bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Iranian guidelines for the diagnosis and management of maple syrup urine disease: an evidence- and consensus- based approach
Authors: Rostampour Noushin , Dalili Setila , Moravej Hossein , Afshar Zhila , Yazdani Negar , Mousavi Seyedeh Tahereh , Rostami Parastoo , Zamanfar Daniel , Yahay Maryam , Nikravesh Abdolhossein , Beyzaei Zahra , Davoodi Mohamad Ahangar , Sedaghat Atefeh , Hakemzadeh Tahora , Talea Ali
Published: January 2025

Maple Syrup Urine Disease (MSUD) disease is a defect in the function of the Branched-chain 2-ketoacid dehydrogenase complex (BCKDH). It is caused by pathogenic biallelic variants in BCKDHA, BCKA decarboxylase, or dihydrolipoamide dehydrogenase. The brain is the major organ involved in MSUD. MSUD happens in about 1 in 86,800 to 185,000 live births. According to some diversity in the management of Iranian patients with MSUD, the development of a national guideline is essential. This guideline is provided through a literature search on articles in PubMed, Scopus, Web of Sciences, Cochrane, and Embase databases from 2001 to 2022 accompanied by a consensus of physicians of different centers in Iran who are experts in the diagnosis and management of this disease. This article considers pathogenesis, epidemiology, clinical manifestations, diagnosis, treatment, and monitoring of MSUD patients with limited recourse.
VCP regulates early tau seed amplification via specific cofactors
Authors: Batra Sushobhna , Vaquer-Alicea Jaime , Valdez Clarissa , Taylor Skyler P. , Manon Victor A. , Vega Anthony R. , Kashmer Omar M. , Kolay Sourav , Lemoff Andrew , Cairns Nigel J. , White Charles L. , Diamond Marc I.
Published: January 2025

Background

Neurodegenerative tauopathies may progress based on seeding by pathological tau assemblies, whereby an aggregate is released from one cell, gains entry to an adjacent or connected cell, and serves as a specific template for its own replication in the cytoplasm. Seeding into the complex cytoplasmic milieu happens within hours, implying the existence of unknown factors that regulate this process.

Methods

We used proximity labeling to identify proteins that control seed amplification within 5 h of seed exposure. We fused split-APEX2 to the C-terminus of tau repeat domain (RD) to reconstitute peroxidase activity 5 h after seeded intracellular tau aggregation. Valosin containing protein (VCP/p97) was the top hit. VCP harbors dominant mutations that underlie two neurodegenerative diseases, multisystem proteinopathy and vacuolar tauopathy, but its mechanistic role is unclear. We used immortalized cells and human neurons to study the effects of VCP on tau seeding. We exposed cells to fibrils or brain homogenates in cell culture media and measured effects on uptake and induction of intracellular tau aggregation following various genetic and pharmacological manipulations of VCP.

Results

VCP knockdown reduced tau seeding. Chemical inhibitors had opposing effects on seeding in HEK293T tau biosensor cells and human neurons: ML-240 increased seeding efficiency, whereas NMS-873 decreased it. The inhibitors only functioned when administered within 8 h of seed exposure, indicating a role for VCP early in seed processing. We screened 30 VCP co-factors in HEK293T biosensor cells by genetic knockout or knockdown. Reduction of ATXN3, NSFL1C, UBE4B, NGLY1, and OTUB1 decreased tau seeding, as did NPLOC4, which also uniquely increased soluble tau levels. By contrast, reduction of FAF2 increased tau seeding.

Conclusions

Divergent effects on tau seeding of chemical inhibitors and cofactor reduction indicate that VCP regulates this process. This is consistent with a cytoplasmic processing complex centered on VCP that directs seeds acutely towards degradation vs. amplification.
Carbohydrate conversion in spent coffee grounds: pretreatment strategies and novel enzymatic cocktail to produce value-added saccharides and prebiotic mannooligosaccharides
Authors: Shaikh-Ibrahim Ali , Curci Nicola , De Lise Federica , Sacco Oriana , Di Fenza Mauro , Castaldi Stefany , Isticato Rachele , Oliveira André , Aniceto José P. S. , Silva Carlos M. , Serafim Luísa Seuanes , M. Krogh Kristian B. R. , Moracci Marco , Cobucci-Ponzano Beatrice
Published: January 2025

Background

Spent coffee grounds (SCG) are the most abundant waste byproducts generated from coffee beverage production worldwide. Typically, these grounds are seen as waste and end up in landfills. However, SCG contain valuable compounds that can be valorized and used in different applications. Notably, they are rich in carbohydrates, primarily galactomannan, arabinogalactan type II, and cellulose. Within the framework of a circular bioeconomy, the targeted degradation of these polysaccharides via a tailored cocktail of carbohydrate-active enzymes offers a promising strategy for producing high-value saccharides from coffee waste.

Results

In this study, various mild pretreatments were evaluated to increase the enzyme accessibility of SCG-derived biomass, reduce lignin content, and minimize hemicellulose loss. Thermostable enzymes were selected to construct an enzymatic cocktail specifically targeting cellulose and hemicelluloses in pretreated SCGs. The approach used achieved a conversion of 52% of the polysaccharide content to oligo- and monosaccharides, producing 17.4 mg of reducing sugars and 5.1 mg of monosaccharides from 50 mg of SCG. Additionally, microwave pretreatment followed by the application of a thermostable endo β-mannanase resulted in the production of 62.3 mg of mannooligosaccharides from 500 mg of SCG. In vitro experiments demonstrated that the produced mannooligosaccharides exhibited prebiotic activity, promoting the growth and biofilm formation of five probiotic bacterial strains.

