bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the effectiveness of the National Health Insurance Fund in providing financial protection to households with hypertension and diabetes patients in Kenya
Authors: Oyando Robinson , Were Vincent , Koros Hillary , Mugo Richard , Kamano Jemima , Etyang Anthony , Murphy Adrianna , Hanson Kara , Perel Pablo , Barasa Edwine
Published: June 2023

Background

Non-communicable diseases (NCDs) can impose a substantial financial burden to households in the absence of an effective financial risk protection mechanism. The national health insurance fund (NHIF) has included NCD services in its national scheme. We evaluated the effectiveness of NHIF in providing financial risk protection to households with persons living with hypertension and/or diabetes in Kenya.

Methods

We carried out a prospective cohort study, following 888 households with at least one individual living with hypertension and/or diabetes for 12 months. The exposure arm comprised households that are enrolled in the NHIF national scheme, while the control arm comprised households that were not enrolled in the NHIF. Study participants were drawn from two counties in Kenya. We used the incidence of catastrophic health expenditure (CHE) as the outcome of interest. We used coarsened exact matching and a conditional logistic regression model to analyse the odds of CHE among households enrolled in the NHIF compared with unenrolled households. Socioeconomic inequality in CHE was examined using concentration curves and indices.

Results

We found strong evidence that NHIF-enrolled households spent a lower share (12.4%) of their household budget on healthcare compared with unenrolled households (23.2%) (p = 0.004). While households that were enrolled in NHIF were less likely to incur CHE, we did not find strong evidence that they are better protected from CHE compared with households without NHIF (OR = 0.67; p = 0.47). The concentration index (CI) for CHE showed a pro-poor distribution (CI: -0.190, p < 0.001). Almost half (46.9%) of households reported active NHIF enrolment at baseline but this reduced to 10.9% after one year, indicating an NHIF attrition rate of 76.7%. The depth of NHIF cover (i.e., the share of out-of-pocket healthcare costs paid by NHIF) among households with active NHIF was 29.6%.

Conclusion

We did not find strong evidence that the NHIF national scheme is effective in providing financial risk protection to households with individuals living with hypertension and/diabetes in Kenya. This could partly be explained by the low depth of cover of the NHIF national scheme, and the high attrition rate. To enhance NHIF effectiveness, there is a need to revise the NHIF benefit package to include essential hypertension and/diabetes services, review existing provider payment mechanisms to explicitly reimburse these services, and extend the existing insurance subsidy programme to include individuals in the informal labour market.
Adaptations to scale-up an early childhood education and care physical activity intervention for real-world availability — Play Active
Authors: Mclaughlin Matthew , Nathan Andrea , Thornton Ashleigh , Schipperijn Jasper , Trost Stewart G. , Christian Hayley
Published: June 2023

Background

Adaptations for scale-up are ubiquitous but are rarely described in detail. Adaptations may be a key reason for the “scale-up penalty” which is when there is a reduction in intervention effect size following scale-up. The Play Active intervention consists of a physical activity policy for early childhood education and care (ECEC) services, with accompanying implementation support strategies. It was first implemented with 81 ECEC services in Perth, Western Australia, in 2021 — with significant positive changes in physical activity practice uptake. The aim of this paper is to describe the extent, type, fidelity consistency, goals, size, scope, and proposed impact of proposed adaptations to the implementation support strategies for scaling-up Play Active.

Methods

Proposed adaptations were defined as planned changes, made prior to making the intervention available. The authors created a list of adaptations from a comparison of the Play Active implementation support strategies, before and after adaptation for proposed statewide availability across Western Australia, Queensland and South Australia, Australia. We used the Framework for Reporting Adaptations and Modifications-Enhanced Implementation Strategies (FRAME-IS) to code adaptations to implementation support strategies. Three authors coded each adaptation and rated their size, scope and proposed impact.

Results

Fifty-three adaptations to Play Active were identified. Most (68%) were proposed for the ‘content’ of implementation strategies, including aspects of their delivery. In practice, this involved changing the delivery mode of implementation support strategies from phone call and email support, to website-based delivery. More than half (56%) of adaptations involved ‘adding elements’ for scale-up. Most adaptations were ‘fidelity consistent’ (95%). The main goals for adaptations were related to ‘increasing the acceptability, appropriateness, or feasibility’ (45%), ‘decreasing the costs’ (19%) and ‘increasing adoption of the evidence-based practice’ (19%). Adaptations were small to medium in size, with most proposed to have a positive (87%) or neutral (8%) effect on the effectiveness of the intervention, rather than negative (4%).

