bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of TAFRO syndrome maintained in remission for 5 years after discontinuation of tocilizumab
Authors: Yamagami Keiko , Hanioka Yusuke , Yao Shuhei , Nakamura Ryota , Nakamura Tomoyuki , Ishii Naomi , Goto Hitoshi
Published: February 2022

TAFRO syndrome is a subtype of idiopathic multicentric Castleman’s disease (iMCD) that is characterised by thrombocytopenia, generalised oedema, fever, bone marrow fibrosis, renal failure, and organ enlargement and has a poor prognosis. The prognosis of TAFRO syndrome is worse than that of iMCD-not otherwise specified, with a high mortality rate. There are only a few long-term follow-up reports after remission of TAFRO syndrome with tocilizumab (TCZ) treatment in a patient in whom all drugs were discontinued after attaining sustained remission. Here, we report a case in which interleukin-6 negativity was confirmed and remission was maintained without relapse for 5 years after all drug treatments, including TCZ, were discontinued.
Aseptic meningitis as initial presentation of subclinical Sjögren’s syndrome: Could the cerebrospinal fluid anti-Ro/SSA and anti-La/SSB antibody system be the culprit?
Authors: Kurotaki Keigo , Fujita Masashi , Aizawa Tomomi , Tsugawa Koji , Tanaka Hiroshi
Published: February 2022

Aseptic meningitis sometimes occurs as a consequence of central nervous system (CNS) involvement in patients with primary Sjögren’s syndrome (SS), even in paediatric-onset cases. However, little information is available regarding the pathological role of CSF anti-Ro/SSA and anti-La/SSB antibodies in the CNS involvement in patients with primary SS. We experienced an 18-year-old adolescent female with a 7-year history of suspicion of subclinical SS who subsequently developed aseptic meningitis as an initial presentation of probable SS. Her CSF exhibited marked elevation of anti-Ro/SSA and anti-La/SSB antibodies. When compared to her CSF IgG/serum IgG ratio (0.0058), her CSF/serum ratios of anti-Ro/SSA and anti-La/SSB antibody titres were higher (0.448 and 0.068, respectively; these were 77.5 and 11.7 times higher than that of IgG, respectively), suggesting that regional production of these antibodies was attributable, at least partly, to the development of meningitis. After the initiation of prednisolone treatment, her clinical manifestations promptly subsided. Since the clinical and pathological roles of the Ro/SSA antibody system in several autoimmune conditions have been postulated, our clinical observation may add novel insight to this theory.
Depth normalization of small RNA sequencing: using data and biology to select a suitable method
Authors: Düren Yannick , Lederer Johannes , Qin Li-Xuan
Published: February 2022

Deep sequencing has become one of the most popular tools for transcriptome profiling in biomedical studies. While an abundance of computational methods exists for ‘normalizing’ sequencing data to remove unwanted between-sample variations due to experimental handling, there is no consensus on which normalization is the most suitable for a given data set. To address this problem, we developed ‘DANA’—an approach for assessing the performance of normalization methods for microRNA sequencing data based on biology-motivated and data-driven metrics. Our approach takes advantage of well-known biological features of microRNAs for their expression pattern and chromosomal clustering to simultaneously assess (i) how effectively normalization removes handling artifacts and (ii) how aptly normalization preserves biological signals. With DANA, we confirm that the performance of eight commonly used normalization methods vary widely across different data sets and provide guidance for selecting a suitable method for the data at hand. Hence, it should be adopted as a routine preprocessing step (preceding normalization) for microRNA sequencing data analysis. DANA is implemented in R and publicly available at https://github.com/LXQin/DANA.
Discovery of potent and versatile CRISPR–Cas9 inhibitors engineered for chemically controllable genome editing
Authors: Song Guoxu , Zhang Fei , Tian Chunhong , Gao Xing , Zhu Xiaoxiao , Fan Dongdong , Tian Yong
Published: February 2022

Anti-CRISPR (Acr) proteins are encoded by many mobile genetic elements (MGEs) such as phages and plasmids to combat CRISPR–Cas adaptive immune systems employed by prokaryotes, which provide powerful tools for CRISPR–Cas-based applications. Here, we discovered nine distinct type II-A anti-CRISPR (AcrIIA24–32) families from Streptococcus MGEs and found that most Acrs can potently inhibit type II-A Cas9 orthologs from Streptococcus (SpyCas9, St1Cas9 or St3Cas9) in bacterial and human cells. Among these Acrs, AcrIIA26, AcrIIA27, AcrIIA30 and AcrIIA31 are able to block Cas9 binding to DNA, while AcrIIA24 abrogates DNA cleavage by Cas9. Notably, AcrIIA25.1 and AcrIIA32.1 can inhibit both DNA binding and DNA cleavage activities of SpyCas9, exhibiting unique anti-CRISPR characteristics. Importantly, we developed several chemically inducible anti-CRISPR variants based on AcrIIA25.1 and AcrIIA32.1 by comprising hybrids of Acr protein and the 4-hydroxytamoxifen-responsive intein, which enabled post-translational control of CRISPR–Cas9-mediated genome editing in human cells. Taken together, our work expands the diversity of type II-A anti-CRISPR families and the toolbox of Acr proteins for the chemically inducible control of Cas9-based applications.
Role of the cellular factor CTCF in the regulation of bovine leukemia virus latency and three-dimensional chromatin organization
Authors: Bellefroid Maxime , Rodari Anthony , Galais Mathilde , Krijger Peter H L , Tjalsma Sjoerd J D , Nestola Lorena , Plant Estelle , Vos Erica S M , Cristinelli Sara , Van Driessche Benoit , Vanhulle Caroline , Ait-Ammar Amina , Burny Arsène , Ciuffi Angela , de Laat Wouter , Van Lint Carine
Published: February 2022

