bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin C activates young LINE-1 elements in mouse embryonic stem cells via H3K9me3 demethylation
Authors: Cheng Kevin C. L. , Frost Jennifer M. , Sánchez-Luque Francisco J. , García-Canãdas Marta , Taylor Darren , Yang Wan R. , Irayanar Branavy , Sampath Swetha , Patani Hemalvi , Agger Karl , Helin Kristian , Ficz Gabriella , Burns Kathleen H. , Ewing Adam , García-Pérez José L. , Branco Miguel R. 
Published: October 2023

AbstractBackgroundVitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells.ResultsHere we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism.ConclusionVitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function.
Memantine administration prevented chorea movement in Huntington’s disease: a case report
Authors: Saigoh Kazumasa , Hirano Makito , Mitsui Yoshiyuki , Oda Itsuki , Ikegawa Atsuko , Samukawa Makoto , Yoshikawa Keisuke , Yamagishi Yuko , Kusunoki Susumu , Nagai Yoshitaka 
Published: October 2023

Abstract
Background
Huntington’s disease is an autosomal dominant inherited disorder characterized by personality changes (such as irritability and restlessness) and psychotic symptoms (such as hallucinations and delusions). When the personality changes become noticeable, involuntary movements (chorea) also develop. The disease is caused by the CAG repeat expansion in the coding region of the HTT gene, and the diagnosis is based on the presence of this expansion. However, there is currently no effective treatment for the progression of Huntington’s disease and its involuntary motor symptoms. Herein, we present a case in which memantine was effective in treating the chorea movements of Huntington’s disease.

Case presentation
A 75-year-old Japanese woman presented to the hospital with involuntary movements of Huntington’s disease that began when she was 73 years old. In a cerebral blood flow test (N-isopropyl-p-iodoamphetamine–single-photon emission computed tomography), decreased blood flow was observed in the precuneus (anterior wedge) and posterior cingulate gyrus. Usually, such areas of decreased blood flow are observed in patients with Alzheimer’s-type dementia. So, we administered memantine for Alzheimer’s-type dementia, and this treatment suppressed the involuntary movements of Huntington’s disease, and the symptoms progressed slowly for 7 years after the onset of senility. In contrast, her brother died of complications of pneumonia during the course of Huntington’s disease.

Conclusions
We recorded changes in parameters such as the results of the N-isopropyl-p-iodoamphetamine–single-photon emission computed tomography and gait videos over 7 years. Treatment with memantine prevented the chorea movement and the progression of Huntington’s disease. We believe this record will provide clinicians with valuable information in diagnosing and treating Huntington’s disease.
Immunomodulatory effects of inactivated Ligilactobacillus salivarius CECT 9609 on respiratory epithelial cells
Authors: Bravo María , Diaz-Chamorro Selene , Garrido-Jiménez Sergio , Blanco Javier , Simón Irene , García Waldo , Montero María José , Gonçalves Pilar , Martínez Carlos , Cumplido-Laso Guadalupe , Benítez Dixan Agustín , Mulero-Navarro Sonia , Centeno Francisco , Román Ángel Carlos , Fernández-Llario Pedro , Cerrato Rosario , Carvajal-González José María 
Published: October 2023

AbstractThe microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives.
Limiting temperatures of embryo growth and seed germination of Fraxinus excelsior L. (Oleaceae): a threshold model approach
Authors: Wawrzyniak Mikołaj Krzysztof , Ley-López Juan Manuel , Martins João Paulo Rodrigues , Chmielarz Paweł 
Published: October 2023

Abstract
Key message
We have examined thermal control for embryo growth and seed germination in European ash. Using historical data (span of 36 years) of embryo index in matured seeds, we showed that maturation is not influenced by the annual average temperature. Secondary dormancy in ash’s seeds is easily induced, and the thermal window for both embryo growth and seed germination was between 10 and 20 °C.

Context
Seed germination plays a crucial role in establishing plant communities. Ash seeds are characterized by deep morphophysiological dormancy, usually overcome by 32 weeks of stratification. Observed climate changes might disrupt ash’s thermal window for embryo growth and seed germination. Thus, proper examination of seed adaptability can be important for forest management.

Aims
We investigated the effect of temperature on the embryo index (ratio between embryo and seed length) as well as embryo growth and germination of European ash (Fraxinus excelsior L.) seeds under different thermal conditions.

Methods
We used seeds collected at the same site in Poland between 1985 and 2021 to first analyze the influence of the growing season on the initial embryo index in mature seeds. Subsequently, we examined embryo growth and germination of seeds at constant temperatures of 3°, 10°, 15°, 20°, 25°, and 30 °C from seeds collected in 2021. Using the modeled rate of embryo growth and germination, we predicted the cardinal temperatures for those processes in ash seeds.

