bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal function and lipid metabolism are major predictors of circumpapillary retinal nerve fiber layer thickness—the LIFE-Adult Study
Authors: Rauscher Franziska G. , Wang Mengyu , Francke Mike , Wirkner Kerstin , Tönjes Anke , Engel Christoph , Thiery Joachim , Stenvinkel Peter , Stumvoll Michael , Loeffler Markus , Elze Tobias , Ebert Thomas 
Published: September 2021

Abstract
Background
Circumpapillary retinal nerve fiber layer thickness (cpRNFLT) as assessed by spectral domain optical coherence tomography (SD-OCT) is a new technique used for the detection and evaluation of glaucoma and other optic neuropathies. Before translating cpRNFLT into clinics, it is crucially important to investigate anthropometric, biochemical, and clinical parameters potentially affecting cpRNFLT in a large population-based dataset.

Methods
The population-based LIFE-Adult Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. All participants underwent standardized systemic assessment of various cardiometabolic risk markers and ocular imaging, including cpRNFLT measurement using SD-OCT (Spectralis, Heidelberg Engineering). After employing strict SD-OCT quality criteria, 8952 individuals were analyzed. Multivariable linear regression analyses were used to evaluate the independent associations of various cardiometabolic risk markers with sector-specific cpRNFLT. For significant markers, the relative strength of the observed associations was compared to each other to identify the most relevant factors influencing cpRNFLT. In all analyses, the false discovery rate method for multiple comparisons was applied.

Results
In the entire cohort, female subjects had significantly thicker global and also sectoral cpRNFLT compared to male subjects (p < 0.05). Multivariable linear regression analyses revealed a significant and independent association between global and sectoral cpRNFLT with biomarkers of renal function and lipid profile. Thus, thinner cpRNFLT was associated with worse renal function as assessed by cystatin C and estimated glomerular filtration rate. Furthermore, an adverse lipid profile (i.e., low high-density lipoprotein (HDL) cholesterol, as well as high total, high non-HDL, high low-density lipoprotein cholesterol, and high apolipoprotein B) was independently and statistically significantly related to thicker cpRNFLT. In contrast, we do not observe a significant association between cpRNFLT and markers of inflammation, glucose homeostasis, liver function, blood pressure, or obesity in our sector-specific analysis and globally.

Conclusions
Markers of renal function and lipid metabolism are predictors of sectoral cpRNFLT in a large and deeply phenotyped population-based study independently of previously established covariates. Future studies on cpRNFLT should include these biomarkers and need to investigate whether incorporation will improve the diagnosis of early eye diseases based on cpRNFLT.
The incidence of necrotic enteritis in turkeys is associated with farm, season and faecal Eimeria oocyst counts
Authors: Kaldhusdal Magne , Skjerve Eystein , Hansen Magne Kjerulf , Hamnes Inger Sofie , David Bruce , Hanssen Skjalg Arne , Løvland Atle 
Published: September 2021

Abstract
Background
Specific studies on the epidemiology of necrotic enteritis in turkeys are absent in the literature. Necrotic enteritis is common in turkeys and a leading cause of use of therapeutic antibiotics. This study describes the incidence of necrotic enteritis in turkey farms, and the association between incidence and bird age, season, faecal oocyst counts, grow-out size and feed mill.

Results
Necrotic enteritis was diagnosed post mortem in 20.2 % of 545 grow-outs of commercial female and male B.U.T. 10 turkeys started during the years 2010–2016. 80 % of all cases occurred at four to seven weeks of age. Median (minimum-maximum) age at disease detection was 37 (18–115) days. Turkey age at detection was influenced by season, and varied from 33 days among grow-outs hatched in February to 42 days among those hatched in July-August. The incidence also varied with season, showing peak occurrence among grow-outs hatched during February-March and the lowest incidence in turkeys hatched in July-August. 59 % of all cases were detected in 25 % of the farms. The incidence per farm varied from below 4 to 59 %. A multilevel mixed-effects logistic regression model indicated clear impacts of farm and season on incidence, and border-line impacts of grow-out size and feed mill. Grow-outs diagnosed with necrotic enteritis had higher counts of faecal Eimeria oocysts than grow-outs without a diagnosis. This difference was particularly clear during the high-risk period at five to seven weeks of age. Necrotic enteritis was the cause of treatment with therapeutic antibiotics in 88.2 % of all cases of treatment.