Bovine leukemia virus (BLV)-induced tumoral development is a multifactorial phenomenon that remains incompletely understood. Here, we highlight the critical role of the cellular CCCTC-binding factor (CTCF) both in the regulation of BLV transcriptional activities and in the deregulation of the three-dimensional (3D) chromatin architecture surrounding the BLV integration site. We demonstrated the in vivo recruitment of CTCF to three conserved CTCF binding motifs along the provirus. Next, we showed that CTCF localized to regions of transitions in the histone modifications profile along the BLV genome and that it is implicated in the repression of the 5′Long Terminal Repeat (LTR) promoter activity, thereby contributing to viral latency, while favoring the 3′LTR promoter activity. Finally, we demonstrated that BLV integration deregulated the host cellular 3D chromatin organization through the formation of viral/host chromatin loops. Altogether, our results highlight CTCF as a new critical effector of BLV transcriptional regulation and BLV-induced physiopathology.
AT-hook peptides bind the major and minor groove of AT-rich DNA duplexes
Authors: Garabedian Alyssa , Jeanne Dit Fouque Kevin , Chapagain Prem P , Leng Fenfei , Fernandez-Lima Francisco
Published: February 2022

The mammalian high mobility group protein AT-hook 2 (HMGA2) houses three motifs that preferentially bind short stretches of AT-rich DNA regions. These DNA binding motifs, known as ‘AT-hooks’, are traditionally characterized as being unstructured. Upon binding to AT-rich DNA, they form ordered assemblies. It is this disordered-to-ordered transition that has implicated HMGA2 as a protein actively involved in many biological processes, with abnormal HMGA expression linked to a variety of health problems including diabetes, obesity, and oncogenesis. In the current work, the solution binding dynamics of the three ‘AT-hook’ peptides (ATHPs) with AT-rich DNA hairpin substrates were studied using DNA UV melting studies, fluorescence spectroscopy, native ion mobility spectrometry-mass spectrometry (IMS-MS), solution isothermal titration calorimetry (ITC) and molecular modeling. Results showed that the ATHPs bind to the DNA to form a single, 1:1 and 2:1, ‘key-locked’ conformational ensemble. The molecular models showed that 1:1 and 2:1 complex formation is driven by the capacity of the ATHPs to bind to the minor and major grooves of the AT-rich DNA oligomers. Complementary solution ITC results confirmed that the 2:1 stoichiometry of ATHP: DNA is originated under native conditions in solution.
Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing
Authors: O’Geen Henriette , Tomkova Marketa , Combs Jacquelyn A , Tilley Emma K , Segal David J
Published: February 2022

Precision epigenome editing has gained significant attention as a method to modulate gene expression without altering genetic information. However, a major limiting factor has been that the gene expression changes are often transient, unlike the life-long epigenetic changes that occur frequently in nature. Here, we systematically interrogate the ability of CRISPR/dCas9-based epigenome editors (Epi-dCas9) to engineer persistent epigenetic silencing. We elucidated cis regulatory features that contribute to the differential stability of epigenetic reprogramming, such as the active transcription histone marks H3K36me3 and H3K27ac strongly correlating with resistance to short-term repression and resistance to long-term silencing, respectively. H3K27ac inversely correlates with increased DNA methylation. Interestingly, the dependance on H3K27ac was only observed when a combination of KRAB-dCas9 and targetable DNA methyltransferases (DNMT3A-dCas9 + DNMT3L) was used, but not when KRAB was replaced with the targetable H3K27 histone methyltransferase Ezh2. In addition, programmable Ezh2/DNMT3A + L treatment demonstrated enhanced engineering of localized DNA methylation and was not sensitive to a divergent chromatin state. Our results highlight the importance of local chromatin features for heritability of programmable silencing and the differential response to KRAB- and Ezh2-based epigenetic editing platforms. The information gained in this study provides fundamental insights into understanding contextual cues to more predictably engineer persistent silencing.
Prevalence and Correlates of Tobacco Use in Young People Presenting to Australian Primary Mental Health Services
Authors: Cotton Sue M , Sharmin Sonia , Gao Caroline X , Brown Ellie , Menssink Jana M , Rickwood Debra , Bedi Gillinder , Hickie Ian , Hetrick Sarah E , Parker Alexandra G , Herrman Helen , Telford Nic , McGorry Patrick D , Filia Kate M
Published: February 2022

Introduction

In Australian youth primary mental health settings it is unclear as to the rates and correlates of tobacco use at service entry.

Aims and Methods

We aimed to delineate the prevalence and correlates of recent tobacco use (eg, cigarettes, chewing tobacco, cigars, etc) in the past 3 months in young people at their first presentation to primary mental health services as a function of age. Cross-sectional self-report measures were collected using a tablet device from young people presenting to one of five Australian primary mental health (headspace) services. Logistic regression assessed correlates of past 3-month tobacco use in adolescents (12–17 years) and young adults (18–25 years).

