bluuebunny/crossref_metadata_2025_split huggingface dataset:
The MAPK/ERK signaling pathway regulates the expression and localization of Cx43 in mouse proximal epididymis
Authors: Kim Bongki , Breton Sylvie 
Published: February 2022

AbstractThis study aimed to clarify the functional role of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2)-signaling pathway in the expression and localization of connexin 43 (Cx43). Mice were treated with the mitogen-activated protein kinase kinase (MEK1/2) inhibitor, PD325901, which induced a progressive decrease in ERK1/2 phosphorylation (pERK) in the proximal epididymis of the mice, without affecting total ERK level. Cx43 staining with punctuated reactive sites was observed in the basolateral membranes in the initial segment (IS) of mouse epididymis. However, PD325901 induced a significant decrease in Cx43 labeling in the basolateral membranes. Interestingly, Cx43, which was undetectable in the apical region of epididymis under control conditions, showed a significant increase in the apical region after PD 325901 treatment. To confirm whether Cx43 was present in tight junctions (TJs) after PD 325901 treatment, PD325901-treated epididymis samples were double-labeled with Cx43 and zonula occludens (ZO)-1 (a TJ protein marker). Thereafter, confocal microscopy showed the colocalization of Cx43 and ZO-1 in the epididymis after PD325901 treatment. Collectively, our results indicated that PD325901 treatment induced a significant increase in Cx43 localization on TJs, where it was colocalized with ZO-1. Therefore, the study suggested that ERK phosphorylation is essential for the proper expression and localization of the gap junction (GJ) protein, and that the relationship between GJs and TJs could play an important role in establishing and maintaining microenvironmental homeostasis for sperm maturation in the IS of mouse epididymis.
Pathological complete response as a surrogate to improved survival in human epidermal growth factor receptor-2-positive breast cancer: systematic review and meta-analysis
Authors: Davey Matthew G. , Browne Ferdia , Miller Nicola , Lowery Aoife J. , Kerin Michael J. 
Published: February 2022

AbstractBackgroundAchieving a pathological complete response (pCR) is believed to correlate with oncological outcomes in human epidermal growth factor receptor-2-positive (HER2+) breast cancer. However, informed estimation of this survival advantage is often difficult to quantify. The aim of this study was to evaluate the role of pCR as a biomarker of survival in patients treated with neoadjuvant therapies for HER2+ breast cancer.MethodsA systematic review was performed in accordance with the PRISMA checklist. Data specific to pCR and survival with respect to event-free survival (EFS), recurrence-free survival (RFS) and overall survival (OS) were expressed as hazard ratio (HR) and 95 per cent confidence intervals (c.i.). pCR and survival at yearly intervals after resection were expressed as dichotomous variables using the Mantel–Haenszel method.ResultsOverall, 78 clinical studies with 25 150 patients were included in this study. pCR predicted better EFS (HR 0.67, 95 per cent c.i. 0.60 to 0.74; 41 studies), RFS (HR 0.69, 95 per cent c.i. 0.57 to 0.83; 18 studies) and OS (HR 0.63, 95 per cent c.i. 0.56 to 0.70; 29 studies) for patients with HER2+ breast cancer. At 5 years, pCR predicted better EFS (HR 0.37, 95 per cent c.i. 0.30 to 0.48; 19 studies), RFS (HR 0.28, 95 per cent c.i. 0.21 to 0.39; 8 studies) and OS (HR 0.26, 95 per cent c.i. 0.20 to 0.33; 10 studies).ConclusionThis study confirms pCR as an informative surrogate biomarker for enhanced survival and suggests that it may be used as an appropriate endpoint for clinical research.
Expectations boost the reconstruction of auditory features from electrophysiological responses to noisy speech
Authors: Corcoran Andrew W , Perera Ricardo , Koroma Matthieu , Kouider Sid , Hohwy Jakob , Andrillon Thomas 
Published: February 2022

