bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer-associated SMARCAL1 loss-of-function mutations promote alternative lengthening of telomeres and tumorigenesis in telomerase-negative glioblastoma cells
Authors: Liu Heng , Xu Cheng , Diplas Bill H , Brown Alexandrea , Strickland Laura M , Yao Haipei , Ling Jinjie , McLendon Roger E , Keir Stephen T , Ashley David M , He Yiping , Waitkus Matthew S 
Published: January 2023

Abstract

Background
Telomere maintenance mechanisms are required to enable the replicative immortality of malignant cells. While most cancers activate the enzyme telomerase, a subset of cancers uses telomerase-independent mechanisms termed alternative lengthening of telomeres (ALT). ALT occurs via homology-directed-repair mechanisms and is frequently associated with ATRX mutations. We previously showed that a subset of adult glioblastoma (GBM) patients with ATRX-expressing ALT-positive tumors harbored loss-of-function mutations in the SMARCAL1 gene, which encodes an annealing helicase involved in replication fork remodeling and the resolution of replication stress. However, the causative relationship between SMARCAL1 deficiency, tumorigenesis, and de novo telomere synthesis is not understood.

Methods
We used a patient-derived ALT-positive GBM cell line with native SMARCAL1 deficiency to investigate the role of SMARCAL1 in ALT-mediated de novo telomere synthesis, replication stress, and gliomagenesis in vivo.

Results
Inducible rescue of SMARCAL1 expression suppresses ALT indicators and inhibits de novo telomere synthesis in GBM and osteosarcoma cells, suggesting that SMARCAL1 deficiency plays a functional role in ALT induction in cancers that natively lack SMARCAL1 function. SMARCAL1-deficient ALT-positive cells can be serially propagated in vivo in the absence of detectable telomerase activity, demonstrating that the SMARCAL1-deficient ALT phenotype maintains telomeres in a manner that promotes tumorigenesis.

Conclusions
SMARCAL1 deficiency is permissive to ALT and promotes gliomagenesis. Inducible rescue of SMARCAL1 in ALT-positive cell lines permits the dynamic modulation of ALT activity, which will be valuable for future studies aimed at understanding the mechanisms of ALT and identifying novel anticancer therapeutics that target the ALT phenotype.
Alternative 3′-untranslated regions regulate high-salt tolerance ofSpartina alterniflora
Authors: Wang Taotao , Ye Wenbin , Zhang Jiaxiang , Li Han , Zeng Weike , Zhu Sheng , Ji Guoli , Wu Xiaohui , Ma Liuyin 
Published: January 2023

AbstractHigh-salt stress continues to challenge the growth and survival of many plants. Alternative polyadenylation (APA) produces mRNAs with different 3′-untranslated regions (3′ UTRs) to regulate gene expression at the post-transcriptional level. However, the roles of alternative 3′ UTRs in response to salt stress remain elusive. Here, we report the function of alternative 3′ UTRs in response to high-salt stress in S. alterniflora (Spartina alterniflora), a monocotyledonous halophyte tolerant of high-salt environments. We found that high-salt stress induced global APA dynamics, and ∼42% of APA genes responded to salt stress. High-salt stress led to 3′ UTR lengthening of 207 transcripts through increasing the usage of distal poly(A) sites. Transcripts with alternative 3′ UTRs were mainly enriched in salt stress-related ion transporters. Alternative 3′ UTRs of HIGH-AFFINITY K+ TRANSPORTER 1 (SaHKT1) increased RNA stability and protein synthesis in vivo. Regulatory AU-rich elements were identified in alternative 3′ UTRs, boosting the protein level of SaHKT1. RNAi-knock-down experiments revealed that the biogenesis of 3′ UTR lengthening in SaHKT1 was controlled by the poly(A) factor CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR 30 (SaCPSF30). Over-expression of SaHKT1 with an alternative 3′ UTR in rice (Oryza sativa) protoplasts increased mRNA accumulation of salt-tolerance genes in an AU-rich element-dependent manner. These results suggest that mRNA 3′ UTR lengthening is a potential mechanism in response to high-salt stress. These results also reveal complex regulatory roles of alternative 3′ UTRs coupling APA and regulatory elements at the post-transcriptional level in plants.
Explaining the physics of transfer learning in data-driven turbulence modeling
Authors: Subel Adam , Guan Yifei , Chattopadhyay Ashesh , Hassanzadeh Pedram 
Published: January 2023

