bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification
Authors: Kaiser Yannick , van der Toorn Janine E , Singh Sunny S , Zheng Kang H , Kavousi Maryam , Sijbrands Eric J G , Stroes Erik S G , Vernooij Meike W , de Rijke Yolanda B , Boekholdt S Matthijs , Bos Daniel 
Published: July 2022

Abstract

Aim
Lipoprotein(a) [Lp(a)] is a potential causal factor in the pathogenesis of aortic valve disease. However, the relationship of Lp(a) with new onset and progression of aortic valve calcium (AVC) has not been studied. The purpose of the study was to assess whether high serum levels of Lp(a) are associated with AVC incidence and progression.

Methods and results
A total of 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men), whose Lp(a) measurements were available, underwent non-enhanced cardiac computed tomography imaging at baseline and after a median follow-up of 14.0 [interquartile range (IQR) 13.9–14.2] years. New-onset AVC was defined as an AVC score &gt;0 on the follow-up scan in the absence of AVC on the first scan. Progression was defined as the absolute difference in AVC score between the baseline and follow-up scan. Logistic and linear regression analyses were performed to evaluate the relationship of Lp(a) with baseline, new onset, and progression of AVC. All analyses were corrected for age, sex, body mass index, smoking, hypertension, dyslipidaemia, and creatinine. AVC progression was analysed conditional on baseline AVC score expressed as restricted cubic splines. Of the 702 individuals without AVC at baseline, 415 (59.1%) developed new-onset AVC on the follow-up scan. In those with baseline AVC, median annual progression was 13.5 (IQR = 5.2–37.8) Agatston units (AU). Lipoprotein(a) concentration was independently associated with baseline AVC [odds ratio (OR) 1.43 for each 50 mg/dL higher Lp(a); 95% confidence interval (CI) 1.15–1.79] and new-onset AVC (OR 1.30 for each 50 mg/dL higher Lp(a); 95% CI 1.02–1.65), but not with AVC progression (β: −71 AU for each 50 mg/dL higher Lp(a); 95% CI −117; 35). Only baseline AVC score was significantly associated with AVC progression (P &lt; 0.001).

Conclusion
In the population-based Rotterdam Study, Lp(a) is robustly associated with baseline and new-onset AVC but not with AVC progression, suggesting that Lp(a)-lowering interventions may be most effective in pre-calcific stages of aortic valve disease.
Designing and conducting qualitative research across countries and cultures: challenges for inclusiveness and rigour
Authors: Cuoco Angela , Arcadi Paola , Figura Maria Chiara , Piervisani Loredana , Alvaro Rosaria , Vellone Ercole , Durante Angela 
Published: July 2022

Abstract
Qualitative research is fundamental to understanding the nature and complexity of human phenomena. While cultural and psychometric validations exist for quantitative tools, the same cannot be said of qualitative ones. There are other many challenges when conducting a multinational qualitative study, which includes different cultural and linguistic ‘biases’. This paper presents some key issues that researchers may encounter when designing and developing multinational and multicultural qualitative studies, and also provides some strategies to overcome difficulties and ensure rigour.
Epidemiology and management of hepatitis B and C in primary care in the Netherlands: data from the Rijnmond Primary Care database
Authors: Brakenhoff Sylvia M , de Man Robert A , de Knegt Robert J , Bindels Patrick J E , de Schepper Evelien I T 
Published: July 2022

Abstract

Background
The Dutch guideline for general practitioners (GPs) advises biannual surveillance of hepatitis B (HBV) patients and referral of every hepatitis C (HCV) patient. We aimed to study the prevalence, incidence, and the management of hepatitis B and C in primary care.

Methods
This is a retrospective cohort study using the Rijnmond Primary Care database (RPCD), including health care data of medical records of GPs of approximately 200,000 patients in the area of Rotterdam, the Netherlands. Patient records were selected based on laboratory results, International Classification of Primary Care (ICPC) codes, and free-text words.

Results
In total, 977 patients were included: 717 HBV, 252 HCV, and 8 HBV/HCV coinfected patients. Between 2013 and 2019, the prevalence of HBV and HCV declined from 5.21 to 2.99/1,000 person-years (PYs) and 1.50 to 0.70/1,000 PYs, respectively. We observed that the majority of the patients had been referred to a medical specialist at least once (71% HBV and 89% HCV patients). However, among chronic patients, we observed that 36.2% of the HBV patients did not receive adequate surveillance by their GP (≥2 alanine aminotransferase checks within 3 years) or a medical specialist. In addition, 44.4% of the HCV patients had no record about successful antiviral treatment.

