bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis of surgical and percutaneous pulmonary valve implants over a 20-year period
Authors: Hribernik Ines , Thomson John , Ho Andrew , English Kate , Van Doorn Carin , Jaber Osama , Bentham James
Published: July 2021

OBJECTIVES

Since percutaneous pulmonary valve implantation (PPVI) was introduced to prolong the lifetime of surgically placed right ventricular to pulmonary artery conduits, valve technology has evolved and the indications for PPVI expanded to native and larger right ventricular outflow tracts. We explore how indications, patient populations and outcomes compare to surgical pulmonary valve replacement (PVR).

METHODS

This is a retrospective cohort study of PPVI and PVR procedures between 1998 and 2020 at a single UK centre. One hundred and twenty-eight patients underwent PPVI and 365 patients PVR. Primary outcome measures were survival, infective endocarditis and reintervention.

RESULTS

The most common indication for PVR was replacement of the native pulmonary valve for pulmonary regurgitation whereas PPVI was more commonly used to treat pulmonary stenosis in a previously placed bioprosthetic conduit or valve. Treatment indications for PPVI expanded over the study to include the native right ventricular outflow tract. Survival was similar for PPVI and PVR (92% PPVI and 96.8% PVR at 5 years; 85.8% PPVI and 95.1% PVR at 10 years). Preprocedural New York Heart Association class 3 and 4 was the most important predictor of poor outcome. Annualized infective endocarditis rate was significantly higher for the Melody PPVI (0.024 vs 0.0024/person/year for PVR, P < 0.05). Both groups showed significant symptomatic improvement postprocedure with remodelling of ventricular volumes and improvement in cardiac output. Long-term follow-up for PVR showed half of patients will need replacement at 10–15 years post-index procedure.

CONCLUSIONS

An increasing number of patients requiring PVR can now be treated percutaneously. A lifetime strategy for re-valving should be considered at the first valve implant.
Sex-specific differences and postoperative outcomes of minimally invasive and sternotomy valve surgery
Authors: Moscarelli Marco , Lorusso Roberto , Angelini Gianni D , Di Bari Nicola , Paparella Domenico , Fattouch Khalil , Albertini Alberto , Nasso Giuseppe , Fiorentino Francesca , Speziale Giuseppe
Published: July 2021

OBJECTIVES

Female sex is an established risk factor for postoperative complications after heart surgery, but the influence of sex on outcomes after minimally invasive cardiac surgery (MICS) for valvular replacement/repair remains controversial. We examined whether the role of sex as a risk factor varies by surgical approach [MICS vs conventional sternotomy (ST)] and further assessed outcomes among female patients including in-hospital mortality and postoperative complications by surgical approach.

METHODS

We analysed data from a multicentre registry for patients who underwent isolated aortic valve and mitral surgery with MICS or ST. The primary outcome was in-hospital mortality. Propensity score matching was used to minimize between-group differences.

RESULTS

Among the 15 155 patients included in the study, 7674 underwent MICS (50.6%). Female sex was equally distributed in the MICS and ST groups (47.3% vs 47.6%, respectively). Risk for surgery was higher in the ST group than in the MICS group {EuroSCORE II: 4.0 [standard deviation (SD): 6.8] vs 3.7 [SD: 6.4]; P = 0.005}, including among female patients only [ST vs MICS 4.6 (SD: 6.9) vs 4.2 (SD: 6.3); P = 0.04]. Mortality did not significantly vary by procedure among women [MICS vs ST, 2.4% vs 2.8%; hazard ratio 1.09, 95% confidence interval 0.71–1.73; P (surgical approach × sex) = 0.51]. The results also did not vary after adjusting for confounders.

CONCLUSIONS

Female sex was associated with higher mortality in patients undergoing valve surgery, regardless of surgical approach. In female patients, MICS did not provide any benefits over ST in terms of in-hospital deaths or postoperative complications.

Subject collection

117, 125.
Improved draft reference genome for the Glassy-winged Sharpshooter (Homalodisca vitripennis), a vector for Pierce’s disease
Authors: Ettinger Cassandra L , Byrne Frank J , Collin Matthew A , Carter-House Derreck , Walling Linda L , Atkinson Peter W , Redak Rick A , Stajich Jason E
Published: July 2021

Homalodisca vitripennis (Hemiptera: Cicadellidae), known as the glassy-winged sharpshooter, is a xylem feeding leafhopper and an important agricultural pest as a vector of Xylella fastidiosa, which causes Pierce’s disease in grapes and a variety of other scorch diseases. The current H. vitripennis reference genome from the Baylor College of Medicine's i5k pilot project is a 1.4-Gb assembly with 110,000 scaffolds, which still has significant gaps making identification of genes difficult. To improve on this effort, we used a combination of Oxford Nanopore long-read sequencing technology combined with Illumina sequencing reads to generate a better assembly and first-pass annotation of the whole genome sequence of a wild-caught Californian (Tulare County) individual of H. vitripennis. The improved reference genome assembly for H. vitripennis is 1.93-Gb in length (21,254 scaffolds, N50 = 650 Mb, BUSCO completeness = 94.3%), with 33.06% of the genome masked as repetitive. In total, 108,762 gene models were predicted including 98,296 protein-coding genes and 10,466 tRNA genes. As an additional community resource, we identified 27 orthologous candidate genes of interest for future experimental work including phenotypic marker genes like white. Furthermore, as part of the assembly process, we generated four endosymbiont metagenome-assembled genomes, including a high-quality near complete 1.7-Mb Wolbachia sp. genome (1 scaffold, CheckM completeness = 99.4%). The improved genome assembly and annotation for H. vitripennis, curated set of candidate genes, and endosymbiont MAGs will be invaluable resources for future research of H. vitripennis.
The Pseudoalteromonas multipartite genome: distribution and expression of pangene categories, and a hypothesis for the origin and evolution of the chromid
Authors: Sonnenberg Cecilie Bækkedal , Haugen Peik
Published: July 2021

