bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular events in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors in Taiwan: a nationwide population-based study
Authors: Yang Yu Chien , Huang Ru Yu , Tsai Hui Jen , Li Po Chih , Yang Yi Hsin , Hsieh Kun Pin 
Published: March 2021

Abstract

Aims
New-generation breakpoint cluster region-Abelson tyrosine kinase inhibitors (TKIs) have a higher incidence of cardiovascular events than imatinib in patients with chronic myeloid leukaemia (CML). However, this knowledge is insufficiently proven. Hence, this study aimed to explore the association between cardiovascular events and TKIs in patients with CML.

Methods and results
This retrospective population-based cohort study enrolled first-time users of imatinib, dasatinib, and nilotinib between 1 January 2007 and 31 December 2016. Arterial thromboembolic events (ATEs) were the primary outcome, while other cardiovascular-related events were the secondary outcomes. The event rates were estimated using Kaplan–Meier estimates, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Additionally, the competing risk was adjusted using the Fine and Gray competing risk model. We included 1207 patients. Nilotinib had a significantly higher ATE risk (subdistribution HR = 4.92, 95% CI = 1.68–14.36) than imatinib. Conversely, no difference was found for other cardiovascular-related events. Risks of ATE and other cardiovascular-related events were similar between dasatinib and imatinib and between nilotinib and dasatinib. The risk of ATE hospitalization consistently increased throughout the main analyses and sensitivity analyses.

Conclusion
Nilotinib-treated patients had a significantly higher risk of developing ATE than imatinib-treated patients. However, the risks of ATE and other cardiovascular-related events were not significantly different between dasatinib and imatinib.
Comparative Study on the Thermal Performance of Three Aedes aegypti (Diptera: Culicidae) Populations From Argentina
Authors: De Majo María Sol , Zanotti Gabriela , Gimenez Javier O , Campos Raúl E , Fischer Sylvia 
Published: March 2021

Abstract
The distribution of Aedes aegypti (L.) (Diptera: Culicidae) is expanding towards colder regions, which could be aided by an adaptation of the immature stages to the local thermal conditions. This study aimed to assess the developmental success at different temperatures in three populations of Ae. aegypti located across a climate gradient in Argentina. Survival to the adult stage, development time, and wing length at 14, 18.5 and 24°C were compared among three populations of Argentina: Resistencia in the subtropical region, and Buenos Aires and San Bernardo in the temperate region. Survival was similar between populations and equal to or higher than 69%, and increased at higher temperatures within the studied range. Development times were similar between populations. A negative effect of temperature was observed and the reduction of development time at increasing temperatures was stronger for males than for females. Wing lengths were negatively affected by increasing temperatures, and the reduction of wing length was stronger for females than for males. Also, the reduction of wing lengths with temperature was stronger for San Bernardo and Resistencia than for Buenos Aires, and differences between sexes were larger for Resistencia than for Buenos Aires or San Bernardo. Although the results do not evidence differences in survival and development time between temperate and tropical populations, the three populations have a higher tolerance to low temperatures than the populations from other regions.
Ethical Issues in Private Practice: A Phenomenological Investigation of Music Therapy Business Owners
Authors: Wilhelm Kyle , Wilhelm Lindsey 
Published: March 2021

Abstract
As a music therapy private practice is both a business and a healthcare service, it should adhere to ethical standards from both disciplines. However, this topic has rarely been examined in the music therapy literature. The purpose of this phenomenological study was to explore ethical dilemmas experienced by music therapy business owners (MTBOs) in their private practice and how MTBOs avoid or address ethical dilemmas. Utilizing convenience and snowball sampling techniques, 21 MTBOs in the United States were interviewed using semi-structured interviews. To answer the two areas of inquiry, we identified three themes and 12 subthemes: (1) Ethical issues related to client welfare, (2) Ethical issues related to business relationships and operation, and (3) Strategies to address or avoid ethical dilemmas. MTBOs also shared how they ensure ethical behavior in themselves, with their employees or independent contractors, and when interacting with professionals outside the private practice. These findings provide a better understanding of MTBOs’ lived experiences of ethics in their private practice and may benefit other music therapists who are in private practice or are wanting to go into private practice. Limitations and recommendations for further research are provided.
A programmable pAgo nuclease with universal guide and target specificity from the mesophilic bacterium Kurthia massiliensis
Authors: Kropocheva Ekaterina , Kuzmenko Anton , Aravin Alexei A , Esyunina Daria , Kulbachinskiy Andrey 
Published: March 2021