Conclusions
Our data indicate that necrotic enteritis incidence in turkeys can be substantially influenced by risk factors at farm level. The incidence showed two seasonal peaks; a moderate peak in turkeys hatched in October/November and a marked peak in turkeys hatched during February/March. Mitigation measures at the farm may therefore be of particular importance during these months in farms located in the Northern temperate zone. Measures which effectively reduce counts of faecal Eimeria oocyst are likely to be among the more promising actions to take both at the farm and at population level.
MAD1L1 and TSNARE gene polymorphisms are associated with schizophrenia susceptibility in the Han Chinese population
Authors: Liu Xianglai , Xie Hailing , Fu Zejuan , Yao Qiankun , Han Tianming , Zhan Dafei , Lin Zhan , Zhu Hong 
Published: September 2021

Abstract
Background
Schizophrenia (SCZ) is a severe mental illness with high heritability. This study aimed to explore the correlation between MAD1L1, TSNARE polymorphisms and SCZ susceptibility.

Methods
A total of 493 SCZ patients and 493 healthy controls were included. The genotypes of MAD1L1 and TSNARE polymorphisms were identified by Agena MassARRAY platform. Odds ratio (OR) and 95% confidence intervals (CIs) were tested via logistic regression analysis in multiple genetic models and different subgroups.

Results
We observed that AG genotype of rs1107592, AG genotype of rs4976976, and CA genotype of rs67756423 decreased the susceptibility to SCZ (p < 0.05). Age stratification analysis showed that the TC genotype of rs12666575, AG genotype of rs1107592, and AG genotype of rs4976976 decreased the risk of SCZ individuals older than 36 years (p < 0.05). In addition, the AG and AA genotype of rs4976976, the CA genotype of rs67756423 were associated with a lower risk of SCZ in males (p < 0.05). In females, the TT genotype of rs12666575 in recessive model, the AG and AA-AG genotype of rs1107592 in heterozygote and dominant model, could reduce the susceptibility to SCZ (p < 0.05). However, no significant association was found after Bonferroni correction.

Conclusions
Our results suggest that MAD1L1 and TSNARE genetic polymorphisms exert a protective role in the risk of SCZ. These findings provide evidence that MAD1L1 and TSNARE may serve as potential biomarkers of SCZ. However, a replication experiment in a cohort with large sample size are required to confirm our findings.
Trial registration Not applicable.
SPECT imaging of pulmonary vascular disease in bleomycin-induced lung fibrosis using a vascular endothelium tracer
Authors: Harel François , Nguyen Quang T. , Nsaibia Mohamed J. , Finnerty Vincent , Morgan Arielle , Sirois Martin , Villeneuve Louis , Calderone Angelino , Bergeron Alexandre , Brochiero Emmanuelle , Tardif Jean-Claude , Shi YanFen , Dupuis Jocelyn 
Published: September 2021

Abstract
Background
Pulmonary hypertension (PH) complicating idiopathic pulmonary fibrosis (IPF) is associated to worse outcome. There is a great need for a non-invasive diagnostic modality to detect and evaluate the severity of pulmonary vascular disease (PVD). 99mTc-PulmoBind is a novel imaging agent that binds to the adrenomedullin (AM) receptor on the pulmonary microvascular endothelium. SPECT imaging employing the endothelial cell tracer 99mTc-PulmoBind was used to assess PVD associated with lung fibrosis.

Methods
Rats with selective right lung bleomycin-induced fibrosis were compared to control rats. SPECT imaging was performed after three weeks with 99mTc-PulmoBind and 99mTc-macroaggregates of albumin (MAA). PH and right ventricular (RV) function were assessed by echocardiography. Lung perfusion was evaluated by fluorescent microangiography. Lung AM receptor expression was measured by qPCR and by immunohistology. Relevance to human IPF was explored by measuring AM receptor expression in lung biopsies from IPF patients and healthy controls.

