bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-cell tumor vaccines desialylated to uncover tumor antigenic Gal/GalNAc epitopes elicit anti-tumor immunity
Authors: Huang Jianmei , Li Meiying , Mei Bingjie , Li Junyang , Zhu Yi , Guo Qiaoshan , Huang Jianming , Zhang Guonan 
Published: October 2022

Abstract
Background
Aberrant sialoglycans on the surface of tumor cells shield potential tumor antigen epitopes, escape recognition, and suppress activation of immunocytes. α2,3/α2,6Gal- and α2,6GalNAc (Gal/GalNAc)-linked sialic acid residues of sialoglycans could affect macrophage galactose-type lectins (MGL) mediated-antigen uptake and presentation and promote sialic acid-binding immunoglobulin-like lectins (Siglecs) mediated-immunosuppression. Desialylating sialoglycans on tumor cells could present tumor antigens with Gal/GalNAc residues and overcome glyco-immune checkpoints. Thus, we explored whether vaccination with desialylated whole-cell tumor vaccines (DWCTVs) triggers anti-tumor immunity in ovarian cancer (OC).

Methods
Sialic acid (Sia) and Gal/GalNAc residues on OC A2780, OVCAR3, and ID8 cells treated with α2-3 neuraminidase (α2-3NA) and α2-6NA, and Sigec-9 or Siglec-E and MGL on DCs pulsed with desialylated OC cells were identified using flow cytometry (FCM); RT-qPCR determined IFNG expression of T cells, TRBV was sequenced using Sanger sequencing and cytotoxicity of αβ T cells was measured with LDH assay; Anti-tumor immunity in vivo was validated via vaccination with desialylated whole-cell ID8 vaccine (ID8 DWCTVs).

Results
Gal/GalNAc but not Sia residues were significantly increased in the desialylated OC cells. α2-3NA-modified DWCTV increased MGL but decreased Siglec-9 or Siglec E expression on DCs. MGLbright/Siglec-9dim DCs significantly up-regulated IFNG expression and CD4/CD8 ratio of T cells and diversified the TCR repertoire of αβ T-cells that showed enhanced cytotoxic activity. Vaccination with α2-3NA-modified ID8 DWCTVs increased MGLbright/Siglec-Edim DCs in draining lymph nodes, limited tumor growth, and extended survival in tumor-challenged mice.

Conclusion
Desialylated tumor cell vaccine could promote anti-tumor immunity and provide a strategy for OC immunotherapy in a clinical setting.
Adeno-associated virus infection and its impact in human health: an overview
Authors: Sant’Anna Thaís B , Araujo Natalia M 
Published: October 2022

AbstractDiscovered as a contaminant of adenovirus stocks in the 1960s, adeno-associated virus (AAV) is a mono-stranded DNA virus that depends on helper factors to replicate. Even though AAV is endemic in the human population (35–80%), it is remarkable that many issues concerning the natural infection by this virus remain unanswered. In this study, we reflect on the main basic aspects of AAV biology and provide an overview of the studies exploring the impact of AAV infection on human health, focusing on three major research areas including, (i) cervical and (ii) liver cancer, and (iii) reproductive system disorders. Conflicting results have been obtained into the association of AAV infection with the occurrence of adverse reproductive outcomes, such as placental complications, spontaneous abortion, and fertility disorders, or with a protective role in HPV-related cervical carcinogenesis. Noteworthy, recent reports have identified AAV insertional mutagenesis as a novel risk factor for the development of hepatocellular carcinoma. This latest finding raises concern regarding the widespread usage of AAV vectors in liver-targeted gene therapy.
The association between parenteral nutrition and pancreatic injury in adult patients: a retrospective observational study
Authors: Zhang Xiao-min , Zhou Yi-quan , Wan Yan-ping , Li Hao-jie , Chen Zhi-qi , Song An-qi , Tang Mo-lian , Xu Renying , Cai Wei 
Published: October 2022

Abstract
Background and objective
Patients on parenteral nutrition (PN) are at high risk of both liver and pancreatic injury. More efforts were focused on liver, however, limited data is available to evaluate the effects of PN on pancreas. Thus, we performed a retrospective observational study to evaluate the association between PN and pancreatic injury in Chinese adult patients.

