bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origins of cryophilous lineages and the role of Beringia: evidence from the cosmopolitan angiosperm genus Stellaria L. (Caryophyllaceae)
Authors: Sharples Mathew T , Manzitto-Tripp Erin A 
Published: June 2023

Abstract
The cosmopolitan angiosperm genus Stellaria L. (Caryophyllaceae) occurs across the Arctic and is most diverse in the high southern Asian mountains, including presence at the most extreme latitudinal and elevational limits of vascular plants. Using the primary fossil record and double digest restriction site-associated DNA sequencing data, we estimated divergence times of Stellaria and relatives across the Caryophyllaceae. We then used ancestral area and ancestral state reconstructions to interpret the biogeographical history of the group. We found that Stellaria originated in the Miocene and gave rise to repeated New World lineages, mostly from temperate Old World regions and probably via Bering Land Bridges. Circumboreal lineages were recovered of recent, Pleistocene origin and several might have originated in southerly mountains of both the Old World and the New World before subsequently colonizing the Arctic. Ancestral state reconstruction of inhabitance of cold vs. temperate climates and of wet vs. dry habitats revealed repeated evolutionary transitions across these extremes by members of the genus worldwide. Our study, which samples nearly all species within a diverse and cosmopolitan lineage of flowering plants, recovers a group characterized by niche lability and helps to support prior findings of temperate origins of many cryophilous plant lineages. Pre-adaptation to cold might have been a prerequisite for colonization of the Arctic.
Actigraphic evidence of persistent sleep disruption following repetitive mild traumatic brain injury in a gyrencephalic model
Authors: Schwerin Susan C , Breehl Nicholas , Obasa Adedunsola , Kim Yeonho , McCabe Joseph , Perl Daniel P , Haight Thaddeus , Juliano Sharon L 
Published: June 2023

Abstract
We studied the effect of multimodal traumatic brain injuries on daily sleep/activity patterns and related histology. Gyrencephalic ferrets wore actigraphs and received military-relevant brain injuries including shockwaves, strong rotational impact, and variable stress, which were evaluated up to 6 months post injury. Sham and Baseline animals exhibited activity patterns occurring in distinct clusters of high activity, interspersed with periods of low activity. In the Injury and Injury + Stress groups, activity clusters diminished and overall activity patterns became significantly more dispersed at 4 weeks post injury with significant sleep fragmentation. Additionally, the Injury + Stress group exhibited a significant decrease in daytime high activity up to 4 months post injury. At 4 weeks post injury, the reactive astrocyte (GFAP) immunoreactivity was significantly greater in both the injury groups compared to Sham, but did not differ at 6 months post injury. The intensity of immunoreactivity of the astrocytic endfeet that surround blood vessels (visualized with aquaporin 4; AQP4), however, differed significantly from Sham at 4 weeks post injury (in both injured groups) and at 6 months (Injury + Stress only). As the distribution of AQP4 plays a key role in the glymphatic system, we suggest that glymphatic disruption occurs in ferrets after the injuries described here.
Spatiotemporal connectivity maps abnormal communication pathways in major depressive disorder underlying gamma oscillations
Authors: Chen Sitong , Liu Xiaoya , Huang Zhenni , Su Fangyue , Zhang Wenquan , Li Jie , Liu Shuang , Ming Dong 
Published: June 2023

AbstractAuditory steady-state response underlying gamma oscillations (gamma-ASSR) have been explored in patients with major depressive disorder (MDD), while ignoring the spatiotemporal dynamic characteristics. This study aims to construct dynamic directed brain networks to explore the disruption of spatiotemporal dynamics underlying gamma-ASSR in MDD. This study recruited 29 MDD patients and 30 healthy controls for a 40 Hz auditory steady-state evoked experiment. The propagation of gamma-ASSR was divided into early, middle, and late time interval. Partial directed coherence was applied to construct dynamic directed brain networks based on graph theory. The results showed that MDD patients had lower global efficiency and out-strength in temporal, parietal, and occipital regions over three time intervals. Additionally, distinct disrupted connectivity patterns occurred in different time intervals with abnormalities in the early and middle gamma-ASSR in left parietal regions cascading forward to produce dysfunction of frontal brain regions necessary to support gamma oscillations. Furthermore, the early and middle local efficiency of frontal regions were negatively correlated with symptom severity. These findings highlight patterns of hypofunction in the generation and maintenance of gamma-band oscillations across parietal-to-frontal regions in MDD patients, which provides novel insights into the neuropathological mechanism underlying gamma oscillations associated with aberrant brain network dynamics of MDD.
Thrombin-activated interleukin-1α drives atherogenesis, but also promotes vascular smooth muscle cell proliferation and collagen production
Authors: Burzynski Laura C , Morales-Maldonado Alejandra , Rodgers Amanda , Kitt Lauren A , Humphry Melanie , Figg Nichola , Bennett Martin R , Clarke Murray C H 
Published: June 2023

