bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging and Alzheimer’s disease have dissociable effects on local and regional medial temporal lobe connectivity
Authors: Hrybouski Stanislau , Das Sandhitsu R , Xie Long , Wisse Laura E M , Kelley Melissa , Lane Jacqueline , Sherin Monica , DiCalogero Michael , Nasrallah Ilya , Detre John , Yushkevich Paul A , Wolk David A 
Published: September 2023

AbstractFunctional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer’s disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer’s disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging. However, the extent to which Alzheimer’s and aging-related pathological processes relate to functional disruption of the medial temporal lobe-dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity alterations in the medial temporal lobe and its immediate functional neighbourhood—the Anterior-Temporal and Posterior-Medial brain networks—in normal agers, individuals with preclinical Alzheimer’s disease and patients with Mild Cognitive Impairment or mild dementia due to Alzheimer’s disease. In the Anterior-Temporal network and in the perirhinal cortex, in particular, we observed an inverted ‘U-shaped’ relationship between functional connectivity and Alzheimer’s stage. According to our results, the preclinical phase of Alzheimer’s disease is characterized by increased functional connectivity between the perirhinal cortex and other regions of the medial temporal lobe, as well as between the anterior medial temporal lobe and its one-hop neighbours in the Anterior-Temporal system. This effect is no longer present in symptomatic Alzheimer’s disease. Instead, patients with symptomatic Alzheimer’s disease displayed reduced hippocampal connectivity within the medial temporal lobe as well as hypoconnectivity within the Posterior-Medial system. For normal aging, our results led to three main conclusions: (i) intra-network connectivity of both the Anterior-Temporal and Posterior-Medial networks declines with age; (ii) the anterior and posterior segments of the medial temporal lobe become increasingly decoupled from each other with advancing age; and (iii) the posterior subregions of the medial temporal lobe, especially the parahippocampal cortex, are more vulnerable to age-associated loss of function than their anterior counterparts. Together, the current results highlight evolving medial temporal lobe dysfunction in Alzheimer’s disease and indicate different neurobiological mechanisms of the medial temporal lobe network disruption in aging versus Alzheimer’s disease.
Case report of progressive renal dysfunction as a consequence of amiodarone-induced phospholipidosis
Authors: Duineveld Mirjam D , Kers Jesper , Vleming Louis-Jean 
Published: September 2023

Abstract

Background
Amiodarone is associated with a range of unwanted effects on pulmonary, thyroid, and liver function. However, the nephrotoxic side effect caused by renal phospholipidosis has hardly received any attention up to now.

Case summary
This is a case of an 86-year-old Caucasian male with an acute on chronic kidney disease 4 months after the initiation of amiodarone. A renal biopsy demonstrated the intracellular accumulation of phospholipids that have previously been demonstrated in association with organ dysfunction because of amiodarone use. Serum creatinine levels subsequently improved from 388 to 314 µmol/L after stopping amiodarone over the course of 2 months.

Discussion
In this case, a diagnosis of partially reversible acute on chronic kidney disease caused by lysosomal phospholipidosis due to amiodarone use was deemed highly likely. Lysosomal dysfunction leads to the accumulation of intra-lysosomal phospholipids (phospholipidosis). This accumulation is accompanied by progressive organ damage and dysfunction, including renal dysfunction, in rare instances. Guidelines advise regular surveillance for liver, lung, and thyroid toxicity during amiodarone treatment but do not mention the potential for renal toxicity. This case suggests that it might be prudent to include screening for renal toxicity in this surveillance.
Cumulative remnant cholesterol predicts cardiovascular outcomes in elderly patients with atherosclerotic cardiovascular disease
Authors: Xiao Zhiwen , Lin Zhongqiu , Xu Lin , Xu Wenlong , Huang Haoxiang , Wang Yuegang , Cao Shiping , Xie Zhiquan , Liao Wangjun , Liao Yulin , Bin Jianping , Feng Weijing , Chen Yanmei 
Published: September 2023

Abstract

Aims
Remnant cholesterol (RC) reportedly mediates residual cardiovascular risk in atherosclerotic cardiovascular diseases (ASCVD). However, few studies have characterized long-term cumulative RC exposure among elderly people. The study aimed to evaluate the association between cumulative exposure to RC and incident major adverse cardiovascular events (MACE) by analysing a cohort of elderly patients with ASCVD.

