bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the levels of depression and anxiety in elderly aortic stenosis patients treated with surgical or transcatheter aortic valve replacement
Authors: Sun Jiao , Meng Qing-Tao , Wang Yu-Wei , Zhao Wei-Long , Sun Feng-Zhi , Liu Ji-Hong , Liu Ji-Yi 
Published: June 2022

Abstract
Objective
Currently, only a few studies have been conducted on the mental status recovery in elderly aortic stenosis (AS) patients after treatment. How transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) differentially impinge on the mental status of elderly AS patients is completely unknown. The present prospective study aims to investigate this question by comparing the post-treatment levels of depression and anxiety, quality of life and frailty.

Methods
A total of 120 elderly patients (age above 70) with symptomatic AS were included, where 78 of them were treated with TAVR and 42 of them were treated with SAVR. Levels of depression and anxiety, quality of life and frailty were assessed by the Chinese version of Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life Instrument-Older Adults Module (WHOQOL-OLD) and clinical frailty scale, respectively. Scores were recorded and compared at admission, 1 month, 4 months and 8 months after treatment.

Results
Before treatment, both patient groups had similar baseline characteristics and all mental parameters. During the follow-up period, patients in the TAVR group demonstrated significant improvement in all assessed mental parameters to certain extent compared to the SAVR group. Specifically, frailty was significantly improved in the TAVR-treated patients at all three follow-up time points. Levels of depression and anxiety were significantly improved 8 months after treatment, although the remaining patient number is limited. Quality of life was only significantly improved 1 month after treatment.

Conclusion
TAVR may provide a better mental recovery outcome in elderly AS patients.
Diagnostic value of congenital pulmonary airway malformation volume ratio for fetal hydrops due to congenital lung malformations: a systematic review and meta-analysis
Authors: Zhu Pei , Cheng Kaisheng , He Mingsheng , Wang Yutong , Shen Pengyue , He Kanglin , Xu Chang , Zhang Ben , Liu Zhenmi 
Published: June 2022

Abstract
Objective
Meta-analysis was used to evaluate the diagnostic value of a CVR cut-off value of 1.6 for fetal hydrops due to congenital lung malformation (CLM).

Methods
A systematic search of PubMed, Embase, Web of Science, CNKI, VIP, and Wanfang published before 7/30/2021 for the value of a congenital pulmonary airway malformation volume ratio (CVR) cut-off value of 1.6 for the diagnosis of fetal hydrops. According to the inclusion and exclusion criteria, the literature that met the requirements were obtained. A total of 75 articles were retrieved, and 12 articles were included for further analysis. The quality of these studies was evaluated according to the Quality Assessment for Studies of Diagnostic Accuracy tool (QUADAS-2) criteria. The Q test and heterogeneity I2 were used to evaluate the heterogeneity due to non-threshold effects, and Stata 15.0 was used for statistical analysis to evaluate the diagnostic value of the CVR cutoff value of 1.6 for fetal hydrops due to CLM.

Results
A total of 12 studies were included. The QUADAS-2 indicated that the risk of bias was relatively low, and the clinical applicability was relatively high. Statistical analysis was performed on included studies using a random effect model. Meta-analysis showed that the pooled sensitivity, specificity, diagnostic ratio and summary receiver operating characteristic (SROC) for the diagnosis of fetal hydrops by CVR were 0.86 (95% CI, 0.72–0.93; I2 = 59.84), 0.90 (95% CI, 0.88–0.93; I2 = 31.94), 58 (95% CI, 22–149; I2 = 100%), 0.93 (95% CI, 0.91–0.95).

Conclusions
The sensitivity and specificity of CVR cut-off value 1.6 for the diagnosis of CLM-induced fetal hydrops were high, no publication bias was observed, and the CVR cut-off value 1.6 is meaningful for the early diagnosis prediction of CLM-induced fetal hydrops.
Inducible localized delivery of an anti-PD-1 scFv enhances anti-tumor activity of ROR1 CAR-T cells in TNBC
Authors: Harrasser Micaela , Gohil Satyen Harish , Lau Hiu , Della Peruta Marco , Muczynski Vincent , Patel Dominic , Miranda Elena , Grigoriadis Kristiana , Grigoriadis Anita , Granger David , Evans Rachel , Nathwani Amit Chunilal 
Published: June 2022

Abstract
Background
Chimeric antigen receptor (CAR)-T cells can induce powerful immune responses in patients with hematological malignancies but have had limited success against solid tumors. This is in part due to the immunosuppressive tumor microenvironment (TME) which limits the activity of tumor-infiltrating lymphocytes (TILs) including CAR-T cells. We have developed a next-generation armored CAR (F i-CAR) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is expressed at high levels in a range of aggressive tumors including poorly prognostic triple-negative breast cancer (TNBC). The F i-CAR-T is designed to release an anti-PD-1 checkpoint inhibitor upon CAR-T cell activation within the TME, facilitating activation of CAR-T cells and TILs while limiting toxicity.