Results

Regular (at least monthly) tobacco use in the past 3 months was found in 23.4% (n = 247, N = 1055) of the sample. Increasing age (odds ratio [OR] =1.47 per year; 95% confidence interval [CI]: 1.15 to 1.89), male sex (OR = 1.98; 95% CI: 1.02 to 3.83), being in a relationship (OR = 1.96; 95% CI: 1.01 to 3.82), and poorer functioning (OR = 0.95 per unit Social and Occupational Functioning Assessment Scale increase; 95% CI: 0.91 to 0.99) predicted regular tobacco use in adolescents, but not in young adults. Living in a regional location (OR = 2.10; 95% CI: 1.40 to 3.13) and not studying (OR = 0.47; 95% CI: 0.31 to 0.73) predicted tobacco use in young adults. Having a diagnosed mental illness other than depression and/or anxiety predicted tobacco use in both groups (adolescents OR = 2.49; 95% CI: 1.26 to 4.94; young adults OR = 1.80; 95% CI: 1.13 to 2.89).

Conclusions

Nearly a quarter of young people with mental illness are using tobacco, supporting the need for early intervention approaches. Adapting treatment targets by age could improve the impact of interventions in adolescents versus young adults. Poor functioning and lack of engagement in education were associated with tobacco use in both age groups, respectively; however, more research is needed to determine the direction of these relationships.

Implications

Young people with mental illness have a high prevalence of recent tobacco use and this is evident when they first present to youth primary mental health services. Youth-oriented mental health settings may provide a unique window for tobacco use prevention and early intervention to reduce smoking in people with mental illness, a priority population. Age-specific targeted approaches might be needed in adolescents and young adults.
Diterpene synthases fromLeonurus japonicuselucidate epoxy-bridge formation of spiro-labdane diterpenoids
Authors: Wang Jian , Mao Yaping , Ma Ying , Yang Jian , Jin Baolong , Lin Huixin , Tang Jinfu , Zeng Wen , Zhao Yujun , Gao Wei , Peters Reuben J , Guo Juan , Cui Guanghong , Huang Luqi
Published: February 2022

Spiro-9,13-epoxy-labdane diterpenoids are commonly found in Leonurus species, particularly in Leonurus japonicus Houtt., which is a medicinal herb of long-standing use in Asia and in which such spiro-heterocycles are present in at least 38 diterpenoids. Here, through generation of a transcriptome and functional characterization of six diterpene synthases (diTPSs) from L. japonicus, including three class II diTPSs (LjTPS1, LjTPS3, and LjTPS4) and three class I diTPSs (LjTPS5, LjTPS6, and LjTPS7), formation of the spiro-9,13-epoxy-labdane backbone was elucidated, along with identification of the relevant diTPSs for production of other labdane-related diterpenes. Similar to what has been found with diTPSs from other plant species, while LjTPS3 specifically produces the carbon-9 (C9) hydroxylated bicycle peregrinol diphosphate (PPP), the subsequently acting LjTPS6 yields a mixture of four products, largely labda-13(16),14-dien-9-ol, but with substantial amounts of viteagnusin D and the C13-S/R epimers of 9,13-epoxy-labda-14-ene. Notably, structure–function analysis identified a critical residue in LjTPS6 (I420) in which single site mutations enable specific production of the 13S epimer. Indeed, extensive mutagenesis demonstrated that LjTPS6:I420G reacts with PPP to both specifically and efficiently produce 9,13S-epoxy-labda-14-ene, providing a specialized synthase for further investigation of derived diterpenoid biosynthesis. The results reported here provide a strong foundation for future studies of the intriguing spiro-9,13-epoxy-labdane diterpenoid metabolism found in L. japonicus.
Cohomology of the Universal Abelian Surface with Applications to Arithmetic Statistics
Authors: Lee Seraphina Eun Bi
Published: February 2022

The moduli stack $\mathcal{A}_2$ of principally polarized abelian surfaces comes equipped with the universal abelian surface $\pi: \mathcal{X}_2 \to \mathcal{A}_2$. The fiber of π over a point corresponding to an abelian surface A in $\mathcal{A}_2$ is A itself. We determine the $\ell$-adic cohomology of $\mathcal{X}_2$ as a Galois representation. Similarly, we consider the bundles $\mathcal{X}_2^n \to \mathcal{A}_2$ and $\mathcal{X}_2^{\textrm{Sym}(n)} \to \mathcal{A}_2$ for all $n \geq 1$, where the fiber over a point corresponding to an abelian surface A is An and $\textrm{Sym}^n A$, respectively. We describe how to compute the $\ell$-adic cohomology of $\mathcal{X}_2^n$ and $\mathcal{X}_2^{\textrm{Sym}(n)}$ and explicitly calculate it in low degrees for all n and in all degrees for n = 2. These results yield new information regarding the arithmetic statistics on abelian surfaces, including an exact calculation of the expected value and variance as well as asymptotics for higher moments of the number of Fq-points.
An Unconditional Explicit Bound on the Error Term in the Sato–tate Conjecture
Authors: Hoey Alexandra , Iskander Jonas , Jin Steven , Trejos Suárez Fernando
Published: February 2022