Methods and results
This retrospective multicentre cohort study enrolled ASCVD participants aged ≥75 years with baseline visits occurring from 2006 to 2012 followed by four in-person visits. Cumulative RC was estimated as the area under the curve using measurements from the first to fourth visits by using 9-year data. The time-weighted average (TWA) RC was expressed as cumulative exposure to RC averaged by years. All outcomes were follow-up from the fourth visit to the year 2021. Outcomes included a composite of MACE (stroke, unstable angina pectoris, myocardial infarction, and cardiac death). We included 4,680 participants (73.1% male, mean age 79.3 ± 2.5 years). The median follow-up duration was 6.1 years (interquartile range: 3.4–6.6 years). In the multivariable model adjusted for traditional cardiovascular risk factors, low-density lipoprotein cholesterol level, and most recent RC level, the hazard ratios for MACE that compared the high and low tertiles of the RC variables were 1.30 [95% confidence interval (CI), 1.16–1.44] for cumulative RC and 1.36 (95% CI, 1.23–1.52) for TWA RC. Consistent significant associations were observed among most propensity score analyses.

Conclusions
Long-term cumulative RC was independently associated with incident MACE in elderly participants with ASCVD, suggesting that achieving and maintaining optimal RC levels later in life may still improve cardiovascular outcomes.
Five-year changes in weight and risk of atrial fibrillation in the Danish Diet, Cancer, and Health Cohort
Authors: Frederiksen Tanja Charlotte , Christiansen Morten Krogh , Benjamin Emelia J , Overvad Kim , Olsen Anja , Dahm Christina Catherine , Jensen Henrik Kjærulf 
Published: September 2023

Abstract

Aims
Obesity is a major risk factor for atrial fibrillation (AF). Compared with stable weight, gaining weight was associated with a higher risk of incident AF in observational studies. The results, however, are conflicting regarding weight loss and risk of AF. This study aimed to assess the association between 5-year weight changes and risk of incident AF.

Methods and results
The study was based on participants from the Danish Diet, Cancer, and Health Cohort. Body mass index (BMI) was assessed at a baseline examination and at a second examination 5 years later. Diagnoses of AF and co-morbidities were retrieved from the Danish National Patient Registry. In total, 43 758 participants without prior AF were included. The median age was 61 years and 54% were female. During a median follow-up of 15.7 years, 5312 individuals had incident AF (incidence rate 8.6/1000 person-years). Compared with stable weight, weight gain between 2.5 and 5 BMI units (kg/m2) was associated with a higher risk of AF [hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09–1.41]. Weight gain of 5 or more BMI units (kg/m2) was associated with a HR of 1.95 (95% CI 1.48–2.56) of incident AF. However, there was no statistically significant association between weight loss and risk of AF.

Conclusion
Five-year weight gain was associated with greater risk of AF compared with stable weight in the Danish Diet, Cancer, and Health Cohort. There was no statistically significant association between weight loss and risk of AF.
A haplotype-resolved chromosome-scale genome for Quercus rubra L. provides insights into the genetics of adaptive traits for red oak species
Authors: Kapoor Beant , Jenkins Jerry , Schmutz Jeremy , Zhebentyayeva Tatyana , Kuelheim Carsten , Coggeshall Mark , Heim Chris , Lasky Jesse R , Leites Laura , Islam-Faridi Nurul , Romero-Severson Jeanne , DeLeo Victoria L , Lucas Sarah M , Lazic Desanka , Gailing Oliver , Carlson John , Staton Margaret 
Published: September 2023