Abstract
Transfer learning (TL), which enables neural networks (NNs) to generalize out-of-distribution via targeted re-training, is becoming a powerful tool in scientific machine learning (ML) applications such as weather/climate prediction and turbulence modeling. Effective TL requires knowing (1) how to re-train NNs? and (2) what physics are learned during TL? Here, we present novel analyses and a framework addressing (1)–(2) for a broad range of multi-scale, nonlinear, dynamical systems. Our approach combines spectral (e.g. Fourier) analyses of such systems with spectral analyses of convolutional NNs, revealing physical connections between the systems and what the NN learns (a combination of low-, high-, band-pass filters and Gabor filters). Integrating these analyses, we introduce a general framework that identifies the best re-training procedure for a given problem based on physics and NN theory. As test case, we explain the physics of TL in subgrid-scale modeling of several setups of 2D turbulence. Furthermore, these analyses show that in these cases, the shallowest convolution layers are the best to re-train, which is consistent with our physics-guided framework but is against the common wisdom guiding TL in the ML literature. Our work provides a new avenue for optimal and explainable TL, and a step toward fully explainable NNs, for wide-ranging applications in science and engineering, such as climate change modeling.
Is There Investment Value in the Soft-Dollar Arrangement? Evidence from Mutual Funds
Authors: Gokkaya Sinan , Liu Xi , Pool Veronika Krepely , Xie Fei , Zhang Jinfan 
Published: January 2023

Abstract
Combining novel data on analyst employment history and mutual fund commission payments, we show that client funds generate higher returns on stocks for which they have access to research by industry expert analysts. The outperformance is greater when funds are more important clients and cannot be attributed to tipping. Client funds place modestly higher weights on stocks covered by industry expert analysts and allocate more commissions to brokers providing such coverage. For identification, we exploit exogenous analyst coverage disruptions. Our findings contribute to the debate on whether mutual funds obtain any investment value from access to analysts through the soft-dollar arrangement.
Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Detection of a rare variant inPSTPIP1through three generations in a family with an initial diagnosis of FMF/MKD-overlapping phenotype
Authors: Özkılınç Önen Merve , Onat Umut İ , Uğurlu Serdal , Timuçin Ahmet C , Öz Arslan Devrim , Everest Elif , Özdoğan Huri , Tahir Turanlı Eda 
Published: January 2023

AbstractObjectiveThe presence of FMF cases without MEFV (MEFV innate immunity regulator, pyrin) pathogenic variants led us to search for other genes’ involvement in the disease development. Here, we describe the presence of genetic heterogeneity in a three-generation family with an FMF/mevalonate kinase deficiency (MKD)-overlapping phenotype without MEFV/MVK (mevalonate kinase) pathogenic variants.MethodTargeted sequencing revealed a rare, fully penetrant variant in PSTPIP1 (p.Arg228Cys, rs781341816). Computational stability analyses of PSTPIP1 protein were performed. PSTPIP1-pyrin protein interaction was examined by immunoprecipitation and immunoblotting in peripheral blood mononuclear cells (PBMCs) of patients and healthy controls. PBMCs were cultured, and inflammation was induced by LPS+ATP treatment, followed by protein level measurements of caspase-1, IL1ß, pyrin and PSTPIP1 in cell lysates and mature caspase-1 and mature IL1ß in supernatants.ResultsThe conserved, rare (GnomAD, 0.000028) PSTPIP1 p.Arg228Cys variant, previously reported in ClinVar as a variant with uncertain significance, showed complete penetrance in the family presenting an autosomal dominant pattern. Computational analyses showed a potentially destabilizing effect of the variant on PSTPIP1 protein. Accordingly, PSTPIP1-pyrin interaction was increased in patients harboring the variant, which resulted in elevated levels of mature caspase-1 and IL1ß in the inflammation-induced patient samples.ConclusionsUnlike previously described cases with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA)-associated PSTPIP1 variants, our patients with the p.Arg228Cys variant presented with an FMF/MKD-overlapping phenotype. As additional data on the genetic heterogeneity in the variable clinical spectrum of autoinflammatory syndromes, we suggest that the p.Arg228Cys variant in PSTPIP1 is related to inflammation responses through strong PSTPIP1-pyrin interaction and pyrin inflammasome activation.
Destroying Democracy for the People: The Economic, Social, and Political Consequences of Populist Rule, 1990 to 2017
Authors: Cole Wade M , Schofer Evan 
Published: January 2023

