bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of De Novo Donor-specific HLA Antibodies and AMR in Renal Transplant Patients Depends on CYP3A5 Genotype
Authors: Friebus-Kardash Justa , Nela Ejona , Möhlendick Birte , Kribben Andreas , Siffert Winfried , Heinemann Falko Markus , Eisenberger Ute 
Published: July 2021

Background.
The single-nucleotide polymorphism CYP3A5 rs776746 is related to a reduction in the metabolizing activity of the CYP3A5 enzyme. People carrying at least one copy of the wild-type allele, defined as CYP3A5 expressers, exhibit higher clearance and lower trough concentrations of tacrolimus than homozygous nonexpressers, and this difference may affect alloimmunization and allograft function.

Methods.
We retrospectively studied 400 kidney transplant recipients treated with a tacrolimus-based immunosuppression regimen to detect CYP3A5 genotype, de novo formation of HLA antibodies and donor-specific antibodies (DSAs), and clinical outcome up to 5 y after transplant.

Results.
We found that 69 (17%) of the 400 patients were CYP3A5 expressers. During the first 3 y after transplant, CYP3A5 expressers tended to have lower tacrolimus trough levels than nonexpressers, although their tacrolimus dosage was as much as 80% higher. De novo DSAs were found more frequently in CYP3A5 expressers than in nonexpressers (13/69 [19%] versus 33/331 [10%], P = 0.02). De novo DSA-free survival rates (P = 0.02) were significantly lower for expressers than for nonexpressers. CYP3A5 genotype had no effect on allograft failure, but CYP3A5 expressers exhibited a significantly higher frequency of antibody-mediated rejection. CYP3A5 expresser status was an independent risk factor for the development of de novo DSAs (relative risk, 2.34, P = 0.01).

Conclusions.
Early detection of CYP3A5 expressers, enabling genotype-based dose adjustment of tacrolimus immediately after renal transplant, may be a useful strategy for reducing the risk of de novo DSA production and antibody-mediated rejection.
Factors Associated With Increased Emergency Department Utilization in Patients With Acute Optic Neuritis
Authors: Muro-Fuentes Elena A. , Moss Heather E. 
Published: July 2021

Background:
Symptoms of acute vision loss and eye pain may lead patients with optic neuritis to seek care in the emergency department (ED). Given the availability of lower cost alternatives for providing medical care for optic neuritis, this study aimed to identify factors associated with higher ED utilization.

Methods:
Subjects with acute optic neuritis were identified through a chart review of adults with International Classification of Diseases-9 (ICD-9) or ICD-10 codes for optic neuritis with corresponding gadolinium contrast enhancement of the optic nerve on MRI in the medical record research repository of a tertiary care institution. Subjects were grouped based on the number of ED visits (0–1 and 2–3) within 2 months of either ICD code or MRI. Demographics, characteristics of disease presentation, type and location of medical care, testing (chest imaging, lumbar puncture, optical coherence tomography, spine MRI, visual field, and laboratory tests), treatment, provider specialty of follow-up visits, and duration of care were extracted from the medical record.

Results:
Of 30 acute optic neuritis subjects (age 41 ± 16 years, range 18–76, 53% [16/30] female), 19 had 0–1 ED visit and 11 had 2–3 ED visits. Most subjects were Caucasian, non-Hispanic (47%), followed by Asian (23%), Hispanic/Latino (17%), Black (10%), and others (3%). Subjects had an initial clinical encounter primarily in the outpatient setting (63%) as compared with the ED (37%). The median time from symptom onset to initial clinical encounter was 4 days with a range of 0–13. Subjects were mostly insured through a private insurance (60%), followed by Medicare/Medicaid (23%) and uninsured (17%). Fewer ED visits were associated with an initial clinical encounter in an outpatient setting (P = 0.02, chi-square), but not residential distance from the hospital or insurance type. Subjects with a higher number of ED visits were more likely to be of Hispanic/Latino ethnicity (P = 0.047, Fisher exact). There was no significant difference in the ophthalmic, radiologic, or laboratory testing performed in both groups. Both groups presented in a similar time frame with similar symptoms and clinical signs. Treatment was similar in both groups.

