bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Work and the ‘Social Doctor’: Bowlby, Social Reproduction and ‘Common Sense’
Authors: Garrett Paul Michael
Published: July 2022

This article furnishes a critical commentary on the work of John Bowlby. It is argued that social work’s critical engagement with his contributions demands that his ideas are historised. An exploration of his rarely examined early articles reveals a figure preoccupied with the wider social world and not simply the dyadic relationship involving the mother and her child. Viewing himself as a ‘social doctor’, Bowlby was also relentlessly intent on shaping public and professional perceptions within the framework of the ‘Fordist’ economic and social settlement after the Second World War. It is maintained that Bowlby and ‘Bowlbyism’ might be more fully understood if examined through the lens of Marxist feminist social reproduction theory and alongside Gramscian ideas about ‘common sense’.
Comparison of four medium cut-off dialyzers
Authors: Maduell Francisco , Broseta José Jesús , Rodríguez-Espinosa Diana , del Risco Jimena , Rodas Lida María , Arias-Guillén Marta , Vera Manel , Fontseré Néstor , Salgado Maria del Carmen , Rico Nayra
Published: July 2022

Background

Recently, several pharmaceutical companies have developed new medium cut-off (MCO) dialyzers for expanded hemodialysis (HDx). This study aimed to compare the safety and efficacy of four MCO dialyzers, against each other and versus high-flux hemodialysis (HD) and post-dilution hemodiafiltration (HDF).

Methods

A prospective study was carried out on 23 patients who underwent six dialysis sessions: two sessions with the FX80 Cordiax in HD and HDF, and four HDx sessions with the Phylther 17-SD, Vie-18X, Elisio HX19 and Theranova 400 dialyzers. The reduction ratios (RRs) of urea, creatinine, β2-microglobulin, myoglobin, kappa free immunoglobulin light chain (κFLC), prolactin, α1-microglobulin, α1-acid glycoprotein, lambda (λFLC) and albumin were compared. Dialysate albumin loss was also measured.

Results

The differences in efficacy between the evaluated dialyzers were minimal in small molecules and even up to the size of β2-microglobulin. The main differences were found between myoglobin, κFLC, prolactin, α1-microglobulin and λFLC RRs, in which all four MCO dialyzers, with similar efficacy, were clearly superior to HD and slightly inferior to HDF treatment. Albumin losses in the dialysate with HD dialyzers were <1 g and between 1.5 and 2.5 g in HDx and HDF. The global removal score values were similar in all four HDx treatments, and again significantly higher than those with HD.

Conclusions

The results of the four MCO dialyzers evaluated in this study showed good efficiency, with no significant performance differences between them while being completely safe in terms of albumin loss. Likewise, the study confirms the superiority of HDx over high-flux HD with an efficacy close to that of post-dilution HDF.
Association of eosinophilic esophagitis with autoimmune and connective tissue disorders, and the impact on treatment response
Authors: Xue Zeyun , Miller Talya L , Abramson Lior , Thakkar Kisan P , Ketchem Corey J , Reddy Sumana , Greenberg Sydney B , Abichandani Sonia , Chang Nicole C , Eluri Swathi , Reed Craig C , Dellon Evan S
Published: July 2022

Eosinophilic esophagitis (EoE) has been associated with autoimmune (AI) and connective tissue disorders (CTDs), but clinical correlates and treatment response to topical corticosteroids (tCS) for patients with both conditions are not well known. We aimed to determine the prevalence and clinical features of AI/CTDs in EoE patients, and assess the response to tCS. In this retrospective cohort study of adults and children newly diagnosed with EoE in the University of North Carolina EoE Clinicopathologic database, we extracted clinical characteristics and treatment response data. We compared EoE patients with and without AI/CTDs, identified independently associated factors, and explored treatment responses. Of 1029 EoE patients, 61 (5.9%) had an AI/CTDs. The most common AI/CTDs were psoriasis/psoriatic arthritis (P/PA) (1.7%), Hashimoto’s (1.2%), and rheumatoid arthritis (RA) (1%). Compared to those without AI/CTDs, AI/CTDs patients were older (35 vs. 28 years, P = 0.004), more likely to be female (51% vs. 30%, P = 0.001), have insurance (93% vs. 78%, P = 0.004) and a longer symptom duration prior to EoE diagnosis (10 vs. 7 years, P = 0.02). Older age, female sex, having insurance, and having allergic rhinitis were independently associated with AI/CTDs. AI/CTD patients with EoE were less likely to have a symptom response (47% vs. 79%, P = 0.003). Overlap between EoE and AI/CTDs was uncommon, seen in approximately 6%, with P/PA, Hashimoto’s, and RA being most frequent. In conclusion, older age, female sex, having insurance, and allergic rhinitis were independently associated with AI/CTDs. EoE patients with AI/CTDs had less symptom response, with trendtowards lower endoscopic and histologic responses, to tCS therapy.
Low Rates of Breakthrough COVID-19 Infection After SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease
Authors: Weaver Kimberly N , Zhang Xian , Dai Xiangfeng , Chen Wenli , Watkins Runa , Adler Jeremy , Dubinsky Marla C , Kastl Arthur , Bousvaros Athos , Strople Jennifer A , Cross Raymond K , Higgins Peter D R , Ungaro Ryan C , Bewtra Meenakshi , Bellaguarda Emanuelle , Farraye Francis A , Craig Riley , Hernandez Cristian , Boccieri Margie E , Firestine Ann , Chun Kelly Y , Long Millie D , Kappelman Michael D
Published: July 2022

