bluuebunny/crossref_metadata_2025 huggingface dataset:
Western And Chinese Development Engagements In Uganda’s Roads Sector: An Implicit Division of Labour
Authors: Zhou Hang
Published: January 2022

How has the process of institution and governance building in Africa, a domain traditionally subject to western development interventions, been changed by Chinese-led development? Taking Uganda’s roads sector, and particularly its main implementing agency the Ugandan National Roads Authority as a case study, I argue that traditional donors’ influence on sectorial institution building has not been replaced or dislodged by China’s growing presence. This presence primarily took the form of Chinese construction companies operating as profit-driven contractors interested mainly in quick project turnaround rather than in systematically shaping sectorial governance in the host country. Moreover, not only did traditional donors’ development financing remain dominant vis-à-vis China, but the ways in which their interventions were designed, exercised, and monitored in the post-conditionality regime characteristically differed from their Chinese counterparts, ensuring their embedded and enduring role in the reforming of sectorial state institutions. As such, a tacit division of labour took shape between Chinese and western engagements in Uganda’s roads sector: China focused on ‘hard’ physical road construction whilst traditional donors on the ‘soft’ aspects of sectorial governance and policy. The availability of both forms of development engagements with their distinctive foci enables issue-specific agency for Uganda to develop its roads sector, and yet they together appear to create favourable conditions for the Ugandan leadership’s increasing authoritarianism.
Anatomy of a Cyberattack
Authors: Frisch Nora K , Gibson Pamela C , Stowman Anne M , Goodwin Andrew , Schwartz Michelle , Cortright Valerie , Hong Tania , Kalof Alexandra
Published: January 2022

Objectives

Our institution was the victim of a cyberattack that necessitated use of manual laboratory systems for more than 25 days. These manual processes had to be created not only to enable us to process our case volume without bottlenecks but also to maintain patient safety and allow for billing.

Methods

Our laboratory needed to create a safe reporting process to ensure ongoing patient safety and error reduction during the downtime. Additionally, we needed to ensure the ability to bill for performed tests in some areas of the lab and maintain compliance with regulatory policies.

Results

Amendment rates in our system were higher than before the attack, but no patient harm was observed. Intraoperative assessments declined, but high-acuity cases continued with a discrepancy rate comparable with the normal state. Many hours and resources (human and otherwise) were necessary to reconcile the work done to bill for services, but we were able to capture revenue through careful planning.

Conclusions

This article records the challenges we faced and the successes we achieved in maintaining compliance and a low error rate in the face of manual processes, the steps necessary to bring the cases into the newly restored electronic health record, and how we billed for the services we rendered.
CAP-ACP Workload Model for Advanced Diagnostics in Precision Medicine
Authors: Park Paul C , Kurek Kyle C , DeCoteau John , Howlett Christopher J , Hawkins Cynthia , Izevbaye Iyare , Carter Michael D , Redpath Margaret , Lo Bryan , Alex Deepu , Yousef George , Yip Stephen , Maung Raymond
Published: January 2022

Objectives

In precision medicine, where oncologic management is tailored to the individual’s clinical and genetic profiles, advanced diagnostic testing provides prognostic information and guides management in a growing number of malignancies. There is a need to capture the work pathologists perform to meet this demand by providing medically relevant, timely, and accurate testing results. This work includes not only direct patient consults (interpretation of results and issuing reports) but the administrative and medical oversight as well as the research needed to provide the necessary quality assurance, quality control, direction, and framework for the laboratory.

Methods

An expert panel of Canadian pathologists involved in advanced diagnostics was convened to establish and beta test a model for workload assessment in advanced diagnostics.

Results

All aspects of the advanced diagnostics workload were detailed and applied to models based on members’ experience, including medical oversight, administration, and the introduction of new testing and platforms. Models for biomarker testing were developed for simple and complex or multiplexed assays, and a detailed model was developed to assess the workload for next-generation sequencing–based assays.

Conclusions

This paper provides the first detailed proposal for capturing an advanced diagnostic workload to enable appropriate pathologist allotment for performing all the steps required to run an advanced diagnostic service.
Tissue Contamination During Transportation of Formalin-Fixed, Paraffin-Embedded Blocks
Authors: Carll Timothy , Fuja Christine , Antic Tatjana , Lastra Ricardo , Poon Rachel , McGary Ryan , Pytel Peter
Published: January 2022

Objectives

Tissue carryovers are contaminants of surgical pathology cases in which extraneous tissue is incorporated into tissue blocks. Carryovers occur most frequently at the grossing or embedding stations, but little is published about them. We sought to analyze their transmission during transit to the histology lab.

Methods

Cassettes of friable donor tissue were mixed with cassettes of spongy recipient tissue in formalin-filled containers and agitated by shipment via pneumatic tube. The tissue cassettes were processed, embedded as blocks, and cut as usual. Liquid samples were prepared from the submission containers as well as from workstation submission containers and histology tissue processor waste.

Results

A high rate of contamination (14.9%) was observed under these artificial conditions. Friable donor tissue, including urothelium and colorectal adenocarcinoma, were promiscuous contaminants, as were placental villi. Fluid from submission containers showed viable tumor cells and fragments, which were also present in workstation submission containers and in tissue processor waste fluid.

