bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decision Tree-Based Classification for Maintaining Normal Blood Pressure Throughout Early Adulthood and Middle Age: Findings From the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Reges Orna , Krefman Amy E , Hardy Shakia T , Yano Yuichiro , Muntner Paul , Lloyd-Jones Donald M , Allen Norrina B 
Published: June 2021

Abstract

Background
For most individuals, blood pressure (BP) is related to multiple risk factors. By utilizing the decision tree analysis technique, this study aimed to identify the best discriminative risk factors and interactions that are associated with maintaining normal BP over 30 years and to reveal segments of a population with a high probability of maintaining normal BP.

Methods
Participants from the Coronary Artery Risk Development in Young Adults study aged 18–30 years with normal BP level at baseline visit (Y0, 1985–1986) were included in this study.

Results
Of 3,156 participants, 1,132 (35.9%) maintained normal BP during the follow-up period and 2,024 (64.1%) developed higher BP. Systolic BP (SBP) within the normal range, race, and body mass index (BMI) were the most discriminative factors between participants who maintained normal BP throughout midlife and those who developed higher BP. Participants with a baseline SBP level ≤92 mm Hg and White women with baseline BMI &lt; 23 kg/m2 were the two segments of the population with the highest probability for maintaining normal BP throughout midlife (69.2% and 59.9%, respectively). Among Black participants aged &gt;26.5 years with BMI &gt; 27 kg/m2, only 5.4% of participants maintained normal BP throughout midlife.

Conclusions
This study emphasizes the importance of early life factors to later life SBP and support efforts to maintain ideal levels of risk factors for hypertension at young ages. Whether policies to maintain lower BMI and SBP well below the clinical thresholds throughout young adulthood and middle age can reduce later age hypertension should be examined in future studies.
Autopolyploids ofArabidopsis thalianaare more phenotypically plastic than their diploid progenitors
Authors: Mattingly Kali Z , Hovick Stephen M 
Published: June 2021

AbstractBackground and AimsPolyploids are often hypothesized to have increased phenotypic plasticity compared with their diploid progenitors, but recent work suggests that the relationship between whole-genome duplication (WGD) and plasticity is not so straightforward. Impacts of WGD on plasticity are moderated by other evolutionary processes in nature, which has impeded generalizations regarding the effects of WGD alone. We assessed shifts in phenotypic plasticity and mean trait values accompanying WGD, as well as the adaptive consequences of these shifts.MethodsTo isolate WGD effects, we compared two diploid lineages of Arabidopsis thaliana wiht corresponding autotetraploids grown across different salt and nutrient conditions in a growth chamber.Key ResultsFor the few cases in which diploids and polyploids differed in plasticity, polyploids were more plastic, consistent with hypotheses that WGD increases plasticity. Under stress, increased plasticity was often adaptive (associated with higher total seed mass), but in other cases plasticity was unrelated to fitness. Mean trait values and plasticity were equally likely to be affected by WGD, but the adaptive consequences of these shifts were often context dependent or lineage specific. For example, polyploids had extended life spans, a shift that was adaptive in one polyploid lineage under amenable conditions but was maladaptive in the other lineage under stress.ConclusionsOur work shows that increased phenotypic plasticity can result from WGD alone, independent of other evolutionary processes. We find that the effects of WGD can differ depending on the genotype of the progenitor and the environmental context. Though our experiment was limited to two genotypes of a single species, these findings support the idea that WGD can indeed increase plasticity.
Why Censorship is Self-Undermining: John Stuart Mill’s Neglected Argument for Free Speech
Authors: Shah Nishi 
Published: June 2021

Abstract
Two prejudices have hampered our understanding of John Stuart Mill’s central argument for free speech. One prejudice is that arguments for free speech can only be made in terms of values or rights. This prejudice causes us to miss the depth of Mill’s argument. He does not argue that silencing speech is harmful or violates rights, but instead that silencing speech is a uniquely self-undermining act; it undermines the ground upon which it is based. But even if we overcome this prejudice and appreciate the self-undermining character of Mill’s argument, the prejudice that epistemic justification is a completable task blinds us to the role of open-mindedness in his argument; and failing to see this leads us to wrongly conclude that his argument is invalid. It is only once we have overcome both prejudices that we can appreciate the depth and power of Mill’s argument for free speech.
Effect of natural pre-luteolytic prostaglandin F2α pulses on the bovine luteal transcriptome during spontaneous luteal regression†
Authors: Mezera Megan A , Li Wenli , Liu Lihe , Meidan Rina , Peñagaricano Francisco , Wiltbank Milo C 
Published: June 2021

