bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discriminating TB lung nodules from early lung cancers using deep learning
Authors: Tan Heng , Bates Jason H. T. , Matthew Kinsey C. 
Published: June 2022

Abstract
Background
In developing countries where both high rates of smoking and endemic tuberculosis (TB) are often present, identification of early lung cancer can be significantly confounded by the presence of nodules such as those due to latent TB (LTB). It is very challenging to distinguish lung cancer and LTB without invasive procedures, which have their own risks of morbidity and even mortality.

Methods
Our method uses a customized VGG16-based 15-layer 2-dimensional deep convolutional neural network (DNN) architecture with transfer learning. The DNN was trained and tested on sets of CT images set extracted from the National Lung Screening Trial and the National Institute of Allergy and Infectious Disease TB Portals. Performance of the DNN was evaluated under locked and step-wise unlocked pretrained weight conditions.

Results
The DNN with unlocked pretrained weights achieved an accuracy of 90.4% with an F score of 90.1%.

Conclusions
Our findings support the potential for a DNN to serve as a noninvasive screening tool capable of reliably detecting and distinguishing between lung cancer and LTB.
Supporting family care: a scoping app review
Authors: Bidenko Katharina , Bohnet-Joschko Sabine 
Published: June 2022

Abstract
Background
Mobile applications (apps) may provide family caregivers of people with chronic diseases and conditions with access to support and good information. However, thorough understanding of how these apps meet the main needs and requirements of the users is currently lacking. The aim of this study was to review the currently available apps for family caregivers and evaluate their relevance to main domains of caregiving activities, caregivers’ personal needs, and caregivers’ groups found in previous research on family caregivers.

Methods
We conducted a scoping review on English-language and German-language apps for family caregivers on two major app stores: Google Play Store and iOS App Store. Apps were included if the main target group were family caregivers. Data were extracted from the app descriptions provided by the app producers in the app stores.

Results
The majority of the apps was designed to assist caregivers in their caregiving activities. Apps were rarely tailored to specific groups of family caregivers such as young carers and their needs. Further, apps addressing caregivers’ personal health, financial security, and work issues were scarce. Commercial apps dominated the market, often intermediating paid services or available for users of specific hardware. Public and non-profit organizations provided best-rated and free-of-charge apps but had a very limited range of services with focus on caregivers’ health and training.

Conclusions
Our results indicate that current apps for family caregivers do not distinguish specific groups of family caregivers, also they rarely address caregivers’ personal needs.
Pinpointing novel risk loci for Lewy body dementia and the shared genetic etiology with Alzheimer’s disease and Parkinson’s disease: a large-scale multi-trait association analysis
Authors: Guo Ping , Gong Weiming , Li Yuanming , Liu Lu , Yan Ran , Wang Yanjun , Zhang Yanan , Yuan Zhongshang 
Published: June 2022

Abstract
Background
The current genome-wide association study (GWAS) of Lewy body dementia (LBD) suffers from low power due to a limited sample size. In addition, the genetic determinants underlying LBD and the shared genetic etiology with Alzheimer’s disease (AD) and Parkinson’s disease (PD) remain poorly understood.

Methods
Using the largest GWAS summary statistics of LBD to date (2591 cases and 4027 controls), late-onset AD (86,531 cases and 676,386 controls), and PD (33,674 cases and 449,056 controls), we comprehensively investigated the genetic basis of LBD and shared genetic etiology among LBD, AD, and PD. We first conducted genetic correlation analysis using linkage disequilibrium score regression (LDSC), followed by multi-trait analysis of GWAS (MTAG) and association analysis based on SubSETs (ASSET) to identify the trait-specific SNPs. We then performed SNP-level functional annotation to identify significant genomic risk loci paired with Bayesian fine-mapping and colocalization analysis to identify potential causal variants. Parallel gene-level analysis including GCTA-fastBAT and transcriptome-wide association analysis (TWAS) was implemented to explore novel LBD-associated genes, followed by pathway enrichment analysis to understand underlying biological mechanisms.