Results
The embryo index of ash seeds varied; however, there was no relationship between the index and year of seed collection. The base temperature for embryo growth was 1.4 ± 1.1 °C, with a ceiling temperature of 29.9 ± 2.0 °C and an optimal temperature of 15.7 ± 0.3 °C. The base temperature for germination was at − 1.8 ± 0.3 °C. Due to the induction of secondary dormancy, the ceiling temperature of germination was impossible to establish.

Conclusions
The initial embryo index of mature ash seeds seems to be an individual trait and was not affected by local average annual temperatures. The most effective temperature ranges for embryo growth and germination were similar, however narrow (between 10 and 15 °C). Temperatures above 20 °C inducted secondary dormancy, hampering embryo growth as well as germination. Such a narrow thermal window for embryo growth can potentially act as a limiting factor for the natural regeneration of ash seeds.
Reich–Krasnoselskii-type fixed point results with applications in integral equations
Authors: Azam Akbar , Mehmood Nayyar , Ahmad Niaz , Ali Faryad 
Published: October 2023

AbstractIn this paper, motivated by Reich contraction and tool of measure of noncompactness, some generalizations of Reich, Kannan, Darbo, Sadovskii, and Krasnoselskii type fixed point results are presented by considering a pair of maps A, B on a nonempty closed subset M of a Banach space X into X. The existence of a solution to the equation $Ax+Bx=x$
A
x
+
B
x
=
x
, where A is k-set contractive and B is a generalized Reich contraction, is established. As applications, it is established that the main result of this paper can be applied to learn conditions under which a solution of a nonlinear integral equation exists. Further we explain this phenomenon with the help of a practical example to approximate such solutions by using fixed point techniques. The graphs of exact and approximate solutions are also given to attract readers for further research activities.
Molecular diagnosis of Chagas disease: a systematic review and meta-analysis
Authors: Pascual-Vázquez Guillermo , Alonso-Sardón Montserrat , Rodríguez-Alonso Beatriz , Pardo-Lledías Javier , Romero Alegría Angela , Fernández-Soto Pedro , Muñoz Bellido Juan Luis , Muro Antonio , Belhassen-García Moncef 
Published: October 2023

Abstract
Background
The complexity of the Chagas disease and its phases is impossible to have a unique test for both phases and a lot of different epidemiological scenarios. Currently, serology is the reference standard technique; occasionally, results are inconclusive, and a different diagnostic technique is needed. Some guidelines recommend molecular testing. A systematic review and meta-analysis of available molecular tools/techniques for the diagnosis of Chagas disease was performed to measure their heterogeneity and efficacy in detecting Trypanosoma cruzi infection in blood samples.

Methods
A systematic review was conducted up to July 27, 2022, including studies published in international databases. Inclusion and exclusion criteria were defined to select eligible studies. Data were extracted and presented according to PRISMA 2020 guidelines. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). A random-effects model was used to calculate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Forest plots and a summary of the receiving operating characteristics (SROC) curves displayed the outcomes. Heterogeneity was determined by I2 and Tau2 statistics and P values. Funnel plots and Deek's test were used to assess publication bias. A quantitative meta-analysis of the different outcomes in the two different clinical phases was performed.

Results
We identified 858 records and selected 32 papers. Studies pertained to endemic countries and nonendemic areas with adult and paediatric populations. The sample sizes ranged from 17 to 708 patients. There were no concerns regarding the risk of bias and applicability of all included studies. A positive and nonsignificant correlation coefficient (S = 0.020; P = 0.992) was obtained in the set of studies that evaluated diagnostic tests in the acute phase population (ACD). A positive and significant correlation coefficient (S = 0.597; P < 0.000) was obtained in the case of studies performed in the chronic phase population (CCD). This resulted in high heterogeneity between studies, with the master mix origin and guanidine addition representing significant sources.

Interpretation/Conclusions and relevance
The results described in this meta-analysis (qualitative and quantitative analyses) do not allow the selection of the optimal protocol of molecular method for the study of Trypanosoma cruzi infection in any of its phases, among other reasons due to the complexity of this infection. Continuous analysis and optimization of the different molecular techniques is crucial to implement this efficient diagnosis in endemic areas.
Human rabies encephalomyelitis in the background of rabies outbreak in animals in Gelephu, Bhutan, 2023: a case report
Authors: Dorji Thinley , Lamichaney Jeewanath , Gyaltshen Choeda , Lungten Lungten , Dhakal Guru Prasad , Dorjee Sithar , Mynak Mimi Lhamu 
Published: October 2023

Abstract
Background
Rabies continues to pose significant public health challenges in many developing countries including Bhutan. A probable case of rabies was admitted to our hospital and its reporting led to the uncovering of an outbreak in domestic and wild animals. We discuss the challenges in the diagnosis and management of rabies in a resource-limited setting.