AbstractThe pulsatile pattern of prostaglandin F2alpha (PGF) secretion during spontaneous luteolysis is well documented, with multiple pulses of exogenous PGF necessary to induce regression using physiologic concentrations of PGF. However, during spontaneous regression, the earliest pulses of PGF are small and not associated with detectable changes in circulating progesterone (P4), bringing into question what, if any, role these early, subluteolytic PGF pulses have during physiologic regression. To investigate the effect of small PGF pulses, luteal biopsies were collected throughout natural luteolysis in conjunction with bihourly blood samples to determine circulating P4 and PGF metabolite to retrospectively assign biopsies to early and later regression. Whole transcriptome analysis was conducted on CL biopsies. Early PGF pulses altered the luteal transcriptome, inducing differential expression of 210 genes (Q &lt; 0.05) during early regression, compared with 4615 differentially expressed genes during later regression. In early regression, few of these differentially expressed genes were directly associated with luteolysis, rather there were changes in local steroid and glutathione metabolism. Most (94%) differentially expressed genes from early regression were also differentially expressed during later regression, with 98% of these continuing to be altered in the same direction compared with CL at a similar stage of the cycle that had not yet been exposed to PGF. Thus, early, subluteolytic PGF pulses impact the luteal transcriptome, though not by altering steroidogenesis or causing direct inhibition of cellular function. Rather, small pulses alter pathways resulting in the removal of cellular support systems, which may sensitize the CL to later pulses of PGF.
Foster Carers’ Receptiveness to New Innovations and Programmes: An Example from the Introduction of Social Pedagogy to UK Foster Care
Authors: McDermid Samantha , Trivedi Helen , Holmes Lisa , Boddy Janet 
Published: June 2021

AbstractFoster carers characterise a highly diverse workforce that shares the choice to provide a home and family for children who can no longer reside with their family. This diversity makes supporting and providing for carers’ training needs a complex task for fostering services. Understanding what might influence their engagement in training would be useful. This article outlines themes related to foster carers’ engagement with social pedagogy, using data from the Head, Heart, Hands (HHH) programme evaluation. Analysis of interviews with seventy-six foster carers over a period of three years is presented. The emerging themes were used to devise an illustrative typology of receptiveness to training. The themes relate to the perceived impact of HHH on their practice and compatibility with the existing children’s social care (CSC) system. The article explores the factors that may influence foster carers’ positioning within the typology. The contributions that such a typology might make to the wider evidence base across CSC, in terms of the implementation and potential impacts of intervention, are discussed.
Contemporary approach to soft-tissue reconstruction of the lower extremity after trauma
Authors: Zeiderman Matthew R , Pu Lee L Q 
Published: June 2021

AbstractThe complex lower extremity wound is frequently encountered by orthopedic and plastic surgeons. Innovations in wound care, soft tissue coverage and surgical fixation techniques allow for improved functional outcomes in this patient population with highly morbid injuries. In this review, the principles of reconstruction of complex lower extremity traumatic wounds are outlined. These principles include appropriate initial evaluation of the patient and mangled extremity, as well as appropriate patient selection for limb salvage. The authors emphasize proper planning for reconstruction, timing of reconstruction and the importance of an understanding of the most appropriate reconstructive option. The role of different reconstructive and wound care modalities is discussed, notably negative pressure wound therapy and dermal substitutes. The role of pedicled flaps and microvascular free-tissue transfer are discussed, as are innovations in understanding of perforator anatomy and perforator flap surgery that have broadened the reconstruction surgeon’s armamentarium. Finally, the importance of a multidisciplinary team is highlighted via the principle of the orthoplastic approach to management of complex lower extremity wounds. Upon completion of this review, the reader should have a thorough understanding of the principles of contemporary lower extremity reconstruction.
Brain and Behavioral Evidence for Reweighting of Vestibular Inputs with Long-Duration Spaceflight
Authors: Hupfeld K E , McGregor H R , Koppelmans V , Beltran N E , Kofman I S , De Dios Y E , Riascos R F , Reuter-Lorenz P A , Wood S J , Bloomberg J J , Mulavara A P , Seidler R D 
Published: June 2021