Lay Summary

We demonstrate low rates of breakthrough coronavirus disease 2019 (COVID-19) infection and mild course of illness following severe acute respiratory syndrome coronavirus 2 vaccination in a large cohort of inflammatory bowel disease patients. Residence in southern United States and lower median anti-receptor binding antibody level were associated with development of COVID-19.
Comment on “South Africa's experimental fisheries closures and recovery of the endangered African penguin” by Sydeman et al. (2021)
Authors: Butterworth D S , Ross-Gillespie A
Published: July 2022

An experiment involving alternating closures to pelagic fishing of the neighbourhoods around two pairs of nearby islands with breeding colonies of African penguins was initiated in South Africa in 2008, with the aim to determine the impact on penguin reproductive success. Based on their analyses of the experiment, Sydeman et al. (2021) assert that the closures reduce competition with fisheries on forage fish, and should be maintained. In contrast, based on analyses conducted in accordance with the recommendations of an international review panel, the South African Government's scientific committee responsible for overseeing and analysing the experiment conclude that when compared to the concerning decline over recent decades of some 5% pa in overall penguin abundance, the effect of maintaining such closures towards arresting that decline would at best be minimal. This Comment summarises the history of the experiment and associated analyses, and then points to a number of shortcomings of Sydeman et al. (2021), most seriously incorrect results from not adequately accounting for the effects of pseudoreplication. It is argued that the present priority is identifying the main factor(s) responsible for the penguin decline, since the experiment has shown that this is not fishing in the neighbourhood of penguin colonies.
Intensive and wide-ranging beach surveys uncover temporal and spatial stranding patterns of marine megafauna
Authors: Prado Jonatas H F , Daudt Nicholas W , Perez Martin S , Castilho Pedro V , Monteiro Danielle S
Published: July 2022

We describe the temporal and spatial patterns of three tetrapod groups (sea turtles, seabirds, and cetaceans) stranded in southeast Brazil, based on daily beach surveys of over >800 km of coastline between 2015 and 2020. Patterns were analysed by stranding rates (individuals/1000 km of coastline) of groups and species; for the 14 most numerous species, we also fitted generalized additive models for location, scale, and shape (GAMLSS) using temporal and spatial explanatory variables. We recorded 53850 animals (22738 sea turtles, 28155 birds, and 2957 cetaceans) of 78 species. Higher stranding numbers were observed during winter/spring for all groups, and could be an effect of a higher occurrence/abundance at the region, driven by productive waters, jointly with higher stranding probabilities due to stronger drifting forces. Most modelled species showed temporal and spatial stranding patterns most likely related to their general occurrence/abundance cycles in southeast Brazil, but for Caretta caretta, Chelonia mydas, Pontoporia blainvillei, and Sotalia guianensis local mortality factors may be influencing stranding numbers. By using intensive, wide ranging beach surveys and including survey effort in the analysis, we provide a comprehensive baseline for stranding numbers in the region, and open a pathway for future hypothesis-testing studies to investigate its drivers.
Exploring Finnic written oral folk poetry through string similarity
Authors: Janicki Maciej , Kallio Kati , Sarv Mari
Published: July 2022

Suomen Kansan Vanhat Runot (Old Poems of the Finnish People) is a collection of nearly 90,000 oral folk poems written down between 1564 and the early 20th century. It is characterized by frequent reoccurrence of similar pieces of text on various levels (from entire poems, through passages to single verses and collocations). However, finding these similarities is challenging due to a high degree of orthographical, morphological, and compositional variation. In this article, we propose a method for automatically identifying equivalent verses, i.e. verses conveying the same meaning with the same words, using a clustering based on cosine similarity of character bigram vectors. The method achieves around 81% F-score and has been successfully used for identifying similarities across the entire SKVR corpus on the level of verse, passage, and poem. The results can be browsed through a Web interface.
Dynamics of fast and slow magnetoacoustic waves in plasma slabs with thermal misbalance
Authors: Agapova D V , Belov S A , Molevich N E , Zavershinskii D I
Published: July 2022

The non-uniformity of the solar atmosphere along with the presence of non-adiabatic processes such as radiation cooling and unspecified heating can significantly affect the dynamics and properties of magnetoacoustic (MA) waves. To address the co-influence of these factors on the dispersion properties of MA waves, we considered a single magnetic slab composed of thermally active plasma. Using perturbation theory, we obtained a differential equation that determines the dynamics of the two-dimensional perturbations. Applying the assumption of strong magnetic structuring, we derived the dispersion relations for the sausage and kink MA modes. A numerical solution of the dispersion relations for coronal conditions was obtained to investigate the interplay between the non-uniformity and the thermal misbalance. For the heating scenario considered, it was found that the phase speed of both the sausage and the kink slow MA waves is strongly affected by the thermal misbalance in the long-wavelength limit. The obtained characteristic time-scales of the slow-wave dissipation coincide with the periods of waves observed in the corona. The phase speed of the fast waves, however, is not affected by the thermal misbalance. The geometry of the magnetic structure remains the main dispersion mechanism for the fast waves. Our analysis reveals that the dissipation of the fast waves is weaker than the dissipation of the slow waves under coronal conditions. The obtained results are of importance for the use of MA waves as a tool for estimating not only plasma parameters but also non-adiabatic processes.
Bayesian data analysis for sky-averaged 21-cm experiments in the presence of ionospheric effects
Authors: Shen Emma , Anstey Dominic , de Lera Acedo Eloy , Fialkov Anastasia
Published: July 2022