Case presentation
A 35-year-old male presented with intermittent fever, bilateral lower limb weakness that was rapidly progressive, urinary incontinence with episodes of palpitations and sweating. He had sustained a Category III bite on the right lower thigh with four bite marks, inflicted by a stray dog. He had received post-exposure prophylaxis with intra-dermal anti-rabies vaccine. On initial examination, the patient was in distress but cooperative for the interview. He had pulse rate ranging from 60 to 100/min with episodes of diaphoresis and palpitations, but with normal capillary blood glucose. In the lower limb, the muscle power was zero with absent tendon reflexes in the lower limb and impaired abdominal reflex below T10 level. He had hyperaesthesia below T8, hydrophobia, aerophobia and photophobia. He had multiple spontaneous fasciculations in both the thighs and right deltoid and these later involved the intercostal muscles, neck and face muscles. He had altered sensorium and desaturation for which he required mechanical ventilation. Polymerase chain reaction for rabies virus was negative in cerebrospinal fluid and saliva. Rabies virus neutralizing antibody was negative in cerebrospinal fluid but had high titres in the serum. He received Human Rabies Immunoglobulin after admission. He was managed in the intensive care unit and died 23 days later. After this case was notified, a rapid response team was deployed in the field, and uncovered rabies outbreak in animals in the locality.

Conclusions
This case called for a serious evaluation of the country’s efforts in achieving zero rabies deaths by 2030. The management of this case identified several critical areas of context-specific interventions in Bhutan. There is also an urgent need to improve diagnostic capabilities at the national reference laboratory and enhance the technical competencies of healthcare workers in the management of dog bite cases.

Graphical Abstract
Is there any influence of biodynamic preparation 501 on the physiological activity of grape leaves cv. Cesanese d’Affile?
Authors: Pettinelli Stefano , Buzzi Laura , Ceccantoni Brunella , Muleo Rosario , Bianchi Alessandro , Brunori Elena , Mencarelli Fabio 
Published: October 2023

Abstract
Background
Biodynamic agriculture is a management approach that aims to reduce the reliance on agrochemicals for production by emphasizing the use of specific natural preparations. A 2-year field trial spanning 2019–2020 was conducted in an established vineyard (Vitis vinifera L., cv. Cesanese d’Affile) to elucidate the impact of the cow horn silica biodynamic preparation (BD-501) on leaf vine physiology, potential resistance via chitinase activity, and analysis of secondary metabolites. The vineyard under biodynamic management was divided into two plots: one treated with BD-501 (BD-501) and the other untreated (BD). Throughout the vine growth season, measurements of carotenoid and chlorophyll levels, polyphenols, and chitinase activity were taken around key phenological phases (BBCH scale). During the ripening phase, a fluorometer was employed to assess chlorophyll fluorescence in the leaves.

Results
Leaves treated with BD-501 exhibited elevated concentrations of polyphenols and increased chitinase activity during the later phenological phases. In contrast, the untreated BD samples demonstrated high values primarily in the central phase of the observation period but not consistently throughout. At the time of harvest, chlorophyll concentration and quantum yield exhibited no statistically significant differences. BD-501 triggered a distinct response in terms of potential defense mechanisms (elevated polyphenols and chitinase activity) during the veraison phase. However, conversely, lower levels of chlorophylls and carotenoids were observed.

Conclusions
Nevertheless, a further round of experimental work is required to thoroughly comprehend the regulatory mechanisms behind this adaptive response and to ascertain the efficacy of BD-501.

Graphical Abstract
Encouraging diversity in family engagement in research: Reflections on the development of knowledge translation tools
Authors: Mah Janet W. T. , Nickerson Katie 
Published: October 2023

Abstract
Background
Family engagement in research is crucial to generating relevant, impactful, and meaningful priorities and outcomes. Although there has been increased awareness and value for patient-oriented research, most patient partners in North America are from Western, educated, industrialized, rich and democratic societies. Encouraging underserviced and marginalized populations to join the partnerships is important. This project demonstrates the development of two knowledge translation tools created to encourage diversity in patient-family and researcher partnerships.

