bluuebunny/crossref_metadata_2025_split huggingface dataset:
B-329 Comparison Between Trough and AUC Monitoring of MPA in Patients With and Without Organ Transplantation. Influence of the Co-administered Immunosuppressant
Authors: Svinarov D 
Published: September 2023

Abstract

Background
Monitoring of mycophenolic acid (MPA) could be performed by measurement of trough concentrations with target therapeutic range of 1.3 to 3.5 mg/L, or by calculation of area under the drug concentration vs time curve (AUC) utilizing 3 or 4 samples within a dosing interval, with a target range of 30 to 60 mg*h/L. AUC is considered more reliable compared to trough levels, and MPA kinetics are dependent on the type of the co-administered calcineurine inhibitor. This study compares trough vs AUC MPA monitoring received alone or in co-administration with Cyclosporine (CsA) or with Tacrolimus (TAC).

Methods
77 transplanted patients receiving MPA, 25 of them on CsA, 49 on TAC, and 20 non-transplanted patients on MPA alone, were evaluated more than once, yielding 260 monitoring consults included for assessment: 45 for MPA alone, 108 for MPA combined with CsA, and 117 consults for the MPA combined with TAC. MPA, CsA, and TAC levels were measured by validated LC/MS/MS methods. Validated pharmacokinetic programs for the calculation of MPA AUC were used, adapted to the type of calcineurine inhibitor. Assessment was made by comparison of the distribution and coincidence between trough levels and AUC with respect to the above therapeutic ranges.

Results
Transplanted patents: when combined with CsA, MPA AUC was in the target range in 61% of cases, under it—in 31%, and in 8%—over it, while trough levels were 52% under, 42.5% within, and 5.5% over the therapeutic range; agreement between trough MPA and MPA AUC was poor—there was coincidence in 37.5% of sub-therapeutic, 63% of therapeutic and 0% of supra-therapeutic ranges, 3 cases were identified with sub-therapeutic trough and supra-therapeutic AUC; when combined with TAC, MPA AUC was in the target range in 63% of cases, under it—in 13%, and in 24%—over it; trough levels being 23% under, 60% within and 17% over the therapeutic range; agreement between trough MPA and MPA AUC was much better, compared to the combination with CsA: there was coincidence in 56% of sub-therapeutic, 84% of therapeutic and 80% of supra-therapeutic ranges. Nevertheless, 1 case was found with sub-therapeutic trough and supra-therapeutic AUC. In non-transplanted patients MPA AUC was in the target range in 47% of cases, under it—in 13%, and in 40%—over it; trough levels being 18% under, 53% within and 29% over the therapeutic range; agreement between trough MPA and MPA AUC showed coincidence in 75% of sub-therapeutic, 75% of therapeutic and 92% of supra-therapeutic ranges.

Conclusion
This study confirms that MPA AUC is more relevant than trough monitoring for dose individualization. It also shows that MPA trough levels are much more concordant with MPA AUC in non-transplanted patients and in transplanted patients on TAC, while in combination with CsA, discordance remains significant.
Estimating pregnancy rate from blubber progesterone levels of a blindly biopsied beluga population poses methodological, analytical and statistical challenges
Authors: Renaud L -A , Bordeleau X , Kellar N M , Pigeon G , Michaud R , Morin Y , Lair S , Therien A , Lesage V 
Published: September 2023