Conclusions
This study demonstrated a declining prevalence in viral hepatitis B and C in primary care in the Netherlands. However, a substantial part of the patients did not receive adequate surveillance or antiviral therapy. It is therefore crucial to involve GPs in case finding and in follow-up after treatment.
Disturbance by soil mixing decreases microbial richness and supports homogenizing community assembly processes
Authors: West Jaimie R , Whitman Thea 
Published: July 2022

AbstractThe spatial heterogeneity of soil’s microhabitats warrants the study of ecological patterns and community assembly processes in the context of physical disturbance that disrupts the inherent spatial isolation of soil microhabitats and microbial communities. By mixing soil at various frequencies in a 16-week lab incubation, we explored the effects of physical disturbance on soil bacterial richness, community composition, and community assembly processes. We hypothesized that well-mixed soil would harbor a less rich microbial community, with community assembly marked by homogenizing dispersal and homogeneous selection. Using 16S rRNA gene sequencing, we inferred community assembly processes, estimated richness and differential abundance, and calculated compositional dissimilarity. Findings supported our hypotheses, with &gt; 20% decrease in soil bacterial richness in well-mixed soil. Soil mixing caused communities to diverge from unmixed controls (Bray–Curtis dissimilarity; 0.75 vs. 0.25), while reducing within-group heterogeneity. Our results imply that the vast diversity observed in soil may be supported by spatial heterogeneity and isolation of microbial communities, and also provide insight into the effects of physical disturbance and community coalescence events. By isolating and better understanding the effects of spatial heterogeneity and disconnectivity on soil microbial communities, we can better extrapolate how anthropogenic disturbances may affect broad soil functions.
Treponema pallidum outer membrane proteins: current status and prospects
Authors: Chen Jinlin , Huang Jielite , Liu Zhuoran , Xie Yafeng 
Published: July 2022

Abstract
The outer membrane proteins (OMPs) of Treponema pallidum subsp. pallidum (T. pallidum), the etiological agent of the sexually transmitted disease syphilis, have long been a hot research topic. Despite many hurdles to studying the pathogen, especially the inability to manipulate T. pallidum in vitro genetically, considerable progress has been made in elucidating the structure, pathogenesis and functions of T. pallidum OMPs. In this review, we integrate this information to garner fresh insights into the role of OMPs in the diagnosis, pathogenicity and vaccine development of T. pallidum. Collectively, the essential scientific discussions herein should provide a framework for understanding the current status and prospects of T. pallidum OMPs.
Age-Related Changes in Skeletal Muscle Iron Homeostasis
Authors: Alves Francesca M , Ayton Scott , Bush Ashley I , Lynch Gordon S , Koopman René 
Published: July 2022

Abstract
Sarcopenia is an age-related condition of slow, progressive loss of muscle mass and strength, which contributes to frailty, increased risk of hospitalization and mortality, and increased health care costs. The incidence of sarcopenia is predicted to increase to &gt;200 million affected older adults worldwide over the next 40 years, highlighting the urgency for understanding biological mechanisms and developing effective interventions. An understanding of the mechanisms underlying sarcopenia remains incomplete. Iron in the muscle is important for various metabolic functions, including oxygen supply and electron transfer during energy production, yet these same chemical properties of iron may be deleterious to the muscle when either in excess or when biochemically unshackled (eg, in ferroptosis), it can promote oxidative stress and induce inflammation. This review outlines the mechanisms leading to iron overload in muscle with aging and evaluates the evidence for the iron overload hypothesis of sarcopenia. Based on current evidence, studies are needed to (a) determine the mechanisms leading to iron overload in skeletal muscle during aging; and (b) investigate whether skeletal muscles are functionally deficient in iron during aging leading to impairments in oxidative metabolism.
Racial Differences in the Dementia Caregiving Experience During the COVID-19 Pandemic: Findings From the National Health and Aging Trends Study (NHATS)
Authors: Moon Heehyul E , Rote Sunshine M , Sears Jeanelle , Schepens Niemiec Stacey L 
Published: July 2022

Abstract

Objectives
Given racial disparities in both dementia and coronavirus disease 2019 (COVID-19), non-Hispanic Black (Black) dementia caregivers (CGs) may be at greater risk for care burden during the COVID-19 pandemic than non-Hispanic White (White) CGs. This study investigates the impact of dementia care provision on CGs’ quality of life by race using the 2020 National Health and Aging Trends Study Family Members and Friends COVID-19 data (FF).