Abstract

Aims
Atherosclerosis is driven by multiple processes across multiple body systems. For example, the innate immune system drives both atherogenesis and plaque rupture via inflammation, while coronary artery-occluding thrombi formed by the coagulation system cause myocardial infarction and death. However, the interplay between these systems during atherogenesis is understudied. We recently showed that coagulation and immunity are fundamentally linked by the activation of interleukin-1α (IL-1α) by thrombin, and generated a novel knock-in mouse in which thrombin cannot activate endogenous IL-1α [IL-1α thrombin mutant (IL-1αTM)].

Methods and results
Here, we show significantly reduced atherosclerotic plaque formation in IL-1αTM/Apoe−/− mice compared with Apoe−/− and reduced T-cell infiltration. However, IL-1αTM/Apoe−/− plaques have reduced vascular smooth muscle cells, collagen, and fibrous caps, indicative of a more unstable phenotype. Interestingly, the reduced atherogenesis seen with thrombin inhibition was absent in IL-1αTM/Apoe−/− mice, suggesting that thrombin inhibitors can affect atherosclerosis via reduced IL-1α activation. Finally, bone marrow chimeras show that thrombin-activated IL-1α is derived from both vessel wall and myeloid cells.

Conclusions
Together, we reveal that the atherogenic effect of ongoing coagulation is, in part, mediated via thrombin cleavage of IL-1α. This not only highlights the importance of interplay between systems during disease and the potential for therapeutically targeting IL-1α and/or thrombin, but also forewarns that IL-1 may have a role in plaque stabilization.
Immune profiling of murine cardiac leukocytes identifies triggering receptor expressed on myeloid cells 2 as a novel mediator of hypertensive heart failure
Authors: Smart Charles Duncan , Fehrenbach Daniel J , Wassenaar Jean W , Agrawal Vineet , Fortune Niki L , Dixon Debra D , Cottam Matthew A , Hasty Alyssa H , Hemnes Anna R , Doran Amanda C , Gupta Deepak K , Madhur Meena S 
Published: June 2023

Abstract

Aims
Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, microvascular dysfunction, and myocardial fibrosis with recent evidence implicating the immune system in orchestrating cardiac remodelling.

Methods and results
Here, we show the mouse model of deoxycorticosterone acetate (DOCA)-salt hypertension induces key elements of HFpEF, including diastolic dysfunction, exercise intolerance, and pulmonary congestion in the setting of preserved ejection fraction. A modified single-cell sequencing approach, cellular indexing of transcriptomes and epitopes by sequencing, of cardiac immune cells reveals an altered abundance and transcriptional signature in multiple cell types, most notably cardiac macrophages. The DOCA-salt model results in differential expression of several known and novel genes in cardiac macrophages, including up-regulation of Trem2, which has been recently implicated in obesity and atherosclerosis. The role of Trem2 in hypertensive heart failure, however, is unknown. We found that mice with genetic deletion of Trem2 exhibit increased cardiac hypertrophy, diastolic dysfunction, renal injury, and decreased cardiac capillary density after DOCA-salt treatment compared to wild-type controls. Moreover, Trem2-deficient macrophages have impaired expression of pro-angiogenic gene programmes and increased expression of pro-inflammatory cytokines. Furthermore, we found that plasma levels of soluble TREM2 are elevated in DOCA-salt treated mice and humans with heart failure.

