bluuebunny/crossref_metadata_2025 huggingface dataset:
A convolutional neural network for common coordinate registration of high-resolution histology images
Authors: Daly Aidan C , Geras Krzysztof J , Bonneau Richard
Published: June 2021

Motivation

Registration of histology images from multiple sources is a pressing problem in large-scale studies of spatial -omics data. Researchers often perform ‘common coordinate registration’, akin to segmentation, in which samples are partitioned based on tissue type to allow for quantitative comparison of similar regions across samples. Accuracy in such registration requires both high image resolution and global awareness, which mark a difficult balancing act for contemporary deep learning architectures.

Results

We present a novel convolutional neural network (CNN) architecture that combines (i) a local classification CNN that extracts features from image patches sampled sparsely across the tissue surface and (ii) a global segmentation CNN that operates on these extracted features. This hybrid network can be trained in an end-to-end manner, and we demonstrate its relative merits over competing approaches on a reference histology dataset as well as two published spatial transcriptomics datasets. We believe that this paradigm will greatly enhance our ability to process spatial -omics data, and has general purpose applications for the processing of high-resolution histology images on commercially available GPUs.

Availability and implementation

All code is publicly available at https://github.com/flatironinstitute/st_gridnet.

Supplementary information

Supplementary data are available at Bioinformatics online.
Righting the Police: How do Officers Make Sense of Human Rights?
Authors: Martin Richard
Published: June 2021

Human rights have become a dominant paradigm in police reform projects worldwide, championed by policymakers, legislators and campaigners alike. Such projects are often premised on, and evaluated according to, a conception of human rights as an autonomous, coherent and legitimate body of norms. It is a paradigm made real through formal training, procedures and oversight. This paper invites a different reading of human rights. Drawing on extensive interviews with junior officers, it reveals how human rights come to be emergent from, and embedded within, the minutia of their working lives. The presence and meaning of human rights are sustained through a series of ‘sensemaking’ narratives arising from the rich intermingling of legal and organizational representations of rights and officers’ own experiences. Subtle variations, inconsistencies and contradictions in officers’ sensemaking are revealed across a four-fold typology which disrupts the stability and coherency of the human rights paradigm, but also generalizations made about police culture.
Community based participatory governance platforms and sharing of mining benefits: evidence from Ghana
Authors: Kasimba Sam A , Lujala Päivi
Published: June 2021

Participatory governance at the community level natural resource revenue management is thought to promote local stakeholders’ interests in how benefits from extraction are shared, strengthen the legitimacy of decisions, and enhance the quality of development projects financed by resource revenues. This article develops a framework to study the potential of localized participatory governance platforms in natural resource revenue management from the viewpoint of the intended beneficiaries, the local community members living in communities hosting large-scale extraction. The study focuses on local benefit-sharing trust funds that receive substantial amounts of funding to finance community development projects. Analysing in-depth two trust funds in Ghana, the article finds that the studied trust funds face three key challenges related to their participatory governance platforms: inadequate inclusion of community members in the processes that established the platforms, lack of relevant knowledge among the platform participants, and power asymmetries. The findings suggest that there is a need to include all intended platform stakeholders already in the processes leading to the platform establishment; ensure the platform’s legitimacy and independence in the eyes of the weaker stakeholders; and build capacity among the platform participants to ensure knowledge-based decisions.
Screening for occult coronary artery disease in potential kidney transplant recipients: time for reappraisal?
Authors: Ferro Charles J , Berry Miriam , Moody William E , George Sudhakar , Sharif Adnan , Townend Jonathan N
Published: June 2021

Screening for occult coronary artery disease in potential kidney transplant recipients has become entrenched in current medical practice as the standard of care and is supported by national and international clinical guidelines. However, there is increasing and robust evidence that such an approach is out-dated, scientifically and conceptually flawed, ineffective, potentially directly harmful, discriminates against ethnic minorities and patients from more deprived socioeconomic backgrounds, and unfairly denies many patients access to potentially lifesaving and life-enhancing transplantation. Herein we review the available evidence in the light of recently published randomized controlled trials and major observational studies. We propose ways of moving the field forward to the overall benefit of patients with advanced kidney disease.
Establishing a core outcome measure for pain in patients with autosomal dominant polycystic kidney disease: a consensus workshop report
Authors: Natale Patrizia , Perrone Ronald D , Tong Allison , Harris Tess , Hannan Elyssa , Ju Angela , Burnette Eva , Casteleijn Niek F , Chapman Arlene , Eastty Sarah , Gansevoort Ron T , Hogan Marie , Horie Shigeo , Knebelmann Bertrand , Lee Richard , Mustafa Reem A , Sandford Richard , Baumgart Amanda , Craig Jonathan C , Rangan Gopala K , Sautenet Bénédicte , Viecelli Andrea K , Amir Noa , Evangelidis Nicole , Guha Chandana , Logeman Charlotte , Manera Karine , Matus Gonzalez Andrea , Howell Martin , Strippoli Giovanni F M , Cho Yeoungjee
Published: June 2021

Background

Pain is the highest prioritized patient-reported outcome in people with autosomal dominant polycystic kidney disease (ADPKD) but remains infrequently and inconsistently measured in clinical trials and poorly managed in clinical settings. A recently completed systematic review of pain in ADPKD identified 26 different outcome measures. None of these measures were considered appropriate as a core outcome measure due to the lack of patient-important dimensions, inadequate content, relatively long duration of completion time and limited evidence to support psychometric robustness.

