bluuebunny/crossref_metadata_2025 huggingface dataset:
Custom Plates in Orthognathic Surgery: A Single Surgeon’s Experience and Learning Curve
Authors: Fleury Christopher M. , Sayyed Adaah A. , Baker Stephen B.
Published: February 2022

Background:

Virtual surgical planning (VSP) now allows for the fabrication of custom plates in orthognathic surgery. The senior author was an early adopter, using VSP and stereolithographic splints for over a decade, before transitioning to custom plates in 2019. The authors present our experience and learning curve with this new technology and compare results to a prior cohort of orthognathic patients.

Methods:

A retrospective chart review identified patients undergoing orthognathic surgery with the senior author between 2016 and 2021. All underwent VSP and stereolithographic splint formation, and then either traditional or custom-plate fixation. Demographics, perioperative variables, and postoperative outcomes were analyzed. Traditional fixation consisted of craniomaxillofacial plates, bent intraoperatively by the surgeon to adapt to the facial skeleton. Custom plates were prefabricated and prebent to fit drill holes outlined by customized cutting guides.

Results:

Forty-three patients underwent surgery in the study period, 25 (58.1%) with traditional fixation hardware and 18 (41.9%) with custom plates. The surgical technique evolved throughout the custom-plate cohort, with the most recent technique involving custom maxillary plate fixation and traditional mandibular plate fixation. When comparing this group of patients to the prior cohort of traditional fixation patients, operative time significantly decreased (mean 233 minutes versus 283 minutes, P = 0.044), without significant difference in complications.

Conclusions:

Patient-specific cutting guides and custom plates allow for precise spatial positioning of the osteotomized jaw in the orthognathic surgery. Unsurprisingly, obstacles must be overcome in adopting this new technology; here, we outline our experience and technical modifications that have resulted in increased surgical efficiency with comparable outcomes.
Sliding Flap for the Wide Upper Eyelid Margin Defect After Cancer Removal
Authors: Mizobuchi Ryo , Nojiri Gaku , Uchiyama Mizuki , Shimizu Azusa , Kamimori Tomoki , Hayashi Ayato
Published: February 2022

Background:

Reconstruction of eyelid margin defects following resection of upper-eyelid skin malignancies is typically performed using a lower eyelid switch flap, including eyelash reconstruction. However, a subsequent procedure for flap separation, and prolonged swelling of the flap may occur as a complication.

Objective:

The authors performed anterior lamellar reconstruction using a sliding flap with excess upper eyelid skin, a procedure that is a less invasive and simpler.

Materials and Methods:

The authors performed anterior lamellar reconstruction using a sliding flap in 7 patients with full-thickness upper eyelid margin defect after skin cancer resection. The mean age of the patients was 76.0 years. The horizontal width of the defect in our cohort ranged from 11 to 25 mm and the vertical width ranged from 5 to 10 mm.

Results:

All the flaps and mucosal grafts were well taken, and none of the patients complained of lack of eyelash reconstruction. However, eyelid margin irregularity, possibly due to flap or mucosal graft contraction, was observed in 2 patients, and 1 patient developed keratoconjunctivitis.

Conclusions:

The sliding flap technique is a minimally invasive and simple procedure for wide eyelid margin reconstruction. However, 2 patients developed eyelid margin irregularities and 1 patient developed keratoconjunctivitis. Those complications might have occurred owing to the condition of posterior lamellar reconstruction. Therefore, for the successful use of a sliding flap for anterior lamellar reconstruction, the form of the eyelid edge and the choice of posterior lamellar reconstruction are key considerations. In future, we plan to establish a better reconstructive technique by accumulating more evidence.
Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Versus the Standard of Care Imaging in the Diagnosis of Peritoneal Carcinomatosis
Authors: Furtado Felipe S. , Wu Mark Z. , Esfahani Shadi A. , Ferrone Cristina R. , Blaszkowsky Lawrence S. , Clark Jeffrey W. , Ryan David P. , Goyal Lipika , Franses Joseph W. , Wo Jennifer Y. , Hong Theodore S. , Qadan Motaz , Tanabe Kenneth K. , Weekes Colin D. , Cusack James C. , Crafa Francesco , Mahmood Umar , Anderson Mark A. , Mojtahed Amirkasra , Hahn Peter F. , Caravan Peter , Kilcoyne Aoife , Vangel Mark , Striar Robin M. , Rosen Bruce R. , Catalano Onofrio A.
Published: February 2022

Objective:

To compare positron emission tomography (PET)/magnetic resonance imaging (MRI) to the standard of care imaging (SCI) for the diagnosis of peritoneal carcinomatosis (PC) in primary abdominopelvic malignancies.

Summary Background Data:

Identifying PC impacts prognosis and management of multiple cancer types.

Methods:

Adult subjects were prospectively and consecutively enrolled from April 2019 to January 2021. Inclusion criteria were: 1) acquisition of whole-body contrast-enhanced (CE) 18F-fluorodeoxyglucose PET/MRI, 2) pathologically confirmed primary abdominopelvic malignancies. Exclusion criteria were: 1) greater than 4 weeks interval between SCI and PET/MRI, 2) unavailable follow-up. SCI consisted of whole-body CE PET/computed tomography (CT) with diagnostic quality CT, and/or CE-CT of the abdomen and pelvis, and/or CE-MRI of the abdomen±pelvis. If available, pathology or surgical findings served as the reference standard, otherwise, imaging followup was used. When SCI and PET/MRI results disagreed, medical records were checked for management changes. Follow-up data were collected until August 2021.