Methods
To bolster potency, we developed a F i-CAR construct capable of IL-2-mediated, NFAT-induced secretion of anti-PD-1 single-chain variable fragments (scFv) within the tumor microenvironment, following ROR1-mediated activation. Cytotoxic responses against TNBC cell lines as well as levels and binding functionality of released payload were analyzed in vitro by ELISA and flow cytometry. In vivo assessment of potency of F i-CAR-T cells was performed in a TNBC NSG mouse model.

Results
F i-CAR-T cells released measurable levels of anti-PD-1 payload with 5 h of binding to ROR1 on tumor and enhanced the cytotoxic effects at challenging 1:10 E:T ratios. Treatment of established PDL1 + TNBC xenograft model with F i-CAR-T cells resulted in significant abrogation in tumor growth and improved survival of mice (71 days), compared to non-armored CAR cells targeting ROR1 (F CAR-T) alone (49 days) or in combination with systemically administered anti-PD-1 antibody (57 days). Crucially, a threefold increase in tumor-infiltrating T cells was observed with F i-CAR-T cells and was associated with increased expression of genes related to cytotoxicity, migration and proliferation.

Conclusions
Our next-generation of ROR1-targeting inducible armored CAR platform enables the release of an immune stimulating payload only in the presence of target tumor cells, enhancing the therapeutic activity of the CAR-T cells. This technology provided a significant survival advantage in TNBC xenograft models. This coupled with its potential safety attributes merits further clinical evaluation of this approach in TNBC patients.
Implicating effector genes at COVID-19 GWAS loci using promoter-focused Capture-C in disease-relevant immune cell types
Authors: Pahl Matthew C. , Le Coz Carole , Su Chun , Sharma Prabhat , Thomas Rajan M. , Pippin James A. , Cruz Cabrera Emylette , Johnson Matthew E. , Leonard Michelle E. , Lu Sumei , Chesi Alessandra , Sullivan Kathleen E. , Romberg Neil , Grant Struan F. A. , Wells Andrew D. 
Published: June 2022

Abstract
Background
SARS-CoV-2 infection results in a broad spectrum of COVID-19 disease, from mild or no symptoms to hospitalization and death. COVID-19 disease severity has been associated with some pre-existing conditions and the magnitude of the adaptive immune response to SARS-CoV-2, and a recent genome-wide association study (GWAS) of the risk of critical illness revealed a significant genetic component. To gain insight into how human genetic variation attenuates or exacerbates disease following SARS-CoV-2 infection, we implicated putatively functional COVID risk variants in the cis-regulatory landscapes of human immune cell types with established roles in disease severity and used high-resolution chromatin conformation capture to map these disease-associated elements to their effector genes.

Results
This functional genomic approach implicates 16 genes involved in viral replication, the interferon response, and inflammation. Several of these genes (PAXBP1, IFNAR2, OAS1, OAS3, TNFAIP8L1, GART) were differentially expressed in immune cells from patients with severe versus moderate COVID-19 disease, and we demonstrate a previously unappreciated role for GART in T cell-dependent antibody-producing B cell differentiation in a human tonsillar organoid model.

Conclusions
This study offers immunogenetic insight into the basis of COVID-19 disease severity and implicates new targets for therapeutics that limit SARS-CoV-2 infection and its resultant life-threatening inflammation.
De novo reconstruction of cell interaction landscapes from single-cell spatial transcriptome data with DeepLinc
Authors: Li Runze , Yang Xuerui 
Published: June 2022