Methods

We convened an international Standardized Outcomes in Nephrology–Polycystic Kidney Disease consensus workshop involving 21 patients/caregivers and 40 health professionals (clinicians, nurses, researchers, policy makers and industry representatives) from 18 countries to discuss the identification or development of a core outcome measure for pain.

Results

Four themes were identified highlighting fundamental issues for the measurement of pain in ADPKD: distressing and disrupting life participation; variability and ambiguity in defining pain; stigma, frustration and adaptation to pain; and ensuring validity and feasibility of pain measures.

Conclusions

Existing measures were found to be insufficient in capturing pain as a core outcome and there was consensus on the need for a new validated measure that is simple, succinct and addresses the impact of pain on life participation. This measure will facilitate the appropriate prioritization of pain in all trials and guide clinical decision making in people with ADPKD.
Policy-Based Editing-Enabled Signatures: Authenticating Fine-Grained and Restricted Data Modification
Authors: Sengupta Binanda , Li Yingjiu , Tian Yangguang , Deng Robert H , Yang Zheng
Published: June 2021

Data owners often encrypt their bulk data and upload it to cloud in order to save storage while protecting privacy of their data at the same time. A data owner can allow a third-party entity to decrypt and access her data. However, if that entity wants to modify the data and publish the same in an authenticated way, she has to ask the owner for a signature on the modified data. This incurs substantial communication overhead if the data is modified often. In this work, we introduce the notion of policy-based editing-enabled signatures, where the data owner specifies a policy for her data such that only an entity satisfying this policy can decrypt the data. Moreover, the entity is permitted to produce a valid signature for the modified data (on behalf of the owner) without interacting with the owner every time the data is modified. On the other hand, a policy-based editing-enabled signature (PB-EES) scheme allows the data owner to choose any set of modification operations applicable to her data and still restricts a (possibly untrusted) entity to authenticate the data modified using operations from that set only. We provide two PB-EES constructions, a generic construction and a concrete instantiation. We formalize the security model for PB-EESs and analyze the security of our constructions. Finally, we evaluate the performance of the concrete PB-EES instantiation.
Inhibition of myocardial cathepsin-L release during reperfusion following myocardial infarction improves cardiac function and reduces infarct size
Authors: He Weihong , McCarroll Charlotte S , Nather Katrin , Ford Kristopher , Mangion Kenneth , Riddell Alexandra , O’Toole Dylan , Zaeri Ali , Corcoran David , Carrick David , Lee Mathew M Y , McEntegart Margaret , Davie Andrew , Good Richard , Lindsay Mitchell M , Eteiba Hany , Rocchiccioli Paul , Watkins Stuart , Hood Stuart , Shaukat Aadil , McArthur Lisa , Elliott Elspeth B , McClure John , Hawksby Catherine , Martin Tamara , Petrie Mark C , Oldroyd Keith G , Smith Godfrey L ,   Oxford Acute Myocardial Infarction (OxAMI) Study, Channon Keith M , Berry Colin , Nicklin Stuart A , Loughrey Christopher M
Published: June 2021

Aims

Identifying novel mediators of lethal myocardial reperfusion injury that can be targeted during primary percutaneous coronary intervention (PPCI) is key to limiting the progression of patients with ST-elevation myocardial infarction (STEMI) to heart failure. Here, we show through parallel clinical and integrative preclinical studies the significance of the protease cathepsin-L on cardiac function during reperfusion injury.

Methods and results

We found that direct cardiac release of cathepsin-L in STEMI patients (n = 76) immediately post-PPCI leads to elevated serum cathepsin-L levels and that serum levels of cathepsin-L in the first 24 h post-reperfusion are associated with reduced cardiac contractile function and increased infarct size. Preclinical studies demonstrate that inhibition of cathepsin-L release following reperfusion injury with CAA0225 reduces infarct size and improves cardiac contractile function by limiting abnormal cardiomyocyte calcium handling and apoptosis.

Conclusion

Our findings suggest that cathepsin-L is a novel therapeutic target that could be exploited clinically to counteract the deleterious effects of acute reperfusion injury after an acute STEMI.
Left main coronary artery thrombus after cannabis consumption: a case report
Authors: Matta Anthony , Elenizi Khaled , Elbaz Meyer , Roncalli Jerome
Published: June 2021

Background

Left main coronary thrombus is a rare angiographic finding associated with serious outcomes such as sudden death and cardiogenic shock. Rupture of an underlying atherosclerotic plaque is the main risk factor. The role of cannabis consumption in the pathophysiology of acute cardiovascular disease is controversial.

Case presentation

We present a case of non-ST-elevation myocardial infarction characterized by a mobile left main coronary thrombus in a young male cannabis consumer successfully treated with manual aspiration, dual anti-platelet, and unfractionated heparin therapy.

Conclusion

Cannabis consumption could be a risk factor for coronary artery thrombosis. The pathophysiology mechanism of action is not well understood. Reaching an optimal management is a potential challenge for physicians.
School performance of children whose parents suffered torture and war—a register-based study in Denmark
Authors: Bager Line , Munk Laursen Thomas , Skipper Niels , Agerbo Esben
Published: June 2021

Background

Young refugees and descendants of refugees have different preconditions for learning than their peers without refugee background. Children growing up in families where parents have suffered torture and war trauma may represent a particularly vulnerable group. This study investigates whether children of torture survivors living in Denmark achieved different test scores throughout primary and secondary school compared to children of non-traumatized parents.