Abstract
Microgravity alters vestibular signaling. In-flight adaptation to altered vestibular afferents is reflected in post-spaceflight aftereffects, evidenced by declines in vestibularly mediated behaviors (e.g., walking/standing balance), until readaptation to Earth’s 1G environment occurs. Here we examine how spaceflight affects neural processing of applied vestibular stimulation. We used fMRI to measure brain activity in response to vestibular stimulation in 15 astronauts pre- and post-spaceflight. We also measured vestibularly-mediated behaviors, including balance, mobility, and rod-and-frame test performance. Data were collected twice preflight and four times postflight. As expected, vestibular stimulation at the preflight sessions elicited activation of the parietal opercular area (“vestibular cortex”) and deactivation of somatosensory and visual cortices. Pre- to postflight, we found widespread reductions in this somatosensory and visual cortical deactivation, supporting sensory compensation and reweighting with spaceflight. These pre- to postflight changes in brain activity correlated with changes in eyes closed standing balance, and greater pre- to postflight reductions in deactivation of the visual cortices associated with less postflight balance decline. The observed brain changes recovered to baseline values by 3 months postflight. Together, these findings provide evidence for sensory reweighting and adaptive cortical neuroplasticity with spaceflight. These results have implications for better understanding compensation and adaptation to vestibular functional disruption.
Monitoring anti-PLA2R antibody titres to predict the likelihood of spontaneous remission of membranous nephropathy
Authors: Jatem-Escalante Elias , Martín-Conde María Luisa , Gràcia-Lavedan Esther , Benítez Ivan D , Gonzalez Jorge , Colás Laura , Garcia-Carrasco Alicia , Martínez Cristina , Segarra-Medrano Alfons 
Published: June 2021

ABSTRACT

Background
In anti-phospholipase A2 receptor (PLA2R) membranous nephropathy (MN) there is controversy whether spontaneous remission (SR) can be predicted using a single titre or by assessing the dynamic changes in anti-PLA2R antibody (ab) titres. The study objective was to identify the optimal dynamics of anti-PLA2Rab titres to predict SR in MN.

Methods
A total of 127 nephrotic patients with anti-PLA2R-MN were prospectively followed up for 6 months under conservative treatment. Anti-PLA2Rabs and proteinuria were assessed at diagnosis and monthly thereafter. The primary endpoint (PEP) was a reduction of proteinuria ≥50% at 6 months. Logistic models with baseline and evolutive anti-PLA2Rab titres were developed to predict the PEP.

Results
A total of 28 patients (22%) reached the PEP. These patients were more frequently female and had significantly lower baseline proteinuria and anti-PLA2Rab titres. An anti-PLA2R titre ≤97.5 RU/mL at diagnosis had a sensitivity of 71% and a specificity of 81% to predict the PEP. The model including baseline anti-PLA2Rabs and a reduction ≥15% at 3 months predicted the PEP with a sensitivity of 93% and a specificity of 80%, with an area under the curve that was significantly greater than that obtained with relative changes of proteinuria in the same period of time {odds ratio [OR] 0.95 [95% confidence interval (CI) 0.91–0.98 versus OR 0.79 [95% CI 0.70–0.88], respectively; P = 0.0013}.

Conclusions
Combining the baseline anti-PLA2Rab titres with their relative changes at 3 months after diagnosis gives the earliest prediction for achieving a reduction of urinary protein excretion ≥50% at 6 months in MN, thereby shortening the observation period currently recommended to make individualized decisions to start immunosuppressive therapy.
Analytical Quality Controls for ddPCR Detection of Minimal Residual Disease in Acute Lymphoblastic Leukemia
Authors: Chen Dan , Sutton Rosemary , Giles Jodie , Venn Nicola C , Huang Libby , Law Tamara , Subhash Vinod Vijay , Trahair Toby N , Henderson Michelle J 
Published: June 2021

Abstract

Background
Droplet digital PCR (ddPCR) is a promising technique for absolute quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL), but there is no comprehensive quality assurance program to enable its application in clinical laboratories. Current guidelines for real-time quantitative PCR (qPCR) assays targeting immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements needed adaptation for ddPCR to cover droplet generation, intraassay variation, and interassay variation in the absence of standard curves.