Bacterial genomes typically consist of one large chromosome, but can also include secondary replicons. These so-called multipartite genomes are scattered on the bacterial tree of life with the majority of cases belonging to Proteobacteria. Within the class gamma-proteobacteria, multipartite genomes are restricted to the two families Vibrionaceae and Pseudoalteromonadaceae. Whereas the genome of vibrios is well studied, information on the Pseudoalteromonadaceae genome is much scarcer. We have studied Pseudoalteromonadaceae with respect to the origin of the chromid, how pangene categories are distributed, how genes are expressed relative to their genomic location, and identified chromid hallmark genes. We calculated the Pseudoalteromonadaceae pangenome based on 25 complete genomes and found that core/softcore are significantly overrepresented in late replicating sectors of the chromid, regardless of how the chromid is replicated. On the chromosome, core/softcore and shell/cloud genes are only weakly overrepresented at the chromosomal replication origin and termination sequences, respectively. Gene expression is trending downwards with increasing distance from the chromosomal oriC, whereas the chromidal expression pattern is more complex. Moreover, we identified 78 chromid hallmark genes, and BLASTp searches suggest that the majority of them were acquired from the ancestral gene pool of Alteromonadales. Finally, our data strongly suggest that the chromid originates from a plasmid that was acquired in a relatively recent event. In summary, this study extends our knowledge on multipartite genomes, and helps us understand how and why secondary replicons are acquired, why they are maintained, and how they are shaped by evolution.
Optimizing the Care and Management of Older Offenders: A Scoping Review
Authors: Hagos Amanuel K , Butler Tony G , Howie Adam , Withall Adrienne L
Published: July 2021

Background and Objectives

The rapid increase in the number of older offenders in many countries presents unique challenges to both correctional and health care systems. In the absence of strong empirical evidence on effective interventions, identifying best practices can help optimize the care and management of this segment of the prisoner population.

Research Design and Methods

We conducted a scoping review of care models, prison programs, and different interventions designed to improve the care and management of older offenders. We searched 5 bibliographic databases and other data sources including OpenGrey, agency documents, and government reports published until December 2020. This review employed commonly used steps for conducting a scoping review and applied additional tools to enhance the methodology.

Results

After title and abstract screening and full-text review, a total of 34 studies were included in the analysis. Four themes emerged from the review: (a) institutional logics, (b) adaptations, (c) multidisciplinary teams, and (d) person-centered care and management.

Discussion and Implications

Best practices identified in this review can help optimize the care and management of older offenders in mainstream prisons. Further action research is recommended to adapt and scale up the interventions.
Enhancing the interoperability of glycan data flow between ChEBI, PubChem, and GlyGen
Authors: Navelkar Rahi , Owen Gareth , Mutherkrishnan Venkatesh , Thiessen Paul , Cheng Tiejun , Bolton Evan , Edwards Nathan , Tiemeyer Michael , Campbell Matthew P , Martin Maria , Vora Jeet , Kahsay Robel , Mazumder Raja
Published: July 2021

Glycans play a vital role in health, disease, bioenergy, biomaterials, and bio-therapeutics. As a result, there is keen interest to identify and increase glycan data in bioinformatics databases like ChEBI and PubChem, and connecting them to resources at the EMBL-EBI and NCBI to facilitate access to important annotations at a global level. GlyTouCan is a comprehensive archival database that contains glycans obtained primarily through batch upload from glycan repositories, glycoprotein databases, and individual laboratories. In many instances, the glycan structures deposited in GlyTouCan may not be fully defined or have supporting experimental evidence and citations. Databases like ChEBI and PubChem were designed to accommodate complete atomistic structures with well-defined chemical linkages. As a result, they cannot easily accommodate the structural ambiguity inherent in glycan databases. Consequently, there is a need to improve the organization of glycan data coherently to enhance connectivity across the major NCBI, EMBL-EBI, and glycoscience databases.