Methods

Using data from a national school test programme, tests from Grades 2–8 were compared for children whose parents had been treated for torture and war trauma as to their peers. Referral to specialized rehabilitation clinics was used to identify the traumatized parent group. The mean score difference was estimated using multilevel linear regression, and outcomes were measured within groups of parental region of origin to allow for region-specific effects. The odds of missing a test were also estimated with multilevel logistic regression.

Results

The study included 854 467 children [median age (interquartile range) =12 (3.3)] of which 7809 were children of the trauma-exposed parents. The analysis revealed that children of torture survivors achieved test scores between −6% (95% CI: −0.13, 0.00) and −38% (95% CI: −0.44, −0.32) of a standard deviation compared to children of non-traumatized parents, adjusted for the main effect of region of origin. They were also more likely to miss a test [OR=4.95 (95% CI: 4.30, 5.71)].

Conclusions

The findings indicate that risk factors for poorer school performance cluster in children of traumatized refugee parents, and reveal the possible adverse educational effects of trauma across generations.
MHC class IIa haplotypes derived by high-throughput SNP screening in an isolated sheep population
Authors: Dicks Kara L , Pemberton Josephine M , Ballingall Keith T , Johnston Susan E
Published: June 2021

Investigating the current evolutionary processes acting on a highly polymorphic gene region, such as the major histocompatibility complex (MHC), requires extensive population data for both genotypes and phenotypes. The MHC consists of several tightly linked loci with both allelic and gene content variation, making it challenging to genotype. Eight class IIa haplotypes have previously been identified in the Soay sheep (Ovis aries) of St. Kilda using Sanger sequencing and cloning, but no single locus is representative of all haplotypes. Here, we exploit the closed nature of the island population of Soay sheep and its limited haplotypic variation to identify a panel of SNPs that enable imputation of MHC haplotypes. We compared MHC class IIa haplotypes determined by Sanger sequence-based genotyping of 135 individuals to their SNP profiles generated using the Ovine Infinium HD BeadChip. A panel of 11 SNPs could reliably determine MHC diplotypes, and two additional SNPs within the DQA1 gene enabled detection of a recombinant haplotype affecting only the SNPs downstream of the expressed genes. The panel of 13 SNPs was genotyped in 5951 Soay sheep, of which 5349 passed quality control. Using the Soay sheep pedigree, we were able to trace the origin and inheritance of the recombinant SNP haplotype. This SNP-based method has enabled the rapid generation of locus-specific MHC genotypes for large numbers of Soay sheep. This volume of high-quality genotypes in a well-characterized population of free-living sheep will be valuable for investigating the mechanisms maintaining diversity at the MHC.
The Nursing Home Older Adult Gut Microbiome Composition Shows Time-dependent Dysbiosis and Is Influenced by Medication Exposures, Age, Environment, and Frailty
Authors: Haran John P , Zeamer Abigail , Ward Doyle V , Dutta Protiva , Bucci Vanni , McCormick Beth A
Published: June 2021

Older adults in nursing homes (NHs) have increased frailty, medication, and antimicrobial exposures, all factors that are known to affect the composition of gut microbiota. Our objective was to define which factors have the greatest association with the NH resident gut microbiota, explore patterns of dysbiosis and compositional changes in gut microbiota over time in this environment. We collected serial stool samples from NH residents. Residents were assessed using the Mini Nutritional Assessment tool and Clinical Frailty Scale. Bacterial composition of resident stool samples was determined by metagenomic sequencing. We used mixed-effect random forest modeling to identify clinical covariates that associate with microbiota. We enrolled and followed 166 residents from 5 NHs collecting 512 stool samples and following 15 residents for > 1 year. Medications, particularly psychoactive and antihypertensive medications, had the greatest effect on the microbiota. Age and frailty also contributed, and were associated with increased and decreased diversity, respectively. The microbiota of residents who had lived in the NH for > 1 year were enriched in inflammatory and pathogenic species and reduced in anti-inflammatory and symbiotic species. We observed intraindividual stability of the microbiome among older adults who had lived in the NH already for >1 year followed with sample collections 1 year apart. Older adult NH gut microbiome is heavily influenced by medications, age, and frailty. This microbiome is influenced by the length of NH residency with dysbiosis becoming evident at 12 months, however, after this point there is demonstrated relative stability over time.
Subjective Successful Aging: Measurement Invariance Across 12 Years
Authors: Wilson-Genderson Maureen , Heid Allison R , Cartwright Francine , Pruchno Rachel
Published: June 2021

Background and Objectives

Debates about how to define successful aging have dominated gerontology for over 60 years. Regardless of how successful aging is conceptualized, in order to accurately understand how the construct changes over time and how it differs between people of varying ages, successful aging must be measured with instruments that are valid, reliable, and have measurement invariance. These analyses focus on subjective successful aging and examine the extent to which a reliable, valid, 3-item scale has measurement invariance across 12 years for individuals aged 50–86.