The ionosphere introduces chromatic distortions on low frequency radio waves, and thus poses a hurdle for 21-cm cosmology. In this paper, we introduce time-varying chromatic ionospheric effects on simulated antenna temperature data of a global 21-cm data analysis pipeline, and try to detect the injected global signal. We demonstrate that given turbulent ionospheric conditions, more than 5 per cent error in our knowledge of the ionospheric parameters could lead to comparatively low evidence and high root-mean-square error (RMSE), suggesting a false or null detection. When using a constant antenna beam for cases that include data at different times, the significance of the detection lowers as the number of time samples increases. It is also shown that for observations that include data at different times, readjusting beam configurations according to the time-varying ionospheric conditions should greatly improve the significance of a detection, yielding higher evidences and lower RMSE, and that it is a necessary procedure for a successful detection when the ionospheric conditions are not ideal.
Introducing EMP-Pathfinder: modelling the simultaneous formation and evolution of stellar clusters in their host galaxies
Authors: Reina-Campos Marta , Keller Benjamin W , Kruijssen J M Diederik , Gensior Jindra , Trujillo-Gomez Sebastian , Jeffreson Sarah M R , Pfeffer Joel L , Sills Alison
Published: July 2022

The formation and evolution of stellar clusters is intimately linked to that of their host galaxies. To study this connection, we present the emp-Pathfindersuite of cosmological zoom-in Milky Way-mass simulations. These simulations contain a subgrid description for stellar cluster formation and evolution, allowing us to study the simultaneous formation and evolution of stellar clusters alongside their host galaxies across cosmic time. As a key ingredient in these simulations, we include the physics of the multiphase nature of the interstellar medium (ISM), which enables studies of how the presence of a cold, dense ISM affects star cluster formation and evolution. We consider two different star formation prescriptions: a constant star formation efficiency per free-fall time, as well as an environmentally dependent, turbulence-based prescription. We identify two key results drawn from these simulations. First, we find that the tidal shock-driven disruption caused by the graininess of the cold ISM produces old ($\tau \gt 10~\mbox{${\rm Gyr}$}$) stellar cluster populations with properties that are in excellent agreement with the observed populations in the Milky Way and M31. Importantly, the addition of the cold ISM addresses the areas of disagreement found in previous simulations that lacked the cold gas phase. Secondly, we find that the formation of stellar clusters is extremely sensitive to the baryonic physics that govern the properties of the cold, dense gas reservoir in the galaxy. This implies that the demographics of the stellar cluster population represent an important diagnostic tool for constraining baryonic physics models in upcoming galaxy formation simulations that also include a description of the cold ISM.
A new method to correct for host star variability in multiepoch observations of exoplanet transmission spectra
Authors: Panwar Vatsal , Désert Jean-Michel , Todorov Kamen O , Bean Jacob L , Stevenson Kevin B , Huitson C M , Fortney Jonathan J , Bergmann Marcel
Published: July 2022

Transmission spectra of exoplanets orbiting active stars suffer from wavelength-dependent effects due to stellar photospheric heterogeneity. WASP-19b, an ultra-hot Jupiter (Teq ∼ 2100 K), is one such strongly irradiated gas-giant orbiting an active solar-type star. We present optical (520–900 nm) transmission spectra of WASP-19b obtained across eight epochs, using the Gemini Multi-Object Spectrograph (GMOS) on the Gemini-South telescope. We apply our recently developed Gaussian Processes regression based method to model the transit light-curve systematics and extract the transmission spectrum at each epoch. We find that WASP-19b’s transmission spectrum is affected by stellar variability at individual epochs. We report an observed anticorrelation between the relative slopes and offsets of the spectra across all epochs. This anticorrelation is consistent with the predictions from the forward transmission models, which account for the effect of unocculted stellar spots and faculae measured previously for WASP-19. We introduce a new method to correct for this stellar variability effect at each epoch by using the observed correlation between the transmission spectral slopes and offsets. We compare our stellar variability corrected GMOS transmission spectrum with previous contradicting MOS measurements for WASP-19b and attempt to reconcile them. We also measure the amplitude and timescale of broad-band stellar variability of WASP-19 from TESS photometry, which we find to be consistent with the effect observed in GMOS spectroscopy and ground-based broad-band photometric long-term monitoring. Our results ultimately caution against combining multiepoch optical transmission spectra of exoplanets orbiting active stars before correcting each epoch for stellar variability.
PHF20 is crucial for epigenetic control of starvation-induced autophagy through enhancer activation
Authors: Park Se Won , Kim Jaehoon , Oh Sungryong , Lee Jeongyoon , Cha Joowon , Lee Hyun Sik , Kim Keun Il , Park Daechan , Baek Sung Hee
Published: July 2022

