bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting Progression in Patients With Different Clinical Presentations of Primary Open-angle Glaucoma
Authors: Abu Sampson L. , Marín-Franch Iván , Racette Lyne 
Published: April 2021

Précis:
Glaucoma progression was more frequently identified by assessing retinal fiber layer thickness than by monitoring visual field (VF) loss for different baseline classifications in primary open-angle glaucoma.

Purpose:
The aim was to compare the detection of glaucoma progression by retinal nerve fiber layer thickness (RNFLT) and VF assessments for different baseline classifications of primary open-angle glaucoma.

Methods:
This study included 194 eyes from 194 patients with a minimum of 9 follow-up visits selected from the Diagnostic Innovation in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). Each eye was classified according to baseline clinical signs: ocular hypertension (n=39), glaucomatous optic neuropathy only (n=60), glaucomatous visual field loss only (GVF, n=39) and definite glaucoma (concurrent optic disc and VF defect, n=56). We assessed progression by performing simple linear regression on global and sectorial mean deviations values generated for RNFLT (RNFLT-MD) and VF data (VF-MD). The proportion of eyes identified as progressing (positive rate) by RNFLT-MD and by VF-MD were compared within each classification.

Results:
Whereas both parameters performed similarly among glaucomatous optic neuropathy only and definite glaucoma eyes, the positive rate obtained with global RNFLT-MD was significantly greater compared with global VF-MD by 33.3% and 30.8% among ocular hypertension eyes and GVF eyes, respectively. This finding was consistent in the inferotemporal sector; however, similar positive rates were obtained for both parameters in the superotemporal sector.

Conclusions:
While both RNFLT and VF parameters showed comparable abilities to identify progression across the different classifications, RNFLT assessment may be better suited to monitor progression, particularly among patients with elevated intraocular pressure and those who present with only GVF defect at baseline.
Rotavirus Strain Surveillance in Estonia After Introduction of Rotavirus Universal Mass Vaccination
Authors: Kõivumägi Kadri , Soeorg Hiie , Toompere Karolin , Kallas Eveli , Jõegeda Ene-Ly , Lass Evely , Huik Kristi , Lutsar Irja 
Published: April 2021

Background:
Estonia implemented the rotavirus (RV) vaccine into its national immunization program in July 2014. We aimed to determine circulating RV genotypes and the clinical profile by genotypes from February 1, 2015, to August 30, 2016, among children 0–18 years hospitalized due to rotavirus gastroenteritis (RVGE).

Methods:
During an observational study in 7 Estonian hospitals, we determined the RV genotypes in stool samples of RVGE patients who met predetermined criteria. Shannon’s diversity index (H´) and Simpson’s index (D) was used to evaluate genotype diversity by season and age and to compare prevaccine period data (2007–2008) for children 0–4 years of age (n = 77) to corresponding data from the postvaccine period (2015–2016, n = 346). The Vesikari Clinical Severity Scoring System was used for clinical profile evaluation.

Results:
Stool samples of 479 RVGE patients were genotyped. Seventy-seven percent of RVGE infections were caused by G4P[8] (n = 150, 31%), G1P[8] (n = 100, 21%), G9P[8] (n = 79, 16%), G2P[4] (n = 23, 5%), G4P[4] (n = 17,  4%). The prevailing genotypes varied seasonally. Diversity increased during the postvaccine period among age groups 0–4: H´1.42 (95% CI: 1.2–1.7) in the prevaccine era versus 1.8 (95% CI: 1.7–2) in the postvaccine era (P = 0.008), and D 0.6 (95% CI: 0.5–0.7) versus 0.78 (0.75–0.80) (P = 0.01), respectively. The off-season period presented higher diversity compared with in-seasons. G2P[8], G1P[8], G4P[4], G9P[8], and G8P[8] presented with a different clinical profile compared with others.