This paper outlines a workflow developed in collaboration between GlyGen, ChEBI, and PubChem to improve the visibility and connectivity of glycan data across these resources. GlyGen hosts a subset of glycans (~29,000) from the GlyTouCan database and has submitted valuable glycan annotations to the PubChem database and integrated over 10,500 (including ambiguously defined) glycans into the ChEBI database. The integrated glycans were prioritized based on links to PubChem and connectivity to glycoprotein data. The pipeline provides a blueprint for how glycan data can be harmonized between different resources. The current PubChem, ChEBI, and GlyTouCan mappings can be downloaded from GlyGen (https://data.glygen.org).
National multisectoral governance challenges of implementing the Philippines’ Reproductive Health Law
Authors: Siy Van Vanessa T , Uy Jhanna , Bagas Joy , Ulep Valerie Gilbert T
Published: July 2021

In recognition of the role of reproductive health in individual and national development, the Responsible Parenthood and Reproductive Health (RPRH) Law of 2012 was passed in the Philippines after 30 years of opposition and debate. Seven years later, this article examined the cohesiveness of national multi-sectoral governance among state and non-state actors and identified challenges in coordination as part of the first comprehensive evaluation of the landmark policy. Using a qualitative intrinsic case study design and guided by the World Health Organization’s systems checklist for governing health equity as our theoretical perspective, we conducted 20 semi-structured interviews with national implementers from health agencies (n = 11), non-health agencies (n = 6) and non-state actors (n = 3) that included civil society organizations (CSOs). Key themes identified through thematic analysis were supported with document reviews of policy issuances, accomplishment reports and meeting transcripts of the RPRH National Implementation Team (NIT). The study found that despite aspirations for vibrant multi-sectoral coordination, the implementation of the RPRH Law in the Philippines was incohesive. National leaders, particularly the health sector, were neither able to rally non-health sector actors around RPRH nor strategically harness the power of CSOs. Local resource limitations associated with decentralization were exacerbated by paternalistic financing, coordination, and monitoring. The absence of multi-agency plans fostered a culture of siloed opportunism, without consideration to integrated implementation. This case study shows that for neutral policies without conflicts in sector objectives, the interest and buy-in of non-health state actors, even with a national law, cannot be assumed. Moreover, possible conflicts in interests and perspectives between state and civil society actors must be managed in national governance bodies. Overall, there is need for participatory policymaking and health-sector advocacy to set health equity as an intersectoral goal, involving subnational leaders in developing concrete action plans, and strengthening NIT’s formal accountability systems.
A pause in time: history writers and the regicide of Charles I
Authors: Wong Matthias Meng Yan
Published: July 2021

The unprecedented trial and execution of Charles I left a nation aghast and bewildered. This article examines how the English reacted to such a disruptive event, namely how the regicide changed ideas of time and the future. Using a diachronic approach, this article examines the work of three history writers and the temporalities embedded within their narratives. Recognizing the significance of the regicide as a singular moment in time, these writers adapted their work to incorporate a sense of changed times. By envisioning futures in their texts, these histories informed but also circumscribed the world views of their readers.
Common variants in SCN10A gene associated with Brugada syndrome
Authors: Huang Yan , Chen Xiao-Meng , Barajas-Martinez Hector , Jiang Hong , Antzelevitch Charles , Hu Dan
Published: July 2021

Genome-wide association studies indicate that SCN10A plays an important role in cardiac electrophysiology. Common and rare SCN10A variants are suggested to contribute to Brugada Syndrome (BrS), an inherited channelopathy resulting from genetic-determined loss-of-function in cardiac sodium channel. This study sought to characterize the role of SCN10A common variants in BrS. Clinical and genetic analyses were performed in 197 patients diagnosed with BrS. Baseline ECG parameters were evaluated in patients carrying each of four common variants associated with BrS. Cellular electrophysiological study was performed in SCN5A-SCN10A co-transfected TSA201 cells to investigate the possible electrophysiological characteristics of the allele of rs6795970, which displayed the most significant association with BrS. Four SCN10A common variants (rs7630989, rs57326399, rs6795970, rs12632942) displayed significant association with BrS susceptibility. There were no evident associations between baseline ECG parameters in BrS patients and the different genotypes of the four variants. Rs6795970 (V1073) was strongly associated with a risk for BrS, which suggests the different electrophysiological characters between these two alleles. Functional study showed a positive shift in steady-state activation (V1/2: −62.2 ± 2.6 vs. –53.5 ± 1.6 for A1073 and V1073 group, respectively; P < 0.05) and slower recovery from inactivation in mutant SCN5A-SCN10A co-transfected cells with, which contribute to the slow conduction in BrS patients with rs6795970. In conclusion, SCN10A common variants are associated with increased susceptibility to BrS. An allele rs6795970 (V1073) increases the risk for BrS. The electrophysiological changes in a positive shift in steady-state activation and slower recovery from inactivation by SCN10A-V1073 contribute to this variant associated BrS.
A Framework for Investigating Rules of Life by Establishing Zones of Influence
Authors: Lawing A Michelle , McCoy Michael , Reinke Beth A , Sarkar Susanta K , Smith Felisa A , Wright Derek
Published: July 2021