Methods
Adult patients (18–80 years), who received PN for a week or longer, and with repeated measurements of pancreatic enzymes, were included in the analysis. Pancreatic injury was confirmed by serum level of pancreatic amylase (P-AMYwas 53 U/L or higher) or lipase (LP was 63 U/L or higher), which were evaluated at baseline and following every week during PN duration. Age, sex, body weight, height, diagnosis of diseases, history of diseases, surgery, white blood cell, c-reactive protein, liver and renal function, fasting blood glucose, lipid profile, and daily energy supplied by PN and enteral nutrition were abstracted from medical records.

Results
A total number of 190 adult patients (125 men, 65 women) were included in the study. The average age and BMI were 61.8 ± 13.0 years and 21.7±3.3 kg/m2, while medium serum level of P-AMY and LP were 29.0 U/L (quartile range: 18.0, 47.0) and 33.0 U/L (quartile range: 19.0, 58.0), respectively at baseline. The median duration of PN was 15 days (quartile range: 11.0, 21.0). The prevalence of pancreatic injury was 42.1% (80/190) while it was 28.4% (54/190), 43.3% (77/178), 47.8% (44/92) after one-, two-, and three-week or longer PN adminstration. The proportion of daily energy supplement by PN (OR = 3.77, 95%CI: 1.87, 7.61) and history of infection were positively (OR = 3.00, 95%CI: 1.23, 7.36), while disease history for diabetes mellitus (OR = 0.38, 95%CI: 0.15, 0.98) and cancer (OR = 0.46, 95%CI: 0.23, 0.95), were negetively associated with pancreatic injury. Total bile acids were associated with the increment of P-AMY (beta = 0.98, 95%CI: 0.39, 1.56) and LP (beta = 2.55, 95%CI: 0.98, 4.12) by multi-variate linear regression.

Conclusion
PN was associated with pancreatic injury, as demonstrated by the increase of both serum P-AMY and LP.
Anastomotic leak after minimally invasive anterior resection for rectal cancer with high versus low ligation of the inferior mesenteric artery: a study protocol for a multicentre randomized clinical trial
Authors: Lee Soo Young , Kim Sohyun , Son Gyung Mo , Kim Hye Jin , Park Soo Yeun , Park Jun Seok , Kim Chang Hyun , Ha Gi Won , Lee Kyung-Ha , Kim Jin Soo , Bae Ki Beom , Bae Sung Uk , Kang Sung Il ,   Korean ColoRectal surgeOn Study group of the Southern province (K-CROSS)
Published: October 2022

Abstract
Background
Although many efforts have been made to decrease the incidence of anastomotic leak (AL), it remains one of the most serious complications of rectal cancer surgery. Many previous studies have reported an association between the ligation level of the inferior mesenteric artery (IMA) (high or low) and the incidence of AL after rectal cancer surgery. However, we cannot draw a solid conclusion because of the low quality and heterogeneity of those studies. Therefore, this study aims to investigate the impact of the IMA ligation level on the occurrence of AL after minimally invasive anterior resection of rectal cancer.

Methods/design
Patients with primary rectal cancer without distant metastases will be included after screening. They will be randomly assigned (1:1) to receive high or low ligation of the IMA. The primary endpoint is AL incidence; secondary endpoints are quality of life; urinary, sexual, and defecatory functions; and 3-year disease-free survival. We hypothesized that the incidence rate of AL would be 15% and 5% in the high- and low-ligation groups, respectively. With a two-sided α of 0.05 and a power of 0.8, the sample size is calculated to be 314 patients (157 per group), considering a 10% dropout rate.