Conclusion:
Since the introduction of universal mass vaccination in Estonia, the circulating RV genotypes have changed compared with those reported in the prevaccine era. Our study adds to knowledge about RV genotype distribution in Europe and expected dynamics after RV universal mass vaccination and provides insight on the clinical profile of prevailing genotypes.
Dynamics of brain function in patients with chronic pain assessed by microstate analysis of resting-state electroencephalography
Authors: May Elisabeth S. , Gil Ávila Cristina , Ta Dinh Son , Heitmann Henrik , Hohn Vanessa D. , Nickel Moritz M. , Tiemann Laura , Tölle Thomas R. , Ploner Markus 
Published: April 2021

Abstract
Chronic pain is a highly prevalent and severely disabling disease that is associated with substantial changes of brain function. Such changes have mostly been observed when analyzing static measures of resting-state brain activity. However, brain activity varies over time, and it is increasingly recognized that the temporal dynamics of brain activity provide behaviorally relevant information in different neuropsychiatric disorders. Here, we therefore investigated whether the temporal dynamics of brain function are altered in chronic pain. To this end, we applied microstate analysis to eyes-open and eyes-closed resting-state electroencephalography data of 101 patients suffering from chronic pain and 88 age- and sex-matched healthy controls. Microstate analysis describes electroencephalography activity as a sequence of a limited number of topographies termed microstates that remain stable for tens of milliseconds. Our results revealed that sequences of 5 microstates, labelled with the letters A to E, consistently described resting-state brain activity in both groups in the eyes-closed condition. Bayesian analysis of the temporal characteristics of microstates revealed that microstate D has a less predominant role in patients than in controls. As microstate D has previously been related to attentional networks and functions, these abnormalities might relate to dysfunctional attentional processes in chronic pain. Subgroup analyses replicated microstate D changes in patients with chronic back pain, while patients with chronic widespread pain did not show microstates alterations. Together, these findings add to the understanding of the pathophysiology of chronic pain and point to changes of brain dynamics specific to certain types of chronic pain.
Patient outcomes after opioid dose reduction among patients with chronic opioid therapy
Authors: Hallvik Sara E. , El Ibrahimi Sanae , Johnston Kirbee , Geddes Jonah , Leichtling Gillian , Korthuis P. Todd , Hartung Daniel M. 
Published: April 2021

Abstract
The net effects of prescribing initiatives that encourage dose reductions are uncertain. We examined whether rapid dose reduction after high-dose chronic opioid therapy (COT) associates with suicide, overdose, or other opioid-related adverse events. This retrospective cohort study included Oregon Medicaid recipients with high-dose COT. Claims were linked with prescription data from the prescription drug monitoring program and death data from vital statistics, 2014 to 2017. Participants were placed into 4 mutually exclusive dose trajectory groups after the high-dose COT period, and Cox proportional hazard models were used to examine the effect of dose changes on patient outcomes in the following year. Of the 14,596 high-dose COT patients, 4191 (28.7%) abruptly discontinued opioid prescriptions, 1648 (11.3%) reduced opioid dose before discontinuing, 6480 (44.4%) had a dose reduction but never discontinued, and 2277 (15.6%) had a stable or increasing dose. Discontinuation, whether abrupt (adjusted hazard ratio [aHR] 3.63; 95% confidence interval [CI] 1.42-9.25) or with dose reduction (aHR 4.47, 95% CI 1.68-11.88) significantly increased risk of suicide compared with those with stable or increasing dose. By contrast, discontinuation or dose reduction reduced the risk of overdose compared with those with a stable or increasing dose (aHR 0.36–0.62, 95% CI 0.20-0.94). Patients with an abrupt discontinuation were more likely to overdose on heroin (vs. prescription opioids) than patients in other groups (P < 0.0001). Our study suggests that patients on COT require careful risk assessment and supportive interventions when considering opioid discontinuation or continuation at a high dose.
Comparison of an in-house acquired brain F-18 FDG PET normal database with commercially available normal data
Authors: Waterschoot Robbe , D’Asseler Yves , Goethals Ingeborg 
Published: April 2021

Introduction
Current guidelines recommend the use of semiautomated assessment of F-18 FDG PET brain studies. Accuracy is influenced by the normal data, which requires knowledge of the included subjects and how they were acquired. Due to confidentiality, such information is often not completely disclosed. Our aim was to determine the variation in FDG uptake between several commercially available and our in-house normal database.

Methods
Our database contains 83 healthy subjects. Outlier detection using SPM further ensured normality, resulting in exclusion of three subjects. The remaining 80 subjects were analyzed using three commercially available software packages. Z-score data per patient and per lobe were extracted and pooled in predefined age groups (18–40, 41–60 and 61–80 years old) with a calculation of mean Z-scores and SD. Correlation between Z-score output of different software was investigated.