Conclusions

A large number of small, fidelity-consistent, adaptations were proposed for Play Active scale-up. Overall, the process of reporting adaptations was found to be feasible. To understand the impact of these adaptations, it will be important to re-evaluate implementation, effectiveness and process outcomes, at-scale.
Early miR-320b and miR-25-3p miRNA levels correlate with multiple sclerosis severity at 10 years: a cohort study
Authors: Gonzalez-Martinez Alicia , Bose Gauruv , Lokhande Hrishikesh , Saxena Shrishti , Healy Brian C. , Polgar-Turcsanyi Mariann , Weiner Howard L. , Chitnis Tanuja
Published: June 2023

Background

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB)-cohort, as well as other international cohorts, as potential disease biomarkers in MS. However, few studies have evaluated the association of miRNA expression early in the MS disease course with long-term outcomes. Therefore, we aimed to evaluate the potential role of three candidate serum miRNAs previously correlated with MS disability in patients with MS, miR-320b, miR-25-3p and miRNA 486-5p, as early biomarkers of MS disability at 10-year follow-up.

Main body

We included 144 patients with serum obtained within three years of MS onset. miRNA expression was measured by RNA extraction followed by RT-PCR. Demographic, clinical, brain MRI and other biomarkers were collected. The primary outcome was the association between early miRNA expression and retaining benign MS, defined as EDSS ≤ 2 at 10-year follow-up. Among the 144 patients, 104 were benign and 40 were not benign at 10-year follow-up. 89 (62%) were women, with mean age at onset 37.7 (SD: 9.6) years. Patients who retained benign MS had lower values of miR-25-3p (p = 0.047) and higher miR-320b (p = 0.025) values. Development of SPMS was associated with higher miR-320b (p = 0.002) levels. Brain parenchymal fraction at year 10 was negatively correlated with miR-25-3p (p = 0.0004) and positively correlated with miR-320b (p = 0.006). No association was found between miR-486-5p and any outcome, and 10-year T2-lesion volume was not associated with any miRNA.

Conclusions

Our results show that miR-320b and miR-25-3p expression are early biomarkers associated with MS severity and brain atrophy. This study provides class III evidence of that miR-320b and miR-25-3p are associated with long-term MS disability which may be a potential tool to risk-stratify patients with MS for early treatment decisions.
Quantification of host proteomic responses to genotype 4 hepatitis E virus replication facilitated by pregnancy serum
Authors: Qian Zhongyao , Cong Chao , Li Yi , Bi Yanhong , He Qiuxia , Li Tengyuan , Xia Yueping , Xu Liangheng , Mickael Houfack K. , Yu Wenhai , Liu Jiankun , Wei Daqiao , Huang Fen
Published: June 2023

Background

Hepatitis E virus (HEV) infection is a common cause of acute hepatitis worldwide and causes approximately 30% case fatality rate among pregnant women. Pregnancy serum (PS), which contains a high concentration of estradiol, facilitates HEV replication in vitro through the suppression of the PI3K–AKT–mTOR and cAMPK–PKA–CREB signaling pathways. However, the proteomics of the complex host responses to HEV infection, especially how PS facilitates viral replication, remains unclear.

Methods

In this study, the differences in the proteomics of HEV-infected HepG2 cells supplemented with fetal bovine serum (FBS) from those of HEV-infected HepG2 cells supplemented with serum from women in their third trimester of pregnancy were quantified by using isobaric tags for relative and absolute quantification technology.

Results

A total of 1511 proteins were identified, among which 548 were defined as differentially expressed proteins (DEPs). HEV-infected cells supplemented with PS exhibited the most significant changes at the protein level. A total of 328 DEPs, including 66 up-regulated and 262 down-regulated proteins, were identified in HEV-infected cells supplemented with FBS, whereas 264 DEPs, including 201 up-regulated and 63 down-regulated proteins, were found in HEV-infected cells supplemented with PS. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that in HEV-infected cells, PS supplementation adjusted more host genes and signaling pathways than FBS supplementation. The DEPs involved in virus–host interaction participated in complex interactions, especially a large number of immune-related protein emerged in HEV-infected cells supplemented with PS. Three significant or interesting proteins, including filamin-A, thioredoxin, and cytochrome c, in HEV-infected cells were functionally verified.