Results
Pairwise LDSC analysis found positive genome-wide genetic correlations between LBD and AD (rg = 0.6603, se = 0.2001; P = 0.0010), between LBD and PD (rg = 0.6352, se = 0.1880; P = 0.0007), and between AD and PD (rg = 0.2136, se = 0.0860; P = 0.0130). We identified 13 significant loci for LBD, including 5 previously reported loci (1q22, 2q14.3, 4p16.3, 4q22.1, and 19q13.32) and 8 novel biologically plausible genetic associations (5q12.1, 5q33.3, 6p21.1, 8p23.1, 8p21.1, 16p11.2, 17p12, and 17q21.31), among which APOC1 (19q13.32), SNCA (4q22.1), TMEM175 (4p16.3), CLU (8p21.1), MAPT (17q21.31), and FBXL19 (16p11.2) were also validated by gene-level analysis. Pathway enrichment analysis of 40 common genes identified by GCTA-fastBAT and TWAS implicated significant role of neurofibrillary tangle assembly (GO:1902988, adjusted P = 1.55 × 10−2).

Conclusions
Our findings provide novel insights into the genetic determinants of LBD and the shared genetic etiology and biological mechanisms of LBD, AD, and PD, which could benefit the understanding of the co-pathology as well as the potential treatment of these diseases simultaneously.
Hepatitis B virus virion secretion is a CRM1-spike-mediated late event
Authors: Su Pei-Yi , Yen Shin-Chwen Bruce , Yang Ching-Chun , Chang Chih-Hsu , Lin Wen-Chang , Shih Chiaho 
Published: June 2022

AbstractBackgroundHepatitis B virus (HBV) is a major human pathogen worldwide. To date, there is no curative treatment for chronic hepatitis B. The mechanism of virion secretion remains to be investigated. Previously, we found that nuclear export of HBc particles can be facilitated via two CRM1-specific nuclear export signals (NES) at the spike tip.MethodsIn this study, we used site-directed mutagenesis at the CRM1 NES, as well as treatment with CRM1 inhibitors at a low concentration, or CRM1-specific shRNA knockdown, in HBV-producing cell culture, and measured the secretion of various HBV viral and subviral particles via a native agarose gel electrophoresis assay. Separated HBV particles were characterized by Western blot analysis, and their genomic DNA contents were measured by Southern blot analysis. Secreted extracellular particles were compared with intracellular HBc capsids for DNA synthesis and capsid formation. Virion secretion and the in vivo interactions among HBc capsids, CRM1 and microtubules, were examined by proximity ligation assay, immunofluorescence microscopy, and nocodazole treatment.ResultsWe report here that the tip of spike of HBV core (HBc) particles (capsids) contains a complex sensor for secretion of both HBV virions and naked capsids. HBV virion secretion is closely associated with HBc nuclear export in a CRM1-dependent manner. At the conformationally flexible spike tips of HBc particles, NES motifs overlap extensively with motifs important for secretion of HBV virions and naked capsids.ConclusionsWe provided experimental evidence that virions and naked capsids can egress via two distinct, yet overlapping, pathways. Unlike the secretion of naked capsids, HBV virion secretion is highly CRM1- and microtubule-dependent. CRM1 is well known for its involvement in nuclear transport in literature. To our knowledge, this is the first report that CRM1 is required for virion secretion. CRM1 inhibitors could be a promising therapeutic candidate for chronic HBV patients in clinical medicine.
Immuno-activated mesenchymal stem cell living electrospun nanofibers for promoting diabetic wound repair
Authors: Gao Shaoying , Chen Tao , Wang Zhen , Ji Ping , Xu Lin , Cui Wenguo , Wang Ying 
Published: June 2022