Abstract
Northern red oak (Quercus rubra L.) is an ecologically and economically important forest tree native to North America. We present a chromosome-scale genome of Q. rubra generated by the combination of PacBio sequences and chromatin conformation capture (Hi-C) scaffolding. This is the first reference genome from the red oak clade (section Lobatae). The Q. rubra assembly spans 739 Mb with 95.27% of the genome in 12 chromosomes and 33,333 protein-coding genes. Comparisons to the genomes of Quercus lobata and Quercus mongolica revealed high collinearity, with intrachromosomal structural variants present. Orthologous gene family analysis with other tree species revealed that gene families associated with defense response were expanding and contracting simultaneously across the Q. rubra genome. Quercus rubra had the most CC-NBS-LRR and TIR-NBS-LRR resistance genes out of the 9 species analyzed. Terpene synthase gene family comparisons further reveal tandem gene duplications in TPS-b subfamily, similar to Quercus robur. Phylogenetic analysis also identified 4 subfamilies of the IGT/LAZY gene family in Q. rubra important for plant structure. Single major QTL regions were identified for vegetative bud break and marcescence, which contain candidate genes for further research, including a putative ortholog of the circadian clock constituent cryptochrome (CRY2) and 8 tandemly duplicated genes for serine protease inhibitors, respectively. Genome–environment associations across natural populations identified candidate abiotic stress tolerance genes and predicted performance in a common garden. This high-quality red oak genome represents an essential resource to the oak genomic community, which will expedite comparative genomics and biological studies in Quercus species.
Did Resilience and Socioeconomic Status Predict Older Adults’ Finding a Silver Lining in COVID?
Authors: Wilder Jocelyn , Lauderdale Diane S , Hawkley Louise 
Published: September 2023

Abstract

Background and Objectives
The coronavirus disease 2019 (COVID-19) pandemic stretched our limits—physically, mentally, and economically. However, some older adults report that it led to positive changes. This study aims to understand whether prepandemic resilience, education, or income predicted older adults’ subsequent likelihood of reporting positive changes in their lives during the pandemic.

Research Design and Methods
We use data from the National Social Life, Heath, and Aging Project, an ongoing panel study with a COVID-19 ancillary supplement (N = 2,650).

Results
The study results aligned with the fundamental cause theory. In demographically adjusted models including resilience, education, and income, as well as the effect of the pandemic on employment and a COVID-disruption score, the odds of reporting any positive change were 2.6 times higher for those with an associate degree (p &lt; .01) and 4.7 times higher for those with a bachelor’s or higher (p &lt; .001), compared to those without a high school degree. In contrast, neither resilience nor income was significantly associated with endorsing a positive change. We also categorize specific changes thematically coded from open-ended responses and examine their demographic distributions. Categories include spirituality, home organization, hygiene practices, and increased quality time with others.

Discussion and Implications
These findings show that older adults with more education could navigate COVID-19 challenges in a way that improved their perspectives on at least one aspect of their lives.
Public perceptions of US for-profit, nonprofit, and public hospitals
Authors: Taylor Lauren A , Franz Berkeley , Zink Amanda , Fair Andrew , Cronin Cory E 
Published: September 2023

Abstract
Nonprofit hospitals have been criticized for behaving like for-profit hospitals. One prominent defense of nonprofit hospitals is contract failure theory, which suggests that nonprofits are important in markets defined by information asymmetries. Unlike for-profits, nonprofit hospitals’ inability to distribute profits may provide patients with an important assurance that they will not be exploited in the course of receiving care. We investigated support for this theory using a sample of 2569 US adults. We assessed (1) relevance of hospital ownership status; (2) respondent preferences for nonprofit, for-profit, or public hospitals; and (3) respondent ability to correctly identify hospital ownership status. We found little evidence that hospital nonprofit status influenced Americans’ decisions about where to seek care. Ownership status was relevant for fewer than 30% of respondents and preference was greatest overall for public hospitals. Only 30–45% of respondents could correctly identify the ownership status of nationally recognized hospitals, and fewer than 30% could identify their local hospitals. These findings suggest that contract failure does not currently provide a justification of nonprofit hospitals’ value; further scrutiny of tax exemption for nonprofit hospitals is warranted.
An elephant in the room—EU policy gaps in the regulation of moderating illegal sexual content on video-sharing platforms
Authors: Sorbán Kinga 
Published: September 2023