Conclusions

This study highlights an effective strategy for the valorization of SCG polysaccharides through mild pretreatment and customized enzymatic cocktails in a circular bioeconomic context. The production of both monosaccharides and oligosaccharides with prebiotic activity illustrates the versatility and commercial potential of SCG as a substrate for high-value saccharides. Furthermore, the use of mild pretreatment methods and thermostable enzymes minimizes chemical inputs and energy demands, aligning with sustainable processing practices. The ability to selectively target and degrade specific polysaccharides within SCG not only enhances the yield of desirable products, but also preserves key structural components, reducing waste and promoting resource efficiency.
Substance use recovery needs among college students seeking recovery services: a thematic qualitative analysis
Authors: Nichols Lindsey M. , Brown Tiffany B. , Allmendinger Angela , Hennessy Emily A. , Tanner-Smith Emily E.
Published: January 2025

Background

College students who are in recovery from substance use disorders face challenges related to abstaining from substance use, finding supportive social networks, and achieving their academic goals. These students may therefore seek out various recovery supports at their institutions to meet their needs and goals.

Methods

This study analyzed previously collected data to explore themes related to students’ experiences of recovery, including their recovery needs and challenges while also attending college. We conducted qualitative thematic analysis of written responses to open-ended prompts posed to 92 college students from one university (47% female; M age = 21.5 years, SD = 5.6) who participated in a larger parent study of Collegiate Recovery Programs in the United States. We used a phenomenological approach to guide the current study, to characterize the meaning and experience within the shared phenomenon of recovery processes among college students.

Results

Two broad categories emerged, representing nine total themes that were coded: (a) intrapersonal factors: recovery-specific challenges, self-care and coping, mental and behavioral health, life challenges, and personal motivations and attributes; and (b) interpersonal/social factors: 12-step recovery supports, external supports and community, college environment, and relationships with others.

Conclusions

Findings offer insight into barriers and facilitators to recovery among colleges students and are discussed in terms of their implications for primary stakeholders at institutions of higher education to support college students in substance use recovery.
The burden of Gastric Cancer and possible risk factors from 1990 to 2021, and projections until 2035: findings from the Global Burden of Disease Study 2021
Authors: Qin Niping , Fan Yangyan , Yang Tao , Yang Zhiping , Fan Daiming
Published: January 2025

Background and objective

Gastric cancer (GC) remains a significant global health challenge, characterized by high incidence and mortality rates, particularly in East Asia. A comprehensive understanding of the disease burden of gastric cancer is crucial for developing effective prevention and treatment strategies. However, comprehensive global assessments of the disease burden of gastric cancer remain limited. This study, based on the Global Burden of Disease (GBD) framework, systematically analyzes global trends in gastric cancer from 1990 to 2021 and projects future trends through 2035, aiming to provide scientific evidence for policymaking.

Methods

The data were derived from the Global Burden of Disease (GBD) Study 2021, covering gastric cancer (GC) incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs), and age-standardized DALY rates (ASRs) across 204 countries and regions from 1990 to 2021. The Bayesian age-period-cohort model was employed to project trends up to 2035.

Results

In comparison with 1990, both the incidence and mortality of GC rose in 2021, with over 1.23 million new cases recorded globally, resulting in 954,373.60 deaths and 22,786,633.10 DALYs. Between 1990 and 2021, the ASIRs, ASDRs, and ASRs decreased by 42% (ranging from 49 to 35%), 49% (ranging from 55 to 43%), and 53% (ranging from 58 to 47%), respectively. The peak ASIRs and ASDRs in 2021 were seen in the high-middle SDI quintile. Males exhibited higher rates of ASDRs, ASIRs, and ASRs compared to females. In 2021, East Asia and high-income North America bore the largest burden of smoking-related GC, while Central Europe experienced the highest burden from high-sodium diets. Forecasts toward 2035 indicate a continued decline in both ASIRs and ASDRs.

Conclusions

Despite notable reductions in both incidence and mortality, GC remains a substantial global burden, affecting various regions and countries. Deaths and DALYs related to high-sodium diets and smoking have shown an overall decline. However, substantial regional and age-related disparities persist. Targeted interventions, such as smoking control and promoting the intake of fresh fruits and vegetables, are essential in diminishing GC risk.
Biglycan-driven risk stratification in ZFTA-RELA fusion supratentorial ependymomas through transcriptome profiling
Authors: Okonechnikov Konstantin , Ghasemi David R. , Schrimpf Daniel , Tonn Svenja , Mynarek Martin , Koster Jan , Milde Till , Zheng Tuyu , Sievers Philipp , Sahm Felix , Jones David T.W. , von Deimling Andreas , Pfister Stefan M. , Kool Marcel , Pajtler Kristian W. , Korshunov Andrey
Published: January 2025

Recent genomic studies have allowed the subdivision of intracranial ependymomas into molecularly distinct groups with highly specific clinical features and outcomes. The majority of supratentorial ependymomas (ST-EPN) harbor ZFTA-RELA fusions which were designated, in general, as an intermediate risk tumor variant. However, molecular prognosticators within ST-EPN ZFTA-RELA have not been determined yet. Here, we performed methylation-based DNA profiling and transcriptome RNA sequencing analysis of 80 ST-EPN ZFTA-RELA investigating the clinical significance of various molecular patterns. The principal types of ZFTA-RELA fusions, based on breakpoint location, demonstrated no significant correlations with clinical outcomes. Multigene analysis disclosed 1892 survival-associated genes, and a metagene set of 100 genes subdivided ST-EPN ZFTA-RELA into favorable and unfavorable transcriptome subtypes composed of different cell subpopulations as detected by deconvolution analysis. BGN (biglycan) was identified as the top-ranked survival-associated gene and high BGN expression levels were associated with poor survival (Hazard Ratio 17.85 for PFS and 45.48 for OS; log-rank; p-value < 0.01). Furthermore, BGN immunopositivity was identified as a strong prognostic indicator of poor survival in ST-EPN, and this finding was confirmed in an independent validation set of 56 samples. Our results indicate that integrating BGN expression (at mRNA and/or protein level) into risk stratification models may improve ST-EPN ZFTA-RELA outcome prediction. Therefore, gene and/or protein expression analyses for this molecular marker could be adopted for ST-EPN ZFTA-RELA prognostication and may help assign patients to optimal therapies in prospective clinical trials.
A novel CUL4B gene variant activating Wnt4/β-catenin signal pathway to karyotype 46, XY female with disorders of sex development
Authors: Wang Chunlin , Chen Hong , Chen Qingqing , Qu Yangbin , Yuan Ke , Liang Li , Yan Qingfeng
Published: January 2025