Abstract
Beluga (Delphinapterus leucas) from the St. Lawrence Estuary, Canada, have been declining since the early 2000s, suggesting recruitment issues as a result of low fecundity, abnormal abortion rates or poor calf or juvenile survival. Pregnancy is difficult to observe in cetaceans, making the ground truthing of pregnancy estimates in wild individuals challenging. Blubber progesterone concentrations were contrasted among 62 SLE beluga with a known reproductive state (i.e. pregnant, resting, parturient and lactating females), that were found dead in 1997 to 2019. The suitability of a threshold obtained from decaying carcasses to assess reproductive state and pregnancy rate of freshly-dead or free-ranging and blindly-sampled beluga was examined using three statistical approaches and two data sets (135 freshly harvested carcasses in Nunavik, and 65 biopsy-sampled SLE beluga). Progesterone concentrations in decaying carcasses were considerably higher in known-pregnant (mean ± sd: 365 ± 244 ng g−1 of tissue) than resting (3.1 ± 4.5 ng g−1 of tissue) or lactating (38.4 ± 100 ng g−1 of tissue) females. An approach based on statistical mixtures of distributions and a logistic regression were compared to the commonly-used, fixed threshold approach (here, 100 ng g−1) for discriminating pregnant from non-pregnant females. The error rate for classifying individuals of known reproductive status was the lowest for the fixed threshold and logistic regression approaches, but the mixture approach required limited a priori knowledge for clustering individuals of unknown pregnancy status. Mismatches in assignations occurred at lipid content &lt; 10% of sample weight. Our results emphasize the importance of reporting lipid contents and progesterone concentrations in both units (ng g−1 of tissue and ng g−1 of lipid) when sample mass is low. By highlighting ways to circumvent potential biases in field sampling associated with capturability of different segments of a population, this study also enhances the usefulness of the technique for estimating pregnancy rate of free-ranging population.
Sublobar resection is not always superior for early-stage lung cancer in high-risk patients
Authors: Fukui Mariko , Matsunaga Takeshi , Hattori Aritoshi , Takamochi Kazuya , Nojiri Shuko , Suzuki Kenji 
Published: September 2023

Abstract

OBJECTIVES
The phase III trial, Japan Clinical Oncology Group 0802, illustrated the superiority of sublobar resection for early-stage lung cancer in terms of overall survival, with more non-lung cancer-related deaths after a lobectomy. The advantages of sublobar resection may be more pronounced in high-risk patients. The goal of this study was to elucidate the prognoses of high-risk patients.

METHODS
Patients with a risk of being ineligible for Japan Clinical Oncology Group 0802 for general conditions were classified as the high-risk group, and those who were not at risk of being ineligible were classified as the normal-risk group. Overall survival and prognostic factors were analysed in the high-risk group.

RESULTS
There were 254 (19.4%) and 1054 patients in the high- and normal-risk groups, respectively. Five-year survival rates were 94.5% and 79.1% in the normal-risk and high-risk groups, respectively (P &lt; 0.001). More patients in the high-risk group died of lung cancer (P &lt; 0.001) and non-lung cancer deaths (P &lt; 0.001) than patients in the normal-risk group.
In the high-risk group, 151 lobectomies and 103 sublobar resections were performed. There was no significant difference in the numbers of lung cancer deaths and of non-lung cancer deaths between the procedures. Stratified survival analyses showed that the diffusing capacity of the lungs for carbon monoxide  &lt; 40% tended to favour sublobar resection; being female and having a high carcinoembryonic antigen level tended to favour a lobectomy.

CONCLUSIONS
Sublobar resection is not always superior for early-stage lung cancer. Even in such cases, the surgical method should be determined by taking into consideration the patient's background and lung cancer surveillance.
Smoking and cardiovascular outcomes after percutaneous coronary intervention: a Korean study
Authors: Ki You-Jeong , Han Kyungdo , Kim Hyo-Soo , Han Jung-Kyu 
Published: September 2023

Abstract

Background and Aims
The authors investigated the impact of smoking and its cessation after percutaneous coronary intervention (PCI) on cardiovascular outcomes.

Methods
Using a nationwide database from the Korean National Health Insurance System, 74 471 patients undergoing PCI between 2009 and 2016 were classified as non-, ex-, or current smokers, depending on smoking status at the first health check-up within 1 year after PCI. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, coronary revascularization, and stroke.

Results
During 4.0 years of follow-up, current smokers had a 19.8% higher rate of MACCE than non-smokers [adjusted hazard ratio (aHR) 1.198; 95% confidence interval (CI) 1.137–1.263], and ex-smokers tended to have a comparable rate with that of non-smokers (aHR 1.036; 95% CI .992–1.081). For 31 887 patients with both pre- and post-PCI health check-up data, the effects of smoking cessation were analysed. Among quitters who stopped smoking after PCI, quitters with cumulative smoking exposure of &lt;20 pack-years (PYs) tended to have a comparable rate of MACCE with that of persistent non-smokers. However, the rate in quitters with cumulative exposure of ≥20 PYs was comparable with that of persistent smokers [aHR (95% CI) for &lt;10 PY, 1.182 (.971–1.438); 10–20 PYs 1.114 (.963–1.290); 20–30 PYs 1.206 (1.054–1.380); ≥ 30 PYs 1.227 (1.113–1.352); persistent smokers 1.223 (1.126–1.328), compared with persistent non-smokers, respectively, P for interaction &lt;.001].