Abstract
With the availability of broadband internet and a significant increase in storage capacity, people are sharing a dynamically growing amount of multimedia content on video-sharing platforms, including sexually explicit content. While sexual content on the internet is not illegal per se and remains in the domain of economic services, there are certain forms of sexually explicit content that are criminally unlawful, such as child pornography or non-consensual pornography. This article explores why the current business-oriented regulatory environment fails to provide effective tools to combat illegal sexual content: first, from the perspective of content moderation on video-sharing platforms, and then from the perspective of substantive criminal law. After mapping the gaps in policy at all levels of content regulation, the article offers recommendations to address these issues, open up a policy debate and influence policy makers.
Wheat crop traits conferring high yield potential may also improve yield stability under climate change
Authors: Stella Tommaso , Webber Heidi , Eyshi Rezaei Ehsan , Asseng Senthold , Martre Pierre , Dueri Sibylle , Rafael Guarin Jose , Pequeno Diego N L , Calderini Daniel F , Reynolds Matthew , Molero Gemma , Miralles Daniel , Garcia Guillermo , Slafer Gustavo , Giunta Francesco , Kim Yean-Uk , Wang Chenzhi , Ruane Alex C , Ewert Frank 
Published: September 2023

Abstract
Increasing genetic wheat yield potential is considered by many as critical to increasing global wheat yields and production, baring major changes in consumption patterns. Climate change challenges breeding by making target environments less predictable, altering regional productivity and potentially increasing yield variability. Here we used a crop simulation model solution in the SIMPLACE framework to explore yield sensitivity to select trait characteristics (radiation use efficiency [RUE], fruiting efficiency and light extinction coefficient) across 34 locations representing the world’s wheat-producing environments, determining their relationship to increasing yields, yield variability and cultivar performance. The magnitude of the yield increase was trait-dependent and differed between irrigated and rainfed environments. RUE had the most prominent marginal effect on yield, which increased by about 45 % and 33 % in irrigated and rainfed sites, respectively, between the minimum and maximum value of the trait. Altered values of light extinction coefficient had the least effect on yield levels. Higher yields from improved traits were generally associated with increased inter-annual yield variability (measured by standard deviation), but the relative yield variability (as coefficient of variation) remained largely unchanged between base and improved genotypes. This was true under both current and future climate scenarios. In this context, our study suggests higher wheat yields from these traits would not increase climate risk for farmers and the adoption of cultivars with these traits would not be associated with increased yield variability.
Treaty influencers: a computational analysis of the development of international investment law
Authors: Lie Runar Hilleren 
Published: September 2023

ABSTRACT
This article uses computational methods to analyse the development of the international investment law regime, seeking to understand how, when, and by whom change in treaty language occurs. The study uses a novel computational method to explore the influence of different states on the language of international investment treaties and the spread of language patterns. The analysis reveals a hegemony of Western European, rather than North American influence, and further highlights a clear early mover advantage for obtaining language spread. The article discusses the implications of these findings for the investment treaty system, particularly the limited impact of hard negotiating power compared to early entrance and convincing legal language.
Recruitment of a Middling Promiscuous Enzyme Drives Adaptive Metabolic Evolution in Escherichia coli
Authors: Campbell Ryan P , Whittington A Carl , Zorio Diego A R , Miller Brian G 
Published: September 2023

Abstract
A key step in metabolic pathway evolution is the recruitment of promiscuous enzymes to perform new functions. Despite the recognition that promiscuity is widespread in biology, factors dictating the preferential recruitment of one promiscuous enzyme over other candidates are unknown. Escherichia coli contains four sugar kinases that are candidates for recruitment when the native glucokinase machinery is deleted—allokinase (AlsK), manno(fructo)kinase (Mak), N-acetylmannosamine kinase (NanK), and N-acetylglucosamine kinase (NagK). The catalytic efficiencies of these enzymes are 103- to 105-fold lower than native glucokinases, ranging from 2,400 M−1 s−1 for the most active candidate, NagK, to 15 M−1 s−1 for the least active candidate, AlsK. To investigate the relationship between catalytic activities of promiscuous enzymes and their recruitment, we performed adaptive evolution of a glucokinase-deficient E. coli strain to restore glycolytic metabolism. We observed preferential recruitment of NanK via a trajectory involving early mutations that facilitate glucose uptake and amplify nanK transcription, followed by nonsynonymous substitutions in NanK that enhance the enzyme's promiscuous glucokinase activity. These substitutions reduced the native activity of NanK and reduced organismal fitness during growth on an N-acetylated carbon source, indicating that enzyme recruitment comes at a cost for growth on other substrates. Notably, the two most active candidates, NagK and Mak, were not recruited, suggesting that catalytic activity alone does not dictate evolutionary outcomes. The results highlight our lack of knowledge regarding biological drivers of enzyme recruitment and emphasize the need for a systems-wide approach to identify factors facilitating or constraining this important adaptive process.
Heating of the neck or elbows alleviates Raynaud’s phenomenon but has different effects on different types of patients with systemic sclerosis
Authors: Shima Yoshihito , Watanabe Akane , Inoue Nobuto , Maruyama Tetsuya , Kunitomo Eiji , Kumanogoh Atsushi 
Published: September 2023

