bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis
Authors: Sun Dandan , Guo Kun , Liu Naixin , Li Yilin , Li Yuansheng , Hu Yan , Li Shanshan , Fu Zhe , Wang Yinglei , Wu Yutong , Zhang Yingxuan , Li Jiayi , Li Chao , Wang Zhuo , Kang Zijian , Sun Jun , Wang Ying , Yang Xinwang 
Published: November 2023

Abstract

Background
Wound management of diabetic foot ulcers (DFUs) is a complex and challenging task, and existing strategies fail to meet clinical needs. Therefore, it is important to develop novel drug candidates and discover new therapeutic targets. However, reports on peptides as molecular probes for resolving issues related to DFUs remain rare. This study utilized peptide RL-QN15 as an exogenous molecular probe to investigate the underlying mechanism of endogenous non-coding RNA in DFU wound healing. The aim was to generate novel insights for the clinical management of DFUs and identify potential drug targets.

Methods
We investigated the wound-healing efficiency of peptide RL-QN15 under diabetic conditions using in vitro and in vivo experimental models. RNA sequencing, in vitro transfection, quantitative real-time polymerase chain reaction, western blotting, dual luciferase reporter gene detection, in vitro cell scratches, and cell proliferation and migration assays were performed to explore the potential mechanism underlying the promoting effects of RL-QN15 on DFU repair.

Results
Peptide RL-QN15 enhanced the migration and proliferation of human immortalized keratinocytes (HaCaT cells) in a high-glucose environment and accelerated wound healing in a DFU rat model. Based on results from RNA sequencing, we defined a new microRNA (miR-4482-3p) related to the promotion of wound healing. The bioactivity of miR-4482-3p was verified by inhibiting and overexpressing miR-4482-3p. Inhibition of miR-4482-3p enhanced the migration and proliferation ability of HaCaT cells as well as the expression of vascular endothelial growth factor B (VEGFB). RL-QN15 also promoted the migration and proliferation ability of HaCaT cells, and VEGFB expression was mediated via inhibition of miR-4482-3p expression by the p38 mitogen-activated protein kinase (p38MAPK) and smad3 signaling pathways.

Conclusions
RL-QN15 is an effective molecule for the treatment of DFUs, with the underlying mechanism related to the inhibition of miR-4482-3p expression via the p38MAPK and smad3 signaling pathways, ultimately promoting re-epithelialization, angiogenesis and wound healing. This study provides a theoretical basis for the clinical application of RL-QN15 as a molecular probe in promoting DFU wound healing.
RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression
Authors: Knop Katarzyna , Gomez-Moreira Carolina , Galloway Alison , Ditsova Dimitrinka , Cowling Victoria H 
Published: November 2023

Abstract
On T cell activation, upregulation of gene expression produces the protein required for the differentiation and proliferation of effector cell populations. RAM (RNMT-Activating Mini protein/RAMAC/Fam103a1), the cofactor of the RNA cap methyltransferase RNMT (RNA guanosine N-7 cap methyltransferase), is upregulated following activation. Formation of the RNA cap protects RNA during synthesis and guides RNA processing and translation. Using conditional gene deletion, we found that Ram expression stabilizes RNMT protein in T cells and is required for its upregulation on activation. When the Ram gene is deleted in naïve T cells, there are major impacts on activation-induced RNA cap formation and gene expression. Activated T cell proliferation is dependent on increased ribosome production; in Ram knockout T cells, activation-induced expression of ribosomal protein genes and snoRNAs is most severely reduced. Consistent with these changes, Ram deletion resulted in reduced protein synthesis, and reduced growth and proliferation of CD4 T cells. Deletion of Ram results in a similar but milder phenotype to Rnmt deletion, supporting the role of RAM as a RNMT cofactor.
Infective endocarditis caused by Paenibacillus thiaminolyticus: a case report and review of literature
Authors: Depta Filip , Pažitný Martin , Trebišovský Michal , Maďarová Tatiana , Deptová Jana 
Published: November 2023

Abstract

Background
Paenibacillus constitutes a genus of gram-positive, facultatively anaerobic, rod-shaped bacteria that act as potentially opportunistic pathogens. With only a few documented case studies to date, Paenibacillus species are rarely the cause of a disease in humans.