Abstract
Based on a deep generative model of variational graph autoencoder (VGAE), we develop a new method, DeepLinc (deep learning framework for Landscapes of Interacting Cells), for the de novo reconstruction of cell interaction networks from single-cell spatial transcriptomic data. DeepLinc demonstrates high efficiency in learning from imperfect and incomplete spatial transcriptome data, filtering false interactions, and imputing missing distal and proximal interactions. The latent representations learned by DeepLinc are also used for inferring the signature genes contributing to the cell interaction landscapes, and for reclustering the cells based on the spatially coded cell heterogeneity in complex tissues at single-cell resolution.
Distal-less and spalt are distal organisers of pierid wing patterns
Authors: Wee Jocelyn Liang Qi , Das Banerjee Tirtha , Prakash Anupama , Seah Kwi Shan , Monteiro Antonia 
Published: June 2022

AbstractTwo genes, Distal-less (Dll) and spalt (sal), are known to be involved in establishing nymphalid butterfly wing patterns. They function in several ways: in the differentiation of the eyespot’s central signalling cells, or foci; in the differentiation of the surrounding black disc; in overall scale melanisation (Dll); and in elaborating marginal patterns, such as parafocal elements. However, little is known about the functions of these genes in the development of wing patterns in other butterfly families. Here, we study the expression and function of Dll and sal in the development of spots and other melanic wing patterns of the Indian cabbage white, Pieris canidia, a pierid butterfly. In P. canidia, both Dll and Sal proteins are expressed in the scale-building cells at the wing tips, in chevron patterns along the pupal wing margins, and in areas of future scale melanisation. Additionally, Sal alone is expressed in the future black spots. CRISPR knockouts of Dll and sal showed that each gene is required for the development of melanic wing pattern elements, and repressing pteridine granule formation, in the areas where they are expressed. We conclude that both genes likely play ancestral roles in organising distal butterfly wing patterns, across pierid and nymphalid butterflies, but are unlikely to be differentiating signalling centres in pierids black spots. The genetic and developmental mechanisms that set up the location of spots and eyespots are likely distinct in each lineage.
Artificial intelligence for radiological paediatric fracture assessment: a systematic review
Authors: Shelmerdine Susan C. , White Richard D. , Liu Hantao , Arthurs Owen J. , Sebire Neil J. 
Published: June 2022

Abstract
Background
Majority of research and commercial efforts have focussed on use of artificial intelligence (AI) for fracture detection in adults, despite the greater long-term clinical and medicolegal implications of missed fractures in children. The objective of this study was to assess the available literature regarding diagnostic performance of AI tools for paediatric fracture assessment on imaging, and where available, how this compares with the performance of human readers.

Materials and methods
MEDLINE, Embase and Cochrane Library databases were queried for studies published between 1 January 2011 and 2021 using terms related to ‘fracture’, ‘artificial intelligence’, ‘imaging’ and ‘children’. Risk of bias was assessed using a modified QUADAS-2 tool. Descriptive statistics for diagnostic accuracies were collated.

Results
Nine eligible articles from 362 publications were included, with most (8/9) evaluating fracture detection on radiographs, with the elbow being the most common body part. Nearly all articles used data derived from a single institution, and used deep learning methodology with only a few (2/9) performing external validation. Accuracy rates generated by AI ranged from 88.8 to 97.9%. In two of the three articles where AI performance was compared to human readers, sensitivity rates for AI were marginally higher, but this was not statistically significant.

Conclusions
Wide heterogeneity in the literature with limited information on algorithm performance on external datasets makes it difficult to understand how such tools may generalise to a wider paediatric population. Further research using a multicentric dataset with real-world evaluation would help to better understand the impact of these tools.
Development and evaluation of a novel xeno-free culture medium for human-induced pluripotent stem cells
Authors: Hua Ying , Yoshimochi Kenji , Li Junjun , Takekita Kazuhiro , Shimotsuma Motoshi , Li Lingjun , Qu Xiang , Zhang Jingbo , Sawa Yoshiki , Liu Li , Miyagawa Shigeru 
Published: June 2022

Abstract
Background
Human-induced pluripotent stem cells (hiPSCs) are considered an ideal resource for regenerative medicine because of their ease of access and infinite expansion ability. To satisfy the sizable requirement for clinical applications of hiPSCs, large-scale, expansion-oriented, xeno-free, and cost-effective media are critical. Although several xeno-free media for hiPSCs have been generated over the past decades, few of them are suitable for scalable expansion of cultured hiPSCs because of their modest potential for proliferation and high cost.