Conclusions

This study implicates liquid transport media as a possible avenue of contamination during submission and transportation of tissue cassettes for histologic processing. Attention should be given to the friability of submitted tissue and physical agitation of the cassettes in transit. Such contaminants may be present in the fluid in tissue submission bins and in tissue processor fluid.
Changes in Surgical Pathology Case Volume and Amendment Rates During the COVID-19 Pandemic
Authors: Harris Cynthia K , Kwong J Y , Cohen M H , Bland Denise K , Fell Geoffrey G , Nosé Vania , Bossuyt Veerle
Published: January 2022

Objectives

Surgical pathology volume decreased during the peak of the coronavirus disease 2019 (COVID-19) pandemic. We looked at the 4 months with the greatest reduction in surgical pathology volume during the COVID-19 pandemic and compared them with those same months in 2019 to determine changes in specimen volume. We compared the amendment rates during those periods and types of amendments issued (identification [ID], report defect [RD], diagnostic information [DI]).

Methods

All pathology reports between March to June 2019 and March to June 2020 were extracted from the pathology information system. All amendments issued were extracted over the same period and then subclassified by two pathologists.

Results

There was a 52.1% reduction in surgical pathology volume between the 4-month periods in 2019 and 2020 (P = .04). The amendment rate was 0.9% in 2019 compared with 1.4% in 2020, representing a 65.5% increase in amendments overall. There was a 53.3% reduction in amendments issued for ID, a 3.8% reduction in RD, and a 23.2% increase in amendments issued for DI. The change in amendments was not statistically significant.

Conclusions

These findings suggest that a reduction in workload would not improve error rates. The circumstances of the pandemic highlight the many factors contributing to error rates in surgical pathology.
Excessive Blood Pressure Response to Clonidine in Hospitalized Patients With Asymptomatic Severe Hypertension
Authors: Hanna Jonathan , Ghazi Lama , Yamamoto Yu , Simonov Michael , Shah Tayyab , Wilson Francis P , Peixoto Aldo J
Published: January 2022

Background

There are limited and nonconcordant data on the rapidity and safety of blood pressure response to clonidine in the setting of asymptomatic severe hypertension. We evaluated the blood pressure response to clonidine in hospitalized patients with asymptomatic severe hypertension.

Methods

We performed a review of hospitalized, noncritically ill patients receiving clonidine within 6 hours of developing asymptomatic severe hypertension (systolic blood pressure [SBP] >180 or diastolic blood pressure [DBP] >110 mm Hg in the absence of acute hypertension-mediated target organ damage). The incidence of mean arterial pressure (MAP) reduction by ≥30% at 4 hours after clonidine was the primary endpoint.

Results

We identified 200 relevant patient encounters (median age 63 years, 48.5% women). Median time to clonidine following asymptomatic severe hypertension was 2.8 hours. A total of 20 (10%) patients had ≥30% MAP reduction within 4 hours after clonidine, and 32 (16%) patients had ≥30% reduction in either SBP, DBP, or MAP. Older age, female sex, and preexisting vascular disease were associated with ≥30% MAP reductions (P < 0.05). Only patient sex and clonidine dose of 0.3 mg were significant in multivariable models. There were 14 adverse events observed within 24 hours of administration of clonidine; most (9) were acute kidney injury. There were no ischemic (myocardial, cerebrovascular) events.

Conclusions

A substantial minority of hospitalized patients with asymptomatic severe hypertension experience precipitous blood pressure decline with clonidine, and though blood pressure declines more precipitously in women and those receiving higher doses (0.3 mg specifically), the response to clonidine is generally not predictable on clinical grounds.
Predicting Out-of-Office Blood Pressure in a Diverse US Population
Authors: Bellows Brandon K , Xu Jingyu , Sheppard James P , Schwartz Joseph E , Shimbo Daichi , Muntner Paul , McManus Richard J , Moran Andrew E , Bryant Kelsey B , Cohen Laura P , Bress Adam P , King Jordan B , Shikany James M , Green Beverly B , Yano Yuichiro , Clark Donald , Zhang Yiyi
Published: January 2022

BACKGROUND

The PRedicting Out-of-OFfice Blood Pressure (PROOF-BP) algorithm accurately predicted out-of-office blood pressure (BP) among adults with suspected high BP in the United Kingdom and Canada. We tested the accuracy of PROOF-BP in a diverse US population and evaluated a newly developed US-specific algorithm (PROOF-BP-US).

METHODS

Adults with ≥2 office BP readings and ≥10 awake BP readings on 24-hour ambulatory BP monitoring from 4 pooled US studies were included. We compared mean awake BP with predicted out-of-office BP using PROOF-BP and PROOF-BP-US. Our primary outcomes were hypertensive out-of-office systolic BP (SBP) ≥130 mm Hg and diastolic BP (DBP) ≥80 mm Hg.

RESULTS

We included 3,058 adults, mean (SD) age was 52.0 (11.9) years, 38% were male, and 54% were Black. The area under the receiver-operator characteristic (AUROC) curve (95% confidence interval) for hypertensive out-of-office SBP was 0.81 (0.79–0.82) and DBP was 0.76 (0.74–0.78) for PROOF-BP. For PROOF-BP-US, the AUROC curve for hypertensive out-of-office SBP was 0.82 (0.81–0.83) and for DBP was 0.81 (0.79–0.83). The optimal predicted out-of-office BP ranges for out-of-office BP measurement referral were 120–134/75–84 mm Hg for PROOF-BP and 125–134/75–84 mm Hg for PROOF-BP-US. The 2017 American College of Cardiology/American Heart Association BP guideline (referral range 130–159/80–99 mm Hg) would refer 93.1% of adults not taking antihypertensive medications with office BP ≥130/80 mm Hg in the National Health and Nutrition Examination Survey for out-of-office BP measurement, compared with 53.1% using PROOF-BP and 46.8% using PROOF-BP-US.