Autophagy is a catabolic pathway that maintains cellular homeostasis under various stress conditions, including conditions of nutrient deprivation. To elevate autophagic flux to a sufficient level under stress conditions, transcriptional activation of autophagy genes occurs to replenish autophagy components. Thus, the transcriptional and epigenetic control of the genes regulating autophagy is essential for cellular homeostasis. Here, we applied integrated transcriptomic and epigenomic profiling to reveal the roles of plant homeodomain finger protein 20 (PHF20), which is an epigenetic reader possessing methyl binding activity, in controlling the expression of autophagy genes. Phf20 deficiency led to impaired autophagic flux and autophagy gene expression under glucose starvation. Interestingly, the genome-wide characterization of chromatin states by Assay for Transposase-Accessible Chromatin (ATAC)-sequencing revealed that the PHF20-dependent chromatin remodelling occurs in enhancers that are co-occupied by dimethylated lysine 36 on histone H3 (H3K36me2). Importantly, the recognition of H3K36me2 by PHF20 was found to be highly correlated with increased levels of H3K4me1/2 at the enhancer regions. Collectively, these results indicate that PHF20 regulates autophagy genes through enhancer activation via H3K36me2 recognition as an epigenetic reader. Our findings emphasize the importance of nuclear events in the regulation of autophagy.
Targeted de novo phasing and long-range assembly by template mutagenesis
Authors: Li Siran , Park Sarah , Ye Catherine , Danyko Cassidy , Wroten Matthew , Andrews Peter , Wigler Michael , Levy Dan
Published: July 2022

Short-read sequencers provide highly accurate reads at very low cost. Unfortunately, short reads are often inadequate for important applications such as assembly in complex regions or phasing across distant heterozygous sites. In this study, we describe novel bench protocols and algorithms to obtain haplotype-phased sequence assemblies with ultra-low error for regions 10 kb and longer using short reads only. We accomplish this by imprinting each template strand from a target region with a dense and unique mutation pattern. The mutation process randomly and independently converts ∼50% of cytosines to uracils. Sequencing libraries are made from both mutated and unmutated templates. Using de Bruijn graphs and paired-end read information, we assemble each mutated template and use the unmutated library to correct the mutated bases. Templates are partitioned into two or more haplotypes, and the final haplotypes are assembled and corrected for residual template mutations and PCR errors. With sufficient template coverage, the final assemblies have per-base error rates below 10–9. We demonstrate this method on a four-member nuclear family, correctly assembling and phasing three genomic intervals, including the highly polymorphic HLA-B gene.
Enhanced polymerase activity permits efficient synthesis by cancer-associated DNA polymerase ϵ variants at low dNTP levels
Authors: Barbari Stephanie R , Beach Annette K , Markgren Joel G , Parkash Vimal , Moore Elizabeth A , Johansson Erik , Shcherbakova Polina V
Published: July 2022

Amino acid substitutions in the exonuclease domain of DNA polymerase ϵ (Polϵ) cause ultramutated tumors. Studies in model organisms suggested pathogenic mechanisms distinct from a simple loss of exonuclease. These mechanisms remain unclear for most recurrent Polϵ mutations. Particularly, the highly prevalent V411L variant remained a long-standing puzzle with no detectable mutator effect in yeast despite the unequivocal association with ultramutation in cancers. Using purified four-subunit yeast Polϵ, we assessed the consequences of substitutions mimicking human V411L, S459F, F367S, L424V and D275V. While the effects on exonuclease activity vary widely, all common cancer-associated variants have increased DNA polymerase activity. Notably, the analog of Polϵ-V411L is among the strongest polymerases, and structural analysis suggests defective polymerase-to-exonuclease site switching. We further show that the V411L analog produces a robust mutator phenotype in strains that lack mismatch repair, indicating a high rate of replication errors. Lastly, unlike wild-type and exonuclease-dead Polϵ, hyperactive variants efficiently synthesize DNA at low dNTP concentrations. We propose that this characteristic could promote cancer cell survival and preferential participation of mutator polymerases in replication during metabolic stress. Our results support the notion that polymerase fitness, rather than low fidelity alone, is an important determinant of variant pathogenicity.
Benchmarking computational methods for B-cell receptor reconstruction from single-cell RNA-seq data
Authors: Andreani Tommaso , Slot Linda M , Gabillard Samuel , Strübing Carsten , Reimertz Claus , Yaligara Veeranagouda , Bakker Aleida M , Olfati-Saber Reza , Toes René E M , Scherer Hans U , Augé Franck , Šimaitė Deimantė
Published: July 2022

Multiple methods have recently been developed to reconstruct full-length B-cell receptors (BCRs) from single-cell RNA sequencing (scRNA-seq) data. This need emerged from the expansion of scRNA-seq techniques, the increasing interest in antibody-based drug development and the importance of BCR repertoire changes in cancer and autoimmune disease progression. However, a comprehensive assessment of performance-influencing factors such as the sequencing depth, read length or number of somatic hypermutations (SHMs) as well as guidance regarding the choice of methodology is still lacking. In this work, we evaluated the ability of six available methods to reconstruct full-length BCRs using one simulated and three experimental SMART-seq datasets. In addition, we validated that the BCRs assembled in silico recognize their intended targets when expressed as monoclonal antibodies. We observed that methods such as BALDR, BASIC and BRACER showed the best overall performance across the tested datasets and conditions, whereas only BASIC demonstrated acceptable results on very short read libraries. Furthermore, the de novo assembly-based methods BRACER and BALDR were the most accurate in reconstructing BCRs harboring different degrees of SHMs in the variable domain, while TRUST4, MiXCR and BASIC were the fastest. Finally, we propose guidelines to select the best method based on the given data characteristics.
Household inequality and remittances in rural Thailand: a life-cycle perspective
Authors: Disney Richard , McKay Andy , Shabab C Rashaad
Published: July 2022