Let $f(z) = \sum_{n=1}^\infty a_f(n)q^n$ be a holomorphic cuspidal newform with even integral weight $k\geq 2$, level N, trivial nebentypus and no complex multiplication. For all primes p, we may define $\theta_p\in [0,\pi]$ such that $a_f(p) = 2p^{(k-1)/2}\cos \theta_p$. The Sato–Tate conjecture states that the angles θp are equidistributed with respect to the probability measure $\mu_{\textrm{ST}}(I) = \frac{2}{\pi}\int_I \sin^2 \theta \; d\theta$, where $I\subseteq [0,\pi]$. Using recent results on the automorphy of symmetric power L-functions due to Newton and Thorne, we explicitly bound the error term in the Sato–Tate conjecture when f corresponds to an elliptic curve over $\mathbb{Q}$ of arbitrary conductor or when f has square-free level. In these cases, if $\pi_{f,I}(x) := \#\{p \leq x : p \nmid N, \theta_p\in I\}$ and $\pi(x) := \# \{p \leq x \}$, we prove the following bound: $$ \left| \frac{\pi_{f,I}(x)}{\pi(x)} - \mu_{\textrm{ST}}(I)\right| \leq 58.1\frac{\log((k-1)N \log{x})}{\sqrt{\log{x}}} \qquad \text{for} \quad x \geq 3. $$ As an application, we give an explicit bound for the number of primes up to x that violate the Atkin–Serre conjecture for f.
Dyspnoea and cough in patients with systemic sclerosis–associated interstitial lung disease in the SENSCIS trial
Authors: Volkmann Elizabeth R , Kreuter Michael , Hoffmann-Vold Anna M , Wijsenbeek Marlies  , Smith Vanessa , Khanna Dinesh , Denton Christopher P , Wuyts Wim A   , Miede Corinna , Alves Margarida , Sambevski Steven , Allanore Yannick 
Published: February 2022

Objective

The aim of these analyses was to investigate the rate of decline in forced vital capacity (FVC) in patients with SSc-associated interstitial lung disease (SSc-ILD) with and without cough or dyspnoea in the SENSCIS trial.

Methods

Patients in the SENSCIS trial were randomized to receive nintedanib or placebo. Subgroups with and without cough or dyspnoea at baseline were defined by responses to the St George’s Respiratory Questionnaire.

Results

At baseline, 114/575 patients (19.8%) did not have cough and 172/574 patients (30.0%) did not have dyspnoea. In the placebo group, the rate of FVC decline over 52 weeks was similar in patients with and without cough (−95.6 and −83.4 mL/year, respectively) or dyspnoea (−95.8 and −87.7 mL/year, respectively). The effect of nintedanib vs placebo on reducing the rate of FVC decline was numerically more pronounced in patients without than with cough [difference: 74.4 (95% CI −11.1, 159.8) vs 31.5 (−11.1, 74.1)] and without than with dyspnoea [79.8 (9.8, 149.7) vs 25.7 (−19.9, 71.3)], but interaction P-values did not indicate heterogeneity in the treatment effect between these subgroups (P = 0.38 and P = 0.20, respectively).

Conclusion

In the placebo group of the SENSCIS trial, the rate of FVC decline was similar irrespective of the presence of cough or dyspnoea at baseline. The effect of nintedanib on reducing the rate of FVC decline was numerically more pronounced in patients without than with cough or dyspnoea at baseline, but no statistically significant heterogeneity was observed between the subgroups.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT02597933.
Estimation of direct and maternal genetic effects and annotation of potential candidate genes for weight and meat quality traits in a genotyped outdoor dual-purpose cattle breed
Authors: Halli Kathrin , Bohlouli Mehdi , Schulz Lisa , Sundrum Albert , König Sven
Published: February 2022

With regard to potential applications of genomic selection in small numbered breeds, we evaluated genomic models and focused on potential candidate gene annotations for weight and meat quality traits in the local Rotes Höhenvieh (RHV) breed. Traits included 6,003 birth weights (BWT), 5,719 200 d-weights (200dw), 4,594 365 d-weights (365dw), and 547 records for intramuscular fat content (IMF). A total of 581,304 SNP from 370 genotyped cattle with phenotypic records were included in genomic analyses. Model evaluations focused on single- and multiple-trait models with direct and with direct and maternal genetic effects. Genetic relationship matrices were based on pedigree (A-matrix), SNP markers (G-matrix), or both (H-matrix). Genome-wide association studies (GWASs) were carried out using linear mixed models to identify potential candidate genes for the traits of interest. De-regressed proofs (DRP) for direct and maternal genetic components were used as pseudo-phenotypes in the GWAS. Accuracies of direct breeding values were higher from models based on G or on H compared to A. Highest accuracies (> 0.89) were obtained for IMF with multiple-trait models using the G-matrix. Direct heritabilities with maternal genetic effects ranged from 0.62 to 0.66 for BWT, from 0.45 to 0.55 for 200dW, from 0.40 to 0.44 for 365dW, and from 0.48 to 0.75 for IMF. Maternal heritabilities for BWT, 200dW, and 365dW were in a narrow range from 0.21 to 0.24, 0.24 to 0.27, and 0.21 to 0.25, respectively, and from 0.25 to 0.65 for IMF. Direct genetic correlations among body weight traits were positive and favorable, and very similar from different models but showed a stronger variation with 0.31 (A), −0.13 (G), and 0.45 (H) between BWT and IMF. In gene annotations, we identified 6, 3, 1, and 6 potential candidate genes for direct genetic effect on BWT, 200dW, 365dW, and IMF traits, respectively. Regarding maternal genetic effects, four (SHROOM3, ZNF609, PECAM1, and TEX2) and two (TMEM182 and SEC11A) genes were detected as potential candidate genes for BWT and 365dW, respectively. Potential candidate genes for maternal effect on IMF were GRHL2, FGA, FGB, and CTNNA3. As the most important finding from a practical breeding perspective, a small number of genotyped RHV cattle enabled accurate breeding values for high heritability IMF.
Gender and Biology
Authors: Erickson-Schroth Laura , Davis Benjamin
Published: February 2022

