bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longevity-associated BPIFB4 gene counteracts the inflammatory signaling
Authors: Cattaneo Monica , Baragetti Andrea , Malovini Alberto , Ciaglia Elena , Lopardo Valentina , Olmastroni Elena , Casula Manuela , Ciacci Carolina , Catapano Alberico L. , Puca Annibale A. 
Published: March 2024

Abstract
Background
Increased levels of pro-inflammatory proteins in plasma can be detected in older individuals and associate with the so called chronic low-grade inflammation, which contributes to a faster progression of aged-related cardiovascular (CV) diseases, including frailty, neurodegeneration, gastro-intestinal diseases and disorders reflected by alterations in the composition of gut microbiota. However, successful genetic programme of long-living individuals alters the trajectory of the ageing process, by promoting an efficient immune response that can counterbalance deleterious effects of inflammation and the CV complications. This is the case of BPIFB4 gene in which, homozygosity for a four single-nucleotide polymorphism (SNP) haplotype, the Longevity-Associated Variant (LAV) correlates with prolonged health span and reduced risk of CV complications and inflammation. The relation between LAV-BPIFB4 and inflammation has been proven in different experimental models, here we hypothesized that also human homozygous carriers of LAV-BPIFB4 gene may experience a lower inflammatory burden as detected by plasma proteomics that could explain their favourable CV risk trajectory over time. Moreover, we explored the therapeutic effects of LAV-BPIFB4 in inflammatory disease and monolayer model of intestinal barrier.

Results
We used high-throughput proteomic approach to explore the profiles of circulating proteins from 591 baseline participants selected from the PLIC cohort according to the BPIFB4 genotype to identify the signatures and differences of BPIFB4 genotypes useful for health and disease management. The observational analysis identified a panel of differentially expressed circulating proteins between the homozygous LAV-BPIFB4 carriers and the other alternative BPIFB4 genotypes highlighting in the latter ones a higher grade of immune-inflammatory markers. Moreover, in vitro studies performed on intestinal epithelial organs from inflammatory bowel disease (IBD) patients and monolayer model of intestinal barrier demonstrated the benefit of LAV-BPIFB4 treatment.

Conclusions
Homozygosity for LAV-BPIFB4 results in the attenuation of inflammation in PLIC cohort and IBD patients providing preliminary evidences for its therapeutic use in inflammatory disorders that need to be further characterized and confirmed by independent studies.
Suffix sorting via matching statistics
Authors: Lipták Zsuzsanna , Masillo Francesco , Puglisi Simon J. 
Published: March 2024

AbstractWe introduce a new algorithm for constructing the generalized suffix array of a collection of highly similar strings. As a first step, we construct a compressed representation of the matching statistics of the collection with respect to a reference string. We then use this data structure to distribute suffixes into a partial order, and subsequently to speed up suffix comparisons to complete the generalized suffix array. Our experimental evidence with a prototype implementation (a tool we call ) shows that on string collections with highly similar strings we can construct the suffix array in time competitive with or faster than the fastest available methods. Along the way, we describe a heuristic for fast computation of the matching statistics of two strings, which may be of independent interest.
Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case
Authors: Pfeifer Mateja , Rehder Helga , Gerykova Bujalkova Maria , Bartsch Christine , Fritz Barbara , Knopp Cordula , Beckers Björn , Dohle Frank , Meyer-Wittkopf Matthias , Axt-Fliedner Roland , Beribisky Alexander V. , Hofer Manuel , Laccone Franco , Schoner Katharina 
Published: March 2024

Abstract
Background
In this study we aimed to describe the morphological and pathogenetic differences between tracheal agenesis and tracheal atresia, which are not clearly distinguished from each other in the literature, and to contribute thereby to the understanding and management of these conditions. Both tracheal agenesis and tracheal atresia represent rare disorders of still unknown aetiology that cannot be detected by prenatal ultrasound. If the affected foetuses survive until birth these conditions result in respiratory failure and in futile attempts to rescue the infant’s life.