Research Design and Methods

We analyzed 5 waves of data collected from a panel of 5,688 community-dwelling people aged 50–74 when recruited in 2006. We tested measurement invariance using the standard 4 nested steps,, introducing increasing parameter constraints at each step. Analyses were conducted using Mplus 7.

Results

Analyses revealed that the 3-item scale measuring subjective successful aging has adequate measurement invariance across time. We demonstrated that the scale has configural, metric, and scalar invariance by most standard metrics. Only residual invariance was not supported. However, because residuals are not part of the latent factor, invariance of the item residuals is inconsequential to interpretation of latent mean differences.

Discussion and Implications

Findings provide the foundation needed for researchers to examine change in subjective successful aging over time, differences in subjective successful aging between people of varying ages, and predictors of subjective successful aging, confident that the scale has adequate measurement invariance.
Does social media provide adequate health education for prevention of COVID-19? A case study of YouTube videos on social distancing and hand-washing
Authors: Bora Kaustubh , Pagdhune Avinash , Patgiri Saurav Jyoti , Barman Bhupen , Das Dulmoni , Borah Probodh
Published: June 2021

Social media offers an opportune platform for educating the public about the recommended interventions during global health emergencies. This case study evaluated information in the popular social media platform YouTube about two key interventions (namely, ‘social distancing’ and ‘hand washing’) recommended during coronavirus disease-2019. Using the keywords ‘social distancing’ and ‘hand washing’, 77 and 78 videos, respectively, were selected from YouTube through pre-defined criteria. The understandability, actionability and quality of information in these videos were assessed. Cumulatively, the social distancing videos received >9 million views and the hand-washing videos received >37 million views. Thirteen social distancing videos (16.9%) and 46 hand-washing videos (58.9%) provided understandable, actionable and good-quality information. The non-understandable, non-actionable or poor-quality videos had paradoxically more viewer engagements than the understandable, actionable or good-quality videos, respectively. Most social distancing videos came from news agencies (68.8%). Hand-washing videos were mostly uploaded by health agencies or academic institutes (52.6%). The videos were less likely to be understandable and actionable and to be of good quality when uploaded by sources other than health agencies or academic institutes. The paucity of adequate information and the limited representation of ‘authoritative’ sources were concerning. Strategies for harnessing social media as an effective medium for public health education are necessary during pandemics.
Constitutional self-negation in Venezuela: Problematizing constitutionalism’s internalization of the theory of constituent power
Authors: Macía Briedis Rafael
Published: June 2021

The article looks at the constitutional underpinnings of the political crisis that has unfolded in Venezuela (around the competing claims to the presidency by Juan Guaidó and Nicolás Maduro), in an effort to understand the structural elements that have enabled that crisis. The central argument of the article is that Venezuela presents an example of “self-negating constitutionalism.” A self-negating constitution is one that, by negating its own position as the exclusive, self-contained source of democratic authorization for a given polity, ultimately ceases to serve as the last instance for the adjudication of institutional conflicts, including conflicts about the proper locus of representation of the “sovereign” demos, thereby undermining the constitutional structure in its entirety and replacing the rule of law with extralegal power as the mechanism for the resolution of political disputes. As the paper will show, this is precisely what the Venezuelan Constitution has done by outsourcing the competency to “transform the state” to an institution supposedly authorized by the people’s “original constituent power.”
Single-step localization and excision of small pulmonary nodules using a mobile 3D C-arm
Authors: Hsieh Ming-Ju , Chou Pin-Li , Fang Hsin-Yueh , Wen Chih-Tsung , Chao Yin-Kai
Published: June 2021

OBJECTIVES

The use of a hybrid operating room equipped with robotic C-arm cone-beam computed tomography for single-step localization and excision of small pulmonary nodules finds high cost barriers. The new generation of 3D C-arm system not only depicts soft tissues with high contrast but also offers a more affordable and sustainable solution. This approach has been chiefly applied in the field of orthopedic surgery. In this case series, we describe the use of a mobile 3D C-arm system for localizing and removing small pulmonary nodules.

METHODS

Between July and September 2020, we identified 14 patients who underwent localization and removal of small pulmonary nodules with a 3D C-arm system. We retrospectively reviewed clinical records to document the feasibility and safety of the procedure.

RESULTS

The median tumour size was 7.5 mm [interquartile range (IQR): 5 − 9.75 mm], with a median distance from the pleural surface of 4.2 mm (IQR: 0.5 − 6.45 mm). We successfully visualized all of the pulmonary lesions by intraoperative CT imaging. Localization was achieved in 13 patients, who subsequently underwent complete thoracoscopic resection. The median time required to localize lesions was 41.5 min (IQR: 33.75 − 53.25 min), with a median radiation exposure (expressed through the skin absorbed dose) of 143.45 mGy (IQR: 86.1 − 194.6 mGy). Failure to localize occurred in 1 patient because of pneumothorax caused by repeated needle puncture. All patients were successfully discharged and the median length of stay was 2.5 days (IQR: 2 − 3 days).

