bluuebunny/crossref_metadata_2025_split huggingface dataset:
High prevalence and genetic diversity of
Treponema paraluisleporidarum
isolates in European lagomorphs
Authors: Knauf Sascha , Hisgen Linda , Ågren Erik O. , Barlow Alexander M. , Faehndrich Marcus , Voigt Ulrich , Fischer Luisa , Grillová Linda , Hallmaier-Wacker Luisa K. , Kik Marja J. L. , Klink Jana C. , Křenová Jitka , Lavazza Antonio , Lüert Simone , Nováková Markéta , Čejková Darina , Pacioni Carlo , Trogu Tiziana , Šmajs David , Roos Christian 
Published: December 2023

ABSTRACT

The bacterium
Treponema paraluisleporidarum
causes syphilis in lagomorphs. In a set of 1,095 samples from four species—European brown hare, mountain hare, Corsican hare, and European rabbit—we tested for infection and genotyped the strains that infect wild lagomorphs. Samples originate from Sweden, the Netherlands, the United Kingdom, Germany, the Czech Republic, and Italy. The phylogenetic analyses of two informative gene targets (
tp0488
and
tp0548
) showed high genetic diversity among the lagomorph-infecting treponemes. More specifically, we found a high number of nucleotide variants and various short repeat units in the
tp0548
locus that have not been described for human syphilis and primate yaws causing
Treponema pallidum
. While the functional aspect of these short repeat units remains subject to ongoing investigations, it likely enables the pathogen to better survive in its lagomorph host. Our data did not support any geographic clustering, which is equally reflected in the host population genetics as shown by mitochondrial genome data corresponding to the sampled lagomorph populations. This is unexpected and in contrast with what has been shown for nonhuman primate infection with
T. pallidum
. In the future, the combination of multi-locus sequence typing and whole genome data from modern and ancient samples from a wide geographic range and multiple lagomorph species will contribute to a better understanding of the epidemiology and evolutionary path of lagomorph-infecting treponemes. In conclusion, our current study demonstrates widespread infection and a high genetic variation of the syphilis-causing pathogen in a higher number of positively PCR-tested European lagomorphs (
n
= 302/1,095).

IMPORTANCE

Syphilis is an ancient disease of humans and lagomorphs caused by two distinct but genetically closely related bacteria (>98% sequence identity based on the whole genome) of the genus
Treponema
. While human syphilis is well studied, little is known about the disease in the lagomorph host. Yet, comparative studies are needed to understand mechanisms in host–pathogen coevolution in treponematoses. Importantly,
Treponema paraluisleporidarum
–infected hare populations provide ample opportunity to study the syphilis-causing pathogen in a naturally infected model population without antibiotic treatment, data that cannot be obtained from syphilis infection in humans. We provide data on genetic diversity and are able to highlight various types of repetitions in one of the two hypervariable regions at the
tp0548
locus that have not been described in the human syphilis-causing sister bacterium
Treponema pallidum
subsp.
pallidum
.
A. castellanii
and
P. aeruginosa
mutually exacerbate damage to corneal cells during coinfection
Authors: Chen Chun-Hsien , Liao Chen-Chieh , Wang Yu-Jen , Huang Fu-Chin , Lin Wei-Chen 
Published: December 2023

ABSTRACT

Microorganisms that are involved in microbial invasion keratitis infiltrate the cornea and cause eye pain. Despite the administration of antimicrobial treatment, patients with amoebic keratitis develop bacterial coinfections.
Pseudomonas aeruginosa
infection accounts for 50% of the reported bacterial coinfections in these patients. However, the role of pathogenic bacteria in amoeba-induced corneal damage remains unclear. In our current study, we conducted assays to examine cytopathic effects and observed increased corneal cell damage in the group with secondary
P. aeruginosa
infections. Imaging revealed that the presence of
A. castellanii
enhanced the accumulation of
P. aeruginosa
in areas of cell monolayer leakage. We demonstrated that treatment of
P. aeruginosa
with amoeba-soluble antigen resulted in higher adhesion ability, increased biofilm formation, and more severe corneal cell damage. Overall, this research significantly contributes to our understanding of the risk of
P. aeruginosa
coinfection in the progression of Acanthamoeba keratitis.