Results
Autopsies and genetic analyses, including singleton or trio exome sequencing, were performed on five neonates/foetuses with tracheal agenesis and three foetuses with tracheal atresia. Tracheal agenesis was characterized by absence of the sublaryngeal trachea and presence of a bronchooesophageal fistula and by pulmonary isomerism and occurred as an isolated malformation complex or as part of a VACTERL association. Special findings were an additional so-called ‘pig bronchus’ and a first case of tracheal agenesis with sirenomelia. Tracheal atresia presenting with partial obliteration of its lumen and persistence of a fibromuscular streak resulted in CHAOS. This condition was associated with normal lung lobulation and single, non-VACTERL type malformations. Trio ES revealed a novel variant of MAPK11 in one tracheal agenesis case. Its involvement in tracheooesophageal malformation is herein discussed, but remains hypothetical.

Conclusion
Tracheal agenesis and tracheal atresia represent different disease entities in terms of morphology, pathogenesis and accompanying anomalies due to a primary developmental and secondary disruptive possibly vascular disturbance, respectively.
COLQ-Congenital myasthenic syndrome in an Iranian cohort: the clinical and genetics spectrum
Authors: Hesami Omid , Ramezani Mahtab , Ghasemi Aida , Fatehi Farzad , Okhovat Ali Asghar , Ziaadini Bentolhoda , Kariminejad Ariana , Nafissi Shahriar 
Published: March 2024

Abstract
Background
Congenital myasthenic syndrome (CMS) is a group of neuromuscular disorders caused by abnormal signal transmission at the motor endplate. Mutations in the collagen-like tail subunit gene (COLQ) of acetylcholinesterase are responsible for recessive forms of synaptic congenital myasthenic syndromes with end plate acetylcholinesterase deficiency. Clinical presentation includes ptosis, ophthalmoparesis, and progressive weakness with onset at birth or early infancy.

Methods
We followed 26 patients with COLQ-CMS over a mean period of 9 years (ranging from 3 to 213 months) and reported their clinical features, electrophysiologic findings, genetic characteristics, and therapeutic management.

Results
In our population, the onset of symptoms ranged from birth to 15 years. Delayed developmental motor milestones were detected in 13 patients ($$\sim$$ 52%), and the most common presenting signs were ptosis, ophthalmoparesis, and limb weakness. Sluggish pupils were seen in 8 ($$\sim$$ 30%) patients. All patients who underwent electrophysiologic study showed a significant decremental response (> 10%) following low-frequency repetitive nerve stimulation. Moreover, double compound muscle action potential was evident in 18 patients ($$\sim$$ 75%). We detected 14 variants (eight novel variants), including six missense, three frameshift, three nonsense, one synonymous and one copy number variation (CNV), in the COLQ gene. There was no benefit from esterase inhibitor treatment, while treatment with ephedrine and salbutamol was objectively efficient in all cases.

Conclusion
Despite the rarity of the disease, our findings provide valuable information for understanding the clinical and electrophysiological features as well as the genetic characterization and response to the treatment of COLQ-CMS.
Liquid–liquid phase separation of H3K27me3 reader BP1 regulates transcriptional repression
Authors: Tang Guangfei , Xia Haoxue , Huang Yufei , Guo Yuanwen , Chen Yun , Ma Zhonghua , Liu Wende 
Published: March 2024

AbstractBackgroundBromo-adjacent homology-plant homeodomain domain containing protein 1 (BP1) is a reader of histone post-translational modifications in fungi. BP1 recognizes trimethylation of lysine 27 in histone H3 (H3K27me3), an epigenetic hallmark of gene silencing. However, whether and how BP1 participates in transcriptional repression remains poorly understood.ResultsWe report that BP1 forms phase-separated liquid condensates to modulate its biological function inFusarium graminearum. Deletion assays reveal that intrinsically disordered region 2 (IDR2) of BP1 mediates its liquid–liquid phase separation. The phase separation of BP1 is indispensable for its interaction with suppressor of Zeste 12, a component of polycomb repressive complex 2. Furthermore, IDR2 deletion abolishes BP1-H3K27me3 binding and alleviates the transcriptional repression of secondary metabolism-related genes, especially deoxynivalenol mycotoxin biosynthesis genes.ConclusionsBP1 maintains transcriptional repression by forming liquid–liquid phase-separated condensates, expanding our understanding of the relationship between post-translational modifications and liquid–liquid phase separation.
The scientific rationale and study protocol for the DPP3, Angiotensin II, and Renin Kinetics in Sepsis (DARK-Sepsis) randomized controlled trial: serum biomarkers to predict response to angiotensin II versus standard-of-care vasopressor therapy in the treatment of septic shock
Authors: Teixeira J. Pedro , Perez Ingles David , Barton Jordan B. , Dean James T. , Garcia Pablo , Kunkel Susan J. , Sarangarm Preeyaporn , Weiss Natalie K. , Schaich Christopher L. , Busse Laurence W. , Nielsen Nathan D. 
Published: March 2024