Discussion
Although many studies have compared the short- and long-term outcomes of high and low ligation of the IMA in rectal cancer surgery, it is still debatable. This trial aims to help draw a more solid conclusion regarding the association between the IMA ligation level and AL incidence after rectal cancer surgery. We also hope to contribute to standardizing the method of rectal cancer surgery in this trial.

Trial registration
Clinical Research Information Service KCT0003523. Registered on February 18, 2019
Preliminary evaluation of the protective effects of recombinant AMA1 and IMP1 against Eimeria stiedae infection in rabbits
Authors: Xiao Jie , Zheng Ruoyu , Bai Xin , Pu Jiayan , Chen Hao , Gu Xiaobin , Xie Yue , He Ran , Xu Jing , Jing Bo , Peng Xuerong , Yang Guangyou 
Published: October 2022

Abstract
Background
Eimeria stiedae parasitizes the bile duct, causing hepatic coccidiosis in rabbits. Coccidiosis control using anticoccidials led to drug resistance and residues; therefore, vaccines are required as an alternative control strategy. Apical membrane antigen 1 (AMA1) and immune mapped protein 1 (IMP1) are surface-located proteins that might contribute to host cell invasion, having potential as candidate vaccine antigens.

Methods
Herein, we cloned and expressed the E. stiedae EsAMA1 and EsIMP1 genes. The reactogenicity of recombinant AMA1 (rEsAMA1) and IMP1 (rEsIMP1) proteins were investigated using immunoblotting. For the vaccination-infection trial, rabbits were vaccinated with rEsAMA1 and rEsIMP1 (both 100 μg/rabbit) twice at 2-week intervals. After vaccination, various serum cytokines were measured. The protective effects of rEsAMA1 and rEsIMP1 against E. stiedae infection were assessed using several indicators. Sera were collected weekly to detect the specific antibody levels.

Results
Both rEsAMA1 and rEsIMP1 showed strong reactogenicity. Rabbits vaccinated with rEsAMA1 and rEsIMP1 displayed significantly increased serum IL-2 (F(4, 25) = 9.53, P = 0.000), IL-4 (F(4, 25) = 7.81, P = 0.000), IL-17 (F(4, 25) = 8.55, P = 0.000), and IFN-γ (F(4, 25) = 6.89, P = 0.001) levels; in the rEsIMP1 group, serum TGF-β1 level was also elevated (F(4, 25) = 3.01, P = 0.037). After vaccination, the specific antibody levels increased and were maintained at a high level. The vaccination-infection trial showed that compared with the positive control groups, rabbits vaccinated with the recombinant proteins showed significantly reduced oocyst output (F(5, 54) = 187.87, P = 0.000), liver index (F(5, 54) = 37.52, P = 0.000), and feed conversion ratio; body weight gain was significantly improved (F(5, 54) = 28.82, P = 0.000).

Conclusions
rEsAMA1 and rEsIMP1 could induce cellular and humoral immunity, protecting against E. stiedae infection. Thus, rEsAMA1 and rEsIMP1 are potential vaccine candidates against E. stiedae.

Graphic abstract
A point-of-care ultrasound education curriculum for pediatric critical care medicine
Authors: Bhargava Vidit , Haileselassie Bereketeab , Rosenblatt Samuel , Baker Mark , Kuo Kevin , Su Erik 
Published: October 2022

Abstract
Background
Diagnostic and procedural point-of-care ultrasound (POCUS) change patient management with the potential to improve outcomes. Pediatric critical care medicine trainees have limited access to education and training opportunities in diagnostic POCUS in the pediatric ICU. A dearth of published pediatric ICU curricular resources restricts these educational opportunities.

Methods
A 7-week longitudinal curriculum including lectures, practical skills sessions, and knowledge assessment covering core modules including (1) machine operation, (2) vascular access, (3) non-vascular procedures, (4) cardiac imaging, (5) hemodynamic assessment, (6) pulmonary imaging, and (7) abdominal imaging, was disseminated to pediatric critical care trainees and faculty at a single tertiary care pediatric hospital.