Methods
Six qPCR MRD assays for Ig/TCR gene rearrangements and a standard albumin control gene assay were migrated to a ddPCR platform and used to test 82 remission samples from 6 patients with ALL. Three analytical quality controls (QC) were developed and evaluated for ddPCR MRD detection.

Results
Analytical QC for droplet number generation (DN-QC), for albumin ddPCR assay performance (Alb-QC) and for patient-specific marker assay performance (PS-QC) were established with pass/fail limits and corresponding QC rules. Compared to established qPCRs, the ddPCR assays had comparable sensitivity and quantitative range. Overall, there was close agreement (91%) of MRD results between qPCR and ddPCR (κ = 0.86, P &lt; 0.0001) and stronger concordance in 32 quantifiable samples (R2 = 0.97, P &lt; 0.0001).

Conclusions
The use of this newly developed quality control system for ddPCR MRD testing avoids the need to repeat standard curves and provides reliable results comparable to standardized qPCR methods for MRD detection in ALL.
Targeting early stages of cardiotoxicity from anti-PD1 immune checkpoint inhibitor therapy
Authors: Michel Lars , Helfrich Iris , Hendgen-Cotta Ulrike Barbara , Mincu Raluca-Ileana , Korste Sebastian , Mrotzek Simone Maria , Spomer Armin , Odersky Andrea , Rischpler Christoph , Herrmann Ken , Umutlu Lale , Coman Cristina , Ahrends Robert , Sickmann Albert , Löffek Stefanie , Livingstone Elisabeth , Ugurel Selma , Zimmer Lisa , Gunzer Matthias , Schadendorf Dirk , Totzeck Matthias , Rassaf Tienush 
Published: June 2021

Abstract

Aims
Cardiac immune-related adverse events (irAEs) from immune checkpoint inhibition (ICI) targeting programmed death 1 (PD1) are of growing concern. Once cardiac irAEs become clinically manifest, fatality rates are high. Cardio-oncology aims to prevent detrimental effects before manifestation of severe complications by targeting early pathological changes. We therefore aimed to investigate early consequences of PD1 inhibition for cardiac integrity to prevent the development of overt cardiac disease.

Methods and results
We investigated cardiac-specific consequences from anti-PD1 therapy in a combined biochemical and in vivo phenotyping approach. Mouse hearts showed broad expression of the ligand PDL1 on cardiac endothelial cells as a main mediator of immune-crosstalk. Using a novel melanoma mouse model, we assessed that anti-PD1 therapy promoted myocardial infiltration with CD4+ and CD8+ T cells, the latter being markedly activated. Left ventricular (LV) function was impaired during pharmacological stress, as shown by pressure–volume catheterization. This was associated with a dysregulated myocardial metabolism, including the proteome and the lipidome. Analogous to the experimental approach, in patients with metastatic melanoma (n = 7) receiving anti-PD1 therapy, LV function in response to stress was impaired under therapy. Finally, we identified that blockade of tumour necrosis factor alpha (TNFα) preserved LV function without attenuating the anti-cancer efficacy of anti-PD1 therapy.

Conclusions
Anti-PD1 therapy induces a disruption of cardiac immune homeostasis leading to early impairment of myocardial functional integrity, with potential prognostic effects on the growing number of treated patients. Blockade of TNFα may serve as an approach to prevent the manifestation of ICI-related cardiotoxicity.
Assessment of the physical performance in children with asymptomatic pre-excitation
Authors: Książczyk Tomasz M , Jaroń Anna , Pietrzak Radosław , Werner Bożena 
Published: June 2021

Abstract

Aims
Pre-excitation syndrome can lead to recurrent supraventricular tachycardias (SVTs) and carries a risk of sudden cardiac death (SCD). However, an underestimated consequence of antegrade conduction through an accessory pathway is fusion of intrinsic and accessory conduction that causes asynchronous activation and myocardial contraction that could be a cause for cardiac dysfunction and dilation. It is not known to what extent pre-excitation affects myocardial and physical performance in those patients. The aim of the study was to assess to what degree ventricular pre-excitation affects physical performance in children, using cardio-pulmonary exercise testing (CPET).