Abstract
Background
Data to support the use of specific vasopressors in septic shock are limited. Since angiotensin II (AT2) was approved by the Food and Drug Administration in 2017, multiple mechanistically distinct vasopressors are available to treat septic shock, but minimal data exist regarding which patients are most likely to benefit from each agent. Renin and dipeptidyl peptidase 3 (DPP3) are components of the renin–angiotensin–aldosterone system which have been shown to outperform lactate in predicting sepsis prognosis, and preliminary data suggest they could prove useful as biomarkers to guide AT2 use in septic shock.

Methods
The DARK-Sepsis trial is an investigator-initiated industry-funded, open-label, single-center randomized controlled trial of the use of AT2 versus standard of care (SOC) vasopressor therapy in patients admitted to the intensive care unit (ICU) with vasodilatory shock requiring norepinephrine ≥ 0.1 mcg/kg/min. In both groups, a series of renin and DPP3 levels will be obtained over the first 24 h of treatment with AT2 or SOC. The primary study outcome will be the ability of these biomarkers to predict response to vasopressor therapy, as measured by change in total norepinephrine equivalent dose of vasopressors at 3 h post-drug initiation or the equivalent timepoint in the SOC arm. To determine if the ability to predict vasopressor response is specific to AT2 therapy, the primary analysis will be the ability of baseline renin and DPP3 levels to predict vasopressor response adjusted for treatment arm (AT2 versus control) and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes will include rates of acute kidney injury, need for mechanical ventilation and kidney replacement therapy, lengths of stay in the ICU and hospital, ICU and hospital mortality, and rates of prespecified adverse events.

Discussion
With an armamentarium of mechanistically distinct vasopressor agents now available, sub-phenotyping patients using biomarkers has the potential to improve septic shock outcomes by enabling treatment of the correct patient with the correct vasopressor at the correct time. However, this approach requires validation in a large definitive multicenter trial. The data generated through the DARK-Sepsis study will prove crucial to the optimal design and patient enrichment of such a pivotal trial.

Trial registration
ClinicalTrials.gov NCT05824767. Registered on April 24, 2023.
Trial Forge Guidance 4: a guideline for reporting the results of randomised Studies Within A Trial (SWATs)
Authors: Arundel C. E. , Clark L. K. , Parker A. , Beard D. , Coleman E. , Cooper C. , Devane D. , Eldridge S. , Galvin S. , Gillies K. , Hewitt C. E. , Sutton C. , Torgerson D. J. , Treweek S. ,   the PROMETHEUS GROUP
Published: March 2024

Abstract
Background
Evidence to support decisions on trial processes is minimal. One way to generate this evidence is to use a Study Within A Trial (SWAT) to test trial processes or explore methodological uncertainties. SWAT evidence relies on replication to ensure sufficient power and broad applicability of findings. Prompt reporting is therefore essential; however, SWAT publications are often the first to be abandoned in the face of other time pressures. Reporting guidance for embedded methodology trials does exist but is not widely used. We sought therefore to build on these guidelines to develop a straightforward, concise reporting standard, which remains adherent to the CONSORT guideline.

Methods
An iterative process was used to develop the guideline. This included initial meetings with key stakeholders, development of an initial guideline, pilot testing of draft guidelines, further iteration and pilot testing, and finalisation of the guideline.

Results
We developed a reporting guideline applicable to randomised SWATs, including replications of previous evaluations. The guideline follows the Consolidated Standards for Reporting Trials (CONSORT) statement and provides example text to ensure ease and clarity of reporting across all domains.

Conclusions
The SWAT reporting guideline will aid authors, reviewers, and journal editors to produce and review clear, structured reports of randomised SWATs, whilst also adhering to the CONSORT guideline.