Abstract
Online speech processing imposes significant computational demands on the listening brain, the underlying mechanisms of which remain poorly understood. Here, we exploit the perceptual “pop-out” phenomenon (i.e. the dramatic improvement of speech intelligibility after receiving information about speech content) to investigate the neurophysiological effects of prior expectations on degraded speech comprehension. We recorded electroencephalography (EEG) and pupillometry from 21 adults while they rated the clarity of noise-vocoded and sine-wave synthesized sentences. Pop-out was reliably elicited following visual presentation of the corresponding written sentence, but not following incongruent or neutral text. Pop-out was associated with improved reconstruction of the acoustic stimulus envelope from low-frequency EEG activity, implying that improvements in perceptual clarity were mediated via top-down signals that enhanced the quality of cortical speech representations. Spectral analysis further revealed that pop-out was accompanied by a reduction in theta-band power, consistent with predictive coding accounts of acoustic filling-in and incremental sentence processing. Moreover, delta-band power, alpha-band power, and pupil diameter were all increased following the provision of any written sentence information, irrespective of content. Together, these findings reveal distinctive profiles of neurophysiological activity that differentiate the content-specific processes associated with degraded speech comprehension from the context-specific processes invoked under adverse listening conditions.
The Effect of Gestational Age at BNT162b2 mRNA Vaccination on Maternal and Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Levels
Authors: Rottenstreich Amihai , Zarbiv Gila , Oiknine-Djian Esther , Vorontsov Olesya , Zigron Roy , Kleinstern Geffen , Wolf Dana G , Porat Shay 
Published: February 2022

AbstractBackgroundCoronavirus disease 2019 (COVID-19) during pregnancy and early infancy can result in severe disease. Evaluating the effect of gestational age at the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on maternal antibody levels and transplacental antibody transfer has important implications for maternal care and vaccination strategies.MethodsMaternal and cord blood sera were collected from mother–newborn dyads (n = 402), following term delivery after antenatal 2-dose SARS-CoV-2 BNT162b2 mRNA vaccination. SARS-CoV-2 spike protein (S) and receptor binding domain (RBD)–specific IgG levels were evaluated in the samples collected.ResultsMedian anti-S and anti–RBD-specific IgG levels in maternal sera at the time of delivery were lowest following first-trimester vaccination (n = 90; anti-S IgG: 76 AU/mL; anti–RBD-specific IgG: 478 AU/mL), intermediate in those vaccinated in the second trimester (n = 124; anti-S IgG: 126 AU/mL; anti–RBD-specific IgG: 1263 AU/mL), and highest after third-trimester vaccination (n = 188; anti-S IgG: 240 AU/mL; anti–RBD-specific IgG: 5855 AU/mL). Antibody levels in neonatal sera followed a similar pattern and were lowest following antenatal vaccination in the first trimester (anti-S IgG: 126 AU/mL; anti–RBD-specific IgG: 1140 AU/mL). In a subgroup of parturients vaccinated in the first trimester (n = 30), a third booster dose was associated with significantly higher maternal and neonatal antibody levels.ConclusionsThese results suggest a considerable antibody waning throughout pregnancy in those vaccinated at early gestation. The observed boosting effect of a third vaccine dose hints at its potential benefit in those who completed the 2-dose vaccine series at early pregnancy or before conception. The impact of antenatal immunization timing on SARS-CoV-2 transplacental antibody transfer may influence neonatal seroprotection.
Low-density lipoprotein cholesterol levels exceed the recommended European threshold for PCSK9i initiation: lessons from the HEYMANS study
Authors: Ray Kausik K , Dhalwani Nafeesa , Sibartie Mahendra , Bridges Ian , Ebenbichler Christoph , Perrone-Filardi Pasquale , Villa Guillermo , Vogt Anja , Bruckert Eric 
Published: February 2022

Abstract

Aims
To describe the characteristics of patients receiving evolocumab in clinical practice across 12 European countries and simulate the association between low-density lipoprotein cholesterol (LDL-C) reduction and cardiovascular (CV) risk reduction.

Methods and results
The characteristics of hyperlipidaemic patients at initiation of evolocumab and treatment patterns study—HEYMANS (n = 1952) is a prospective registry of patients ≥18 years old who initiated evolocumab from 1 August 2015 onwards. Mean (standard deviation) age was 60 (10.8), 85% had a prior CV event, 45% were diagnosed with familial hypercholesterolaemia (FH), and 60% had statin intolerance. At evolocumab initiation, 43% were receiving any statin, 16% were receiving ezetimibe without statin, and 41% received no background lipid-lowering therapy (LLT), with LDL-C levels reflecting local proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) reimbursement criteria. Median LDL-C decreased from 3.98 to 1.63 mmol/L within 3 months of evolocumab initiation and was maintained over 24 months. Overall, 58% achieved risk-based 2019 European Society of Cardiology/European Atherosclerosis Society LDL-C goals but that proportion was higher (68%) in patients receiving background LLT compared with those not receiving background LLT (44%). In patients with atherosclerotic cardiovascular disease without FH, the simulated relative CV risk reduction associated with evolocumab treatment was 34% (25–44%).