This chapter discusses the biological differences
between males and females. Typical male and female bodies differ from each other in predictable
ways, such as height, strength, and genital/reproductive capacity, but there are many
exceptions. Indeed, there is a large group of people who are intersex, a term used to describe
those who do not fit neatly into male or female boxes. Moreover, to date, there are no decisive,
reliable, category-defining differences between the brains of men and women. People often talk
about estrogen and testosterone as causing biological differences in the way men and women think
and behave. However, there is no clear evidence that these hormones lead to the stereotypical
differences people often associate with them. The chapter also addresses why women live longer
than men and reflects on what is known about sex and gender in nonhuman species.
The Future of Gender
Authors: Erickson-Schroth Laura , Davis Benjamin
Published: February 2022

This chapter explores the future of gender. The
prospects for future reproductive technologies are almost beyond our imaginations. The creation
of “artificial” sperm and eggs could open up possibilities for all kinds of changes in our
reproductive capacity. On a basic level, it could allow those who are infertile, either because
of low sperm count or age-related changes in eggs, to create brand-new viable sperm or eggs. But
even beyond that, stem cells from someone of any sex could theoretically be used to create
either sperm or eggs, allowing transgender men to produce sperm or transgender women to produce
eggs if they wanted. It could also allow same-sex couples to have biological children together.
The chapter then looks at genderless or gender-neutral parenting. It also considers how new
technologies might shape our ability to modify our gendered bodies and discusses the current
frontiers in gender equality.
Arabia Felix—An Early History of Yemen
Authors: Orkaby Asher
Published: February 2022

This chapter presents an early history of Yemen. What is the connection between the biblical
story of Noah's flood and Yemen? The answer to this question can tell us a great deal about how
ancient chroniclers and modern-day Yemenis view their own country. According to local tradition,
Noah's son Shem exited the ark after the flood in search of a place to live and came across the
fertile lands of South Arabia. It is here that Noah built Sana'a, which tradition claims to have
been the world's first city. The self-proclaimed centrality of Yemen to the history of the world
and to Islam specifically is further espoused in the local belief that the name Yemen is a
description of the country's position relative to Mecca and Medina. Arabia Felix, or Happy
Arabia, dates to Greco-Roman times and was an expression of pleasant surprise at discovering the
highlands of Yemen in South Arabia. The chapter then assesses what is unique about Yemen's
geography and climate, as well as the importance of the port of Aden in Yemen's history. It also
looks at archeological surveys of Yemen.
Agriculture and Economy
Authors: Orkaby Asher
Published: February 2022

This chapter assesses agriculture and economy in Yemen. Yemen was a latecomer to the Arabian oil
market, as significant reserves were discovered only in 1986 by the Hunt Oil Company. Contracts
between Yemen and foreign oil companies began as a production-sharing agreement that gradually
allotted the government a greater share of oil revenue as initial investment was recouped. The
discovery of oil was one of the main factors that facilitated the union between North and South
Yemen in 1990. Aside from oil, Yemen's main exports include coffee and qat. The chapter then
looks at the water crisis in Yemen; the typical Yemeni cuisine; and the main ports, markets, and
banking systems in Yemen.
Education and Society
Authors: Orkaby Asher
Published: February 2022

This chapter describes education in Yemen. Beginning in the 19th century, there was a transition
from oral to written religious instruction and legal decisions. Oral shariah
instruction from teacher to student gave way to written dissemination through the gradual
evolution of print and the influence of Ottoman and British educational styles on Yemeni
society. While the written word insured longevity, the absence of the oral tradition obscured
original meanings hidden within the tones of verbal recitation. Yemen's state school curriculum
along with official correspondence and records are mostly in fusha Arabic. The
chapter then looks at the literacy rate in the general Yemeni population, before considering the
tradition of higher education. It also discusses the state of women's rights in Yemen, assessing
whether there are any Yemeni women who have managed to succeed despite the obstacles. Finally,
the chapter examines the role of civil society and the state of healthcare in Yemen.
Effect of Electronic Medical Record Quality on Nurses' Perceived Usefulness and Ease of Use
Authors: Lee Seonah
Published: February 2022

Electronic medical records have been adopted in Korean clinical settings for a few decades. However, there is a lack of studies on the quality, usefulness, and easy use of electronic medical records examined from the perspective of nurses. This study sought the effect of the system quality, information quality, and service quality of an electronic medical record on nurses' perceived usefulness and ease of use of the electronic medical record. A total of 278 nurses from four hospitals completed a self-administered questionnaire using a 5-point Likert scale. The data were analyzed using descriptive statistics and hierarchical multiple regression methods. The results showed that the system, information, and service quality of the electronic medical records explained 36.2% of the variance in perceived usefulness (F = 51.760, P < .001) and 43.4% of the variance in perceived ease of use (F = 70.019, P < .001). Thus, these three qualities were significant factors predicting perceived usefulness and ease of use. The close cooperation of stakeholders including administrators, healthcare providers including nurses, and researchers involved in clinical practice will improve electronic medical record quality leading to user-friendly electronic medical record implementation. This study provided statistical interpretations to help in understanding regression analysis.
Two-Tier Instant-Feedback Assessment Strategy for Improvement of Student Concentration
Authors: Lin Kai-Yin
Published: February 2022