Case summary
We report a case involving a 64-year-old male with known mild mitral regurgitation, who presented with fever and dyspnoea. Initially treated with empirical antibiotics, his blood cultures cultivated Paenibacillus thiaminolyticus, a previously unreported cause of endocarditis. Transoesophageal echocardiography demonstrated vegetations on the both leaflets of mitral valve along with severe mitral regurgitation, thus confirming a diagnosis of endocarditis. The patient was referred for cardiac surgery; however, the procedure was delayed due to complications related to a known hepatic cyst and additionally contraction of COVID-19 infection. The patient subsequently underwent mitral valve replacement without complications.

Discussion
Because of its rarity, guidelines to recommend specific antibiotics to treat Paenibacillus infective endocarditis are absent. To confirm the pathogen, molecular methods such as mass spectrometry or 16S rRNA sequencing are required. Early targeted antibiotic therapy and cardiac surgery are warranted to achieve good clinical outcomes.
A case series of patients with filamin-C truncating variants attending a specialized cardiac genetic clinic
Authors: Hespe Sophie , Isbister Julia C , Duflou Johan , Puranik Raj , Bagnall Richard D , Semsarian Christopher , Gray Belinda , Ingles Jodie 
Published: November 2023

Abstract

Background
FLNC encodes for filamin-C, a protein expressed in Z-discs of cardiac and skeletal muscle, involved in intracellular signalling and mechanical stabilization. Variants can cause diverse phenotypes with skeletal (myofibrillar or distal myopathy) and/or cardiac (hypertrophic, restrictive, and arrhythmogenic cardiomyopathies) manifestations. Truncating variants have recently been implicated in arrhythmogenic cardiomyopathy (ACM) without skeletal disease.

Case summary
Retrospective review of medical records, including cardiac investigations, was performed for families attending a specialized clinic with a FLNC truncating variant (FLNCtv). Variants were classified according to accepted variant interpretation criteria. Of seven families identified, six had primary cardiac phenotypes with one nonsense and five frameshift variants (nonsense-mediated decay competent) identified. One family had no cardiac phenotype, with a pathogenic variant (p.Arg2467Alafs*62) identified as secondary genetic finding. Of the six with cardiac phenotypes, proband age at diagnosis ranged 27–35 years (four females). Five families experienced sudden cardiac death (SCD) of a young relative (age range: 30–43 years), and one patient listed for cardiac transplant. Left ventricular (LV) ejection fraction ranged from 13 to 46%, with LV fibrosis (late gadolinium enhancement) on cardiac imaging or on postmortem histology seen in three families. Two families had one genotype-positive/phenotype-negative relative.

Discussion
The FLNCtv causes a left-sided ACM phenotype with a high risk of severe cardiac outcomes including end-stage heart failure and SCD. Incomplete penetrance is observed with implications for reporting secondary genetic findings.
Smashing Statues: Re-evaluating Iconoclasm in History
Authors: Dwyer Philip , Orr Nikolas 
Published: November 2023

Abstract
In 2020, as statues around the world were pulled down, intellectuals scrambled to make sense of the phenomenon. Veteran voices joined new experts from varied disciplines in contributing to the established field of iconoclasm studies, adding to the ongoing debates around history, memory, politics and public monuments. This seemingly global movement was fuelled by, and indeed fuelled, debates among the broader public about the meaning of statues in public life, and whether colonial statues of white men with dubious political and moral histories should remain in place or be removed from sight. The movement also met with a certain amount of backlash from conservative commentators who positioned themselves as the champions of Empire and a particular version of history in Britain, and from right-wing groups attempting to defend what they saw as an attack on white culture. The debate around statues, in other words, quickly became politically fraught. The authors ask what four recent works on iconoclasm add to an already extensive literature. What do they bring to the debates around history, memory, politics and public monuments? Two of the books (Thompson and Tunzelmann) are aimed at a broader readership, while the other two (Freedberg and Tugendhaft) are more specialised in their approach. We conclude that what is missing from these works is a global and comparative approach to the destruction of racist statues that also considers struggles against colonialism in national independence and Indigenous resistance movements throughout the modern and early modern periods.
A short tool to screen self-care preparedness: cross-sectional study in general practice
Authors: Mikkonen Ulla , Tusa Nina , Sinikallio Sanna , Kautiainen Hannu , Mäntyselkä Pekka 
Published: November 2023

Abstract

Background
Self-care is crucial in the prevention and treatment of chronic diseases. It is important to identify patients who need support with self-care.

