bluuebunny/crossref_metadata_2025_split huggingface dataset:
Keratan sulfate proteoglycan: putative template for neuroblast migratory and axonal fascicular pathways and fetal expression in globus pallidus, thalamus, and olfactory bulb
Authors: Sarnat Harvey B , Yu Weiming 
Published: July 2024

Abstract
Keratan sulfate (KS) is a proteoglycan secreted in the fetal brain astrocytes and radial glia into extracellular parenchyma as granulofilamentous deposits. KS surrounds neurons except dendritic spines, repelling glutamatergic and facilitating GABAergic axons. The same genes are expressed in both neuroblast migration and axonal growth. This study examines timing of KS during morphogenesis of some normally developing human fetal forebrain structures. Twenty normal human fetal brains from 9-41 weeks gestational age were studied at autopsy. KS was examined by immunoreactivity in formalin-fixed paraffin sections, plus other markers including synaptophysin, S-100β protein, vimentin and nestin. Radial and tangential neuroblast migratory pathways from subventricular zone to cortical plate were marked by KS deposits as early as 9wk GA, shortly after neuroblast migration initiated. During later gestation this reactivity gradually diminished and disappeared by term. Long axonal fascicles of the internal capsule and short fascicles of intrinsic bundles of globus pallidus and corpus striatum also appeared as early as 9-12wk, as fascicular sleeves before axons even entered. Intense KS occurs in astrocytic cytoplasm and extracellular parenchyma at 9wk in globus pallidus, 15wk thalamus, 18wk corpus striatum, 22wk cortical plate, and hippocampus postnatally. Corpus callosum and anterior commissure do not exhibit KS at any age. Optic chiasm shows reactivity at the periphery but not around intrinsic subfasciculi. We postulate that KS forms a chemical template for many long and short axonal fascicles before axons enter and neuroblast migratory pathways at initiation of migration. Cross-immunoreactivity with aggrecan may render difficult molecular distinction.
Intraorganizational mobility and employees’ work-related contact patterns: evidence from panel data in the European Commission
Authors: Vantaggiato Francesca P , Murdoch Zuzana , Kassim Hussein , Geys Benny , Connolly Sara 
Published: July 2024

Abstract
Programs to encourage staff to move within public-sector organizations have become increasingly widespread in recent decades. Yet, although there are some anecdotal accounts, the effects of such intraorganizational mobility remain largely unexplored. Building on insights from organization theory and social psychology, we argue that intraorganizational mobility entails an important trade-off: it undermines movers’ depth of work-related contacts within the (new) department, while it increases the breadth of their work-related contacts outside it. Our empirical analysis evaluates this trade-off using a two-way fixed effects model for a longitudinal dataset of movers (N = 149) and stayers (N = 473) across two survey waves among European Commission officials in 2014 and 2018. Our main findings confirm that intraorganizational mobility is connected in opposing ways to employees’ intra- and extra-departmental work-related contact patterns. In line with theoretical expectations, we find these relationships to be stronger for employees who have previously experienced intraorganizational moves (“repeat-movers”).
Learning local cascading failure pattern from massive network failure data
Authors: Xiao Xun , Ye Zhisheng , Revie Matthew 
Published: July 2024

Abstract
This article proposes a novel multivariate point process regression model for a large-scale physically distributed network infrastructure with two failure modes, i.e. primary failures caused by the long-term usage and degradation of assets, and cascading failures triggered by primary failures in a short period. We exploit large-scale field pipe failure data from a UK-based water utility to support the rationale of considering the two failure modes. The two modes are not self-revealed in the data. To make the inference of the large-scale problem possible, we introduce a time window for cascading failures, based on which the likelihood of the pipe failure process can be decomposed into two parts, one for the primary failures and the other for the cascading failure processes modulated by the primary failure processes. The window length for cascading failures is treated as a tuning parameter, and determined through maximizing the likelihood based on all failure data. To illustrate the effectiveness of the model, two case studies are presented based on real data from the UK-based water utility. Interesting features of the cascading failures are identified from massive field pipe failure data. The results provide insights on advanced modelling and practical decision-making for both researchers and practitioners.
Effect of semaglutide on kidney function across different levels of baseline HbA1c, blood pressure, body weight and albuminuria in SUSTAIN 6 and PIONEER 6
Authors: Apperloo Ellen M , Cherney David Z I , Kuhlman Anja Birk , Mann Johannes F E , Rasmussen Søren , Rossing Peter , Tuttle Katherine R , Vrhnjak Blaz , Heerspink Hiddo J L 
Published: July 2024