AbstractDiabetic wound is the leading cause of non-traumatic amputations in which oxidative stress and chronic inflammation are main factors affecting wound healing. Although mesenchymal stem cells (MSCs) as living materials can promote skin regeneration, they are still vulnerable to oxidative stress which limits their clinical applications. Herein, we have prepared (polylactic-co-glycolic acid) (PLGA) nanofibers electrospun with LPS/IFN-γ activated macrophage cell membrane. After defining physicochemical properties of the nanofibers modified by LPS/IFN-γ activated mouse RAW264.7 cell derived membrane (RCM-fibers), we demonstrated that the RCM-fibers improved BMMSC proliferation and keratinocyte migration upon oxidative stress in vitro. Moreover, bone marrow derived MSCs (BMMSCs)-loaded RCM-fibers (RCM-fiber-BMMSCs) accelerated wound closure accompanied by rapid re-epithelialization, collagen remodeling, antioxidant stress and angiogenesis in experimental diabetic wound healing in vivo. Transcriptome analysis revealed the upregulation of genes related to wound healing in BMMSCs when co-cultured with the RCM-fibers. Enhanced healing capacity of RCM-fiber-BMMSCs living material was partially mediated through CD200-CD200R interaction. Similarly, LPS/IFN-γ activated THP-1 cell membrane coated nanofibers (TCM-fibers) exhibited similar improvement of human BMMSCs (hBMMSCs) on diabetic wound healing in vivo. Our results thus demonstrate that LPS/IFN-γ activated macrophage cell membrane-modified nanofibers can in situ immunostimulate the biofunctions of BMMSCs, making this novel living material promising in wound repair of human diabetes.Graphical Abstract
Outcomes of adolescent and young patients with hepatocellular carcinoma after curative liver resection: a retrospective study
Authors: Zhang Zheng-Yun , Guan Jiao , Wang Xin-Ping , Hao Di-Si , Zhou Zun-Qiang 
Published: June 2022

Abstract
Background
The risk of HCC is documented to be age-related. The outcomes of young HCC patients on postoperative prognosis are not well understood. The study aims to compare the characteristic differences between adolescent and young (AYA) and non-AYA HCC patients.

Methods
We performed a retrospective analysis of the clinical and pathological findings and the survival of 243 HCC patients who underwent operations between 2007 and 2018.

Results
The AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05). AYA patients had more unfavorable pathological characteristics including bigger lesion size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation (P < 0.01). Age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). Patients under 30 years old had an even poorer disease-free survival than those aged 30–40 (P = 0.047).

Conclusions
AYA patients exhibited a higher recurrence rate and disease-related death rate with more unfavorable pathological characteristics. Enhanced follow-up for young HCC patients should be applied.
Secretion of miRNA-326-3p by senescent adipose exacerbates myocardial metabolism in diabetic mice
Authors: Lin Hao , Chen Xiaonan , Pan Jianan , Ke Jiahan , Zhang Alian , Liu Yangyang , Wang Changqian , Chang Alex Chia Yu , Gu Jun 
Published: June 2022

Abstract
Background
Adipose tissue homeostasis is at the heart of many metabolic syndromes such as diabetes. Previously it has been demonstrated that adipose tissues from diabetic patients are senescent but whether this contributes to diabetic cardiomyopathy (DCM) remains to be elucidated.

Methods
The streptozotocin (STZ) type 1 diabetic mice were established as animal model, and adult mouse ventricular myocytes (AMVMs) isolated by langendorff perfusion as well as neonatal mouse ventricular myocytes (NMVMs) were used as cell models. Senescent associated β galactosidase (SA-β-gal) staining and RT-qPCR were used to identify the presence of adipose senescence in diabetic adipose tissue. Senescent adipose were removed either by surgery or by senolytic treatment. Large extracellular vesicles (LEVs) derived from adipose tissue and circulation were separated by ultracentrifugation. Cardiac systolic and diastolic function was evaluated through cardiac ultrasound. Cardiomyocytes contraction function was evaluated by the Ionoptix HTS system and live cell imaging, mitochondrial morphology and functions were evaluated by transmission electron microscope, live cell fluorescent probe and seahorse analysis. RNA-seq for AMVMs and miRNA-seq for LEVs were performed, and bioinformatic analysis combined with RT-qPCR and Western blot were used to elucidate underlying mechanism that senescent adipose derives LEVs exacerbates myocardial metabolism.

Results
SA-β-gal staining and RT-qPCR identified the presence of adipose tissue senescence in STZ mice. Through surgical as well as pharmacological means we show that senescent adipose tissue participates in the pathogenesis of DCM in STZ mice by exacerbates myocardial metabolism through secretion of LEVs. Specifically, expression of miRNA-326-3p was up-regulated in LEVs isolated from senescent adipose tissue, circulation, and cardiomyocytes of STZ mice. Up-regulation of miRNA-326-3p coincided with myocardial transcriptomic changes in metabolism. Functionally, we demonstrate that miRNA-326-3p inhibited the expression of Rictor and resulted in impaired mitochondrial and contractile function in cardiomyocytes.