Methods
In this study, we developed a xeno-free ON2/AscleStem PSC medium (ON2) and cultured 253G1 hiPSCs on different matrices, including iMatrix-511 and gelatin nanofiber (GNF) in ON2. Over 20 passages, we evaluated cell proliferation by doubling times; pluripotency by flow cytometry, immunofluorescence staining and qRT-PCR; and differentiation ability by three germ layer differentiation in vitro and teratoma formation in severe combined immunodeficiency mice, followed by histological analysis. In addition, we compared the maintenance effect of ON2 on hiPSCs with StemFit® AK02 (AK02N) and Essential 8™ (E8). Besides 253G1 hiPSCs, we cultivated different hiPSC lines, including Ff-l01 hiPSCs, ATCC® ACS-1020™ hiPSCs, and Down’s syndrome patient-specific ATCC® ACS-1003™ hiPSCs in ON2.

Results
We found that 253G1 hiPSCs in ON2 demonstrated normal morphology and karyotype and high self-renewal and differentiation abilities on the tested matrices for over 20 passages. Moreover, 253G1 hiPSCs kept on GNF showed higher growth and stemness, as verified by the shorter doubling time and higher expression levels of pluripotent markers. Compared to AK02N and E8 media, 253G1 hiPSCs grown in ON2 showed higher pluripotency, as demonstrated by the increased expression level of pluripotent factors. In addition, all hiPSC lines cultivated in ON2 were able to grow for at least 10 passages with compact clonal morphology and were positive for all detected pluripotent markers.

Conclusions
Our xeno-free ON2 was compatible with various matrices and ideal for long-term expansion and maintenance of not only healthy-derived hiPSCs but also patient-specific hiPSCs. This highly efficient medium enabled the rapid expansion of hiPSCs in a reliable and cost-effective manner and could act as a promising tool for disease modeling and large-scale production for regenerative medicine in the future.
Long-term observation after transplantation of cultured human corneal endothelial cells for corneal endothelial dysfunction
Authors: Sun Peng , Shen Lin , Li Yuan-Bin , Du Li-Qun , Wu Xin-Yi 
Published: June 2022

Abstract
Background
Corneal transplantation is the only way to treat serious corneal diseases caused by corneal endothelial dysfunction. However, the shortage of donor corneal tissues and human corneal endothelial cells (HCECs) remains a worldwide challenge. We cultivated HCECs by the use of a conditioned medium from orbital adipose-derived stem cells (OASC-CM) in vitro. Then the HCECs were used to treat animal corneal endothelial dysfunction models via cell transplantation. The purpose of this study was to conduct a long-term observation and evaluation after cell transplantation.

Methods
Orbital adipose-derived stem cells (OASCs) were isolated to prepare the conditioned medium (CM). HCECs were cultivated and expanded by the usage of the CM (CM-HCECs). Then, related corneal endothelial cell (CEC) markers were analyzed by immunofluorescence. The cell proliferation ability was also tested. CM-HCECs were then transplanted into monkey corneal endothelial dysfunction models by injection. We carried out a 24-month postoperative preclinical observation and verified the long-term effect by histological examination and transcriptome sequencing.

Results
CM-HCECs strongly expressed CEC-related markers and maintained polygonal cell morphology even after 10 passages. At 24 months after cell transplantation, there was a CEC density of more than 2400 cells per square millimeter (range, 2408–2685) in the experimental group. A corneal thickness (CT) of less than 550 μm (range, 490–510) was attained. Gene sequencing showed that the gene expression pattern of CM-HCECs was similar to that of transplanted cells and HCECs.

Conclusions
Transplantation of CM-HCECs into monkey corneal endothelial dysfunction models resulted in a transparent cornea after 24 months. This research provided a promising prospect of cell-based therapy for corneal endothelial diseases.
Misdiagnosis of COVID-19 infection before molecular confirmation in Sulaimaniyah City, Iraq
Authors: Mustafa Hemn Muhammed , Abdulateef Darya Saeed , Rahman Heshu Sulaiman 
Published: June 2022

Abstract
Background
During the last 2 years, in the Kurdistan Region, Northern Iraq, there were thousands of COVID-19 cases that have not been reported officially, but diagnosed and confirmed by private laboratories and private hospitals, or clinicians based on typical clinical signs, as well as few people using home self-test after appearing of some flu-like clinical symptoms. Thus, this study aims to assess the misdiagnosis and mismanagement of cases before COVID-19 confirmation.