This article studies the dynamics of income inequality among a panel of rural households in Thailand. In contrast to the many cross-section studies of income inequality, the article exploits a long panel data set to examine lifetime trajectories of household inequality. It finds that income inequality is decreasing over time within cohorts delineated by decennial birth dates of heads of household. This decline in inequality primarily arises from differences in receipt of remittances from adult children of the head of household who live outside the village of origin. On average, poorer households receive remittances from a larger number of children, the annual amount remitted per child is a greater proportion of household income than in richer households, and the importance of remittances in household incomes grows as the head of household ages.
Patient-Reported Outcomes in Early Phase Clinical Trials: An Opportunity to Actively Promote Patient-Centered Care
Authors: Bergerot Cristiane Decat , Pal Sumanta K , Tripathi Abhishek
Published: July 2022

This commentary highlights the potential relevance of including patient-reported outcomes in early phase trials and the barriers to such inclusion.
Temporal analysis of Lassa virus infection and transmission in experimentally infected Mastomys natalensis
Authors: Safronetz David , Rosenke Kyle , Meade-White Kimberley , Sloan Angela , Maiga Ousmane , Bane Sidy , Martellaro Cynthia , Scott Dana P , Sogoba Nafomon , Feldmann Heinz
Published: July 2022

Little is known about the temporal patterns of infection and transmission of Lassa virus (LASV) within its natural reservoir (Mastomys natalensis). Here, we characterize infection dynamics and transmissibility of a LASV isolate (Soromba-R) in adult lab-reared M. natalensis originating from Mali. The lab-reared M. natalenesis proved to be highly susceptible to LASV isolates from geographically distinct regions of West Africa via multiple routes of exposure, with 50% infectious doses of < 1 TCID50. Postinoculation, LASV Soromba-R established a systemic infection with no signs of clinical disease. Viral RNA was detected in all nine tissues examined with peak concentrations detected between days 7 and 14 postinfection within most organs. There was an overall trend toward clearance of virus within 40 days of infection in most organs. The exception is lung specimens, which retained positivity throughout the course of the 85-day study. Direct (contact) and indirect (fomite) transmission experiments demonstrated 40% of experimentally infected M. natalensis were capable of transmitting LASV to naïve animals, with peak transmissibility occurring between 28 and 42 days post-inoculation. No differences in patterns of infection or transmission were noted between male and female experimentally infected rodents. Adult lab-reared M. natalensis are highly susceptible to genetically distinct LASV strains developing a temporary asymptomatic infection associated with virus shedding resulting in contact and fomite transmission within a cohort.
A Puzzle with Missing Pieces: Explaining the Effectiveness of World Bank Development Projects
Authors: Ashton Louise , Friedman Jed , Goldemberg Diana , Hussain Mustafa Zakir , Kenyon Thomas , Khan Akib , Zhou Mo
Published: July 2022

The identification of key determinants of aid effectiveness is a long-standing question in the development community. This paper reviews the literature on aid effectiveness at the project level and then extends the inquiry in a variety of dimensions with new data on World Bank investment project financing. It confirms that the country institutional setting and quality of project supervision are associated with project success, as identified previously. However, many aspects of the development project cycle, especially project design, have been difficult to measure and therefore under-investigated. The paper finds that project design, as proxied by the estimated value added of design staff, the presence of prior analytic work, and other specially collected measures, is a significant predictor of ultimate project success. These factors generally grow in predictive importance as the income level of the country rises. The results also indicate that a key determinant of the staff's contribution is their experience with previous World Bank projects, but not other characteristics such as age, education, or country location. Key inputs to the project production process associated with subsequent performance are not captured in routine data systems, although it is feasible to do so. Further, the conceptualization and measurement of the success of project-based aid should be revisited by evaluative bodies to reflect a project's theorized contribution to development outcomes.
Chronic Drought Differentially Alters the Belowground Microbiome of Drought-Tolerant and Drought-Susceptible Genotypes of Populus trichocarpa
Authors: Kristy Brandon , Carrell Alyssa A. , Johnston Eric , Cumming Jonathan R. , Klingeman Dawn M. , Gwinn Kimberly , Syring Kimberly C. , Skalla Caroline , Emrich Scott , Cregger Melissa A.
Published: July 2022