Synopsis

The incredible complexity of biological processes across temporal and spatial scales hampers defining common underlying mechanisms driving the patterns of life. However, recent advances in sequencing, big data analysis, machine learning, and molecular dynamics simulation have renewed the hope and urgency of finding potential hidden rules of life. There currently exists no framework to develop such synoptic investigations. Some efforts aim to identify unifying rules of life across hierarchical levels of time, space, and biological organization, but not all phenomena occur across all the levels of these hierarchies. Instead of identifying the same parameters and rules across levels, we posit that each level of a temporal and spatial scale and each level of biological organization has unique parameters and rules that may or may not predict outcomes in neighboring levels. We define this neighborhood, or the set of levels, across which a rule functions as the zone of influence. Here, we introduce the zone of influence framework and explain using three examples: (a) randomness in biology, where we use a Poisson process to describe processes from protein dynamics to DNA mutations to gene expressions, (b) island biogeography, and (c) animal coloration. The zone of influence framework may enable researchers to identify which levels are worth investigating for a particular phenomenon and reframe the narrative of searching for a unifying rule of life to the investigation of how, when, and where various rules of life operate.
Surgical glue-induced left main trunk stenosis removed by directional coronary atherectomy
Authors: Kitamura Hideki , Tamaki Mototsugu , Kawaguchi Yasuhiko
Published: July 2021

A 55-year-old man underwent aortic repair for acute aortic dissection. The pseudolumen of the Valsalva sinus was reapproximated with BioGlue by placing a sponge inside of it to prevent the BioGlue from entering. Postoperative contrast-enhanced computed tomography showed stenosis of the left main trunk. Directional coronary atherectomy was performed; complete release of the stenosis was achieved. Various fragments retrieved from the left main trunk were pathologically consistent with BioGlue. When we reapproximated the dissected aortic wall, inserting a sponge into the aorta did not prevent the surgical glue from entering. Directional coronary atherectomy was a good therapeutic option to treat glue-induced coronary artery stenosis.
A review of modeling of luminescent coupling effect in multi-junction solar cell based on diode equation
Authors: Liu Zhezhi , Lv Hui , Hu Yue , Liao Jun , Zhou Hang , Su Yuehong
Published: July 2021

The luminescent coupling effect in multi-junction solar cell is a phenomenon where extra photocurrent in one sub-cell is driven by radiative recombination of electron–hole pairs in another sub-cell. This paper focuses on the analysis of the modeling of luminescent coupling effect in multi-junction solar cell. These modelings are based on the two-diode equivalent circuit. Finally, it concludes that the study of the luminescent coupling effect requires not only a suitable modeling but also a good experimental method for detecting the characteristics of sub-cells in multi-junction solar cell.
Tear film dynamics with blinking and contact lens motion
Authors: Anderson Daniel M , Corsaro Maria , Horton Jonathan , Reid Tim , Seshaiyer Padmanabhan
Published: July 2021

We develop a lubrication theory-based mathematical model that describes the dynamics of a tear film during blinking and contact lens (CL) wear. The model extends previous work on pre-corneal tear film dynamics during blinking by coupling the partial differential equation for tear film thickness to a dynamic model for CL motion. We explore different models for eyelid motion and also account for possible voluntary and involuntary globe (eyeball) rotation that may accompany blinking. Boundary conditions for mass flux at the eyelids are also adapted to account for the presence and motion of the CL. Our predictions for CL motion compare reasonably with existing data. Away from the eyelids the pre-lens tear film (PrLTF) is shifted, relative to its pre-corneal counterpart, in the direction of CL motion. Near the eyelids, the inflow/outflow of fluid under the eyelids also influences the PrLTF profile. We also compare our PrLTF dynamics to existing in vivo tear film thickness measurements.
Predicting brain function status changes in critically ill patients via Machine learning
Authors: Yan Chao , Gao Cheng , Zhang Ziqi , Chen Wencong , Malin Bradley A , Ely E Wesley , Patel Mayur B , Chen You
Published: July 2021

Objective

In intensive care units (ICUs), a patient’s brain function status can shift from a state of acute brain dysfunction (ABD) to one that is ABD-free and vice versa, which is challenging to forecast and, in turn, hampers the allocation of hospital resources. We aim to develop a machine learning model to predict next-day brain function status changes.

Materials and Methods

Using multicenter prospective adult cohorts involving medical and surgical ICU patients from 2 civilian and 3 Veteran Affairs hospitals, we trained and externally validated a light gradient boosting machine to predict brain function status changes. We compared the performances of the boosting model against state-of-the-art models—an ABD predictive model and its variants. We applied Shapley additive explanations to identify influential factors to develop a compact model.

Results

There were 1026 critically ill patients without evidence of prior major dementia, or structural brain diseases, from whom 12 295 daily transitions (ABD: 5847 days; ABD-free: 6448 days) were observed. The boosting model achieved an area under the receiver-operating characteristic curve (AUROC) of 0.824 (95% confidence interval [CI], 0.821-0.827), compared with the state-of-the-art models of 0.697 (95% CI, 0.693-0.701) with P < .001. Using 13 identified top influential factors, the compact model achieved 99.4% of the boosting model on AUROC. The boosting and the compact models demonstrated high generalizability in external validation by achieving an AUROC of 0.812 (95% CI, 0.812-0.813).

