bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recognition of 5-methyl-CG and CG base pairs in duplex DNA with high stability using antiparallel-type triplex-forming oligonucleotides with 2-guanidinoethyl-2′-deoxynebularine
Authors: Notomi Ryotaro , Sasaki Shigeki , Taniguchi Yosuke 
Published: December 2022

Abstract
The formation of triplex DNA is a site-specific recognition method that directly targets duplex DNA. However, triplex DNA formation is generally formed for the GC and AT base pairs of duplex DNA, and there are no natural nucleotides that recognize the CG and TA base pairs, or even the 5-methyl-CG (5mCG) base pair. Moreover, duplex DNA, including 5mCG base pairs, epigenetically regulates gene expression in vivo, and thus targeting strategies are of biological importance. Therefore, the development of triplex-forming oligonucleotides (TFOs) with artificial nucleosides that selectively recognize these base pairs with high affinity is needed. We recently reported that 2′-deoxy-2-aminonebularine derivatives exhibited the ability to recognize 5mCG and CG base pairs in triplex formation; however, this ability was dependent on sequences. Therefore, we designed and synthesized new nucleoside derivatives based on the 2′-deoxy-nebularine (dN) skeleton to shorten the linker length connecting to the hydrogen-bonding unit in formation of the antiparallel motif triplex. We successfully demonstrated that TFOs with 2-guanidinoethyl-2′-deoxynebularine (guanidino-dN) recognized 5mCG and CG base pairs with very high affinity in all four DNA sequences with different adjacent nucleobases of guanidino-dN as well as in the promoter sequences of human genes containing 5mCG base pairs with a high DNA methylation frequency.
Implementing re-configurable biological computation with distributed multicellular consortia
Authors: Canadell David , Ortiz-Vaquerizas Nicolás , Mogas-Diez Sira , de Nadal Eulàlia , Macia Javier , Posas Francesc 
Published: December 2022

AbstractThe use of synthetic biological circuits to deal with numerous biological challenges has been proposed in several studies, but its implementation is still remote. A major problem encountered is the complexity of the cellular engineering needed to achieve complex biological circuits and the lack of general-purpose biological systems. The generation of re-programmable circuits can increase circuit flexibility and the scalability of complex cell-based computing devices. Here we present a new architecture to produce reprogrammable biological circuits that allow the development of a variety of different functions with minimal cell engineering. We demonstrate the feasibility of creating several circuits using only a small set of engineered cells, which can be externally reprogrammed to implement simple logics in response to specific inputs. In this regard, depending on the computation needs, a device composed of a number of defined cells can generate a variety of circuits without the need of further cell engineering or rearrangements. In addition, the inclusion of a memory module in the circuits strongly improved the digital response of the devices. The reprogrammability of biological circuits is an intrinsic capacity that is not provided in electronics and it may be used as a tool to solve complex biological problems.
Transcription elongator SPT6L regulates the occupancies of the SWI2/SNF2 chromatin remodelers SYD/BRM and nucleosomes at transcription start sites in Arabidopsis
Authors: Shu Jie , Ding Ning , Liu Jun , Cui Yuhai , Chen Chen 
Published: December 2022

Abstract
Chromatin remodelers have been thought to be crucial in creating an accessible chromatin environment before transcription activation. However, it is still unclear how chromatin remodelers recognize and bind to the active regions. In this study, we found that chromatin remodelers SPLAYED (SYD) and BRAHMA (BRM) interact and co-occupy with Suppressor of Ty6-like (SPT6L), a core subunit of the transcription machinery, at thousands of the transcription start sites (TSS). The association of SYD and BRM to chromatin is dramatically reduced in spt6l and can be restored mainly by SPT6LΔtSH2, which binds to TSS in a RNA polymerase II (Pol II)-independent manner. Furthermore, SPT6L and SYD/BRM are involved in regulating the nucleosome and Pol II occupancy around TSS. The presence of SPT6L is sufficient to restore the association of the chromatin remodeler SYD to chromatin and maintain normal nucleosome occupancy. Our findings suggest that the two chromatin remodelers can form protein complexes with the core subunit of the transcription machinery and regulate nucleosome occupancy in the early transcription stage.
The Complex Association of Daily Opioid Dose with Visits for Pain in Sickle Cell Disease: Tolerance or Treatment-Refractory Pain?
Authors: Prince Elizabeth J , Pecker Lydia H , Lanzkron Sophie , Carroll C Patrick 
Published: December 2022

