bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain pharmacokinetics of mono- and bispecific amyloid-β antibodies in wild-type and Alzheimer’s disease mice measured by high cut-off microdialysis
Authors: Julku Ulrika , Xiong Mengfei , Wik Elin , Roshanbin Sahar , Sehlin Dag , Syvänen Stina 
Published: December 2022

Abstract
Background
Treatment with amyloid-β (Aβ) targeting antibodies is a promising approach to remove Aβ brain pathology in Alzheimer's disease (AD) and possibly even slow down or stop progression of the disease. One of the main challenges of brain immunotherapy is the restricted delivery of antibodies to the brain. However, bispecific antibodies that utilize the transferrin receptor (TfR) as a shuttle for transport across the blood–brain barrier (BBB) can access the brain better than traditional monospecific antibodies. Previous studies have shown that bispecific Aβ targeting antibodies have higher brain distribution, and can remove Aβ pathology more efficiently than monospecific antibodies. Yet, there is only limited information available on brain pharmacokinetics, especially regarding differences between mono- and bispecific antibodies.

Methods
The aim of the study was to compare brain pharmacokinetics of Aβ-targeting monospecific mAb3D6 and its bispecific version mAb3D6-scFv8D3 that also targets TfR. High cut-off microdialysis was used to measure intravenously injected radiolabelled mAb3D6 and mAb3D6-scFv8D3 antibodies in the interstitial fluid (ISF) of hippocampus in wild-type mice and the AppNL−G−F mouse model of AD. Distribution of the antibodies in the brain and the peripheral tissue was examined by ex vivo autoradiography and biodistribution studies.

Results
Brain concentrations of the bispecific antibody were elevated compared to the monospecific antibody in the hippocampal ISF measured by microdialysis and in the brain tissue at 4–6 h after an intravenous injection. The concentration of the bispecific antibody was approximately twofold higher in the ISF dialysate compared to the concentration of monospecific antibody and eightfold higher in brain tissue 6 h post-injection. The ISF dialysate concentrations for both antibodies were similar in both wild-type and AppNL−G−F mice 24 h post-injection, although the total brain tissue concentration of the bispecific antibody was higher than that of the monospecific antibody at this time point. Some accumulation of radioactivity around the probe area was observed especially for the monospecific antibody indicating that the probe compromised the BBB to some extent at the probe insertion site.

Conclusion
The BBB-penetrating bispecific antibody displayed higher ISF concentrations than the monospecific antibody. The concentration difference between the two antibodies was even larger in the whole brain than in the ISF. Further, the bispecific antibody, but not the monospecific antibody, displayed higher total brain concentrations than ISF concentrations, indicating association to brain tissue.
A low-cost and open-source solution to automate imaging and analysis of cyst nematode infection assays for Arabidopsis thaliana
Authors: Kranse Olaf Prosper , Ko Itsuhiro , Healey Roberta , Sonawala Unnati , Wei Siyuan , Senatori Beatrice , De Batté Francesco , Zhou Ji , Eves-van den Akker Sebastian 
Published: December 2022

AbstractBackgroundCyst nematodes are one of the major groups of plant-parasitic nematode, responsible for considerable crop losses worldwide. Improving genetic resources, and therefore resistant cultivars, is an ongoing focus of many pest management strategies. One of the major bottlenecks in identifying the plant genes that impact the infection, and thus the yield, is phenotyping. The current available screening method is slow, has unidimensional quantification of infection limiting the range of scorable parameters, and does not account for phenotypic variation of the host. The ever-evolving field of computer vision may be the solution for both the above-mentioned issues. To utilise these tools, a specialised imaging platform is required to take consistent images of nematode infection in quick succession.ResultsHere, we describe an open-source, easy to adopt, imaging hardware and trait analysis software method based on a pre-existing nematode infection screening method in axenic culture. A cost-effective, easy-to-build and -use, 3D-printed imaging device was developed to acquire images of the root system ofArabidopsis thalianainfected with the cyst nematodeHeterodera schachtii, replacing costly microscopy equipment. Coupling the output of this device to simple analysis scripts allowed the measurement of some key traits such as nematode number and size from collected images, in a semi-automated manner. Additionally, we used this combined solution to quantify an additional trait, root area before infection, and showed both the confounding relationship of this trait on nematode infection and a method to account for it.ConclusionTaken together, this manuscript provides a low-cost and open-source method for nematode phenotyping that includes the biologically relevant nematode size as a scorable parameter, and a method to account for phenotypic variation of the host. Together these tools highlight great potential in aiding our understanding of nematode parasitism.
Diagnostic accuracy of ultrasound for the assessment of Baker’s cysts: a meta-analysis
Authors: Liu Ke , Li Xiaoxiao , Weng Qianlin , Lei Guanghua , Jiang Ting 
Published: December 2022