Methods
This study features a secondary analysis of FF data (2020–2021), including 216 Black and 1,204 White CGs. We used ANOVA to determine differences in caregiving stressors (i.e., changes in providing help with activities of daily living [ADL], instrumental ADL [IADL], and emotional support). Ordinary least square regression was used to investigate the moderating effects of dementia care on the associations of race with perceived well-being, care burden, and self-reported health and to conduct subgroups analyses of Black and White dementia CGs.

Results
Black dementia CGs provided significantly more help with ADL before and during the COVID-19 pandemic than Black nondementia, White dementia, and White nondementia CGs. Dementia care status did not moderate the associations between race and CG outcomes. For Black dementia CGs, changes in objective stressors (assistance with ADL and IADL) were associated with care burden and well-being. For White CGs, the provision of emotional support was associated with care burden and well-being.

Discussion
This study highlights that increased caregiving demands during the pandemic amplified racial differences in CG stress. Findings suggest that outreach to reduce CG stress and burden is critical for Black dementia CGs.
Precise exogenous insertion and sequence replacements in poplar by simultaneous HDR overexpression and NHEJ suppression using CRISPR-Cas9
Authors: Movahedi Ali , Wei Hui , Zhou Xiaohong , Fountain Jake C , Chen Zhong-Hua , Mu Zhiying , Sun Weibo , Zhang Jiaxin , Li Dawei , Guo Baozhu , Varshney Rajeev K , Yang Liming , Zhuge Qiang 
Published: July 2022

AbstractCRISPR-mediated genome editing has become a powerful tool for the genetic modification of biological traits. However, developing an efficient, site-specific, gene knock-in system based on homology-directed DNA repair (HDR) remains a significant challenge in plants, especially in woody species like poplar. Here, we show that simultaneous inhibition of non-homologous end joining (NHEJ) recombination cofactor XRCC4 and overexpression of HDR enhancer factors CtIP and MRE11 can improve HDR efficiency for gene knock-in. Using this approach, the BleoR gene was integrated onto the 3′ end of the MKK2 MAP kinase gene to generate a BleoR-MKK2 fusion protein. Based on fully edited nucleotides evaluated by TaqMan real-time PCR, the HDR-mediated knock-in efficiency was up to 48% when using XRCC4 silencing incorporated with a combination of CtIP and MRE11 overexpression compared with no HDR enhancement or NHEJ silencing. Furthermore, this combination of HDR enhancer overexpression and NHEJ repression also increased genome targeting efficiency and gave 7-fold fewer CRISPR-induced insertions and deletions (InDels), resulting in no functional effects on MKK2-based salt stress responses in poplar. Therefore, this approach may be useful not only in poplar and plants or crops but also in mammals for improving CRISPR-mediated gene knock-in efficiency.
Characteristics of community-acquired carbapenem-resistant Enterobacterales
Authors: Shrestha Rima , Luterbach Courtney L , Dai Weixiao , Komarow Lauren , Earley Michelle , Weston Gregory , Herc Erica , Jacob Jesse T , Salata Robert , Wong Darren , Anderson Deverick , Rydell Kirsten B , Arias Cesar A , Chen Liang , van Duin David ,   MDRO Investigators, Weston Gregory , Ostrowsky Belinda , Lok Judith J , Bonomo Robert A , Domitrovic T Nicholas , Hujer Kristine M , Hujer Andrea M , Rudin Susan D , Marshall Steven H , Salata Robert A , Perez Federico , Cober Eric , Richter Sandra S , Arias Rebekka , Hill Carol , Fowler Vance G , Anderson Deverick J , Jacob Jesse T , Wang Minggui , Chen Liang , Desai Samit , Kreiswirth Barry N , Manca Claudia , Mediavilla Jose R , Patel Gopi , Huskins W Charles , Patel Robin , Revolinski Sara , Wortmann Glenn , Kalayjian Robert C , Kim Angela , Garcia-Diaz Julia , Fries Bettina C , Eilertson Brandon , Gallagher Jason C , Earley Michelle , Evans Scott , Komarow Lauren , Garner Omai B , Chambers Henry F , Farrell John J , Abbo Lilian M , Kaye Keith S , Luterbach Courtney , van Duin David , Han Jennifer H , Doi Yohei , Paterson David L , Wong Darren , Arias Cesar A , Hanson Blake , Dinh An , Panesso Diana , Shropshire William , Tran Truc T , Banerjee Ritu , Dhar Sorabh , Satlin Michael J , Grant Matthew 
Published: July 2022