Abstract

Introduction
Opioids are used for acute and chronic pain in patients with sickle cell disease. How outpatient opioid regimens relate to acute care visits is of interest given the risks of high opioid doses and high hospital utilization. A prior study by our group suggested that outpatient opioid treatment for chronic pain could contribute to a vicious cycle of treatment-refractory acute pain, greater acute care utilization, and escalating opioid doses. The present larger naturalistic observational study was undertaken to determine whether the results were reliable across multiple acute care settings.

Methods
One year of clinical data on patients (n = 291) followed in the Sickle Cell Center for Adults (August 2018 to July 2019) were extracted, including visits to the emergency department, visits to the infusion center, and inpatient admissions. Outpatient opioid dosage was used to predict acute care treatment in generalized linear models that were controlled for patient, disease, and treatment characteristics.

Results
Outpatient opioid dosage predicted dosage during visits but did not predict visit length or pain relief. Higher outpatient opioid dosage was associated with greater number of visits. However, in post hoc analyses, this relationship was nonlinear, with a clear positive association only for those prescribed the lowest 50% of dosages.

Discussion
Higher outpatient opioid dosage predicted higher dosages during acute care visits to achieve the same pain score improvement, which is more consistent with opioid tolerance than with treatment-refractory pain. The relationship of outpatient opioid dosage with number of acute care visits was more complex, which suggests that opioid consumption at lower levels is driven by intermittent acute pain and opioid consumption at higher levels is driven by chronic pain.
Economic Inequality, the Working Poor, and Belief in the American Dream
Authors: Newman Benjamin J 
Published: December 2022

AbstractDoes exposure to economic inequality undermine belief in the American dream? Scholarship has long argued that the availability of meritocratic ideologies like the American dream inoculates people against exposure to inequality by leading them to rationalize unequal outcomes by viewing wealth as due to hard work and poverty as due to indolence. The existence of inequality where the “have-nots” are working poor, however, could serve to undermine such a process because their employment status casts them as “deserving poor” and limits the applicability of agency-based explanations for poverty. Across two experiments embedded in national surveys, exposure to inequality alone did not cause significant reductions in belief in the American dream; however, exposure to inequality where the have-nots were working poor significantly reduced belief in the American dream. Moderation and mediation analyses indicate these effects were most pronounced among lower-income Americans and indirectly heightened support for government reduction of inequality.
SKY LTD (FORMERLY SKY PLC) v SKYKICK UK LTD
Authors:   Court of Appeal
Published: December 2022

Abstract
H1 Trade Marks — European trade marks — SKY — Validity — Broad specifications of goods and services — Bad faith — Requirement of clarity and precision — Lack of bona fide intention to use — Declarations of intention to use — “Computer software” — Partial validity — Case management — “Electronic mail services” — Infringement — Likelihood of confusion — Lack of evidence of confusion — Whether necessary to consider all alleged acts of infringement — Passing off — Application of the judgment on reference to Court of Justice — Appeal to Court of Appeal
Both Diet and Sociality Affect Primate Brain-Size Evolution
Authors: Grabowski Mark , Kopperud Bjørn T , Tsuboi Masahito , Hansen Thomas F 
Published: December 2022

Abstract
Increased brain size in humans and other primates is hypothesized to confer cognitive benefits but brings costs associated with growing and maintaining energetically expensive neural tissue. Previous studies have argued that changes in either diet or levels of sociality led to shifts in brain size, but results were equivocal. Here we test these hypotheses using phylogenetic comparative methods designed to jointly account for and estimate the effects of adaptation and phylogeny. Using the largest current sample of primate brain and body sizes with observation error, complemented by newly compiled diet and sociality data, we show that both diet and sociality have influenced the evolution of brain size. Shifting from simple to more complex levels of sociality resulted in relatively larger brains, while shifting to a more folivorous diet led to relatively smaller brains. While our results support the role of sociality, they modify a range of ecological hypotheses centered on the importance of frugivory, and instead indicate that digestive costs associated with increased folivory may have resulted in relatively smaller brains. [adaptation; allometry; bayou; evolutionary trend; energetic constraints; phylogenetic comparative methods; primate brain size; Slouch; social-brain hypothesis.]
Bone morphogenetic protein 4 is involved in cadmium-associated bone damage
Authors: Wan Yu , Mo Li-jun , Wu Lu , Li Dong-li , Song Jia , Hu You-kun , Huang Hai-bin , Wei Qin-zhi , Wang Da-peng , Qiu Jian-min , Zhang Zi-ji , Liu Qi-zhan , Yang Xing-fen 
Published: December 2022