Conclusion

The inputs of the compact model are based on several simple questions that clinicians can quickly answer in practice, which demonstrates the model has direct prospective deployment potential into clinical practice, aiding in critical hospital resource allocation.
Community development with externalities and corrective taxation
Authors: Barseghyan Levon , Coate Stephen
Published: July 2021

This paper studies the impact of granting a community the authority to tax development when growth imposes negative externalities on existing residents. Taxes are chosen in each period by the residents who are fully forward-looking. Residents’ policy choices reflect not only the desire to counter negative externalities but also their wish to raise tax revenues and the value of their homes. There exists an equilibrium in which taxes are gradually lowered to close to optimal levels, resulting in falling housing prices and increasing community size. In addition, there exist equilibria in which taxes are set much too high and development is permanently stalled. In these equilibria, residents anticipate that lowering taxes will cause a sharp fall in the value of their homes. This multiplicity of equilibrium means that, for a broad range of initial conditions, allowing residents to tax development can increase or decrease social welfare. Regulating growth with zoning generates even worse outcomes, but allowing the community to charge developers impact fees does better.
Cross-Sectional Associations among Components of Injustice Appraisals and Functioning in Adolescents With Chronic Pain
Authors: Lynch Milder Mary K , Miller Megan M , Williams Amy E , Michel Martha A , Tolley James , Scott Eric L , Hirsh Adam T
Published: July 2021

Objective

Pain-related appraisals, including pain-related injustice, impact the development and maintenance of chronic pain. This cross-sectional study aimed to examine the relationship between the cognitive-emotional components of pain-related injustice—blame/unfairness and severity/irreparability of loss—and functioning in a mixed sample of adolescents with chronic pain.

Methods

Pediatric patients age 11–18 years (N = 408) completed forms assessing pain-related injustice, pain intensity, and physical and psychosocial functioning as part of their routine assessment in a pediatric chronic pain clinic between January 2014 and January 2019. A series of hierarchical regressions were used to evaluate the relationships among the separate components of pain-related injustice appraisals and functioning.

Results

Pain intensity and blame/unfairness appraisals were significantly associated with emotional functioning with blame/unfairness being the stronger association (β = −.27). Blame/unfairness appraisals, severity/irreparability appraisals, and pain intensity were significantly associated with physical functioning with pain intensity being the strongest association (β = .36). Pain intensity, blame/unfairness appraisals, and severity/irreparability appraisals were significantly associated with social functioning with blame/unfairness being the strongest association (β = −.34). Pain intensity and severity/irreparability appraisals were significantly associated with school functioning with severity/irreparability being the stronger association (β = −.19).

Conclusions

These results lend further support to incorporating pain-related injustice appraisals in standard clinical pain assessments. Treatment practices should target the specific injustice appraisals and domains of functioning impacted for each pediatric patient with chronic pain.
Digital clubbing as first sign of giant solitary fibrous tumor. A case report
Authors: Mejías-Lafontaine Emanuel , Galarza Sandra , Gonzalez-Cancel Ivan
Published: July 2021

Solitary fibrous tumors are rare pleural tumors. Most of the time they are benign tumors and identified incidentally once they cause symptoms secondary to their mass effect. Here we present an interesting case of a 54-year-old female found with a giant solitary fibrous tumor with signs of hypertrophic pulmonary osteoarthropathy with associated digital clubbing 6 month before identifying the tumor. The initial percutaneous biopsy revealed pathologic findings consistent with benign solitary fibrous tumor, but after complete mass excision diagnosis was upgraded to a malignant solitary fibrous tumor. Percutaneous biopsy results should not guide therapy in these patients; this is why complete excision continues to be the treatment of choice.
‘Spikelet stop’ determines the maximum yield potential stage in barley
Authors: Thirulogachandar Venkatasubbu , Schnurbusch Thorsten
Published: July 2021

Determining the grain yield potential contributed by grain number is a step towards advancing the yield of cereal crops. To achieve this aim, it is pivotal to recognize the maximum yield potential (MYP) of the crop. In barley (Hordeum vulgare L.), the MYP is defined as the maximum spikelet primordia number of a spike. Many barley studies assumed the awn primordium (AP) stage to be the MYP stage regardless of genotypes and growth conditions. From our spikelet-tracking experiments using the two-rowed cultivar Bowman, we found that the MYP stage can be different from the AP stage. Importantly, we find that the occurrence of inflorescence meristem deformation and its loss of activity coincided with the MYP stage, indicating the end of further spikelet initiation. Thus, we recommend validating the barley MYP stage with the shape of the inflorescence meristem and propose this approach (named ‘spikelet stop’) for MYP staging. To clarify the relevance of AP and MYP stages, we compared the MYP stage and the MYP in 27 barley accessions (two- and six-rowed accessions) grown in the greenhouse and in the field. Our results reveal that the MYP stage can be reached at various developmental stages, which greatly depend on the genotype and growth conditions. Furthermore, we propose that the MYP stage and the time to reach the MYP stage can be used to determine yield potential in barley. Based on our findings, we suggest key steps for the identification of the MYP stage in barley that may also be applied in a related crop such as wheat.
Morphometric relationships and their contribution to biomass and cannabinoid yield in hybrids of hemp (Cannabis sativa)
Authors: Carlson Craig H , Stack George M , Jiang Yu , Taşkıran Bircan , Cala Ali R , Toth Jacob A , Philippe Glenn , Rose Jocelyn K C , Smart Christine D , Smart Lawrence B
Published: July 2021

