intimately linked. The aim of this review is to describe emerging preclinical models and to provide an overview of selected drugs recently developed in oncology.

Recent findings
Preclinical models reproducing human immune-tumor interactions, 3D cell cultures and microfluidic platforms are of great interest for the development of immunotherapies and combination therapies and offer the opportunity to better understand the interplay between cancer and stromal cells.
Following a better biological understanding of cancer and advances in precision oncology, new exciting drugs (e.g. antibodies-drugs conjugates [ADCs], immunotherapeutic strategies, molecular-targeted therapies) have entered the field of clinical research and even clinical practice.

Summary
Recent improvements in preclinical models will allow an accurate selection of drug candidates for clinical research. Innovative drugs are currently being developed from early to later phases of development. An important remaining challenge in drug development is to set up a new model of patient-centered clinical research to facilitate quick access to innovation and target-oriented trials.
Are advancements in screening technology contributing to breast cancer over-diagnosis?
Authors: Jatoi Ismail 
Published: July 2021

Purpose of review
Advancements in breast screening technology have increased the sensitivity of screening and thereby increased the detection rates of nonlethal cancers. Thus, improvements in breast screening technology may contribute to ‘over-diagnosis’, which refers to detection of cancers that pose no threat to life and that, in the absence of screening, might never have been detected. The purpose of this review is to draw attention to risks of over-diagnosis and provide a rationale for evaluating screening clinical breast examination (CBE) as an alternative to modern technology-based (mammography) screening.

Recent findings
Novel screening technologies have been adopted largely on the basis of their abilities to increase tumor-detection rates. However, as breast cancer treatments have improved, the mortality benefits of screening have declined. Moreover, there is evidence suggesting that, in the modern era of effective adjuvant systemic therapies, the mortality benefit of screening CBE may now be comparable to that of modern screening mammography, but screening CBE carries less risk of over-diagnosis.

Summary
A randomized trial comparing modern mammography screening versus screening CBE is warranted. If confirmed that the mortality benefits of the two screening strategies are now comparable, then screening CBE might be considered a reasonable alternative to mammography screening.
Barriers to Respite Care for Children with Special Health Care Needs
Authors: Graaf Genevieve , Baiden Philip , Boyd George , Keyes Latocia 
Published: July 2021

ABSTRACT:

Objective:
The objective of this study was to estimate time-specific, population-based prevalence of 14 specific barriers to respite services, as reported by parents of children with special health care needs (CSHCN) with and without emotional, behavioral, or developmental problems (EBDPs), and to identify individual, family, and environmental characteristics associated with the most common barriers to respite care for families of CSHCN.

Methods:
Descriptive, bivariate, and multivariable logistic regression analyses were used to examine data from the National Survey of Children with Special Health Care Needs for 2005/2006 and 2009/2010.

Results:
Among families reporting unmet need for respite care services, service availability or transportation barriers (23.8%) and cost barriers (19.8%) were the most commonly reported obstacles among all CSHCN, followed by lack of knowledge about where to obtain respite services (12.1%) and inconvenient service times (11.3%). Reports of location or availability barriers decreased significantly from 2005 to 2009, but service time barriers increased simultaneously. All types of barriers to respite services were reported significantly more frequently by CSHCN with EBDPs than those without, even when other demographic factors were controlled for. CSHCN conditional severity and discontinuity in insurance were positively associated with cost barriers, whereas CSHCN public health coverage was associated with reduced rates of reported cost and information barriers to respite care.

Conclusion:
Increased understanding of parent-reported barriers to respite care for families of CSHCN is critical to creating structural and practice-oriented solutions that address obstacles and increase access to respite care for these vulnerable families.
Evaluation of the Safety and Immunogenicity of M-M-RII (Combination Measles-mumps-rubella Vaccine)
Authors: Nyaku Mawuli , Richardson Elizabeth , Martinon-Torres Federico , Kuter Barbara J. 
Published: July 2021

Background:
The safety and immunogenicity of M-M-RII (measles, mumps and rubella virus vaccine live, Merck & Co., Inc., West Point, PA)—the only combined measles, mumps and rubella vaccine licensed for use in the United States—were previously reported in pre- and postlicensure clinical trials conducted from 1988 to 2009. M-M-RII continues to be evaluated as a comparator in clinical trials of other vaccines. Here, we review safety and efficacy data from more recent clinical trials of M-M-RII.

Methods:
We performed a systematic literature review of trials using M-M-RII published from 2010 to 2019.