Results
The bleomycin group developed preferential right lung fibrosis with remodeling and reduced perfusion as assessed with fluorescent microangiography. These rats developed PH with RV hypertrophy and dysfunction. 99mTc-PulmoBind uptake was selectively reduced by 50% in the right lung and associated with reduced AM receptor expression, PH and RV hypertrophy. AM receptor was co-expressed with the endothelial cell protein CD31 in alveolar capillaries, and markedly reduced after bleomycin. Quantitative dynamic analysis of 99mTc-PulmoBind uptake in comparison to 99mTc-MAA revealed that the latter distributed only according to flow, with about 60% increased left lung uptake while left lung uptake of 99mTc-PulmoBind was not affected. Lung from human IPF patients showed important reduction in AM receptor expression closely associated with CD31.

Conclusions
SPECT imaging with 99mTc-PulmoBind detects PVD and its severity in bleomycin-induced lung fibrosis. Reduced AM receptor expression in human IPF supports further clinical development of this imaging approach.
Increased CD9 expression predicts favorable prognosis in human cancers: a systematic review and meta-analysis
Authors: Koh Hyun Min , Jang Bo Gun , Lee Dong Hui , Hyun Chang Lim 
Published: September 2021

Abstract
Background
CD9 is implicated in cancer progression and metastasis by its role in suppressing cancer cell proliferation and survival. However, the prognostic and clinicopathological significance of CD9 expression is controversial. Therefore, the current meta-analysis was conducted to determine the prognostic and clinicopathological significance of CD9 expression in cancer patients.

Methods
Eligible studies were selected through database search of PubMed, Embase and Cochrane library up to April 5 2020. The necessary data were extracted from the included studies. Pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the prognostic and clinicopathological significance of CD9 expression in cancer patients.

Results
A total of 17 studies consisting of 3456 cancer patients were included in this meta-analysis. An increased CD9 expression was significantly associated with a more favorable overall survival (OS) (HR 0.47, 95% CI 0.31–0.73, p = 0.001) and disease-free survival (DFS) (HR 0.48, 95% CI 0.30–0.79, p = 0.003). In subgroup analysis of cancer type, an increased CD9 expression was associated with increased OS in breast cancer and digestive system cancer, and with increased DFS in head and neck cancer and leukemia/lymphoma. Additionally, an increased CD9 expression significantly correlated with lower overall stage (OR 0.45, 95% CI 0.29–0.72, p = 0.001).

Conclusion
An increased CD9 expression was associated with favorable survival in cancer patients suggesting that CD9 expression could be a valuable survival factor in cancer patients.
Therapeutic potential of a novel semi-synthetic-sulfated-polysaccharide to suppress inflammatory mediators in P. gingivalis LPS stimulated human monocytes/macrophages
Authors: Gu Ying , Raja Veena , Lee Hsi-Ming , Hong Houlin , Prestwich Glenn , Ryan Maria E. 
Published: September 2021

AbstractBackgroundChronic periodontitis is associated with an increased risk for systemic conditions such as cardiovascular disease, diabetes, and osteoporosis. During chronic periodontitis, endotoxin (lipopolysaccharide, LPS) produced byP. gingivalisprovokes monocyte accumulation and differentiation into macrophages and increased secretion of pro-inflammatory cytokines and matrix metalloproteases (MMPs). While normal levels of MMPs are important in cellular function, increased levels of cytokines and MMPs can cause connective tissue destruction.ResultsIn the current study, we investigated the therapeutic capability of a novel semi-synthetic sulfated polysaccharide (SAGE) on the production of cytokines and MMPs by cultured human mononuclear cells and macrophages stimulated with endotoxin LPS produced byP. gingivalis, a periodontally-relevant cell culture model. Our research demonstrated SAGE inhibited the LPS induced synthesis of inflammatory mediators including TNF-α, IL-1β, PGE2, and MMP-9 in this periodontal-relevant cell culture model. In addition, TLR-2 and TLR-4 levels were also reduced with the SAGE treatment.ConclusionsThe therapeutic potential of this novel semi-synthetic sulfated polysaccharide compound may help to prevent tissue damage and bone loss in patients with periodontal disease or other inflammatory diseases.
Development of theranostic dual-layered Au-liposome for effective tumor targeting and photothermal therapy
Authors: Jeon Miyeon , Kim Gaeun , Lee Wooseung , Baek Seungki , Jung Han Na , Im Hyung-Jun 
Published: September 2021

