bluuebunny/crossref_metadata_2025_split huggingface dataset:
PCSK9 Activity Is Potentiated Through HDL Binding
Authors: Burnap Sean A. , Sattler Katherine , Pechlaner Raimund , Duregotti Elisa , Lu Ruifang , Theofilatos Konstantinos , Takov Kaloyan , Heusch Gerd , Tsimikas Sotirios , Fernández-Hernando Carlos , Berry Sarah E. , Hall Wendy L. , Notdurfter Marlene , Rungger Gregorio , Paulweber Bernhard , Willeit Johann , Kiechl Stefan , Levkau Bodo , Mayr Manuel 
Published: October 2021

Rationale:
PCSK9 (proprotein convertase subtilisin/kexin type 9) circulates in a free and lipoprotein-bound form, yet the functional consequence of the association between PCSK9 and HDL (high-density lipoprotein) remains unexplored.

Objective:
This study sought to interrogate the novel relationship between PCSK9 and HDL in humans.

Methods and Results:
Comparing lipoprotein and apolipoprotein profiles by nuclear magnetic resonance spectroscopy and targeted mass spectrometry measurements with PCSK9 levels in the community-based Bruneck study (n=656) revealed a positive association of plasma PCSK9 with small HDL, alongside a highly significant positive correlation between plasma levels of PCSK9 and apolipoprotein C3 (apoC3), an inhibitor of lipoprotein lipase. The latter association was replicated in an independent cohort, the SAPHIR study (Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk; n=270). Thus, PCSK9-HDL association was determined during the postprandial response in two dietary studies (n=20 participants each, 8 time points). Peak triglyceride levels coincided with an attenuation of the PCSK9-HDL association, a loss of apoC3 from HDL, and lower levels of small HDL as measured by nuclear magnetic resonance spectroscopy. Crosslinking mass spectrometry upon isolated HDL identified PCSK9 as a potential HDL-binding partner. PCSK9 association with HDL was confirmed through size-exclusion chromatography and immuno-isolation. Quantitative proteomics upon HDL isolated from patients with coronary artery disease (n=172) returned PCSK9 as a core member of the HDL proteome. Combined interrogation of the HDL proteome and lipidome revealed a distinct cluster of PCSK9, phospholipid transfer protein, clusterin, and apolipoprotein E within the HDL proteome that was altered by sex and positively correlated with sphingomyelin content. Mechanistically, HDL facilitated PCSK9-mediated low-density lipoprotein receptor degradation and reduced low-density lipoprotein uptake through the modulation of PCSK9 internalization and multimerization.

Conclusions:
This study reports HDL as a binder of PCSK9 and regulator of its function. The combination of -omic technologies revealed postprandial lipemia as a driver of PCSK9 and apoC3 release from HDL.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03191513; URL:
https://www.isrctn.com
; Unique identifier: ISRCTN20774126.
Complex Profiles of Cerebrovascular Disease Pathologies in the Aging Brain and Their Relationship With Cognitive Decline
Authors: Lamar Melissa , Leurgans Sue , Kapasi Alifiya , Barnes Lisa L. , Boyle Patricia A. , Bennett David A. , Arfanakis Konstantinos , Schneider Julie A. 
Published: October 2021

Background and Purpose:
Cerebrovascular disease (CVD) pathologies including vessel disease (atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy) and tissue injury (macroinfarcts and microinfarcts) each contribute to Alzheimer and other forms of dementia. CVD is often a complex mix of neuropathologies, with little known about the frequencies of differing combinations or their associations with cognition.

Methods:
We investigated 32 possible CVD combinations (3 types of vessel disease and 2 types of tissue injury) using autopsy data from 1474 decedents (≈88 years at death; 65% female) of Rush Alzheimer’s Disease Center studies. We determined frequencies of all 32 CVD combinations and their relationships with global and domain-specific cognitive decline using mixed-effect models adjusted for demographics, neuropathologies, time before death, and interactions of these variables with time.

Results:
Of the 1184 decedents with CVD neuropathology (80% of the total sample), 37% had a single CVD (67–148 decedents/group) while 63% had mixed CVD profiles (11–54 decedents/group). When considered as 2 distinct groups, the mixed CVD profile group (but not the single CVD profile group) showed a faster cognitive decline across all domains assessed compared with decedents without CVD neuropathology. Most mixed CVD profiles, especially those involving both atherosclerosis and arteriolosclerosis, showed faster cognitive decline than any single CVD profile considered alone; specific mixed CVD profiles differentially associated with individual cognitive domains.