Trial registration
EQUATOR Network – Guidelines Under Development (https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/#SWAT). Registered on 25 March 2021.
The efficacy and safety of deucravacitinib compared to methotrexate, in patients with vulvar lichen planus who have failed topical therapy with potent corticosteroids: a study protocol for a single-centre double-blinded randomised controlled trial
Authors: Wijaya Marlene , Fischer Gayle , Saunderson Rebecca Bronwyn 
Published: March 2024

Abstract
Background
Vulvar lichen planus (VLP) is a chronic vulvar dermatosis that is difficult to treat and can severely impair quality of life in the absence of adequate treatment. There is a lack of high-quality evidence to direct therapy for VLP. This randomised controlled trial will be the first double-blinded study comparing systemic treatments in VLP and aims to investigate the safety and efficacy of deucravacitinib compared to methotrexate, in patients with VLP who have failed treatment with potent topical corticosteroids.

Methods
A total of 116 women aged ≥ 18 years with moderate to severe VLP (Genital Erosive Lichen Planus (GELP) score ≥ 5) will be recruited. All participants will initially be treated with Diprosone® OV daily, and their outcome will be assessed using the GELP score. At 8 weeks’ follow-up, responders (GELP < 5) will be continued on Diprosone® OV. Non-responders (GELP ≥ 5) will be randomised 1:1 in a blinded fashion to receive (i) methotrexate 10 mg weekly + placebo tablet twice daily + folic acid 5 mg weekly or (ii) deucravacitinib 6 mg twice daily + placebo tablet weekly + folic acid 5 mg weekly. The primary endpoint is the difference in the mean change of GELP scores from baseline to week 32 between deucravacitinib and methotrexate groups.

Discussion
High-quality evidence guiding the management of women with VLP is lacking. Once completed, this will be the first double-blinded RCT to compare systemic treatments in VLP. The results of this study will provide valuable, high-quality data to guide second-line therapy options for VLP that is recalcitrant to potent topical corticosteroids.

Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12623000682640. Registered on 26 June 2023.
Diversity of Culicoides in the middle belt of Ghana with Implications on the transmission of Mansonella perstans; a molecular approach
Authors: Debrah Linda Batsa , Arthur Joseph F. , Yeboah Augustine , Owusu Dorcas O. , Adankwah Ernest , Acheampong Isaac , Minadzi Difery , Lamptey Millicent , Opoku Vera Serwaa , Aniagyei Wilfred , Vivekanandan Monika M. , Abass Mohammed K. , Gawusu Amidu , Wanji Samuel , Debrah Alexander Y. , Jacobsen Marc , Phillips Richard O. 
Published: March 2024

Abstract
Background
Culicoides, also known as biting midges, carry pathogens which include Mansonella perstans. Mansonella perstans is a nematode parasite implicated in a number of disease outcomes. Even though a high prevalence of about 75% M. perstans infection has been recorded in some communities in the middle belt of Ghana, and a wide diversity of Culicoides species has been identified, the exact Culicoides species transmitting M. perstans in Ghana has not yet been deciphered. This study therefore aimed at assessing the species diversity of Culicoides and their role in the transmission of M. perstans in the middle belt of Ghana.

Methods
Culicoides species were sampled from 11 communities in the Asante-Akim North and Sene West districts in the middle belt of Ghana. Centre for Disease Control (CDC) UV light traps, as well as human bait (i.e. human landing catch and engorged catch) methods were used to assess the species abundance and diversity of Culicoides in the study communities in the wet and dry season. A colorimetric Loop-Mediated Isothermal Amplification (LAMP) assay was performed to assess the vector competence of the various Culicoides species.

Results
A total of 4810 Culicoides from 6 species were sampled. These included Culicoides inornatipennis, C. milnei, C. schultzei, C. grahamii, C. neavei, and C. imicola. Culicoides imicola was the most abundant species (56%) followed by C. grahamii (16%). Light traps sampled the most diverse species (6 species). Human landing catch and engorged catch methods identified three anthropophilic species, C. grahamii, C. milnei, and C. inornatipennis, with C. grahamii being the most anthropophilic with a peak biting time between the hours of 5 p.m. to 6 p.m. Generally, there was relatively higher species abundance in the wet than dry season. LAMP assay identified C. grahamii as the potential vector for M. perstans transmission in the middle belt of Ghana.