ABSTRACT

Background
This post hoc analysis explored the effects of semaglutide on estimated glomerular filtration (eGFR) slope by baseline glycemic control, blood pressure (BP), body mass index (BMI) and albuminuria status in people with type 2 diabetes and high cardiovascular risk.

Methods
Pooled SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes) data were analyzed for change in eGFR slope by baseline hemoglobin A1c (HbA1c) (&lt;8%/≥8%; &lt;64/≥64 mmol/mol), systolic BP (&lt;140/90/≥140/90 mmHg) and BMI (&lt;30/≥30 kg/m2). SUSTAIN 6 data were analyzed by baseline urinary albumin:creatinine ratio (UACR; &lt;30/30–300/&gt;300 mg/g).

Results
The estimated absolute treatment differences overall in eGFR slope (95% confidence intervals) favored semaglutide versus placebo in the pooled analysis [0.59 (0.29; 0.89) mL/min/1.73 m2/year] and in SUSTAIN 6 [0.60 (0.24; 0.96) mL/min/1.73 m2/year]; the absolute benefit was consistent across all HbA1c, BP, BMI and UACR subgroups (all P-interaction &gt;.5).

Conclusion
A clinically meaningful reduction in risk of chronic kidney disease progression was observed with semaglutide versus placebo regardless of HbA1c, BP, BMI, and UACR levels.
Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients
Authors: Foca Marc , Demirhan Salih , Munoz Flor M , Valencia Deray Kristen G , Bocchini Claire E , Sharma Tanvi S , Sherman Gilad , Muller William J , Heald-Sargent Taylor , Danziger-Isakov Lara , Blum Samantha , Boguniewicz Juri , Bacon Samantha , Joseph Tuhina , Smith Jodi , Ardura Monica I , Su Yin , Maron Gabriela M , Ferrolino Jose , Herold Betsy C 
Published: July 2024

Abstract

Background
Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes.

Methods
A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models.

Results
Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk.

Conclusions
CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.
A Diagnostic Stewardship Intervention to Improve Utilization of 1,3 β-D-Glucan Testing at a Single Academic Center: Five-Year Experience
Authors: Colson Jordan D , Kendall Jonathan A , Yamamoto Takeru , Mizusawa Masako 
Published: July 2024

Abstract

Background
(1,3)- β-D-glucan (BDG) testing is one of the noninvasive tests to aid diagnosis of invasive fungal infections (IFIs). The study results have been heterogenous, and diagnostic performance varies depending on the risks for IFI. Thus, it is important to select appropriate patients for BDG testing to prevent false-positive results. An algorithmic diagnostic stewardship intervention was instituted at a single academic medical center to improve BDG test utilization.

Methods
The BDG test order in the electronic health record was replaced with the BDG test request order, which required approval to process the actual test order. The approval criteria were (1) immunocompromised or intensive care unit patient and (2) on empiric antifungal therapy, or inability to undergo invasive diagnostic procedures. A retrospective observational study was conducted to evaluate the efficacy of the intervention by comparing the number of BDG tests performed between 1 year pre- and post-intervention. Safety was assessed by chart review of the patients for whom BDG test requests were deemed inappropriate and rejected.

Results
The number of BDG tests performed per year decreased by 85% from 156 in the pre-intervention period to 24 in the post-intervention period. The average monthly number of BDG tests performed was significantly lower between those periods (P = .002). There was no delay in IFI diagnosis or IFI-related deaths in the patients whose BDG test requests were rejected. The sustained effectiveness of the intervention was observed for 5 years.