Conclusions:
Mixed CVD, more common than single CVD, is associated with cognitive decline, and distinct mixed CVD profiles show domain-specific associations with cognitive decline. CVD is not monolithic but consists of heterogenous person-specific combinations with distinct contributions to cognitive decline.
National Institutes of Health Stroke Scale: comparison of original and modified versions for Singapore culture
Authors: Lim Shu Han , Guek Tai Yan , Woon Fung Peng , Tay Deirdre Danyi , Ho Shu Swen , Ng Szu Chyi , De Silva Deidre Anne 
Published: October 2021

Abstract

Introduction:
The National Institutes of Health Stroke Scale (NIHSS), originally designed in the United States of America, contains items on dysphasia and dysarthria that are deemed culturally unsuitable for the Singapore context. We compared the error rates of dysphasia objects, dysphasia phrases and dysarthria words between the original and alternative items in a cohort of Singaporean subjects without dysphasia or dysarthria.

Methods:
In this prospective study, 140 English-speaking Singaporean subjects without impairments of dysphasia or dysarthria had an assessment of NIHSS items 9 and 10 using the original and alternative items. Paired analyses were conducted for comparison of error rates.

Results:
The error rates were high for four original dysphasia objects (Hammock: 62.9%, Cactus: 38.6%, Feather: 23.6%, Glove: 20.7%) and significantly lower for alternative items (Snail: 5%, Horse: 1.4%, Hanger: 1.4%, Car: 0%) (P < 0.001). For dysphasia phrases and dysarthria words, the error rates were low and there were no differences in error rates between the original and alternative items.

Conclusion:
There are cultural issues with several dysphasia objects in the original NIHSS as evidenced by the high error rates, which were lowered with more culturally suitable alternatives. This study formed a basis to derive a more suitable version of the NIHSS for English-speaking subjects in Singapore.
Association of the FRAIL scale with rehabilitation outcomes in the community hospital setting
Authors: Jiang Jeffrey , Han Audrey Yan Yi , Goh Joel 
Published: October 2021

Introduction:
Frailty is associated with adverse health outcomes and can be measured using the FRAIL scale. In Singapore, its use has been studied in tertiary hospitals but not in community hospitals. A tool to predict rehabilitation outcomes would allow for better risk stratification and allocation of resources. We aimed to determine whether the FRAIL scale is associated with rehabilitation outcomes in patients admitted to the community hospital setting, where post-acute care and rehabilitation are primarily delivered.

Methods:
This was a retrospective cohort study. The FRAIL scale was utilised to screen 560 older adults who were admitted to a community hospital for rehabilitation. Data were analysed to determine the relationship between baseline characteristics and frailty status, with rehabilitation outcome measures of absolute functional gain, rehabilitation effectiveness, rehabilitation efficiency, length of stay and discharge destination.

Results:
The combined score of the FRAIL scale showed significant negative association with absolute functional gain (P < 0.001), rehabilitation effectiveness (P < 0.001) and rehabilitation efficiency (P < 0.001), whereas it was positively associated with increased length of stay (P < 0.05) and a need for continued support in increased care settings (P < 0.001). Individual components of the FRAIL scale, in particular, the ‘fatigue’, ‘ambulation’ and ‘loss of weight’ components, appeared to be highly associated with rehabilitation effectiveness and efficiency, especially among pre-frail patients.

Conclusion:
The utility of the FRAIL scale as an indicator of frailty status and its association with rehabilitative outcomes in the post-acute care setting were demonstrated. Moreover, the FRAIL scale may better predict the rehabilitative progress of pre-frail patients.
A UK national audit of the laboratory investigation of phaeochromocytoma and paraganglioma
Authors: Boot Christopher , Toole Barry , Harris Sharman , Tetlow Lisa , Wassif Wassif S 
Published: October 2021