AbstractBackgroundCommunity-acquired carbapenem-resistant Enterobacterales (CA-CRE) are an important threat.MethodsIn CRACKLE-2, we defined patients with CA-CRE as admitted from home, without pre-existing conditions, and a positive culture within 48 h of admission. Healthcare-associated CRE (HA-CRE) were those with the lowest likelihood of community acquisition, not admitted from home and cultured &gt;48 h after admission. Specific genetic markers in carbapenemase-producing Klebsiella pneumoniae were evaluated through random forest modelling.ResultsCA-CRE and HA-CRE were detected in 83 (10%) and 208 (26%) of 807 patients. No significant differences were observed in bacterial species or strain type distribution. K. pneumoniae (204/291, 70%) was the most common CRE species, of these 184/204 (90%) were carbapenemase producers (CPKP). The top three genetic markers in random forest models were kpi_SA15, fimE, and kpfC. Of these, kpi_SA15 (which encodes a chaperone/usher system) was positively associated (OR 3.14, 95% CI 1.13–8.87, P = 0.026), and kpfC negatively associated (OR 0.21, 95% CI 0.05–0.72, P = 0.015) with CA-CPKP.ConclusionsTen percent of CDC-defined CRE were CA. The true proportion of CA-CRE in hospitalized patients is likely lower as patients may have had unrecorded prior healthcare exposure. The kpi_SA15 operon was associated with the CA phenotype.
Individual target pharmacokinetic/pharmacodynamic attainment rates among meropenem-treated patients admitted to the ICU with hospital-acquired pneumonia
Authors: Rohani Roxane , Scheetz Marc H , Donnelly Helen K , Donayre Alvaro , Kang Mengjia , Diaz Estefani , Dedicatoria Kay , Hauser Alan R , Ozer Egon A , Nozick Sophia , Qi Chao , Pawlowski Anna E , Neely Michael N , Misharin Alexander V , Wunderink Richard G , Rhodes Nathaniel J ,   NU SCRIPT Study investigators, Abdala-Valencia Hiam , Alexander Michael J , Arnold Jason M , Bailey Joseph Isaac , Bartom Elizabeth T , Bharat Ankit , Bolig Thomas , Borkowski Nicole , Budinger G R Scott , Chandel Navdeep S , Clepp Rebecca K , Coleman John , Cuttica Michael J , Cybulski Thaddeus R , Dematte Jane E , Deters Joseph S , Fiala Justin A , Gadhvi Gaurav T , Gao Catherine A , Gates Khalilah L , Gatesy Samuel W M , Giri Ritika , Go Pearl D , Gottardi Cara J , Grant Rogan A , Green Stefan J , Gusman Elen , Guzman Estefany R , Han SeungHye , Hartmann Erica Marie , Horvath Curt M , Hukamdad Mishaal , Hyder Sydney M , Jain Manu , Joudi Anthony M , Kadar Rachel B , Kalhan Ravi , Kamp David W , Kandpal Manoj , Kidd David A , Kihshen Hermon , Klug Zasu M , Korth Erin A , Kruser Jacqueline M , Lawrence Romy , Leibenguth Emily M , Levenson Anne R , Gradone Lindsey D , Liu Gabrielle Y , Lomasney Jon W , Lombardo Theresa A , Lu Ziyan , Ludwig Amy , Mahmoud Ali , Malsin Elizabeth S , Markov Nikolay S , McQuattie-Pimentel Alexandra C , Meza Daniel , Morales Felix Leonardo , Morales-Nebreda Luisa , Morimoto Richard I , Mylvaganam Ruben J , Nannapaneni Prasanth , Amaral Luís A Nunes , Patel Radhika , Pesce Lorenzo L , Pickens Chiagozie O , Politanska Yuliya , Poor Taylor A , Prickett Michelle Hinsch , Querrey Melissa , Rasmussen Luke V , Ren Ziyou , Ridge Karen M , Rosenbaum Madeline L , Rosenberg Sharon R , Rowe Timothy , Russell Susan R , Sala Marc A , Schneider Daniel , Schroedl Clara J , Secunda Katharine , Seed Patrick C , Senkow Karolina J , Shamaly Todd , Shanes Elisheva D , Shen Jiaxian , Shilatifard Ali , Sichizya Lango , Singer Benjamin D , Smith Sean , Sporn Peter H S , Starren Justin , Stoeger Thomas , Sumner Jack , Swaminathan Suchitra , Sznajder Jacob I , Navarro Heliodoro Tejedor , Textor Lindsey N , Thakkar Sanket , Tomic Rade , Tran Betty , Vitale Kaitlyn , Wagh Ajay A , Walter James M , Wehbe Firas , Winter Deborah R , Wolfe Alexis Rose , Wolfe Lisa F , Yeldandi Anjana V 
Published: July 2022

Abstract

Objectives
Critical illness reduces β-lactam pharmacokinetic/pharmacodynamic (PK/PD) attainment. We sought to quantify PK/PD attainment in patients with hospital-acquired pneumonia.