AbstractCadmium (Cd) is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. Bone morphogenetic protein (BMP)/SMAD signaling pathway can mediate osteogenic differentiation, but the association between Cd and BMP/SMAD signaling pathway is yet to be illuminated. To understand what elements of BMPs and SMADs are affected by Cd to influence osteogenic differentiation and if BMPs can be the biomarkers of which Cd-induced osteoporosis, human bone marrow mesenchymal stem cells (hBMSCs) were treated with cadmium chloride (CdCl2) in vitro to detect the expression of BMPs and SMADs, and 134 subjects were enrolled to explore if the BMPs can be potential biomarkers of Cd-associated bone damage. Our results showed that Cd exposure significantly promoted the adipogenic differentiation of hBMSCs and inhibited its osteogenic differentiation by inhibiting the expression of BMP-2/4, SMAD4, and p-SMAD1/5/9 complex. And mediation analyses yielded that BMP-4 mediated 39.32% (95% confidence interval 7.47, 85.00) of the total association between the Cd and the risk of Cd-associated bone damage. Moreover, during differentiation, BMP-4 had the potential to enhance mineralization compared with CdCl2 only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for Cd-associated bone damage.
Systolic and diastolic left ventricular function in children with primary hypertension: a systematic review and meta-analysis
Authors: Rus Rina R. , Pac Michał , Obrycki Łukasz , Sağsak Elif , Azukaitis Karolis , Sinha Manish D. , Jankauskiene Augustina , Litwin Mieczysław 
Published: December 2022

Objective:
Evaluation of left ventricular function provides early evidence of target-organ damage in children with primary hypertension. We performed a systematic review and meta-analysis of left ventricular systolic and diastolic function in children and adolescents with primary hypertension.

Methods:
Literature search was performed in PubMed database and out of 718 articles (published between 2000 and 2021) 22 studies providing comparison of left ventricular function parameters between children with primary hypertension and normotensive controls were selected.

Results:
Overall, 3460 children (5–21 years) with primary hypertension were analyzed. Meta-analysis showed that hypertensive patients when compared with normotensives, had an increased heart rate (mean difference [MD] 5.59; 95% confidence interval [CI] 3.28, 7.89; 10 studies) and increased fractional shortening (MD 1.04; 95% CI 0.48, 1.60; 9 studies) but did not differ in ejection fraction (MD −0.03; 95% CI −1.07, 1.02; 12 studies). Stroke volume was higher in one out of three studies, whereas no differences in cardiac output were found in two studies with available data. Hypertensive children had also lower E/A values (MD −0.21; −0.33, −0.09; 14 studies), greater values of E/e′ (MD 0.59; 0.36, 0.82; 8 studies) and greater global longitudinal stress (MD 2.50; 2.03, 2.96; 4 studies) when compared to those with normotension.

Conclusion:
Our results indicate that hypertensive children and adolescents present with signs of hyperkinetic function of the left ventricle, demonstrate evidence of increased left ventricular strain and impaired diastolic function compared to normotensive controls.
Systolic blood pressure at age 40 and cognitive function 25 years later: the Akershus Cardiac Examination (ACE) 1950 Study
Authors: Walle-Hansen Marte M. , Berge Trygve , Vigen Thea , Myrstad Marius , Hagberg Guri , Ihle-Hansen Hege , Sandset Else C. , Thommessen Bente , Ariansen Inger K.H. , Lyngbakken Magnus N. , Røsjø Helge , Rønning Ole M. , Tveit Arnljot , Ihle-Hansen Håkon 
Published: December 2022

Objectives:
Hypertension in midlife is a risk factor for cognitive impairment. Still, the ideal midlife blood pressure (BP) remains unknown. We examined associations between different systolic blood pressure (SBP) levels at the age of 40–43 years and change in SBP over a 25-year period with cognitive function at age 62–65 years.