Results
The knowledge of trainees and participating faculty in procedural and diagnostic POCUS improved after implementing the curriculum. Pre-test scores mean and standard deviation (59.30% ± 14.15%) improved significantly (75.60% ± 9.43%) for all learners (p < 0.001). The overall self-reported comfort in diagnostic and procedural ultrasound improved for all learners. 100% of the learners reported utilizing diagnostic POCUS in their clinical practice four months after disseminating the curriculum.

Discussion
We describe a single center’s approach to POCUS education with improvement in knowledge, self-reported comfort, and attitudes towards procedural and diagnostic POCUS. The curricular resources for adaptation in a similar educational context are provided.
Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report
Authors: Küronya Zsófia , Danyi Tímea , Balatoni Tímea , Liszkay Gabriella , Tóth Erika , Biró Krisztina , Géczi Lajos 
Published: October 2022

Abstract
Background
The use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers.

Case presentation
A 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient’s inadequate compliance, and within 2 years, the patient’s cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient’s basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection.

Conclusions
Our patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.
Copy number variant analysis for syndromic congenital heart disease in the Chinese population
Authors: Li Ping , Chen Weicheng , Li Mengru , Zhao Zhengshan , Feng Zhiyu , Gao Han , Suo Meijiao , Xu Ziqing , Tian Guixiang , Wu Feizhen , Wei Sheng , Huang Guoying 
Published: October 2022

Abstract
Background
Syndromic congenital heart disease (CHD) is among the most severe conditions in the pediatric population. Copy number variant (CNV) is an important cause of syndromic CHD, but few studies focused on CNVs related to these patients in China. The present study aimed to identify pathogenic CNVs associated with syndromic CHD in the Chinese population.

Methods
A total of 109 sporadic patients with syndromic CHD were applied chromosomal microarray analysis (CMA). Phenotype spectrum of pathogenic or likely pathogenic CNVs was analyzed. CHD-related genes were prioritized from genes within pathogenic or likely pathogenic CNVs by VarElect, OVA, AMELIE, and ToppGene.

Results
Using CMA, we identified 43 candidate CNVs in 37/109 patients. After filtering CNVs present in the general population, 29 pathogenic/likely pathogenic CNVs in 24 patients were identified. The diagnostic yield of CMA for pathogenic/likely pathogenic CNVs was 23.1% (24/104), excluding 5 cases with aneuploidies or gross chromosomal aberrations. The overlapping analysis of CHD-related gene lists from different prioritization tools highlighted 16 CHD candidate genes.

Conclusion
As the first study focused on CNVs in syndromic CHD from the Chinese population, this study reveals the importance of CMA in exploring the genetic etiology of syndromic CHD and expands our understanding of these complex diseases. The bioinformatic analysis of candidate genes suggests several CHD-related genes for further functional research.
Can a parental sleep intervention in an individual setting improve the maternal and paternal sense of competence and parent–child interaction in parents of young sleep-disturbed children? findings from a single-arm pilot intervention study
Authors: Schnatschmidt Marisa , Lollies Friederike , Schlarb Angelika A. 
Published: October 2022

Abstract
Background
In early childhood sleep and regulatory problems, parental factors are often impaired but essential to overcoming them. This study aims to examine, in parents of young sleep-disturbed children, whether mothers’ and fathers’ sense of parenting competence were increased and dysfunctional parent–child interactions reduced with a parental sleep intervention, whether these changes were sustained over a 12-month follow-up period and if children’s symptomatic parameters could be related factors.

Methods
A total of 57 families with sleep-disturbed children aged 6 months to 4 years entered this single-arm pilot study. Each parent pair participated in six weekly individual face-to-face sessions of a multimodal cognitive-behavioral sleep intervention. The Parenting Sense of Competence Scale, Parental Stress Index Short Form, Child’s Sleep Diary and Child’s Questionnaire on Crying, Eating and Sleeping were obtained pre-, post-, 3, 6 and 12 months after the intervention.