Background

Karyotype 46, XY female disorders of sex development (46, XY female DSD) are congenital conditions due to irregular gonadal development or androgen synthesis or function issues. Genes significantly influence DSD; however, the underlying mechanisms remain unclear. This study identified a Chinese family with 46, XY female DSD due to the CUL4B gene.

Methods

The proband medical history and pedigree were investigated. Whole-exome sequencing was performed to analyze different variations. Transiently transfected testicular teratoma (NT2/D1), KGN ovarian cells with either mutant or wild-type CUL4B gene, and knock-in Cul4b mouse models were confirmed. The expression levels of sex-related genes were analyzed.

Results

A 9.5-year-old girl was diagnosed with 46, XY DSD. A hemizygous variant c.838 T > A of the CUL4B gene was detected. The mRNA and protein levels of WNT4 and FOXL2 genes were higher than those in the wild-type group; however, CTNNB1, SOX9, and DMRT1 were lower in the wild-type group in NT2/D1 cells. In KGN ovarian cells of the mutant group, the mRNA and protein levels for WNT4 and CTNNB1 were elevated. Damaged testicular vasculature and underdeveloped seminal vesicles were observed in Cul4bL337M mice.

Conclusions

A missense CUL4B variant c.838 T > A associated with 46, XY female DSD was identified, and may activate the Wnt4/β-catenin pathway. Our findings provide novel insights into the molecular mechanisms of 46, XY female DSD.
Development and Validation of Emoji Response Scales for Assessing Patient-Reported Outcomes
Authors: Thompson Carrie A. , Novotny Paul J. , Yost Kathleen , Bartz Alicia C. , Rogak Lauren , Dueck Amylou C.
Published: January 2025

PURPOSE

Emoji are digital images or icons used to express an idea or emotion in electronic communication. The purpose of this study was to develop and evaluate the psychometric properties of two patient-reported scales that incorporate emoji.

METHODS

The Emoji Response Scale developed for this study has two parts: the Emoji-Ordinal and Emoji-Mood scales. A pilot study was designed to validate the ordinal nature of the Emoji-Ordinal Scale. Twenty patients were shown all possible pairs of five emoji and asked to select the most positive from each pair. The psychometric ordering was assessed using Coombs unfolding and Thurstone scaling. A separate pilot study was designed to determine which emoji to include in the Emoji-Mood Scale. Ten common feelings experienced by patients with cancer were chosen by the study team. Patients and providers were asked to select the one emoji that best represented each feeling from the selection. The most commonly selected emotions and representative emoji were chosen for the Emoji-Mood Scale. In a randomized study of 294 patients, Spearman correlations, Wilcoxon tests, and Bland-Altman analyses determined the construct validity of the scales compared with Linear Analog Scale Assessments (LASA) and Patient-Reported Outcomes Measurement Information System (PROMIS) scores.

RESULTS

Ninety-five percent of patients selected the same ordering among the ordinal emoji, and Thurstone scaling confirmed the ordinal nature of the response scale. The construct validity of the scales was high with correlations between the Emoji-Ordinal Scale and the LASA scale of 0.70 for emotional well-being, 0.72 for physical well-being, 0.74 for overall quality of life, and –0.81 for fatigue. Emoji-Mood Scale ratings were strongly related to PROMIS global mental, global physical, fatigue, anxiety, sleep disturbance, and social activity scales (
P
< .0001).

CONCLUSION

This study provides evidence that scales incorporating emoji are valid for collecting patient-reported outcomes.
Molecular Profiling of Biliary Tract Cancers in African American and Caucasian Patients
Authors: Hu Zishuo Ian , Pavlick Dean C. , Ross Jeffrey S. , Lee Sunyoung S. , Eluri Madhulika , Javle Milind
Published: January 2025

PURPOSE

Biliary tract cancers (BTCs) include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancers. BTCs have a number of genomic alterations, including isocitrate dehydrogenase 1 (
IDH1
) mutations, fibroblast growth factor receptor 2 (
FGFR2
) rearrangements, and
ERBB2
amplifications. Therapies targeting these alterations have shown clinical benefit in patients with BTCs in the United States. However, molecular differences between races in BTCs are largely unknown. In particular, the genomic profiles of African American (AA) patients with BTCs have been infrequently reported. We sought to identify key genomic differences between AA and Caucasian patients with BTCs in the United States in the Foundation Medicine and American Association for Cancer Research (AACR) GENIE databases.

METHODS

BTC patients from AA and Caucasian patients from the Foundation Medicine and AACR GENIE databases were retrospectively reviewed. BTCs were divided into ICC, ECC, and GBCs in the Foundation Medicine database. BTCs were divided into cholangiocarcinomas and GBCs in the AACR GENIE database.