The breeding of hybrid cultivars of hemp (Cannabis sativa L.) is not well described, especially the segregation and inheritance of traits that are important for yield. A total of 23 families were produced from genetically diverse parents to investigate the inheritance of morphological traits and their association with biomass accumulation and cannabinoid yield. In addition, a novel classification method for canopy architecture was developed. The strong linear relationship between wet and dry biomass provided an accurate estimate of final dry stripped floral biomass. Of all field and aerial measurements, basal stem diameter was determined to be the single best selection criterion for final dry stripped floral biomass yield. Along with stem diameter, canopy architecture and stem growth predictors described the majority of the explainable variation of biomass yield. Within-family variance for morphological and cannabinoid measurements reflected the heterozygosity of the parents. While selfed populations suffered from inbreeding depression, hybrid development in hemp will require at least one inbred parent to achieve uniform growth and biomass yield. Nevertheless, floral phenology remains a confounding factor in selection because of its underlying influence on biomass production, highlighting the need to understand the genetic basis for flowering time in the breeding of uniform cultivars.
Does Chance Undermine Would?
Authors: Kocurek Alexander W
Published: July 2021

Counterfactual scepticism holds that most ordinary counterfactuals are false. The main argument for this view appeals to a ‘chance undermines would’ principle: if ψ would have some chance of not obtaining had ϕ obtained, then ϕ □→ ψ is false. This principle seems to follow from two fairly weak principles, namely, that ‘chance ensures could’ and that ϕ □→ ψ and ϕ ⋄→ ¬ ψ clash. Despite their initial plausibility, I show that these principles are independently problematic: given some modest closure principles, they entail absurdities. Moreover, on the most promising strategy for saving these principles, they do not, in the relevant sense, entail the chance-undermines-would principle. Instead, they entail a principle that only supports counterfactual indeterminism, the view that most ordinary counterfactuals are chancy, that is, not settled true. I demonstrate this by developing an indeterminist semantics that vindicates the clash and chance-ensures-could principles but not the chance-undermines-would principle. This view, I argue, offers a better account of our credal and linguistic judgements than counterfactual scepticism.
Discovery of orbital eccentricity and evidence for orbital period increase of SS433
Authors: Cherepashchuk A M , Belinski A A , Dodin A V , Postnov K A
Published: July 2021

The examination of long-term (1979–2020) photometric observations of SS433 enabled us to discover a non-zero orbital eccentricity of e = 0.05 ± 0.01. We have also found evidence for a secular increase in the orbital period at a rate of $\dot{P}_\mathrm{b}=(1.0\pm 0.3)\times 10^{-7}$ s s−1. The binary orbital period increase rate makes it possible to improve the estimate of the binary mass ratio q = MX/MV > 0.8, where MX and MV are the masses of the relativistic object and the optical star, respectively. For an optical star mass of 10 M⊙, the mass of the relativistic object (a black hole) is MX > 8 M⊙. A neutron star in SS433 is reliably excluded because in that case the orbital period should decrease, in contradiction to observations. The derived value of $\dot{P}_\mathrm{b}$ sets a lower limit on the mass-loss rate in the Jeans mode from the binary system ≳7 × 10−6 M⊙ yr−1. The discovered orbital ellipticity of SS433 is consistent with the model of the slaved accretion disc tracing the precession of the misaligned optical star’s rotational axis.
Trauma-Informed Care in Music Therapy: Principles, Guidelines, and a Clinical Case Illustration
Authors: Heiderscheit Annie , Murphy Kathleen M
Published: July 2021

The 2019 National Survey on Drug Use and Health reports that 9.5 million Americans aged 18 and older have been diagnosed with more than one mental disorder. Music therapists working in mental health treatment settings are likely to work with individuals who have a complex diagnosis defined here as 2 or more of the following: depression, eating disorder, generalized anxiety disorder, substance use disorder, and severe mental illness. Additionally, adverse childhood events or posttraumatic stress disorder often complicate the clinical profile. Given this, a trauma-informed approach to music therapy treatment is necessary to improve outcomes and minimize harm. The risks, contraindications, and ethical considerations necessary to effectively treat and care for these clients in music therapy will be reviewed. Methods of identifying, assessing, and treating these complex clinical issues in music therapy are discussed with the goal of helping clinicians understand: (1) where treatment needs to begin to ensure therapeutic goals addressing primary issues prior to addressing secondary issues and (2) the appropriate use of music therapy methods. The necessity for music therapists to understand the power of the music in the music therapy process is explored, to ensure that clinicians are meeting client needs, not triggering symptomatology, traumatic memories, or experiences. The importance of a clinician knowing their scope of practice, when they are adequately trained and prepared to work with clients with complex disorders, and how to utilize support such as consultation and supervision to support their effective treatment with client(s) is presented.
Pyrophosphate release acts as a kinetic checkpoint during high-fidelity DNA replication by the Staphylococcus aureus replicative polymerase PolC
Authors: Fagan Sean P , Mukherjee Purba , Jaremko William J , Nelson-Rigg Rachel , Wilson Ryan C , Dangerfield Tyler L , Johnson Kenneth A , Lahiri Indrajit , Pata Janice D
Published: July 2021