Conclusions:
Subjects with their first clinical encounter for optic neuritis in the ED had more visits to the ED overall when compared with those first seen in an outpatient setting and thus strategies aimed at facilitating outpatient care may help reduce unnecessary ED visits, although some, such as insurance status, may be difficult to modify. Further study in a larger sample is needed to refine these observations.
Recent trends in the management of depression in persons with cancer
Authors: Panjwani Aliza A. , Li Madeline 
Published: July 2021

Purpose of review
Depression is a prevalent comorbidity in cancer that significantly increases the risk for numerous negative health outcomes. This review updates the current evidence base for management of depression in cancer, highlighting new research directions based on the inflammatory hypothesis of depression.

Recent findings
Research on pharmacotherapy and psychotherapy for depression in cancer has shown mixed efficacy partly because of methodological issues arising from the phenomenology of depression in cancer. After decades of stagnancy, more recent high-quality clinical trials are beginning to provide an evidence base to guide treatment. Inflammatory cytokine-associated depression is a subtype of depression that may have particular relevance in cancer, opening new avenues to explore therapeutic targets and biobehavioral impacts of interventions, which may improve cancer outcomes.

Summary
The continuum of severity in cancer-related depression is important to consider in management approaches. Choice of treatment should be personalized to the patient and their symptom profile as there is currently insufficient evidence to recommend any particular medication or psychotherapy over another. Psychological interventions should be considered first line for mild-to-moderate depression, and pharmacological treatment added for more severe depression, which can be optimally delivered within a collaborative care model.

Video abstract

http://links.lww.com/YCO/A62
Synergistic motion compensation strategies for positron emission tomography when acquired simultaneously with magnetic resonance imaging
Authors: Polycarpou Irene , Soultanidis Georgios , Tsoumpas Charalampos 
Published: July 2021

Subject motion in positron emission tomography (PET) is a key factor that degrades image resolution and quality, limiting its potential capabilities. Correcting for it is complicated due to the lack of sufficient measured PET data from each position. This poses a significant barrier in calculating the amount of motion occurring during a scan. Motion correction can be implemented at different stages of data processing either during or after image reconstruction, and once applied accurately can substantially improve image quality and information accuracy. With the development of integrated PET-MRI (magnetic resonance imaging) scanners, internal organ motion can be measured concurrently with both PET and MRI. In this review paper, we explore the synergistic use of PET and MRI data to correct for any motion that affects the PET images. Different types of motion that can occur during PET-MRI acquisitions are presented and the associated motion detection, estimation and correction methods are reviewed. Finally, some highlights from recent literature in selected human and animal imaging applications are presented and the importance of motion correction for accurate kinetic modelling in dynamic PET-MRI is emphasized.This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 2’.
Motion estimation and correction for simultaneous PET/MR using SIRF and CIL
Authors: Brown Richard , Kolbitsch Christoph , Delplancke Claire , Papoutsellis Evangelos , Mayer Johannes , Ovtchinnikov Evgueni , Pasca Edoardo , Neji Radhouene , da Costa-Luis Casper , Gillman Ashley G. , Ehrhardt Matthias J. , McClelland Jamie R. , Eiben Bjoern , Thielemans Kris 
Published: July 2021