CONCLUSIONS

PROOF-BP and PROOF-BP-US accurately predicted out-of-office hypertension in a diverse sample of US adults.
Efficacy of Tranexamic Acid in Reducing Seroma and Hematoma Formation Following Reduction Mammaplasty
Authors: Weissler Jason M , Kuruoglu Doga , Antezana Luis , Curiel Daniel , Kerivan Lauren , Alsayed Ahmed , Banuelos Joseph , Harless Christin A , Sharaf Basel A , Vijayasekaran Aparna , Martinez-Jorge Jorys , Tran Nho V , Nguyen Minh-Doan T
Published: January 2022

Background

Tranexamic acid (TXA) has gained increasing recognition as a valuable pharmacologic agent within plastic surgery.

Objectives

The aim of this study was to investigate the value and safety profile of both intravenous and topically administered TXA in the setting of bilateral reduction mammaplasty.

Methods

A retrospective review was performed to identify consecutive patients who underwent bilateral reduction mammaplasty for symptomatic macromastia (January 2016-July 2021). Pertinent preoperative, intraoperative, and postoperative details were collected/reviewed. Primary outcome measures included hematoma requiring surgical evacuation and clinically significant/symptomatic seroma formation mandating percutaneous aspiration. Patients taking anticoagulation/antiplatelet medication or those with a history of thromboembolic diseases were excluded. Patients who had received TXA were compared to a historical control group who did not receive TXA within the same consecutive cohort.

Results

A total of 385 consecutive patients (770 breasts) were included. TXA was used in 514 (66.8%) cases (topical, 318 [61.9%]; intravenous, 170 [33.1%]; intravenous and topical, 26 [5.1%]). Neither seroma nor hematoma were impacted/reduced with TXA (P > 0.05). Increased age (hazards ratio, 1.06 per 1-year increase; 95% CI, 1.004-1.118) significantly increased the risk of hematoma (P = 0.032). The use of drains significantly decreased the risk of seroma (P < 0.0001). Increased BMI increased the risk of seroma (hazards ratio, 1.16 per 1-kg/m2 increase; 95% CI, 1.06-1.26; P = 0.0013). The use of TXA did not impact drain duration.

Conclusions

This study, the largest to date on the use of IV and topical TXA, did not find any reduction in risk when using TXA in breast reduction surgery.

Level of Evidence: 3
Identifying drug–target interactions via heterogeneous graph attention networks combined with cross-modal similarities
Authors: Jiang Lu , Sun Jiahao , Wang Yue , Ning Qiao , Luo Na , Yin Minghao
Published: January 2022

Accurate identification of drug–target interactions (DTIs) plays a crucial role in drug discovery. Compared with traditional experimental methods that are labor-intensive and time-consuming, computational methods are more and more popular in recent years. Conventional computational methods almost simply view heterogeneous networks which integrate diverse drug-related and target-related dataset instead of fully exploring drug and target similarities. In this paper, we propose a new method, named DTIHNC, for $\mathbf{D}$rug–$\mathbf{T}$arget $\mathbf{I}$nteraction identification, which integrates $\mathbf{H}$eterogeneous $\mathbf{N}$etworks and $\mathbf{C}$ross-modal similarities calculated by relations between drugs, proteins, diseases and side effects. Firstly, the low-dimensional features of drugs, proteins, diseases and side effects are obtained from original features by a denoising autoencoder. Then, we construct a heterogeneous network across drug, protein, disease and side-effect nodes. In heterogeneous network, we exploit the heterogeneous graph attention operations to update the embedding of a node based on information in its 1-hop neighbors, and for multi-hop neighbor information, we propose random walk with restart aware graph attention to integrate more information through a larger neighborhood region. Next, we calculate cross-modal drug and protein similarities from cross-scale relations between drugs, proteins, diseases and side effects. Finally, a multiple-layer convolutional neural network deeply integrates similarity information of drugs and proteins with the embedding features obtained from heterogeneous graph attention network. Experiments have demonstrated its effectiveness and better performance than state-of-the-art methods. Datasets and a stand-alone package are provided on Github with website https://github.com/ningq669/DTIHNC.
BACPI: a bi-directional attention neural network for compound–protein interaction and binding affinity prediction
Authors: Li Min , Lu Zhangli , Wu Yifan , Li YaoHang
Published: January 2022

Motivation

The identification of compound–protein interactions (CPIs) is an essential step in the process of drug discovery. The experimental determination of CPIs is known for a large amount of funds and time it consumes. Computational model has therefore become a promising and efficient alternative for predicting novel interactions between compounds and proteins on a large scale. Most supervised machine learning prediction models are approached as a binary classification problem, which aim to predict whether there is an interaction between the compound and the protein or not. However, CPI is not a simple binary on–off relationship, but a continuous value reflects how tightly the compound binds to a particular target protein, also called binding affinity.