RESULTS

The mean age of AA patients with BTCs was lower compared with Caucasians.
TP53
and
FGFR2
alterations were significantly more frequent in AA patients compared with Caucasian patients with BTCs.
IDH1
mutations in Caucasian patients with BTCs were double that of AA patients.

CONCLUSION

The results of this study suggest that significant genomic differences exist between races and warrant further investigation.
LGP-DS: A novel algorithm for identifying influential nodes in complex networks based on multi-dimensional evidence fusion
Authors: Xu Gui-Qiong , Miao Jia-Le , Dong Chen
Published: January 2025

Identifying influential nodes in complex networks is crucial in various application scenarios, such as blocking the spread of rumors, containing disease transmission and facilitating precise targeting of product advertisements. Existing researches have presented various centrality measures to identify influential nodes in the network, but most measures evaluate the importance of nodes from limited dimensions. To fill this gap, we propose a novel algorithm called Local-Global-Position based on the Dempster-Shafer evidence theory (LGP-DS) to solve the problem of identifying influential nodes. The proposed LGP-DS algorithm first calculates the information about propagation capability of nodes based on the global, local and position attributes, and thus obtains multiple evidence dimensions. Next, information entropy is employed to assess the contribution of different evidence dimensions, and the information is aggregated using Dempster-Shafer evidence theory, which facilitates the evaluation of nodal importance within a network. The effectiveness of the LGP-DS algorithm is validated by several simulated experiments on real-world networks. The results demonstrate that the proposed algorithm outperforms eight widely used algorithms in terms of discrimination power, top-10 nodes, and ranking accuracy.
Approach to the Patient Using Diabetes Technology in Pregnancy
Authors: Dickens Laura T , Gonzalez Maritza G
Published: January 2025

Diabetes in pregnancy increases risk for complications for the pregnant patient and neonate. Tight glycemic control to maintain glucose levels as close to nondiabetic ranges as possible can lower risk for these complications. Achieving strict glycemic targets can be challenging, and technologies including continuous glucose monitors (CGMs) and hybrid closed-loop (HCL) insulin pumps have the potential to improve diabetes control and pregnancy outcomes. The aim of this review is to present and appraise the current data about use of these technologies in pregnancy. In pregnancies with type 1 diabetes (T1D), CGM can improve glycemic control and reduce risk for neonatal complications. International consensus guidelines recommend more than 70% time in pregnancy target range (TIR) of 63 to 140 mg/dL (3.5-7.8 mmol/L), and there are data to suggest higher TIR in pregnancies with T1D can reduce risk for neonatal complications including fetal overgrowth and pregnancy complications like preeclampsia. Recent randomized controlled trials have demonstrated improved glycemic outcomes with use of HCL insulin pumps in pregnancy with T1D, though the results vary depending on the system used and available glycemic targets. In pregnancies with type 2 diabetes (T2D) and gestational diabetes mellitus (GDM), retrospective data suggest CGM can improve glycemia but there are limited data about outcomes or optimal CGM targets. Studies have reported glycemic measures for pregnancies without diabetes, which may serve as a guide for further outcomes studies of T2D and GDM. Access to diabetes technology and the necessary health care systems to support use of these devices may be barriers that contribute to health care disparities.
Testosterone Replacement Therapy and Risk of COVID-19 and Effect of COVID-19 on Testosterone's Treatment Effect
Authors: Pencina Karol M , Lincoff A Michael , Klein Eric A , Nissen Steven E , Shang Yili Valentine , Khan Nader , Li Xue , Chan Anna , Miller Michael G , Bhasin Shalender
Published: January 2025

Context

Whether circulating testosterone, dihydrotestosterone, and estradiol levels or testosterone replacement therapy (TRT) affects the risk of COVID-19 and whether COVID-19 affects response to TRT remains unknown.

Objective

The study evaluated whether baseline testosterone, dihydrotestosterone, and estradiol levels or TRT are associated with risk of developing COVID-19 and whether COVID-19 affects treatment response to TRT.

Methods

Among 5204 men, aged 45 to 80 years, with hypogonadism in the TRAVERSE trial, 379 developed COVID-19. We compared baseline and on-treatment hormone levels, and safety and efficacy in participants with and without COVID-19 diagnosis.

Results

Neither baseline nor on-treatment testosterone, estradiol, and dihydrotestosterone levels prior to COVID-19 differed significantly between men with and without COVID-19 diagnosis. Incidence of COVID-19 was similar in participants randomized to TRT or placebo groups (3-year Kaplan-Meier incidence 8.0% in TRT and 8.6% in placebo group, P = .823). Incidences of COVID-19-related hospitalizations (38.5% vs 32.8%, P = .222) and deaths (12.8% vs 8.9%, P = .247) were similar in the TRT and placebo groups. Changes in hypogonadal symptoms, libido, energy, and hemoglobin/hematocrit in response to TRT were attenuated in testosterone-treated men who developed COVID-19. Incidences of major adverse cardiovascular events, venous thromboembolism, and acute kidney injury were similar in those with COVID-19 diagnosis and those without.