Background Phaeochromocytomas and paragangliomas (PPGL) are catecholamine secreting tumours associated with significant morbidity and mortality. Timely diagnosis and management are essential. A range of laboratory tests can be utilised in the investigation of PPGL. There is scope for significant variation in practice between centres. We aimed to investigate how the laboratory investigation of PPGL is performed in laboratories across the United Kingdom. Methods A questionnaire consisting of 21 questions was circulated to Clinical Biochemistry laboratories in the United Kingdom via the Association for Clinical Biochemistry and Laboratory Medicine office. The survey was designed to allow audit against Endocrine Society Guidelines on the Investigation and Management of PPGL and to obtain information on other important aspects not included in these guidelines. Results Responses were received from 58 laboratories and the data were compiled. The majority of laboratories use either urine or plasma metanephrines in first-line testing for PPGL, although a number of different combinations of biochemistry tests are utilised in different centres. All laboratories measuring metanephrines or catecholamines in-house use LC or LC-MS/MS methods. There are some marked differences between laboratories in urine metanephrines reference ranges used and sample requirements. Conclusions There is evidence of good practice in UK laboratories (as assessed against Endocrine Society Guidelines) such as widespread use of urine/plasma metanephrines and appropriate analytical methodologies used. However, there is also evidence of variations in practice in some areas that should be addressed.
A Neural Networks Approach to Determine Factors Associated With Self-Reported Discomfort in Picking Tasks
Authors: Haj Mahmoud Olfa , Pontonnier Charles , Dumont Georges , Poli Stéphane , Multon Franck 
Published: October 2021

Objective A neural networks approach has been proposed to handle various inputs such as postural, anthropometric and environmental variables in order to estimate self-reported discomfort in picking tasks. An input reduction method has been proposed, reducing the input variables to the minimum data required to estimate self-reported discomfort with similar accuracy as the neural network fed with all variables. Background Previous works have attempted to explore the relationship between several factors and self-reported discomfort using observational methods. The results showed that this relationship was not a simple linear relationship. Another study used neural networks to model the function returning reported discomfort according to static posture, age, and anthropometrics variables. The results demonstrated the model’s ability to predict reported discomfort. But all the available variables were used to design the neural network. Method Eleven subjects carried-out picking tasks with various masses (0, 1, 3 kg) and imposed duration (5, 10, or 15 s). Continuous REBA score, anthropometric and environmental data were computed, and subjects’ discomfort were collected. The data set of this work consisted in the computed continuous REBA score, anthropometric, environmental data and collected subjects’ discomfort. Results The results showed that the correlation between the estimated and experimental tested data was equal to 0.775 when using all the 14 available variables. After data reduction, only 6 variables were left, with a very close performance when predicting discomfort. Conclusion A neural network approach has been proposed to estimate self-reported discomfort according to a minimum set of postural, anthropometric and environmental variables in picking tasks. Application This method has the potential to support ergonomists in workstation designing processes, by adding discomfort prediction to virtual manikins’ behaviors in simulation tools.
Self-Regulation of Driving Behavior Under the Influence of Cannabis: The Role of Driving Complexity and Driver Vision
Authors: Ortiz-Peregrina Sonia , Oviedo-Trespalacios Oscar , Ortiz Carolina , Anera Rosario G. 
Published: October 2021

Objective This study analyzed the self-regulation behaviors of drivers under the influence of cannabis and its relationship with road complexity and some driver traits, including visual deterioration. Background Cannabis is the illicit drug most often detected in drivers; its use results in significant negative effects in terms of visual function. Self-regulation behaviors involve the mechanisms used by drivers to maintain or reduce the risk resulting from different circumstances or the driving environment. Methods Thirty-one young, occasional cannabis users were assessed both in a baseline session and after smoking cannabis. We evaluated the visual function (visual acuity and contrast sensitivity) and driver self-regulation variables of both longitudinal and lateral control as the speed adaptation and standard deviation of lateral position (SDLP). Results Visual function was significantly impaired after cannabis use. Recreational cannabis use did not result in self-regulation, although some road features such as curved roads did determine self-regulation. Male participants adopted mean faster driving speeds with respect to the speed limit. Driver age also determined better lateral control with lower SDLPs. In addition, visual impairment resulting from cannabis use (contrast sensitivity) was linked with self-regulation by changes in longitudinal and lateral control. Conclusion Contrast sensitivity could be a good indicator of individual visual status to help determine how drivers self-regulate their driving both in normal conditions and while under the influence of cannabis. Application The findings provide new insights about driver self-regulation under cannabis effects and are useful for policy making and awareness campaigns.
Surgical septal myectomy for hypertrophic cardiomyopathy. The Iranian experience
Authors: Ghavidel Alireza Alizadeh , Alizadehasl Azin , Khalilipur Ehsan , Amirghofran Ahmadali , Nezhadbahram Hanieh , Azarfarin Rasoul 
Published: October 2021