SIRF is a powerful PET/MR image reconstruction research tool for processing data and developing new algorithms. In this research, new developments to SIRF are presented, with focus on motion estimation and correction. SIRF’s recent inclusion of the adjoint of the resampling operator allows gradient propagation through resampling, enabling the MCIR technique. Another enhancement enabled registering and resampling of complex images, suitable for MRI. Furthermore, SIRF’s integration with the optimization library CIL enables the use of novel algorithms. Finally, SPM is now supported, in addition to NiftyReg, for registration. Results of MR and PET MCIR reconstructions are presented, using FISTA and PDHG, respectively. These demonstrate the advantages of incorporating motion correction and variational and structural priors.
This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 2’.
Investigating the contributions of circadian pathway and insomnia risk genes to autism and sleep disturbances
Authors: Tesfaye Rackeb , Huguet Guillaume , Smiliovich Zoe , Loum Mor Absa , Douard Elise , Jean-Louis Martineau , Martinot Jean Luc , Whelan Rob , Desrivieres Sylvane , Heinz Andreas , Schumann Gunter , Hayward Caroline , Elsabbagh Mayada , Jacquemont Sebastien 
Published: July 2021

AbstractSleep disturbance is prevalent in youth with Autism Spectrum Disorder (ASD). Researchers have posited that circadian dysfunction may contribute to sleep problems or exacerbate ASD symptomatology. However, there is limited genetic evidence of this. It is also unclear how insomnia risk genes identified through GWAS in a general population are related to ASD risk and common sleep problems like insomnia in ASD. We investigated the contribution of copy number variants (CNVs) encompassing circadian pathway genes and insomnia risk genes to ASD risk as well as parent reported sleep disturbances in children diagnosed with ASD. We studied 5860 ASD probands and 2092 unaffected siblings from the Simons Simplex Collection and MSSNG database, as well as 7463 individuals from two unselected populations (IMAGEN and Generation Scotland). We identified 320 and 626 rare CNVs encompassing circadian genes and insomnia risk genes respectively. Deletions and duplications with circadian genes were overrepresented in ASD probands compared to siblings and unselected controls. For insomnia-risk genes, deletions (but not duplications) were also associated with ASD. Results remained significant after adjusting for cognitive ability. CNVs containing circadian pathway and insomnia risk genes showed a stronger association with ASD, compared to CNVs containing other genes. Duplications containing circadian genes were associated with shorter sleep duration (22 minutes). Only insomnia risk genes intolerant to haploinsufficiency increased insomnia traits when duplicated. Overall, CNVs encompassing circadian and insomnia risk genes increase ASD risk despite small impacts on sleep disturbances.
Facilitators and Barriers to Compliance with COVID-19 Guidelines: A Structural Topic Modelling Analysis of Free-Text Data from 17,500 UK Adults
Authors: Wright Liam , Paul Elise , Steptoe Andrew , Fancourt Daisy 
Published: July 2021

AbstractBackgroundDuring the COVID-19 pandemic, the UK government has implemented a series of guidelines, rules, and restrictions to change citizens’ behaviour to tackle the spread of the virus, such as the promotion of face-masks and the imposition of lockdown stay-at-home orders. The success of these measures requires active co-operation on the part of citizens, but compliance has not been complete. Detailed data is required on the factors aiding or hindering compliance with these measures.MethodsTo understand the facilitators and barriers to compliance with COVID-19 guidelines, we used structural topic modelling, a text mining technique, to extract themes from over 26,000 free-text survey responses from 17,500 UK adults, collected between 17 November and 23 December 2020.ResultsThe main factors facilitating compliance were desires to reduce risk to one’s self and one’s family and friends and to, a lesser extent, the general public. Also of importance were a desire to return to normality, the availability of activities and technological means to contact family and friends, and the ability to work from home. Identified barriers were difficulties maintaining social distancing in public (due to the actions of other people or environmental constraints), the need to provide or receive support from family and friends, social isolation, missing loved one, and mental health impacts, perceiving the risks as low, social pressure to not comply, and difficulties understanding and keep abreast of changing rules. Several of the barriers and facilitators raised were related to participant characteristics. Notably, women were more likely to discuss needing to provide or receive mental health support from friends and family.ConclusionThe results demonstrate an array of factors contribute to compliance with guidelines. Of particular policy importance, the results suggest that government communications that emphasizes the potential risks of COVID-19 and provides simple, consistent guidance on how to reduce the spread of the virus would improve compliance with preventive behaviours.
Implications of COVID-19 vaccination and public health countermeasures on SARS-CoV-2 variants of concern in Canada: evidence from a spatial hierarchical cluster analysis
Authors: Adeyinka Daniel A , Camillo Cheryl A. , Marks Wendie , Muhajarine Nazeem 
Published: July 2021