Populus trichocarpa is an ecologically important tree species and economically important biofeedstock. Belowground, P. trichocarpa interacts with diverse microorganisms in the rhizosphere and root endosphere. These plant–microbe interactions can bolster a variety of plant processes, ranging from pathogen suppression to drought tolerance, yet we know little about the impact of chronic drought stress on P. trichocarpa’s belowground microbiomes. To investigate the interactive effect of chronic drought on belowground microbial communities across genetically different P. trichocarpa hosts, we assessed archaeal/bacterial and fungal communities within the root endosphere, rhizosphere, and surrounding bulk soil of selected genotypes in a long-term drought experiment in Boardman, OR, U.S.A. We sequenced the 16S ribosomal RNA and internal transcribed spacer 2 gene region on samples collected from 16 distinct P. trichocarpa genotypes in plots with full or reduced irrigation. Eight of these genotypes have been previously identified as drought tolerant while the other eight genotypes were drought susceptible. Although reduced irrigation influenced the composition of every archaeal or bacterial microbiome compartment, fungal communities were only affected in the rhizosphere and bulk soil compartments. Drought-tolerant bacteria such as Actinobacteria were differentially abundant in reduced irrigation across all belowground microbiomes. Host drought tolerance influenced plant-associated microbiome compartments but had little impact on the bulk soil compartment. Drought-tolerant trees were enriched for potential growth-promoting microorganisms in the root endosphere and rhizosphere, including Sphingomonas bacteria and ectomycorrhizal fungi. Overall, associations of growth-promoting microbes in drought-resistant P. trichocarpa genotypes can be leveraged to improve biofeedstock productivity in regions prone to periodic drought.
The REPAIR Project: A Prospectus for Change Toward Racial Justice in Medical Education and Health Sciences Research: REPAIR Project Steering Committee
Authors:   REPAIR Project Steering Committee
Published: July 2022

Amidst ongoing efforts to address racial injustice, U.S. medical institutions are grappling with the structural roots of anti-Black racism. The REPAIR (REParations and Anti-Institutional Racism) Project is a 3-year strategic initiative at the University of California, San Francisco aiming to address anti-Black racism and augment the presence and voices of people of color in science, medicine, and health care. The REPAIR Project was designed in response to an unmet need for critical dialogue, cross-disciplinary research, and curriculum development addressing structural racism. It offers a framework for thinking and acting to achieve repair in relation to racial injustice and is anchored by 3 concepts—reparations, abolition, and decolonization—which have been deployed as annual themes in academic years 2020–2021, 2021–2022, and 2022–2023, respectively.

The theme of medical reparations builds on the longstanding call for slavery reparations and the paying of debts owed to Black Americans for the harms of slavery. The REPAIR Project focuses on the specific debts owed to Black Americans for racial harm in health care settings. The theme of medical abolition examines the intersections of incarceration, policing, and surveillance in health care and the role of clinicians in furthering or stopping oppressive practices that bind patterns of Black incarceration to health and health care. The theme of decolonizing the health sciences targets “othering” practices entrenched in scientific methodologies that have arisen from colonial-era beliefs and practices around imperialism, including how the colonial-era concept of race contributes to ongoing racial harm.

In this article, the authors describe the REPAIR Project, preliminary outcomes from its first year, and potential future lines of inquiry for medical educators and health sciences researchers. The authors argue that the full damage from slavery and its legacies cannot be undone, but everyone can work in new ways that reduce or eliminate harm.
Learning Together: Co-Learning Among Faculty and Trainees in the Clinical Workplace
Authors: Haddock Lindsey , Rivera Josette , O’Brien Bridget C.
Published: July 2022

Purpose

Studies of workplace learning largely focus on how individuals (clinicians and trainees) learn in the clinical workplace. By focusing on individuals, these studies miss opportunities to explore the co-constructive nature of learning that may result in clinician–educators and trainees learning alongside each other (co-learning). The purpose of this study was to explore whether and how co-learning occurs in the workplace and what value co-learning holds.

Method

Using a constructivist grounded theory approach, the authors interviewed 34 faculty clinician–educators from 10 specialties at one academic institution to explore whether and how co-learning occurred in their practice and how faculty perceived its value for faculty and for trainees. Interviews were conducted and recorded June to December 2019. Through iterative analysis, the authors refined a conceptual model of co-learning.

Results

In a 3-part model of co-learning derived from faculty interviews, faculty and trainees jointly identify learning opportunities during work-related activities and choose learning strategies for learning that lead to interpretation and construction of meaning; these activities produce learning outcomes, such as understanding or insight. The model also accounts for asymmetry in experience and position between faculty and trainees. All faculty participants valued co-learning and elucidated barriers and facilitators to using it in the workplace. How faculty managed asymmetries shaped the nature of the co-learning. When faculty worked to lessen asymmetry between teacher and trainee, co-learning was often collaborative.

Conclusions

The model of co-learning makes explicit the concept of asymmetry in workplace learning and aids consideration of how related dynamics affect the nature of learning. Faculty must be intentional in managing asymmetries to fully leverage learning opportunities afforded by the workplace.
Application of Bayesian Methods to Help Interpret the VANCO Trial Results
Authors: O'Hara Nathan N. , Castillo Renan C. , Carlini Anthony R. , Joshi Manjari , Murray Clinton K. , Allen Lauren E. , Huang Yanjie , Gary Joshua L. , Bosse Michael J. , Obremskey William T. , McKinley Todd O. , Schmidt Andrew H. , O'Toole Robert V. ,   and METRC
Published: July 2022

Objective:

To determine whether a Bayesian analysis changes the results of the VANCO trial.

Design:

A secondary analysis of a randomized clinical trial using Bayesian methods.

Setting:

Thirty-six US trauma centers.

Patients:

Patients ages 18–80 years with a tibial plateau or pilon fracture deemed high risk of infection and definitively treated with plate and screw fixation.