Conclusions
Institution of the diagnostic stewardship intervention successfully and safely improved BDG test utilization.
Effectiveness of BNT162b2 XBB Vaccine Against XBB and JN.1 Sublineages
Authors: Tartof Sara Y , Slezak Jeff M , Puzniak Laura , Frankland Timothy B , Ackerson Bradley K , Jodar Luis , McLaughlin John M 
Published: July 2024

Abstract
We provide updated results (11 October 2023 through 29 February 2024) from our previously conducted test-negative case-control study in Kaiser Permanente Southern California to evaluate sublineage-specific effectiveness of the BNT162b2 XBB1.5-adapted vaccine. Results suggest that XBB1.5-adapted vaccines may have reduced effectiveness against JN.1 versus XBB sublineages.
Nondifferentiable activity in the brain
Authors: Tsubo Yasuhiro , Shinomoto Shigeru 
Published: July 2024

Abstract
Spike raster plots of numerous neurons show vertical stripes, indicating that neurons exhibit synchronous activity in the brain. We seek to determine whether these coherent dynamics are caused by smooth brainwave activity or by something else. By analyzing biological data, we find that their cross-correlograms exhibit not only slow undulation but also a cusp at the origin, in addition to possible signs of monosynaptic connectivity. Here we show that undulation emerges if neurons are subject to smooth brainwave oscillations while a cusp results from nondifferentiable fluctuations. While modern analysis methods have achieved good connectivity estimation by adapting the models to slow undulation, they still make false inferences due to the cusp. We devise a new analysis method that may solve both problems. We also demonstrate that oscillations and nondifferentiable fluctuations may emerge in simulations of large-scale neural networks.
Atrial anatomical variations on computed tomography angiography associated with atrial fibrillation and those predicting recurrence following pulmonary vein isolation
Authors: Abazid Rami M , Smettie Osama , Romsa Jonathan G , Warrington James , Akincioglu Cigdem , Tzemos Nikolaos , Vezina William C , Khan Habib Rehman 
Published: July 2024

Abstract

Background
We aim to investigate the atrial anatomical variations in patients with and without atrial fibrillation (AF) using cardiac-computed tomography angiography (CCTA) and identify features associated with AF recurrence following pulmonary vein isolation.

Materials and Methods
We retrospectively reviewed 502 CCTAs of patients with AF performed prior to a pulmonary vein isolation procedure with 1058 CCTAs of patients without AF performed to rule out coronary artery disease between 2014 and 2017. Anatomical variations of both atria including left atrial diverticula (LAD), right atrial diverticula (RAD), Bachmann bundle shunt (BBS), and pulmonary vein anatomy were assessed.

Results
We found that patients with AF were older (67 ± 14 vs 63 ± 13 years, P = .039), had a higher prevalence of diabetes (24.4%) versus (14.7%), P = .006, and cerebrovascular accidents (3.8%) versus (0.9%), P = .044 when compared with patients without AF. Furthermore, on CCTAs patients with AF demonstrated a significantly higher prevalence of BBS (11% vs 4.1%, P &lt; .001), LAD (19% vs 7.7%, P &lt; .001), and RAD (9.8% vs 2.1%, P &lt; .001) when compared to patients without AF. Logistic multivariable regression analyses of CCTA findings demonstrated increased odd ratios (OR) in those with AF of BBS (OR = 3.51, 95% CI, 2.32-5.35, P &lt; .001), LAD (OR = 2.94, 95% CI, 2.12-4.07, P &lt; .001), RAD (OR = 1.54, 95% CI, 1.19-2.11, P = .03), LA diameter (OR = 2.42, 95% CI, 1.65-3.39, P &lt; .001). Importantly, multivariate Cox regression showed that the LA dimension is a predictor of AF recurrence (HR = 1.019, 95% CI, 1.001-1.051, P = .02).