Abstract
Argonaute proteins are programmable nucleases that are found in both eukaryotes and prokaryotes and provide defense against invading genetic elements. Although some prokaryotic argonautes (pAgos) were shown to recognize RNA targets in vitro, the majority of studied pAgos have strict specificity toward DNA, which limits their practical use in RNA-centric applications. Here, we describe a unique pAgo nuclease, KmAgo, from the mesophilic bacterium Kurthia massiliensis that can be programmed with either DNA or RNA guides and can precisely cleave both DNA and RNA targets. KmAgo binds 16–20 nt long 5′-phosphorylated guide molecules with no strict specificity for their sequence and is active in a wide range of temperatures. In bacterial cells, KmAgo is loaded with small DNAs with no obvious sequence preferences suggesting that it can uniformly target genomic sequences. Mismatches between the guide and target sequences greatly affect the efficiency and precision of target cleavage, depending on the mismatch position and the nature of the reacting nucleic acids. Target RNA cleavage by KmAgo depends on the formation of secondary structure indicating that KmAgo can be used for structural probing of RNA. These properties of KmAgo open the way for its use for highly specific nucleic acid detection and cleavage.
Structural and functional studies of SF1B Pif1 from Thermus oshimai reveal dimerization-induced helicase inhibition
Authors: Dai Yang-Xue , Chen Wei-Fei , Liu Na-Nv , Teng Fang-Yuan , Guo Hai-Lei , Hou Xi-Miao , Dou Shuo-Xing , Rety Stephane , Xi Xu-Guang 
Published: March 2021

Abstract
Pif1 is an SF1B helicase that is evolutionarily conserved from bacteria to humans and plays multiple roles in maintaining genome stability in both nucleus and mitochondria. Though highly conserved, Pif1 family harbors a large mechanistic diversity. Here, we report crystal structures of Thermus oshimai Pif1 (ToPif1) alone and complexed with partial duplex or single-stranded DNA. In the apo state and in complex with a partial duplex DNA, ToPif1 is monomeric with its domain 2B/loop3 adopting a closed and an open conformation, respectively. When complexed with a single-stranded DNA, ToPif1 forms a stable dimer with domain 2B/loop3 shifting to a more open conformation. Single-molecule and biochemical assays show that domain 2B/loop3 switches repetitively between the closed and open conformations when a ToPif1 monomer unwinds DNA and, in contrast with other typical dimeric SF1A helicases, dimerization has an inhibitory effect on its helicase activity. This mechanism is not general for all Pif1 helicases but illustrates the diversity of regulation mechanisms among different helicases. It also raises the possibility that although dimerization results in activation for SF1A helicases, it may lead to inhibition for some of the other uncharacterized SF1B helicases, an interesting subject warranting further studies.
Transcriptome screening followed by integrated physicochemical and structural analyses for investigating RNA-mediated berberine activity
Authors: Satpathi Sagar , Endoh Tamaki , Podbevšek Peter , Plavec Janez , Sugimoto Naoki 
Published: March 2021

Abstract
Non-coding RNAs are regarded as promising targets for the discovery of innovative drugs due to their abundance in the genome and their involvement in many biological processes. Phytochemicals (PCs) are the primary source of ligand-based drugs due to their broad spectrum of biological activities. Since many PCs are heterocyclic and have chemical groups potentially involved in the interaction with nucleic acids, detailed interaction analysis between PCs and RNA is crucial to explore the effect of PCs on RNA functions. In this study, an integrated approach for investigating interactions between PCs and RNAs were demonstrated to verify the RNA-mediated PCs functions by using berberine (BRB) as a model PC. RNA screening of a transcriptome library followed by sequence refinement found minimal RNA motif consisting of a cytosine bulge with U-A and G-U neighbouring base pairs for interaction with BRB. NMR-based structure determination and physicochemical analyses using chemical analogues of BRB demonstrated the importance of electrostatic and stacking interactions for sequence selective interaction and RNA stabilization. The selective interaction with a relatively small RNA motif based on a chemical structure of a planer heterocyclic highlights the biological activities of various PCs mediated by the interactions with particular functional RNAs. In addition, the systematic and quantitative investigations demonstrated in this study could be useful for the development of therapeutic chemicals targeting functional RNAs, based on the PCs, in the future.
Do We Nurture Our Young? Qualitative Conceptual Analysis of Worst and Best Mentorship Experiences Among Neonatal Advanced Practice Providers
Authors: Morris April L. , Bosque Elena M. 
Published: March 2021