Bacterial replication is a fast and accurate process, with the bulk of genome duplication being catalyzed by the α subunit of DNA polymerase III within the bacterial replisome. Structural and biochemical studies have elucidated the overall properties of these polymerases, including how they interact with other components of the replisome, but have only begun to define the enzymatic mechanism of nucleotide incorporation. Using transient-state methods, we have determined the kinetic mechanism of accurate replication by PolC, the replicative polymerase from the Gram-positive pathogen Staphylococcus aureus. Remarkably, PolC can recognize the presence of the next correct nucleotide prior to completing the addition of the current nucleotide. By modulating the rate of pyrophosphate byproduct release, PolC can tune the speed of DNA synthesis in response to the concentration of the next incoming nucleotide. The kinetic mechanism described here would allow PolC to perform high fidelity replication in response to diverse cellular environments.
The clinical importance of tandem exon duplication-derived substitutions
Authors: Martinez Gomez Laura , Pozo Fernando , Walsh Thomas A , Abascal Federico , Tress Michael L
Published: July 2021

Most coding genes in the human genome are annotated with multiple alternative transcripts. However, clear evidence for the functional relevance of the protein isoforms produced by these alternative transcripts is often hard to find. Alternative isoforms generated from tandem exon duplication-derived substitutions are an exception. These splice events are rare, but have important functional consequences. Here, we have catalogued the 236 tandem exon duplication-derived substitutions annotated in the GENCODE human reference set. We find that more than 90% of the events have a last common ancestor in teleost fish, so are at least 425 million years old, and twenty-one can be traced back to the Bilateria clade. Alternative isoforms generated from tandem exon duplication-derived substitutions also have significantly more clinical impact than other alternative isoforms. Tandem exon duplication-derived substitutions have >25 times as many pathogenic and likely pathogenic mutations as other alternative events. Tandem exon duplication-derived substitutions appear to have vital functional roles in the cell and may have played a prominent part in metazoan evolution.
The splicing regulator SLU7 is required to preserve DNMT1 protein stability and DNA methylation
Authors: Recalde Miriam , Gárate-Rascón María , Elizalde María , Azkona María , Latasa M Ujue , Bárcena-Varela Marina , Sangro Bruno , Fernández-Barrena Maite G , Ávila Matías A , Arechederra María , Berasain Carmen
Published: July 2021

Gene expression is finely and dynamically controlled through the tightly coordinated and interconnected activity of epigenetic modulators, transcription and splicing factors and post-translational modifiers. We have recently identified the splicing factor SLU7 as essential for maintaining liver cell identity and genome integrity and for securing cell division both trough transcriptional and splicing mechanisms. Now we uncover a new function of SLU7 controlling gene expression at the epigenetic level. We show that SLU7 is required to secure DNMT1 protein stability and a correct DNA methylation. We demonstrate that SLU7 is part in the chromatome of the protein complex implicated in DNA methylation maintenance interacting with and controlling the integrity of DNMT1, its adaptor protein UHRF1 and the histone methyl-transferase G9a at the chromatin level. Mechanistically, we found that SLU7 assures DNMT1 stability preventing its acetylation and degradation by facilitating its interaction with HDAC1 and the desubiquitinase USP7. Importantly, we demonstrate that this DNMT1 dependency on SLU7 occurs in a large panel of proliferating cell lines of different origins and in in vivo models of liver proliferation. Overall, our results uncover a novel and non-redundant role of SLU7 in DNA methylation and present SLU7 as a holistic regulator of gene expression.
eIF4G is retained on ribosomes elongating and terminating on short upstream ORFs to control reinitiation in yeast
Authors: Mohammad Mahabub Pasha , Smirnova Anna , Gunišová Stanislava , Valášek Leoš Shivaya
Published: July 2021

Translation reinitiation is a gene-specific translational control mechanism. It is characterized by the ability of short upstream ORFs to prevent full ribosomal recycling and allow the post-termination 40S subunit to resume traversing downstream for the next initiation event. It is well known that variable transcript-specific features of various uORFs and their prospective interactions with initiation factors lend them an unequivocal regulatory potential. Here, we investigated the proposed role of the major initiation scaffold protein eIF4G in reinitiation and its prospective interactions with uORF’s cis-acting features in yeast. In analogy to the eIF3 complex, we found that eIF4G and eIF4A but not eIF4E (all constituting the eIF4F complex) are preferentially retained on ribosomes elongating and terminating on reinitiation-permissive uORFs. The loss of the eIF4G contact with eIF4A specifically increased this retention and, as a result, increased the efficiency of reinitiation on downstream initiation codons. Combining the eIF4A-binding mutation with that affecting the integrity of the eIF4G1–RNA2-binding domain eliminated this specificity and produced epistatic interaction with a mutation in one specific cis-acting feature. We conclude that similar to humans, eIF4G is retained on ribosomes elongating uORFs to control reinitiation also in yeast.
Reliability and validity of a novel cognitive self-assessment tool for patients with cancer
Authors: Zarrella Giuliana V , Perez Alice , Dietrich Jorg , Parsons Michael W
Published: July 2021

Background

Subjective cognitive function is an important outcome measure in oncology. The Functional Assessment of Cancer Therapy—Brain (FACT-Br) is a quality of life (QoL) measure that includes indices of physical, emotional, social, and neurologic aspects of disease but does not measure cognitive function. This study seeks to validate a novel index of cognition derived from the FACT-Br.