CONCLUSIONS

This case series demonstrates the feasibility of single-step localization and excision of small pulmonary nodules using a mobile 3D C-arm.
Gene Conversion Facilitates the Adaptive Evolution of Self-Resistance in Highly Toxic Newts
Authors: Gendreau Kerry L , Hornsby Angela D , Hague Michael T J , McGlothlin Joel W
Published: June 2021

Reconstructing the histories of complex adaptations and identifying the evolutionary mechanisms underlying their origins are two of the primary goals of evolutionary biology. Taricha newts, which contain high concentrations of the deadly toxin tetrodotoxin (TTX) as an antipredator defense, have evolved resistance to self-intoxication, which is a complex adaptation requiring changes in six paralogs of the voltage-gated sodium channel (Nav) gene family, the physiological target of TTX. Here, we reconstruct the origins of TTX self-resistance by sequencing the entire Nav gene family in newts and related salamanders. We show that moderate TTX resistance evolved early in the salamander lineage in three of the six Nav paralogs, preceding the proposed appearance of tetrodotoxic newts by ∼100 My. TTX-bearing newts possess additional unique substitutions across the entire Nav gene family that provide physiological TTX resistance. These substitutions coincide with signatures of positive selection and relaxed purifying selection, as well as gene conversion events, that together likely facilitated their evolution. We also identify a novel exon duplication within Nav1.4 encoding an expressed TTX-binding site. Two resistance-conferring changes within newts appear to have spread via nonallelic gene conversion: in one case, one codon was copied between paralogs, and in the second, multiple substitutions were homogenized between the duplicate exons of Nav1.4. Our results demonstrate that gene conversion can accelerate the coordinated evolution of gene families in response to a common selection pressure.
Engineering large-scale chromosomal deletions by CRISPR-Cas9
Authors: Eleveld Thomas F , Bakali Chaimaa , Eijk Paul P , Stathi Phylicia , Vriend Lianne E , Poddighe Pino J , Ylstra Bauke
Published: June 2021

Large-scale chromosomal deletions are a prevalent and defining feature of cancer. A high degree of tumor-type and subtype specific recurrencies suggest a selective oncogenic advantage. However, due to their large size it has been difficult to pinpoint the oncogenic drivers that confer this advantage. Suitable functional genomics approaches to study the oncogenic driving capacity of large-scale deletions are limited. Here, we present an effective technique to engineer large-scale deletions by CRISPR-Cas9 and create isogenic cell line models. We simultaneously induce double-strand breaks (DSBs) at two ends of a chromosomal arm and select the cells that have lost the intermittent region. Using this technique, we induced large-scale deletions on chromosome 11q (65 Mb) and chromosome 6q (53 Mb) in neuroblastoma cell lines. A high frequency of successful deletions (up to 30% of selected clones) and increased colony forming capacity in the 11q deleted lines suggest an oncogenic advantage of these deletions. Such isogenic models enable further research on the role of large-scale deletions in tumor development and growth, and their possible therapeutic potential.
Association Between Smoke-Free Legislation in Hospitality Venues and Smoking Behavior of Young People: A Systematic Review
Authors: Garritsen Heike H , da Costa Senior Yoël Y , Rozema Andrea D , Kunst Anton E , Kuipers Mirte A G
Published: June 2021

Introduction

While evaluations of indoor smoke-free legislation have demonstrated major public health benefits among adults, their impact on the smoking behavior of young people remains unclear. Therefore, we performed a systematic review of the association between smoke-free legislation in hospitality venues and smoking behavior of young people.

Aims and Methods

A systematic search was conducted in PubMed, Scopus, and Embase in June 2020. We searched for studies that assessed the association of any form of smoke-free legislation in any hospitality venue (eg, bar and restaurant) with a smoking behavior outcome (eg, initiation and current smoking) among young people (aged 10–24 years). .

Results

Our search yielded 572 articles of which 31 were screened based on full-text and 9 were included in the analysis. All studies were published between 2005 and 2016. The majority of studies used a quasi-experimental design. Four studies evaluated smoke-free legislation in hospitality venues specifically. Two studies reported that comprehensive, but not weaker, smoke-free legislation decreases progression to established smoking. Two other studies provided mixed results on which level of comprehensiveness of legislation would be effective, and which smoking outcomes would be affected. Five studies evaluated legislation that also included other workplaces. Out of these five studies, three studies found significant decreases in current smoking, smoking frequency, and/or smoking quantity, whereas two other studies did not.

Conclusions

Most of the studies found that smoke-free legislation in hospitality venues is associated with a decrease in smoking behavior among young people. Their results indicate the need for comprehensive smoke-free legislation without exemptions.

Implications

This is the first systematic review to provide insight into the relationship between smoke-free legislation in hospitality venues and smoking behavior of young people. Our findings show that there is a need for comprehensive smoke-free legislation without exemptions (such as designated smoking areas).
Influence of d-wave superconductor orientation on Josephson current and phase difference in junctions with inhomogeneous ferromagnet
Authors: Djurdjević Stevan , Popović Zorica
Published: June 2021