Results:

One hundred sixty-four subjects were included, 85 (52%) were female, and the median age was 60 years (interquartile range 50–69). At a subject level, PET/MRI had higher sensitivity (0.97, 95% CI 0.86–1.00) than SCI (0.54, 95% CI 0.37–0.71), P < 0.001, without a difference in specificity, of 0.95 (95% CI 0.90–0.98) for PET/MRI and 0.98 (95% CI 0.93–1.00) for SCI, P ¼ 0.250. PET/MRI and SCI results disagreed in 19 cases. In 5/19 (26%) of the discordant cases, PET/MRI findings consistent with PC missed on SCI led to management changes.

Conclusion:

PET/MRI improves detection of PC compared with SCI which frequently changes management.
The Longitudinal Course of Low-anterior Resection Syndrome
Authors: Varghese Chris , Wells Cameron I. , O’Grady Greg , Christensen Peter , Bissett Ian P. , Keane Celia ,   on behalf of the Longitudinal LARS Group∗
Published: February 2022

Objective:

We aimed to better understand the longitudinal course of low anterior resection syndrome (LARS) to guide patient expectations and identify those at risk of persisting dysfunction.

Summary Background Data:

LARS describes disordered bowel function after rectal resection that significantly impacts quality of life.

Methods:

MEDLINE, EMBASE, CENTRAL, and CINAHL databases were systematically searched for studies that enrolled adults undergoing anterior resection for rectal cancer and used the LARS score to assess bowel function at ≥2 postoperative time points. Regression analyses were performed on deidentified patient-level data to identify predictors of change in LARS score from baseline (3–6months) to 12-months and 18–24 months.

Results:

Eight studies with a total of 701 eligible patients were included. The mean LARS score improved over time, from 29.4 (95% confidence interval 28.6–30.1) at baseline to 16.6 at 36 months (95% confidence interval 14.2%–18.9%). On multivariable analysis, a greater improvement in mean LARS score between baseline and 12 months was associated with no ileostomy formation [mean difference (MD) –1.7 vs 1.7, P < 0.001], and presence of LARS (major vs minor vs no LARS) at baseline (MD –3.8 vs –1.7 vs 5.4, P < 0.001). Greater improvement in mean LARS score between baseline and 18–24 months was associated with partial mesorectal excision vs total mesorectal excision (MD–8.6 vs 1.5, P < 0.001) and presence of LARS (major vs minor vs no LARS) at baseline (MD –8.8 vs –5.3 vs 3.4, P < 0.001).

Conclusions:

LARS improves by 18 months postoperatively then remains stable for up to 3 years. Total mesorectal excision, neoadjuvant radiotherapy, and ileostomy formation negatively impact upon bowel function recovery.
Introduction to the theme issue ‘Species' ranges in the face of changing environments’
Authors: Rafajlović Marina , Alexander Jake M. , Butlin Roger K. , Johannesson Kerstin
Published: February 2022

Understanding where, when and how species’ ranges will be modified is both a fundamental problem and essential to predicting how spatio-temporal environmental changes in abiotic and biotic factors impact biodiversity. Notably, different species may respond disparately to similar environmental changes: some species may overcome an environmental change only with difficulty or not at all, while other species may readily overcome the same change. Ranges may contract, expand or move. The drivers and consequences of this variability in species' responses remain puzzling. Importantly, changes in a species’ range creates feedbacks to the environmental conditions, populations and communities in its previous and current range, rendering population genetic, population dynamic and community processes inextricably linked. Understanding these links is critical in guiding biodiversity management and conservation efforts. This theme issue presents current thinking about the factors and mechanisms that limit and/or modify species' ranges. It also outlines different approaches to detect changes in species’ distributions, and illustrates cases of range modifications in several taxa. Overall, this theme issue highlights the urgency of understanding species' ranges but shows that we are only just beginning to disentangle the processes involved. One way forward is to unite ecology with evolutionary biology and empirical with modelling approaches.

This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
Mosaics of climatic stress across species' ranges: tradeoffs cause adaptive evolution to limits of climatic tolerance
Authors: Parmesan Camille , Singer Michael C.
Published: February 2022

Studies in birds and trees show climatic stresses distributed across species' ranges, not only at range limits. Here, new analyses from the butterflyEuphydryas edithareveal mechanisms generating these stresses: geographic mosaics of natural selection, acting on tradeoffs between climate adaptation and fitness traits, cause some range-central populations to evolve to limits of climatic tolerance, while others remain resilient. In one ecotype, selection for predator avoidance drives evolution to limits of thermal tolerance. In a second ecotype, the endangered Bay Checkerspot, selection on fecundity drives evolution to the climate-sensitive limit of ability to complete development within the lifespans of ephemeral hosts, causing routinely high mortality from insect–host phenological asynchrony. The tradeoff between maternal fecundity and offspring mortality generated similar values of fitness on different dates, partly explaining why fecundity varied by more than an order of magnitude. Evolutionary response to the tradeoff rendered climatic variability the main driver of Bay Checkerspot dynamics, and increases in this variability, associated with climate change, were a key factor behind permanent extinction of a protected metapopulation. Finally, we discuss implications for conservation planning of our finding that adaptive evolution can reduce population-level resilience to climate change and generate geographic mosaics of climatic stress.

