bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-Care Capacity and Its Relationship to Age, Disability, and Perceived Well-Being in Medicare Beneficiaries
Authors: Hauenstein Emily J. , Davey Adam , Clark Rachael S. , Daly Suzanne , You Wei , Merwin Elizabeth I. 
Published: September 2021

Background
Self-care is a multicomponent set of capacities that influence beliefs about health and well-being.

Objectives
We examined the relationship between self-care capacity, age, and disability status with two perceptions of well-being in a cohort of Medicare beneficiaries.

Methods
The current study is part of a multisite research project to determine factors associated with cross-sectional and longitudinal morbidity and mortality trajectories observed in Medicare beneficiaries. Variable selection was informed by the health disparities and outcomes model. Using data from the 2013 Medicare Current Beneficiary Survey and logistic regression models, we determined associations between self-care capacity, including indicators of self-care ability and self-care agency and two perceptions of well-being. Participants were divided into four groups based on how they qualified for Medicare: (a) over 65 years of age, and below 65 years of age and disabled because of (b) physical or (c) mental disorder, or (d) disabled and could not be classified as physically or mentally disabled as the primary cause of eligibility.

Results
Self-care ability limitations in activities of daily living (ADL), instrumental activities of living (IADL), and social activity participation were associated with both health perceptions. Those with physical disabilities reported more ADL and IADL limitations when compared with the other eligibility groups and were significantly more likely to have negative health perceptions. Those with serious mental illness were most likely to report the most severe IADL limitations. The over 65 years of age group reported less self-care incapacity than the other three eligibility types. Other components of self-care, including health literacy, agency, and health behaviors, significantly influenced perceptions of health. Women and people identifying as non-Whites were more likely to have negative health perceptions.

Discussion
Self-care capacity is a complex construct, and its varied elements have differential relationships with perceptions of well-being. Those with physical disabilities reported more self-care limitations, poorer perceived health, and more health worries than the other groups. Still, there were different patterns of self-care capacities in the serious mental illness type—especially in IADL limitations. The study adds empirical evidence to previous research documenting inequities in health outcomes for women and non-Whites. Findings provide empirical support for the health disparities and outcomes model.
Histologic and Molecular Characterization of Non−Small Cell Lung Carcinoma With Discordant ROS1 Immunohistochemistry and Fluorescence In Situ Hybridization
Authors: Wilcock Diane M. , Schmidt Robert L. , Furtado Larissa V. , Matynia Anna P. , Deftereos Georgios , Sirohi Deepika 
Published: September 2021

Introduction:
ROS1 immunohistochemical (IHC) positivity requires follow-up with confirmatory testing such as fluorescence in situ hybridization (FISH). Identifying predictive characteristics of false positive ROS1 IHC cases could aid in optimizing testing algorithms, decrease testing costs and preserve tissue.

Materials and Methods:
Retrospective results were retrieved for 2054 patients with non−small cell lung carcinoma submitted to our laboratory for molecular testing. Reflex ROS1 FISH was done on all ROS1 immunoreactive cases using ROS1 D4D6 antibody. Staining intensity and histo-score was recorded for all ROS1 immunoreactive cases. Results of any additional molecular testing (KRAS, BRAF, EGFR, ALK FISH, RET FISH, MET FISH) were also tabulated.

Results:
ROS1 immunoreactivity was seen in 305/2054 (14.8%) cases. Immunoreactivity was weak in majority of the cases with only 4.6% cases having an histo-score >100 and 5.9% of cases had moderate staining intensity. FISH was negative in 99% (302/305) cases with any degree of IHC expression (discordant cases) while 3 cases were positive by FISH. Diffuse strong IHC staining in greater than 90% of the tumor was noted in 6 cases, 3 (0.98%) of which were confirmed to have ROS1 rearrangement by FISH. The discordant cases had significantly higher rates of EGFR mutations (P<0.0005) in comparison to ROS1 IHC negative cases, were seen more often in adenocarcinoma and adenosquamous cell carcinoma (P<0.0005) with lepidic and acinar patterns, and more likely to occur in primary lung carcinomas (P<0.0005).