Conclusions
Smoking is associated with a higher risk of adverse outcomes in patients undergoing PCI. Quitters after PCI with &lt;20 PYs were associated with a risk comparable with that of non-smokers.
Disparities in cannabis use outcomes, perceived risks and social norms across sexual orientation groups of US young adult women and men
Authors: Romm Katelyn F , Cohn Amy M , Beebe Laura A , Berg Carla J 
Published: September 2023

Abstract
Little research has examined mechanisms driving cannabis use disparities among sexual minority (SM; versus heterosexual) young adults (YAs). Participants were US YA women (N = 1345; 24.8% bisexual, 6.1% lesbian) and men (N = 998: 8.9% bisexual, 13.8% gay). Bivariate analyses examined associations between sexual orientation (heterosexual, gay/lesbian, bisexual) and cannabis use outcomes (past 30-day [current] use, use frequency, cannabis-tobacco dual use, use intentions), perceived risks (harm, addictiveness) and social norms (social acceptability, peer use). Regressions examined sexual orientation, perceived risks and social norms as correlates of cannabis outcomes. Bisexual and lesbian (versus heterosexual) women reported lower cannabis-related perceived risks, greater social norms and higher odds of current use. Bisexual (versus heterosexual) women reported more days of use, higher odds of cannabis-tobacco dual use and greater use intentions. Gay (versus heterosexual) men reported lower perceived addictiveness, greater social norms and higher odds of current use. Lower perceived risks and greater social norms predicted greater use outcomes for women and men. Bisexual women displayed higher odds of several cannabis use outcomes, whereas lesbian women and gay men displayed higher odds of current cannabis use only. Cannabis-related perceptions and social norms may be important targets for public health messaging for SMYAs.
Disrupted phase behavior of FUS underlies poly-PR-induced DNA damage in amyotrophic lateral sclerosis
Authors: Wang Yixin , Liu Liu , Chen Hui , Yang Yinxue , Mu Chenchen , Ren Haigang , Liu Yanli , Yu Liqiang , Fang Qi , Wang Guanghui , Hao Zongbing 
Published: September 2023

Abstract
GGGGCC (G4C2) hexanucleotide repeat expansion (HRE) in the first intron of the chromosome 9 open reading frame 72 (C9ORF72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Among the five dipeptide repeat proteins translated from G4C2 HRE, arginine-rich poly-PR (proline:arginine) is extremely toxic. However, the molecular mechanism responsible for poly-PR-induced cell toxicity remains incompletely understood. Here, we found that poly-PR overexpression triggers severe DNA damage in cultured cells, primary cortical neurons, and the motor cortex of a poly-PR transgenic mouse model. Interestingly, we identified a linkage between poly-PR and RNA-binding protein fused in sarcoma (FUS), another ALS-related gene product associated with DNA repair. Poly-PR interacts with FUS both in vitro and in vivo, phase separates with FUS in a poly-PR concentration-dependent manner, and impairs the fluidity of FUS droplets in vitro and in cells. Moreover, poly-PR impedes the recruitment of FUS and its downstream protein XRCC1 to DNA damage foci after microirradiation. Importantly, overexpression of FUS significantly decreased the level of DNA damage and dramatically reduced poly-PR-induced cell death. Our data suggest the severe DNA damage caused by poly-PR and highlight the interconnection between poly-PR and FUS, enlightening the potential therapeutic role of FUS in alleviating poly-PR-induced cell toxicity.
The evolving story of catadromy in the European eel (Anguilla anguilla)
Authors: Durif C M F , Arts M , Bertolini F , Cresci A , Daverat F , Karlsbakk E , Koprivnikar J , Moland E , Olsen E M , Parzanini C , Power M , Rohtla M , Skiftesvik A B , Thorstad E , Vøllestad L A , Browman H I 
Published: September 2023