Results

In this study, we propose an end-to-end neural network model, called BACPI, to predict CPI and binding affinity. We employ graph attention network and convolutional neural network (CNN) to learn the representations of compounds and proteins and develop a bi-directional attention neural network model to integrate the representations. To evaluate the performance of BACPI, we use three CPI datasets and four binding affinity datasets in our experiments. The results show that, when predicting CPIs, BACPI significantly outperforms other available machine learning methods on both balanced and unbalanced datasets. This suggests that the end-to-end neural network model that predicts CPIs directly from low-level representations is more robust than traditional machine learning-based methods. And when predicting binding affinities, BACPI achieves higher performance on large datasets compared to other state-of-the-art deep learning methods. This comparison result suggests that the proposed method with bi-directional attention neural network can capture the important regions of compounds and proteins for binding affinity prediction.

Availability and implementation

Data and source codes are available at https://github.com/CSUBioGroup/BACPI
The taxonomy of Leucanthemum ircutianum (Asteraceae, Anthemideae) in the Apennine Peninsula based on AFLP fingerprinting, plastid DNA sequence variation and eco-climatological niche reconstruction
Authors: Oberprieler Christoph , Conti Fabio , Dorfner Marco , Eder Sarah-Maria , Heuschneider Anja , Ott Tankred , Scheunert Agnes , Vogt Robert
Published: January 2022

The tetraploid species Leucanthemum ircutianum (Asteraceae, Anthemideae) is represented in the Apennine Peninsula by three infraspecific taxa, L. ircutianum subsp. ircutianum, L. ircutianum subsp. asperulum and L. ircutianum subsp. leucolepis. The present study uses AFLP fingerprinting and sequencing of the petN–psbM intergenic spacer (IGS) region of the plastid genome for inferring genetic relationships among these three subspecies and aims at the elaboration of an appropriate taxonomic treatment of these taxa. Due to the amphi-Adriatic distribution of these taxa, additional samples from the Balkan Peninsula and representatives of L. ircutianum subsp. ircutianum from north-western Italy, south-eastern France, Romania and southern Germany were included. Genetic analyses reveal that L. ircutianum subsp. asperulum from southern Italy and L. ircutianum subsp. leucolepis from the Balkan Peninsula and the northern and central Apennine Peninsula are identical and should be treated as a single taxon. The observation of genetically intermediate individuals throughout the overlapping distributional ranges of L. ircutianum subspp. ircutianum and leucolepis and in a surveyed mixed stand of the two taxa indicate that these are not reproductively isolated from each other. The analysis of eco-climatological niches of the two subspecies indicates that L. ircutianum subsp. ircutianum is found in more temperate regions, whereas L. ircutianum subsp. leucolepis prefers the Mediterranean fringe of the total distributional range of the species. A hybrid-zone analysis based on AFLP ‘allele frequency’ clines along a transect from Germany to southern Italy is interpreted as supporting a scenario of secondary contact of the two entities after some diversification in allopatry. On the basis of our results, we provide a taxonomic treatment of the species L. ircutianum for Italy, including the designation of three lectotypes.
Perceptual coupling and decoupling are associated with individual differences in working memory encoding and maintenance
Authors: Zhang Meichao , McNab Fiona , Smallwood Jonathan , Jefferies Elizabeth
Published: January 2022

Working memory (WM) allows goal-relevant information to be encoded and maintained in mind, even when the contents of WM are incongruent with the immediate environment. While regions of heteromodal cortex are important for WM, the neural mechanisms that relate to individual differences in the encoding and maintenance of goal-relevant information remain unclear. Here, we used behavioral correlates of two large-scale heteromodal networks at rest, the default mode (DMN) and frontoparietal (FPN) networks, to understand their contributions to distinct features of WM. We assessed each individual’s ability to resist distracting information during the encoding and maintenance phases of a visuospatial WM task. Individuals with stronger connectivity of DMN with medial visual and retrosplenial cortex were less affected by encoding distraction. Conversely, weaker connectivity of both DMN and FPN with visual regions was associated with better WM performance when target information was no longer in the environment and distractors were presented in the maintenance phase. Our study suggests that stronger coupling between heteromodal cortex and visual–spatial regions supports WM encoding by reducing the influence of concurrently presented distractors, while weaker visual coupling is associated with better maintenance of goal-relevant information because it relates to the capacity to ignore task-irrelevant changes in the environment.
Perioperative stroke and survival in coronary artery bypass grafting patients: a SWEDEHEART study
Authors: Jonsson Kristjan , Barbu Mikael , Nielsen Susanne J , Hafsteinsdottir Brynhildur , Gudbjartsson Tomas , Jensen Elin M , Silverborn Martin , Jeppsson Anders
Published: January 2022

OBJECTIVES

Perioperative stroke is a severe complication of cardiac surgery. We assessed the incidence of stroke over time, the association between stroke and mortality and identified preoperative factors independently associated with perioperative stroke, in a large nationwide cardiac surgery population.

METHODS

All patients who underwent coronary artery bypass grafting in Sweden 2006–2017 were included in a registry-based observational cohort study based on prospectively collected data. Multivariable logistic and Cox regression models were used to assess associations between perioperative stroke and mortality and to identify factors associated with stroke. The median follow-up was 6 years (range 0–12).

