bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of cancer on traditional, complementary and alternative medicine utilization in Korea: a fixed effect analysis using Korea Health Panel data
Authors: Kim Dongsu , Sung Soo-Hyun , Shin Seungwon , Park Minjung 
Published: May 2022

Abstract
Background
Cancer-related incidence and mortality rates are rapidly increasing worldwide. However, no studies have examined the effect of cancer as a single factor on the use of traditional, complementary, and alternative medicine (T&CAM). We aimed to determine the effect of cancer occurrence on T&CAM utilization using Korea Health Panel (KHP) data.

Methods
We analyzed longitudinal data (49,380 observations) derived from 12,975 Korean adult participants with complete KHP data from 2011 to 2014 and 2016, and divided them into two groups based on cancer diagnosis. A panel multinomial logit model was used to assess whether the participants used T&CAM or conventional medicine or both in outpatient settings. Additionally, a negative binomial regression model was used to examine the effect of cancer on the number of outpatient visits for T&CAM.

Results
In total, 25.54% of the study participants in the cancer group used T&CAM, which was higher than that in the non-cancer group (18.37%, p < 0.0001). A panel multinomial logistic regression analysis using KHP data showed that cancer occurrence was significantly more likely to be associated with ‘Using both Korean medicine and conventional medicine’ (Coef. = 0.80, p = 0.017) and ‘Not using Korean medicine but using conventional medicine’ (Coef. = 0.85, p = 0.008) than ‘Not using Korean medicine and conventional medicine.’ A panel negative binomial regression showed a significant effect of cancer on increasing the number of T&CAM outpatient visits (Coef. = 0.11, p = 0.040).

Conclusions
Our findings showed that cancer occurrence within an individual led to the simultaneous use of conventional medicine and T&CAM. In addition, the occurrence of cancer significantly increased the number of T&CAM outpatient visits among participants already using T&CAM. It was also found that T&CAM has been utilized more often by the most vulnerable people, such as medical beneficiaries and those with a low level of education.
A qualitative study of senior management perspectives on the leadership skills required in regional and rural Australian residential aged care facilities
Authors: Dawes Nathan , Topp Stephanie M. 
Published: May 2022

Abstract
Background
With increasing recognition of the quality and safety issues in residential aged care, there is an urgent need to better understand what skills senior managers require to deliver on the spectrum of leadership functions in residential aged care facilities. This qualitative study sought to explore the leadership skills that positively influence the quality of care within Australian residential aged care facilities and better understand the professional development needs of senior managers to positively influence care within these complex environments.

Methods
We conducted semi-structured interviews with 19 senior managers purposively recruited from 14 high-performing non-government residential aged care facilities of varying geographical remoteness in northern Queensland, Australia. Participants held a range of professional roles, including Chief Executive Officer, Director of Nursing and Facility Manager, and had various professional qualifications. We used inductive thematic analysis to identify and categorise senior managers’ perspectives on the leadership skills and related strategies to promote quality of care.

Results
Senior managers reported leadership skills in five major domains: i) communication and relationship management, ii) stewardship, iii) professional development, iv) health care knowledge and v) information technology and finance. Most participants highlighted communication and relationship management skills and responding to regulatory change as influential to residential aged care quality performance. Participants with different professional backgrounds often emphasised different skills.

Conclusions
Participants identified a broad range of skills and strategies required by senior managers in Australian residential aged care facilities. Identifying different skills by differently trained individuals suggests more work is needed to understand and develop sector-specific professional development approaches to better prepare individuals to lead in this complex service environment.
MAIT cell counts are associated with the risk of hospitalization in COPD
Authors: Pincikova Terezia , Parrot Tiphaine , Hjelte Lena , Högman Marieann , Lisspers Karin , Ställberg Björn , Janson Christer , Malinovschi Andrei , Sandberg Johan K. 
Published: May 2022

Abstract
Background
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with chronic inflammation in the airways. Mucosal-associated invariant T (MAIT) cells are unconventional, innate-like T cells highly abundant in mucosal tissues including the lung. We hypothesized that the characteristics of MAIT cells in circulation may be prospectively associated with COPD morbidity.

Methods
COPD subjects (n = 61) from the Tools for Identifying Exacerbations (TIE) study were recruited when in stable condition. At study entry, forced expiratory volume in 1 s (FEV1) was measured and peripheral blood mononuclear cells were cryopreserved for later analysis by flow cytometry. Patients were followed for 3 years to record clinically meaningful outcomes.