Conclusions:
False positive ROS1 immunoreactivity was very frequent, occurred more commonly in primary NSCLC cases with acinar and/or lepidic histologies and was more likely in EGFR mutated cases. Using higher positivity thresholds for ROS1 IHC and incorporating the histologic and molecular correlates into algorithmic strategies could result in increased specificity and clinical utility of ROS1 IHC assay.
Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy – naive adults with HIV-1 infection
Authors: Cahn Pedro , Sierra Madero Juan , Arribas José R. , Antinori Andrea , Ortiz Roberto , Clarke Amanda E. , Hung Chien-Ching , Rockstroh Jürgen K. , Girard Pierre-Marie , Sievers Jörg , Man Choy Y. , Urbaityte Rimgaile , Brandon Daisy J. , Underwood Mark , Pappa Keith A. , Curtis Lloyd , Smith Kimberly Y. , Gartland Martin , Aboud Michael , van Wyk Jean , Wynne Brian 
Published: September 2021

Objective:
To assess efficacy and safety of dolutegravir (DTG) + lamivudine (3TC) vs. DTG + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naive adults with HIV-1 in the prespecified 144-week secondary analyses of GEMINI-1 and GEMINI-2.

Design:
Identical, multicenter, phase III, randomized, non-inferiority studies (double-blind through 96 weeks).

Methods:
Participants with HIV-1 RNA ≤500 000 copies/ml and no major viral resistance mutations to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, or protease inhibitors were randomized 1:1 to once-daily DTG + 3TC or DTG + TDF/FTC.

Results:
At week 144, DTG + 3TC (N = 716) was noninferior to DTG + TDF/FTC (N = 717) in proportion of participants achieving HIV-1 RNA <50 copies/ml (Snapshot algorithm) in the pooled analysis (82% vs. 84%, respectively; adjusted treatment difference [95% confidence interval (CI)], −1.8% [−5.8, 2.1]), GEMINI-1 (−3.6% [−9.4, 2.1]), and GEMINI-2 (0.0% [−5.3, 5.3]). Twelve DTG + 3TC participants and nine DTG + TDF/FTC participants met protocol-defined confirmed virologic withdrawal (CVW) criteria; none developed treatment-emergent resistance. One DTG + 3TC participant who did not meet CVW criteria developed M184V at week 132 and R263R/K at week 144, conferring a 1.8-fold change in susceptibility to DTG; non-adherence to therapy was reported. Significantly fewer drug-related adverse events occurred with DTG + 3TC vs. DTG + TDF/FTC (20% vs. 27%; relative risk [95% CI], 0.76 [0.63–0.92]). Renal and bone biomarker changes favored DTG + 3TC.

Conclusions:
Three-year durable efficacy, long-term tolerability, and high barrier to resistance support first-line use of DTG + 3TC for HIV-1 treatment (see Supplemental Digital Content 1, http://links.lww.com/QAD/C297; video abstract).
Dose optimisation of antibiotics used for meningitis
Authors: Heffernan Aaron J. , Roberts Jason A. 
Published: September 2021

Purpose of review
Central nervous system (CNS) infections such as ventriculitis and meningitis are associated with significant morbidity and mortality. In part, this may be due to increased difficulties in achieving a therapeutic antibiotic concentration at the site of infection due to both the pharmacokinetic (PK) changes observed during critical illness and the reduced antibiotic penetration through the blood brain barrier. This paper reviews the pharmacodynamics (PD) and CNS PKs of antibiotics used for Gram-negative bacterial CNS infections to provide clinicians with practical dosing advice.

Recent findings
Recent PK studies have shown that currently used intravenous antibiotic dosing regimens may not achieve a therapeutic exposure within the CNS, even for reportedly ‘susceptible’ bacteria per the current clinical meningitis breakpoints. Limited data exist for new β-lactam antibiotic/β-lactamase inhibitor combinations, which may be required for multidrug resistant infections. Intraventricular antibiotic administration, although not a new concept, has further evidence demonstrating improved patient outcomes compared with intravenous therapy alone, despite the ongoing paucity of PK studies guiding dosing recommendations.