Utilizing a microscopic Bogoliubov–de Gennes approach, we study the Josephson effect in arbitrarily oriented d-wave superconductors connected through two ferromagnets with noncollinear magnetizations, by solving the scattering problem. The critical Josephson current is calculated for various parameters of the junction. The mutual influence of d-wave superconducting electrodes’ orientation and angle $$\alpha$$ between magnetization in a ferromagnetic bilayer of thickness $$d$$ is analyzed. For various orientations of the superconducting electrodes, we calculate a $$(d,\alpha)$$ phase diagram and discuss the possibility of achieving not only the coexistence of two stable states $$0$$ and $$\pi$$ but also the coexistence of three stable states $$0$$, $$\pi$$ and $$\pi/2$$, by varying the angle between magnetizations. We also observe areas of coexistence of stable and metastable states.
PERFORMANCE OF HANDHELD NAI(TL) SPECTROMETERS AS DOSIMETERS BY LABORATORY AND FIELD DOSE RATE MEASUREMENTS
Authors: Clouvas A , Xanthos S , Boziari A , Leontaris F , Kaissas I , Omirou M
Published: June 2021

In the framework of the IAEA Coordinated Research Project (CRP) J02012 on ‘Advancing Radiation Detection Equipment for Detecting Nuclear and Other Radioactive Material Out of Regulatory Control’, the properties of two commercial instruments (1) InSpector 1000 analyzer (Canberra), with a 2″ × 2″ NaI(Tl) scintillator and (2) RIIDEYE M-G3 analyzer (Thermo Scientific), with a 3″ × 3″ NaI(Tl) scintillator, were evaluated as dosimeters by laboratory and field measurements. In the Ionizing Radiation Calibration Laboratory (IRCL) of the Greek Atomic Energy Commission, the NaI(Tl) spectrometers were tested in order to measure Ambient gamma Dose Equivalent Rate (ADER). The NaI(Tl) scintillators were irradiated in a homogeneous field with 662 keV photons with different ADER values from 0.17 to 100 μSv h−1 at 0° incidence (irradiation field perpendicular to the detector’s front window) and at 90° incidence. For each irradiation, the measured ADER by the spectrometers and the ‘true’ ADER values (provided by the IRCL) were compared. In addition, the angular dependence (0–359°) of the ADER response of the spectrometers was studied with a 152Eu source placed at 1, 2 and 3 m from the spectrometers. The ADER dependence as function of the distance from the 152Eu source (at 0° incidence) measured by the two detectors was compared with the theoretical one. In the field studies, ADER was measured by the spectrometers at seven locations belonging to the Greek Early Warning System Network (which is based on Reuter-Stokes ionization chambers). These locations have different ADER values ranging from 20 to 120 nSv h−1. In these locations, gamma ADER were also deduced (1) by in situ gamma spectrometry measurements with portable Germanium HPGe detectors and (2) by the Reuter-Stokes ionization chambers (by subtraction of the cosmic radiation). Gamma dose measurements were also performed with the InSpector 1000 and RIIDEYE M-G3 detectors in 25 locations (beaches) of Northern Greece and compared with the ADER values deduced by sand sample analysis with gamma spectroscopy. Beaches with sand are good candidates for such type of measurements since they are commonly flat and in principle the natural radionuclides are homogenously distributed.
The new Uruguayan private international law: an open door to party autonomy in international contracts
Authors: Florio de León Eduardo
Published: June 2021

On 17 November 2020, the General Law on Private International Law (Law 19.920) was approved. This Law resulted from a process of hard work that took over two decades of discussions and debates.1 With this Law, Uruguay becomes one of a group of countries that have already carried out this kind of reform, particularly in regard to international commercial law and international contracts. The new Law 19.920 allows parties to choose the applicable law (State or non-State law) to regulate their international contractual obligations. This reform has a real disruptive imprint since Uruguay leaves behind its old and anachronistic regulation of the matter. This article provides a general analysis of the regulation of international commercial law under Law 19.920 (Articles 13 and 51) and the new regime applicable to international contracts, including the parties’ right to choose the applicable law (Article 45) (State or non-State law), which increases their autonomy in comparison with the previous regime.
Should We Scan Hidradenitis Suppurativa Patients? A Systematic Review of Radiologic Findings
Authors: Gutfilen-Schlesinger Gabriel , Lopes de Souza Sergio Augusto , Gutfilen Bianca
Published: June 2021

OBJECTIVE

To bring awareness and close gaps between dermatologists and radiologists about the contribution of imaging techniques for diagnosis, treatment, and follow-up of hidradenitis suppurativa (HS).

DATA SOURCES

Investigators searched the PubMed database for articles on HS and radiology techniques.

STUDY SELECTION

Databases were searched up to December 2018. The query retrieved 257 publications, of which 103 were unique; of these, 7 were inaccessible. From the remaining 96, 33 were irrelevant (did not discuss HS lesion features). After applying the inclusion criteria, 63 studies were relevant to this study.

DATA EXTRACTION

A standardized form was constructed to extract data from eligible studies by two independent authors.

DATA SYNTHESIS

Imaging techniques are significant and useful tools in HS management. Imaging should be carried out to evaluate disease severity, subclinical features, treatment success, and intraoperative patient assessment. Providers should consider nonconventional radiology techniques, which are underused in clinical management of HS. Further, dermatology and radiology require a shared terminology of disease features to better understand patient status.