Conclusion

In men with hypogonadism and cardiovascular disease (CVD) or increased risk of CVD, baseline and pre-COVID-19 on-treatment testosterone, dihydrotestosterone, and estradiol levels were similar in those who developed COVID-19 and those who did not. TRT did not affect the risk of COVID-19. COVID-19 attenuated the treatment response to TRT.
Dr. Joan Venes: A Pioneer of Pediatric Neurosurgery
Authors: Satpathy Yasoda , Stone Lauren E. , Ben-Haim Sharona
Published: January 2025

Dr. Joan Venes (1935-2010) is a well-respected pioneer of pediatric neurosurgery. She was the third board-certified female neurosurgeon in the United States and was the first female neurosurgery resident to be accepted by her residency program at Yale University. She was the recipient of numerous awards, including the prestigious Van Wagenen Fellowship, which sparked her interest in furthering research around pediatric intracranial pressure monitoring. Throughout her career, Dr. Venes was a prolific researcher, publishing extensively on pediatric shunts, procedural techniques, and the use of technology in pediatric neurosurgery. She was one of the founding members of the American Society of Pediatric Neurosurgeons and the first female chairman of the Pediatric Section of the American Association of Neurological Surgeons and Congress of Neurological Surgeons. In the latter half of her career, Dr. Venes developed a strong interest in health policy, becoming a Pew Fellow in Health Policy at the University of Michigan and, subsequently, a Robert Wood Johnson Foundation Health Policy Fellow. Her leadership and mentorship laid the groundwork for an exponential increase of female neurosurgeons and her research continues to be impactful today.
Acute and Lifelong Endurance Exercise Yields Differential Effects During Circadian Disruption in Mice
Authors: Nelson Cole F. , Wyatt Cole R. , Johnson Evan C. , Todd William D. , Schmitt Emily E.
Published: January 2025

Introduction: Circadian rhythms are responsible for physiological and behavioral processes coordinated in a 24-hour cycle. We investigated whether untimed, long-term voluntary wheel access mitigated circadian disruption and facilitated re-entrainment. Methods: Thirty-four C57Bl/6 J mice (n = 21 males, n = 14 females) were used in this experiment. Long-term exercised (LTEx) mice ran from 3 wks to 12 mo of age. At 12 mo animals were circadian disrupted for 14 d and then re-entrained for 7 d. Long-term sedentary (LTSed) animals were disrupted but had no access to a wheel. Another long-term sedentary group had access to a wheel only during disruption (LTSed+Ex). SubCue dataloggers were used to track internal rhythm of core body temperature (Tb). RNA was extracted from skeletal muscle and RT-qPCR was used to analyze gene expression. Results: Overall, all three experimental groups had an initial entrained period lengths of ~24 h at baseline. There was a main effect of time (p = 0.012), treatment (p = 0.005) and interaction of time x treatment (p = 0.033) from baseline to disruption. A post-hoc analysis within group one-way ANOVAs showed no difference between baseline and disruption period lengths in the LTSed+Ex treatment, yet a difference from baseline to disruption in LTSed and LTEx. Lastly, there is a difference in entrained period lengths between all three treatment groups at the re-entrainment time point (p = 0.026) with a difference in change between disruption and re-entrainment with LTEx being lower than LTSed+Ex. Conclusions: Our results suggest that acute-like exercise during circadian disruption aided in mitigating circadian disruption. When all treatment groups were re-entrained back to a normal rhythm, the LTEx animals that had access to a wheel prior to, during, and after disruption had period lengths closest to baseline values.
SF3B1: from core splicing factor to oncogenic driver
Authors: Bak-Gordon Pedro , Manley James L.
Published: January 2025

Highly recurrent somatic mutations in the gene encoding the core splicing factor SF3B1 are drivers of multiple cancer types. SF3B1 is a scaffold protein that orchestrates multivalent protein–protein interactions within the spliceosome that are essential for recognizing the branchsite (BS) and selecting the 3′ splice site during the earliest stage of pre-mRNA splicing. In this review, we first describe the molecular mechanism by which multiple oncogenicSF3B1mutations disrupt splicing. This involves perturbation of an early spliceosomal trimeric protein complex necessary for accurate BS recognition in a subset of introns, which leads to activation of upstream branchpoints and selection of cryptic 3′ splice sites. We next discuss how specific transcripts affected by aberrant splicing inSF3B1-mutant cells contribute to the initiation and progression of cancer. Finally, we highlight the prognostic value and disease phenotypes of different cancer-associatedSF3B1mutations, which is critical for developing new targeted therapeutics againstSF3B1-mutant cancers still lacking in the clinic.
Θρησκεία, διεθνείς σχέσεις και πολιτική
Authors: Αλμπάνη Χρυσούλα
Published: January 2025