Abstract
Background
Baker’s cyst is the most common cystic disease of the knee, and a fast and accurate diagnosis of Baker’s cyst is essential for a better management. Ultrasound is a rapid, portable, widely available, inexpensive and noninvasive imaging modality. However, the diagnostic accuracy of ultrasound on Baker’s cyst still remains undetermined. We conducted the first meta-analysis to comprehensively assess the accuracy of ultrasound for the detection of Baker’s cyst.

Methods
PubMed, Embase and Web of Science were searched from inception to July 14, 2022, without language restrictions. Studies providing cross-tabulations of ultrasound versus pathology (gold standard) or MRI (standard imaging technique) for diagnosis of Baker’s cyst were included. Indicators for the diagnostic accuracy of ultrasound, including sensitivity, specificity and area under the curve, were calculated using a bivariate model. Sensitivity analysis was conducted to evaluate the heterogeneity and robustness of the results.

Results
A total of 13 studies with 1,011 subjects (mean age 32.2 years; men 53.5%) met the inclusion criteria. The pooled sensitivity, specificity and area under the curve of ultrasound for diagnosis of Baker’s cyst, compared with pathology, were 0.97 (95% confidence intervals: 0.73–1.00), 1.00 (0.98–1.00) and 1.00 (0.99–1.00), respectively. The pooled estimates of ultrasound versus MRI were 0.94 (0.87–0.98) for sensitivity, 1.00 (0.83–1.00) for specificity and 0.97 (0.95–0.98) for area under the curve. Sensitivity analysis did not change the results materially.

Conclusion
Ultrasound shows excellent diagnostic accuracy for the assessment of Baker’s cyst and provides similar diagnostic information (absent or present) compared to MRI. Because of its advantages of low cost, portability and accessibility, ultrasound is likely to be a choice of imaging technique for screening Baker’s cyst in clinical and population settings as well as in follow-ups.
The mutational dynamics of short tandem repeats in large, multigenerational families
Authors: Steely Cody J. , Watkins W. Scott , Baird Lisa , Jorde Lynn B. 
Published: December 2022

Abstract
Background
Short tandem repeats (STRs) compose approximately 3% of the genome, and mutations at STR loci have been linked to dozens of human diseases including amyotrophic lateral sclerosis, Friedreich ataxia, Huntington disease, and fragile X syndrome. Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. To estimate the genome-wide pattern of mutations at STR loci, we analyze blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. These pedigrees contain both sets of grandparents, the parents, and an average of 9 grandchildren per family.

Results
We use HipSTR to identify de novo STR mutations in the 2nd generation of these pedigrees and require transmission to the third generation for validation. Analyzing approximately 1.6 million STR loci, we estimate the empirical de novo STR mutation rate to be 5.24 × 10−5 mutations per locus per generation. Perfect repeats mutate about 2 × more often than imperfect repeats. De novo STRs are significantly enriched in Alu elements.

Conclusions
Approximately 30% of new STR mutations occur within Alu elements, which compose only 11% of the genome, but only 10% are found in LINE-1 insertions, which compose 17% of the genome. Phasing these mutations to the parent of origin shows that parental transmission biases vary among families. We estimate the average number of de novo genome-wide STR mutations per individual to be approximately 85, which is similar to the average number of observed de novo single nucleotide variants.
Artificial intelligence and the future of radiographic scoring in rheumatoid arthritis: a viewpoint
Authors: Bird Alix , Oakden-Rayner Lauren , McMaster Christopher , Smith Luke A. , Zeng Minyan , Wechalekar Mihir D. , Ray Shonket , Proudman Susanna , Palmer Lyle J. 
Published: December 2022

