bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal associations between chronic hepatitis B and COVID-19 in East Asian populations
Authors: Liu Zhenguo , Song Linnan , Chen Junling , Zhou Yongjun , Wang Yuhao , Tang Libo , Li Yongyin 
Published: June 2023

Abstract
Background
The relationship between chronic hepatitis B (CHB) and Coronavirus disease 2019 (COVID-19) has been inconsistent in traditional observational studies.

Methods
We explored the total causal and direct causal associations between CHB and the three COVID-19 outcomes using univariate and multivariate Mendelian randomization (MR) analyses, respectively. Genome-wide association study datasets for CHB and COVID-19 were obtained from the Japan Biobank and the COVID-19 Host Genetics Initiative, respectively.

Results
Univariate MR analysis showed that CHB increased the risk of SARS-CoV-2 infection (OR = 1.04, 95% CI 1.01–1.07, P = 3.39E−03), hospitalized COVID-19 (OR = 1.10, 95% CI 1.06–1.13, P = 7.31E−08), and severe COVID-19 (OR = 1.16, 95%CI 1.08–1.26, P = 1.43E−04). A series of subsequent sensitivity analyses ensured the stability and reliability of these results. In multivariable MR analyses adjusting for type 2 diabetes, body mass index, basophil count, and smoking, genetically related CHB is still positively associated with increased risk of SARS-CoV-2 infection (OR = 1.06, 95% CI 1.02–1.11, P = 1.44E−03) and hospitalized COVID-19 (OR = 1.12, 95% CI 1.07–1.16, P = 5.13E−07). However, the causal link between CHB and severe COVID-19 was attenuated after adjustment for the above variables. In addition, the MR analysis did not support the causal effect of COVID-19 on CHB.

Conclusions
This study provides evidence that CHB increases COVID-19 susceptibility and severity among individuals of East Asian ancestry.
Cumulative genetic score of KIAA0319 affects reading ability in Chinese children: moderation by parental education and mediation by rapid automatized naming
Authors: Zhao Jingjing , Yang Qing , Cheng Chen , Wang Zhengjun 
Published: June 2023

AbstractKIAA0319, a well-studied candidate gene, has been shown to be associated with reading ability and developmental dyslexia. In the present study, we investigated whether KIAA0319 affects reading ability by interacting with the parental education level and whether rapid automatized naming (RAN), phonological awareness and morphological awareness mediate the relationship between KIAA0319 and reading ability. A total of 2284 Chinese children from primary school grades 3 and 6 participated in this study. Chinese character reading accuracy and word reading fluency were used as measures of reading abilities. The cumulative genetic risk score (CGS) of 13 SNPs in KIAA0319 was calculated. Results revealed interaction effect between CGS of KIAA0319 and parental education level on reading fluency. The interaction effect suggested that individuals with a low CGS of KIAA0319 were better at reading fluency in a positive environment (higher parental educational level) than individuals with a high CGS. Moreover, the interaction effect coincided with the differential susceptibility model. The results of the multiple mediator model revealed that RAN mediates the impact of the genetic cumulative effect of KIAA0319 on reading abilities. These findings provide evidence that KIAA0319 is a risk vulnerability gene that interacts with environmental factor to impact reading abilities and demonstrate the reliability of RAN as an endophenotype between genes and reading associations.
Evaluation of anterior translation in total knee arthroplasty utilizing stress radiographs
Authors: Ryan Sean P. , Cochrane Niall H. , Jiranek William A. , Seyler Thorsten M. , Wellman Samuel S. , Bolognesi Michael P. 
Published: June 2023

Abstract
Background
Flexion instability is a common cause for revision after total knee arthroplasty (TKA); however, little objective criteria exist to determine excessive laxity in flexion. This study sought to determine the reliability of stress radiographs for flexion laxity using manual stress as well as a commercially available flexion stress device, with the hypothesis that a commercially available force device would provide increased translation compared to manual stress, and radiographic measurements would be reproducible.

Methods
Ten patients who previously underwent TKA with non-hinged components were prospectively and consecutively enrolled at a single center to undergo stress radiographs. Three lateral radiographs with the knee at 90° of flexion were obtained for each patient: rest, commercial stress device at 150N, and manual stress. Calibrated radiographs were evaluated by two raters, and inter-rater and intra-rater reliability were determined using intraclass correlation coefficients (ICC).