Conclusions
Together, our data provide an atlas of immunological alterations that can lead to improved diagnostic and therapeutic strategies for HFpEF. We provide our dataset in an easy to explore and freely accessible web application making it a useful resource for the community. Finally, our results suggest a novel cardioprotective role for Trem2 in hypertensive heart failure.
GeniePool: genomic database with corresponding annotated samples based on a cloud data lake architecture
Authors: Hadar Noam , Weintraub Grisha , Gudes Ehud , Dolev Shlomi , Birk Ohad S 
Published: June 2023

Abstract
In recent years, there are a huge influx of genomic data and a growing need for its phenotypic correlations, yet existing genomic databases do not allow easy storage and accessibility to the combined phenotypic–genotypic information. Freely accessible allele frequency (AF) databases, such as gnomAD, are crucial for evaluating variants but lack correlated phenotype data. The Sequence Read Archive (SRA) accumulates hundreds of thousands of next-generation sequencing (NGS) samples tagged by their submitters and various attributes. However, samples are stored in large raw format files, inaccessible for a common user. To make thousands of NGS samples and their corresponding additional attributes easily available to clinicians and researchers, we generated a pipeline that continuously downloads raw human NGS data uploaded to SRA using SRAtoolkit and preprocesses them using GATK pipeline. Data are then stored efficiently in a cloud data lake and can be accessed via a representational state transfer application programming interface (REST API) and a user-friendly website. We thus generated GeniePool, a simple and intuitive web service and API for querying NGS data from SRA with direct access to information related to each sample and related studies, providing significant advantages over existing databases for both clinical and research usages. Utilizing data lake infrastructure, we were able to generate a multi-purpose tool that can serve many clinical and research use cases. We expect users to explore the meta-data served via GeniePool both in daily clinical practice and in versatile research endeavours.
Database URL https://geniepool.link
Step by step daily management of short-term mechanical circulatory support for cardiogenic shock in adults in the intensive cardiac care unit: a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology SC, the European Society of Intensive Care Medicine, the European branch of the Extracorporeal Life Support Organization, and the European Association for Cardio-Thoracic Surgery
Authors: Møller Jacob Eifer , Sionis Alessandro , Aissaoui Nadia , Ariza Albert , Bělohlávek Jan , De Backer Daniel , Färber Gloria , Gollmann-Tepeköylu Can , Mebazaa Alexandre , Price Susanna , Swol Justyna , Thiele Holger , Hassager Christian 
Published: June 2023

Abstract
The use of mechanical circulatory support using percutaneous ventricular assist devices (pVAD) has increased rapidly during the last decade without substantial new evidence for their effect on outcome. In addition, many gaps in knowledge still exist such as timing and duration of support, haemodynamic monitoring, management of complications, concomitant medical therapy, and weaning protocols. This clinical consensus statement summarizes the consensus of an expert panel of the Association for Acute CardioVascular Care, European Society of Intensive Care Medicine, European Extracorporeal Life Support Organization, and European Association for Cardio-Thoracic Surgery. It provides practical advice regarding the management of patients managed with pVAD in the intensive care unit based on existing evidence and consensus on best current practice.
Telehealth for All? Assessing Remote Service Delivery for Latinx Immigrants
Authors: Hodges James , Calvo Rocío 
Published: June 2023

Abstract
The COVID-19 pandemic spurred a widespread shift to remotely delivered health services. Telehealth has shown promise in making healthcare more accessible. Little research has looked at the effects of this change on access to healthcare for Latinx immigrants. This qualitative study explored the shift to remote services during the COVID-19 pandemic in a new immigrant destination. Authors interviewed 23 service providers to assess if telehealth increased access to healthcare for Latinx immigrants. Results showed that telehealth improved access to services overall. Still, barriers to care remained. Immigrants experienced (a) limited access to technology and low digital literacy, (b) lack of privacy during the provision of services, (c) inability to utilize certain digital platforms due to confidentiality regulations, and (d) decreased quality of services. Findings suggest that telehealth is a promising modality to decrease healthcare disparities, but providers need to thoughtfully address barriers unique to Latinx immigrants to ensure their full participation.
A Curvature Estimate for Stable Marginally Outer Trapped Hypersurface With a Free Boundary
Authors: Chai Xiaoxiang 
Published: June 2023