This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
Effects of species interactions on the potential for evolution at species' range limits
Authors: Alexander Jake M. , Atwater Daniel Z. , Colautti Robert I. , Hargreaves Anna L.
Published: February 2022

Species’ ranges are limited by both ecological and evolutionary constraints. While there is a growing appreciation that ecological constraints include interactions among species, like competition, we know relatively little about how interactions contribute to evolutionary constraints at species' niche and range limits. Building on concepts from community ecology and evolutionary biology, we review how biotic interactions can influence adaptation at range limits by impeding the demographic conditions that facilitate evolution (which we term a ‘demographic pathway to adaptation’), and/or by imposing evolutionary trade-offs with the abiotic environment (a ‘trade-offs pathway’). While theory for the former is well-developed, theory for the trade-offs pathway is not, and empirical evidence is scarce for both. Therefore, we develop a model to illustrate how fitness trade-offs along biotic and abiotic gradients could affect the potential for range expansion and niche evolution following ecological release. The model shows that which genotypes are favoured at species' range edges can depend strongly on the biotic context and the nature of fitness trade-offs. Experiments that characterize trade-offs and properly account for biotic context are needed to predict which species will expand their niche or range in response to environmental change.

This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
Understanding the biology of species' ranges: when and how does evolution change the rules of ecological engagement?
Authors: Bridle Jon , Hoffmann Ary
Published: February 2022

Understanding processes that limit species' ranges has been a core issue in ecology and evolutionary biology for many decades, and has become increasingly important given the need to predict the responses of biological communities to rapid environmental change. However, we still have a poor understanding of evolution at range limits and its capacity to change the ecological ‘rules of engagement’ that define these communities, as well as the time frame over which this occurs. Here we link papers in the current volume to some key concepts involved in the interactions between evolutionary and ecological processes at species' margins. In particular, we separate hypotheses about species’ margins that focus on hard evolutionary limits, which determine how genotypes interact with their environment, from those concerned with soft evolutionary limits, which determine where and when local adaptation can persist in space and time. We show how theoretical models and empirical studies highlight conditions under which gene flow can expand local limits as well as contain them. In doing so, we emphasize the complex interplay between selection, demography and population structure throughout a species' geographical and ecological range that determines its persistence in biological communities. However, despite some impressively detailed studies on range limits, particularly in invertebrates and plants, few generalizations have emerged that can predict evolutionary responses at ecological margins. We outline some directions for future work such as considering the impact of structural genetic variants and metapopulation structure on limits, and the interaction between range limits and the evolution of mating systems and non-random dispersal.

This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
Population genomics of Bacillus anthracis from an anthrax hyperendemic area reveals transmission processes across spatial scales and unexpected within-host diversity
Authors: Forde Taya L. , Dennis Tristan P. W. , Aminu O. Rhoda , Harvey William T. , Hassim Ayesha , Kiwelu Ireen , Medvecky Matej , Mshanga Deogratius , Van Heerden Henriette , Vogel Adeline , Zadoks Ruth N. , Mmbaga Blandina T. , Lembo Tiziana , Biek Roman
Published: February 2022

Genomic sequencing has revolutionized our understanding of bacterial disease epidemiology, but remains underutilized for zoonotic pathogens in remote endemic settings. Anthrax, caused by the spore-forming bacterium

Bacillus anthracis

, remains a threat to human and animal health and rural livelihoods in low- and middle-income countries. While the global genomic diversity of

B. anthracis

has been well-characterized, there is limited information on how its populations are genetically structured at the scale at which transmission occurs, critical for understanding the pathogen’s evolution and transmission dynamics. Using a uniquely rich dataset, we quantified genome-wide SNPs among 73

B. anthracis

isolates derived from 33 livestock carcasses sampled over 1 year throughout the Ngorongoro Conservation Area, Tanzania, a region hyperendemic for anthrax. Genome-wide SNPs distinguished 22 unique

B. anthracis

genotypes (i.e. SNP profiles) within the study area. However, phylogeographical structure was lacking, as identical SNP profiles were found throughout the study area, likely the result of the long and variable periods of spore dormancy and long-distance livestock movements. Significantly, divergent genotypes were obtained from spatio-temporally linked cases and even individual carcasses. The high number of SNPs distinguishing isolates from the same host is unlikely to have arisen during infection, as supported by our simulation models. This points to an unexpectedly wide transmission bottleneck for

B. anthracis

, with an inoculum comprising multiple variants being the norm. Our work highlights that inferring transmission patterns of

B. anthracis

from genomic data will require analytical approaches that account for extended and variable environmental persistence, as well as co-infection.
Optimal intervention strategies for minimizing total incidence during an epidemic
Authors: Britton Tom , Leskelä Lasse
Published: February 2022