AbstractRheumatoid arthritis is an autoimmune condition that predominantly affects the synovial joints, causing joint destruction, pain, and disability. Historically, the standard for measuring the long-term efficacy of disease-modifying antirheumatic drugs has been the assessment of plain radiographs with scoring techniques that quantify joint damage. However, with significant improvements in therapy, current radiographic scoring systems may no longer be fit for purpose for the milder spectrum of disease seen today. We argue that artificial intelligence is an apt solution to further improve upon radiographic scoring, as it can readily learn to recognize subtle patterns in imaging data to not only improve efficiency, but can also increase the sensitivity to variation in mild disease. Current work in the area demonstrates the feasibility of automating scoring but is yet to take full advantage of the strengths of artificial intelligence. By fully leveraging the power of artificial intelligence, faster and more sensitive scoring could enable the ongoing development of effective treatments for patients with rheumatoid arthritis.
Malignant complications of celiac disease: a case series and review of the literature
Authors: Packova Barbora , Kohout Pavel , Dastych Milan , Prokesova Jitka , Grolich Tomas , Kroupa Radek 
Published: December 2022

Abstract
Background
Celiac disease is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Diagnosis is based on evaluating specific autoantibodies and histopathologic findings of duodenal biopsy specimens. The only therapy for celiac disease is a gluten-free diet. Celiac disease can be complicated by malnutrition, other autoimmune diseases, refractoriness to treatment, and gastrointestinal tumors. This article presents seven cases of malignancies in patients with celiac disease. Its objective is to raise awareness of the malignant complications of celiac disease, leading to earlier diagnosis and improved outcomes.

Case presentation
Seven cases of malignant complications of celiac disease occurred among 190 patients followed at the Department of Internal Medicine and Gastroenterology, University Hospital Brno from 2014 to 2021. We describe these cases and the presentation, diagnostic process, course, management, and outcomes for each, along with proposed potential risk factors of malignant complications. There was one Caucasian man who was 70 years old and six Caucasian women who were 36, 46, 48, 55, 73, and 82 years old in our cohort. Of the seven cases of malignancies in our cohort, four patients were diagnosed with small bowel adenocarcinoma, one with diffuse large B-cell lymphoma, one with carcinoma of the tongue, and one with colorectal carcinoma.

Conclusions
Malignancies occurred in 3.7% of patients followed up for celiac disease. Awareness of the malignant complications of celiac disease, risk factors, presentation, and disease course could lead to earlier diagnosis and improved outcomes.
Sex-dependent expression of neutrophil gelatinase-associated lipocalin in aortic stenosis
Authors: Jover Eva , Matilla Lara , Martín-Núñez Ernesto , Garaikoetxea Mattie , Navarro Adela , Fernández-Celis Amaya , Gainza Alicia , Arrieta Vanessa , García-Peña Amaia , Álvarez Virginia , Sádaba Rafael , Jaisser Frederic , López-Andrés Natalia 
Published: December 2022

AbstractBackgroundAccumulating evidence suggest the existence of sex-related differences in the pathogenesis of aortic stenosis (AS) with inflammation, oxidative stress, fibrosis and calcification being over-represented in men. Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in a myriad of tissues and cell types, and it is associated with acute and chronic pathological processes comprising inflammation, fibrosis or calcification. Sex-dependent signatures have been evidenced for NGAL which expression has been associated predominantly in males to metabolic and cardiovascular disorders. We aimed to analyse sex-related differences of NGAL in AS and its role in the inflammatory and fibrocalcific progression of AS.Methods and results220 (60.45% men) patients with severe AS elective for surgical aortic valve (AV) replacement were recruited. Immunohistochemistry revealed higher expression of NGAL in calcific areas of AVs and that was validated by qPCR in in 65 (60% men) donors. Valve interstitial cells (VICs) were a source of NGAL in these samples. Proteome profiler analyses evidenced higher expression of NGAL in men compared to women, and that was further validated by ELISA. NGAL expression in the AV was correlated with inflammation, oxidative stress, and osteogenic markers, as well as calcium score. The expression of NGAL, both intracellular and secreted (sNGAL), was significantly deregulated only in calcifying male-derived VICs. Depletion of intracellular NGAL in calcifying male-derived VICs was associated with pro-inflammatory profiles, dysbalanced matrix remodelling and pro-osteogenic profiles. Conversely, exogenous NGAL mediated inflammatory and dysbalanced matrix remodelling in calcifying VICs, and all that was prevented by the pharmacological blockade of NGAL.ConclusionsOwing to the over-expression of NGAL, the AV from men may be endowed with higher expression of inflammatory, oxidative stress, matrix remodelling and osteogenic markers supporting the progression of calcific AS phenotypes. The expression of NGAL in the VIC emerges as a potential therapeutic checkpoint, with its effects being potentially reverted by the pharmacological blockade of extracellular NGAL.
Impact of the COVID-19 pandemic on tuberculosis patients and tuberculosis control programs in Turkey, review and analysis
Authors: Ozdemir Sule , Oztomurcuk Derya , Oruc Muhammet Ali 
Published: December 2022