Methods
Meropenem plasma PK data (n = 70 patients) were modelled, PK/PD attainment rates were calculated for empirical and definitive targets, and between-patient variability was quantified [as a coefficient of variation (CV%)].

Results
Attainment of 100% T&gt;4×MIC was variable for both empirical (CV% = 92) and directed (CV% = 33%) treatment.

Conclusions
Individualization is required to achieve suggested PK/PD targets in critically ill patients.
Impact of the COVID-19 pandemic on hospital antimicrobial consumption in Croatia
Authors: Vlahović-Palčevski Vera , Rubinić Igor , Payerl Pal Marina 
Published: July 2022

Abstract

Objectives
The aim of the study was to assess the impact of the COVID-19 pandemic on antimicrobial consumption (AMC) in the hospital sector in Croatia by analysing data reported to the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) between 2016 and 2020.

Methods
AMC was measured as the number of DDDs/1000 inhabitants/day and as the number of DDDs/100 bed days. To assess trends, linear regression was performed. To assess the impact of the pandemic on AMC, the compound annual growth rate was calculated for the years preceding the pandemic based on which AMC for 2020 was forecasted and compared with the actual consumption.

Results
While hospital AMC expressed as DDDs/1000 inhabitants/day between 2019 and 2020 decreased by 17%, when expressed as DDDs/100 bed days, an 8% increase was observed. Hospital consumption of antibacterials for systemic use in the 5 year period did not significantly change when expressed as DDDs/1000 inhabitants/day, while it statistically significantly increased when expressed as DDDs/100 bed days. An increasing trend in consumption of broad-spectrum antimicrobials was found.

Conclusions
During the pandemic there was an increase in hospital AMC with a shift towards broad-spectrum antimicrobials requiring further in-depth qualitative analysis based on patient-level data. Contrasting results obtained using different denominators indicate that the metric DDDs/1000 inhabitants/day is not sensitive enough to evaluate hospital AMC. When assessing hospital AMC, the population under surveillance should be relevant for healthcare context. Antimicrobial stewardship remains one of the most important strategies to tackle antimicrobial resistance and antimicrobial surveillance methods must be as sensitive as possible.
Plasma and cerebrospinal fluid concentrations of cefiderocol during successful treatment of carbapenem-resistant Acinetobacter baumannii meningitis
Authors: Kufel Wesley D , Abouelhassan Yasmeen , Steele Jeffrey M , Gutierrez Ramiro L , Perwez Talha , Bourdages George , Nicolau David P 
Published: July 2022

Abstract

Background
To date, no real-world data are available to describe cefiderocol use in carbapenem-resistant Acinetobacter baumannii (CRAB) meningitis. Furthermore, cefiderocol pharmacokinetic (PK) data to support CNS penetration in human subjects are limited. These gaps pose a significant concern for clinicians who are faced with treating such infections when considering cefiderocol use.

Objectives
To describe cefiderocol CSF and plasma PK and pharmacodynamic (PD) data from two different dosing regimens [2 g IV q6h (regimen 1) and 2 g IV q8h (regimen 2)] during treatment of CRAB meningitis.

Patients and methods
A 61-year-old woman with CRAB meningitis was treated with cefiderocol and intraventricular gentamicin. Steady-state plasma and CSF cefiderocol concentrations were evaluated on Day 19 (regimen 1) and Day 24 (regimen 2) during the cefiderocol treatment course.

Results
CSF AUC was 146.49 and 118.28 mg·h/L, as determined by the linear-log trapezoidal method for regimens 1 and 2, respectively. Penetration into CSF estimated as the AUCCSF/AUCfree plasma ratio was 68% and 60% for regimens 1 and 2, respectively. Estimated free plasma and CSF concentrations exceeded the MIC of the isolate for 100% of the dosing interval. Microbiological and clinical cure were achieved, and no cefiderocol-associated adverse effects were observed.

Conclusions
Cefiderocol, when given as 2 g q8h and 2 g q6h, attained CSF concentrations that exceeded the organism-specific MIC and the CLSI susceptible breakpoint (≤4 mg/L) for 100% of the dosing interval.