Results
Patients who required hospitalization at one or more occasions during the 3-year follow-up (n = 21) had lower MAIT cell counts in peripheral blood at study inclusion, compared with patients who did not get hospitalized (p = 0.036). In contrast, hospitalized and never hospitalized patients did not differ in CD8 or CD4 T cell counts (p = 0.482 and p = 0.221, respectively). Moreover, MAIT cells in hospitalized subjects showed a more activated phenotype with higher CD38 expression (p = 0.014), and there was a trend towards higher LAG-3 expression (p = 0.052). Conventional CD4 and CD8 T cells were similar between the groups. Next we performed multi-variable logistic regression analysis with hospitalizations as dependent variable, and FEV1, GOLD 2017 group, and quantity or activation of MAIT and conventional T cells as independent variables. MAIT cell count, CD38 expression on MAIT cells, and LAG-3 expression on both MAIT and CD8 T cells were all independently associated with the risk of hospitalization.

Conclusions
These findings suggest that MAIT cells might reflect a novel, FEV1-independent immunological dimension in the complexity of COPD. The potential implication of MAIT cells in COPD pathogenesis and MAIT cells’ prognostic potential deserve further investigation.
Notch ankyrin domain: evolutionary rise of a thermodynamic sensor
Authors: Vujovic Filip , Hunter Neil , Farahani Ramin M. 
Published: May 2022

AbstractNotch signalling pathway plays a key role in metazoan biology by contributing to resolution of binary decisions in the life cycle of cells during development. Outcomes such as proliferation/differentiation dichotomy are resolved by transcriptional remodelling that follows a switch from Notchon to Notchoff state, characterised by dissociation of Notch intracellular domain (NICD) from DNA-bound RBPJ. Here we provide evidence that transitioning to the Notchoff state is regulated by heat flux, a phenomenon that aligns resolution of fate dichotomies to mitochondrial activity. A combination of phylogenetic analysis and computational biochemistry was utilised to disclose structural adaptations of Notch1 ankyrin domain that enabled function as a sensor of heat flux. We then employed DNA-based micro-thermography to measure heat flux during brain development, followed by analysis in vitro of the temperature-dependent behaviour of Notch1 in mouse neural progenitor cells. The structural capacity of NICD to operate as a thermodynamic sensor in metazoans stems from characteristic enrichment of charged acidic amino acids in β-hairpins of the ankyrin domain that amplify destabilising inter-residue electrostatic interactions and render the domain thermolabile. The instability emerges upon mitochondrial activity which raises the perinuclear and nuclear temperatures to 50 °C and 39 °C, respectively, leading to destabilization of Notch1 transcriptional complex and transitioning to the Notchoff state. Notch1 functions a metazoan thermodynamic sensor that is switched on by intercellular contacts, inputs heat flux as a proxy for mitochondrial activity in the Notchon state via the ankyrin domain and is eventually switched off in a temperature-dependent manner.
Certificate-of-need laws and substance use treatment
Authors: Bailey James , Lu Thanh , Vogt Patrick 
Published: May 2022

Abstract
Background
Certificate-of-need (CON) laws in place in most US states require healthcare providers to prove to a state board that their proposed services are necessary in order to be allowed to open or expand. While CON laws most commonly target hospital and nursing home beds, many states require CONs for other types of healthcare providers and services. As of 2020, 23 states retain CON laws specifically for substance use treatment, requiring providers to prove their “economic necessity” before opening or expanding. In contrast to the extensive academic literature on how hospital and nursing home CON laws affect costs and access, substance use CON laws are essentially unstudied.

Methods
Using 2002–19 data on substance use treatment facilities from the Substance Abuse and Mental Health Services Administration’s National Survey of Substance Abuse Treatment Services, we measure the effect of CON laws on access to substance use treatment. Using fixed-effects analysis of states enacting and repealing substance use CON laws, we measure how CON laws affect the number of substance use treament facilities and beds per capita in a state.

Results
We find that CON laws have no statistically significant effect on the number of facilities, beds, or clients and no significant effect on the acceptance of Medicare. However, they reduce the acceptance of private insurance by a statistically significant 6.0%.

Conclusions
Policy makers may wish to reconsider whether substance use CON laws are promoting their goals.
TTCOV19: timing of tracheotomy in SARS-CoV-2-infected patients: a multicentre, single-blinded, randomized, controlled trial
Authors: Eeg-Olofsson Måns , Pauli Nina , Hafsten Louise , Jacobsson Josephine , Lundborg Christopher , Brink Magnus , Larsson Helen , Lindell Ellen , Löwhagen Karin , Gisslén Magnus , Bergquist Henrik 
Published: May 2022

Abstract
Background
Critically ill COVID-19 patients may develop acute respiratory distress syndrome and the need for respiratory support, including mechanical ventilation in the intensive care unit. Previous observational studies have suggested early tracheotomy to be advantageous. The aim of this parallel, multicentre, single-blinded, randomized controlled trial was to evaluate the optimal timing of tracheotomy.