This article considers the minimization of the total number of infected individuals over the course of an epidemic in which the rate of infectious contacts can be reduced by time-dependent nonpharmaceutical interventions. The societal and economic costs of interventions are taken into account using a linear budget constraint which imposes a trade-off between short-term heavy interventions and long-term light interventions. We search for an optimal intervention strategy in an infinite-dimensional space of controls containing multiple consecutive lockdowns, gradually imposed and lifted restrictions, and various heuristic controls based for example on tracking the effective reproduction number. Mathematical analysis shows that among all such strategies, the global optimum is achieved by a single constant-level lockdown of maximum possible magnitude. Numerical simulations highlight the need of careful timing of such interventions, and illustrate their benefits and disadvantages compared to strategies designed for minimizing peak prevalence. Rather counterintuitively, adding restrictions prior to the start of a well-planned intervention strategy may even increase the total incidence.
Automated identification of unstandardized medication data: A scalable and flexible data standardization pipeline using RxNorm on GEMINI multicenter hospital data
Authors: Waters Riley , Malecki Sarah , Lail Sharan , Mak Denise , Saha Sudipta , Jung Hae Young , Razak Fahad , Verma Amol
Published: February 2022

Objective

Patient data repositories often assemble medication data from multiple sources, necessitating standardization prior to analysis. We implemented and evaluated a medication standardization procedure for use with a wide range of pharmacy data inputs across all drug categories, which supports research queries at multiple levels of granularity.

Methods

The GEMINI-RxNorm system automates the use of multiple RxNorm tools in tandem with other datasets to identify drug concepts from pharmacy orders. GEMINI-RxNorm was used to process 2,090,155 pharmacy orders from 245,258 hospitalizations between 2010 and 2017 at 7 hospitals in Ontario, Canada. The GEMINI-RxNorm system matches drug-identifying information from pharmacy data (including free-text fields) to RxNorm concept identifiers. A user interface allows researchers to search for drug terms and returns the relevant original pharmacy data through the matched RxNorm concepts. Users can then manually validate the predicted matches and discard false positives. We designed the system to maximize recall (sensitivity) and enable excellent precision (positive predictive value) with minimal manual validation. We compared the performance of this system to manual coding (by a physician and pharmacist) of 13 medication classes.

Results

Manual coding was performed for 1,948,817 pharmacy orders and GEMINI-RxNorm successfully returned 1,941,389 (99.6%) orders. Recall was greater than 98.5% in all 13 drug classes, and the F-Measure and precision remained above 90.0% in all drug classes, facilitating efficient manual review to achieve 100.0% precision. GEMINI-RxNorm saved time substantially compared to manual standardization, reducing the time taken to review a pharmacy order row from an estimated 30 seconds to 5 seconds and reducing the number of rows needed to be reviewed by up to 99.99%.

Discussion and Conclusion

GEMINI-RxNorm presents a novel combination of RxNorm tools and other datasets to enable accurate, efficient, flexible, and scalable standardization of pharmacy data. By facilitating efficient minimal manual validation, the GEMINI-RxNorm system can allow researchers to achieve near-perfect accuracy in medication data standardization.
SPECIFICATIONS OF THE ACMG/AMP VARIANT CURATION GUIDELINES FOR MYOCILIN: RECOMMENDATIONS FROM THE CLINGEN GLAUCOMA EXPERT PANEL
Authors: Burdon Kathryn P , Graham Patricia , Hadler Johanna , Hulleman John D , Pasutto Francesca , Boese Erin A , Craig Jamie E , Fingert John H , Hewitt Alex W , Siggs Owen M , Whisenhunt Kristina , Young Terri L , Mackey David A , Dubowsky Andrew , Souzeau Emmanuelle
Published: February 2022

The standardization of variant curation criteria is essential for accurate interpretation of genetic results and clinical care of patients. The variant curation guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 are widely used but are not gene specific. To address this issue, the Clinical Genome Resource (ClinGen) Variant Curation Expert Panels (VCEP) have been tasked with developing gene-specific variant curation guidelines. The Glaucoma VCEP was created to develop rule specifications for genes associated with primary glaucoma, including myocilin (MYOC), the most common cause of Mendelian glaucoma. Of the 28 ACMG/AMP criteria, the Glaucoma VCEP adapted 15 rules to MYOC, and deemed 13 rules not applicable. Key specifications included determining minor allele frequency thresholds, developing an approach to counting probands and segregations, and reviewed functional assays. The rules were piloted on 81 variants and led to a change in classification in 38% of those that were classified in ClinVar with functional evidence influencing the classification of 18 variants. The standardized variant curation guidelines for MYOC provide a framework for the consistent application of the rules between laboratories, to improve MYOC genetic testing in the management of glaucoma.
Factors Associated with Food Insecurity among Pregnant Women in Gedeo Zone Public Hospitals, Southern Ethiopia
Authors: Areba Abriham Shiferaw , Haile Arega , Abire Belayneh Genoro , Debela Berhanu Gidisa , Legesse Miheret Tesfu , Andarge Sewitemariam Desalegn , Kanno Girum Gebremeskel , Gondol Belay Negassa , Abame Desta Erkalo
Published: February 2022

Background

Food insecurity refers to a lack of consistent access to sufficient food for active, better health. Around two billion people worldwide suffer from food insecurity and hidden hunger. Food insecurity and associated factors among pregnant women in Gedeo Zone Public Hospitals, Southern Ethiopia, are the focus of this study.