Conclusions
For the first time, we have demonstrated that C. grahamii is the potential competent vector for M. perstans transmission in the middle belt of Ghana. It is more abundant in the rainy season and has a peak biting time between the hours of 5 and 6 p.m.

Graphical Abstract
Genetic characterization of schistosome species from cattle in Côte d’Ivoire
Authors: Giovanoli Evack Jennifer , Kouadio Jules N. , Achi Louise Y. , Bonfoh Bassirou , N’Goran Eliézer K. , Zinsstag Jakob , Utzinger Jürg , Balmer Oliver 
Published: March 2024

Abstract
Background
Schistosomiasis is a water-based parasitic disease that affects humans, livestock and wild animals. While considerable resources are dedicated to the surveillance, disease mapping, control and elimination of human schistosomiasis, this is not the case for livestock schistosomiasis. Indeed, there are important data and knowledge gaps concerning the species present, population genetic diversity, infection prevalence, morbidity and economic impact. This study aimed to identify circulating schistosome species in cattle across Côte d’Ivoire and to investigate their population diversity and structuring.

Methods
Overall, 400 adult schistosomes were collected from slaughtered cattle at six sites across Côte d’Ivoire. Additionally, 114 miracidia were collected from live cattle at one site: Ferkessédougou, in the northern part of Côte d’Ivoire. DNA from all specimens was extracted and the cox1 and ITS1/2 regions amplified and analysed to confirm species. The genetic diversity and structuring of the schistosome populations were investigated using 12 microsatellite markers.

Results
All adult schistosomes and miracidia presented Schistosoma bovis mitochondrial cox1 profile. Nuclear ITS1/2 data were obtained from 101 adult schistosomes and four miracidia, all of which presented an S. bovis profile. Genetic diversity indices revealed a deficiency of heterozygotes and signals of inbreeding across all sites, while structure analyses displayed little geographic structuring and differentiation. Cattle in Côte d’Ivoire thus appear to be mono-species infected with S. bovis. Hybrids of Schistosoma haematobium × S. bovis have not been identified in this study. Cattle schistosomes appear to be panmictic across the country.

Conclusions
Our results contribute to a deeper understanding of schistosome populations in Ivorian cattle and emphasize a One Health approach of joint human and animal surveillance and prevention and control programmes for schistosomiasis.

Graphical Abstract
Remnant cholesterol, iron status and diabetes mellitus: a dose–response relationship and mediation analysis
Authors: Hu Xiangming , Lin Yan , Appleton Allison A. , Wang Weimian , Yu Bingyan , Zhou Langping , Li Guang , Zhou Yingling , Ou Yanqiu , Dong Haojian 
Published: March 2024

Abstract
Background
Remnant cholesterol (RC) is recognized as a risk factor for diabetes mellitus (DM). Although iron status has been shown to be associated with cholesterol metabolism and DM, the association between RC, iron status, and DM remains unclear. We examined the relationship between RC and iron status and investigated the role of iron status in the association between RC and DM.

Methods
A total of 7308 patients were enrolled from the China Health and Nutrition Survey. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Iron status was assessed as serum ferritin (SF) and total body iron (TBI). DM was ascertained by self-reported physician diagnosis and/or antidiabetic drug use and/or fasting plasma glucose ≥ 126 mg/dL and/or glycated haemoglobin ≥ 6.5%. General linear models were used to evaluate the relationships between RC and iron status. Restricted cubic splines were used to assess the association between RC and DM. Mediation analysis was used to clarified the mediating role of iron status in the association between the RC and DM.

Results
The average age of the participants was 50.6 (standard deviation = 15.1) years. Higher RC was significantly associated with increased SF (β = 73.14, SE = 3.75, 95% confidence interval [CI] 65.79–80.49) and TBI (β = 1.61, SE = 0.08, 95% CI 1.44–1.78). J-shape relationships were found in the association between RC levels with DM, as well as iron status with DM. Significant indirect effects of SF and TBI in the association between RC and DM were found, with the index mediated at 9.58% and 6.37%, respectively.

Conclusions
RC has a dose–response relationship with iron status. The association between RC and DM was mediated in part by iron status. Future studies are needed to confirm these findings and further clarify the underlying mechanism.