IMPORTANCE

At the National Cheng Kung University Hospital, numerous cases of amoebic keratitis had been identified with concurrent bacterial infections. Among these bacterial coinfections,
Pseudomonas aeruginosa
accounted for 50% of the reported cases. However, the impact of pathogenic bacteria on amoeba-induced corneal damage remains unclear. In our study, we successfully demonstrated that
P. aeruginosa
accumulated on the
Acanthamoeba castellanii
surface and caused more severe corneal damage. We also indicated that the exposure of
P. aeruginosa
to amoeba-soluble antigens enhanced its adhesion ability, promoted biofilm formation, and led to more severe corneal cell damage. These findings significantly contributed to our understanding of the risk associated with
P. aeruginosa
coinfection in the progression of amoeba keratitis.
Mycobiomes of two distinct clades of ambrosia gall midges (Diptera: Cecidomyiidae) are species-specific in larvae but similar in nutritive mycelia
Authors: Pyszko Petr , Šigutová Hana , Kolařík Miroslav , Kostovčík Martin , Ševčík Jan , Šigut Martin , Višňovská Denisa , Drozd Pavel 
Published: December 2023

ABSTRACT

Ambrosia gall midges (AGMs) are mostly host plant-specific. In their galls, they harbor fungal symbionts on which they feed. Therefore, they represent unique steps in the evolution of the gall-forming Cecidomyiidae (Diptera). Gall-associated fungi have been studied predominantly by cultivations, and potential larval endosymbionts have been completely neglected. Using ITS2 rRNA metabarcoding, we characterized the mycobiomes of individual gall compartments (gall surface, gall interior, and larva) of six species from two phylogenetically separated tribes (Asphondyliini and Lasiopterini). Compared to the gall surface and interior, the larvae harbored significantly higher fungal richness and taxonomic diversity, and a larger pool of indicator taxa. Larval mycobiome composition was more species-specific; however, the fungal genera
Fusarium
,
Filobasidium
,
Tilletiopsis
,
Alternaria
, and
Aureobasidium
were indicator taxa shared among species. Overall, the larvae harbored 29% of unique taxa that can play a functional role in the host (e.g., initiation of gall development or selection of the mycelia composition). The mycobiome of the gall interior was assembled least stochastically, and its composition was the least species-specific, being dominated by
Botryosphaeria dothidea
(except for
Lasioptera arundinis
). Therefore, the interior of ambrosia galls offers a unique environment that supports the growth of similar fungi, regardless of the host plant species and the phylogenetic distance between the AGM tribes. Our study illustrates a range of fungal microorganisms indicative of individual gall compartments, but their potential function, especially in larvae, remains to be solved.

IMPORTANCE

Ambrosia gall midges are endophagous insect herbivores whose larvae live enclosed within a single gall for their entire development period. They may exhibit phytomycetophagy, a remarkable feeding mode that involves the consumption of plant biomass and mycelia of their cultivated gall symbionts. Thus, AGMs are ideal model organisms for studying the role of microorganisms in the evolution of host specificity in insects. However, compared to other fungus-farming insects, insect–fungus mutualism in AGMs has been neglected. Our study is the first to use DNA metabarcoding to characterize the complete mycobiome of the entire system of the gall-forming insects as we profiled gall surfaces, nutritive mycelia, and larvae. Interestingly, larval mycobiomes were significantly different from their nutritive mycelia, although
Botryosphaeria dothidea
dominated the nutritive mycelia, regardless of the evolutionary separation of the tribes studied. Therefore, we confirmed a long-time hypothesized paradigm for the important evolutionary association of this fungus with AGMs.
Chronic kidney disease and its predictors among highly active antiretroviral therapy naïve and experienced HIV-infected individuals at the selected hospitals, Southwest Ethiopia: a comparative cross-sectional study
Authors: Belay Alemayehu Sayih , Manaye Gizachew Ayele , Kebede Kindie Mitiku , Abateneh Dejene Derseh , Debebe Shibihon 
Published: December 2023