Method

From May to June 2021 G.C. institutional-based cross-sectional study was conducted among pregnant women in Gedeo zone public hospitals. A sample of 506 women has been used, and a multistage cluster sampling technique was used. An adjusted odds ratio (AOR) and their 95% confidence intervals (CI) were calculated to determine the association between various factors and outcomes. A p-value of less than 0.05 was considered significant in multivariable regression.

Results

Food insecurity was found to be prevalent in 67.4% of pregnant mothers. The results of a multivariable logistic regression revealed that pregnant women from rural areas [AOR=0.532, 95 % CI: 0.285, 0.994], married [AOR=0.232, 95% CI: 0.072, 0.750], have a secondary education [AOR=0.356, 95%CI: 0.154, 0.822], and be employed [AOR=0.453, 95% CI: 0.236, 0.872], income between 1000 and 2000 [AOR=0.163, 95% CI: 0.066, 0.399], and income greater than 2000 [AOR=0.125, 95% CI: 0.053,0.293], the wealth index middle and rich [AOR=0.441, 95% CI: 0.246, 0.793] were significant predictors of food insecurity among pregnant mothers [AOR=0.24, 95 % CI: 0.128, 0.449].

Conclusion

The study area had a high prevalence of food insecurity. Food insecurity was reduced in those who lived in rural areas, were married, had a secondary education, earned between 1000 and 2000 ETB and more than 2000 ETB, and had a wealth index of middle and rich.
Effects of bilateral sequential theta-burst stimulation on functional connectivity in treatment-resistant depression: first results
Authors: Stöhrmann Peter , Godbersen Godber Mathis , Reed Murray Bruce , Unterholzner Jakob , Klöbl Manfred , Baldinger-Melich Pia , Vanicek Thomas , Hahn Andreas , Lanzenberger Rupert , Kasper Siegfried , Kranz Georg S.
Published: February 2022

Background

Previous studies suggest that transcranial magnetic stimulation exerts antidepressant effects by altering functional connectivity (FC). However, knowledge about this mechanism is still limited. Here, we aimed to investigate the effect of bilateral sequential theta-burst stimulation (TBS) on FC in treatment-resistant depression (TRD) in a sham-controlled longitudinal study.

Methods

TRD patients (n = 20) underwent a three-week treatment of intermittent TBS of the left and continuous TBS of the right dorsolateral prefrontal cortex (DLPFC). Upon this trial’s premature termination, 15 patients had received active TBS and five patients sham stimulation. Resting-state functional magnetic resonance imaging was performed at baseline and after treatment. FC (left and right DLPFC) was estimated for each participant, followed by group statistics (T-tests). Furthermore, depression scores were analyzed (linear mixed models analysis) and tested for correlation with FC.

Results

Both groups exhibited reductions of depression scores, however, there was no significant main effect of group, or group and time. Anticorrelations between DLPFC and the subgenual cingulate cortex (sgACC) were observed for baseline FC, corresponding to changes in depression severity. Treatment did not significantly change DLPFC-sgACC connectivity, but significantly reduced FC between the left stimulation target and bilateral anterior insula.

Conclusions

Our data is compatible with previous reports on the relevance of anticorrelation between DLPFC and sgACC for treatment success. Furthermore, FC changes between left DLPFC and bilateral anterior insula highlight the effect of TBS on the salience network.

Limitations

Due to the limited sample size, results should be interpreted with caution and are of exploratory nature.
Periductal bile acid exposure causes cholangiocyte injury and fibrosis
Authors: Dotan Miri , Fried Sophia , Har-Zahav Adi , Shamir Raanan , Wells Rebecca G , Waisbourd-Zinman Orith
Published: February 2022

Introduction

Bile duct integrity is essential for the maintenance of the structure and function of the biliary tree. We previously showed that cholangiocyte injury in a toxic model of biliary atresia leads to increased monolayer permeability. Increased epithelial permeability was also shown in other cholangiopathies. We hypothesized that after initial cholangiocyte injury, leakage of bile acids into the duct submucosa propagates cholangiocyte damage and fibrosis. We thus aimed to determine the impact of bile acid exposure on cholangiocytes and the potential therapeutic effect of a non-toxic bile acid.

Materials and methods

Extrahepatic bile duct explants were isolated from adult and neonatal BALB/c mice. Explants were cultured with or without glycochenodeoxycholic acid and ursodeoxycholic acid. They were then fixed and stained.

Results

Explants treated with glycochenodeoxycholic acid demonstrated cholangiocyte injury with monolayer disruption and partial lumen obstruction compared to control ducts. Masson’s trichrome stains revealed increased collagen fibers. Myofibroblast marker α-SMA stains were significantly elevated in the periductal region. The addition of ursodeoxycholic acid resulted in decreased cholangiocyte injury and reduced fibrosis.