Conclusion
AF patients have a higher prevalence of BBS, LAD, and RAD in comparison to patients without AF. Mean LA diameter predicts AF recurrence after the pulmonary vein isolation procedure.
Research progresses on mitochondrial-targeted biomaterials for bone defect repair
Authors: Wang Shuze , Liu Jialin , Zhou Linxi , Xu Hao , Zhang Dan , Zhang Xing , Wang Qiang , Zhou Qing 
Published: July 2024

Abstract
In recent years, the regulation of the cell microenvironment has opened up new avenues for bone defect repair. Researchers have developed novel biomaterials to influence the behavior of osteoblasts and immune cells by regulating the microenvironment, aiming to achieve efficient bone repair. Mitochondria, as crucial organelles involved in energy conversion, biosynthesis and signal transduction, play a vital role in maintaining bone integrity. Dysfunction of mitochondria can have detrimental effects on the transformation of the immune microenvironment and the differentiation of stem cells, thereby hindering bone tissue regeneration. Consequently, targeted therapy strategies focusing on mitochondria have emerged. This approach offers a wide range of applications and reliable therapeutic effects, thereby providing a new treatment option for complex and refractory bone defect diseases. In recent studies, more biomaterials have been used to restore mitochondrial function and promote positive cell differentiation. The main directions are mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial quality control. In this review, we investigated the biomaterials used for mitochondria-targeted treatment of bone defect repair in recent years from the perspective of progress and strategies. We also summarized the micro-molecular mechanisms affected by them. Through discussions on energy metabolism, oxidative stress regulation and autophagy regulation, we emphasized the opportunities and challenges faced by mitochondria-targeted biomaterials, providing vital clues for developing a new generation of bone repair materials.
XIILiterature 1780–1830: The Romantic Period
Authors: Davis Amanda Blake , Wride Sarah , Fancett Anna , Senkiw Anna 
Published: July 2024

Abstract
This chapter has three sections: 1. General and Prose; 2. The Novel; 3. Drama. Section 1 is by Amanda Blake Davis; section 2 is by Sarah Wride and Anna Fancett; section 3 is by Anna Senkiw. There is no poetry section this year; Romantic poetry for this year will be added to next year’s contribution.
An epidermal growth factor receptor‐targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer
Authors: Huang Mei , Park Jisoo , Seo Jina , Ko Sanghwan , Yang Yoon Hee , Lee Yeaji , Kim Hyo Jeong , Lee Bok‐Soon , Lee Yun Sang , Ko Byoung Joon , Jung Sang Teak , Park Deachan , Yoo Tae Hyeon , Kim Chul‐Ho 
Published: July 2024

AbstractThe epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti‐EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR‐targeting immunotoxin consisting of a clinically proven anti‐EGFR IgG (cetuximab; CTX) and a toxin fragment (LR‐LO10) derived from Pseudomonas exotoxin A (PE) using a novel site‐specific conjugation technology (peptide‐directed photo‐crosslinking reaction), as an alternative option. The immunotoxin (CTX‐LR‐LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor‐2. Treatment of EGFR‐positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX‐LR‐LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR‐LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX‐LR‐LO10 may serve as a new therapeutic agent targeting EGFR‐positive cancers.
FOXK2 facilitates the airway remodeling during chronic asthma by promoting glycolysis in a SIRT2‐dependent manner
Authors: Shan Lishen , Chen Li , Shen Wenxin , Zhou Qianlan , Liu Si , Han Lina , Zhang Qinzhen , Dai Bing , Zhao Yuhong 
Published: July 2024