Intervention:

Patients were randomly allocated to receive 1000 mg of intrawound vancomycin powder at their definitive fixation or to a control group that received no topical antibiotics.

Main Outcome Measurements:

A deep surgical site infection requiring operative treatment within 6 months of definitive fixation. Secondary outcomes included gram-positive and gram-negative–only deep surgical site infections.

Results:

Of the 980 patients randomized, 874 (89%) had at least 140 days of follow-up and were included in this Bayesian analysis. The estimated probability that intrawound vancomycin powder reduces the risk of a deep surgical site infection is >98% [relative risk (RR), 0.66; 95% credible interval (CrI), 0.46–0.98]. There is a >99% chance intrawound vancomycin powder reduces gram-positive infections and an 80% chance the magnitude of this risk reduction exceeds 35% (RR, 0.52; 95% CrI, 0.33–0.84) exists. It is unlikely (44%) that intrawound vancomycin powder prevents gram-negative surgical site infections (RR, 1.06; 95% CrI, 0.48–2.45).

Conclusions:

There is a high probability (>98%) that intrawound vancomycin powder reduces deep surgical site infections in patients with tibial plateau or pilon fractures at high risk of infection and even more likely it reduces deep infections with gram-positive pathogens (>99%).

Level of Evidence:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Burden of pancreatitis and associated risk factors in China, 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019
Authors: Han Ke , Chen Shimin , Song Yang , Du Chen , Gao Fei , Liu Shaohua , He Yao , Chai Ningli , Linghu Enqiang , Liu Miao
Published: July 2022

Background:

Pancreatitis is a common disease of the digestive system. Acute pancreatitis is one of the most common reasons for gastrointestinal hospital admission, and chronic pancreatitis significantly reduces quality of life. However, national epidemiological data on pancreatitis in China are lacking. This study aimed to quantify the disease burden of pancreatitis in China from 1990 to 2019.

Methods:

This study was based on the Global Burden of Disease Study 2019 dataset. Age-standardized rates of incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) were used to describe the disease burden of pancreatitis, and estimated annual percentage change (EAPC) was used to indicate the average change in age-standardized rates. We also described the trend of pancreatitis-related mortality and DALYs, which are attributable to alcohol use by age and sex.

Results:

From 1990 to 2019, the ASIR, ASPR, ASMR, and age-standardized DALYs of pancreatitis in China decreased by 10.90, 1.50, 0.49, and 15.54 per 100,000, respectively, with EAPCs of −1.35 (95% uncertainty interval [UI]: −1.67, −1.02) and −0.37 (95% UI: −0.43, −0.31), −2.01 (95% UI: −2.07, −1.94) and −2.32 (95% UI: −2.37, −2.28), respectively. Recently, the numbers of incident and prevalent cases have risen, with estimates of 380,018 (95% UI: 308,669–462,767) and 493,765 (95% UI: 416,705–578,675), respectively, in 2019. Among men, the disease burden of pancreatitis was more severe than among women, and with variances in the distribution among different age groups. Age-standardized DALYs caused by alcohol-related pancreatitis have gradually worsened in the past decade, accounting for 34.09% of the total in 2019.

Conclusions:

The disease burden of pancreatitis in China has declined in the past 30 years, but the exacerbation of population aging poses a challenge to prevention and control of pancreatitis. Alcohol use has gradually become an important factor in the disease burden of pancreatitis in recent years.
Treating non-small cell lung cancer by targeting the PI3K signaling pathway
Authors: Jiang Lin , Zhang Jingbo , Xu Yan , Xu Heng , Wang Mengzhao
Published: July 2022

The phosphosphatidylinositol-3-kinase (PI3K) signaling pathway is one of the most important intracellular signal transduction pathways affecting cell functions, such as apoptosis, translation, metabolism, and angiogenesis. Lung cancer is a malignant tumor with the highest morbidity and mortality rates in the world. It can be divided into two groups, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for >85% of all lung cancers. There are currently many clinical treatment options for NSCLC; however, traditional methods such as surgery, chemotherapy, and radiotherapy have not been able to provide patients with good survival benefits. The emergence of molecular target therapy has improved the survival and prognosis of patients with NSCLC. In recent years, there have been an increasing number of studies on NSCLC and PI3K signaling pathways. Inhibitors of various parts of the PI3K pathway have appeared in various phases of clinical trials with NSCLC as an indication. This article focuses on the role of the PI3K signaling pathway in the occurrence and development of NSCLC and summarizes the current clinical research progress and possible development strategies.
Gut microbiota: a new insight into neurological diseases
Authors: Liu Lanxiang , Wang Haiyang , Chen Xueyi , Xie Peng
Published: July 2022