In this study, a two-tier instant-feedback assessment model was constructed using the Zuvio instant-feedback system and oral questions; this model was applied to conduct formative assessments for an introductory computer course. We adopted a one-group pretest-posttest approach with 52 first-year nursing students. The course ran for 6 weeks with two classes per week. The course content of mBlock language and the educational robotic kit mbot was introduced in the first 2 weeks. From the third to the sixth week, the two-tier instant assessment strategy was added. At the end of the teaching experiment, surveys on concentration and course satisfaction were administered. Our results were as follows: (1) two-tier instant-feedback assessment can enhance student concentration, as the results showed that students' concentration improved; (2) in the subscale, the “competitive selection” dimension reached a significant difference; and (3), the students held positive views toward the incorporation of two-tier instant-feedback assessment into the course.
Effect of Telehealth Interventions on Blood Pressure Control
Authors: Demir Avci Yasemin , Gözüm Sebahat , Karadag˘ Engin
Published: February 2022

The aim of this study was to find out the effects of telehealth interventions on blood pressure control by conducting a meta-analysis. Six databases were used. The literature review covered the period between December 1, 2020, and January 26, 2021. The meta-analysis was conducted by comprehensive Meta-Analysis Software version 2.2. Categorical variables were analyzed by odds ratios at a confidence interval of 95%. In data formatting and analysis, independent groups (sample size, P value); independent groups (mean, SD); Cohen's d, SE; and paired groups (N, P value) were used. The bias risk was assessed based on the Revised Cochrane Risk-of-Bias Tool for Randomized Trials. Total sample size including 22 studies was 11 120. It was determined that interventions performed through telehealth applications had a significant effect on blood pressure control (odds ratio = −0.14; 95% confidence interval = −0.20 to −0.08; P < .001). In telehealth applications, blood pressure values decreased more when the application was performed through a Web site (−0.31; 95% confidence interval = −0.49 to −0.13), duration of the intervention was 12 months or shorter (−0.18; 95% confidence interval = −0.28 to −0.010), stroke developed in case of hypertension (−0.31, 95% confidence interval = −0.76 to 0.12), and the study was conducted in the Far East countries (−0.24; 95% confidence interval = 0.40 to −0.07). Interventions with telehealth applications are effective in blood pressure management. PROSPERO ID: CRD42021228536.
Improved cutaneous melanoma survival stratification through integration of 31-gene expression profile testing with the American Joint Committee on Cancer 8th Edition Staging
Authors: Wisco Oliver J. , Marson Justin W. , Litchman Graham H. , Brownstone Nicholas , Covington Kyle R. , Martin Brian J. , Quick Ann P. , Siegel Jennifer J. , Caruso Hillary G. , Cook Robert W. , Winkelmann Richard R. , Rigel Darrell S.
Published: February 2022

Cutaneous melanoma (CM) survival is assessed using averaged data from the American Joint Committee on Cancer 8th edition (AJCC8). However, subsets of AJCC8 stages I–III have better or worse survival than the predicted average value. The objective of this study was to determine if the 31-gene expression profile (31-GEP) test for CM can further risk-stratify melanoma-specific mortality within each AJCC8 stage. This retrospective multicenter study of 901 archival CM samples obtained from patients with stages I–III CM assessed 31-GEP test predictions of 5-year melanoma-specific survival (MSS) using Kaplan–Meier and Cox proportional hazards. In stage I–III CM population, patients with a Class 2B result had a lower 5-year MSS (77.8%) than patients with a Class 1A result (98.7%) and log-rank testing demonstrated significant stratification of MSS [χ
2 (2df, n = 901) = 99.7, P < 0.001). Within each stage, 31-GEP data provided additional risk stratification, including in stage I [χ
2 (2df, n = 415) = 11.3, P = 0.004]. Cox regression multivariable analysis showed that the 31-GEP test was a significant predictor of melanoma-specific mortality (MSM) in patients with stage I–III CM [hazard ratio: 6.44 (95% confidence interval: 2.61–15.85), P < 0.001]. This retrospective study focuses on Class 1A versus Class 2B results. Intermediate results (Class 1B/2A) comprised 21.6% of cases with survival rates between Class 1A and 2B, and similar to 5-year MSS AJCC stage values. Data from the 31-GEP test significantly differentiates MSM into lower (Class 1A) and higher risk (Class 2B) groups within each AJCC8 stage. Incorporating 31-GEP results into AJCC8 survival calculations has the potential to more precisely assess survival and enhance management guidance.
Partnering with patients in clinical trials of pain treatments: a narrative review
Authors: Holzer Katherine J. , Veasley Christin , Kerns Robert D. , Edwards Robert R. , Gewandter Jennifer S. , Langford Dale J. , Yaeger Lauren H. , McNicol Ewan , Ferguson McKenzie , Turk Dennis C. , Dworkin Robert H. , Haroutounian Simon
Published: February 2022

The interest and the rationale for meaningful engagement of patients as partners in clinical trials of pain treatments has been increasing. No specific guidance on patient engagement for pain research studies currently exists; thus, the goal of this narrative review was to provide a historical perspective and a current evaluation of the literature on engaging patients as partners in clinical studies in general and in pain-related studies more specifically. We described how regulatory and funding agencies have developed approaches to incorporate input from patients and patient partners in their decision-making processes. We provided an overview on key practices of patient recruitment and engagement as partners in clinical research and highlighted the perceived benefits and challenges of such partnerships. We summarized factors that can facilitate or hinder meaningful patient engagement in clinical trials of pain treatments and outlined gaps that future research should address to optimize patient-centered clinical research.
Amygdalar functional connectivity during resting and evoked pain in youth with functional abdominal pain disorders
Authors: Cunningham Natoshia R. , Nahman-Averbuch Hadas , Lee Gregory R. , King Christopher D. , Coghill Robert C.
Published: February 2022