Background:
There is increasing demand for neonatal advanced practice providers (APPs) and a shortage of neonatal nurse practitioners (NNPs). In many neonatal intensive care units, neonatal physician assistants are trained and hired, as well as new graduate NNPs. Neonatal APPs are utilized as mentors in a regional neonatology program in the Pacific Northwest. As part of a long-term goal to develop an educational program for neonatal APP mentors, an initial survey was administered.

Purpose:
The purpose of this survey was to raise personal insight and identify themes about 51 neonatal APP mentors' recollections of one's own worst and best mentorship experiences.

Methods:
The design used in this content analysis of survey responses included a phenomenological, qualitative approach. The participants received an online survey consisting of 2 questions asking them to describe their worst and best mentorship experiences. The blinded results were analyzed via content analysis by 2 coinvestigators.

Results:
Consistent themes about worst experiences include “Eat our young,” “I am better than you,” “Thrown under bus,” and “Unwanted.” Consistent themes about best experiences include “Validation,” “Empowerment,” “Positivity,” and “Inclusion.”

Implications for Practice:
Recommendations for successful neonatal APP mentorship based upon the recurrent themes include use of consistent, engaged, trained, and supported mentors, provision of on-time constructive feedback, avoidance of public criticism, private and public praise, focus on the learner, preparation for tasks, and semiautonomy, with adequate support.

Implications for Research:
Absenteeism, recruitment, retention, and satisfaction data may be measured to determine whether structured mentorship programs are beneficial.
UNILATERAL CHEMOSIS, BULLOUS SEROUS RETINAL DETACHMENT, AND PRESUMED BACILLARY LAYER DETACHMENT IN SEVERE PREECLAMPSIA
Authors: Zatreanu Luca , Iyer Neel S. 
Published: March 2021

Background/Purpose:
To report a case of unilateral chemosis, serous retinal detachment (SRD), and presumed bacillary layer detachment in pregnancy.

Methods:
Clinical examination and multimodal imaging findings were reviewed and analyzed.

Results:
A 17-year-old female patient with severe preeclampsia was found to have unilateral chemosis and bullous SRD. Postpartum optical coherence tomography revealed thickened choroid and presumed bacillary layer detachment. Two weeks later, chemosis and SRD resolved, leaving behind mottled hyperpigmentation, drusen, and subretinal drusenoid deposits.

Conclusion:
The combination of chemosis and SRD in preeclampsia is exceedingly, rare and it has never previously been reported to occur unilaterally. With delivery, visual acuity, chemosis, choroidal thickness, and SRD all normalize.
In Vivo Modeling of Zebrafish Zinc Finger, MIZ-Type Containing 1 Expression and Its Effect on Pigmentation
Authors: Sun Yong-Hu , Liu Ting-Ting , Mi Zi-Hao , Wang Chuan , Sun Lu-Lu , Ge Kang-Kang , Sheng Dong-Lai , Liu Hong , Zhang Fu-Ren 
Published: March 2021

Objective:
The zinc finger, MIZ-type containing 1 (ZMIZ1) gene has been identified as a possible susceptibility gene associated with vitiligo, therefore we conducted this study to investigate the role of ZMIZ1 in pigmentation.

Methods:
We generate a zebrafish loss-of-function model using morpholino oligonucleotides (MOs), and two orthologs of human ZMIZ1 have been annotated (ZMIZ1a and ZMIZ1b). The expression profiles of ZMIZ1a and ZMIZ1b and their effects on the pigmentation in zebrafish were evaluated by using whole-mount in situ hybridization and melanin quantification. Statistical analysis was performed using the unpaired Student t-test or one-way analysis.