ObjectiveThis study aimed to determine the prevalence of chronic kidney disease (CKD) and its predictors among highly active antiretroviral therapy (HAART) naïve and experienced HIV-infected individuals.Method and analysisHospital-based comparative cross-sectional study design was used at Mizan-Tepi University Teaching Hospital, Bonga General Hospital and Tepi General Hospital. A total of 616 naïve and experienced HIV-infected individuals participated. A systematic random sampling and consecutive sampling methods were applied to select the HAART experienced and naïve HIV-infected individuals, respectively. Descriptive statistics were used for all study variables. Independent t-test and logistic regression analysis were performed to compare the mean between naïve and experienced patients and to identify its predictor variables considering a <0.05 and 95% CI, respectively.ResultsA total of 616 HIV-positive respondents were enrolled in this study. The prevalence of CKD was 41 (29.3%) of 140 and 78 (16.4%) of 476 HAART-naïve and HAART-experienced HIV patients, respectively. Rural residency, being anaemic, being hypertensive, having had a family history of kidney disease and stage IV current WHO) clinical stage were independent risk factors of CKD among naïve HIV patients, whereas, rural residency, utilisation of drinking water per day below the recommended amount, being anaemic, being hypertensive, stage IV current WHO clinical stage and obesity were predictors of CKD among experienced HIV patients. Statistically significant difference was observed between HAART naïve and HAART experienced participants with regard to the mean glomerular filtration rate level (t=−3.987, 95% CI −18.29 to −6.22).ConclusionCKD was higher among HAART-naïve than HAART-experienced study participants. Therefore, early initiation of antiretroviral therapy (ART) drugs, modification of lifestyles to decrease obesity and early detection and treatment of comorbidities such as anaemia and hypertension may have profound effects in reducing CKD and increasing patients’ quality of life.
HER2 and HLA-A*02 dual CAR-T cells utilize LOH in a NOT logic gate to address on-target off-tumor toxicity
Authors: Bassan David , Weinberger Leehee , Yi Jason , Kim Tanya , Weist Michael R , Adams Gregor B , Foord Orit , Chaim Neta , Tabak Sarit , Bujanover Nir , Lopesco Yael , Vucci Kristina , Schnair Caitlin , Levy-Knafo Limor , Kendall Richard L , Calzone Frank J , Sharbi-Yunger Adi 
Published: December 2023

BackgroundOne of the major challenges in chimeric antigen receptor (CAR)-T cell therapy for solid tumors is the potential for on-target off-tumor toxicity due to the expression of CAR tumor antigens in essential tissues and organs. Here, we describe a dual CAR NOT gate incorporating an inhibitory CAR (iCAR) recognizing HLA-A*02 (“A2”) that enables effective treatment with a potent HER2 activating CAR (aCAR) in the context of A2 loss of heterozygosity (LOH).MethodsA CAR-T cell screen was conducted to identify inhibitory domains derived from natural immune receptors (iDomains) to be used in a NOT gate, to kill A2−HER2+lung cancer cell lines but spare A2+HER2+lung cancer cell-lines with high specificity. The extensive analysis of lead candidates included T-cell activation and killing, assays of reversibility and durability in sequential challenges, target cell specificity in mixed 3D spheroids and 2D cultures, and the characterization of CAR expression level and cell-trafficking.ResultsA leukocyte immunoglobulin-like receptor B1 (LIR1) iDomain iCAR was identified as most effective in regulating the cytotoxicity of a second generation HER2 aCAR. Target transfer experiments demonstrated that the ‘on’ and ‘off’ cell state of the LIR1 NOT gate CAR-T cell is both durable and reversible. Protection required iCAR signaling and was associated with reduced aCAR and iCAR surface expression. iCAR regulation was sufficient to generate high target specificity in a 3D adjacent spheroid assay designed to model the interface between clonal A2 LOH foci and normal tissue. However, we observed significant bystander killing of A2+cells in admix culture through aCAR dependent and independent mechanisms. LIR1 NOT gate CAR-T cells conferred protection against H1703-A2+tumors and high efficacy against H1703-A2−tumors in-vivo. We observed that the iCAR is inactive in A2+donors due to cis-binding, but Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) knockout of HLA-A fully restored iCAR activity.ConclusionsWe have preclinically validated an iCAR NOT gate technology broadly applicable for targeting HER2 expression in the context of A2 LOH. This approach is designed to prevent off tumor toxicity while allowing highly potent antitumor activity.
Multimorbidity of cardiovascular disease subtypes in a prospective cohort of 1.2 million UK women
Authors: Suh Jae Won , Floud Sarah , Reeves Gillian K , Cairns Benjamin J , Wright F Lucy 
Published: December 2023