Pediatric functional abdominal pain disorders (FAPD) are highly prevalent, difficult to diagnose, and challenging to treat. The brain systems supporting FAPD remain poorly understood. This investigation examined the neuromechanisms of FAPD during a well-tolerated visceral pain induction task, the water load symptom provocation task (WL-SPT). Youth between the ages of 11 and 17 years participated. Functional connectivity (FC) was examined through the blood oxygenation level–dependent effect using the left and right amygdala (AMY) as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. Arterial spin labeling was used to assess regional brain activation by examining cerebral blood flow. Increased FC between the left AMY with regions associated with nociceptive processing (eg, thalamus) and right AMY FC changes with areas associated with cognitive functioning (dorsolateral prefrontal cortex) and the default mode network (DMN; parietal lobe) were observed in youth with FAPD after the WL-SPT. These changes were related to changes in pain unpleasantness. Amygdala FC changes post–WL-SPT were also related to changes in pain intensity. Amygdala FC with the DMN in youth with FAPD also differed from healthy controls. Global cerebral blood flow changes were also noted between FAPD and healthy controls, but no significant differences in grey matter were detected either between groups or during the WL-SPT in youth with FAPD. Findings confirm youth with FAPD undergo changes in brain systems that could support the development of biomarkers to enhance understanding of the mechanisms of pain and treatment response.
Can Steps per Day Reflect Symptoms in Children and Adolescents Undergoing Cancer Treatment?
Authors: Withycombe Janice S. , McFatrich Molly , Hinds Pamela S. , Bennett Antonia , Lin Li , Maurer Scott H. , Lucas Nicole R. , Mann Courtney M. , Castellino Sharon M. , Baker Justin N. , Reeve Bryce B.
Published: February 2022

Background

Multiple symptoms occur in children receiving cancer therapy. Decreased steps per day may be associated with burdensome symptoms.

Objective

To evaluate associations between self-reported symptoms (pain interference, anxiety, depressive symptoms, psychological stress, and fatigue) and function (physical function-mobility and physical activity) and cumulative symptom count with steps per day.

Methods

Five sites enrolled English-speaking children, 8 to 17 years, receiving treatment for a first cancer diagnosis. Patient-reported outcome (PRO) surveys were administered before (T1) and after (T2) a course of chemotherapy. Garmin VivoFit 3 (Garmin International, Olathe, KS) accelerometers were worn 7 days prior to each data point. Univariate changes in scores over time were evaluated with dependent-sample t tests. Pearson correlations examined associations between PRO domains and step count. Multivariable mixed-effect models examined associations between steps and PROs.

Results

Participants’ (n = 65) steps per day decreased during treatment (4099 [T1] and 3135 [T2]; P < .01), with larger reductions observed during hospitalization and in younger children compared with adolescents. Steps significantly correlated with PROMIS (Patient-Reported Outcome Measurement Information System) Pediatric physical activity and physical function-mobility. Decreased steps per day were associated with increased fatigue and cumulative symptom count.

Conclusions

In children and adolescents with cancer, steps per day can serve as an indicator of fatigue, cumulative symptom count, physical activity, and physical functioning-mobility.

Implications for Practice

Child self-reports of physical activity and physical function are valid during cancer therapy and should be captured. In the absence of self-report, decreasing step count may prompt additional assessments related to fatigue or cumulative symptom count and trigger early interventions to support physical activity and physical function-mobility.
Machine Learning–Based Prediction of Hospital Admission Among Children in an Emergency Care Center
Authors: Hatachi Takeshi , Hashizume Takao , Taniguchi Masashi , Inata Yu , Aoki Yoshihiro , Kawamura Atsushi , Takeuchi Muneyuki
Published: February 2022

Objectives

Machine learning–based prediction of hospital admissions may have the potential to optimize patient disposition and improve clinical outcomes by minimizing both undertriage and overtriage in crowded emergency care. We developed and validated the predictive abilities of machine learning–based predictions of hospital admissions in a pediatric emergency care center.

Methods

A prognostic study was performed using retrospectively collected data of children younger than 16 years who visited a single pediatric emergency care center in Osaka, Japan, between August 1, 2016, and October 15, 2019. Generally, the center treated walk-in children and did not treat trauma injuries. The main outcome was hospital admission as determined by the physician. The 83 potential predictors available at presentation were selected from the following categories: demographic characteristics, triage level, physiological parameters, and symptoms. To identify predictive abilities for hospital admission, maximize the area under the precision-recall curve, and address imbalanced outcome classes, we developed the following models for the preperiod training cohort (67% of the samples) and also used them in the 1-year postperiod validation cohort (33% of the samples): (1) logistic regression, (2) support vector machine, (3) random forest, and (4) extreme gradient boosting.

Results

Among 88,283 children who were enrolled, the median age was 3.9 years, with 47,931 (54.3%) boys and 1985 (2.2%) requiring hospital admission. Among the models, extreme gradient boosting achieved the highest predictive abilities (eg, area under the precision-recall curve, 0.26; 95% confidence interval, 0.25–0.27; area under the receiver operating characteristic curve, 0.86; 95% confidence interval, 0.84–0.88; sensitivity, 0.77; and specificity, 0.82). With an optimal threshold, the positive and negative likelihood ratios were 4.22, and 0.28, respectively.