Methods:
We included 2424 individuals born in 1950 who had participated both in the Age 40 Program (1990–1993) and the Akershus Cardiac Examination (ACE) 1950 Study (2012–2015). The exposure was SBP at age 40–43 years and the outcome was cognitive function at age 62–65 years, assessed with Montreal Cognitive Assessment, Delayed recall trial from the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task, and Trail Making Test part B (TMT B).

Results:
Participants were 40.1 ± 0.3 years old with mean SPB 128 ± 13 mmHg at the Age 40 Program, and 63.9 ± 0.6 years old with mean SPB 138 ± 18 at the ACE 1950 Study. Adjusted linear regressions showed no associations between SBP and subsequent cognitive function. In logistic regressions, individuals with SBP ≥140 mmHg, compared to individuals with SBP <120 mmHg (odds ratio 2.29, 95% confidence interval 1.28–4.10, P-value 0.005) had increased risk of an abnormal TMT B-score. Change in SBP during the 25-year follow-up was not associated with cognitive function.

Conclusions:
SBP ≥140 mmHg at age 40–43 was associated with reduced capacity on TMT B, a domain specific cognitive test sensitive to vascular impairment. No other associations were found between SBP, or change in SBP, and cognitive function.
Impact of oscillometric measurement artefacts in ambulatory blood pressure monitoring on estimates of average blood pressure and of its variability: a pilot study
Authors: Bothe Tomas L. , Bilo Grzegorz , Parati Gianfranco , Haberl Ralph , Pilz Niklas , Patzak Andreas 
Published: December 2022

Objective:
Ambulatory blood pressure monitoring (ABPM) plays an important role in the diagnosis of hypertension. However, methodological factors and the measurement conditions affect the results and may lead to incorrect classification of the patient. We performed a pilot study to evaluate the impact of oscillometric measurement artefacts on ABPM-derived variables.

Methods:
Four classes of artefacts have been detected: motor activity artefacts, cuff errors, cardiovascular arousals, and arrhythmias. The data consisted of uncorrected measurements (all data), corrected measurements (all artefact free data), and artefact affected data.

Results:
A total of 30 individuals (9 female/21 male), aged between 36 and 86 years, mean: 65.5 (standard deviation: 9.5) were included in the study. The average blood pressure (BP) was higher in artefacts-affected measurements compared the artefact-free measurements both for systolic (4.6 mmHg) and diastolic (1.3 mmHg) measurements. Further, artefact-affected systolic BP (SBP) was 6.4 mmHg higher than artefact-free measurements during daytime. Nocturnal measurements showed no artefact-depended differences. Individual comparisons yielded that 23% of the participants crossed the threshold for BP classification for either 24-h, daytime or nocturnal hypertension when comparing uncorrected and artefact-free measurements. Dipping classification changed within 24% of participants. BP variability was 21 and 12% higher for SPB and DBP, respectively, during daytime. These differences were even higher (27% for SBP and 21% for DPB) during night-time.

Conclusion:
The study reveals that measurement artefacts are frequently present during cuff-based ABPM and do relevantly affect measurement outcome. Exclusion of measurement artefacts is a promising approach to improving cuff-based ABPM accuracy.
Reflections on the Process of Implementing Trauma-Informed Education Lunch and Learns
Authors: Najjar Rana , Jacobs Sarah , Keeney Sarah , Vidal Graciela , Noone Joanne 
Published: December 2022

Background:
The trauma-informed education (TIE) framework can help create an equitable learning environment supportive of all learners.

Problem:
Stress and trauma can be impediments to academic success for students, particularly from backgrounds historically excluded from nursing.

Approach:
This article shares the initial steps of a training program on implementing a series of Lunch and Learns (LLs) on TIE in a school of nursing to introduce TIE to faculty and staff and obtain their feedback on facilitators and barriers to implementing recommended approaches.

Outcomes:
The series was well attended, averaging 33 participants per session. Using experts in TIE positively impacted the learning but contributed to inconsistencies in presentation style and scaffolding of content across sessions.