ObjectiveCardiovascular multimorbidity (CVM) is the co-occurrence of multiple cardiovascular disease subtypes (CVDs) in one person. Because common patterns and incidence of CVM are not well-described, particularly in women, we conducted a descriptive study of CVM in the Million Women Study, a large population-based cohort of women.MethodsUK women aged 50–64 years were followed up using hospital admissions and mortality records for an average of 19 years. CVM was defined as having ≥2 of 19 selected CVDs. The age-specific cumulative incidence of CVM between age 60 and 80 years was estimated. The numbers and proportions of individual, pairs and other combinations of CVDs that comprised incident CVM were calculated. For each individual CVD subtype, age-standardised proportions of the counts of other co-occurring CVDs were estimated.ResultsThe age-specific likelihood of having CVM nearly doubled every 5 years between age 60 and 80 years. Among 1.2 million women without CVD at study baseline, 16% (n=196 651) had incident CVM by the end of follow-up. Around half of all women with CVM had a diagnosis of ischaemic heart disease (n=102 536) or atrial fibrillation (n=96 022), almost a third had heart failure (n=72 186) and a fifth had stroke (n=40 442). The pair of CVDs with the highest age-adjusted incidence was ischaemic heart disease and atrial fibrillation (18.95 per 10 000 person-years). Over 60% of individuals with any given CVD subtype also had other CVDs, after age standardisation.ConclusionsCVM is common. The majority of women with any specific CVD subtype eventually develop at least one other. Clinical and public health guidelines for CVD management should acknowledge this high likelihood of CVM.
Adult congenital heart disease training in Europe: current status, disparities and potential solutions
Authors: McMahon Colin J , Voges Inga , Jenkins Petra , Brida Margarita , van der Bosch Annemien E , Dellborg Mikael , Heying Ruth , Stein Jörg I , Georgiev Borislav , Mesihovic-Dinarevic Senka , Prokšelj Katja , Oskarsson Gylfi , Frogoudaki Alexandra , Karagöz Tevfik , Jossif Antonis , Doros Gabriela , Nielsen Dorte , Jalanko Mikko , Sanchez Perez Inmaculada , Alvares Sílvia , Estensen Mette-Elise , Petropoulos Andreas , Tagen Raili , Gumbienė Lina , Michel-Behnke Ina , Olejnik Peter , Clift Paul F , Sendzikaite Skaiste , Albert-Brotons Dimpna C , Rhodes Mark , Pitkänen Olli , Bassareo Pier Paolo , Gatzoulis Michael A , Walsh Kevin , Milanesi Ornella , Ladouceur Magalie , Chessa Massimo , Budts Werner 
Published: December 2023

ObjectivesThis study aimed to determine the status of training of adult congenital heart disease (ACHD) cardiologists in Europe.MethodsA questionnaire was sent to ACHD cardiologists from 34 European countries.ResultsRepresentatives from 31 of 34 countries (91%) responded. ACHD cardiology was recognised by the respective ministry of Health in two countries (7%) as a subspecialty. Two countries (7%) have formally recognised ACHD training programmes, 15 (48%) have informal (neither accredited nor certified) training and 14 (45%) have very limited or no programme. Twenty-five countries (81%) described training ACHD doctors ‘on the job’. The median number of ACHD centres per country was 4 (range 0–28), median number of ACHD surgical centres was 3 (0–26) and the median number of ACHD training centres was 2 (range 0–28). An established exit examination in ACHD was conducted in only one country (3%) and formal certification provided by two countries (7%). ACHD cardiologist number versus gross domestic product Pearson correlation coefficient=0.789 (p<0.001).ConclusionFormal or accredited training in ACHD is rare among European countries. Many countries have very limited or no training and resort to ‘train people on the job’. Few countries provide either an exit examination or certification. Efforts to harmonise training and establish standards in exit examination and certification may improve training and consequently promote the alignment of high-quality patient care.
Long-lasting improvement of refractory antisynthetase syndrome with tocilizumab: a report of two cases
Authors: Baumann Benvenuti Fleur , Dudler Jean 
Published: December 2023