RESULTS

There were 441 perioperative strokes in 36 898 patients. The mean incidence was 1.2% and decreased marginally over time [adjusted odds ratio (OR) 0.97 per year (95% confidence interval 0.94–1.00), P = 0.035]. Stroke patients had a higher overall mortality risk during follow-up [adjusted hazard ratio 2.30 (2.00–2.64), P < 0.001], with the highest risk during the first 30 postoperative days [adjusted hazard ratio (7.29 (5.58–9.54), P < 0.001]. The strongest independent preoperative factors associated with stroke were prior cardiac surgery [adjusted OR 2.89 (1.40–5.96)], critical preoperative condition [adjusted OR 2.55 (1.73–3.76)], previous stroke [adjusted OR 1.77 (1.35–2.33)], preoperative angina requiring intravenous nitrates [adjusted OR 1.67 (1.28–2.17)], peripheral vascular disease [OR 1.63 (1.25–2.13)] and advanced age [OR 1.05 (1.03–1.06) per year].

CONCLUSIONS

The incidence of perioperative stroke after coronary artery bypass grafting has remained stable. Patients with perioperative stroke had a markedly higher adjusted risk of death early after surgery. The risk declined over time but remained higher during the entire follow-up period.
Caring Together: Trajectories of Paid and Family Caregiving Support to Those Living in the Community With Dementia
Authors: Reckrey Jennifer M , Li Lihua , Zhan Serena , Wolff Jennifer , Yee Cynthia , Ornstein Katherine A
Published: January 2022

Objectives

Paid caregivers (e.g., home health aides) often work with family caregivers to support persons living with dementia at home. We identify (a) unique trajectories of paid and family caregiving support among persons living with dementia with high care needs and (b) factors associated with these trajectories.

Methods

We used group-based multiple trajectory modeling to identify distinct trajectories of paid and family caregiving hours among National Health and Aging Trends Study respondents with dementia who died or moved to a nursing home (n = 334, mean follow-up 5.5 years). We examined differences between trajectory groups and identified factors associated with group membership using generalized estimating equation modeling.

Results

A 3-group model best fit our data: (a) “low/stable care” (61.3% of respondents) with stable, low/no paid care and moderate family care, (b) “increasing paid care” with increasing, moderate paid and family care, and (c) “high family care” with increasing, high family care and stable, low paid care. While both the “increasing paid care” and “high family care” groups were more functionally impaired than the “low/stable care” group, the “high family care” group was also more likely to be non-White and experience multiple medical comorbidities, depression, and social isolation.

Discussion

Study findings highlight the importance of considering unique arrangements in dementia care. Receipt of paid care was not only determined by patient care needs. Creating equitable access to paid care may be a particularly important way to support both persons living with dementia and their family caregivers as care needs grow.
Medical Cannabis and Utilization of Nonhospice Palliative Care Services: Complements and Alternatives at End of Life
Authors: Croker James A , Bobitt Julie , Arora Kanika , Kaskie Brian
Published: January 2022

Background and Objectives

There is a need to know more about cannabis use among terminally diagnosed older adults, specifically whether it operates as a complement or alternative to palliative care. The objective is to explore differences among the terminal illness population within the Illinois Medical Cannabis Program (IMCP) by their use of palliative care.

Research Design and Methods

The study uses primary, cross-sectional survey data from 708 terminally diagnosed patients, residing in Illinois, and enrolled in the IMCP. We compared the sample on palliative care utilization through logistic regression models, examined associations between palliative care and self-reported outcome improvements using ordinary least squares regressions, and explored differences in average pain levels using independent t-tests.

Results

115 of 708 terminally diagnosed IMCP participants were receiving palliative care. We find increased odds of palliative care utilization for cancer (odds ratio [OR] [SE] = 2.15 [0.53], p < .01), low psychological well-being (OR [SE] = 1.97 [0.58], p < .05), medical complexity (OR [SE] = 2.05 [0.70], p < .05), and prior military service (OR [SE] = 2.01 [0.68], p < .05). Palliative care utilization is positively associated with improvement ratings for pain (7.52 [3.41], p < .05) and ability to manage health outcomes (8.29 [3.61], p < .01). Concurrent use of cannabis and opioids is associated with higher pain levels at initiation of cannabis dosing (p < .05).

Discussion and Implications

Our results suggest that cannabis is largely an alternative to palliative care for terminal patients. For those in palliative care, it is a therapeutic complement used at higher levels of pain.
A novel Fontan Y-graft for interrupted inferior vena cava and azygos continuation
Authors: Lashkarinia S Samaneh , Cicek Murat , Kose Banu , Rezaeimoghaddam Mohammad , Yılmaz Emine Hekim , Aydemir Numan Ali , Rasooli Reza , Ozkok Sercin , Yurtseven Nurgul , Erdem Hasan , Pekkan Kerem , Sasmazel Ahmet
Published: January 2022

OBJECTIVES

To evaluate the hemodynamicdynamic advantage of a new Fontan surgical template that is intended for complex single-ventricle patients with interrupted inferior vena cava-azygos and hemi-azygos continuation. The new technique has emerged from a comprehensive pre-surgical simulation campaign conducted to facilitate a balanced hepatic flow and somatic Fontan pathway growth after Kawashima procedure.