Conclusions

Bile acid leakage into the submucosa after initial cholangiocyte injury may serve as a possible mechanism of disease propagation and progressive fibrosis in cholangiopathies.
Characterization of small fiber neuropathy in hypermobile Ehlers Danlos Syndrome
Authors: Fernandez Aurore , Aubry-Rozier Bérengère , Vautey Mathieu , Berna Chantal , Suter Marc R.
Published: February 2022

Hypermobile Ehlers Danlos Syndrome (hEDS)/hypermobility spectrum disorders (HSD) are incapacitating and painful syndromes involving a generalized connective tissue disorder with joint hypermobility and musculoskeletal complications. A neuropathic component is clinically likely given frequent burning sensations, hypoesthesia, or allodynia. Small fiber neuropathy (SFN) refers to the dysfunction or damage of A-δ and C-fibers, which relay thermal and nociceptive information as well as mediating autonomic function. SFN has been suggested by prior studies in hEDS but these early findings (case series N≤20) with sole reliance on intraepidermal nerve fiber density (IENFD) called for a larger sample combined with functional testing.

In this retrospective chart extraction from 79 hEDS/HSD patients referred to a pain center due to neuropathic pain or dysautonomia, both functional (Quantitative Sensory Testing (QST), N=79) and structural (IENFD, N=69) evaluations of small nerve fibers were analyzed in combination with clinical data and standardized questionnaires.

All the patients reported moderate to severe pain interfering with daily life. A decreased thermal detection (QST) was shown in 55/79 patients (70%) and a decreased IENFD in 54/69 patients (78%). Hence a small fiber neuropathy (both abnormal IENFD and QST) was definite in 40/69 patients (58%), possible in 23/69 patients (33%) and excluded in only 6/69 patients (9%).

These results add strong evidence for a peripheral neuropathic contribution to pain symptoms in hEDS/HSD, in addition to the known nociceptive and central sensitization components. Such neuropathic contribution could raise the hypothesis of a neurological cause of hEDS, the only EDS syndrome still without a known genetic cause. Hence, our data is leading the way to a better stratification of this very heterogeneous population, which could improve symptom management and expand pathophysiological research.
Community engaged tick surveillance and tickMAP as a public health tool to track the emergence of ticks and tick-borne diseases in New York
Authors: Hart Charles E , Bhaskar Jahnavi Reddy , Reynolds Erin , Hermance Meghan , Earl Martin , Mahoney Matthew , Martinez Ana , Petzlova Ivona , Esterly Allen T , Thangamani Saravanan
Published: February 2022

A community engaged passive surveillance program was utilized to acquire ticks and associated information throughout New York state. Ticks were speciated and screened for several tick-borne pathogens. Of these ticks, only I. scapularis was commonly infected with pathogens of human relevance, including B. burgdorferi, B. miyamotoi, A. phagocytophilum, B. microti, and Powassan virus. In addition, the geographic and temporal distribution of tick species and pathogens was determined. This enabled the construction of a powerful visual analytical mapping tool, tickMAP to track the emergence of ticks and tick-borne pathogens in real-time. The public can use this tool to identify hot-spots of disease emergence, clinicians for supportive evidence during differential diagnosis, and researchers to better understand factors influencing the emergence of ticks and tick-borne diseases in New York. Overall, we have created a community-engaged tick surveillance program and an interactive visual analytical tickMAP that other regions could emulate to provide real-time tracking and an early warning for the emergence of tick-borne diseases.
Spatial Correlation of Left Atrial Low Voltage Substrate in Sinus Rhythm versus Atrial Fibrillation: Identifying the Pathological Substrate Irrespective of the Rhythm
Authors: Nairn Deborah , Eichenlaub Martin , Lehrmann Heiko , Müller-Edenborn Björn , Chen Juan , Huang Taiyuan , Nagel Claudia , Sánchez Jorge , Luongo Giorgio , Arentz Thomas , Dössel Olaf , Jadidi Amir , Loewe Axel
Published: February 2022

Background

Low voltage substrate (LVS) identified during electroanatomical mapping is a potential target for atrial fibrillation (AF) ablation. However, it is not clear how the location and extent of LVS correlate between mapping in sinus rhythm (SR) and AF.

Objectives

(1) Identify voltage dissimilarities between mapping in SR and AF. (2) Identification of regional voltage thresholds that improve cross-rhythm sub-strate detection. (3) Comparison of LVS between SR and native vs. induced AF.

Methods

Forty-one ablation-naive persistent AF patients underwent high-density voltage mapping in SR and AF. Each patient’s voltage information was mapped to a joint geometry for analysis. Global and regional voltage thresholds in AF were identified which best match LVS<0.5mV and <1.0mV in SR. Additionally, the correlation between SR-LVS with induced vs. native AF LVS was assessed.

Results

Substantial voltage differences (median: 0.52, IQR: 0.33-0.69, max: 1.19mV) with predominance of the posterior/inferior LA wall exist between the rhythms. An AF threshold of 0.34mV for the entire atrium provides an accuracy, sensitivity and specificity of 69%, 67% and 69% to identify SR-LVS<0.5mV, respectively. Lower thresholds for the posterior wall (0.27 mV) and inferior wall (0.3mV) result in higher spatial concordance to SR-LVS (4% and 7% increase). Concordance with SR-LVS was higher for induced AF compared to native AF (AUC: 0.80 vs. 0.73). AF-LVS<0.5mV corresponds to SR-LVS<0.97mV using high-definition mapping (AUC: 0.73).