Η παρούσα διδακτορική διατριβή αποπειράται να διερευνήσει τη σχέση της θρησκείας με τη διεθνή πολιτική και την πολύπτυχη αλληλεπίδρασή της με το πεδίο των διεθνών σχέσεων, εστιάζοντας ειδικότερα στον τρόπο με τον οποίο η σχέση μεταξύ των τριών μεταβλητών αντανακλάται στη χάραξη πολιτικής της Ευρωπαϊκής Ένωσης (EE). Η εν λόγω ερευνητική μελέτη εδράζεται αναλυτικά στο κοινωνιολογικό έργο του Ul. Beck, σχετικά με τον αναθεωρημένο κοινωνικό και πολιτικό ρόλο της θρησκευτικής αναφοράς στο θεωρητικό πλαίσιο της Δεύτερης Νεωτερικότητας (Second Modernity). Κατά τον Beck, η συζήτηση για την παγκόσμια «αναβίωση» της θρησκείας ή την «επιστροφή της από την εξορία», στις σύγχρονες ευρωπαϊκές κοινωνίες, εκφράζει στην πραγματικότητα την αναγκαιότητα επαναθεώρησης της δυναμικής και του αντίκτυπου του θρησκευτικού παράγοντα στο ευρωπαϊκό πολιτικό πλαίσιο. Τα ερευνητικά δεδομένα προκύπτουν μέσα από ημιδομημένες συνεντεύξεις βάθους (semi-structured, in-depth interviews), οι οποίες απευθύνθηκαν: σε εκπροσώπους των ευρωπαϊκών θεσμικών οργάνων, σε εκπροσώπους διεθνών και ευρωπαϊκών θρησκευτικών οργανισμών που εκπροσωπούνται στην ΕΕ και μετέχουν ενεργά στον θεσμοθετημένο διάλογό της με τους φορείς του θρησκευτικού πεδίου, αλλά και σε εκπροσώπους ευρωπαϊκών μη-κυβερνητικών οργανώσεων, οι οποίοι συνδράμουν στις ευρύτερες προσπάθειες σε ευρωπαϊκό επίπεδο στα πεδία επίλυσης των συγκρούσεων και οικοδόμησης της ειρήνης. Σκοπός της έρευνας είναι να φωτίσει τον τρόπο με τον οποίο οι ερωτώμενοι αντιλαμβάνονται και ερμηνεύουν την επαναφορά της θρησκείας στη διεθνή δημόσια σφαίρα, αλλά και το πώς αξιολογούν τη συμβολή του θρησκευτικού παράγοντα ως μεταβλητή «ήπιας ισχύος» στις πολιτικές πρωτοβουλίες της Ευρωπαϊκής Ένωσης, στην εξωτερική πολιτική και τη διπλωματία, στις ειρηνευτικές διαδικασίες και σε θέματα που αφορούν στην προστασία των ανθρωπίνων δικαιωμάτων. Ζητούμενο είναι ακόμη να διερευνηθεί ο βαθμός κατά τον οποίο η συμπερίληψη της θρησκείας, σε επίπεδο ευρωπαϊκής πολιτικής, μπορεί να επηρεάσει τη σχέση της ΕΕ με τρίτες χώρες και τη θέση αυτής στο διεθνές σύστημα. Τα αποτελέσματα της έρευνας φανερώνουν ότι η θρησκεία εξακολουθεί να αποτελεί μια κινητοποιό δύναμη, η οποία νοηματοδοτεί και πλαισιώνει την ανθρώπινη δράση, ότι η αλληλεπίδρασή της με την πολιτική συνεχίζεται αδιάλειπτα, παρότι η εκκοσμίκευση παραμένει μια διαδικασία εν εξελίξει στο ευρωπαϊκό πλαίσιο, και ότι αναμφίβολα συνιστά μια περιοχή μελέτης με ιδιαίτερο ερευνητικό ενδιαφέρον για το επιστημονικό πεδίο των Διεθνών Σχέσεων και την παγκόσμια πολιτική.
The effect of aerobic and resistance exercise on markers of atherosclerosis. A narrative review of meta-analyses and systematic reviews.
Authors: Bokou Nikoleta-Maria , Dimitriadis Nikolaos , Arnaoutis Giannis , Panagiotakos Demosthenes
Published: January 2025

Background: Atherosclerosis, a chronic inflammatory vascular disease with lipid metabolism abnormalities, serves as a major pathological foundation for ischemic coronary heart disease (CHD). As lifestyle-related habits transform to sedentarism and unhealthy eating, the incidence of atherosclerosis increases. The beneficial impact of physical activity on the cardiovascular system is well-documented and widely acknowledged. Major health organisations strongly recommend regular participation in aerobic exercise for individuals to reduce all-cause and cardiovascular disease mortality and morbidity, whereas resistance exercise is suggested with caution.
Method and Material: A literature search of the PubMed and Scopus databases was performed where 9 meta-analyses were retrieved, published in the English language from the past 10 years. This narrative review aims to evaluate the latest scientific evidence regarding the role of aerobic and/or resistance exercise in relation to atherosclerosis development, through the evaluation of its effect on lipids, and inflammatory markers.
Results: The findings of the studies summarised here are inconsistent concerning which type of exercise exerts the maximum effect on atherosclerotic biomarkers. There is a moderate level of evidence suggesting that a combination of aerobic and resistance exercise is likely to provide the greatest benefit.
Conclusions: Nevertheless, minimising sedentary behaviour on a population level, lowers the risk of several major chronic diseases, thereby decreasing healthcare costs. Thus, effective interventions to increase physical activity levels or reduce sedentary behaviour should be implemented.
COMSOL Simulation of Ion Dynamics in an Inertial Electrostatic Confinement System
Authors: Gong Myles Y , Puri Rohan , Ziehm Erik P , Miley George H
Published: January 2025

The complex structure of Inertial Electrostatic Confinement (IEC) plasmas creates difficulties in accurately modeling electric field geometries and charged particle motion within such systems. Additionally, current models of IEC physics have fallen short of fully explaining the formation of key plasma structures, such as ion microchannels and virtual electrodes, which are critical to the operation and scaling of these devices. In order to optimize IEC systems to achieve breakeven fusion conditions, refined models are needed to explain the dynamics of IEC plasmas on a first-principles basis. This study presents several computational models of a spherical IEC fusion device using COMSOL Multiphysics. Electrostatic simulations using the AC/DC module indicate that the high-voltage feedthrough stalk and cathode grid asymmetries significantly distort the intended potential structure, thus producing perturbations in the plasma. The effects of electrode geometry on the internal electrostatic field structure are compared for two stalk designs with different ceramic insulation thicknesses as well as two geodesic grid designs: symmetric and asymmetric. Lastly, single particle trajectories of various ion species are presented, which provide preliminary insights into ion dynamics under several IEC configurations. The results of these simulations reveal that the complex field generated by the stalk significantly alters ion trajectories, reducing ion recirculation and total confinement time for all simulated ion species.
Spory o nielegalne praktyki lecznicze pomiędzy balwierzami a katami w Elblągu w XVII w.
Authors: Kaczor Dariusz
Published: January 2025