METHODS

For 9 patients, aged 2 to18 years, majority having poor preoperative oxygen saturation, a pre-surgical computational fluid dynamics customization is conducted. Both the traditional Fontan pathways and the proposed novel Y-graft templates are considered. Numerical model was validated against in vivo phase-contrast magnetic resonance imaging data and in vitro experiments.

RESULTS

The proposed template is selected and executed for 6 out of the 9 patients based on its predicted superior hemodynamic performance. Pre-surgical simulations performed for this cohort indicated that flow from the hepatic veins (HEP) do not reach to the desired lung. The novel Y-graft template, customized via a right- or left-sided displacement of the total cavopulmonary connection anastomosis location resulted a drastic increase in HEP flow to the desired lung. Orientation of HEP to azygos direct shunt is found to be important as it can alter the flow pattern from 38% in the caudally located direct shunt to 3% in the cranial configuration with significantly reversed flow. The postoperative measurements prove that oxygen saturation increased significantly (P-value = 0.00009) to normal levels in 1 year follow-up.

CONCLUSIONS

The new Y-graft template, if customized for the individual patient, is a viable alternative to the traditional surgical pathways. This template addresses the competing hemodynamic design factors of low physiological venous pressure, high postoperative oxygen saturation, low energy loss and balanced hepatic growth factor distribution possibly assuring adequate lung development.

Date and number of IRB approval

25 October 2019, 280011928-604.01.01.
π1—smallDivisors and Fundamental Groups of Varieties
Authors: Hao Feng
Published: January 2022

Lasell and Ramachandran show that the existence of rational curves of positive self-intersection on a smooth projective surface $X$ implies that all the finite dimensional linear representations of the fundamental group $\pi _1(X)$ are finite. In this article, we generalize Lasell and Ramachandran’s result to the case of $\pi _1-small$ divisors on quasiprojective varieties. We also study $\pi _1-small$ curves and hyperbolicity properties of smooth projective surfaces of general type with infinite fundamental groups.
Defining AMIA’s artificial intelligence principles
Authors: Solomonides Anthony E , Koski Eileen , Atabaki Shireen M , Weinberg Scott , McGreevey John D , Kannry Joseph L , Petersen Carolyn , Lehmann Christoph U
Published: January 2022

Recent advances in the science and technology of artificial intelligence (AI) and growing numbers of deployed AI systems in healthcare and other services have called attention to the need for ethical principles and governance. We define and provide a rationale for principles that should guide the commission, creation, implementation, maintenance, and retirement of AI systems as a foundation for governance throughout the lifecycle. Some principles are derived from the familiar requirements of practice and research in medicine and healthcare: beneficence, nonmaleficence, autonomy, and justice come first. A set of principles follow from the creation and engineering of AI systems: explainability of the technology in plain terms; interpretability, that is, plausible reasoning for decisions; fairness and absence of bias; dependability, including “safe failure”; provision of an audit trail for decisions; and active management of the knowledge base to remain up to date and sensitive to any changes in the environment. In organizational terms, the principles require benevolence—aiming to do good through the use of AI; transparency, ensuring that all assumptions and potential conflicts of interest are declared; and accountability, including active oversight of AI systems and management of any risks that may arise. Particular attention is drawn to the case of vulnerable populations, where extreme care must be exercised. Finally, the principles emphasize the need for user education at all levels of engagement with AI and for continuing research into AI and its biomedical and healthcare applications.
Burn Injuries in People Who Used Drug, 2009 to 2017: A Case–Control Study in Shiraz, Southern Iran
Authors: Hoghoughi Mohammad Ali , Marzban Mohammad Reza , Shahrbaf Mohammad Amin , Shahriarirad Reza , Kamran Hooman , Meimandi Farzaneh Zahmatkesh , Salimi Maryam , Hosseinpour Hamidreza
Published: January 2022

Burn injury is a critical health issue, which is associated with several morbidities and mortalities. Substance abuse, which is an important public health problem in Iran, can affect burn injury outcomes and etiologies in victims. This study was aimed to evaluate different aspects of burn injuries in people who used drug (PWUD) in two referral centers in the south of Iran. This case–control study was conducted on burn victims referred to Amir-al Momenin Hospital and Ghotb-al-din Hospital from 2009 to 2017. Patients with a history of drug consumption were selected from the database and compared to randomly selected burn victims with no history of drug use. Demographics, burn etiology, underlying disease, total body surface area, hospitalization duration, and also the outcomes were collected and recorded in both groups. Data analysis was done by SPSS software. A total of 5912 inpatients were included in this study, of which 2397 of them (40.54%) were female. The mean age of the patients was 26.12 ± 19.18. Drug history was positive in 659 patients (11.15%). Familial issues and mental disorders were significantly higher in the PWUD group compared to the control group (P < .001). Explosion etiology was significantly higher in the PWUD group (P < .001). Psychiatric disorders (P < .001), total body surface area (P = .023), and hospital stay (P < .001) were significantly higher in PWUD; however, the mortality rate had no statistically significant differences between the groups (P = .583). Substance abuse is a risk factor in burn victims, which can affect burn etiology and burn-related morbidities.
Global Externalities, Local Policies, and Firm Selection
Authors: Ahlvik Lassi , Liski Matti
Published: January 2022