Methods

Patients with heterogeneous cancer diagnoses (N = 214) completed neuropsychological evaluation and self-report measures. Nine FACT-Br items regarding cognition were combined to form the FACT-Br-cognitive index (CI). Reliability was evaluated by exploratory factor analysis and internal consistency. Concurrent validity was assessed by correlating FACT-Br-CI with the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive-8 scales. Discriminant validity was assessed by correlating FACT-Br-CI with other FACT-Br indices and the Beck Depression and Anxiety Inventories (BDI, BAI). Exploratory analyses evaluated the impact of cognitive performance and disease variables on FACT-Br-CI.

Results

The FACT-Br-CI consisted of a single factor that demonstrated high internal consistency (α = 0.867) and strong concurrent validity, correlating strongly with PROMIS Cognitive-8 scales (r = 0.675-0.782). The relationship between the FACT-Br-CI and other FACT subscales ranged from moderate to strong (r = 0.372-0.601), as did correlations with measures of depression (BDI, r = −0.621) and anxiety (BAI, r = −0.450). Modest correlations were observed with neuropsychological measures (rs = 0.249-0.300).

Conclusions

The FACT-Br-CI is a reliable and valid measure of self-reported cognition. Studies that included the FACT-Br could be retrospectively analyzed to assess subjective cognitive outcomes, enriching the information from prior research. Integration of the FACT-Br-CI in routine clinical care may be an efficient method of monitoring cognition.
Occupational burnout among clinical research associates in China
Authors: Fu Z , Yuan Y , Jiang M
Published: July 2021

Background

Clinical research associates (CRAs) play an important role in pharmaceutical research and development. Despite growing concern about occupational burnout among CRAs in China, little is known about this topic.

Aims

We evaluated the factors associated with occupational burnout among CRAs in China and assessed the extent and nature of this syndrome in order to develop effective countermeasures.

Methods

In October 2020, we collected data from a convenience sample of 438 CRAs from 26 major cities across China using a custom-designed questionnaire. We evaluated their psychopathological status and degree of occupational burnout based on the Maslach Burnout Inventory. Factors associated with burnout were identified using the Wilcoxon rank test, Kruskal–Wallis test, Spearman’s rank correlation and multivariable ordinal logistic regression.

Results

Of the 438 CRAs analyzed, 82% showed signs of occupational burnout, with a large proportion experiencing moderate burnout (50%). Burnout in Chinese CRAs manifested as emotional exhaustion (77%), depersonalization (66%) and low sense of accomplishment (15%). The severity of burnout was significantly affected by mode of working (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.04–2.34), average number of working hours per week (OR 1.68, 95% CI 1.14–2.46), support provided by the hospital (OR 3.13, 95% CI 1.40–6.99) and likelihood of receiving a promotion (OR 4.05, 95% CI 1.34–12.22) (all P < 0.05).

Conclusions

The incidence of occupational burnout among CRAs in China is high. Companies and hospitals must take effective measures to establish support systems for CRAs in order to alleviate this situation and thereby ensure the quality of clinical trials.
To Die Is Gain
Authors: Schellenberg Ryan S.
Published: July 2021

This chapter locates incarceration within a broader economy of violence in the Roman world. Prison was legible, it argues, in relation to embodied scripts of honor and shame, self-mastery and slavishness, and what might be called the somatic grammar of subjugation. Among the elite, who were accustomed to bodily inviolability, imprisonment breached a key symbolic boundary that distinguished persons of honor from those subject to them. For Paul, however, as for others among the non-elite, prison was an acute instance of an all too familiar reality—namely, subjection to the mastery of more powerful men. Paul’s desire to die and be with Christ (Phil 1:23) must therefore be read alongside his vision of glorious somatic transformation, a transformation that is also and not incidentally an inversion of power relations, with Paul now sharing the sovereign glory of Christ, before whom all knees must finally bow.
Conscious Mind, Resonant Brain
Authors: Grossberg Stephen
Published: July 2021

The book is the culmination of 50 years of intensive research by the author, who is broadly acknowledged to be the most important pioneer and current research leader who models how brains give rise to minds, notably how neural circuits in multiple brain regions interact together to generate psychological functions. The book provides a unified understanding of how, where, and why our brains can consciously see, hear, feel, and know about the world, and effectively plan and act within it. It hereby embodies a revolutionary Principia of Mind that clarifies how autonomous adaptive intelligence is achieved, thereby providing mechanistic explanations of multiple mental disorders, biological bases of morality, religion, and the human condition, as well as solutions to large-scale problems in machine learning, technology, and Artificial Intelligence. Because brains embody a universal developmental code, unifying insights also emerge about all living cellular tissues and about how mental laws reflect laws of the physical world.