CONCLUSIONS

Publications on HS lesion imaging have increased over the years. Imaging techniques have proven useful for determining HS severity and treatment effectiveness, as well as intraoperative patient assessment. These authors strongly recommend the use of these techniques in routine clinical practice for patients with HS.
Induction of Neurogenesis and Angiogenesis in a Rat Hemisection Spinal Cord Injury Model With Combined Neural Stem Cell, Endothelial Progenitor Cell, and Biomimetic Hydrogel Matrix Therapy
Authors: Marrotte Eric J. , Johnson Khari , Schweller Ryan M. , Chapla Rachel , Mace Brian E. , Laskowitz Daniel T. , West Jennifer L.
Published: June 2021

OBJECTIVES:

Acute spinal cord injury is a devastating injury that may lead to loss of independent function. Stem-cell therapies have shown promise; however, a clinically efficacious stem-cell therapy has yet to be developed. Functionally, endothelial progenitor cells induce angiogenesis, and neural stem cells induce neurogenesis. In this study, we explored using a multimodal therapy combining endothelial progenitor cells with neural stem cells encapsulated in a bioactive biomimetic hydrogel matrix to facilitate stem cell–induced neurogenesis and angiogenesis in a rat hemisection spinal cord injury model.

DESIGN:

Laboratory experimentation.

SETTING:

University laboratory.

SUBJECTS:

Female Fischer 344 rats.

INTERVENTIONS:

Three groups of rats: 1) control, 2) biomimetic hydrogel therapy, and 3) combined neural stem cell, endothelial progenitor cell, biomimetic hydrogel therapy underwent right-sided spinal cord hemisection at T9–T10. The blinded Basso, Beattie, and Bresnahan motor score was obtained weekly; after 4 weeks, observational histologic analysis of the injured spinal cords was completed.

MEASUREMENTS AND MAIN RESULTS:

Blinded Basso, Beattie, and Bresnahan motor score of the hind limb revealed significantly improved motor function in rats treated with combined neural stem cell, endothelial progenitor cell, and biomimetic hydrogel therapy (p < 0.05) compared with the control group. The acellular biomimetic hydrogel group did not demonstrate a significant improvement in motor function compared with the control group. Immunohistochemistry evaluation of the injured spinal cords demonstrated de novo neurogenesis and angiogenesis in the combined neural stem cell, endothelial progenitor cell, and biomimetic hydrogel therapy group, whereas, in the control group, a gap or scar was found in the injured spinal cord.

CONCLUSIONS:

This study demonstrates proof of concept that multimodal therapy with endothelial progenitor cells and neural stem cells combined with a bioactive biomimetic hydrogel can be used to induce de novo CNS tissue in an injured rat spinal cord.
CD38-specific Chimeric Antigen Receptor Expressing Natural Killer KHYG-1 Cells: A Proof of Concept for an “Off the Shelf” Therapy for Multiple Myeloma
Authors: Stikvoort Arwen , van der Schans Jort , Sarkar Subhashis , Poels Renée , Ruiter Ruud , Naik Jyoti , Yuan Huipin , de Bruijn Joost D. , van de Donk Niels W. C. J. , Zweegman Sonja , Themeli Maria , Groen Richard , O’Dwyer Michael , Mutis Tuna
Published: June 2021

Chimeric antigen receptor (CAR) T cells are highly successful in the treatment of hematologic malignancies. We recently generated affinity-optimized CD38CAR T cells, which effectively eliminate multiple myeloma (MM) cells with little or no toxicities against nonmalignant hematopoietic cells. The lack of universal donors and long manufacturing times however limit the broad application of CAR T cell therapies. Natural killer (NK) cells generated from third party individuals may represent a viable source of “off the shelf” CAR-based products, as they are not associated with graft-versus-host disease unlike allogeneic T cells. We therefore explored the preclinical anti-MM efficacy and potential toxicity of the CD38CAR NK concept by expressing affinity-optimized CD38CARs in KHYG-1 cells, an immortal NK cell line with excellent expansion properties. KHYG-1 cells retrovirally transduced with the affinity-optimized CD38CARs expanded vigorously and mediated effective CD38-dependent cytotoxicity towards CD38high MM cell lines as well as primary MM cells ex vivo. Importantly, the intermediate affinity CD38CAR transduced KHYG-1 cells spared CD38neg or CD38int nonmalignant hematopoietic cells, indicating an optimal tumor nontumor discrimination. Irradiated, short living CD38CAR KHYG-1 cells also showed significant anti-MM effects in a xenograft model with a humanized bone marrow-like niche. Finally, CD38CAR KHYG-1 cells effectively eliminated primary MM cells derived from patients who are refractory to CD38 antibody daratumumab. Taken together, the results of this proof-of-principle study demonstrate the potential value of engineering affinity-optimized CD38CARs in NK cells to establish effective anti-MM effects, with an excellent safety profile, even in patients who failed to response to most advanced registered myeloma therapies, such as daratumumab.
Predictors of Burden and Resilience in Family Caregivers of Individuals With Opioid Use Disorder
Authors: Tyo Mirinda Brown , McCurry Mary K. , Horowitz June Andrews , Elliott Kathleen
Published: June 2021

Background

Family caregivers are an essential resource for individuals with opioid use disorder (OUD). Overburdened caregivers often experience detrimental effects to their emotional and physical well-being.

Method

A cross-sectional, nonexperimental, correlational study was used to identify correlates and predictors of burden and resilience in caregivers of care recipients with OUD. Pearson product–moment correlation and multiple regression analysis were used to explore the relationships between caregiver characteristics, care recipient characteristics, the caregiver–care-recipient dyad characteristics, and burden and resilience among caregivers of individuals with OUD and to determine the best predictive model. Participants (N = 152) completed the study using an online electronic survey.