How to fight global problems with local tools? When only firms know what externality-producing activities can be relocated, policies shape the location distribution of firm types with different social values. We find that, because of this selection effect, the optimal local policies confront firms’ mobility with elevated corrective externality prices, in contrast with the common remedies for the relocation risk. Our mechanism incentivizes also moving firms to limit the externality, and it influences strategically the distribution of moving firms that comply with policies elsewhere. The magnitude of these effects is illustrated by a quantification for the key sectors in the European Union emissions trading system.
Extrapolation of design strategies for lignocellulosic biomass conversion to the challenge of plastic waste
Authors: Jarboe Laura R , Khalid Ammara , Rodriguez Ocasio Efrain , Noroozi Kimia Fashkami
Published: January 2022

The goal of cost-effective production of fuels and chemicals from biomass has been a substantial driver of the development of the field of metabolic engineering. The resulting design principles and procedures provide a guide for the development of cost-effective methods for degradation, and possibly even valorization, of plastic wastes. Here, we highlight these parallels, using the creative work of Lonnie O'Neal (Neal) Ingram in enabling production of fuels and chemicals from lignocellulosic biomass, with a focus on ethanol production as an exemplar process.
Environmental Scan of Parent-Facing Health Information About Antibiotics in US Children’s Hospital Websites
Authors: Mangal Sabrina , Arcia Adriana , Carter Eileen
Published: January 2022

Nearly half of free-standing children’s hospital websites contain parent-facing resources about antibiotics. Most resources have information on safe antibiotic use, antibiotic resistance, and questions to ask clinicians. Accessibility can be improved by increasing readability, available languages, and multimedia. Future research should evaluate information accuracy, actionability, and comprehension with target audiences.
Determination of Glyphosate and AMPA in Blood Can Predict the Severity of Acute Glyphosate Herbicide Poisoning
Authors: Cellier M , Anthony N , Bruneau C , Descatha A
Published: January 2022

Objective

To evaluate a potential association between blood and urine concentration of glyphosate and its metabolite, aminomethylphosphonic acid (AMPA), with severity of acute glyphosate (herbicide) poisoning.

Methods

In our retrospective study of acute glyphosate poisoning, we examined records from the French National Database of Poisonings, dated between January 1, 2004, and December 31, 2016. We compared the severity of poisoning among case individuals using the Fisher exact test and Wilcoxon test. Also, we calculated ROC curves to determine the cutoff for blood and urine concentration.

Results

A total of 17 plasma glyphosate, 11 urine glyphosate, 13 plasma AMPA, and 10 urine AMPA specimens were included in our study, with collection dates ranging from January 1, 2004, through December 31, 2016.

Conclusion

The optimal cutoff we discovered for blood concentration of AMPA was 0.88 mg/L; for glyphosate, it was 600 mg/L. The cutoff plasma concentration of AMPA has never been described in the literature, to our knowledge.
Genomic patterns of transcription–replication interactions in mouse primary B cells
Authors: St Germain Commodore P , Zhao Hongchang , Sinha Vrishti , Sanz Lionel A , Chédin Frédéric , Barlow Jacqueline H
Published: January 2022

Conflicts between transcription and replication machinery are a potent source of replication stress and genome instability; however, no technique currently exists to identify endogenous genomic locations prone to transcription–replication interactions. Here, we report a novel method to identify genomic loci prone to transcription–replication interactions termed transcription–replication immunoprecipitation on nascent DNA sequencing, TRIPn-Seq. TRIPn-Seq employs the sequential immunoprecipitation of RNA polymerase 2 phosphorylated at serine 5 (RNAP2s5) followed by enrichment of nascent DNA previously labeled with bromodeoxyuridine. Using TRIPn-Seq, we mapped 1009 unique transcription–replication interactions (TRIs) in mouse primary B cells characterized by a bimodal pattern of RNAP2s5, bidirectional transcription, an enrichment of RNA:DNA hybrids, and a high probability of forming G-quadruplexes. TRIs are highly enriched at transcription start sites and map to early replicating regions. TRIs exhibit enhanced Replication Protein A association and TRI-associated genes exhibit higher replication fork termination than control transcription start sites, two marks of replication stress. TRIs colocalize with double-strand DNA breaks, are enriched for deletions, and accumulate mutations in tumors. We propose that replication stress at TRIs induces mutations potentially contributing to age-related disease, as well as tumor formation and development.
High-grade ovarian cancer associated H/ACA snoRNAs promote cancer cell proliferation and survival
Authors: Faucher-Giguère Laurence , Roy Audrey , Deschamps-Francoeur Gabrielle , Couture Sonia , Nottingham Ryan M , Lambowitz Alan M , Scott Michelle S , Abou Elela Sherif
Published: January 2022

Small nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, assessing the nature and extent of snoRNAs’ contribution to cancer biology has been largely limited by difficulties in detecting highly structured RNA. In this study, we used a dedicated midsize non-coding RNA (mncRNA) sensitive sequencing technique to accurately survey the snoRNA abundance in independently verified high-grade serous ovarian carcinoma (HGSC) and serous borderline tumour (SBT) tissues. The results identified SNORA81, SNORA19 and SNORA56 as an H/ACA snoRNA signature capable of discriminating between independent sets of HGSC, SBT and normal tissues. The expression of the signature SNORA81 correlates with the level of ribosomal RNA (rRNA) modification and its knockdown inhibits 28S rRNA pseudouridylation and accumulation leading to reduced cell proliferation and migration. Together our data indicate that specific subsets of H/ACA snoRNAs may promote tumour aggressiveness by inducing rRNA modification and synthesis.
A comprehensive framework for analysis of microRNA sequencing data in metastatic colorectal cancer
Authors: Høye Eirik , Fromm Bastian , Böttger Paul H M , Domanska Diana , Torgunrud Annette , Lund-Andersen Christin , Abrahamsen Torveig Weum , Fretland Åsmund Avdem , Dagenborg Vegar J , Lorenz Susanne , Edwin Bjørn , Hovig Eivind , Flatmark Kjersti
Published: January 2022