Conclusion
Across Europe, LDL-C levels at evolocumab initiation were three times higher than recommended thresholds for PCSK9i initiation, reflecting disparities between implementation and guidelines. More patients attained risk-based LDL-C goals when receiving evolocumab in combination with LLT vs. those not receiving combination therapy. Population health could be improved and LDL-C goals better attained if LDL-C thresholds for PCSK9i reimbursement were lowered, enabling more patients to receive combination therapy when needed.
Augmentation of the posterior mitral leaflet in secondary mitral valve insufficiency, mid-term results
Authors: Lakew Fitsum , Sodah Ayman , Zacher Michael , Batz Gerhard , Perier Patrick , Urbanski Paul , Diegeler Anno 
Published: February 2022

Abstract

OBJECTIVES
We evaluate the mid-term results of mitral valve (MV) repair with patch augmentation of the posterior leaflet in secondary mitral regurgitation.

METHODS
Patients were included after diagnosis of a severe symptomatic secondary MV insufficiency with grade III and IV according to the Carpentier classification IIIb. Indication for a patch augmentation technique was a dilatation of the left ventricle leading to a displacement of the papillary muscles, causing restricted leaflet motion and a marked leaflet tenting height. Data were collected prospectively between December 2011 and March 2020.

RESULTS
In total, 174 patients (mean age: 65 ± 12 years) received an MV repair with patch augmentation of the posterior leaflet and a true-sized remodelling annuloplasty (mean size 30.8 mm). Causes of the MV incompetence were dilatative cardiomyopathy in 126 patients and ischaemic myocardial disease in 48 patients. Concomitant bypass surgery was performed in 28 patients, and the tricuspid valve was repaired in 68 patients. The mean follow-up was 40 ± 28.2 months. There was no 30-day mortality. In-hospital mortality was 1.2% (n = 2); late mortality was 10.9% (n = 19). At 8 years, overall survival was 62.48%, freedom from moderate or severe recurrent mitral regurgitation was 91.9% and freedom from reoperation due to MV insufficiency was 97.1%.

CONCLUSIONS
Augmentation of the posterior MV leaflet in addition to remodelling annuloplasty is a safe and reproducible mitral reconstruction technique that renders sustainable MV competence.
Age Profiles of Cognitive Decline and Dementia in Late Life in the Aging, Demographics, and Memory Study
Authors: Walsh Christine E , Yang Yang C , Oi Katsuya , Aiello Allison , Belsky Daniel , Harris Kathleen Mullan , Plassman Brenda L 
Published: February 2022

Abstract

Objectives
To better understand the temporal dynamics of progression from cognitive decline to onset of dementia in the dementia-free older population in the United States.

Methods
We used longitudinal data from a diverse national population-based sample of older adults (N = 531) in the Aging, Demographics, and Memory Study from the Health and Retirement Study with repeated measures of cognitive function and dementia diagnosis during 12 years of follow-up from 1996 to 2009. We employed joint latent class mixed models to estimate the association between cognitive change and competing risks of dementia and nondementia death and identify heterogeneity in the age profiles of such association adjusting for baseline characteristics.

Results
Our analyses found 3 latent classes with distinct age profiles of cognitive decline and associated risk of dementia and mortality: “Rapid Cognitive Decline” (19.6%), “Moderate Progression” (44.6%), and “Optimal Cognitive Aging” (35.8%). When simultaneously accounting for cognitive trajectories and time-to-dementia/death, we also found associations of baseline covariates with slope of cognitive decline (e.g., steeper decline among non-Hispanic Blacks and more educated) and risk of dementia (e.g., greater risk for females and apolipoprotein E-4 carriers, but no difference by education level) that differ substantially from those in separate longitudinal mixed models or survival models.