ABSTRACT

Objectives
We previously reported that heating of the neck or elbows alleviated Raynaud’s phenomenon in patients with systemic sclerosis and upregulated capillary extension factor angiopoietin-1 (Angpt-1) in the fingertips. In this study, we investigated which cases responded better to the effect of heating of the neck or elbows.

Methods
The pre- to postheating change in the visual analogue scale (ΔVAS) for Raynaud’s phenomenon was examined for correlation with age, disease duration, autoantibodies, disease types, corticosteroid dose, capillaroscopic nailfold capillary damage, fingertip Angpt-1 concentrations at baseline, and increased rate of Angpt-1 concentration.

Results
The ΔVAS for elbow heating correlated positively with the baseline Angpt-1 concentration, whereas opposite correlation was observed for neck heating. The other items did not significantly correlate with the ΔVAS; however, the ΔVAS for elbow heating tended to be larger in patients with advanced capillary damage, whereas an opposite trend was observed for neck heating.

Conclusions
Elbow and neck heating alleviated Raynaud’s phenomenon to a similar extent, but their mechanism was different. Heating of the elbows had a greater effect on patients with advanced capillary damage and lower fingertip Angpt-1 concentrations.
Karnofsky Performance Status and quality of life in patients with relapsed or refractory primary CNS lymphoma from a phase I/II study of tirabrutinib
Authors: Arakawa Yoshiki , Narita Yoshitaka , Nagane Motoo , Mishima Kazuhiko , Terui Yasuhito , Yonezawa Hajime , Asai Katsunori , Fukuhara Noriko , Sugiyama Kazuhiko , Shinojima Naoki , Aoi Arata , Nishikawa Ryo 
Published: September 2023

Abstract

Background
Tirabrutinib, a second-generation inhibitor of Bruton’s tyrosine kinase, was approved in March 2020 for the treatment of relapsed or refractory primary central nervous system lymphoma (r/r PCNSL) based on phase I/II studies in Japan. We previously reported the overall response rate and safety profile. We describe Karnofsky Performance Status (KPS) and the quality of life (QoL) in patients with r/r PCNSL receiving tirabrutinib based on more than 1-year follow-up data.

Methods
Patients with r/r PCNSL, age ≥20 years, and KPS ≥70 were treated with tirabrutinib once daily at a dose of 320, 480, or 480 mg under fasted conditions. QoL was assessed using questionnaires issued by the European Organization for Research and Treatment of Cancer (EORTC), namely EORTC QLQ-C30, EORTC QLQ-BN20, and EuroQol 5 dimensions 3-level (EQ-5D-3L) along with KPS.

Results
Forty-four patients (mean age, 60 years [range 29–86]) were enrolled. The median follow-up period was 14.9 months (range, 1.4–27.7). The median KPS of the patients at baseline was 80.0 (range, 70–100), and this remained constant during the treatment. The global health status/QoL in the QLQ-C30 showed significant improvements from baseline through cycles 3–17 and remained relatively constant thereafter until cycle 23. Improvements were also seen in emotional functioning and constipation in the QLQ-C30 segments. Other items of QLQ-C30 and QLQ-BN20, EQ-5D visual analog scales, and EQ-5D index were maintained during the treatment.

Conclusions
Tirabrutinib generally maintains KPS and QoL scores with some improvements in specific QoL items in patients with r/r PCNSL.