In the last decade, it has become increasingly recognized that a balanced gut microbiota plays an important role in maintaining the health of the host. Numerous clinical and preclinical studies have shown that changes in gut microbiota composition are associated with a variety of neurological diseases, e.g., Parkinson's disease, Alzheimer's disease, and myasthenia gravis. However, the underlying molecular mechanisms are complex and remain unclear. Behavioral phenotypes can be transmitted from humans to animals through gut microbiota transplantation, indicating that the gut microbiota may be an important regulator of neurological diseases. However, further research is required to determine whether animal-based findings can be extended to humans and to elucidate the relevant potential mechanisms by which the gut microbiota regulates neurological diseases. Such investigations may aid in the development of new microbiota-based strategies for diagnosis and treatment and improve the clinical management of neurological disorders. In this review, we describe the dysbiosis of gut microbiota and the corresponding mechanisms in common neurological diseases, and discuss the potential roles that the intestinal microbiome may play in the diagnosis and treatment of neurological disorders.
Recurrent PTPN14 Mutations in Trichilemmoma: Evidence for Distinct Pathways of Molecular Pathogenesis
Authors: Russell-Goldman Eleanor , Dong Fei , Hanna John
Published: July 2022

Trichilemmoma is a benign cutaneous neoplasm that recapitulates the outer root sheath of the hair follicle. Trichilemmomas may occur sporadically or in association with Cowden syndrome, which is characterized by germline mutations in the lipid phosphatase PTEN (phosphatase and tensin homolog on chromosome 10). Interestingly, most sporadic trichilemmomas do not show PTEN aberrations, but rather activating mutations in HRAS. Despite these important advances, a comprehensive genetic analysis of trichilemmoma has not been reported. Here, we used a next-generation DNA sequencing platform to study 9 sporadic trichilemmoma cases. Seven cases (7/9; 78%) harbored activating mutations in HRAS, consistent with previous findings. Unexpectedly, we identified recurrent mutations in the tyrosine phosphatase PTPN14 (protein tyrosine phosphatase nonreceptor type 14) in 4 cases (4/9; 44%). Three of these cases also harbored HRAS mutations, whereas one case occurred in the absence of a HRAS mutation and showed evidence of biallelic inactivation of PTPN14. Finally, one case (1/9; 11%) showed biallelic inactivation of PTEN in the absence of a HRAS (or PTPN14) mutation. These data suggest at least 3 distinct pathways of molecular pathogenesis in sporadic trichilemmoma and identify PTPN14 as a potentially important contributor to trichilemmoma biology.
Virtual Reality Improves Patient Experience and Anxiety During In-office Carpal Tunnel Release
Authors: Miller McKenzie B. , Gabel Shelley A. , Gluf-Magar Lindsay C. , Haan Pam S. , Lin Judith C. , Clarkson James H. W.
Published: July 2022

Background:

This study examined how wide- awake local anesthesia no tourniquet (WALANT) surgery in the office versus the standard operating room (OR) impacts patient experience, and the effect wide awake virtual reality (WAVR) has in conjunction with WALANT on patient experience.

Methods:

This is a patient-reported outcome study of patients undergoing carpal tunnel release by a single surgeon between August 2017 and March 2021. Patients were classified by location; traditional OR versus WALANT in-office. In-office patients were further classified by whether they chose to use WAVR or not. Patients rated overall experience, enjoyability, and anxiety using a Likert scale (1–7).

Results:

The online survey had a 44.8% response rate. OR patients were twice as likely to report a neutral or negative experience (23% versus 11%, P = 0.03), significantly lower enjoyment scores (44% versus 20%, P = 0.0007)‚ and higher anxiety (42% versus 26%, P = 0.04) compared with office-based WALANT patients. With the addition of WAVR, office patients reported higher enjoyment than those who did not use WAVR (85% versus 73%, P = 0.05). Patients reporting an anxiety disorder were more likely to choose WAVR when compared with patients without anxiety disorder (73.8% versus 56.4%). When they chose WAVR, they had greater anxiolysis (79% versus 47%, P = 0.01)‚ and increased enjoyment (90% versus 59%, P = 0.005).

Conclusions:

This study demonstrates improved patient experience in the office setting, further amplified by WAVR. Preexisting anxiety disorder is a positive predictive variable toward the patients’ choice to use WAVR.
Effect of Collagenase A on Descemet Membrane Endothelial Keratoplasty Scroll Tightness
Authors: Moolla Luqmaan , Mimouni Michael , Din Nizar , Cohen Eyal , Slomovic Allan R. , Rootman David S. , Chan Clara C.
Published: July 2022

Purpose:

The scrolling properties of the Descemet membrane endothelial keratoplasty (DMEK) graft are essential for surgical success. Currently, there is limited knowledge on what dictates the tightness of the DMEK scroll. The purpose of this study was to determine the impact of temperature and protein digestion on DMEK graft scroll tightness.

Methods:

For the temperature experiment, a total of 28 eyes were used for this study. Scrolls in the cold group were kept at 4°C while scrolls in the hot group were kept at 37°C. Scroll width was recorded at the 5-, 15-, and 30-minute mark. For the protein digestion experiment, a total of 18 eyes were exposed to collagenase A (10 CDU/mL) in Optisol solution. Scroll width was recorded at the time points of 1, 3, 5, 10, and 20 minutes.

Results:

The results of the temperature experiment did not yield any statistically significant changes in the mean scroll width of the DMEK scrolls across both temperature ranges and observation times. For the protein digestion experiment, the mean scroll width grew from 1.85 mm to 2.13 mm from the beginning of the experiment until the final observation at 20 minutes. This is a 14.7% change over 20 minutes with a P value (<0.001), exemplifying a statistically significant change in scroll width.

Conclusions:

Temperature did not have any significant effect over scroll tightness, but scroll tightness decreased with collagenase exposure.