Conclusions

The results of this study provide new and comprehensive insight for exploring virus–host interactions and will benefit future studies on the pathogenesis of HEV in pregnant women.
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

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

KIAA0319, 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

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

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

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

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

Background

Macroalgal 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.

Results

We 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.

Conclusions

Our 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

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

The 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

Progressive 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

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.
Demography, common disorders and mortality of Boxer dogs under primary veterinary care in the UK
Authors: O’Neill Dan G. , Skipper Alison M. , Barrett Kate , Church David B. , Packer Rowena M. A. , Brodbelt Dave C.
Published: June 2023

Background

The Boxer is a popular dog breed with a distinctive appearance. However, the breed has been linked with several health conditions, some of which have been associated with its moderately brachycephalic conformation and its white colouration. Anonymised primary-care veterinary clinical records were explored to extract data on the demography, common disorders and mortality of Boxers in the UK in 2016.

Results

The study population of 336,865 dogs included 3,219 (0.96%) Boxers, of which 10.71% were recorded as white. The mean adult bodyweight was 30.43 kg (SD 5.73 kg). Annual disorder counts did not differ statistically between the sexes or between white and non-white Boxers. The most prevalent fine-level precision disorders were otitis externa (n = 230, 7.15%), epulis (188, 5.84%), corneal ulceration (161, 5.00%) and periodontal disease (149, 4.63%). Of the 34 most common fine-level disorders, none differed in prevalence between white and non-white dogs. The most prevalent disorder groups were skin disorder (n = 571, 17.74%), neoplasia (457, 14.20%) and ear disorder (335, 10.41%). White Boxers had higher prevalence than non-white Boxers for two disorder groups: dental disorder and brain disorder. The median longevity of 346 Boxers that died during the study was 10.46 years (IQR 9.00–11.98, range 2.76–18.00). Median longevity did not differ statistically between the sexes or between white and non-white Boxers. The most common grouped causes of death were death – unrecorded cause (n = 73, 21.10%), neoplasia (43, 12.43%) and brain disorder (33, 9.54%).

Conclusions

There was minimal evidence of substantial health differences between white and non-white Boxers. Among the four most common disorders recorded in Boxers, two were typically common across all types of dogs (otitis externa and periodontal disease) while two suggested strong predispositions for the Boxer breed (epulis and corneal ulceration), showing the value of eliciting breed-specific disorder patterns for insights for potential health reforms. The overall longevity of Boxer dogs was consistent with other breeds of similar body size.
Posterior stability of the shoulder depends on acromial anatomy: a biomechanical study of 3D surface models
Authors: Hochreiter Bettina , Beeler Silvan , Hofstede Simon , Sigrist Bastian , Snedeker Jess G. , Gerber Christian
Published: June 2023

Purpose

Primary glenohumeral osteoarthritis is commonly associated with static posterior subluxation of the humeral head. Scapulae with static/dynamic posterior instability feature a superiorly and horizontally oriented acromion. We investigated whether the acromion acts as a restraint to posterior humeral translation.

Methods

Five three‐dimensional (3D) printed scapula models were biomechanically tested. A statistical shape mean model (SSMM) of the normal scapula of 40 asymptomatic shoulders was fabricated. Next, a SSMM of scapular anatomy associated with posterior subluxation was generated using data of 20 scapulae (“B1”). This model was then used to generate three models of surgical correction: glenoid version, acromial orientation, and acromial and glenoid orientation. With the joint axially loaded (100N) and the humerus stabilized, an anterior translation force was applied to the scapula in 35°, 60° and 75° of glenohumeral flexion. Translation (mm) was measured.

Results

In the normal scapula, the humerus translates significantly less to contact with the acromion compared to all other configurations (p < .000 for all comparisons; i.e. 35°: “normal” 8,1 mm (± 0,0) versus “B1” 11,9 mm (± 0,0) versus “B1 Acromion Correction” 12,2 mm (± 0,2) versus “B1 Glenoid Correction” 13,3 mm (± 0,1)). Restoration of normal translation was only achieved with correction of glenoid and acromial anatomy (i.e. 75°: “normal” 11 mm (± 0,8) versus “B1 Acromion Correction” 17,5 mm (± 0,1) versus “B1 Glenoid Correction” 19,7 mm (± 1,3) versus “B1 Glenoid + Acromion Correction” 11,5 mm (± 1,1)).