Abstract
Anguillid eels were once considered to be the classic example of catadromy. However, alternative life cycles have been reported, including skipping the freshwater phase and habitat shifting between fresh, brackish, and saltwater throughout the growth phase. There is a lack of knowledge regarding these alternate life strategies, for example, the proportion of individuals in the population that adopt them compared to classic catadromy. We provide a description of these alternate life cycle strategies in temperate anguillids, their possible drivers, and the methods available to investigate them. These methods (lethal and non-lethal), include otolith microchemistry, fatty acid and stable isotope analyses, parasite identification, blood transcriptomics, and electronic tags. We argue that since the current management framework for the European eel and other temperate eels is based mainly on the freshwater component of the population, it ignores eels growing in saline waters. Many of the factors that are thought to be responsible for the precipitous decline of the eel population are more prevalent in freshwater systems. Therefore, the contribution of saline eels may be more important than currently estimated. The habitat-shifting ability of eels may be all the more crucial for the persistence and recovery of those species that are endangered.
Using BCG Vaccine to Enhance Nonspecific Protection of Health Care Workers During the COVID-19 Pandemic: A Randomized Controlled Trial
Authors: Madsen Anne Marie Rosendahl , Schaltz-Buchholzer Frederik , Nielsen Sebastian , Benfield Thomas , Bjerregaard-Andersen Morten , Dalgaard Lars Skov , Dam Christine , Ditlev Sisse Bolm , Faizi Gulia , Azizi Mihnaz , Hameed Zainab Nadhim , Johansen Isik Somuncu , Kofoed Poul-Erik , Krause Tyra Grove , Kristensen Gitte Schultz , Loekkegaard Ellen Christine Leth , Mogensen Christian Backer , Mohamed Libin , Oedegaard Emilie Sundhaugen , Ostenfeld Anne , Soerensen Marcus Kjaer , Wejse Christian , Netea Mihai G , Aaby Peter , Benn Christine Stabell 
Published: September 2023

Abstract

Background
The BCG (Bacillus Calmette-Guérin) vaccine can induce nonspecific protection against unrelated infections. We aimed to test the effect of BCG on absenteeism and health of Danish health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic.

Methods
A single-blinded randomized controlled trial included 1221 HCWs from 9 Danish hospitals. Participants were randomized 1:1 to standard dose BCG or placebo. Primary outcome was days of unplanned absenteeism. Main secondary outcomes were incidence of COVID-19, all-cause hospitalization, and infectious disease episodes.

Results
There was no significant effect of BCG on unplanned absenteeism. Mean number of days absent per 1000 workdays was 20 in the BCG group and 17 in the placebo group (risk ratio, 1.23; 95% credibility interval, 0.98–1.53). BCG had no effect on incidence of COVID-19 or all-cause hospitalization overall. In secondary analyses BCG revaccination was associated with higher COVID-19 incidence (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.07–5.71), but also reduced risk of hospitalization (HR, 0.28; 95% CI, .09–.86). The incidence of infectious disease episodes was similar between randomization groups (HR, 1.09; 95% CI, .96–1.24).

Conclusions
In this relatively healthy cohort of HCWs, there was no overall effect of BCG on any of the study outcomes.

Clinical Trials Registration
NCT0437329 and EU Clinical Trials Register (EudraCT number 2020-001888-90).
IL-27 regulates NLRP3 inflammasome activation of MDSCs in experimental Sjögren’s syndrome
Authors: Xia Xiaoyu , Long Qiqiang , Zha Jie , Jiang Tingting , Guo Junqiao , Jiang Bo , Li Xiaojing , Yao Genhong 
Published: September 2023

Abstract
Excessive NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation has an important function in the pathogenesis of Sjögren’s syndrome (SS). Increased and dysfunctional myeloid-derived suppressor cells (MDSCs) promoted SS. However, NLRP3 inflammasome activation of MDSCs in SS and its regulated components are unclear. Splenic MDSCs were purified by immunomagnetic beads and cultured. Western blot was used to assess NLRP3 inflammasomes. Interleukin-1β (IL-1β) and IL-18 were measured using enzyme-linked immunosorbent assay. Here we showed that the NLRP3 inflammasome was activated in non-obese diabetic (NOD) mice with SS-like manifestations. We found that NLRP3 inflammasome activation was augmented in MDSCs of SS mice and NLRP3 inflammasome activation was suppressed in IL-27-deficient NOD mice. Consistent with findings of SS mice in vivo, we observed that NLRP3 inflammasome activation by adenosine triphosphate and lipopolysaccharide was remarkably intensified in MDSCs with IL-27 treatment in vitro. Collectively, our data highlighted that IL-27 regulates NLRP3 inflammasome activation of MDSCs in experimental SS.
The use of natural language processing in detecting and predicting falls within the healthcare setting: a systematic review
Authors: Trinh Vincent Quoc-Nam , Zhang Steven , Kovoor Joshua , Gupta Aashray , Chan Weng Onn , Gilbert Toby , Bacchi Stephen 
Published: September 2023