Results:
Investigation of the temporal and spatial expressions of these two transcripts suggested that the expressions of ZMIZ1a and ZMIZ1b in the brain start to emerge in a ubiquitous fashion from 2 days post-fertilization onwards. After the successful design and validation of MOs, we observed that ZMIZ1a and ZMIZ1b MOs caused embryonic developmental delays and malformations in zebrafish. Further analysis of the melanin content in the morphants revealed that ZMIZ1a significantly (49.1% for 0.667 mmol/L in ZMIZI1a group, P = 0.03) reduced the melanin content in a dose-dependent manner, but only the highest concentration of injected ZMIZ1b MOs significantly (50% for 0.667 mmol/L in ZMIZ1b group, P = 0.02) reduced the melanin content. A tyrosinase inhibition assay indicated no significant difference between the morphants and wild-type zebrafish.

Conclusion:
This study successfully modeled a susceptibility gene identified by genome-wide association studies in a zebrafish loss-of-function model and provides insights into the biological mechanism of pigmentation.
Blood pressure from the optical Aktiia Bracelet: a 1-month validation study using an extended ISO81060-2 protocol adapted for a cuffless wrist device
Authors: Vybornova Anna , Polychronopoulou Erietta , Wurzner-Ghajarzadeh Arlène , Fallet Sibylle , Sola Josep , Wuerzner Gregoire 
Published: March 2021

Objective
The objective of this study (NCT04027777) was to assess the accuracy and precision of the Aktiia Bracelet, a CE-marked noninvasive optical blood pressure (BP) monitor worn at the wrist, over a period of 1 month.

Methods
In this study, participants aged between 21 and 65 years were recruited. The clinical investigation extended the ISO81060-2:2013 standard to the specificities of cuffless devices. Each BP assessment consisted of the simultaneous recording of optical signals with Aktiia Bracelet and double-blinded auscultation by two trained observers in the standard sitting position. The algorithms of Aktiia Bracelet further processed the recorded optical signals to perform a signal quality check and to calculate uncalibrated estimates of systolic BP (SBP) and diastolic BP (DBP). These estimates were transformed into mmHg using a subject-dependent calibration parameter, which was calculated using the first two available reference measurements per subject.

Results
Eighty-six participants were included in the analysis. The mean and SD of the differences between Aktiia Bracelet estimates and the reference (ISO81060-2 criterion 1) were 0.46 ± 7.75 mmHg for SBP and 0.39 ± 6.86 mmHg for DBP. The SD of the averaged paired difference per subject (ISO81060-2 criterion 2) were 3.9 mmHg for SBP and 3.6 mmHg for DBP.

Conclusion
After initialization and during 1 month, the overall accuracy of Aktiia Bracelet satisfied validation criteria 1 and 2 of ISO81060-2 in the sitting position. The Aktiia Bracelet can be recommended for BP measurement in the adult population.
Racial/Ethnic Disparities in Longitudinal Emotional–Behavioral Functioning Among Youth Born to Women Living With HIV
Authors: Bather Jemar R. , Williams Paige L. , Broadwell Carly , Smith Renee , Patel Kunjal , Garvie Patricia A. , Karalius Brad , Kacanek Deborah , Mellins Claude A. , Malee Kathleen ,   for the Pediatric HIV/AIDS Cohort Study (PHACS)
Published: March 2021

Background:
Youth with perinatal HIV exposure have demonstrated high rates of emotional–behavioral problems. Few studies have longitudinally examined racial/ethnic disparities in such functioning across adolescence, a critical time for targeting prevention/intervention efforts.

Setting:
The Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol is one of the largest US-based cohort studies of youth with perinatal HIV (YPHIV) infection or HIV exposed but uninfected (YPHEU).

Methods:
Youth and caregivers individually completed the Behavior Assessment System for Children, second edition, every 2 years between ages 7 and 19 years. We used adjusted mixed-effects models to evaluate whether mean youth-reported emotional concerns and caregiver-reported behavioral concerns differed by race/ethnicity. We used group-based trajectory models to identify groups having similar emotional–behavioral trajectories, followed by multinomial models to determine which factors predicted group membership.