AbstractBackgroundThe influence of coronavirus disease-2019 (COVID-19) containment measures on variants of concern (VOC) has been understudied in Canada. Our objective was to identify provinces with disproportionate prevalence of VOC relative to COVID-19 mitigation efforts in provinces and territories in Canada.MethodsWe analyzed publicly available provincial- and territorial-level data on the prevalence of VOCs in relation to mitigating factors (summarized in three measures: 1. strength of public health countermeasures: stringency index, 2. how much people moved about outside their homes: mobility index, and 3. vaccine intervention: proportion of Canadian population fully vaccinated). Using spatial agglomerative hierarchical cluster analysis (unsupervised machine learning), the provinces and territories were grouped into clusters by stringency index, mobility index and full vaccine coverage. Kruskal-Wallis test was used to determine the differences in the prevalence of VOC (Alpha, or B.1.1.7, Beta, or B.1.351, Gamma, or P.1, and Delta, or B.1.617.2 variants) between the clusters.ResultsThree clusters of vaccine uptake and countermeasures were identified. Cluster 1 consisted of the three Canadian territories, and characterized by higher degree of vaccine deployment and lesser degree of countermeasures. Cluster 2 (located in Central Canada and Atlantic region) was typified by lesser implementation of vaccine deployment and moderate countermeasures. The third cluster was formed by provinces in the Pacific region, Central Canada, and Prairie region, with moderate vaccine deployment but stronger countermeasures. The overall and variant-specific prevalence were significantly different across the clusters.InterpretationThis study found that implementation of COVID-19 public health measures varied across the provinces and territories. Considering the high prevalence of VOCs in Canada, completing the second dose of COVID-19 vaccine in a timely manner is crucial.
Examining the Relationship between COVID-19 Vaccinations and Reported Incidence
Authors: Shacham Enbal , Scroggins Stephen , Garza Alexander 
Published: July 2021

AbstractAs COVID-19 has caused significant morbidity and mortality throughout the world, the development and distribution of an effective vaccine have been swift but not without challenges. Earlier demand and access barriers have seemingly been addressed with more free and accessible vaccines now available for a wide variety of ages. While rates of COVID-19 have decreased overall, some geographic areas continue to experience rapid outbreaks. The purpose of this study was to examine the relationship between vaccination uptake and weekly COVID-19 cases throughout locations in the state of Missouri.MethodsAmong all Missouri counties and two cities (n=117), weekly COVID-19 incidence and cumulative proportion of residents fully vaccinated were abstracted from the Missouri Department of Health and Senior Services during a 25-week period from January 4 to Jun 26, 2021. Additional ecological variables known to be associated with COVID-19 incidence and prevalence were collected from the U.S. Census Bureau and integrated into data: total population, proportion of nonwhite residents, annual median household income, proportion of residents working in public facing occupations. Descriptive and inferential statistics were completed which included the calculation of both linear and nonlinear models using repeated measure data to determine the quantitative association between vaccination uptake and reported COVID-19 cases in the presence of location characteristics.ResultsThroughout the 25 weeks of observations, the average weekly number of COVID-19 cases reported was 66.1 (SD=260.8) while the average cumulative proportion vaccinated individuals at the end of the 25 weeks was 25.8% (SD=6.8%) among study locations. While graphing seemed to suggest a more nonlinear relationship between COVID-19 incidence and proportion vaccinated, comparison of crude linear and nonlinear models pointed to the relationship likely being linear during study period. The final adjusted linear model exhibited a significant relationship between COVID-19 cases and proportion vaccinated, specifically every percent increase in population vaccinated resulted in 3 less weekly COVID-19 cases being reported (β -3.74, p<0.001. Additionally, when controlling for other factors, the adjusted model revealed locations with higher proportions of nonwhite residents were likely to experience less weekly COVID-19 cases (β -1.48, p=0.037).DiscussionOverall, this study determined that increasing the proportion of residents vaccinated decreases COIVD-19 cases by a substantial amount over time. These findings provide insights into possible messaging strategies that can be leveraged to develop more effective implementation and uptake. As the COVID-19 pandemic persists and vaccination numbers begin to plateau, diverse communication strategies become a critical necessity to reach a wider population.
Attempted Suicide and Criminal Justice System in a Sample of Forensic Psychiatric Patients in Malaysia
Authors: Khamis Johari , Panirselvam Ravivarma Rao , Badruddin Norhameza Ahmad , Ab Rahman Farynna Hana , Chan Lai Fong 
Published: July 2021