No standardised and universal treatment is available for antisynthetase syndrome. In particular, there is an unmet need for a single efficient treatment acting on its various manifestations, including interstitial lung disease, myositis and polyarthritis.We describe the cases of two patients with multiple and severe manifestations, including joint, muscular and lung involvement, both refractory to various treatments, including rituximab, who demonstrated significant improvement of all their manifestations, including joint, muscular and lung diseases on tocilizumab. The response was also long-lasting, with both patients still being in full remission after >10 years of treatment.Our experience shows that interleukin-6 inhibition could be a very effective treatment option in antisynthetase syndrome, with efficacy on a wide spectrum of manifestations.
The earliest iconographic record of Gobioides broussonnetii La Cepède, 1800 (Gobiiformes: Gobiidae): the species identity of the “Caramuru” paintings of Dutch Brazil (1624-1654)
Authors: Trevisan João Pedro , Bockmann Flávio A. 
Published: December 2023

During the Mauritian period of Dutch Brazil (1637‑1644), a great deal of information about the biota of northeastern Brazil was obtained, consisting of both written records and paintings. Among them is an eel-like fish, depicted in two paintings labeled “Caramurû” and “Caramuru”, whose taxonomic identity is controversial. One of them, attributed to Albert Eckhout, is part of the Theatrum Rerum Naturalium Brasiliae collection, stored at the Jagiellonian University Library, in Poland. This painting was possibly a model for the second “Caramuru”, of unknown authorship, which is deposited at the Archive of the Russian Academy of Sciences. These paintings are doubtfully identified as the snake eel Echiophis intertinctus (Ophichthidae, Anguilliformes), a proposal likely induced by the vulgar name “caramuru”, which is applied to muraenids and ophichthids in Brazil. After careful examination of these two paintings regarding the anatomical details depicted, we concluded that the fish corresponds, with great certainty, to Gobioides broussonnetii (Gobiidae, Gobiiformes), popularly known as “aimoré” and “tajasica”. Furthermore, we suggest the possibility that the written counterpart of these paintings is the description associated with the woodcut of the fish labeled as “Tajasica” in the Historia Naturalis Brasiliae (Marggraf in de Laet, 1648). The confusion probably stems from mismatches between Georg Marggraf’s descriptions and the images of organisms produced at the time, perhaps before the return of Johan Maurits van Nassau-Siegen’s entourage to Europe. In an attempt to support our conclusions about the identity of that fish, as well as for historical purposes, we also discuss the vernacular names applied to G. broussonnetii and the authorship of the notes made on those paintings.
Prediction of Venous Thromboembolism in Diverse Populations Using Machine Learning and Structured Electronic Health Records
Authors: Chen Robert , Petrazzini Ben Omega , Malick Waqas A. , Rosenson Robert S. , Do Ron 
Published: December 2023

BACKGROUND:
Venous thromboembolism (VTE) is a major cause of morbidity and mortality worldwide. Current risk assessment tools, such as the Caprini and Padua scores and Wells criteria, have limitations in their applicability and accuracy. This study aimed to develop machine learning models using structured electronic health record data to predict diagnosis and 1-year risk of VTE.

METHODS:

We trained and validated models on data from 159 001 participants in the Mount Sinai Data Warehouse. We then externally tested them on 401 723 participants in the UK Biobank and 123 039 participants in All of Us. All data sets contain populations of diverse ancestries and clinical histories. We used these data sets to develop small, medium, and large models with increasing features on a range of optimizing portability to maximizing performance. We make trained models publicly available in click-and-run format at
https://doi.org/10.17632/tkwzysr4y6.6
.

RESULTS:
In the holdout and external test sets, respectively, models achieved areas under the receiver operating characteristic curve of 0.80 to 0.83 and 0.72 to 0.82 for VTE diagnosis prediction and 0.76 to 0.78 and 0.64 to 0.69 for 1-year risk prediction, significantly outperforming the Padua score. Models also demonstrated robust performance across different VTE types and patient subsets, including ethnicity, age, and surgical and hospitalization status. Models identified both established and novel clinical features contributing to VTE risk, offering valuable insights into its underlying pathophysiology.

CONCLUSIONS:
Machine learning models using structured electronic health record data can significantly improve VTE diagnosis and 1-year risk prediction in diverse populations. Model probability scores exist on a continuum, affecting mortality risk in both healthy individuals and VTE cases. Integrating these models into electronic health record systems to generate real-time predictions may enhance VTE risk assessment, early detection, and preventative measures, ultimately reducing the morbidity and mortality associated with VTE.