Niniejszy tekst podejmuje kwestię sporów kompetencyjnych pomiędzy koncesjonowanymi chirurgami-balwierzami a miejskimi katami w Elblągu na przestrzeni XVII w. w zakresie dokonywania przez tych ostatnich nielegalnych zabiegów leczniczych na szkodę cechowych cyrulików. Podstawę źródłową stanowią decyzje dotyczące formalnego rozstrzygania sporów pomiędzy obiema grupami przez władze miejskie oraz supliki balwierzy do Rady w tych sprawach. W tekście zostały omówione aspekty związane z zakresem kuracji podejmowanych nielegalnie przez katów, przynależnością społeczną ich klienteli i powodami szukania przez mieszczan pomocy medycznej u miejskich oprawców. Poruszone zostały także wątki częstego podejmowania się tego rodzaju zabiegów przez żony katów bądź wdowy po nich (jako przyczynek do roli kobiet w zakresie świadczenia usług leczniczych w mieście wczesnej epoki nowożytnej) oraz roli władz miejskich jako instytucji dbającej o porządek publiczny i prowadzącej mediacje w sytuacji konfliktu społecznego.
Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) after silicone breast implants
Authors: Yousfi Jaouad , Oumlil Soukaina , Essaadouni Lamiaa
Published: January 2025

Autoimmune/inflammatory syndrome is a complex condition characterized by various autoimmune and inflammatory symptoms following the exposure to an adjuvant such as silicone. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is challenging to diagnose because it can mimic other autoimmune diseases and requires specific criteria for identification. We report a case of a 35-year-old woman who developed inflammatory joint pain, fatigue and myalgia after receiving silicone breast implants. Symptoms improved significantly after administration of steroids. Based on the fulfilment of the ASIA diagnostic criteria, the diagnosis was made. This case emphasizes the importance of understanding this condition in patients with unexplained systemic symptoms after exposure to adjuvants.
Representatividade surda em mangás
Authors: Baalbaki Angela Correa Ferreira , De Mamedes Arruda Ana Beatriz , DE SOUSA COSTA ANA BEATRIZ , Dias Tostis Ana Paula , Mendes Sobral Daniel , Pavão Ribeiro Gustavo , Marques Leite Pinto Joice Bianca , Carvalho Chagas Juliana , da Silva Nóbrega Louise Helene , de Souza Caldas Pinho Milena , Ribeiro Barros Verônica
Published: January 2025

O presente artigo tem como objetivo apontar as características e ferramentas utilizadas pela autora e ilustradora Kohske ao expressar uma representação surda em sua coleção de manga (quadrinhos de origem japonesa) “GANGSTA." (2011). Na história narrada, destaca-se um dos personagens principais da obra, Nicolas Brown que é surdo. Nossa proposta é apresentar como a língua de sinais, especificamente a língua de sinais japonesa, foi incorporada ao gênero mangá e como a autora explora a vivência de Nicolas como uma pessoa surda e suas interações com personagens ouvintes. A análise foi feita a partir dos oito volumes publicados pela editora JBC no Brasil. Como resultado, identificamos a inserção de sinais tanto nos balões do personagem surdo quanto de alguns personagens ouvintes.
Exercícios de afeto em redes plurais epistêmicas
Authors: Monteiro Fróes Maira , Marques S. Ferreira Vinícius , Cesar de Oliveira Renata , Reis Joanne , Simões Peres Marta , Tamiasso Martinhon Priscila
Published: January 2025

Este artigo compartilha experiências extensionistas que buscam promover a formação e o funcionamento criativo de redes inter/trans epistêmicas (ou inter/transdisciplinares). As ações que compuseram estas experiências se deram em torno do filme O Poço, e de três mesas de apresentação e debate realizadas no contexto do Festival do Conhecimento da Universidade Federal do Rio de Janeiro. Uma análise de palavras foi realizada com o material textual escrito e transcrito, gerado durante estas ações. Cada palavra foi classificada em uma de três categorias, denominadas termos de carga subjetiva afetiva, termos de carga conceitual e termos de contextualização e propriedades, portanto, considerados valores de primeiro plano sugeridos pela experiência cognitivo afetiva dos sujeitos envolvidos, depreensíveis pela narrativa. De teor empírico, nossa avaliação de indicadores de discurso sugere que nossos co-partícipes vivenciaram estados de enredamento subjetivo, envolvendo qualificadores afetivos, éticos, estéticos, plurais, multimodais enfim. Nossa análise sugere que nossos trânsitos afetivos convivem com nossos sistemas de conhecimento. Tais estados, ao contrário da blindagem do pensamento objetivo aos nossos sujeitos na prática de análise técnica, científica, apontam para a coexistência, nestes indivíduos, de sujeitos e objetos, de tecituras narrativas que a despeito de  racionais em nossa experiência intensa de trocas, tanto internas ao grupo, quanto na perspectiva do público em geral, são também encharcadas de emoções. Portanto, há convivência de razão e emoção como elementos de construção de conhecimento.
Bonos verdes en la República Argentina: notas en torno al encuadre normativo y dinámica de su mercado
Authors: Alonso Jose Fernandez
Published: January 2025

El mercado de bonos verdes ha evidenciado un desarrollo significativo a escala global durante los últimos años. Este proceso estuvo alentado tanto por el diseño y ejecución de regulaciones específicas por parte de los decisores político-económicos nacionales como asimismo por el interés creciente de firmas y gobiernos de distintos niveles de acceder a financiamiento mediante estos instrumentos “temáticos”. La República Argentina no quedó marginada de estos desarrollos. El presente artículo se propone analizar el encuadre normativo y la dinámica del mercado de bonos verdes en la República Argentina entre 2019 y 2023. El estudio se articula sobre teorizaciones propias de la Economía Política Internacional (EPI) y de la Ecología Política. En términos de su diseño metodológico, el artículo recurre al análisis documental de las normativas sobre la problemática en ciernes y de las 37 emisiones de bonos verdes realizadas en el país entre diciembre de 2019 y octubre de 2023.
Entre O Sol E O Dragão: Oportunidades E Desafios Da Asean No Século XXI | Between The Sun And The Dragon: Opportunities And Challenges For Asean In The 21st Century
Authors: Carvalho Neves Bárbara , Borges Ramos Dias Maurício Luiz , Simán Tainá
Published: January 2025