Summary
Clinicians should obtain the bacterial minimum inhibitory concentration when treating patients with CNS Gram-negative bacterial infections and consider the underlying PK/PD principles when prescribing antibiotics. Therapeutic drug monitoring, where available, should be considered to guide dosing. Intraventricular therapy should also be considered for patients with ventricular drains to optimise clinical outcomes.
Reducing Time and Patient Radiation of Computed Tomography–guided Thoracic Needle Biopsies With Single-rotation Axial Acquisitions
Authors: Goiffon Reece J. , Best Till D. , Wrobel Maria M. , McDermott Shaunagh , Sharma Amita , Chang Connie Y. , Yang Kai , Fintelmann Florian J. 
Published: September 2021

Purpose:
To investigate the effect on procedure time and patient radiation indices of replacing helical acquisitions for needle guidance during thoracic needle biopsy (TNB) with intermittent single-rotation axial acquisitions.

Materials and Methods:
This retrospective intervention study included 215 consecutive TNBs performed by a single operator from 2014 to 2018. Characteristics of patients, lesions, and procedures were compared between TNBs guided only by helical acquisitions initiated in the control room (helical group, n=141) and TNBs guided in part by intermittent single-rotation axial computed tomography controlled by foot pedal (single-rotation group, n=74). Procedure time and patient radiation indices were primary outcomes, complications, and radiologist radiation dose were secondary outcomes.

Results:
Patient, lesion, and procedural characteristics did not differ between helical and single-rotation groups. Use of single-rotation axial acquisitions decreased procedure time by 10.5 minutes (95% confidence interval [CI]: 8.2-12.8 min) or 27% (95% CI: 22%-32%; P<0.001). Patient dose in cumulative volume computed tomography dose index decreased by 23% (95% CI: 12%-33%) or 8 mGy (95% CI: 4.3-31.6 mGy; P=0.01). Dose-length product decreased by 50% (95% CI: 40%-60%) or 270 mGy cm (95% CI: 195-345 mGy cm; P<0.001). No operator radiation exposure was detected. Rate of diagnostic result, pneumothorax, hemoptysis, and hemorrhage did not differ between groups.

Conclusions:
Replacing helical acquisitions with intermittent single-rotation axial acquisitions significantly decreases TNB procedure time and patient radiation indices without adversely affecting diagnostic rate, procedural complications, or operator radiation dose.
Comparison of Triple-Rule-Out Prospectively ECG-triggered Systolic and Diastolic Acquisition Protocol in Patients With Acute Chest Pain
Authors: Fusaro Michele , Caruso Damiano , Tessarin Giovanni , de Santis Domenico , Balestriero Giovanni , Bortolanza Carlo , Panvini Nicola , Polidori Tiziano , Laghi Andrea , Morana Giovanni 
Published: September 2021

Purpose:
The purpose of this study was to compare image quality and coronary interpretability of triple-rule-out systolic and diastolic protocols in patients with acute chest pain.

Materials and Methods:
From March 2016 to October 2017 the authors prospectively enrolled patients with undifferentiated acute chest pain, who were at low to intermediate cardiovascular risk. Those with heart rate >75 bpm underwent a systolic prospectively triggered acquisition (systolic triggering [ST]), and in those with ≤75 bpm, end-diastolic triggering (DT) was instead performed. Examinations were evaluated for coronary artery disease, aortic dissection, and pulmonary embolism. Image quality was assessed using a Likert scale. Coronary arteries interpretability was evaluated both on a per-vessel and a per segment basis. The occurrence of major adverse cardiovascular events was investigated.

Results:
The final study population was 189 patients. Fifty-two patients (27.5%) underwent systolic acquisition and 137 (72.5%) underwent diastolic acquisition. No significant differences in overall image quality were observed between DT and ST groups (median score 5 [interquartile ranges 4 to 5] vs. 4 [interquartile ranges 4 to 5], P=0.074). Although both DT and ST protocols showed low percentages of noninterpretable coronary arteries on a per-vessel (1.5% and 6.7%, respectively) and per-segment analysis (1% and 4.7%, respectively), these percentages resulted significantly higher for ST groups (P<0.001). Obstructive coronary stenosis was observed in 18 patients. Only one case of pulmonary embolism was diagnosed and no cases of aortic dissection were found in our population. No death or major adverse cardiovascular events were observed during follow-up among the 2 groups.