ABSTRACT
The recent populist wave has raised questions about the implications of populism for democracy. Some scholars express optimism that populism may be a source of democratic revitalization, bringing about sweeping changes in accordance with the majority will. More often, populism is viewed as a threat to liberal democracy, combining calls for radical change with disdain for core democratic institutions and norms. We consider the possibility that these outcomes may not be mutually exclusive and develop a conceptual typology for understanding the consequences of populist rule. We then use cross-national panel fixed-effects models to analyze the effects of populist leadership between 1990 and 2017. We first examine whether populists have economic and social effects in line with their core aspirations. Left-wing populists are quite effective at implementing their agenda: they reduce income inequality, regulate markets, and incorporate marginalized groups. Right-wing populists are also fairly impactful: for instance, they raise tariffs, cut taxes, and restrict the rights of women and gay people. However, populists of all stripes are associated with the rapid and severe erosion of liberal democratic institutions. Populists, we conclude, often destroy democracy in the name of the people.
A process for converting an in-person training to increase church capacity to implement physical activity and healthy eating practices and policies to an online format
Authors: Wilcox Sara , Saunders Ruth P , Stucker Jessica , Kaczynski Andrew T , Day Kelsey R , Kinnard Deborah , Decker Lindsay , Bernhart John A 
Published: January 2023

AbstractThe implementation of evidence-based public health programs into practice is critical for improving health, but trainings for organizational change agents are often not scalable.To describe the process of converting a training that targets faith-based organizational capacity development from an in-person to an online format.We engaged in an iterative process to convert the training delivery mode from in-person to online that included assessing stakeholder support, consulting the literature on best practices, seeking a design team, consolidating content, designing engaging lessons, and building an online site. Feedback from end-users and other audiences was incorporated throughout. Pilot participants with characteristics like intended training users were then recruited via community and faith-based partner networks. They rated their agreement with statements about the effectiveness as well as design and functionality of each lesson and the overall training (1 = strongly disagree, 5 = strongly agree) and participated in a structured follow-up interview.Nine pilot participants (representing 9 churches in 7 states; 6 African American, 5 with health ministries) rated the online lessons favorably (all ratings ≥ 4.5). Most (90.4%) perceived the lesson duration to be “just right” and spent 52.5 ± 9.9 minutes/lesson. Participants evaluated the overall training positively (all ratings ≥ 4.7). Lesson content, resources, multimedia, and program ideas were most-liked aspects of lessons, while content, staff responsiveness, discussion board, and pace were most-liked aspects of the overall training in open-ended and interview responses.This paper shares a replicable process for converting training modalities from in-person to online with the goal of increased scalability.
Do Women Contribute More Effort than Men to a Real Public Good?
Authors: Alger Ingela , Juarez Laura , Juarez-Torres Miriam , Miquel-Florensa Josepa 
Published: January 2023