AbstractCriminalization of suicide attempts is an archaic barrier to suicide prevention. Globally, clinical profiles of prosecuted suicide attempters are an under-researched area. This retrospective study aims to describe the clinical profiles of individuals who were charged for attempted suicide and subsequently sent for criminal responsibility and fitness to plead evaluation in a forensic psychiatric unit in Malaysia from January 1, 2008, to December 31, 2019. We identified 22 cases who were mostly adult males (90.9%). Seventy-three percent have a psychiatric disorder. Mood disorders were more prevalent (32%) followed by psychotic disorders and substance use disorders. For most of these individuals, this was the first contact with any form of mental health services and 41% defaulted their treatment before arrest. This sample illustrates a vulnerable group who has been disengaged with mental healthcare. Future research is warranted to further investigate mechanisms that are effective in addressing unmet needs of persons in suicidal crisis as opposed to utilizing the criminal justice pathway.
Treatment of sarcoidosis with cutaneous involvement with tofacitinib
Authors: Damsky William , Wang Alice , Young Bryan D. , Ayasun Ruveyda , Ryu Changwan , McGeary Meaghan K. , Fazzone-Chettiar Ramesh , Pucar Darko , Gulati Mridu , Miller Edward J. , Bosenberg Marcus , Flavell Richard A. , King Brett 
Published: July 2021

AbstractSarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids and there are no approved steroid-sparing medications. There is emerging evidence that Janus kinase (JAK) inhibitors, which inhibit JAK-dependent cytokine activity, may hold promise in sarcoidosis. In this open-label trial, 10 patients with recalcitrant sarcoidosis with cutaneous involvement were treated with tofacitinib 5 mg twice daily. There was no washout period and patients were permitted to continue, taper, or discontinue other treatments. The primary outcome was the change in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) activity score after 6 months. Change in internal organ disease activity was also assessed using total lesion glycolysis (TLG) determined by full-body positron emission tomography. A mean reduction in the CSAMI activity score of 82.7% was observed, with 6 patients showing a complete response. Internal organ response data was available in 8 patients; a decrease in TLG of ≥50% was noted in 5 patients, with complete or near complete resolution in 3 (>98% reduction in TLG). Patients were generally able to significantly taper or discontinue their baseline immunosuppressive regimen, which included prednisone in 5 patients. Single cell RNA-sequencing, bulk RNA-sequencing, and high-throughput proteomic analyses were performed on skin and blood as a function of treatment in order to delineate changes in immunologic signals with therapy. We identified CD4+ T cell derived IFN-γ as a central cytokine driver of sarcoidosis and inhibition of its activity was achieved with tofacitinib and correlated closely with clinical improvement. Tofacitinib appears to have impressive activity in treatment of sarcoidosis and likely acts by inhibiting IFN-γ, larger, controlled studies are warranted.