Results
In the 18–40 years age group, frontotemporal hypermetabolism was found with all software. Decreased cerebellar uptake was found with two software packages. Mean Z-scores are closer to zero in the 41–60 years age group compared to the younger group, and mostly within the normal range in the 61–80 years age group with all software. A moderate to high linear correlation between Z-score output was found, but individual Z-scores varied widely.

Conclusions
The three software packages yielded varying Z-score output, partially explained by an age mismatch between our subjects and subjects in their normal databases. A definitive explanation for the remaining differences is lacking. This emphasizes the importance of age-matched normal data and knowledge of the included databases to allow adequate preprocessing.
A retrospective multicenter study of quantitative bone SPECT/CT to predict the surgical removal of the accessory navicular bone
Authors: Kim Ji-Young , Kim Ji Young , Park Soo Bin , Kim Chulhan , Lee Won Woo 
Published: April 2021

Objective
The maximum standardized uptake value (SUVmax) in single-photon emission computed tomography/computed tomography (SPECT/CT) can help quantify disease activity of the accessory navicular bone (ANB). In this multicenter quantitative bone SPECT/CT study, we investigated whether SUVmax was correlated with ANB severity, thereby allowing prediction of surgical resection for ANB treatment.

Methods
Two-hundred forty-six patients (men:women = 135:111, mean age = 39.3 years), who had undergone quantitative Tc-99m diphosphonate SPECT/CT of the feet, were recruited from four hospitals. SUVmax was measured using vendor-provided quantitation software. The SUVmax values were compared in relation to ANB type (type 1 = 62, type 2 = 136 and type 3 = 14), presence of pain and surgical treatment.

Results
SUVmax (mean ± SD) was the highest in type 2 ANB (4.41 ± 5.2; P = 0.0101). The 17 resected ANBs showed greater SUVmax (8.27 ± 5.23; P < 0.0001) than the 141 asymptomatic ANBs (2.30 ± 1.68) or the 54 symptomatic ANBs without surgery (6.15 ± 4.40). Since surgery is exclusively indicated for ANB type 2, surgical resection was investigated only in these cases. In univariate analysis, young age and SUVmax were significantly associated with surgical treatment, but only SUVmax was a significant predictor of surgery in multivariate analysis (P < 0.0001). Type 2 ANBs were treated by surgery in 32.5% (13/40) of the cases when SUVmax was ≥5, and in only 1.35% (1/74) of the cases when SUVmax was <5 (P < 0.0001).

Conclusion
ANB disease activity and excision were strongly associated with the SUVmax derived from quantitative bone SPECT/CT. Our study suggests an absolute SUVmax cutoff for ultimate ANB surgical treatment, but additional prospective studies are required to validate this finding.
Lipids Responsible for Intestinal or Hepatic Disorder
Authors: Sissaoui Samira , Cochet Manon , Poinsot Pierre , Bordat Claire , Collardeau‐Frachon Sophie , Lachaux Alain , Lacaille Florence , Peretti Noël 
Published: April 2021

ABSTRACTFamilial intestinal hypocholesterolemias, such as abetalipoproteinemia, hypobetalipoproteinemia, and chylomicron retention disease, are rare genetic diseases that result in a defect in the synthesis or secretion of lipoproteins containing apolipoprotein B.In children, these conditions present with diarrhoea and growth failure, whereas adults present with neuromuscular, ophthalmological, and hepatic symptoms. Simple laboratory investigations have shown that diagnosis can be made from findings of dramatically decreased cholesterol levels, deficiencies in fat‐soluble vitamins (mostly vitamin E), endoscopic findings of the characteristic white intestinal mucosa, and fat‐loaded enterocytes in biopsy samples. Genetic analysis is used to confirm the diagnosis. Treatment is based on a low‐fat diet with essential fatty acid supplementation, high doses of fat‐soluble vitamins, and regular and life‐long follow‐up.The present study examines cases and literature findings of these conditions, and emphasises the need to explore severe hypocholesterolemia and deficiencies in fat‐soluble vitamins to not miss these rare, but easy to diagnose and treat, disorders.
Effect of standing and sitting positions on energy expenditure in people with transtibial amputation compared to age- and sex-matched controls
Authors: Cheever Sarah M. , Kramer Patricia A. , Morgan Sara J. , Hafner Brian J. 
Published: April 2021

Background:
Energy expenditure (EE) is often greater in people with lower-limb amputation, compared with healthy controls, because of the biomechanical compensations needed to walk with a prosthesis. Compensatory movements are required to stand with a prosthesis; however, little is known about whether standing with a prosthesis also requires greater EE.