Conclusions:
Results showed that triple-rule-out computed tomography angiography is a reliable technique in patients with acute chest pain and that an ST acquisition protocol could be considered an alternative acquisition protocol in patients with higher heart rate, reaching a good image quality.
Quantitative Image Analysis at Chronic Lung Allograft Dysfunction Onset Predicts Mortality
Authors: Weigt S. Samuel , Kim Grace-Hyun J. , Jones Heather D. , Ramsey Allison L. , Amubieya Olawale , Abtin Fereidoun , Pourzand Lila , Lee Jihey , Shino Michael Y. , DerHovanessian Ariss , Stripp Barry , Noble Paul W. , Sayah David M. , Saggar Rajan , Britton Ian , Lynch Joseph P. , Belperio John A. , Goldin Jonathan 
Published: September 2021

Background.
Chronic lung allograft dysfunction (CLAD) phenotype determines prognosis and may have therapeutic implications. Despite the clarity achieved by recent consensus statement definitions, their reliance on radiologic interpretation introduces subjectivity. The Center for Computer Vision and Imaging Biomarkers at the University of California, Los Angeles (UCLA) has established protocols for chest high-resolution computed tomography (HRCT)-based computer-aided quantification of both interstitial disease and air-trapping. We applied quantitative image analysis (QIA) at CLAD onset to demonstrate radiographic phenotypes with clinical implications.

Methods.
We studied 47 first bilateral lung transplant recipients at UCLA with chest HRCT performed within 90 d of CLAD onset and 47 no-CLAD control HRCTs. QIA determined the proportion of lung volume affected by interstitial disease and air-trapping in total lung capacity and residual volume images, respectively. We compared QIA scores between no-CLAD and CLAD, and between phenotypes. We also assigned radiographic phenotypes based solely on QIA, and compared their survival outcomes.

Results.
CLAD onset HRCTs had more lung affected by the interstitial disease (P = 0.003) than no-CLAD controls. Bronchiolitis obliterans syndrome (BOS) cases had lower scores for interstitial disease as compared with probable restrictive allograft syndrome (RAS) (P < 0.0001) and mixed CLAD (P = 0.02) phenotypes. BOS cases had more air-trapping than probable RAS (P < 0.0001). Among phenotypes assigned by QIA, the relative risk of death was greatest for mixed (relative risk [RR] 11.81), followed by RAS (RR 6.27) and BOS (RR 3.15).

Conclusions.
Chest HRCT QIA at CLAD onset appears promising as a method for precise determination of CLAD phenotypes with survival implications.
Liver or Kidney Transplantation After SARS-CoV-2 Infection: Prevalence, Short-term Outcome, and Kinetics of Serum IgG Antibodies
Authors: Verbeek Jef , Vrij Casper , Vermeersch Pieter , Van Elslande Jan , Vets Sofie , Lagrou Katrien , Vos Robin , van Cleemput Johan , Jochmans Ina , Monbaliu Diethard , Pirenne Jacques , Kuypers Dirk , Nevens Frederik 
Published: September 2021

Background.
There is a paucity of data on the prevalence, adequate timing, and outcome of solid organ transplantation after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and the kinetics of immunoglobulin G (IgG) antibodies in these patients.

Methods.
SARS-CoV-2 antinucleocapsid (N) IgG and polymerase chain reaction via a nasopharyngeal swab were analyzed in all patients within 24 h before liver or kidney transplantation. Kinetics of IgG antibodies were analyzed and compared with an immunocompetent cohort.

Results.
Between May 1, 2020, and March 18, 2021, 168 patients underwent liver or kidney transplantation in our center, of which 11 (6.54%) patients with a previous SARS-CoV-2 infection were identified. The median interval between SARS-CoV-2 infection and transplantation was 4.5 mo (range, 0.9–11). After a median posttransplant follow-up of 4.9 mo, 10 out of 11 patients were alive without clinical signs of viral shedding or recurrent or active infection. One patient without symptom resolution at time of transplantation died after combined liver-kidney transplantation. In 9 out of 11 patients with previously polymerase chain reaction-confirmed infection, SARS-CoV-2 anti-N and antispike (S) IgG were detectable at day of transplantation. Absolute levels of anti-N and anti-S IgG were positively correlated, declined over time in all patients, and were significantly lower compared with immunocompetent individuals. All patients remained anti-S IgG positive until the last posttransplant follow-up, whereas 3 patients became anti-N negative.