Objectives
This study introduces a self-care preparedness index (SCPI) and examines its associations with health-related quality of life (HRQoL) and other outcomes.

Methods
A cross-sectional study of adults (n = 301) with hypertension, coronary artery disease, or diabetes in primary health care. Based on the self-care questionnaire, SCPI was formed. A higher SCPI value indicated better self-care preparedness. We examined correlations and a hypothesis of linearity between SCPI and HRQoL (15D), depressive symptoms (BDI), patient activation (PAM), and health-related outcomes (self-rated health, life satisfaction, physical activity, body mass index [BMI], waist, low-density lipoprotein). Exploratory factor analysis was used to test the construct validity of SCPI.

Results
A total of 293 patients with a mean age of 68 (54.3% women) were included in the analysis. BDI, BMI, and waist had a negative linear trend with SCPI. Self-rated health, physical activity, patient activity, and life satisfaction had a positive linear trend with SCPI. SCPI correlated with HRQoL (r = 0.31 [95% CI: 0.20 to 0.41]). Exploratory factor analysis of the SCPI scores revealed 3 factors explaining 82% of the total variance.

Conclusions
SCPI seems to identify individuals with different levels of preparedness in self-care. This provides means for health care providers to individualize the levels of support and counselling. SCPI seems to be a promising tool in primary health care but needs further validation before use in large scale trials or clinical practice.
kGWASflow: a modular, flexible, and reproducible Snakemake workflow for k-mers-based GWAS
Authors: Corut Adnan Kivanc , Wallace Jason G 
Published: November 2023

Abstract
Genome-wide association studies (GWAS) have been widely used to identify genetic variation associated with complex traits. Despite its success and popularity, the traditional GWAS approach comes with a variety of limitations. For this reason, newer methods for GWAS have been developed, including the use of pan-genomes instead of a reference genome and the utilization of markers beyond single-nucleotide polymorphisms, such as structural variations and k-mers. The k-mers-based GWAS approach has especially gained attention from researchers in recent years. However, these new methodologies can be complicated and challenging to implement. Here, we present kGWASflow, a modular, user-friendly, and scalable workflow to perform GWAS using k-mers. We adopted an existing kmersGWAS method into an easier and more accessible workflow using management tools like Snakemake and Conda and eliminated the challenges caused by missing dependencies and version conflicts. kGWASflow increases the reproducibility of the kmersGWAS method by automating each step with Snakemake and using containerization tools like Docker. The workflow encompasses supplemental components such as quality control, read-trimming procedures, and generating summary statistics. kGWASflow also offers post-GWAS analysis options to identify the genomic location and context of trait-associated k-mers. kGWASflow can be applied to any organism and requires minimal programming skills. kGWASflow is freely available on GitHub (https://github.com/akcorut/kGWASflow) and Bioconda (https://anaconda.org/bioconda/kgwasflow).
The use of bivalve shells by the shellback crabsHypoconcha arcuataStimpson, 1858 andH. parasitica(Linnaeus, 1763) (Brachyura: Dromiidae: Hypoconchinae) in southeastern Brazil
Authors: Garcia-Bento Maria A , Zara Fernando J , Paschoal Lucas R P 
Published: November 2023

AbstractWe describe the use of abraded bivalve shells by the shellback crabs Hypoconcha arcuataStimpson, 1858 and H. parasitica (Linnaeus, 1763) in southeastern Brazil. Shells from four species of bivalves were associated with the crabs: Eucallista purpurata (Lamarck, 1818), Chionopsis crenata (Gmelin, 1791), and Tivela zonaria (Lamarck, 1818) (Veneridae), and, most frequently (50%), Dallocardia delicatula (E.A. Smith, 1915) (Cardiidae). This was the first documented record of shellback crabs using valves of veneriid bivalves, as well as the first report of a crab-shell association for Hypoconcha in the South Atlantic Ocean. The relationship between the increase in size of shellback crabs and the size of the chosen shell was discussed.
Climate Constitutionalism as a Foundation for Climate Litigation in Latin America
Authors: de Carvalho Délton Winter , da Rosa Rafaela Santos Martins 
Published: November 2023