Conclusions

Machine learning–based prediction of hospital admissions may support physicians' decision-making for hospital admissions. However, further improvements are required before implementing these models in real clinical settings.
Effects of Kilohertz Frequency, Burst Duty Cycle, and Burst Duration on Evoked Torque, Perceived Discomfort and Muscle Fatigue
Authors: Modesto Karenina Arrais Guida , Bastos Júlia Aguillar Ivo , Vaz Marco Aurélio , Durigan João Luiz Quagliotti
Published: February 2022

Kilohertz-frequency alternating current is used to minimize muscle atrophy and muscle weakness and improve muscle performance. However, no systematic reviews have evaluated the best Kilohertz-frequency alternating current parameters for this purpose. We investigated the effects of the carrier frequency, burst duty cycles, and burst durations on evoked torque, perceived discomfort, and muscle fatigue. A search of eight data sources by two independent reviewers resulted in 13 peer-reviewed studies being selected, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and rated using the PEDro scale to evaluate the methodological quality of the studies. Most studies showed that carrier frequencies up to 1 kHz evoked higher torque, while carrier frequencies between 2.5 and 5 kHz resulted in lower perceived discomfort. In addition, most studies showed that shorter burst duty cycles (10%–50%) induced higher evoked torque and lower perceived discomfort. Methodological quality scores ranged from 5 to 8 on the PEDro scale. We conclude that Kilohertz-frequency alternating current develops greater evoked torque for carrier frequencies between 1 and 2.5 kHz and burst duty cycles less than 50%. Lower perceived discomfort was generated using Kilohertz-frequency alternating currents between 2.5 and 5 kHz and burst duty cycles less than 50%.
Competency Assessment in Physical Medicine and Rehabilitation Resident Education
Authors: Malmut Laura , Kline-Quiroz Cristina , Cushman Daniel M.
Published: February 2022

Objective

The aim of this systematic review was to examine the scope and quality of research in physical medicine and rehabilitation resident education as it pertains to the six core competencies defined by the Accreditation Council for Graduate Medical Education.

Design

All indexed years of Medline, Embase, and ERIC were searched using key words related to physical medicine and rehabilitation and medical education. Data were extracted on core competencies, content categories, teaching interventions, and study quality.

Results

From a sample of 2544 articles, 62 studies were included in this review. Frequencies of core competencies studied were: patient care 62.9%, medical knowledge 56.5%, systems-based practice 22.6%, practice-based learning and improvement 14.5%, professionalism 25.8%, and interpersonal and communication skills 22.6%. Musculoskeletal and pain medicine was the most frequently studied content category (33.9%). There was no significant difference in quality of studies between the six core competency groups (P = 0.31).

Conclusions

Available research is highly concentrated in patient care and medical knowledge competencies and in the musculoskeletal and pain medicine content category. This systematic review outlines the current state of education literature and highlights areas for further inquiry. This is an important step toward the translation of research into evidence-based educational practices.
Modified Reconstruction of Brown II Defects With Anterolateral Thigh Flaps Following Tumor Resection
Authors: Zeng Wei , Rui Tao , Liu Zhixin , Fu Min , Yao Lin , Zhang Zhili , Hong Lei , Zhou Bin , Wang Youyuan
Published: February 2022

Objective:

Maxillary defects reconstructed with flaps usually cause nasalomaxillary fistula, discomfort oral lining, and poor function of denture. To resolve these problems, this study introduces a modified method of anterolateral thigh flap (ALTF) with skin and myofascial paddles to reconstruct nasal and oral lining of maxillary defects.

Methods:

This study retrospectively reviewed 66 consecutive patients of Brown II maxillary defects following tumor resection reconstructed with ALTFs of modified or conventional methods. In modified group, oral lining was reconstructed with myofascial paddle and nasal lining was reconstructed with skin paddle. The functional and aesthetic outcomes, and the scores based on the University of Washington quality of life questionnaire were assessed.

Results:

All flaps were successful in reconstruction of Brown II maxillary defects. No nasalomaxillary fistula and obstruction of the nasal cavity were found in modified ALTFs group. The functions of removable denture were better in modified ALTFs group. There was no significant difference about tumor recurrence, range of mouth opening, and aesthetic outcomes between the 2 groups.

Conclusions:

The modified method of ALTF with skin and myofascial piddle to reconstruct Brown IIa and IIb defects following tumor resection is simple and reliable, which improves the oral comfortability and function of denture, and avoids obstruction of the nasal cavity.
Pseudochrobactrum algeriensis sp. nov., isolated from lymph nodes of Algerian cattle
Authors: Loperena-Barber Maite , Khames Mammar , Leclercq Sébastien O. , Zygmunt Michel S. , Babot Esteban D. , Zúñiga-Ripa Amaia , Gutiérrez Ana , Oumouna Mustapha , Moriyón Ignacio , Cloeckaert Axel , Conde-Álvarez Raquel
Published: February 2022

Three Gram-negative, rod-shaped, oxidase-positive, non-spore-forming, non-motile strains (C130915_07T, C150915_16 and C150915_17) were isolated from lymph nodes of Algerian cows. On the basis of 16S rRNA gene and whole genome similarities, the isolates were almost identical and clearly grouped in the genus

Pseudochrobactrum

. This allocation was confirmed by the analysis of fatty acids (C19:cyclo, C18 : 1, C18 : 0, C16 : 1 and C16 : 0) and of polar lipids (major components: phosphatidylethanolamine, ornithine-lipids, phosphatidylglycerol, cardiolipin and phosphatidylcholine, plus moderate amounts of phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine and other aminolipids). Genomic, physiological and biochemical data differentiated these isolates from previously described

Pseudochrobactrum

species in DNA relatedness, carbon assimilation pattern and growth temperature range. Thus, these organisms represent a novel species of the genus

Pseudochrobactrum

, for which the name Pseudochrobactrum algeriensis sp. nov. is proposed (type strain C130915_07T=CECT30232T=LMG 32378T).