Abstract
A marginally outer trapped hypersurface is a generalization of minimal hypersurfaces originated from general relativity. We show a curvature estimate for stable marginally outer trapped hypersurfaces up to the free boundary satisfying a uniform area bound. Our proof is based on an iteration argument. The curvature estimate was previously known via a blowup argument for stable minimal hypersurfaces.
Rainfall Shocks, Livelihood Diversification and Welfare: Evidence from Rural Togo
Authors: Weyori Alirah E , Liebenehm Sabine 
Published: June 2023

Abstract
Theory suggests that rural farm households exposed to greater risk should diversify their income portfolios to reduce variation in welfare caused by adverse events such as rainfall shocks. Rainfall shocks, however, can also degrade asset stocks and make diversification more costly. Using a panel dataset of small-scale cattle farmers from rural Togo and long-term historical rainfall data, we first examine whether and in what direction rural portfolio diversification is related to historical rainfall shocks. Second, we test whether diversification is associated with stabilised welfare in the face of recent rainfall shocks. Our results show that historical rainfall shock exposure reduces income diversification. In terms of mitigation, we find that diversification is generally not effective in insulating against welfare losses. We conclude that there is a need to stimulate rural diversification as a means of building resilient livelihoods to cope with increasing weather variability by strengthening credit, agricultural and market institutions.
Energy Transition Metals: Bottleneck for Net-Zero Emissions?
Authors: Boer Lukas , Pescatori Andrea , Stuermer Martin 
Published: June 2023

Abstract
The energy transition requires substantial amounts of metals, including copper, nickel, cobalt, and lithium. Are these metals a bottleneck? We identify metal-specific demand shocks, estimate supply elasticities, and study the price impact of the transition in a structural scenario analysis. Prices of these four metals would reach previous historical peaks but for an unprecedented, sustained period in a net-zero emissions scenario, potentially derailing the energy transition. Their production value would rise nearly four-fold to USD 11 trillion for the period 2021–2040. These four metals markets alone could become as important to the global economy as the oil market.
Loblolly Pine Planting Densities for Landowners in Areas with Poor Pulpwood Markets: Some Considerations
Authors: VanderSchaaf Curtis L 
Published: June 2023

AbstractLoblolly pine plantations in the southeastern United States contribute significantly to local and state timber supply and economies. Planting density greatly affects reforestation costs. It also influences when vegetation starts competing inter- (and intra)-specifically for limited site resources, and when thinnings occur. Planting 600 seedlings per acre essentially forces landowners into two thinnings prior to a final clearcut. However, many landowners are finding it difficult to conduct first thinnings; poor pulpwood markets and lack of interest from loggers have become common. Reforestation costs have increased due to inflation. Thus, given better seedlings, a need for reduced reforestation costs, and the inability of landowners to conduct pulpwood-dominated thinnings, most landowners should plant near 450 seedlings per acre. Here, landowners have more flexibility to adjust to market conditions. If pulpwood markets improve they can participate, but a “pulpwood” first thinning is not absolutely needed. Plus, entry into more valuable chip-n-saw and sawlog markets should occur sooner.
ATM phosphorylates the FATC domain of DNA-PKcs at threonine 4102 to promote non-homologous end joining
Authors: Lu Huiming , Zhang Qin , Laverty Daniel J , Puncheon Andrew C , Augustine Mathew M , Williams Gareth J , Nagel Zachary D , Chen Benjamin P C , Davis Anthony J 
Published: June 2023

Abstract
Ataxia-telangiectasia mutated (ATM) drives the DNA damage response via modulation of multiple signal transduction and DNA repair pathways. Previously, ATM activity was implicated in promoting the non-homologous end joining (NHEJ) pathway to repair a subset of DNA double-stranded breaks (DSBs), but how ATM performs this function is still unclear. In this study, we identified that ATM phosphorylates the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a core NHEJ factor, at its extreme C-terminus at threonine 4102 (T4102) in response to DSBs. Ablating phosphorylation at T4102 attenuates DNA-PKcs kinase activity and this destabilizes the interaction between DNA-PKcs and the Ku-DNA complex, resulting in decreased assembly and stabilization of the NHEJ machinery at DSBs. Phosphorylation at T4102 promotes NHEJ, radioresistance, and increases genomic stability following DSB induction. Collectively, these findings establish a key role for ATM in NHEJ-dependent repair of DSBs through positive regulation of DNA-PKcs.
Safety and Effectiveness of Direct Oral Anticoagulants for the Treatment of Gastrointestinal Cancer-Associated Venous Thromboembolism
Authors: Ullah Fauzia , Song Juhee , Rojas Hernandez Cristhiam M , Kroll Michael H , Escalante Carmelita P , Toale Katy M 
Published: June 2023

Abstract

Background
Patients with gastrointestinal cancer (GICA) are at high risk for venous thromboembolism (VTE). Data from randomized clinical trials in cancer-associated VTE suggest that direct oral anticoagulants (DOACs) conferred similar or superior efficacy but a heterogeneous safety profile in patients with GICA. We compared the safety and effectiveness of DOACs in patients with GICA and VTE at MD Anderson Cancer Center.