Abstract
Background
Many infectious diseases, including Tuberculosis (TB), have been put in the background with the COVID-19 pandemic. This study aimed to evaluate the changes in the number of TB patients, the parameters of the TB patients and tuberculosis control programs in the first year of the COVID-19 pandemic in Turkey when compared to the previous year.

Methods
All TB patients who were recorded in Samsun province between March 1, 2019 and February 28, 2021 were included in this retrospective study. The data were analyzed in 2 groups as the COVID-19 period (March 2020 and February 2021) and the Pre-COVID-19 period (March 2019 and February 2020),the demographic and microbiological characteristics of the tuberculosis patients in both periods were compared according to months and years p < 0.05 was considered statistically significant.

Results
The total number of TB patients was 320, although it was 172 in the Pre-COVID-19 period, it was 148 in the COVID-19 pandemic period. It was found that the TB incidence rate (IR) was 15.32%, the total number of examinations performed in TB dispensary decreased 33.54%, and the total number of contact examinations decreased by 53.54% during the pandemic period. The mean age of the patients decreased significantly during the COVID-19 period (p = 0.047), and it was found that culture positivity rates and smear positivity rates increased compared to the previous year (7.97%, p = 0.166, 1.86%; p = 0.507, respectively). SARS-CoV-2 PCR test result was found to be (−) in 46 (82.1%) of the 56 TB patients who were examined.

Conclusions
In the present study, it was found that the incidence of TB, the number of examinations, and the number of contact examinations decreased at significant levels. The decrease in TB patients was mostly in the first 3 months when COVID-19 precautions and restrictions were intense. As a conclusion, it was observed that the application of TB patients to the healthcare institution and TB control were affected negatively by the COVID-19 pandemic.
Evaluation of the diagnostic performance of a commercially available point-of-care test for post weaning diarrhoea in pigs-a pilot study
Authors: Jakobsen Nadia , Goecke Nicole Bakkegård , Pedersen Ken Steen 
Published: December 2022

Abstract
Background
Post weaning diarrhoea is expected to become an increasing problem in pig herds following the outphasing of medicinal Zinc Oxide. Currently, no equally effective substitute has been found and an increase in metaphylactic batch medication with antibiotics is expected. However, prudent use of antibiotics is needed to mitigate antibiotic resistance development and one option could be pre-treatment diagnostics. Employing a point-of-care test in a herd could provide fast diagnostics and help guide antibiotic treatment. Hence, the aim of this study was to evaluate the diagnostic performance of a commercially available point-of-care test for enterotoxigenic Escherichia coli (ETEC) F4, ETEC F18 and rotavirus in weaned pigs.

Results
In total 115 diarrheic samples from two conventional herds were included in the evaluation of the Rainbow Piglet Scours test, which was compared to microbiological PCR analyses. The comparison yielded a diagnostic sensitivity, diagnostic specificity, positive and negative predictive value of 0.28, 0.99, 0.92 and 0.70 for ETEC F4, 0.40, 0.92, 0.91 and 0.45 for ETEC F18 and 0.67, 0.88, 0.91 and 0.61 for rotavirus.

Conclusions
The point-of-care test yielded a low diagnostic sensitivity and a high diagnostic specificity for ETEC F4, ETEC F18 and rotavirus. Due to the high level of false negatives, the test cannot be recommended for individual diagnostics on pig-level.
Determinants of coronavirus disease 2019 vaccine acceptance, hesitancy, and barriers among healthcare workers in Ismailia, Egypt: a mixed methods study
Authors: Waheed Amani , Abu Bakr Elsaid Noha M. , Ghweeba Mayada , Elmaraghy Nermine , Al-Touny Shimaa A. , Nemr Nader , Kishk Rania M. , Aly Hebatalla M. 
Published: December 2022

Abstract
Background
Coronavirus disease 2019 vaccine acceptance among healthcare workers (HCWs) plays a fundamental role in combating the COVID-19 pandemic. Vaccination acceptance depends on perceptions of competence and motives of the providers, producers, health professionals, and policymakers. This study aimed to identify the frequency and determinants of COVID-19 vaccine uptake acceptance, hesitancy, and barriers among HCWs.