AbstractAsthma is a chronic pulmonary disease with the worldwide prevalence. The structural alterations of airway walls, termed as “airway remodeling”, are documented as the core contributor to the airway dysfunction during chronic asthma. Forkhead box transcription factor FOXK2 is a critical regulator of glycolysis, a metabolic reprogramming pathway linked to pulmonary fibrosis. However, the role of FOXK2 in asthma waits further explored. In this study, the chronic asthmatic mice were induced via ovalbumin (OVA) sensitization and repetitive OVA challenge. FOXK2 was upregulated in the lungs of OVA mice and downregulated after adenovirus‐mediated FOXK2 silencing. The lung inflammation, peribronchial collagen deposition, and glycolysis in OVA mice were obviously attenuated after FOXK2 knockdown. Besides, the expressions of FOXK2 and SIRT2 in human bronchial epithelial cells (BEAS‐2B) were increasingly upregulated upon TGF‐β1 stimulation and downregulated after FOXK2 knockdown. Moreover, the functional loss of FOXK2 remarkably suppressed TGF‐β1‐induced epithelial‐mesenchymal transition (EMT) and glycolysis in BEAS‐2B cells, as manifested by the altered expressions of EMT markers and glycolysis enzymes. The glycolysis inhibitor 2‐deoxy‐d‐glucose (2‐DG) inhibited the EMT in TGF‐β1‐induced cells, making glycolysis a driver of EMT. The binding of FOXK2 to SIRT2 was validated, and SIRT2 overexpression blocked the FOXK2 knockdown‐mediated inhibition of EMT and glycolysis in TGF‐β1‐treated cells, which suggests that FOXK2 regulates EMT and glycolysis in TGF‐β1‐treated cells in a SIRT2‐dependnet manner. Collectively, this study highlights the protective effect of FOXK2 knockdown on airway remodeling during chronic asthma.
Aerobic training attenuates cardiac remodeling in mice post‐myocardial infarction by inhibiting the p300/CBP‐associated factor
Authors: Huang Chuan , Ding Xinyu , Shao Jingrong , Yang Mengxue , Du Dongdong , Hu Jiayi , Wei Ya , Shen Qiu , Chen Ze , Zuo Shengkai , Wan Chunxiao 
Published: July 2024

AbstractAerobic training (AT), an effective form of cardiac rehabilitation, has been shown to be beneficial for cardiac repair and remodeling after myocardial infarction (MI). The p300/CBP‐associated factor (PCAF) is one of the most important lysine acetyltransferases and is involved in various biological processes. However, the role of PCAF in AT and AT‐mediated cardiac remodeling post‐MI has not been determined. Here, we found that the PCAF protein level was significantly increased after MI, while AT blocked the increase in PCAF. AT markedly improved cardiac remodeling in mice after MI by reducing endoplasmic reticulum stress (ERS). In vivo, similar to AT, pharmacological inhibition of PCAF by Embelin improved cardiac recovery and attenuated ERS in MI mice. Furthermore, we observed that both IGF‐1, a simulated exercise environment, and Embelin protected from H2O2‐induced cardiomyocyte injury, while PCAF overexpression by viruses or the sirtuin inhibitor nicotinamide eliminated the protective effect of IGF‐1 in H9C2 cells. Thus, our data indicate that maintaining low PCAF levels plays an essential role in AT‐mediated cardiac protection, and PCAF inhibition represents a promising therapeutic target for attenuating cardiac remodeling after MI.
Addressing Confusion and Inconsistencies Surrounding the Provider Role in Medical Cannabis Programs
Authors: Tang Yi-Lang , McCord Elizabeth , Earley Paul H. , Drexler Karen 
Published: July 2024

Abstract
More than 40 states in the United States have established medical cannabis programs that authorize the use of cannabis for specific medical conditions. Initially, these medical cannabis programs aimed to offer compassionate care primarily for terminal or rare, untreatable conditions. However, the scope of these programs has broadened to include nonterminal and more common conditions, including various medical and mental disorders. This expansion introduces several health care challenges: a lack of robust research evidence for many listed conditions, a sense of unpreparedness among providers, and a disparity in provider roles, expectations, and responsibilities across different states, leading to potential confusion. To address these issues, medical organizations need to develop expert consensus or guidelines that underscore evidence-based shared decision-making and patient monitoring standards. Medical education should also include such training. Concurrently, medical providers must prioritize evidence-based treatment over public opinion, exercise clinical judgment, and take responsibility for their recommendations.