Although microRNAs (miRNAs) contribute to all hallmarks of cancer, miRNA dysregulation in metastasis remains poorly understood. The aim of this work was to reliably identify miRNAs associated with metastatic progression of colorectal cancer (CRC) using novel and previously published next-generation sequencing (NGS) datasets generated from 268 samples of primary (pCRC) and metastatic CRC (mCRC; liver, lung and peritoneal metastases) and tumor adjacent tissues. Differential expression analysis was performed using a meticulous bioinformatics pipeline, including only bona fide miRNAs, and utilizing miRNA-tailored quality control and processing. Five miRNAs were identified as up-regulated at multiple metastatic sites Mir-210_3p, Mir-191_5p, Mir-8-P1b_3p [mir-141–3p], Mir-1307_5p and Mir-155_5p. Several have previously been implicated in metastasis through involvement in epithelial-to-mesenchymal transition and hypoxia, while other identified miRNAs represent novel findings. The use of a publicly available pipeline facilitates reproducibility and allows new datasets to be added as they become available. The set of miRNAs identified here provides a reliable starting-point for further research into the role of miRNAs in metastatic progression.
InterTADs: integration of multi-omics data on topologically associated domains, application to chronic lymphocytic leukemia
Authors: Tsagiopoulou Maria , Pechlivanis Nikolaos , Maniou Maria Christina , Psomopoulos Fotis
Published: January 2022

The integration of multi-omics data can greatly facilitate the advancement of research in Life Sciences by highlighting new interactions. However, there is currently no widespread procedure for meaningful multi-omics data integration. Here, we present a robust framework, called InterTADs, for integrating multi-omics data derived from the same sample, and considering the chromatin configuration of the genome, i.e. the topologically associating domains (TADs). Following the integration process, statistical analysis highlights the differences between the groups of interest (normal versus cancer cells) relating to (i) independent and (ii) integrated events through TADs. Finally, enrichment analysis using KEGG database, Gene Ontology and transcription factor binding sites and visualization approaches are available. We applied InterTADs to multi-omics datasets from 135 patients with chronic lymphocytic leukemia (CLL) and found that the integration through TADs resulted in a dramatic reduction of heterogeneity compared to individual events. Significant differences for individual events and on TADs level were identified between patients differing in the somatic hypermutation status of the clonotypic immunoglobulin genes, the core biological stratifier in CLL, attesting to the biomedical relevance of InterTADs. In conclusion, our approach suggests a new perspective towards analyzing multi-omics data, by offering reasonable execution time, biological benchmarking and potentially contributing to pattern discovery through TADs.
A comparison on predicting functional impact of genomic variants
Authors: Wang Dong , Li Jie , Wang Yadong , Wang Edwin
Published: January 2022

Single-nucleotide polymorphism (SNPs) may cause the diverse functional impact on RNA or protein changing genotype and phenotype, which may lead to common or complex diseases like cancers. Accurate prediction of the functional impact of SNPs is crucial to discover the ‘influential’ (deleterious, pathogenic, disease-causing, and predisposing) variants from massive background polymorphisms in the human genome. Increasing computational methods have been developed to predict the functional impact of variants. However, predictive performances of these computational methods on massive genomic variants are still unclear. In this regard, we systematically evaluated 14 important computational methods including specific methods for one type of variant and general methods for multiple types of variants from several aspects; none of these methods achieved excellent (AUC ≥ 0.9) performance in both data sets. CADD and REVEL achieved excellent performance on multiple types of variants and missense variants, respectively. This comparison aims to assist researchers and clinicians to select appropriate methods or develop better predictive methods.
Identification of differentially distributed gene expression and distinct sets of cancer-related genes identified by changes in mean and variability
Authors: Roberts Aedan G K , Catchpoole Daniel R , Kennedy Paul J
Published: January 2022

There is increasing evidence that changes in the variability or overall distribution of gene expression are important both in normal biology and in diseases, particularly cancer. Genes whose expression differs in variability or distribution without a difference in mean are ignored by traditional differential expression-based analyses. Using a Bayesian hierarchical model that provides tests for both differential variability and differential distribution for bulk RNA-seq data, we report here an investigation into differential variability and distribution in cancer. Analysis of eight paired tumour–normal datasets from The Cancer Genome Atlas confirms that differential variability and distribution analyses are able to identify cancer-related genes. We further demonstrate that differential variability identifies cancer-related genes that are missed by differential expression analysis, and that differential expression and differential variability identify functionally distinct sets of potentially cancer-related genes. These results suggest that differential variability analysis may provide insights into genetic aspects of cancer that would not be revealed by differential expression, and that differential distribution analysis may allow for more comprehensive identification of cancer-related genes than analyses based on changes in mean or variability alone.