Objective:
The goal of this study was to examine the effect of standing and sitting positions on EE in people with transtibial amputation and matched controls.

Study Design:
This is a secondary analysis.

Methods:
Energy expenditure data from people with unilateral, transtibial amputation because of nondysvascular causes were compared with data from age- and sex-matched controls without amputation. Energy expenditure was defined as the mean volumetric rate of oxygen consumed over the last 2 of 5 minutes in each position and measured with a portable breath-by-breath metabolic analyzer. Repeated-measures analysis of variance was used to examine the effects of position (sitting and standing) and group (amputation and control) on EE.

Results:
A significant interaction effect indicated participants with amputation showed a significantly greater increase in standing EE relative to sitting EE (26.2%) than did controls (13.4%). Simple main effects showed EE in standing was significantly greater than EE in sitting for both groups, but there were no significant differences in EE between groups during sitting or standing.

Conclusions:
Energy expenditure in standing, when measured relative to EE in sitting, is significantly greater in people with amputation. This result indicates that additional energy may be required to maintain an upright position with a lower-limb prosthesis.
Identifying HIV-related digital social influencers using an iterative deep learning approach
Authors: Zheng Cheng , Wang Wei , Young Sean D. 
Published: April 2021

Objective(s):
Community popular opinion leaders have played a critical role in HIV prevention interventions. However, it is often difficult to identify these ‘HIV influencers’ who are qualified and willing to promote HIV campaigns, especially online, because social media influencers change frequently. We sought to use an iterative deep learning framework to automatically discover HIV-related online social influencers.

Design and method:
Out of 1.15 million Twitter users’ data from March 2018 to March 2020, we extracted tweets from 1099 Twitter users who had mentioned the keywords ‘HIV’ or ‘AIDS’. Two Twitter users determined to be ‘online HIV influencers’ based on their conversation topics and engagement were hand-picked by domain experts and used as a seed training dataset. We modelled social influence and discovered new potential influencers based on these seeds using a graph neural network model. We tested the model's precision and recall compared with other baseline model approaches. We validated the results through manual verification.

Results:
The model identified 23 new (manually verified) HIV-related influencers, including health and research organizations and local HIV advocates across the United States. Our proposed model achieved the highest accuracy/recall, with an average improvement of 38.5% over the other baseline models.

Conclusion:
Results suggest that iterative deep learning models can be used to automatically identify new and changing key HIV-related influencers online. We discuss the implications and potential of HIV researchers/departments applying this approach across online big data (e.g. hundreds of millions of social media posts per day) to help promote HIV prevention campaigns to affected communities.
The impact of immune checkpoint therapy on the latent reservoir in HIV-infected individuals with cancer on antiretroviral therapy
Authors: Lau Jillian S.Y. , McMahon James H. , Gubser Celine , Solomon Ajantha , Chiu Chris Y.H. , Dantanarayana Ashanti , Chea Socheata , Tennakoon Surekha , Zerbato Jennifer M. , Garlick Jill , Morcilla Vincent , Palmer Sarah , Lewin Sharon R. , Rasmussen Thomas A. 
Published: April 2021

Objective:
The aim of this study was to quantify HIV-specific immunological and virological changes in people with HIV (PWH) on antiretroviral therapy (ART) with malignancy who received immune checkpoint blockade (ICB).

Design:
An observational cohort study.

Methods:
Blood samples were collected before and after four cycles of ICB in HIV-positive adults on ART. Virological assessments performed on CD4+ T cells included cell-associated unspliced HIV RNA, cell-associated HIV DNA, Tat/rev-induced limiting dilution assay (TILDA) and plasma HIV RNA using a single copy assay (SCA). Flow cytometry was used to assess the frequency of precursor exhausted T cells (Tpex) and exhausted T cells (Tex), and Gag-specific CD4+ and CD8+ T cells positive for IFN-γ, TNF-α or CD107a by intracellular cytokine staining (ICS).