Methods
SARS-CoV-2-infected patients within the Region Västra Götaland of Sweden who needed intubation and mechanical respiratory support were included and randomly assigned to early tracheotomy (≤ 7 days after intubation) or late tracheotomy (≥ 10 days after intubation). The primary objective was to compare the total number of mechanical ventilation days between the groups.

Results
One hundred fifty patients (mean age 65 years, 79% males) were included. Seventy-two patients were assigned to early tracheotomy, and 78 were assigned to late tracheotomy. One hundred two patients (68%) underwent tracheotomy of whom sixty-one underwent tracheotomy according to the protocol. The overall median number of days in mechanical ventilation was 18 (IQR 9; 28), but no significant difference was found between the two treatment regimens in the intention-to-treat analysis (between-group difference: − 1.5 days (95% CI − 5.7 to 2.8); p = 0.5). A significantly reduced number of mechanical ventilation days was found in the early tracheotomy group during the per-protocol analysis (between-group difference: − 8.0 days (95% CI − 13.8 to − 2.27); p = 0.0064). The overall correlation between the timing of tracheotomy and days of mechanical ventilation was significant (Spearman’s correlation: 0.39, p < 0.0001). The total death rate during intensive care was 32.7%, but no significant differences were found between the groups regarding survival, complications or adverse events.

Conclusions
The potential superiority of early tracheotomy when compared to late tracheotomy in critically ill patients with COVID-19 was not confirmed by the present randomized controlled trial but is a strategy that should be considered in selected cases where the need for MV for more than 14 days cannot be ruled out.
Trial registrationNCT04412356, registered 05/24/2020.

Graphic abstract
Rapid molecular diagnostics of tuberculosis resistance by targeted stool sequencing
Authors: Sibandze Doctor B. , Kay Alexander , Dreyer Viola , Sikhondze Welile , Dlamini Qiniso , DiNardo Andrew , Mtetwa Godwin , Lukhele Bhekumusa , Vambe Debrah , Lange Christoph , Glenn Dlamini Muyalo , Ness Tara , Mejia Rojelio , Kalsdorf Barbara , Heyckendorf Jan , Kuhns Martin , Maurer Florian P. , Dlamini Sindisiwe , Maphalala Gugu , Niemann Stefan , Mandalakas Anna 
Published: May 2022

Abstract
Background
Stool is an important diagnostic specimen for tuberculosis in populations who struggle to provide sputum, such as children or people living with HIV. However, the culture of Mycobacterium tuberculosis (M. tuberculosis) complex strains from stool perform poorly. This limits the opportunity for phenotypic drug resistance testing with this specimen. Therefore, reliable molecular methods are urgently needed for comprehensive drug resistance testing on stool specimens.

Methods
We evaluated the performance of targeted next-generation sequencing (tNGS, Deeplex® Myc-TB) for the detection of mutations associated with M. tuberculosis complex drug resistance on DNA isolated from stool specimens provided by participants from a prospective cohort of patients treated for tuberculosis in Eswatini (n = 66; 56 with and 10 participants without M. tuberculosis complex DNA detected in stool by real-time quantitative PCR), and an independent German validation cohort of participants with culture-confirmed tuberculosis (n = 21).

Results
The tNGS assay detected M. tuberculosis complex DNA in 38 of 56 (68%) samples; for 28 of 38 (74%) samples, a full M. tuberculosis complex drug resistance prediction report was obtained. There was a high degree of concordance with sputum phenotypic drug susceptibility results (κ = 0.82). The ability to predict resistance was concentration-dependent and successful in 7/10 (70%), 18/25 (72%), and 3/21 (14%) of samples with stool PCR concentration thresholds of > 100 femtogram per microliter (fg/μl), 1 to 100 fg/μl, and < 1 fg/μl, respectively (p = 0.0004). The German cohort confirmed these results and demonstrated a similarly high concordance between stool tNGS and sputum phenotypic drug susceptibility results (κ = 0.84).

Conclusions
tNGS can identify drug resistance from stool provided by tuberculosis patients. This affords the opportunity to obtain critical diagnostic information for tuberculosis patients who struggle to provide respiratory specimens.
Paradoxical venous air embolism detected with point-of-care ultrasound: a case report
Authors: Ruiz Avila Hector Andres , García-Araque Hans Fred , Acosta-Gutiérrez Estivalis 
Published: May 2022