Conclusion

The proposed voltage thresholds during AF maximise the consistency of LVS identification as determined during SR. Regional thresholds can further improve concordance.
Enabling interpretable machine learning for biological data with reliability scores
Authors: Ahlquist K. D. , Sugden Lauren , Ramachandran Sohini
Published: February 2022

Machine learning has become an important tool across biological disciplines, allowing researchers to draw conclusions from large datasets, and opening up new opportunities for interpreting complex and heterogeneous biological data. Alongside the rapid growth of machine learning, there have also been growing pains: some models that appear to perform well have later been revealed to rely on features of the data that are artifactual or biased; this feeds into the general criticism that machine learning models are designed to optimize model performance over the creation of new biological insights. A natural question thus arises: how do we develop machine learning models that are inherently interpretable or explainable? In this manuscript, we describe reliability scores, a new concept for scientific machine learning studies that assesses the ability of a classifier to produce a reliable classification for a given instance. We develop a specific implementation of a reliability score, based on our work in Sugden et al. 2018 in which we introduced SWIF(r), a generative classifier for detecting selection in genomic data. We call our implementation the SWIF(r) Reliability Score (SRS), and demonstrate the utility of the SRS when faced with common challenges in machine learning including: 1) an unknown class present in testing data that was not present in training data, 2) systemic mismatch between training and testing data, and 3) instances of testing data that are missing values for some attributes. We explore these applications of the SRS using a range of biological datasets, from agricultural data on seed morphology, to 22 quantitative traits in the UK Biobank, and population genetic simulations and 1000 Genomes Project data. With each of these examples, we demonstrate how interpretability tools for machine learning like the SRS can allow researchers to interrogate their data thoroughly, and to pair their domain-specific knowledge with powerful machine-learning frameworks. We hope that this tool, and the surrounding discussion, will aid researchers in the biological machine learning space as they seek to harness the power of machine learning without sacrificing rigor and biological understanding.
Cardiac myosin filaments are directly regulated by calcium
Authors: Ma Weikang , Gong Henry , Qi Lin , Nag Suman , Irving Thomas C.
Published: February 2022

Contraction of cardiac and skeletal muscle is initiated by calcium (Ca2+) binding to regulatory proteins on actin-containing thin filaments. During muscle contraction, structural changes in Ca2+-dependent thin filament allow the binding of myosin motors to drive muscle contraction1. The dynamic switching between the resting off states and the active on states of myosin is also critical in regulating muscle contractility2–4. However, the molecular switch on the myosin-containing thick filament that drives this process is not understood. Here we show that cardiac thick filaments are directly Ca2+-regulated. We find that Ca2+ progressively moves the myosin heads from ordered off states close to the thick filament backbone to disordered on states closer to the thin filaments. This Ca2+-dependent structural shift of myosin is accompanied by a biochemically defined transition from the inactive super-relaxed state(s) to the active disordered relaxed state(s)3. Furthermore, we find that this Ca2+-mediated molecular switching is an intrinsic property of cardiac myosin but only when assembled into thick filaments. This novel concept of Ca2+ as a regulatory modulator of the thick filament provides a fresh perspective on cardiac muscle regulation, which may be particularly valuable for devising restorative treatments for pathologies altering the Ca2+ sensitivity of the sarcomere.
Active hydraulics and odd elasticity of muscle fibers
Authors: Shankar Suraj , Mahadevan L.
Published: February 2022

Muscle is a complex hierarchically organized soft contractile engine. To understand the limits on the rate of contraction and muscle energetics, we construct a coarse-grained multiscale model that integrates over molecular details and describes muscle as an active sponge. Our analysis of existing experiments highlights the importance of spatially heterogeneous strains and local volumetric deformations in muscular contractions across species and muscle type. The minimal theoretical model shows how contractions generically induce intracellular fluid flow and power active hydraulic oscillations, which determine the limits of ultrafast muscular contractions. We further demonstrate that the viscoelastic response of muscle is naturally nonreciprocal – or odd – owing to its active and anisotropic nature. This points to an alternate mode of muscular power generation from periodic cycles in spatial strain alone, contrasting with previous descriptions based on temporal cycles. Our work suggests the need for a revised view of muscle dynamics that emphasizes the multiscale spatio-temporal origins of soft hydraulic power, with potential implications for physiology, biomechanics and locomotion.
Les déterminants d'accès à l'eau potable au Cameroun*
Authors: Dhin Etia Frank Charles , Mvogo Gregory , Honoré Bidiasse
Published: February 2022