Results
Ten patients (seven female) with mean age 72 (range 55–82) years and average duration from surgery 36 (range 12–96) months were evaluated. The commercial stress device provided significantly less anterior translation than manual stress (− 0.3 mm vs. 3.9 mm; p < 0.01). Two patients reported pain with use of the stress device. Inter-observer reliability of measurements was good for commercial stress (ICC = 0.86) and excellent for manual stress (ICC = 0.94). Eighty-five percent of measurements were within 1 mm between observers. Intra-observer reliability of measurements was good to excellent for both the stress device and manual stress.

Conclusions
Lateral stress radiographs may assist in the objective evaluation of flexion instability. A commercially available product provided less translation than manual stress; however, measurements were reliable and reproducible between observers. Further research is required to correlate translation with stress radiographs to patient outcomes following revision arthroplasty.
Feasibility study for the automatic surgical planning method based on statistical model
Authors: Nguyen Hang Phuong , Lee Hyun-Joo , Kim Sungmin 
Published: June 2023

Abstract
Purpose
In this study, we proposed establishing an automatic computer-assisted surgical planning approach based on average population models.

Methods
We built the average population models from humerus datasets using the Advanced Normalization Toolkits (ANTs) and Shapeworks. Experiments include (1) evaluation of the average population models before surgical planning and (2) validation of the average population models in the context of predicting clinical landmarks on the humerus from the new dataset that was not involved in the process of building the average population model. The evaluation experiment consists of explained variation and distance model. The validation experiment calculated the root-mean-square error (RMSE) between the expert-determined clinical ground truths and the landmarks transferred from the average population model to the new dataset. The evaluation results and validation results when using the templates built from ANTs were compared to when using the mean shape generated from Shapeworks.

Results
The average population models predicted clinical locations on the new dataset with acceptable errors when compared to the ground truth determined by an expert. However, the templates built from ANTs present better accuracy in landmark prediction when compared to the mean shape built from the Shapeworks.

Conclusion
The average population model could be utilized to assist anatomical landmarks checking automatically and following surgical decisions for new patients who are not involved in the dataset used to generate the average population model.
Hemophagocytic lymphohistiocytosis as a rare complication of dengue haemorrhagic fever: a case report
Authors: Pradeep Chamila , Karunathilake Parackrama , Abeyagunawardena Shamali , Ralapanawa Udaya , Jayalath Thilak 
Published: June 2023

Abstract
Background
Haemophagocytic lymphohistiocytosis (HLH) is an uncommon systemic inflammatory syndrome that can happen secondary to numerous conditions. It rarely occurs due to dengue infection causing significant mortality and morbidity even with appropriate treatment. The outcome is further poor if the diagnosis of HLH is delayed or left untreated. Therefore, a high degree of clinical suspicion is paramount in diagnosing HLH.

Case presentation
A 17-year-old Sinhalese boy was admitted to a tertiary care hospital in Sri Lanka with a 4-day history of fever, headache, nausea, vomiting, and diarrhea. He was hemodynamically stable, and the serological investigation confirmed a dengue infection. On the fifth day of fever, he entered the critical phase of dengue infection, confirmed by ultrasound evidence of plasma leaking. However, he had ongoing high fever spikes during the critical phase, and even after the critical phase was over, the fever spikes continued. Simultaneously, hepatosplenomegaly was noticed, and he showed persistent thrombocytopenia, neutropenia, and anemia despite the resolution of the critical phase. Further, the workup revealed a serum ferritin level of > 3000 ng/mL triglyceride level of 314 mg/dL, and the bone marrow biopsy revealed an increased haemophagocytic activity. Secondary HLH was diagnosed on the basis of criteria used in the HLH-2004 trial and successfully managed with intravenous dexamethasone 10 mg/body surface area/day for the first 2 weeks, followed by a tapering regimen over 8 weeks.