Abstract
Climate emergency is one of the facets shaping the current stage of ecological imbalance and requires action to be taken. The trend to address conflicts involving climate change by legal means is clearly on the rise, and the article argues that this calls for an evolving constitutional dialogue on human rights. The article examines the phenomenon, particularly in Latin American countries, explaining how past development of constitutions in the region, for all its precarious effectiveness, has already served to consolidate a path demanding judicial review in matters affecting human rights of constitutional stature. It argues that this path is being pursued by the ongoing climate litigation in Latin America. Based on case discussions, the article demonstrates how compliance with the Paris Agreement has been assimilated as a commitment to constitutional protection of human rights in the region, and how this process must deepen, taking into account regional vulnerabilities and future developments, in order to strengthen the fundamental human right not only to mitigation, but also to adaptation and equitable transitions.
Seasonal roost characteristics and fall behavior of coastal populations of Northern Myotis (Myotis septentrionalis)
Authors: Hoff Samantha , Pendergast Casey , Johnson Luanne , Olson Elizabeth , O’Dell Danielle , Dowling Zara R , Gorman Katherine M , Herzog Carl , Turner Wendy C 
Published: November 2023

Abstract
Temperate bats exhibit seasonal and sex differences in resource selection and activity patterns that are influenced by ambient conditions. During fall, individuals face energetic trade-offs as they make choices relating to migration, mating, and hibernation that may diverge for populations throughout their range. However, research has largely focused on the summer maternity and winter hibernation seasons, whereas the prehibernation period remains comparatively understudied. Northern Myotis (Myotis septentrionalis) have experienced precipitous population declines from white-nose syndrome (WNS), leading to their protected status in the United States and Canada. Therefore, understanding their ecology throughout the year is paramount to inform conservation. We compared seasonal roosts and documented fall behaviors between study sites and sexes on 3 islands: Long Island (New York), Martha’s Vineyard, and Nantucket Island (Massachusetts). Between 2017 and 2020, we radio-tracked 54 individuals to analyze activity patterns and characterize fall roosts to compare with previously known summer roosts. Summer tree roosts were of smaller diameter, later stages of decay, and lower canopy closure than those used in fall. Both sexes selected trees of similar diameter and decay stage during fall. Anthropogenic roost use was documented in both seasons but use of anthropogenic structures was greater during fall and increased as the season progressed. Bats made short inter-roost movements with males traveling greater distances than females on average. Activity occurred until late November, with males exhibiting a longer active period than females. We tracked 23% of tagged bats to local hibernacula in subterranean anthropogenic structures, the majority of which were crawlspaces underneath houses. Use of anthropogenic structures for roosts and hibernacula may facilitate survival of this species in coastal regions despite the presence of WNS infections. Timing of restrictions on forest management activities for bat conservation may be mismatched based on prehibernation activity observed in these coastal populations, and the conservation of habitat surrounding anthropogenic roosts or hibernacula may be warranted if the structures themselves cannot be protected.
Sex and age mediate the effects of rapid environmental change for a forest carnivore, the Fisher (Pekania pennanti)
Authors: Kuntze Corbin C , Peery M Zachariah , Green Rebecca E , Purcell Kathryn L , Pauli Jonathan N 
Published: November 2023

Abstract
Rapid environmental changes—in climate, land use, and biotic interactions—are accelerating species extinctions and extirpations globally. Identifying drivers that threaten populations is essential for conservation yet can be difficult given the variable nature of the response of an organism to biotic and abiotic stressors. We analyzed a long-term monitoring data set to explore demographic responses of fishers (Pekania pennanti) to rapid environmental change in the southern Sierra Nevada, California, United States. Fisher survival was sensitive to both biotic and abiotic factors, although the strength and direction of these effects were ultimately mediated by age and sex. Specifically, male survival was lower among young individuals and decreased with increasing temperatures and fungi consumption. Female survival was resilient to age effects and diet but increased with greater forest heterogeneity and decreased with increasing temperatures and snow depth. Our findings suggest that continued climate change will likely have consequences for fishers through both incremental stressors and extreme weather events, but increasing forest heterogeneity may help to buffer against the impacts of such change. Further, we illustrate the importance of disentangling the effects of intrinsic and extrinsic factors on survival, especially among species with distinct sexual or ontogenetic differences. As global drivers of environmental change intensify in strength and frequency, understanding these complex relationships will allow practitioners to best manage for population persistence and habitat resilience concurrently.
Adaptive hybrid control design for comparative clinical trials with historical control data
Authors: Guo Beibei , Laird Glen , Song Yang , Chen Josh , Yuan Ying 
Published: November 2023