Methods and results
The study group consisted of 30 asymptomatic children, aged 8–17 years, with pre-excitation and no history or documentation of SVT compared to 31 healthy controls matched according to sex and age. All patients underwent routine cardiology assessment and then CPET. Echocardiography showed there were no differences in the left ventricular size and function between the study and control group. During the CPET both, patients and controls achieved maximal effort. Patients in the study group showed significantly lower values of VO2max and anaerobic threshold when compared to controls. The most affected subgroup was patients with persistent pre-excitation throughout the exercise.

Conclusions
Physical performance is affected in children with pre-excitation. This effect is stronger in patients with persistent delta wave observed throughout the exercise.
Male–Female Differences in the Effects of Age on Performance Measures Recorded for 23 Hours in Mice
Authors: Tran Trang , Mach John , Gemikonakli Gizem , Wu Harry , Allore Heather , Howlett Susan E , Little Christopher B , Hilmer Sarah N 
Published: June 2021

AbstractFunctional independence is an important aspect of successful aging and differs with age and by sex in humans. Physical performance often declines earlier than other age-associated functional impairments. Rodent models are used to study pharmacological/toxicological effects of human therapies. However, physical outcomes in mice are usually assessed for short periods, with limited information on the influence of age and sex. Here, we investigated how age and sex affected murine physical performance over 23 hours of continuous observation. Young (3 months) and old (22 months) C57BL/6JArc male and female mice were assessed using the Laboratory Animal Behavior Observation, Registration, and Analysis System. Mice were individually housed for recording of distance travelled, mean gait speed, and durations of different physical activities. Compared to young mice of the same sex, old mice travelled significantly shorter distances with slower gait speeds and shorter durations of locomotion, rearing, climbing, and immobility. Older mice groomed significantly more than young mice. Old females reared more during the light cycle than old males. Young females climbed substantially more than young males. Significant Age * Sex interactions were detected for rearing and climbing, whereby an age-related decline was greater in males than in females. Our results suggest that old age reduces exploratory activities and increases grooming in mice. Age-related declines vary between sexes and tend to be greater in males. This noninvasive assessment can be applied to investigate how different interventions affect rodents of different ages and sexes, through the day–night cycle.
Squirt flow in partially saturated cracks: a simple analytical model
Authors: Solazzi Santiago G , Lissa Simón , Rubino J Germán , Holliger Klaus 
Published: June 2021

SUMMARY
Obtaining the seismic response of rocks containing cracks whose scales are much smaller than the prevailing wavelengths is a classic and important problem in rock physics. Seminal analytical models yield the seismic signatures of cracked rocks saturated with a single fluid phase. However, in a wide variety of practically relevant scenarios, cracks may be partially saturated with multiple immiscible fluids of contrasting compressibilities, such as gas and water. When a passing seismic wave deforms the medium, fluid pressure gradients arise within such partially saturated cracks, which, in turn, tend to relax through a process commonly known as squirt flow. The corresponding viscous dissipation may greatly affect the seismic amplitudes and velocities, as well as the anisotropic behaviour of the medium. To date, extensions of classical analytical models to include squirt flow occurring within isolated partially saturated cracks remain limited either in the saturation or in the frequency range. In this work, we present a simple analytical model to compute the seismic response of rocks containing partially saturated aligned cracks accounting for squirt flow effects. First, we solve the linearized Navier–Stokes equations within a partially saturated penny-shaped crack subjected to an oscillatory strain. Then, we obtain a closed analytical expression for a complex-valued frequency-dependent effective fluid bulk modulus which accounts for the stiffness variations of each crack due to squirt flow. Using classic effective medium models, together with such an effective saturating fluid, we retrieve the effective compliance matrix of the probed partially saturated cracked rock. The proposed analytical solution is validated by comparison with corresponding 3-D numerical simulations and existing analytical models.