Methods
A total of 500 HCWs from 3 different hospital affiliations in Ismailia Governorate, Egypt, were included in this mixed methods study. The study was conducted between March and April 2021 through two phases. Phase 1 included a cross-sectional study using a self-administered questionnaire with inquiries about different determinants of vaccine acceptance, hesitancy, and barriers, which was completed either electronically in a Google form or a hard printed copy. Phase 2 included four focus group discussions to explore the determinants in depth.

Results
The mean age of participants was 33.9 ± 7.9 years, 70% were females, 51.2% were nurses, and 28.6% were physicians. Of the 500 HCWs, only 27.8% accepted taking the vaccine immediately, 49.2% refused, and 23% were hesitant. Vaccine safety was the highest associated factor with vaccine acceptance (odds ratio (OR) = 6.3, 95% confidence interval (CI) 3.132–12.619), followed by previous uptake of influenza vaccine (OR = 3.3, 95% CI 2.048–5.217) and vaccine effectiveness (OR = 2.6, 95% CI 1.282–5.262). The main barriers to vaccine acceptance were mistrust in governmental policies during the pandemic or in the healthcare facility they work in. Hesitancy was common among females and nurses and was attributed to three prominent factors, including safety concerns, negative stories, and personal knowledge.

Conclusions
The vaccine acceptance frequency among HCWs was considered low, as the majority either refused or was hesitant about taking the vaccine. Concerns about vaccine safety and effectiveness were significant determinants of vaccine acceptance. Factors related to trust were the main barriers to vaccine uptake. The health authority should establish a surveillance system for side effects of the COVID-19 vaccine and communicate this information between HCWs to decrease their worries about safety and increase vaccine uptake.
Integrating Methylome and Transcriptome Signatures Expands the Molecular Classification of the Pituitary Tumors
Authors: Silva-Júnior Rui M Patrício da , Bueno Ana Carolina , Martins Clarissa Silva , Coelli-Lacchini Fernanda , Ozaki Jorge Guilherme Okanobo , Almeida-e-Silva Danillo Cunha de , Marrero-Gutiérrez Junier , Santos Antônio Carlos dos , Garcia-Peral Carlos , Machado Hélio Rubens , Santos Marcelo Volpon dos , Elias Paula Lamparelli , Moreira Ayrton C , Colli Leandro M , Vêncio Ricardo Z N , Antonini Sonir R , de Castro Margaret 
Published: December 2022

Abstract

Objective
To explore pituitary tumors by methylome and transcriptome signatures in a heterogeneous ethnic population.

Methods
In this retrospective cross-sectional study, clinicopathological features, methylome, and transcriptome were evaluated in pituitary tumors from 77 patients (61% women, age 12-72 years) followed due to functioning (FPT: GH-secreting n = 18, ACTH-secreting n = 14) and nonfunctioning pituitary tumors (NFPT, n = 45) at Ribeirao Preto Medical School, University of São Paulo.

Results
Unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65 out of 77) revealed 3 clusters each: one enriched by FPT, one by NFPT, and a third by ACTH-secreting and NFPT. Comparison between each omics-derived clusters identified 3568 and 5994 differentially methylated and expressed genes, respectively, which were associated with each other, with tumor clinical presentation, and with 2017 and 2022 WHO classifications. UHCA considering 11 transcripts related to pituitary development/differentiation also supported 3 clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; and TBX19 in few NFPTs).

Conclusion
This large heterogenic ethnic Brazilian cohort confirms that integrated methylome and transcriptome signatures classify FPT and NFPT, which are associated with clinical presentation and tumor invasiveness. Moreover, the cluster NFPT/ACTH-secreting adenomas raises interest regarding tumor heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO definition regarding the discrepancy, in rare cases, between clinical presentation and pituitary lineage markers. Finally, making our data publicly available enables further studies to validate genes/pathways involved in pituitary tumor pathogenesis and prognosis.