Methods
This study enrolled 100 consecutive patients who visited an outpatient clinic of Shar Hospital that had symptoms highly suspicious of COVID-19 infection while misdiagnosed previously to have other types of disease. Detailed questionnaires were filled for all studied patients, including age, gender, main presenting symptoms, and duration of these symptoms with the following questions: who made the false diagnosis, depending on which diagnostic test the false diagnosis was made, which medication was used for the false diagnosis, who prescribed those medications, and how long those medications were used. They were investigated by RT-PCR on their nasopharyngeal swab for confirmation.

Results
Most of the false diagnoses were typhoid (63%), influenza (14%), pneumonia (9%), gastroenteritis (5%), common cold (4%), brucellosis (4%), and meningitis (1%). Regarding the false diagnosis of cases, 92% were made by non-physician healthcare workers, and only 8% were made by physicians. All false diagnoses with typhoid, gastroenteritis, and common cold were made by non-physician healthcare workers, together with about half of the diagnosis of pneumonia and brucellosis, with statistically significant results (P < 0.001).

Conclusions
We realized that some patients had been misdiagnosed before the COVID-19 infection confirmation. Their health conditions improved drastically after correct diagnosis and treatment, and this research is considered the first research to be conducted in Iraq in this regard.
Early-life galacto-oligosaccharides supplementation alleviates the small intestinal oxidative stress and dysfunction of lipopolysaccharide-challenged suckling piglets
Authors: Tian Shiyi , Wang Jue , Gao Ren , Wang Jing , Zhu Weiyun 
Published: June 2022

Abstract
Background
Galacto-oligosaccharides (GOS) are non-digestible food ingredients that promote the growth of beneficial bacteria in the gut. This study investigated the protective effect of the early-life GOS supplement on the piglets’ gut function against the oxidative stress induced by lipopolysaccharide (LPS)-challenge.

Methods
Eighteen neonatal piglets were assigned to three groups including CON, LPS and LPS + GOS groups. The piglets in CON group and LPS group received physiological saline, while those in LPS + GOS group received GOS solution for 13 d after birth. On d 14, the piglets in LPS group and LPS + GOS group were injected with LPS solutions, while the piglets in CON group were injected with the same volume of physiological saline.

Results
The results showed that the early-life GOS supplement blocked the LPS-induced reactive oxygen species (ROS) secretion, malondialdehyde (MDA) production and the increase of pro-apoptotic factor expression. Meanwhile, the early-life GOS supplement improved the activities of antioxidant enzymes, disaccharidase enzymes activities, and digestive enzymes activities, and increased the mRNA abundance of the gene related to nutrient digestion and absorption and the relative protein expression of tight junction. The study also showed that the early-life GOS supplement improved the expression of Hemeoxygenase-1 (HO-1) and NAD(P)H/quinone acceptor oxidoreductase-1 (NQO-1), and activated the AMP-activated protein kinase (AMPK).

Conclusions
These results suggested that GOS enhanced the gut function, reduced the ROS production and pro-apoptotic factors gene expression, and activated the AMPK signaling pathway in LPS-challenged piglets.
Inclusion body myositis and associated diseases: an argument for shared immune pathologies
Authors: Nelke Christopher , Kleefeld Felix , Preusse Corinna , Ruck Tobias , Stenzel Werner 
Published: June 2022

AbstractInclusion body myositis (IBM) is the most prevalent idiopathic inflammatory myopathy (IIM) affecting older adults. The pathogenic hallmark of IBM is chronic inflammation of skeletal muscle. At present, we do not classify IBM into different sub-entities, with the exception perhaps being the presence or absence of the anti-cN-1A-antibody. In contrast to other IIM, IBM is characterized by a chronic and progressive disease course. Here, we discuss the pathophysiological framework of IBM and highlight the seemingly prototypical situations where IBM occurs in the context of other diseases. In this context, understanding common immune pathways might provide insight into the pathogenesis of IBM. Indeed, IBM is associated with a distinct set of conditions, such as human immunodeficiency virus (HIV) or hepatitis C—two conditions associated with premature immune cell exhaustion. Further, the pathomorphology of IBM is reminiscent of other muscle diseases, notably HIV-associated myositis or granulomatous myositis. Distinct immune pathways are likely to drive these commonalities and senescence of the CD8+T cell compartment is discussed as a possible mechanism of pathogenesis. Future effort directed at understanding the co-occurrence of IBM and associated diseases could prove valuable to better understand the enigmatic IBM pathophysiology.