Conclusions

Persistence or recurrence of static/dynamic posterior instability after correction of glenoid version alone may be related to incomplete restoration of the intrinsic stability that is conferred by a normal acromial anatomy.

Level of Evidence V

biomechanical study
Diel variability in the vertical distribution of coastal barnacle larvae in the Bay of Cartagena, Chile
Authors: Bonicelli Jessica , Jeneral María José , Bularz Bryan , Weidberg Nicolas , Plummer Katalin A. , Calderón Ricardo , Cifuentes Ursula , Alarcón Darly , Navarrete Sergio A.
Published: June 2023

Background

Vertical distribution of zooplankton is an important biological factor that can modulate zooplankton transport, dispersal, and survival in the ocean. Seawater temperature and the associated formation of a thermocline can affect the spatial distribution of organisms in the water column and possibly modulate larval vertical distribution in coastal waters. In this study, we examined larval vertical distribution over small spatial scales where environmental conditions could exhibit strong and fairly predictable variability.

Methods

Diel variation in vertical distributions of barnacle larvae across the thermocline was characterized within the Bay of Cartagena of central Chile. Two intensive 21- and 24-h surveys were conducted in the northern (ECIM) and southern (CTGN) extremes of the bay in summer 2016 and spring 2017. In each survey, vertical tows were conducted at both sites every 3 h above and below the thermocline.

Results

During summer 2016, larval vertical distribution differed between taxa (balanids and verrucids), barnacle stages (nauplii, cyprids), and sites within the bay. Of all taxa analyzed Balanid nauplii at ECIM were more abundant in the bottom layer during the day and at the surface during the night, suggesting they can control their vertical distribution and follow a diel pattern.Acording to the results all barnacle larvae were found in diferent positions in the water column between day and night during periods of high stratification in this survey.. In spring 2017 all barnacle larvae were confined to the upper layer, despite the strength of stratification, potentially as a result of the intrusion of hypoxic water (< 2 mL L−1) at the bottom, which reached up to around 5 m deep.

Conclusions

We conclude that diel vertical distribution is not uniform across different barnacle larvae taxa and stages within the Bay of Cartagena and is not affected by stratification. Of all the taxa analyzed, only balanid nauplii showed a pattern of diel vertical migration across the thermocline under certain hydrographic conditions.
Abrupt increased serum creatinine in a hyperferritinemia patient treated with deferoxamine after cord blood transplantation: a case report with literature review
Authors: Nakayama Hirokazu , Kamoda Yoshimasa , Tanuma Michiya , Kato Toshiaki , Usuki Kensuke
Published: June 2023

Background

Erythrocyte transfusion is an indispensable component of supportive care after hematopoietic stem cell transplantation (HSCT). However, HSCT recipients are susceptible to the development of acute kidney injury (AKI) with multifactorial causes. We report a case of a rapid elevation in serum creatinine associated with deferoxamine after cord blood transplantation (CBT).

Case presentation

A 36-year-old Japanese male diagnosed with relapsed Philadelphia-positive acute lymphoblastic leukemia received CBT. At day 88 post-CBT, multidrug-resistant Pseudomonas aeruginosa (MDRP) was isolated from urine culture. Subsequently, colistin 200 mg/day was administered parenterally for treatment of epididymitis from day 91 to 117 post-CBT. Despite concomitant administration of potential nephrotoxic agents such as piperacillin-tazobactam, acyclovir, and liposomal amphotericin B, no development of AKI was observed during this period. At day 127 post-CBT, MDRP was detected in blood and urine cultures, and colistin 200 mg/day was re-started parenterally. Due to extremely higher ferritin level, deferoxamine was administered intravenously at day 133 post-CBT. While serum creatinine was 1.03 mg/dL before starting deferoxamine, the level increased to 1.36 mg/dL one day after commencing deferoxamine (day 134 post-CBT), and further increased to 2.11 mg/dL at day 141. Even though colistin was discontinued at day 141 post-CBT, serum creatinine continued to increase. Deferoxamine was withdrawn at day 145 post-CBT, when serum creatinine peaked at 2.70 mg/dL. In addition, no cylinduria is observed during the period of development of AKI. In adverse drug reaction (ADR) assessment using Naranjo probability score, the scores of 3 in deferoxamine and 2 in colistin, respectively, indicated “possible” ADR. However, while colistin-associated AKI manifested early onset, recovery time within 2 weeks after discontinuation and development of cylinduria, this case was discordant with the properties. Furthermore, in the literature review, development of AKI within 1 day, including sudden increase in serum creatinine or abrupt reduction in urine volume, was reported in 3 identified cases.