Conclusion
This case emphasizes the need to consider HLH as a potential complication when persistent fever and cytopenias are present after recovering from dengue fever, particularly in patients with unusual clinical features like hepatosplenomegaly. Early recognition and prompt treatment with appropriate immunosuppressive therapy, such as intravenous dexamethasone, can lead to a successful response and good prognosis.
The complementary role of PSMA expression and [18F]FDG PET/CT in predicting thyroid cancer outcome: from black and white to shades of gray, in the era of precision oncology
Authors: Sollini Martina , Kirienko Margarita , di Tommaso Luca , Pini Cristiano , Gelardi Fabrizia , Ariano Salvatore , Lania Andrea Gerardo , Mazziotti Gherardo , Mercante Giuseppe , Chiti Arturo 
Published: June 2023

Abstract
Background
The value of Prostate Specific Membrane Antigen (PSMA) in thyroid carcinoma (TC) is still unknown. We aimed to test the potential complementary role of PSMA expression and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake on PET/CT as biomarkers for TC outcome prediction.

Materials and methods
From a retrospective cohort of TC patients we selected those fulfilling the following inclusion/exclusion criteria: thyroidectomy in our Institution, available primary tumor tissue PSMA immunostaining, [18F]FDG PET/CT and follow-up data. PSMA staining was visually assessed. PET/CT was considered positive in case of [18F]FDG uptake higher than the background at the site of TC confirmed by cyto-/histology, and/or follow-up. Disease recurrence, radioiodine refractoriness (RAI-R) and status at last follow-up (LFU) were used as outcome endpoints.

Results
We included 23 subjects. Disease recurrence occurred in 18 patients (median time 11 months, range 1–40); among these 12/18 developed RAI-R (median time 28 months, range 2–221), and 13/18 had evidence of disease at LFU. PSMA expression was negative in 6/23 cases. PET/CT was negative in 11/23 patients (7/11 experienced recurrence). PET/CT was positive in 9/12 patients showing RAI-R and 10/13 cases with evidence of disease at LFU. All patients with positive PET/CT had a positive PSMA immunostaining. Six out of 11 patients with negative PET/CT were positive at immunostaining, showing lower PSMA expression (median score of 30%, range 0–80%) than patients with positive PET/CT. The TC samples without PSMA expression belonged to patients who resulted negative also at PET/CT (3 experienced recurrence, 2 were RAI-R, and 1 had disease at LFU). Four out of 11 patients who resulted negative at PET/CT exhibited very high PSMA expression (≥ 70%) and although 3 of them experienced recurrence, none resulted RAI-R, and only 1 had persistent disease at LFU.

Conclusions
Primary tumor PSMA expression and [18F]FDG uptake seem to play a complementary prognostic role in TC. The majority of patients who expressed PSMA recurred. In the intermediate ATA risk class, patients with negative PSMA immunostaining recurred less than patients expressing PSMA. Additionally, although patients with a negative [18F]FDG PET/CT had a favourable long-term outcome, PSMA assessment might be useful to timely identify subjects at higher risk of recurrence.
Epiphytic common core bacteria in the microbiomes of co-located green (Ulva), brown (Saccharina) and red (Grateloupia, Gelidium) macroalgae
Authors: Lu De-Chen , Wang Feng-Qing , Amann Rudolf I. , Teeling Hanno , Du Zong-Jun 
Published: June 2023

AbstractBackgroundMacroalgal epiphytic microbial communities constitute a rich resource for novel enzymes and compounds, but studies so far largely focused on tag-based microbial diversity analyses or limited metagenome sequencing of single macroalgal species.ResultsWe sampled epiphytic bacteria from specimens ofUlvasp. (green algae),Saccharinasp. (brown algae),Grateloupiasp. andGelidiumsp. (both red algae) together with seawater and sediment controls from a coastal reef in Weihai, China, during all seasons. Using 16S rRNA amplicon sequencing, we identified 14 core genera (consistently present on all macroalgae), and 14 dominant genera (consistently present on three of the macroalgae). Core genera represented ~ 0.7% of all genera, yet accounted for on average 51.1% of the bacterial abundances. Plate cultivation from all samples yielded 5,527 strains (macroalgae: 4,426) representing 1,235 species (685 potentially novel). Sequencing of selected strains yielded 820 non-redundant draft genomes (506 potentially novel), and sequencing of 23 sampled metagenomes yielded 1,619 metagenome-assembled genomes (MAGs), representing further 1,183 non-redundant genomes. 230 isolates and 153 genomes were obtained from the 28 core/dominant genera. We analyzed the genomic potential of phycosphere bacteria to degrade algal polysaccharides and to produce bioactive secondary metabolites. We predicted 4,451 polysaccharide utilization loci (PULs) and 8,810 biosynthetic gene clusters (BGCs). These were particularly prevalent in core/dominant genera.ConclusionsOur metabolic annotations and analyses of MAGs and genomes provide new insights into novel species of phycosphere bacteria and their ecological niches for an improved understanding of the macroalgal phycosphere microbiome.
ICOS DNA methylation regulates melanoma cell-intrinsic ICOS expression, is associated with melanoma differentiation, prognosis, and predicts response to immune checkpoint blockade
Authors: Ralser Damian J. , Herr Emmanuelle , de Vos Luka , Kulcsár Zsófi , Zarbl Romina , Klümper Niklas , Gielen Gerrit H. , Maas Alexander Philippe , Hoffmann Friederike , Dietrich Jörn , Kuster Pia , Mustea Alexander , Glodde Nicole , Kristiansen Glen , Strieth Sebastian , Landsberg Jennifer , Dietrich Dimo 
Published: June 2023