Abstract
Falls are a common problem associated with significant morbidity, mortality, and economic costs. Current fall prevention policies in local healthcare settings are often guided by information provided by fall risk assessment tools, incident reporting, and coding data. This review was conducted with the aim of identifying studies which utilized natural language processing (NLP) for the automated detection and prediction of falls in the healthcare setting. The databases Ovid Medline, Ovid Embase, Ovid Emcare, PubMed, CINAHL, IEEE Xplore, and Ei Compendex were searched from 2012 until April 2023. Retrospective derivation, validation, and implementation studies wherein patients experienced falls within a healthcare setting were identified for inclusion. The initial search yielded 2611 publications for title and abstract screening. Full-text screening was conducted on 105 publications, resulting in 26 unique studies that underwent qualitative analyses. Studies applied NLP towards falls risk factor identification, known falls detection, future falls prediction, and falls severity stratification with reasonable success. The NLP pipeline was reviewed in detail between studies and models utilizing rule-based, machine learning (ML), deep learning (DL), and hybrid approaches were examined. With a growing literature surrounding falls prediction in both inpatient and outpatient environments, the absence of studies examining the impact of these models on patient and system outcomes highlights the need for further implementation studies. Through an exploration of the application of NLP techniques, it may be possible to develop models with higher performance in automated falls prediction and detection.
Innovative approaches to analysing aged care falls incident data: international classification for patient safety and correspondence analysis
Authors: Seaman Karla , Meulenbroeks Isabelle , Nguyen Amy , Silva Sandun , Wabe Nasir , Huang Guogui , Hibert Peter , Paudel Pramilia , Westbrook Johanna 
Published: September 2023

Abstract
Falls in residential aged care facilities (RACFs) are common and can have significant health consequences. Understanding how and why falls occur in RACFs is an essential step to design targeted fall prevention and intervention programmes; however, little is known about falls’ mechanisms in RACFs. This study aims to use international incident classification systems and novel analysis techniques to describe factors that contribute to falls requiring hospitalization in RACFs. Retrospective data of falls assessed by nurses as requiring hospitalization from 429 residents in 22 Australian RACFs in 2019 were used. Data were reviewed using a modified version of the International Classification for Patient Safety (ICPS), which categorizes patient safety into incident types and contributing factors using a three-tiered structure. The ICPS codes were summarized using the descriptive statistics. The association between assigned ICPS codes were analysed using correspondence analysis. Six hundred and three falls assessed as requiring hospitalization were classified into 659 incident types, with the most common incident type being ‘patient incidents’ (injury sustained/adverse effect in the health care system) (603, 91.5%) at Level 1, ‘falls’ (601, 91.2%) at Level 2, and ‘falls involving bedrooms’ (214, 32.5%) at Level 3. The 603 falls had 1082 contributing factors, with the most common contributing factor being ‘patient factors’ (events affected by factors associated with the patient) (982, 90.8%) at Level 1, ‘patient not elsewhere classified’ (characteristics of the patient contributed to the incident not classified elsewhere) (571, 52.8%) at Level 2, and ‘loss of balance’ (361, 33.4%) at Level 3. In a correspondence analysis, three dimensions were responsible for 81.2% of the variation in falls incidents and environmental and organizational factors were important factors contributing to falls. The application of the ICPS demonstrated that personal factors (e.g. pre-existing physical and psychological health or impairment) were the most common contributing factors to falls assessed as requiring hospitalization, while the correspondence analysis highlighted the role of environmental and organizational factors. The results signal the need for more research into multifactorial falls prevention interventions in RACFs.