Conclusions

We considered the rapid creatinine elevation to be the result of deferoxamine rather than ADR caused by colistin. Therefore, careful monitoring of kidney function is required in recipients of HSCT treated with deferoxamine.
The microbiome of Riccia liverworts is an important reservoir for microbial diversity in temporary agricultural crusts
Authors: Wicaksono Wisnu Adi , Semler Bettina , Pöltl Martina , Berg Christian , Berg Gabriele , Cernava Tomislav
Published: June 2023

Background

The microbiota of liverworts provides an interesting model for plant symbioses; however, their microbiome assembly is not yet understood. Here, we assessed specific factors that shape microbial communities associated withRicciatemporary agricultural crusts in harvested fields by investigating bacterial, fungal and archaeal communities in thalli and adhering soil from different field sites in Styria and Burgenland, Austria combining qPCR analyses, amplicon sequencing and advanced microscopy.

Results

Riccia spec. div.was colonized by a very high abundance of bacteria (101016S rRNA gene copies per g of thallus) as well as archaea and fungi (108ITS copies per g of thallus). EachRicciathallus contain approx. 1000 prokaryotic and fungal ASVs. The field type was the main driver for the enrichment of fungal taxa, likely due to an imprint on soil microbiomes by the cultivated crop plants. This was shown by a higher fungal richness and different fungal community compositions comparing liverwort samples collected from pumpkin fields, with those from corn fields. In contrast, bacterial communities linked to liverworts are highly specialized and the soil attached to them is not a significant source of these bacteria. Specifically, enrichedCyanobacteria, BacteroidetesandMethylobacteriasuggest a symbiotic interaction. Intriguingly, compared to the surrounding soil, the thallus samples were shown to enrich several well-known bacterial and fungal phytopathogens indicating an undescribed role of liverworts as potential reservoirs of crop pathogens.

Conclusions

Our results provide evidence that a stable bacterial community but varying fungal communities are colonizing liverwort thalli. Post-harvest, temporary agricultural biocrusts are important reservoirs for microbial biodiversity but they have to be considered as potential reservoirs for pathogens as well.
Effects of a High-Volume 7-Week Pectoralis Muscle Stretching Training on Muscle Function and Muscle Stiffness
Authors: Reiner Marina , Gabriel Anna , Sommer Daniel , Bernsteiner Daniel , Tilp Markus , Konrad Andreas
Published: June 2023

Background

There is evidence that high-volume static stretching training of the lower limbs can increase the range of motion (ROM) while decreasing muscles stiffness. However, to date, there is no evidence on the effects of upper limb stretching training or its effect mechanism. Therefore, this study aimed to investigate the effects of a comprehensive 7-week static stretching training program of the pectoralis major muscle (PMa) on glenohumeral joint ROM, muscle force, and muscle stiffness.

Methods

Thirty-eight healthy, physically active participants (23 male, 15 female) were randomly assigned to either the PMa-static stretching intervention (PMa-SS) group or the control group. The PMa-SS group performed a 7-week intervention comprising three sessions a week for 15 min per session, including three static stretching exercises of the PMa for 5 min each. Before and after the intervention period, shoulder extension ROM, muscle stiffness of the PMa (pars clavicularis), and maximal voluntary isometric contraction (MVIC) peak torque (evaluated at both long (MVIClong) and short (MVICshort) muscle lengths) were investigated on a custom-made testing device at 45° shoulder abduction.

Results

In the PMa-SS group, the shoulder extension ROM (+ 6%; p < 0.01; d = 0.92) and the MVIClong (+ 11%; p = 0.01; d = 0.76) increased. However, there were no significant changes in MVICshort or in PMa muscle stiffness in the PMa-SS group. In the control group, no changes occurred in any parameter.

Conclusion

In addition to the increase in ROM, we also observed an improved MVIC at longer but not shorter muscle lengths. This potentially indicates an increase in fascicle length, and hence a likely increase in sarcomeres in series.