AbstractBackgroundPhotothermal therapy (PTT) is an emerging anti-cancer therapeutic strategy that generates hyperthermia to ablate cancer cells under laser irradiation. Gold (Au) coated liposome (AL) was reported as an effective PTT agent with good biocompatibility and excretory property. However, exposed Au components on liposomes can cause instability in vivo and difficulty in further functionalization.ResultsHerein, we developed a theranostic dual-layered nanomaterial by adding liposomal layer to AL (LAL), followed by attaching polyethylene glycol (PEG) and radiolabeling. Functionalization with PEG improves the in vivo stability of LAL, and radioisotope labeling enables in vivo imaging of LAL. Functionalized LAL is stable in physiological conditions, and64Cu labeled LAL (64Cu-LAL) shows a sufficient blood circulation property and an effective tumor targeting ability of 16.4%ID g−1from in vivo positron emission tomography (PET) imaging. Also, intravenously injected LAL shows higher tumor targeting, temperature elevation in vivo, and better PTT effect in orthotopic breast cancer mouse model compared to AL. The tumor growth inhibition rate of LAL was 3.9-fold higher than AL.ConclusionBased on these high stability, in vivo imaging ability, and tumor targeting efficiency, LAL could be a promising theranostic PTT agent.Graphic Abstract
Single-cell transcriptome and cell-specific network analysis reveal the reparative effect of neurotrophin-4 in preantral follicles grown in vitro
Authors: Guo Yingchun , Chen Peigen , Li Tingting , Jia Lei , Zhou Yi , Huang Jiana , Liang Xiaoyan , Zhou Chuanchuan , Fang Cong 
Published: September 2021

AbstractBackgroundIn-vitro-grow (IVG) of preantral follicles is essential for female fertility preservation, while practical approach for improvement is far from being explored. Studies have indicated that neurotrophin-4 (NT-4) is preferentially expressed in human preantral follicles and may be crucial to preantral follicle growth.MethodsWe observed the location and expression of Tropomyosin-related kinase B (TRKB) in human and mouse ovaries with immunofluorescence and Western blot, and the relation between oocyte maturation and NT-4 level in follicular fluid (FF). Mice model was applied to investigate the effect of NT-4 on preantral follicle IVG. Single-cell RNA sequencing of oocyte combined with cell-specific network analysis was conducted to uncover the underlying mechanism of effect.ResultsWe reported the dynamic location of TRKB in human and mouse ovaries, and a positive relationship between human oocyte maturation and NT-4 level in FF. Improving effect of NT-4 was observed on mice preantral follicle IVG, including follicle development and oocyte maturation. Transcriptome analysis showed that the reparative effect of NT-4 on oocyte maturation might be mediated by regulation of PI3K-Akt signaling and subsequent organization of F-actin. Suppression of advanced stimulated complement system in granulosa cells might contribute to the improvement. Cell-specific network analysis revealed NT-4 may recover the inflammation damage induced by abnormal lipid metabolism in IVG.ConclusionsOur data suggest that NT-4 is involved in ovarian physiology and may improve the efficiency of preantral follicle IVG for fertility preservation.
SARS-CoV-2 and regular patient treatment – from the use of rapid antigen testing up to treatment specific precaution measures
Authors: Durner Jürgen , Beikler Thomas , Watts David C. , Becker Marc , Draenert Miriam E. 
Published: September 2021

Abstract
Introduction
The COVID-19 pandemic poses a continued challenge for all parties involved especially for the dentist as routine operation must be resumed. Rapid Antigen Tests (RATs) are actually recommended to identify and minimize infectious risks. However, there is still no guideline on the implementation of RATs in a dental or medical setting.

Methods
Based on data and an extensive literature research regarding rapid antigen testing and reflecting the recommendations given by the various professional societies a task force was formed to determine a specific testing and treatment strategy.

Results
A comprehensive test and treatment strategy and risk analysis was developed with practical suggestions for a wide range of typical activities in dental and medical offices.
The transmission of SARS-CoV-2 and its variants via aerosols and droplets as well as the difficulties to maintain the minimum distance form special challenges to the dental routine. RATs might in addition to optimal and necessary hygienic standards in combination with the use of adequate personal protection equipment be an important instrument in managing the challenges.