Case study
Our diverse cross-Canadian team embodies the family-researcher partnership as it consists of two research personnel from non-Western origins with immigrant experiences, a parent with lived experience, and a project director. All group members have experience in the field of mental health and neurodevelopmental conditions. Four infographics were created: 3 patient-oriented ones (in English, Chinese, and Farsi) and 1 researcher-targeted one. Content for the infographics were generated to address common barriers to patient engagement identified from literature reviews, as well as key concepts discussed during the McMaster University Continuing Education Family Engagement in Research Certificate Course sponsored by CanChild & Kids Brain Health Network. Peer consultations helped to improve the infographics to be more culturally sensitive and appealing. The patient-oriented infographic presents concise bullet points about 5 main topics: (1) what is research, (2) reasons to join, (3) your role, (4) talking to researchers, and (5) how to join. The researcher-targeted infographic presents concise bullet points about 4 topics: 1) why team up with diverse patient partners, (2) ways to partner, (3) how to connect, and (4) talking to diverse partners.

Conclusion
Infographics were co-designed to encourage diversity in family engagement in research. Lessons learned throughout the project include barriers encountered (e.g., team collaboration considerations, design limitations) and strategies that facilitated the project (e.g., online collaboration platforms). Future directions include translations into other languages, increased dissemination across agencies, and evaluating the effectiveness of the infographic tools.
Self-microemulsifying system of an ethanolic extract of Heliopsis longipes root for enhanced solubility and release of affinin
Authors: Marrero-Morfa Dailenys , Ibarra-Alvarado César , Luna-Vázquez Francisco J. , Estévez Miriam , Ledesma Eremy Miranda , Rojas-Molina Alejandra , Quirino-Barreda Carlos T. 
Published: October 2023

AbstractSelf-microemulsifying or self-nanoemulsifying drug delivery systems (SMEDDS/SNEDDS) are well known to improve the dissolution and increase the oral bioavailability of hydrophobic drugs, including herbal extracts. Organic extracts of Heliopsis longipes root and affinin, its main component, induce a vasodilator effect; however, they are poorly water soluble and therefore are difficult to administer and dose by the oral route. This research aimed to develop, through pseudo-ternary phase diagrams, a self-microemulsifying system prepared from an ethanolic extract of H. longipes root (HL-SMDS). In addition, the optimized lipid-based formulation was characterized and its in vitro gastrointestinal simulated dissolution was determined. The formulation composed of Transcutol, 55% (solubilizer); Tween80/PG, 10% (surfactant/co-solvent); Labrasol, 35% (surfactant); and the herbal extract was selected as optimal and identified as a SMEDDS, since when coming into contact with water, it forms a micro-emulsion with droplet sizes less than 100 nm. The stability tests showed that HL-SMDS remained stable over time under extreme conditions. Furthermore, the amount of affinin released from HL-SMDS at pH 1 and 6.8 was higher than that of the ethanolic extract from H. longipes root. These results indicate that HL-SMDS is a novel alternative to improve the aqueous solubility and therefore the oral bioavailability of the ethanolic extract of H. longipes root.
Validation of brain parenchyma sonography as a marker of neurodegeneration in multiple sclerosis
Authors: Kishk Nirmeen A. , Hamdy Sherif , Amer Hanan , Shalaby Nevin M. , Othman Alshimaa S. , Mohammad Mohammad Edrees 
Published: October 2023

Abstract
Background
Multiple sclerosis (MS) is widely known to cause brain atrophy due to neurodegeneration. Neuroimaging investigations revealed a direct link between brain atrophy detected by MRI and impairment. Transcranial sonography is a safe, feasible and cost-effective imaging technique. In this study, we aimed to validate B-mode transcranial sonography (TCS) as a marker of neurodegeneration in MS. This study is the first study directed to set cut-off point for brain parenchyma measurement in Egyptian population. An observational, case–control study, conducted on 125 subjects; divided into 2 groups: first group, 71 healthy volunteers and patients’ group (54 patients) with relapsing–remitting multiple sclerosis (RRMS). All studied subjects were assessed using B-mode TCS. Transcranial sonography findings were categorized into: first, assessment of brain atrophy parameters by measuring diameter (cm) of third ventricle and both frontal horns of lateral ventricles. Then, the echogenicity of thalamus and brainstem structures (substantia nigra (SN), red nucleus) planimetric surface area (cm2) were assessed along with their abnormal echogenicity (cm2), while brainstem raphe was assessed semi-quantitatively for its echogenicity (intact or interrupted).

Results
Quantitative measures of brain atrophy: in normal control group the third ventricle diameter mean was 0.2 cm (± 0.08), right and left frontal horn diameter were 0.3 cm (± 0.13) and 0.28 cm (± 0.1), respectively, brain atrophy parameters could differentiate between MS patients and normal control group as a statistically significant (p< 0.001) larger ventricular diameter was found in MS patients. On the other hand, assessment of brain stem structures and thalamus showed no statistical significance between MS patients and normal control except in surface area of both red nuclei.

Conclusions
Brain parenchymal sonography may be used as a tool in assessment of neurodegeneration in MS patients.