AbstractWe propose an adaptive hybrid control causal (AHCC) design to leverage historical control data to reduce the sample size demanded by standard randomised controlled trials (RCT). Under the causal inference framework, we define the causal estimand of the average treatment effect and derive the corresponding estimator based on the trial data and historical control data. The AHCC design takes a multistage or group sequential approach. The number of patients randomised to the concurrent control is adaptively adjusted based on the amount of information borrowed from the historical control data. At each stage, based on the interim data, the contribution of the historical control data, quantified by the effective sample size, is updated and used to determine the randomisation ratio between the treatment and control arms for the next stage, with the goal to resemble a standard RCT upon the completion of the trial. Simulation studies show that the AHCC design has desirable operating characteristics. For example, it saves on sample size when substantial information can be borrowed from the historical control, and it maintains power when little information can be borrowed from the historical control.
LTBK-09. RESULTS OF BMX-HGG STUDY: A MULTI-INSTITUTIONAL, RANDOMIZED PHASE 2 CLINICAL TRIAL OF CONCURRENT CHEMORADIATION WITH OR WITHOUT BMX-001 IN PATIENTS WITH NEWLY DIAGNOSED HIGH GRADE GLIOMA
Authors: Peters Katherine , Cohen Adam , Butowski Nicholas , Villano John , Mendez Joe , Giglio Pierre , McGranahan Tresa , Zhang Chi , Smeltzer Jacob , Raza Shahzad , Nabors Burt , Lobbous Mina , Herndon James , Buckley Evan , MacLeod David , Penchev Sara , Silberstein David , Batinic-Haberle Ines , Spasojevic Ivan , Gad Shayne , Radoff David , Barboriak Daniel , Crapo James 
Published: November 2023

Abstract

BACKGROUND
Standard treatment for high grade glioma (HGG) remains neurosurgical resection followed by concurrent radiation therapy (RT) and temozolomide (TMZ). Overall survival (OS) for GBM is roughly 12-16 months. RT is associated with cognitive and quality of life (QoL) impairments. Advances are needed to improve OS while mitigating injury to the normal brain. BMX-001 is a novel metalloporphyrin that radiosensitizes cancer cells and radioprotects normal tissue.

METHODS
This multi-institutional, open-label, phase 2 trial randomized newly diagnosed HGG patients to receive RT/TMZ with or without BMX-001 (NCT02655601). Both arms received 6 weeks RT/TMZ (75 mg/m2). BMX-001 was administered as a loading dose of 28 mg sc before RT, followed by 14 mg twice weekly for 8 weeks. Randomization was stratified by tumor grade and institution. Key eligibility criteria include histologically confirmed HGG, age ≥ 18 years, and KPS ≥ 70%. The primary endpoint was OS. Key secondary/exploratory outcomes included cognition, QoL, and white matter integrity using advanced imaging. OS evaluation occurred after 84 deaths when a 1-tailed logrank test (α=0.2) had 90% power to detect a hazard ratio of 0.63. Two interim analyses and a final analysis were conducted using an O’Brien-Fleming stopping boundary.

RESULTS
Of the 160 patients randomized, 72.5% had GBM, and 62.5% were male. Analyses focused on 145 patients who completed RT/TMZ (74 with BMX-001, 71 without BMX-001). Median OS of BMX-001+RT/TMZ group (31.3 [95% CI, 21.6, not reached] months) was longer than RT/TMZ group (24.7 [95% CI, 19.6-32.6] months), HR=0.735; p=0.079 (significant at the predefined α level). Common toxicities (Grade 1-2) attributed to BMX-001 were injection site reactions (64), tachycardia (24), and pruritus (17) with no related Grade 4-5. Diffusion tensor MR imaging indicated mitigation of dose-related white matter damage in BMX-001+RT/TMZ group.

CONCLUSIONS
BMX-001 is safe, and there is improved OS in HGG patients receiving BMX-001.