Materials and Methods
This was a retrospective chart review of patients with GICA and VTE receiving treatment with DOACs for a minimum of 6 months. Primary outcomes were the proportion of patients experiencing major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and recurrent VTE. Secondary outcomes were time to bleeding and recurrent VTE.

Results
A cohort of 433 patients with GICA who were prescribed apixaban (n = 300), or rivaroxaban (n = 133) were included. MB occurred in 3.7% (95% confidence interval [CI] 2.1-5.9), CRNMB in 5.3% (95% CI 3.4-7.9), and recurrent VTE in 7.4% (95% CI 5.1-10.3). The cumulative incidence rates of CRNMB and recurrent VTE were not significantly different when comparing apixaban to rivaroxaban.

Conclusion
Apixaban and rivaroxaban had a similar risk of recurrent VTE and bleeding and could be considered as anticoagulant options in selected patients with GICA and VTE.
A Proposed Modified Staging System for Medullary Thyroid Cancer: A SEER Analysis With Multicenter Validation
Authors: Wang Zhengshi , Fan Xin , Zha Xiaojuan , Xu Yong , Yin Zhiqiang , Rixiati Youlutuziayi , Yu Fei 
Published: June 2023

Abstract

Background
The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for medullary thyroid cancer (MTC) was implemented in 2018. However, its ability to predict prognosis remains controversial.

Patients and Methods
Patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and multicenter datasets. Overall survival was the primary end-point of the present study. The concordance index (C-index) was used to assess the efficacy of various models to predict prognostic outcomes.

Results
A total of 1450 MTC patients were selected from the SEER databases and 349 in the multicenter dataset. According to the AJCC staging system, there were no significant survival differences between T4a and T4b categories (P = .299). The T4 category was thus redefined as T4a’ category (≤3.5 cm) and T4b’ category (&gt;3.5 cm) based on the tumor size, which was more powerful for distinguishing the prognosis (P = .003). Further analysis showed that the T category was significantly associated with both lymph node (LN) location and count (P &lt; .001). Therefore, the N category was modified by combining the LN location and count. Finally, the above-mentioned novel T and N categories were adopted to modify the 8th AJCC classification using the recursive partitioning analysis principle, and the modified staging system outperformed the current edition (C-index, 0.811 vs. 0.792).

Conclusions
The 8th AJCC staging system was improved based on the intrinsic relationship among the T category, LN location, and LN count, which would have a positive impact on the clinical decision-making process and appropriate surveillance.
Scoping review: exploring the equity impact of current digital health design practices
Authors: Evans Laura , Evans Jay , Pagliari Claudia , Källander Karin 
Published: June 2023

ABSTRACT

Background
Digital health interventions designed through human-centered design (HCD) have shown potential to impact health equity. This scoping review aims to understand how HCD approaches in digital health impact health equity.

Methodology
A scoping review was undertaken. Searches were conducted on PubMed, EMBASE, Web of Science, AMC Digital Library, ProQuest Thesis and Dissertations and Global Medicus Index databases.

Results
A total of 6169 references were identified, and 40 of them fulfilled the inclusion criteria for analysis. The application of HCD methodologies varied greatly as did the digital health interventions. The HCD methodologies had an impact on health equity for those individuals included in the development of the digital health tools, but beyond those persons, the impact was harder to establish.

Conclusion
There is optimism for the role that HCD in digital health can have in reducing health inequities; however, the evidence is not robust. Most projects failed to scale up to maturity or failed to apply evaluation mechanisms to assess the health equity impact. Recommendations include rigorous application of HCD methodologies, scaling digital health tools beyond pilot projects, and embedding evaluation to determine the impact on health equity.