Conclusions
The present work gives recommendations for dental routine operation (dental practices, outpatient clinics) to provide the necessary dental care for the population while protecting the doctor, practice team and patient at the same time.
Obese people benefit from lumbar spinal stenosis surgery as much as people of normal weight
Authors: Myllykangas Henni , Ristolainen Leena , Hurri Heikki , Lohikoski Jouni , Kautiainen Hannu , Puisto Ville , Österman Heikki , Manninen Mikko 
Published: September 2021

Abstract
Background
Lumbar spinal stenosis (LSS) is a common degenerative condition of the spine that causes back pain radiating to the lower extremity. Surgical treatment is indicated to treat progressive radical symptoms. Obesity has been associated with inferior results in the domains of quality of life (QoL) following an LSS operation, but the research findings have been limited. This paper aims to identify whether obesity affects QoL due to back pain among patients who underwent an operation for LSS.

Methods
This study is based on a series of patients operated on for LSS between 2012 and 2018. Operated patients who returned for follow-up forms within the first or second years were included. A total of 359 patients were selected, 163 males (45%) and 196 females (55%). The mean age was 68.9 years. The EuroQol five-dimension scale (EQ-5D) questionnaire was chosen to measure QoL and the Oswestry Disability Index (ODI) for functional disability.

Results
QoL, as measured by EQ-5D, was preoperatively lower in those patients with a BMI ≥ 30. One year after the operation, all groups had a similar trend of improved QoL. At the second year, the results in all groups levelled off even though there was no statistical difference in clinical outcomes (p = 0.92).
The ODI was preoperatively statistically higher in patients with a BMI ≥ 30 (p < 0.001). Two years after the surgery, all groups had improved ODI scores, but there was no statistical difference in ODI between the BMI groups (p = 0.54).

Conclusion
Surgical intervention for debilitating or longstanding symptoms of LSS should be considered as a treatment option for suitable patients in spite of an elevated BMI.
Acceptability and feasibility of enhanced cognitive behavioral therapy (eCBT) for children and adolescents with obsessive–compulsive disorder
Authors: Babiano-Espinosa Lucía , Wolters Lidewij H. , Weidle Bernhard , Compton Scott N. , Lydersen Stian , Skokauskas Norbert 
Published: September 2021

Abstract
Introduction
Obsessive–compulsive disorder (OCD) is a disabling mental health disorder affecting 1–3% of children and adolescents. Cognitive behavioral therapy (CBT) is recommended as the first-line treatment, but is limited by accessibility, availability, and, in some cases, response to treatment. Enhancement with Internet technologies may mitigate these challenges.

Methods
We developed an enhanced CBT (eCBT) treatment package for children and adolescents with OCD to improve treatment effect as well as user-friendliness. This study aims to explore the feasibility, acceptability, and preliminary effectiveness of the eCBT intervention. The eCBT protocol consists of 10 face-to-face and 12 webcam sessions delivered in 14 weeks. CBT is enhanced by a smartphone application (app) for children and parents to support and monitor treatment, psychoeducative videos, and therapist-guided webcam exposure exercises conducted at home. Assessments were performed at baseline, post-treatment, and at 3- and 6-month follow-up. Primary measures of outcomes were the the Client Satisfaction Questionnaire-8 (CSQ-8) (acceptability), treatment drop-out (feasibility) and the Children’s Yale-Brown Obsessive–Compulsive Scale (CY-BOCS) (preliminary effectiveness).

Results
This paper describes 25 patients with OCD (aged 8–17 years) treated with eCBT. Results indicated that children and parents were satisfied with eCBT, with CSQ-8 mean scores of 27.58 (SD 0.67) and 29.5 (SD 3.74), respectively (range 8–32). No patients dropped out from treatment. We found a mean of 63.8% symptom reduction on the CY-BOCS from baseline to post-treatment. CY-BOCS scores further decreased during 3-month and 6-month follow-up.

Conclusion
In this explorative study, eCBT for pediatric OCD was a feasible, acceptable intervention demonstrating positive treatment outcomes.