Abstract
Background
Inducible T cell costimulator ICOS is an emerging target in immuno-oncology. The aim of this study was to investigate the epigenetic regulation of ICOS in melanoma by DNA methylation.

Methods
We comprehensively investigate ICOS DNA methylation of specific CpG sites and expression pattern within the melanoma microenvironment with regard to immune correlates, differentiation, clinical outcomes, and immune checkpoint blockade (ICB) response.

Results
Our study revealed a sequence-contextual CpG methylation pattern consistent with an epigenetically regulated gene. We found a cell type-specific methylation pattern and locus-specific correlations and associations of CpG methylation with ICOS mRNA expression, immune infiltration, melanoma differentiation, prognosis, and response to ICB. High ICOS mRNA expression was identified as a surrogate for enriched immune cell infiltration and was associated with favorable overall survival (OS) in non-ICB-treated patients and predicted response and a prolonged progression-free survival (PFS) following ICB therapy initiation. ICOS hypomethylation, however, significantly correlated with poor OS in non-ICB patients but predicted higher response and prolonged PFS and OS in ICB-treated patients. Moreover, we observed cytoplasmic and sporadically nuclear tumor cell-intrinsic ICOS protein expression. Tumor cell-intrinsic ICOS protein and mRNA expression was inducible by pharmacological demethylation with decitabine.

Conclusion
Our study identified ICOS DNA methylation and mRNA expression as promising prognostic and predictive biomarkers for immunotherapy in melanoma and points towards a hitherto undescribed role of ICOS in tumor cells.
Differential effects of familial Alzheimer’s disease-causing mutations on amyloid precursor protein (APP) trafficking, proteolytic conversion, and synaptogenic activity
Authors: Schilling Sandra , Pradhan Ajay , Heesch Amelie , Helbig Andrea , Blennow Kaj , Koch Christian , Bertgen Lea , Koo Edward H. , Brinkmalm Gunnar , Zetterberg Henrik , Kins Stefan , Eggert Simone 
Published: June 2023

AbstractThe amyloid precursor protein (APP) is a key player in Alzheimer`s disease (AD) and the precursor of the Aβ peptide, which is generated by consecutive cleavages of β- and γ-secretases. Familial Alzheimer’s disease (FAD) describes a hereditary subgroup of AD that represents a low percentage of AD cases with an early onset of the disease. Different APP FAD mutations are thought to have qualitatively different effects on its proteolytic conversion. However, few studies have explored the pathogenic and putative physiological differences in more detail. Here, we compared different FAD mutations, located at the β- (Swedish), α- (Flemish, Arctic, Iowa) or γ-secretase (Iberian) cleavage sites. We examined heterologous expression of APP WT and FAD mutants in non-neuronal cells and their impact on presynaptic differentiation in contacting axons of co-cultured neurons. To decipher the underlying molecular mechanism, we tested the subcellular localization, the endocytosis rate and the proteolytic processing in detail by immunoprecipitation–mass spectrometry. Interestingly, we found that only the Iberian mutation showed altered synaptogenic function. Furthermore, the APP Iowa mutant shows significantly decreased α-secretase processing which is in line with our results that APP carrying the Iowa mutation was significantly increased in early endosomes. However, most interestingly, immunoprecipitation–mass spectrometry analysis revealed that the amino acid substitutions of APP FAD mutants have a decisive impact on their processing reflected in altered Aβ profiles. Importantly, N-terminally truncated Aβ peptides starting at position 5 were detected preferentially for APP Flemish, Arctic, and Iowa mutants containing amino acid substitutions around the α-secretase cleavage site. The strongest change in the ratio of Aβ40/Aβ42 was observed for the Iberian mutation while APP Swedish showed a substantial increase in Aβ1–17 peptides. Together, our data indicate that familial AD mutations located at the α-, β-, and γ-secretase cleavage sites show considerable differences in the underlying pathogenic mechanisms.
Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration
Authors: Koga Shunsuke , Metrick Michael A. , Golbe Lawrence I. , Santambrogio Alessia , Kim Minji , Soto-Beasley Alexandra I. , Walton Ronald L. , Baker Matthew C. , De Castro Cristhoper Fernandez , DeTure Michael , Russell David , Navia Bradford A. , Sandiego Christine , Ross Owen A. , Vendruscolo Michele , Caughey Byron , Dickson Dennis W. 
Published: June 2023

AbstractProgressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are distinct clinicopathological subtypes of frontotemporal lobar degeneration. They both have atypical parkinsonism, and they usually have distinct clinical features. The most common clinical presentation of PSP is Richardson syndrome, and the most common presentation of CBD is corticobasal syndrome. In this report, we describe a patient with a five-year history of Richardson syndrome and a family history of PSP in her mother and sister. A tau PET scan (18F-APN-1607) revealed low-to-moderate uptake in the substantia nigra, globus pallidus, thalamus and posterior cortical areas, including temporal, parietal and occipital cortices. Neuropathological evaluation revealed widespread neuronal and glial tau pathology in cortical and subcortical structures, including tufted astrocytes in the motor cortex, striatum and midbrain tegmentum. The subthalamic nucleus had mild-to-moderate neuronal loss with globose neurofibrillary tangles, consistent with PSP. On the other hand, there were also astrocytic plaques, a pathological hallmark of CBD, in the neocortex and striatum. To further characterize the mixed pathology, we applied two machine learning-based diagnostic pipelines. These models suggested diagnoses of PSP and CBD depending on the brain region – PSP in the motor cortex and superior frontal gyrus and CBD in caudate nucleus. Western blots of insoluble tau from motor cortex showed a banding pattern consistent with mixed features of PSP and CBD, whereas tau from the superior frontal gyrus showed a pattern consistent with CBD. Real-time quaking-induced conversion (RT-QuIC) using brain homogenates from the motor cortex and superior frontal gyrus showed ThT maxima consistent with PSP, while reaction kinetics were consistent with CBD. There were no pathogenic variants in MAPT with whole genome sequencing. We conclude that this patient had an unclassified tauopathy and features of both PSP and CBD. The different pathologies in specific brain regions suggests caution in diagnosis of tauopathies with limited sampling.
Psychopathology and Theory of Mind in patients with personality disorders
Authors: Burghardt Juliane , Gradl Silvia , Knopp Magdalena , Sprung Manuel 
Published: June 2023

Abstract
Objective
People with mental disorders frequently suffer from deficits in the ability to infer other’s mental states (Theory of Mind; ToM). Individuals with borderline personality disorder (BPD) show ToM deficits characterized by exceeding ToM (over-attributions of mental states). The present study analyzed associations between ToM, BPD severity, and depression severity in patients with BPD and other personality disorders.

Method
We analyzed ToM abilities in 128 patients with BPD and 82 patients with ‘mixed and other personality disorders’ (MOPD). MOPD are diagnosed if symptoms of multiple personality disorders are present without any set of symptoms being dominant enough to allow a specific diagnosis. We used the movies for the assessment of social cognition (MASC) to measure ToM abilities, the Patient Health Questionnaire (PHQ-9) to assess severity of depression and the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) to assess the severity of BPD symptoms.

Results
Both symptoms of BPD and depression were associated with exceeding ToM in separate regressions. Using a stepwise regression, only the association of depression severity with exceeding ToM was reliable. Patients with BPD and MOPD did not differ in exceeding ToM. Age was most reliably associated with ToM.

Conclusion
The results imply that exceeding ToM is associated with general psychopathology instead of BPD-symptoms in specific. Patients with MOPD show deficits similar to BPD patients.