Results:
Participant (P)1 received avelumab (anti-PD-L1) for Merkel cell carcinoma. P2 and P3 received ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) for metastatic melanoma. An increase in CA-US RNA following each infusion was noted in all three participants. There were no consistent changes in HIV DNA or the proportion of cells with inducible MS HIV RNA. P2 demonstrated a striking increase in the frequency of gag-specific central and effector memory CD8+ T cells producing IFN-γ, TNF-α and CD107a following anti-PD1 and anti-CTLA-4. The frequency of CD8+ Tpex cells pre-ICB was also highest in this participant.

Conclusion:
In three PWH with cancer on ART, we found that ICB activated latent HIV and enhanced HIV-specific T cell function but with considerable variation.
High Prevalence of NRTI and NNRTI Drug Resistance Among ART-Experienced, Hospitalized Inpatients
Authors: Bossard Claire , Schramm Birgit , Wanjala Stephen , Jain Lakshmi , Mucinya Gisèle , Opollo Valarie , Wiesner Lubbe , van Cutsem Gilles , Poulet Elisabeth , Szumilin Elisabeth , Ellman Tom , Maman David 
Published: April 2021

Background:
Patients hospitalized with advanced HIV have a high mortality risk. We assessed viremia and drug resistance among differentiated care services and explored whether expediting the switching of failing treatments may be justified.

Setting:
Hospitals in the Democratic Republic of (DRC) Congo (HIV hospital) and Kenya (general hospital including HIV care).

Methods:
Viral load (VL) testing and drug resistance (DR) genotyping were conducted for HIV inpatients ≥15 years, on first-line antiretroviral therapy (ART) for ≥6 months, and CD4 ≤350 cells/µL. Dual-class DR was defined as low-, intermediate-, or high-level DR to at least 1 nucleoside reverse transcriptase inhibitor and 1 non-nucleoside reverse transcriptase inhibitor. ART regimens were considered ineffective if dual-class DR was detected at viral failure (VL ≥1000 copies/mL).

Results:
Among 305 inpatients, 36.7% (Kenya) and 71.2% (DRC) had VL ≥1000 copies/mL, of which 72.9% and 73.7% had dual-class DR. Among viral failures on tenofovir disoproxil fumarate (TDF)-based regimens, 56.1% had TDF-DR and 29.8% zidovudine (AZT)-DR; on AZT regimens, 71.4% had AZT-DR and 61.9% TDF-DR, respectively. Treatment interruptions (≥48 hours during past 6 months) were reported by 41.7% (Kenya) and 56.7% (DRC). Approximately 56.2% (Kenya) and 47.4% (DRC) on TDF regimens had tenofovir diphosphate concentrations <1250 fmol/punch (suboptimal adherence). Among viral failures with CD4 <100 cells/µL, 76.0% (Kenya) and 84.6% (DRC) were on ineffective regimens.

Conclusions:
Many hospitalized, ART-experienced patients with advanced HIV were on an ineffective first-line regimen. Addressing ART failure promptly should be integrated into advanced disease care packages for this group. Switching to effective second-line medications should be considered after a single high VL on non-nucleoside reverse transcriptase inhibitor–based first-line if CD4 ≤350 cells/µL or, when VL is unavailable, among patients with CD4 ≤100 cells/µL.
Virtual Surgical Planning and Three-Dimensional Printing to Aid the Anatomical Reduction of an Old Malunited Fracture of the Mandible
Authors: Ding Qian , Fu Zhen-Zhen , Yue Jin , Xu Yao-Xiang , Xue Ling-Fa , Xiao Wen-Lin 
Published: April 2021

Abstract
Mandible fracture is a common injury in maxillofacial surgery. It causes not only maxillofacial dysfunction but also facial deformities. Malunited fractures of the mandible have been a vast challenge in clinical treatment due to the misalignment of the broken ends and the occurrence of occlusal disorders. This case report describes using virtual surgical planning and three-dimensional printing to treat a patient with malunited fracture of the mandible. Failing to perform mandibular surgery due to severe brain trauma after the car accident, the patient got malunited healing of mandible. The authors applied virtual surgical planning to perform preoperative analysis and surgical design on this patient, three-dimensional printing to fabricate occlusal plate, and models of the preoperative and postoperative mandible to guide the operation. Finally, the authors achieved the reduction and reconstruction of the mandible with satisfactory clinical results.