AbstractThis study presents evidence from a lab-in-the-field experiment, conducted in eight small, rural villages in Mexico, in which subjects choose to exert real effort to fund real health centers in their own and other localities. The results show that women are more willing than men to exert effort to fund the health center in another locality, relative to the one in their locality. This gender gap is mostly due to women who have some trust in the way the government spends taxes, and to those who benefit from a government program that targets women and fosters healthcare use. These results also suggest that women might be aware of their higher willingness to exert effort for a public good that does not benefit them directly, compared to men, because they seem to reduce their individual effort the more female their environment is.
Loss of Adgra3 causes obstructive azoospermia with high penetrance in male mice
Authors: Nybo Maja L. , Kvam Jone M. , Nielsen John E. , Frederiksen Hanne , Spiess Katja , Jensen Kristian H. R. , Gadgaard Sarina , Walser Anna L. S. , Thomsen Jesper S. , Cowin Pamela , Juul Anders , Blomberg Jensen Martin , Rosenkilde Mette M. 
Published: January 2023

AbstractThe adhesion receptor ADGRA3 (GPR125) is a known spermatogonial stem cell marker, but its impact on male reproduction and fertility has not been examined. Using a mouse model lacking Adgra3 (Adgra3−/−), we show that 55% of the male mice are infertile from puberty despite having normal spermatogenesis and epididymal sperm count. Instead, male mice lacking Adgra3 exhibited decreased estrogen receptor alpha expression and transient dilation of the epididymis. Combined with an increased estradiol production, this indicates a post‐pubertal hormonal imbalance and fluid retention. Dye injection revealed a blockage between the ejaculatory duct and the urethra, which is rare in mice suffering from infertility, thereby mimicking the etiologies of obstructive azoospermia found in human male infertility. To summarize, male reproductive tract development is dependent on ADGRA3 function that in concert with estrogen signaling may influence fluid handling during sperm maturation and storage.
High and low permeability of human pluripotent stem cell–derived blood–brain barrier models depend on epithelial or endothelial features
Authors: Girard Stéphane D. , Julien‐Gau Ingrid , Molino Yves , Combes Benjamin F. , Greetham Louise , Khrestchatisky Michel , Nivet Emmanuel 
Published: January 2023

AbstractThe search for reliable human blood–brain barrier (BBB) models represents a challenge for the development/testing of strategies aiming to enhance brain delivery of drugs. Human‐induced pluripotent stem cells (hiPSCs) have raised hopes in the development of predictive BBB models. Differentiating strategies are thus required to generate endothelial cells (ECs), a major component of the BBB. Several hiPSC‐based protocols have reported the generation of in vitro models with significant differences in barrier properties. We studied in depth the properties of iPSCs byproducts from two protocols that have been established to yield these in vitro barrier models. Our analysis/study reveals that iPSCs derivatives endowed with EC features yield high permeability models while the cells that exhibit outstanding barrier properties show principally epithelial cell‐like (EpC) features. We found that models containing EpC‐like cells express tight junction proteins, transporters/efflux pumps and display a high functional tightness with very low permeability, which are features commonly shared between BBB and epithelial barriers. Our study demonstrates that hiPSC‐based BBB models need extensive characterization beforehand and that a reliable human BBB model containing EC‐like cells and displaying low permeability is still needed.
Interface Fluid Syndrome After Descemet Membrane Endothelial Keratoplasty in Patients With History of LASIK
Authors: Izquierdo Luis , Ben-Shaul Or , Larco Pablo , Pereira Nicolas , Mannis Mark J. , Henriquez Maria A. 
Published: January 2023

Purpose:
The aim of this study was to evaluate the visual, pachymetric, tomographic, and biomicroscopic findings in a series of cases with laser in situ keratomileusis (LASIK) flap interface fluid syndrome (IFS) after Descemet membrane endothelial keratoplasty (DMEK).

Methods:
Six cases were included in this study; all patients had a history of LASIK and underwent DMEK for the treatment of bullous keratopathy. After uneventful surgery, all patients presented with corneal edema and IFS under the LASIK flap, which was demonstrated with anterior segment optical coherence tomography (AS-OCT). Visual acuity, clinical findings, pachymetry, endothelial cell count, and AS-OCT were documented during the management of these cases.

Results:
IFS appears 2.33 days (±1.03) after DMEK. One case improved with conservative treatment. In 5 cases, the LASIK flap was lifted, the fluid was drained, and the flap was replaced. The mean best-corrected visual acuity after fluid drainage was 0.44 logMAR (range 0.18–1.0) and mean central corneal thickness was 538 μm ± 160. Total resolution of the IFS was achieved at 14.5 days (range 4–30) after DMEK. AS-OCT showed resolution of the flap interface in 5 of 6 cases, while 1 patient required second DMEK due to reaccumulation of the interface fluid.