Results

The standardized regression coefficients indicated that supervision of care recipient behavioral problems (β = .29), dyadic interaction (β = .29), caregiver stress (β = .28), and care recipient opioid use (β = .12) were the strongest predictors of caregiver burden, whereas caregiver mental health (β = −.31) and physical health (β = .30) were the strongest predictors of caregiver resilience.

Conclusions

Caregiver and care recipient characteristics, and their dyadic interaction, directly influence the degree of burden and resilience reported by family caregivers. Caregivers experiencing increased stress who are tasked with supervising problematic care recipient behaviors are more likely to experience higher levels of burden. In contrast, caregivers with good physical and mental health and adequate resources showed higher levels of resilience.
Citalopram and Cannabidiol
Authors: Anderson Lyndsey L. , Doohan Peter T. , Oldfield Lachlan , Kevin Richard C. , Arnold Jonathon C. , Berger Maximus , Amminger G. Paul , McGregor Iain S.
Published: June 2021

Background

Cannabidiol (CBD), a major nonintoxicating constituent of cannabis, exhibits anxiolytic properties in preclinical and human studies and is of interest as a novel intervention for treating anxiety disorders. Existing first-line pharmacotherapies for these disorders include selective serotonin reuptake inhibitor and other antidepressants. Cannabidiol has well-described inhibitory action on cytochrome P450 (CYP450) drug-metabolizing enzymes and significant drug-drug interactions (DDIs) between CBD and various anticonvulsant medications (eg, clobazam) have been described in the treatment of epilepsy. Here, we examined the likelihood of DDIs when CBD is added to medications prescribed in the treatment of anxiety.

Methods

The effect of CBD on CYP450-mediated metabolism of the commonly used antidepressants fluoxetine, sertraline, citalopram, and mirtazapine were examined in vitro. Cannabidiol-citalopram interactions were also examined in vivo in patients (n = 6) with anxiety disorders on stable treatment with citalopram or escitalopram who received ascending daily doses of adjunctive CBD (200–800 mg) over 12 weeks in a recent clinical trial.

Results

Cannabidiol minimally affected the metabolism of sertraline, fluoxetine, and mirtazapine in vitro. However, CBD significantly inhibited CYP3A4 and CYP2C19-mediated metabolism of citalopram and its stereoisomer escitalopram at physiologically relevant concentrations, suggesting a possible in vivo DDI. In patients on citalopram or escitalopram, the addition of CBD significantly increased citalopram plasma concentrations, although it was uncertain whether this also increased selective serotonin reuptake inhibitor–mediated adverse events.

Conclusions

Further pharmacokinetic examination of the interaction between CBD and citalopram/escitalopram is clearly warranted, and clinicians should be vigilant around the possibility of treatment-emergent adverse effects when CBD is introduced to patients taking these antidepressants.
The Association Between Traditional Chinese Medicine Body Constitution Deviation and Essential Hypertension: A Case–Control Study
Authors: LIAO Yung-Cheng , CHEN Li-Li , WANG Hsiao-Chiao , LIN Jui-Shan , LIN Tin-Kwang , LIN Shu-Chuan Amy
Published: June 2021

Background

The prevention and treatment of hypertension is valued globally. The World Health Organization advocates combining traditional medicines in the prevention and treatment of diseases. Traditional Chinese medicine (TCM) assumes that diseases originate from the attenuation of one's body constitution. A few studies have found that hypertension is correlated with TCM body constitution. However, body constitution is also affected by living environment. Therefore, investigating the correlation between deviations in body constitution and essential hypertension in different living environments is necessary to provide the basis for using TCM in combination with conventional Western medicine to prevent and treat hypertension.

Purpose

The aim of this study was to explore the association between TCM body constitution deviation and essential hypertension.

Methods

A case–control study was designed. Participants were selected from the outpatient clinics and neighboring communities of a regional teaching hospital in southern Taiwan. The study included 210 hypertension and 210 nonhypertension cases. Blood pressures were measured using an electronic sphygmomanometer to confirm the presence or absence of hypertension. The TCM Body Constitution Questionnaire, demographic datasheet, and hypertension-related factors questionnaire were used to collect data.

Results

A higher proportion of patients with body constitution deviation were found in the hypertension group than the nonhypertension group. The proportions of patients with Yin-Xu, Yang-Xu, and stasis constitution were 44.8%, 32.4%, and 30.6%, respectively, in the hypertension group and 28.6%, 25.2%, and 19.6%, respectively, in the nonhypertension group. After performing univariate analysis, the results showed significant differences between the two groups in terms of average body mass index; emotional traits of anger, worry, and fear; hyperlipidemia; hyperuricemia; Yin-Xu constitution; and stasis constitution. However, the multivariate analysis revealed having a Yin-Xu constitution to be a risk factor of essential hypertension after adjusting for age, gender, body mass index, emotional traits, drinking habit, hyperlipidemia, and hyperuricemia.

Conclusions/Implications for Practice

The results suggest that Yin-Xu and stasis constitutions are respectively associated with essential hypertension. The findings offer a valuable reference to governments and healthcare professionals to prevent the risk of essential hypertension. Screening and healthcare measures for TCM Yin-Xu or stasis constitution may be included in related prevention plans to minimize public exposure to the risk factors of essential hypertension.