Conclusion:
Purposeful recruitment and engagement of faculty during the development of the LLs were effective in increasing attendance. Multiple sessions require early planning and meetings with team and presenters to ensure consistency and better use of resources.
Persistently Elevated Risk of Syphilis Among Human Immunodeficiency Virus-Positive Men Receiving Care in a Status-Neutral Setting: A Retrospective Analysis
Authors: Shalev Noga , Castor Delivette , Morrison Ellen , Quigee Daniela , Huang Simian , Zucker Jason 
Published: December 2022

Background
Over the past decade, the incidence of primary and secondary syphilis has increased dramatically in the United States and Western Europe. Men living with human immunodeficiency virus (HIV) and those at risk of HIV infection experience disproportionately high rates of early syphilis (ES). We compared the odds of ES among HIV-positive and HIV-negative men participating in a status-neutral comprehensive HIV prevention and treatment program (CHP).

Methods
We conducted a retrospective analysis of men aged 18 to 65 years with ≥ 1 CHP visit and ≥2 rapid plasma reagin (RPR) tests performed between January 1, 2018, and December 31, 2021. Early syphilis was defined as newly reactive RPR with a minimum titer of ≥1:4 or a ≥ 4-fold increase in the RPR titer. Multiple logistic regression analyses were performed to determine predictors of ES.

Results
A total of 2490 men met the inclusion criteria, of whom 1426 (57.3%) were HIV-positive and 1064 (42.7%) were HIV-negative. Of the 393 men with ES, 284 (72.3%) were HIV-positive and 109 (27.7%) were HIV-negative. Human immunodeficiency virus-positive men had higher adjusted odds of ES (adjusted odds ratio, 2.86; 95% confidence interval, 2.45–3.27) than HIV-negative men did. Chlamydia or gonorrhea infection did not differ according to HIV status (adjusted odds ratio, 0.93; 95% confidence interval, 0.82–1.04).

Conclusions
In our status-neutral care setting, HIV-positive status was associated with significantly higher odds of ES, but not chlamydia or gonorrhea. Our findings emphasize the vulnerability of HIV-positive men to syphilis in an era of effective HIV biomedical prevention.
INCREASE IN CHLORIDE IS ASSOCIATED WITH MAJOR ADVERSE KIDNEY EVENTS IN CRITICALLY ILL PATIENTS
Authors: Zhou Dingxin , Jiang Jun , Zhang Jing , Cao Fengsheng , Peng Zhiyong 
Published: December 2022

ABSTRACT

Purpose: This study aimed to identify the association between hyperchloremia at intensive care unit (ICU) admission and/or the increase of blood chloride levels and the incidence of major adverse kidney events within 30 days (MAKE30) in critically ill adults. Methods: We conducted a retrospective study to analyze the data of all adult patients admitted to the ICU of a tertiary academic hospital in China between April 2020 and April 2022. Patients were categorized based on their admission chloride levels (hyperchloremia ≥110 mmol/L and nonhyperchloremia <110 mmol/L) and stratified on the increased chloride levels 48 h after ICU admission (∆Cl ≥5 mmol/L and ∆Cl <5 mmol/L). The primary outcome was the MAKE30 incidence, including in-hospital death, new receipt of renal replacement therapy (RRT), and persistent renal dysfunction (PRD). Association between hyperchloremia at ICU admission and/or the increase of chloride and the incidence of MAKE30 were assessed using logistic regression. Result: A total of 2,024 patients with a median age of 67 years (interquartile range [IQR], 55–76 years) and a median Acute Physiology and Chronic Health Evaluation II score of 22 (IQR, 17–28) were included. Hyperchloremia occurred in 30.9% (n = 625), and ΔCl ≥5 mmol/L occurred in 18.5% (n = 375) of all ICU patients. The overall MAKE30 incidence was 33.6% (n = 680), including a 10.9% of 30-day hospital mortality (n = 220; as well as overall in-hospital mortality, 11.8% [n = 238]), a 20.2% (n = 408) of PRD, and a 18.0% (n = 365) of new RRT. After adjusted for confounders, it was found that ΔCl ≥5 mmol/L (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.096–1.93; P = 0.010), but not hyperchloremia (OR, 0.99; 95% CI, 0.77–1.28; P = 0.947), was associated with increased incidence of MAKE30. Conclusion: An increased chloride level in the first 48 h of ICU admission was an independent risk factor for MAKE30, whereas hyperchloremia at ICU admission was not associated with an increased incidence of MAKE30. Large-scale prospective studies are needed to verify our findings.