Conclusions:
IFS can occur after DMEK in patients with previous LASIK. AS-OCT is a valuable tool for monitoring these cases preoperatively and postoperatively. Early surgical management is often needed to achieve resolution.
Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial
Authors: Roilides Emmanuel , Ashouri Negar , Bradley John S. , Johnson Matthew G. , Lonchar Julia , Su Feng-Hsiu , Huntington Jennifer A. , Popejoy Myra W. , Bensaci Mekki , De Anda Carisa , Rhee Elizabeth G. , Bruno Christopher J. 
Published: January 2023

Background:
Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant Gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.

Methods:
This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age. The primary objective was safety and tolerability. Key secondary end points included clinical cure and per-participant microbiologic response rates at end of treatment (EOT) and test of cure (TOC) visits.

Results:
The microbiologic modified intent-to-treat (mMITT) population included 95 participants (ceftolozane/tazobactam, n = 71; meropenem, n = 24). The most common diagnosis and pathogen were pyelonephritis (ceftolozane/tazobactam, 84.5%; meropenem, 79.2%) and Escherichia coli (ceftolozane/tazobactam, 74.6%; meropenem, 87.5%); 5.7% (ceftolozane/tazobactam) and 4.8% (meropenem) of E. coli isolates were extended-spectrum β-lactamase-producers. Rates of adverse events were similar between treatment groups (any: ceftolozane/tazobactam, 59.0% vs. meropenem, 60.6%; drug-related: ceftolozane/tazobactam, 14.0% vs. meropenem, 15.2%; serious: ceftolozane/tazobactam, 3.0% vs. meropenem, 6.1%). Rates of clinical cure for ceftolozane/tazobactam and meropenem at EOT were 94.4% and 100% and at TOC were 88.7% and 95.8%, respectively. Rates of microbiologic eradication for ceftolozane/tazobactam and meropenem at EOT were 93.0% and 95.8%, and at TOC were 84.5% and 87.5%, respectively.

Conclusions:
Ceftolozane/tazobactam had a favorable safety profile in pediatric participants with cUTI; rates of clinical cure and microbiologic eradication were high and similar to meropenem. Ceftolozane/tazobactam is a safe and effective new treatment option for children with cUTI, especially due to antibacterial-resistant Gram-negative pathogens.
Teledermatology during the COVID 19 pandemic in a developing country – Could this be the answer to improving the reach of dermatology care?
Authors: Gold-Olufadi Shakirat , Jesuyajolu Damilola , Cole-Adeife Olufolakemi , Emokpare Didi , Enigbokan Omololu 
Published: January 2023

Introduction:
The COVID-19 pandemic has changed the way telemedicine is utilized globally, with most countries reporting an increase in its adoption. The first review of teledermatology in Nigeria reported poor service use. This present report outlines an improvement in the adoption of telemedicine and factors that may account for this increased utilization.

Methods:
We performed a retrospective review of all patients who registered through two telemedicine platforms to access dermatology services during a 1-year period. Data were collated with an online questionnaire and analyzed with SPSS software.

Results:
Sixty patients booked appointments through the platform, with 38 and 22 patients booking virtual and physical consultations, respectively. The response rate was 68.4% and 50.0% for those that booked virtual and physical consultations, respectively, with no significant age difference between the groups. More women booked appointments, and all respondents were educated to at least college level. The majority learned about booking a dermatologist appointment through social media. There was no difference in the clinical outcome between patients who booked a virtual or physical consultation.

Conclusion:
More patients are resorting to teledermatology services because of the convenience; however, most of these patients are situated in urban areas. Because this study showed no significant differences in the clinical outcome between patients who booked virtual and physical consultations, the adoption of teledermatology may be the answer to increasing coverage of dermatology services in developing countries where specialists are limited. Efforts must be made to increase the reach of teledermatology to rural areas.