Sur la base des données de la Cinquième Enquête Démographique de Santé réalisée auprès de 33 988 ménages au Cameroun, cet article identifie les déterminants d'accès à l'eau potable. De l'estimation d'une régression logistique multinomiale non ordonnée, les résultats montrent qu'il existe: une relation positive entre les ménages dirigés par les femmes et les probabilités d'accès à l'eau potable par robinet et par borne‐fontaine; une relation négative entre l'augmentation de la taille du ménage et ces probabilités d'accès. Une relation positive entre le quintile du bien‐être économique (catégorie la plus riche) et les probabilités d'accès à l'eau potable par robinet et forage; une relation positive entre le raccordement à l'électricité d'un ménage et la probabilité d'accès à l'eau potable par robinet. Enfin, une relation positive entre les ménages vivant en zones urbaines et les probabilités d'accès à ces trois catégories de sources d'eau potable améliorée que sont: l'eau par robinet, borne‐fontaine et forage. Sur ces déterminants, nous discutons les leçons pratiques de politiques publiques afin de favoriser l'accès à l'eau pour tous.
The effects of achievement goals and perceived reading instruction on Chinese student reading performance: Evidence from PISA 2018
Authors: Qian Quan , Lau Kit‐ling
Published: February 2022

Background

Research has shown that achievement goals and reading instruction play important roles in students' reading performance. However, little is known about the specific effects of different types of achievement goals and reading instructional practices on reading performance in mainland China.

Methods

This study used Programme of International Student Assessment (PISA) 2018 data to examine the effects of Chinese students' achievement goals and perceived reading instruction on reading performance. Four districts in mainland China, Beijing, Shanghai, Jiangsu, and Zhejiang (B–S–J–Z), participated in PISA 2018. A profile of B–S–J–Z students' achievement goals and perceived reading instruction compared with those in other East Asian societies is presented. The relative contributions of different achievement goals, instructional practices at the student and school levels, and their interactive effects on reading performance are then examined by using hierarchical linear modelling.

Results

The results show that performance and avoidance goals are important for B–S–J–Z students' reading performance when classroom and school teaching environments are considered. The disciplinary climate, adaptative instruction and teachers' stimulation are positively related to reading performance at both the student and school levels. Some cross‐level interactions between personal achievement goals and school reading instruction are found.

Conclusions

The findings suggest that achievement goals and reading instructional practices at both the student and school levels contribute to Chinese students' reading performance. The relationships between school reading instruction practices and students' reading performance vary for different achievement goals.
Political socialization, political gender gaps and the intergenerational transmission of left‐right ideology
Authors: VAN DITMARS MATHILDE M.
Published: February 2022

While left and right are the main terms to distinguish political views in Western Europe, the family socialization of citizens has mainly been studied in terms of partisan preferences rather than identification with these ideological blocks. Therefore, this study investigates the intergenerational transmission of left‐right ideological positions in two European multiparty systems. To investigate expectations regarding gendered patterns in political socialization, ideological transmission between mothers, fathers, daughters and sons are analyzed, making use of German and Swiss household data. The results underline the relevance of the family in the transmission of political ideology in multiparty systems, showing high contemporary parent–child concordance in ideological positioning in line with classic work in political socialization. Moreover, the study demonstrates how the gender‐generation gap in political ideology is consequential for this process. Young women consistently place themselves on the left of men across all combinations of parental ideology, which indicates that the gender‐generation gap trumps other gendered patterns in intergenerational transmission. Consequently, daughters are less likely than sons to take over their parents’ rightist positions, while parent–son transmission is equally large on the left and the right. This also means that left‐leaning parents have a general advantage over right‐leaning parents in having their ideological identification reproduced by their daughters. The study highlights the importance of differentiating between the transmission of left‐ and right‐wing ideology in political socialization processes. Moreover, it demonstrates that the distinction by offspring gender is imperative when studying the intergenerational transmission of traits that display gender differences within and between parental and offspring generations. The findings point at the active role of especially female offspring in the political socialization process, as they seem to be more strongly impacted by influences outside the family that sustain generational processes of further gender realignment.
Can “race‐neutral” program eligibility requirements in criminal justice have disparate effects? An examination of race, ethnicity, and prison industry employment
Authors: Anderson Claudia N. , Wooldredge John , Cochran Joshua C.
Published: February 2022

Research Summary

This study assesses whether racial and ethnic disparities exist in prison industry employment and whether seemingly race‐ and ethnicity‐neutral eligibility requirements contribute to any such disparities. We examine whether there are racial/ethnic disparities in industrial prison work, the extent to which disparities are explained by administrative policies, and the conditions under which disparities are most pronounced. Using 10 years of prison administrative data from Ohio, this study employs multilevel and mediation analyses to examine the effects of race and ethnicity on the odds of working an industrial prison job. Results suggest that Black and Hispanic incarcerated persons (IPs) are less likely to work industry jobs than White IPs. The majority of this disparity stems from program requirements; however, some disparities maintain even when accounting for requirements. Black IPs who do not meet program requirements are less likely to work than White IPs who do not meet program requirements. Racial disparities are smaller in facilities with greater racial heterogeneity among correctional staff.

Policy Implications

In our discussion, we underscore how prison policies can contribute to racially and ethnically disparate incarceration experiences. The results suggest the importance of evaluating prison and other correctional policies that utilize selection criteria that appear race neutral but are likely to be disparate in their consequences. Moreover, policies aimed at diversifying staff may contribute to more equitable prison experiences for non‐White incarcerated people, although doing so does not directly address underlying policy problems that lead to inequalities.