Results
Maternal sense of competence and dysfunctional mother–child interaction improved significantly up to 6 months after the intervention. Factors related to lower maternal competence were the child’s more frequent nightly food intake and more crying due to defiance; factors related to dysfunctional mother–child interaction were more frequent crying episodes, more crying due to defiance and more eating difficulties; factors related to increased maternal competence were less duration of child’s night waking, less bed-sharing and lower frequency of crying episodes; factors related to increased paternal competence were less child’s nightly food intake and fewer episodes of unexplained and unsoothable crying; and factors related to improved father–child interaction were less frequent child’s night waking and fewer unexplained and unsoothable crying episodes.

Conclusion
For parents of sleep-disturbed young children, an intervention that addresses the child’s sleep could be promising to increase the parental sense of competence and reduce dysfunctional parent–child interactions, especially for mothers. Child symptomatic parameters may change, together with the parental sense of competence and parent–child interaction of both parents, after the intervention. Mothers with children with more severe symptomatology perceive their parenting competence as lower on average and their mother–child interaction as more dysfunctional. Future research with a larger sample and a randomized controlled design is needed.

Trial registration:
The study was retrospectively registered at the German Clinical Trials Register (ID: DRKS00028578; registration date: 21.03.2022).
Artificial intelligence-derived neurofibrillary tangle burden is associated with antemortem cognitive impairment
Authors: Marx Gabriel A. , Koenigsberg Daniel G. , McKenzie Andrew T. , Kauffman Justin , Hanson Russell W. , Whitney Kristen , Signaevsky Maxim , Prastawa Marcel , Iida Megan A. , White Charles L. , Walker Jamie M. , Richardson Timothy E. , Koll John , Fernandez Gerardo , Zeineh Jack , Cordon-Cardo Carlos , Crary John F. , Farrell Kurt ,   The PART working group
Published: October 2022

AbstractTauopathies are a category of neurodegenerative diseases characterized by the presence of abnormal tau protein-containing neurofibrillary tangles (NFTs). NFTs are universally observed in aging, occurring with or without the concomitant accumulation of amyloid-beta peptide (Aβ) in plaques that typifies Alzheimer disease (AD), the most common tauopathy. Primary age-related tauopathy (PART) is an Aβ-independent process that affects the medial temporal lobe in both cognitively normal and impaired subjects. Determinants of symptomology in subjects with PART are poorly understood and require clinicopathologic correlation; however, classical approaches to staging tau pathology have limited quantitative reproducibility. As such, there is a critical need for unbiased methods to quantitatively analyze tau pathology on the histological level. Artificial intelligence (AI)-based convolutional neural networks (CNNs) generate highly accurate and precise computer vision assessments of digitized pathology slides, yielding novel histology metrics at scale. Here, we performed a retrospective autopsy study of a large cohort (n = 706) of human post-mortem brain tissues from normal and cognitively impaired elderly individuals with mild or no Aβ plaques (average age of death of 83.1 yr, range 55–110). We utilized a CNN trained to segment NFTs on hippocampus sections immunohistochemically stained with antisera recognizing abnormal hyperphosphorylated tau (p-tau), which yielded metrics of regional NFT counts, NFT positive pixel density, as well as a novel graph-theory based metric measuring the spatial distribution of NFTs. We found that several AI-derived NFT metrics significantly predicted the presence of cognitive impairment in both the hippocampus proper and entorhinal cortex (p < 0.0001). When controlling for age, AI-derived NFT counts still significantly predicted the presence of cognitive impairment (p = 0.04 in the entorhinal cortex;p = 0.04 overall). In contrast, Braak stage did not predict cognitive impairment in either age-adjusted or unadjusted models. These findings support the hypothesis that NFT burden correlates with cognitive impairment in PART. Furthermore, our analysis strongly suggests that AI-derived metrics of tau pathology provide a powerful tool that can deepen our understanding of the role of neurofibrillary degeneration in cognitive impairment.