RESUMO
Os mecanismos regionais se apresentam não somente como instrumentos de convergência de esforços para alcançar objetivos comuns, mas também refrear e enfrentar ameaças identificadas. Ao atentar-se para o desenvolvimento da Associação das Nações do Sudeste Asiático (ASEAN), foi possível visualizar um instrumento que tem sido exitoso tanto na promoção da globalização defendida por seus Estados-membros, como no fortalecimento e ampliação do comércio, investimento e relações extrarregionais do bloco. Entretanto, nas últimas décadas, constataram-se crescentes mudanças e disputas de poder na dinâmica internacional que apresentam novos desafios aos projetos e esforços regionais. Entre os atores de disputa que pressionam o Sudeste Asiático em suas tomadas de decisão e cooperação estão a China e o Japão. Através de uma análise qualitativa e documental, este artigo tem como objetivo avaliar a trajetória da ASEAN, buscando compreender sua atuação e direcionamento em um mundo em transição, de disputas e mudanças, tendo como foco de análise as condutas da China e do Japão diante do bloco e seus impactos tanto no nível de interação regional, como de sua projeção internacional. Argumenta-se que, apesar de ser percebida como um fórum de discussão com limitadas capacidades de ação, a ASEAN, na realidade, tem sido bem-sucedida em garantir a autonomia e legitimidade do bloco e de seus Estado-membros - mesmo perante um mundo em transição.
Palavras-chave: ASEAN; China; Japão.
 
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ABSTRACT
Regional mechanisms present themselves not only as instruments for converging efforts to achieve common goals but also to curb and address identified threats. By focusing on the development of the Association of Southeast Asian Nations (ASEAN), it was possible to see an instrument that has been successful both in promoting the globalization advocated by its member states and in strengthening and expanding the bloc's trade, investment, and extra-regional relations. However, in recent decades, there have been increasing changes and power struggles in the international dynamic that present new challenges to regional projects and efforts. Among the disputing actors pressuring Southeast Asia in its decision-making and cooperation are China and Japan. Through a qualitative and documentary analysis, this article aims to evaluate the trajectory of ASEAN, seeking to understand its performance and direction in a world in transition, marked by disputes and changes, with a focus on the conduct of China and Japan towards the bloc and their impacts both on the level of regional interaction and on its international projection. It is argued that, despite being perceived as a discussion forum with limited capacities for action, ASEAN has been successful in ensuring the autonomy and legitimacy of the bloc and its member states—even in the face of a world in transition.
Keywords: ASEAN; China; Japan.
As Trajetórias Paralelas Da Cooperação Internacional Para O Desenvolvimento E Do Regionalismo Latino-Americano: Uma Análise Comparativa Histórico-Estrutural | The Parallel Trajectories Of International Cooperation For Development And Latin American Regionalism: A Historical-Structural Comparative Analysis
Authors: Vieira da Silva Rafael
Published: January 2025

RESUMO
O artigo examina a trajetória desde a segunda metade do século XX até a contemporaneidade do regionalismo latino-americano e a compara com a trajetória da Cooperação Internacional para o Desenvolvimento no mesmo período. São delineados em contornos gerais três períodos do regionalismo latino-americano: o regionalismo fechado (ou desenvolvimentista), o regionalismo aberto (ou neoliberal) e o regionalismo pós-neoliberal ou (pós-hegemônico). Esses recortes são comparados com três momentos-chave da história da cooperação internacional: a proposta da Nova Ordem Econômica Internacional, a ascensão do discurso neoliberal no Sistema Internacional de Cooperação para o Desenvolvimento e a consolidação dos BRICS como articuladores de uma nova cooperação Sul-Sul no século XXI. Utiliza-se a análise histórica comparativa em conjunto com a perspectiva teórica neogramsciana e o materialismo histórico transnacional associado a esta. Por meio do conceito abrangente de controle associado a cada um dos recortes avaliados, argumenta-se que há uma convergência dialética entre as trajetórias da integração regional latino-americana e da cooperação internacional, indicando que as limitações de ambas têm a mesma fonte estrutural: o padrão de acumulação de capital dominante.
Palavras-chave: Regionalismo latino-americano; Cooperação Internacional para o Desenvolvimento; Materialismo histórico transnacional.
 
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ABSTRACT
This article examines the trajectory of Latin American regionalism from the second half of the 20th century to the present and compares it with the trajectory of International Cooperation for Development during the same period. Three general periods of Latin American regionalism are outlined: closed (or developmentalist) regionalism, open (or neoliberal) regionalism, and post-neoliberal (or post-hegemonic) regionalism. These periods are compared with three key moments in the history of international cooperation: the proposal of the New International Economic Order, the rise of neoliberal discourse in the international development cooperation System, and the consolidation of the BRICS as articulators of a new South-South cooperation in the 21st century. The comparative historical analysis is used in conjunction with the neo-Gramscian theoretical perspective and the transnational historical materialism associated with it. Through the comprehensive concept of control associated with each evaluated period, it is argued that there is a dialectical convergence between the trajectories of Latin American regional integration and international cooperation, indicating that the limitations of both have the same structural source: the dominant pattern of capital accumulation.
Keywords: Latin American regionalismo; International Cooperation for Development; transnational historical materialism.