Results:
Three hundred ninety-one YPHIV and 209 YPHEU (7% White non-Hispanic, 21% White Hispanic, 66% Black non-Hispanic, and 6% Black Hispanic) completed a median of 4 assessments over follow-up. Adjusted models showed more caregiver-reported behavioral concerns for Black non-Hispanic YPHEU than for Black non-Hispanic YPHIV, White Hispanic YPHIV, and White Hispanic YPHEU, particularly later in adolescence. Race/ethnicity did not predict membership in subgroups of youth-reported emotional or caregiver-reported behavioral functioning identified using group-based trajectory models. However, factors predicting membership in vulnerable youth-reported emotional and caregiver-reported behavioral groups included experiencing a stressful life event and living with a caregiver who was married or screened positive for a psychiatric condition.

Conclusions:
Our study revealed that Black non-Hispanic YPHEU are a vulnerable subgroup. Contributing factors that could inform interventions include the caregiver's health, household characteristics, and psychiatric status.
Relationships Between Viral Load, Neuroimaging, and NP in Persons Living With HIV
Authors: Cooley Sarah A. , Navid Jaimie , Wisch Julie K. , Boerwinkle Anna , Doyle John , Paul Robert H. , Ances Beau M. 
Published: March 2021

Background:
This study examined whether recommended viral load (VL) classifications by the Department of Health and Human Services map onto changes in brain integrity observed in people living with HIV (PLWH).

Methods:
Three hundred forty-nine PLWH on combination antiretroviral therapy meeting criteria for virologic suppression (VS) (VL ≤ 20 copies/mL; n = 206), “low-level viremia” (20–200 copies/mL; n = 63), or virologic failure (VF) (>200 copies/mL; n = 80) and 195 demographically similar HIV-negative controls were compared for cognition and brain volumes from 10 regions of interest that are sensitive to HIV. Changes in cognition and brain volumes were examined in a subset of PLWH (n = 132) who completed a follow-up evaluation (mean interval = 28 months) and had no change in treatment regimen.

Results:
Significant differences in cognition and brain volumes were observed between the HIV-negative control and VS groups compared with those in the VF groups, with few differences observed between the 3 PLWH subgroups. Longitudinally, PLWH who continued to have VF exhibited a greater decline in cognition and brain volumes compared with PLWH who remained with VS. Observed longitudinal changes in cognition correlated with brain volume changes.

Conclusion:
PLWH with continued VF (consecutive VL measurements of >200 copies/mL) represent a cause for clinical concern and may benefit from change in treatment in addition to consideration of other potential etiologies of VF to reduce loss of brain integrity.
The Effect of Priority Given to Donor Card Holders on the Allocation of Livers for Transplant—Evidence From 7 Years of the Israeli Priority Program
Authors: Ashkenazi Tamar , Stoler Avraham , Mor Eytan 
Published: March 2021

Background.
The Israeli Transplant Law grants priority in organ allocation to patients signing a donor card. Liver transplant candidates get additional 2 points on their Model for End Stage Liver Disease score for signing a donor card, 0.1 points for a relative holding a card, and 5 points if a relative donated an organ. We studied the effect of the priority program on waiting list mortality and allocation changes due to priority.

Methods.
Using Israeli Transplant data of 531 adult liver transplant candidates with chronic liver disease listed between 2012 and 2018 we compared waitlist mortality and transplant rate of candidates with and without priority. Then we analyzed liver allocations resulting from additional priority points and followed outcome of patients who were skipped in line.

Results.
Of the 519 candidates, 294 did not sign a donor card, 82 signed, 140 had a relative sign, and for 3, a relative donated an organ. The rates of waitlist mortality in these 4 groups were 22.4%, 0%, 21.4%, and 0%, respectively, and the transplant rates were 50%, 59.8%, 49.3%, and 100%, respectively. Of the 30 patients who were skipped because of priority, 24 subsequently underwent transplant, 2 are on the waiting list, and 4 died within 0.75, 1.75, 7, and 17 mo.

Conclusions.
The 2 points added to the Model for End Stage Liver Disease score were associated with lower waitlist mortality and higher transplant rate for candidates signing a donor card without significantly affecting access to transplant during allocation. Further research and consideration of optimal policy when granting priority for candidates signing a donor card should continue.