Introduction Hypertrophic obstructive cardiomyopathy (HOCM) is a hereditary heart muscle disorder characterized by significant myocardial hypertrophy. we assessed perioperative and long-term follow-up data of Iranian HOCM patients who underwent SM in 2 pioneering centers. Methods Clinical data of patients with HOCM septal myectomy are collected. Thirty-day outcome and long-term follow-up data for recurrence of gradient and mortality are reported. Results Ninety-six patients in two different centers enrolled in the study. Most patients of 52 patients in center 1 were male (34/52 [65.3%]).and the mean age was of 36.7  ±  19 years. Syncope before admission was reported in 5.7%, the mean left ventricular ejection fraction on admission was 53  ±  8%, the mean left ventricular outflow tract gradient was 66.3  ±  20.4 mm Hg, and the mean preoperativeseptal thickness was 25.4  ±  6.7 mm. A redo SM was performed in 3 patients (5.8%), mitral valve repair in 5 patients (9.6%), and atrioventricular repair in 5 patients (9.6%). A residual systolic anterior motion was detected in 4 patients (7.7%), the mean postoperative septal thickness was 19  ±  6 mm (25.1% septal thickness reduction), and in-hospital mortality was 5.8% (n  =  3). A longer-term follow-up showed death in 3 patients (5.8%) and late recurrent left ventricular outflow tract obstruction in 1 patient. Conclusions Transaortic myectomy is an effective surgery with acceptable early and late mortality rates. Improvements in functional status are seen in almost all patients. Appropriate SM is crucial to a good clinical outcome. Long-term survival is excellent and cardiac sudden death is extremely rare after a good surgical treatment.
Biophysical properties of electrospun chitosan-grafted poly(lactic acid) nanofibrous scaffolds loaded with chondroitin sulfate and silver nanoparticles
Authors: Júnior Alexandre F , Ribeiro Charlene A , Leyva Maria E , Marques Paulo S , Soares Carlos R J , Alencar de Queiroz Alvaro A 
Published: October 2021

The aim of this work was to study the biophysical properties of the chitosan-grafted poly(lactic acid) (CH-g-PLA) nanofibers loaded with silver nanoparticles (AgNPs) and chondroitin-4-sulfate (C4S). The electrospun CH-g-PLA:AgNP:C4S nanofibers were manufactured using the electrospinning technique. The microstructure of the CH-g-PLA:AgNP:C4S nanofibers was investigated by proton nuclear magnetic resonance (1H-NMR), scanning electron microscopy (SEM), UV-Visible spectroscopy (UV-Vis), X-ray diffraction (XRD), and Fourier transform infrared (ATR-FTIR) spectroscopy. ATR-FTIR and 1H-NMR confirm the CH grafting successfully by PLA with a substitution degree of 33.4%. The SEM measurement results indicated apparently smooth nanofibers having a diameter range of 340 ± 18 nm with porosity of 89 ± 3.08% and an average pore area of 0.27 μm2. UV-Vis and XRD suggest that silver nanoparticles with the size distribution of 30 nm were successfully incorporated into the electrospun nanofibers. The water contact angle of 12.8 ± 2.7° reveals the hydrophilic nature of the CH-g-PLA:AgNP:C4S nanofibers has been improved by C4S. The electrospun CH-g-PLA:AgNP:C4S nanofibers are found to release ions Ag+ at a concentration level capable of rendering an antimicrobial efficacy. Gram-positive bacteria ( S.aureus) were more sensitive to CH-g-PLA:AgNP:C4S than Gram-negative bacteria ( E. coli). The electrospun CH-g-PLA:AgNP:C4S nanofibers exhibited no cytotoxicity to the L-929 fibroblast cells, suggesting cytocompatibility. Fluorescence microscopy demonstrated that C4S promotes the adhesion and proliferation of fibroblast cells onto electrospun CH-g-PLA:AgNP:C4S nanofibers.
Sticking to What Matters: A Matched Comparative Study of Fibrin Glue and Mechanical Fixation for Split-Thickness Skin Grafts in the Lower Extremity
Authors: Othman Sammy , Messa Charles A. , Elfanagely Omar , Bormann Bradford , Mellia Joseph A. , Broach Robyn B. , Kovach Stephen J. , Fischer John P. 
Published: October 2021