AbstractVenous air embolism (VAE) is an uncommon event consistent in the entrainment of air from any communication between the environment and the venous vasculature that could occur during central venous catheter (CVC) manipulation, and might trigger circulatory shock within minutes depending on the amount of air embolized. We present a case of a critical care patient who presented sudden clinical hemodynamic deterioration after the removal of central venous catheter. Hemodynamic evaluation with point-of-care ultrasound (POCUS) showed bubbles in both right and left heart cavities wherewith air embolism facilitated by heart septal defect was suspected. Therefore, the patient was reintubated, supported with vasopressors and a new CVC was inserted to proceed with air aspiration. Shortly after, the patient’s hemodynamic status improved in terms of vital signs stabilization. 6 h after the event with optimal perfusion markers and diminished sedation, the patient showed left hemiparesis therefore a cerebral magnetic resonance (MRI) was also performed showing hyperintensity in the right precentral gyrus, so ischemic stroke without hemorrhagic transformation diagnosis was made, because of paradoxical embolism. This case report demonstrates the value of POCUS application as a diagnostic tool in the hemodynamically unstable patient.
Contribution of a novel gene to lysergic acid amide synthesis in Metarhizium brunneum
Authors: Britton Kelcie N. , Steen Chey R. , Davis Kyle A. , Sampson Jessi K. , Panaccione Daniel G. 
Published: May 2022

Abstract
Objective
The fungus Metarhizium brunneum produces ergot alkaloids of the lysergic acid amide class, most abundantly lysergic acid α-hydroxyethylamide (LAH). Genes for making ergot alkaloids are clustered in the genomes of producers. Gene clusters of LAH-producing fungi contain an α/β hydrolase fold protein-encoding gene named easP whose presence correlates with LAH production but whose contribution to LAH synthesis in unknown. We tested whether EasP contributes to LAH accumulation through gene knockout studies.

Results
We knocked out easP in M. brunneum via a CRISPR/Cas9-based approach, and accumulation of LAH was reduced to less than half the amount observed in the wild type. Because LAH accumulation was reduced and not eliminated, we identified and mutated the only close homolog of easP in the M. brunneum genome, a gene we named estA. An easP/estA double mutant did not differ from the easP mutant in lysergic acid amide accumulation, indicating estA had no role in the pathway. We conclude EasP contributes to LAH accumulation but is not absolutely required. Either a gene encoding redundant function and lacking sequence identity with easP resides outside the ergot alkaloid synthesis gene cluster, or EasP plays an accessory role in the synthesis of LAH.
Differentially methylated CpGs in response to growth hormone administration in children with idiopathic short stature
Authors: Shao Xiaojian , Le Stunff Catherine , Cheung Warren , Kwan Tony , Lathrop Mark , Pastinen Tomi , Bougnères Pierre 
Published: May 2022

Abstract
Background
Recombinant human growth hormone (rhGH) has shown a great growth-promoting potential in children with idiopathic short stature (ISS). However, the response to rhGH differs across individuals, largely due to genetic and epigenetic heterogeneity. Since epigenetic marks on the methylome can be dynamically influenced by GH, we performed a comprehensive pharmacoepigenomics analysis of DNA methylation changes associated with long-term rhGH administration in children with ISS.

Results
We measured DNA methylation profiles before and after GH treatment (with a duration of ~ 18 months in average) on 47 healthy children using customized methylC-seq capture sequencing. Their changes were compared and associated with changes in plasma IGF1 by adjusting sex, age, treatment duration and estimated blood proportions. We observed a considerable inter-individual heterogeneity of DNA methylation changes responding to GH treatment. We identified 267 response-associated differentially methylated cytosines (DMCs) that were enriched in promoter regions, CpG islands and blood cell-type-specific regulatory elements. Furthermore, the genes associated with these DMCs were enriched in the biology process of “cell development,” “neuron differentiation” and “developmental growth,” and in the TGF-beta signaling pathway, PPAR Alpha pathway, endoderm differentiation pathway, adipocytokine signaling pathway as well as PI3K-Akt signaling pathway, and cAMP signaling pathway.

Conclusion
Our study provides a first insight in DNA methylation changes associated with rhGH administration, which may help understand mechanisms of epigenetic regulation on GH-responsive genes.
Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort
Authors: Grasset Leslie , Proust-Lima Cécile , Mangin Jean-François , Habert Marie-Odile , Dubois Bruno , Paquet Claire , Hanon Olivier , Gabelle Audrey , Ceccaldi Mathieu , Annweiler Cédric , David Renaud , Jonveaux Therese , Belin Catherine , Julian Adrien , Rouch-Leroyer Isabelle , Pariente Jérémie , Locatelli Maxime , Chupin Marie , Chêne Geneviève , Dufouil Carole ,   on behalf of the Memento Cohort Study group
Published: May 2022

Abstract
Background
This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer’s disease and related dementia (ADRD), and cognition.

Methods
The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition.

Results
Participants’ mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct β = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total β = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct β = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect β = 0.066 (0.042; 0.090) and direct β =  − 0.116 (− 0.153; − 0.079)), but not through AD pathology nor SVD.

Conclusions
Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.