Discussion
The differential age patterns of cognitive decline predicting dementia incidences identified in this study suggest variation in the course of cognitive aging in older adults that may inform future etiological and intervention studies.
Prevalence of PCOS and related hyperandrogenic traits in premenopausal women with type 1 diabetes: a systematic review and meta-analysis
Authors: Bayona Ane , Martínez-Vaello Victoria , Zamora Javier , Nattero-Chávez Lía , Luque-Ramírez Manuel , Escobar-Morreale Héctor F 
Published: February 2022

Abstract

BACKGROUND
An increased prevalence of functional hyperandrogenism—including polycystic ovary syndrome (PCOS)—has been described in women with type 1 diabetes (T1D). However, heterogeneity between studies is frequent, and prevalence rates vary according to different criteria used for the diagnosis of PCOS and the population studied.

OBJECTIVE AND RATIONALE
We aimed to perform a systematic review and meta-analysis of the prevalence of PCOS and related hyperandrogenic traits in premenopausal women with T1D. This way, we intend to increase the precision of the estimates of prevalence of PCOS and related traits in women with T1D, and to explore sources of heterogeneity while providing prevalence estimates for clinically relevant subgroups such as the different phenotypes.

SEARCH METHODS
We conducted a systematic review of the literature using Medline-OVID and Embase databases (Open Science Framework registry for systematic review protocols, https://osf.io/6cv9p/). Studies published up to 29 March 2021 were considered. We selected cross-sectional or prospective studies that reported, in patients with T1D, prevalence data on PCOS according to current definitions and different phenotypes, and/or prevalence rates of other related traits (hirsutism, hyperandrogenaemia, oligo-amenorrhoea and/or polycystic ovarian morphology: PCOM). Exclusion criteria for the review were studies addressing types of diabetes other than T1D; and studies using diagnostic definitions of PCOS different than those mentioned above. Two independent researchers performed data extraction. To assess the risk of bias, we used a tool developed specifically to appraise population-based prevalence studies.

OUTCOMES
We selected 19 studies (1042 women) reporting the prevalence of PCOS and/or other hyperandrogenic traits. Regarding bias, 12 studies were considered of low-risk, and the remaining seven studies were considered intermediate risk. The pooled prevalence of PCOS when considering all possible phenotypes (ESHRE- American Society for Reproductive Medicine criteria) in T1D was 26% (95% CI: 19–34%; 13 studies, 684 women). Pooled prevalence of classic PCOS (US National Institutes of Health criteria) was 16% (95% CI: 10–22%; 9 studies, 614 women). Pooled prevalence of hyperandrogenic PCOS (Androgen Excess and PCOS Society criteria) was 26% (95% CI: 16–41%; 5 studies, 329 women). Hirsutism (24%), hyperandrogenaemia (29%), oligomenorrhoea (24%) and PCOM (34%) were also prevalent. Heterogeneity was high in almost all these meta-analyses.

WIDER IMPLICATIONS
This systematic review and meta-analysis showed that PCOS and related hyperandrogenic traits are present in approximately one in every four women with T1D. Larger studies are needed to confirm this association, to address the effect of different variables on the occurrence of PCOS.
On a Conjecture of J. Shallit About Apéry-Like Numbers
Authors: Shen Zhao 
Published: February 2022

AbstractPut $a(n)=\sum \limits _{k=0}^{n} {{n}\choose{k}} {{n+k}\choose{k}}$ and $b(n)=v_{3}(a(n))$ for all integers $n\geqslant 0$, where $v_{3}$ is the $3$-adic valuation. In this work, we confirm a formula about $b(n)$, conjectured by J. Shallit in 2000. As an application, we show that the sequence $(b(n))_{n\geqslant 0}$ is $3$-regular.
Genomic Epidemiology Suggests Community Origins of Healthcare-Associated USA300 Methicillin-Resistant Staphylococcus aureus
Authors: Thiede Stephanie N , Snitkin Evan S , Trick William , Payne Darjai , Aroutcheva Alla , Weinstein Robert A , Popovich Kyle J 
Published: February 2022

Abstract

Background
Hospital-onset (HO) methicillin-resistant Staphylococcus aureus (MRSA) infections have declined over the past decade due to infection control strategies; community-onset (CO) and healthcare-associated community-onset (HACO) MRSA, particularly USA300, has declined less. We examined the role of community strains to explain the difference.

Methods
We performed whole-genome sequencing (WGS) on MRSA clinical isolates from Cook County Health patients during 2011–2014. We defined infections as CO, HO, or HACO epidemiologically. We integrated genomic, community exposure, and statewide hospital discharge data to infer MRSA origin.