Background: Split-thickness skin grafts (STSGs) remain a valuable tool in the reconstructive surgeons’ armamentarium. Staple or suture mechanical fixation (MF) serves as the gold standard of care, though fibrin glue (FG) has gained popularity as a fixation modality. We compare STSG outcomes following application of FG versus MF through a study of lower extremity wounds. Methods: A retrospective review (2016-2019) of patients who underwent a STSG was performed. Two cohorts consisting of patients undergoing a STSG with FG or MF (suture or staple) were matched according to wound size, wound location, and body mass index. Results: A total of 67 patients with 79 wounds were included (FG: n = 30, wounds = 39; MF: n = 37; wounds = 40). There was no significant difference between groups regarding time to 100% graft take (FG: 39 days, MF: 35.1 days; P < .384) or 180-day graft complications (FG: 10.3%, MF: 15%; P < .737). Adjusted operative time for FG (51.8 min) was lower than for MF cases (67.5 min) at a level that approached significance ( P < .094). FG patients were significantly less likely to require a postoperative wound vacuum-assisted closure (VAC) (FG: 16.7%; MF: 76.7%; P < .001) and required a significantly lower number of 30-day postoperative visits (FG: 1.5 ± .78 visits; MF: 2.5 ± .03 visits; P < .001). The MF group had higher mean aggregate charges ($211,090) compared with the FG group (mean: $149,907), although these were not statistically significant ( P > .05). Conclusion: The use of FG for STSG shows comparable clinical outcomes to MF, with a significantly decreased need for postoperative wound VAC, the number of 30-day postoperative visits, and a lower wound-adjusted operative time.
Self-efficacy in disadvantaged communities: Perspectives of healthcare providers and clients
Authors: Hardman Ruth , Begg Stephen , Spelten Evelien 
Published: October 2021

Objective Most chronic disease self-management interventions emphasise the integral role of self-efficacy in achieving behaviour change. We explored the applicability of this model in a low-income setting, from the perspective of both patients and clinicians. Methods Interviews with multimorbid patients and their health providers at two rural community health centres in Victoria, Australia. We used a phenomenological methodology, exploring themes of confidence to manage health, outcome expectations and goals. Results Many assumptions in which the self-efficacy model is grounded did not apply to this population. Past experiences and resource constraints, especially poverty and healthcare access, influenced confidence, expectations and the ability to achieve desired outcomes. Discussion The focus of traditional self-management support on individual behaviour change disadvantages rural low-income patients, who face barriers related to life experience and resource constraints. For this group, self-management support needs to return to its roots, moving away from a narrow conception of behaviour change and reinstating the role of ‘support’ into ‘self-management support’ interventions. Health providers working in rural low-income settings should recognise the limits inherent in self-efficacy focussed interventions and think broadly about engaging with their clients in whatever way supports them to find a life with meaning and purpose.
Healthcare professionals’ experiences during Operation Ancient Babylon in Iraq: A qualitative study
Authors: Calamassi Diletta , Pucci Christabel , Bambi Stefano 
Published: October 2021

Background Healthcare professionals are usually employed in civilian inpatient and outpatient settings but can also work in countries experiencing military conflict. Aims To explore the lived experiences of healthcare professionals during the operation “Ancient Babylon” in Iraq to understand their feelings and problems encountered. Methods Hermeneutic phenomenological study. In-depth interviews of nine nurses and one physician who took part in the operation between 2003 and 2006 were performed. Data from the collected narrations were analyzed to identify recurrent themes. Results Seven main themes emerged: “Living in an extreme setting,” “Living in a theatre of war,” “Strong emotions,” “The team as a family,” “A professional development experience,” “An eye-opening experience,” and “Advice for anyone who wants to join such a mission”. The experience was perceived as physically challenging and emotionally difficult. The relationship between colleagues was strong. It was based on reciprocal trust, enthusiasm, and compensated for the sense of distance that the participants felt from their own families. Conclusion Advice and recommendations for those who are interested in pursuing similar experiences: they must develop decision-making skills, be able to rely on one’s own abilities, have good professional training to fall back on, participate in exercises and simulations before the mission, and also be adaptable and innovative, flexible and able to stay mentally grounded.