Results:
In the 15 studies that met the inclusion criteria, a total of 12,032 subjects were vaccinated: 7667 persons received a first dose only, 2137 participated in 2-dose studies (128 received 1 dose and 2009 received both) and 2063 received a single dose of M-M-RII as their second dose. Dose number was not specified for 165 participants, ≥6 years old, in 2 studies in which a single dose of M-M-RII was administered. Similar to previous reports, M-M-RII was well tolerated and immunogenic when administered alone or concomitantly with other routinely recommended vaccinations. The most common adverse events included transient injection site pain and fever. Serious adverse events were extremely rare, with only 4 probable or potential vaccine-related events reported among the 12,032 participating subjects.

Conclusions:
In trials published from 2010 to 2019, M-M-RII continued to be safe and immunogenic in all age groups studied. These data, along with the results of earlier trials, indicate that the performance of the vaccine has been consistent across more than 30 years of postlicensure studies.
Ultrasound delivery of Chinese rhubarb promotes early recovery of gastrointestinal function after gastrectomy: a prospective randomized controlled study
Authors: Jia Hengbo , Wang Shaofeng , Shen Lujun , You Jun , Yang Fan , Abe Masanobu , Xu Yingying , Zong Liang 
Published: July 2021

Objective:
Chinese rhubarb is a promising Chinese medicine for the promotion of gastrointestinal function. This study was conducted to investigate the safety and efficacy of Chinese rhubarb administered via ultrasound delivery in promoting the early recovery of gastrointestinal function after gastrectomy.

Methods:
In this prospective randomized controlled study, 100 patients who were scheduled to undergo total or subtotal gastrectomy in Changzhi People’s Hospital or Subei People’s Hospital from August 2017 to January 2018 were recruited. These patients were randomly assigned into two equal groups before surgery: 50 in the experimental (Chinese rhubarb) group, and 50 in the control (routine nursing) group. After surgery, time to flatus, bowel movement, clear liquid diet, and removal of nasogastric tube were recorded and analyzed. In addition, postoperative pain, postoperative bowel movement-related complications, and postoperative hospital stay duration were also recorded and analyzed. The study was approved by The protocol was approved by the Institutional Review Board of Changzhi People’s Hospital and Subei People’s Hospital on July 1, 2017 and registered with the Chinese Clinical Trial Registry on December 17, 2018 (registration number: ChiCTR1800020143).

Results:

Time to flatus (control group 85.68±22.00 hours vs experimental group 73.06±23.42 hours;
P
=0.007), bowel movement (5.52±1.56 vs 4.40±1.21 days;
P
<0.001), clear liquid diet (6.72±1.16 vs 6.22±1.28 days;
P
=0.044), and removal of nasogastric tube (6.30±1.52 vs 5.65±1.58 days;
P
=0.044) were significantly shorter in the experimental group compared with the control group, as was the postoperative hospital stay duration (14.30±3.46 vs 12.86±1.36 days;
P
=0.006). In addition, better pain relief (
P
=0.003) and a lower incidence of postoperative bowel movement-related complications (6 vs 21;
P
=0.001) were noted in the experimental group.

Conclusion:
Ultrasound delivery of Chinese rhubarb is useful to promote the early recovery of gastrointestinal function after gastrectomy.
Bridging the Gap Between Pilot and Scale-Up: A Model of Antenatal Testing for Curable Sexually Transmitted Infections From Botswana
Authors: Wynn Adriane , Moucheraud Corrina , Martin Natasha K. , Morroni Chelsea , Ramogola-Masire Doreen , Klausner Jeffrey D. , Leibowitz Arleen 
Published: July 2021

Background

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are common sexually transmitted infections (STIs) associated with adverse outcomes, yet most countries do not test and conduct syndromic management, which lacks sensitivity and specificity. Innovations allow for expanded STI testing; however, cost is a barrier.

Methods
Using inputs from a pilot program in Botswana, we developed a model among a hypothetical population of 50,000 pregnant women to compare 1-year costs and outcomes associated with 3 antenatal STI testing strategies: (1) point-of-care, (2) centralized laboratory, and (3) a mixed approach (point of care at high-volume sites, and hubs elsewhere), and syndromic management.

Results
Syndromic management had the lowest delivery cost but was associated with the most infections at delivery, uninfected women treated, CT/NG-related low-birth-weight infants, disability-adjusted life years, and low birth weight hospitalization costs. Point-of-care CT/NG testing would treat and cure the most infections but had the highest delivery cost. Among the testing scenarios, the mixed scenario had the most favorable cost per woman treated and cured ($534/cure). Compared with syndromic management, the mixed approach resulted in a mean incremental cost-effectiveness ratio of $953 per disability-adjusted life years averted, which is cost-effective under World Health Organization's one-time per-capita gross domestic product willingness-to-pay threshold.

Conclusions
As countries consider new technologies to strengthen health services, there is an opportunity to determine how to best deploy resources. Compared with point-of-care, centralized laboratory, and syndromic management, the mixed approach offered the lowest cost per infection averted and is cost-effective if policy makers' willingness to pay is informed by the World Health Organization's gross domestic product/capita threshold.