Results
Among 1020 individuals with available WGS, most were USA300 wound infections (580 CO, 143 HO, 297 HACO). USA300 HO, CO, and HACO infections were intermixed on the USA300 phylogeny, consistent with common strains circulating across community and healthcare settings. Community exposures (eg, substance abuse, incarceration, homelessness) were associated with HACO and HO infections, and genetically linked individuals from both groups had little overlap in healthcare facilities, supporting community origins. Most repeat infections—over months to years—occurred in individuals persistently carrying their own strains. These individuals were more likely to have genetic linkages, suggesting a role of persistent colonization in transmission.

Conclusions
Efforts to reduce presumed nosocomial USA300 spread may require understanding and controlling community sources and transmission networks, particularly for repeat infections.
Exhibition of antifungal resistance by sterol-auxotrophic strains ofCandida glabratawith intact virulence
Authors: Nagi Minoru , Tanabe Koichi , Tanaka Kazuko , Ueno Keigo , Nakayama Hironobu , Ishikawa Jun , Abe Masahiro , Yamagoe Satoshi , Umeyama Takashi , Nakamura Shigeki , Sugai Motoyuki , Hazen Kevin C. , Miyazaki Yoshitsugu 
Published: February 2022

AbstractBackgroundCandida glabrata is an emerging fungal pathogen in immune-compromised hosts. Previously undetected C. glabrata isolates were successfully recovered from clinical specimens by adding sterols to the growth medium. The clinical isolates are unable to synthesize ergosterol but can take up exogenous sterols under aerobic conditions.ObjectivesThis study characterizes the sterol-auxotrophic C. glabrata strains, examines the mutation(s) in sterol synthesis genes, characterizes the drug susceptibility and evaluates the virulence in a mouse infection model.MethodsDrug susceptibility of the C. glabrata strains was evaluated in a sterol-supplemented medium. The coding sequences of the sterol synthesis genes were analysed in six sterol-auxotrophic strains of C. glabrata. The fungal burden of mice infected with C. glabrata strain was determined.ResultsThe sterol-auxotrophic strains showed high-level resistance to both azoles and amphotericin B when sterols were supplied in the test medium. Additionally, the strains harbour missense mutations in either ERG1 or ERG7. Significant differences in fungal burden were not observed between the sterol-auxotrophic strain and the sterol-competent strain with the mice infection models.ConclusionsThe sterol-auxotrophic C. glabrata strain investigated in this study seemed to maintain intact virulence, probably due to the supply of exogenous sterols from host organ(s). This suggests that exogenous sterol uptake develops antifungal resistance during infection.
Enhancing cancer prevention and survivorship care with a videoconferencing model for continuing education: a mixed-methods study to identify barriers and incentives to participation
Authors: Milgrom Zheng Z , Severance Tyler S , Scanlon Caitlin M , Carson Anyé T , Janota Andrea D , Burns John L , Vik Terry A , Duwve Joan M , Dixon Brian E , Mendonca Eneida A 
Published: February 2022

AbstractObjectiveTo enhance cancer prevention and survivorship care by local health care providers, a school of public health introduced an innovative telelearning continuing education program using the Extension for Community Healthcare Outcomes (ECHO) model. In ECHO’s hub and spoke structure, synchronous videoconferencing connects frontline health professionals at various locations (“spokes”) with experts at the facilitation center (“hub”). Sessions include experts’ didactic presentations and case discussions led by spoke site participants. The objective of this study was to gain a better understanding of the reasons individuals choose or decline to participate in the Cancer ECHO program and to identify incentives and barriers to doing so.Materials and methodsStudy participants were recruited from the hub team, spoke site participants, and providers who attended another ECHO program but not this one. Participants chose to take a survey or be interviewed. The Consolidated Framework for Implementation Research guided qualitative data coding and analysis.ResultsWe conducted 22 semistructured interviews and collected 30 surveys. Incentives identified included the program’s high-quality design, supportive learning climate, and access to information. Barriers included a lack of external incentives to participate and limited time available. Participants wanted more adaptability in program timing to fit providers’ busy schedules.ConclusionAlthough the merits of the Cancer ECHO program were widely acknowledged, adaptations to facilitate participation and emphasize the program’s benefits may help overcome barriers to attending. As the number of telelearning programs grows, the results of this study point to ways to expand participation and spread health benefits more widely.