Conclusions.
We observed an uncomplicated course of liver or kidney transplantation after SARS-CoV-2 infection in selected patients. Although having lower absolute IgG antibody levels than immunocompetent individuals, all seroconverted patients remained anti-S IgG positive. These encouraging data need validation in larger studies.
Anopheles salivary antigens as serological biomarkers of vector exposure and malaria transmission: A systematic review with multilevel modelling
Authors: Kearney Ellen A , Agius Paul A , Chaumeau Victor , Cutts Julia C , Simpson Julie A , Fowkes Freya JI 
Published: September 2021

AbstractBackgroundEntomological surveillance for malaria is inherently resource-intensive and produces crude population-level measures of vector exposure which are insensitive in low-transmission settings. Antibodies against Anopheles salivary proteins measured at the individual-level may serve as proxy biomarkers for vector exposure and malaria transmission, but their relationship is yet to be quantified.MethodsA systematic review of studies measuring antibodies against Anopheles salivary antigens (PROSPERO: CRD42020185449). Multilevel modelling estimated associations between seroprevalence with Anopheles human biting rate (HBR) and malaria transmission measures.ResultsFrom 3981 studies identified in literature searches, 42 studies across 16 countries were included contributing 393 meta-observations of anti-Anopheles salivary antibodies determined in 42,764 samples. A positive non-linear association between HBR and seroprevalence was found; overall a 50% increase in HBR was associated with a 13% increase in odds of seropositivity (OR: 1.13, 95%CI: 1.06-1.20, p<0.001). The association between HBR and Anopheles salivary antibodies was strongest with concordant, rather than discordant Anopheles species. Seroprevalence was also significantly positively associated with established epidemiological measures of malaria transmission: entomological inoculation rate, Plasmodium spp. prevalence, and malarial endemicity class.ConclusionsAnopheles salivary antibody biomarkers can serve as a proxy measure for HBR and malaria transmission, and could monitor vectorial capacity and malaria receptivity of a population to sustain malaria transmission. Validation of Anopheles species-specific biomarkers are important given the global heterogeneity in the distribution of Anopheles species. Salivary biomarkers have the potential to transform surveillance by replacing impractical, inaccurate entomological investigations, especially in areas progressing towards malaria elimination.FundingAustralian National Health and Medical Research Council, Wellcome Trust.
Inhibition of sodium conductance by cannabigerol contributes to a reduction of neuronal dorsal root ganglion excitability
Authors: Ghovanloo Mohammad-Reza , Estacion Mark , Zhao Peng , Dib-Hajj Sulayman , Waxman Stephen G. 
Published: September 2021

ABSTRACTCannabigerol (CBG), a non-psychotropic phytocannabinoid, is a precursor for cannabis derivatives, Δ9-tetrahydrocannabinol and cannabidiol (CBD). Like CBD, CBG has been suggested as an analgesic. A previous study reported CBG (10 μM) blocks voltage-gated sodium (Nav) currents in CNS neurons. However, the manner in which CBG inhibits Nav channels, and whether this effect contributes to CBG’s potential analgesic behavior remain unknown. Genetic and functional studies have validated Nav1.7 as an opportune target for analgesic drug development. The efforts to develop therapeutic selective Nav1.7 blockers have been unsuccessful thus far, possibly due to issues in occupancy; drugs have been administered at concentrations many folds above IC50, resulting in loss of isoform-selectivity, and increasing off-target effects. We reasoned that an alternative approach could use compounds possessing 2 important properties: ultra-hydrophobicity and functional selectivity. Hydrophobicity could enhance absorption into neuronal cells especially with local administration. Functional selectivity could reduce likelihood of side-effects. As CBG is ultra-hydrophobic (cLogD=7.04), we sought to determine whether it also possesses functional selectivity against Nav channels that are expressed in dorsal root ganglion (DRG). We found that CBG is a ~10-fold state-dependent Nav inhibitor (KI-KR: ~2-20 μM) with an average Hill-slope of ~2. We determined that at lower concentrations, CBG predominantly blocks sodium Gmax and slows recovery from inactivation; however, as concentration is increased, CBG also hyperpolarizes Nav inactivation curves. Our modeling and multielectrode array recordings suggest that CBG attenuates DRG excitability, which is likely linked with Nav inhibition. As most Nav1.7 channels are inactivated at DRG resting membrane potential, they are more likely to be inhibited by lower CBG concentrations, suggesting functional selectivity against Nav1.7 compared to other Navs (via Gmax block).