Conclusion
We demonstrate for the first time that senescent adipose derived LEVs exacerbates myocardial metabolism through up-regulated miRNA-326-3p which inhibits Rictor in cardiomyocytes. Furthermore, reducing senescence burden in adipose tissue is capable of relieving myocardial metabolism disorder in diabetes mellitus.
Advances of exosomes in periodontitis treatment
Authors: Lin Hongbing , Chen Huishan , Zhao Xuetao , Ding Tong , Wang Yawei , Chen Zhen , Tian Yue , Zhang Peipei , Shen Yuqin 
Published: June 2022

AbstractPeriodontitis is an inflammatory disease initiated by dysbiosis of the local microbial community. Periodontitis can result in destruction of tooth-supporting tissue; however, overactivation of the host immune response is the main reason for alveolar bone loss. Periodontal tissue cells, immune cells, and even further activated osteoclasts and neutrophils play pro-inflammatory or anti-inflammatory roles. Traditional therapies for periodontitis are effective in reducing the microbial quantities and improving the clinical symptoms of periodontitis. However, these methods are non-selective, and it is still challenging to achieve an ideal treatment effect in clinics using the currently available treatments and approaches. Exosomes have shown promising potential in various preclinical and clinical studies, including in the diagnosis and treatment of periodontitis. Exos can be secreted by almost all types of cells, containing specific substances of cells: RNA, free fatty acids, proteins, surface receptors and cytokines. Exos act as local and systemic intercellular communication medium, play significant roles in various biological functions, and regulate physiological and pathological processes in numerous diseases. Exos-based periodontitis diagnosis and treatment strategies have been reported to obtain the potential to overcome the drawbacks of traditional therapies. This review focuses on the accumulating evidence from the last 5 years, indicating the therapeutic potential of the Exos in preclinical and clinical studies of periodontitis. Recent advances on Exos-based periodontitis diagnosis and treatment strategies, existing challenges, and prospect are summarized as guidance to improve the effectiveness of Exos on periodontitis in clinics.
Positive interaction between GPER and β-alanine in the dorsal root ganglion uncovers potential mechanisms: mediating continuous neuronal sensitization and neuroinflammation responses in neuropathic pain
Authors: Xu Zhenzhen , Xie Wanli , Feng Yiqi , Wang Yanting , Li Xia , Liu Jie , Xiong Yue , He Yuyao , Chen Lu , Liu Guoyang , Wu Qingping 
Published: June 2022

Abstract
Background
The pathogenesis of neuropathic pain and the reasons for the prolonged unhealing remain unknown. Increasing evidence suggests that sex oestrogen differences play a role in pain sensitivity, but few studies have focused on the oestrogen receptor which may be an important molecular component contributing to peripheral pain transduction. We aimed to investigate the impact of oestrogen receptors on the nociceptive neuronal response in the dorsal root ganglion (DRG) and spinal dorsal horn using a spared nerve injury (SNI) rat model of chronic pain.

Methods
We intrathecally (i.t.) administered a class of oestrogen receptor antagonists and agonists intrathecal (i.t.) administrated to male rats with SNI or normal rats to identify the main receptor. Moreover, we assessed genes identified through genomic metabolic analysis to determine the key metabolism point and elucidate potential mechanisms mediating continuous neuronal sensitization and neuroinflammatory responses in neuropathic pain. The excitability of DRG neurons was detected using the patch-clamp technique. Primary culture was used to extract microglia and DRG neurons, and siRNA transfection was used to silence receptor protein expression. Immunofluorescence, Western blotting, RT-PCR and behavioural testing were used to assess the expression, cellular distribution, and actions of the main receptor and its related signalling molecules.

Results
Increasing the expression and function of G protein-coupled oestrogen receptor (GPER), but not oestrogen receptor-α (ERα) and oestrogen receptor-β (ERβ), in the DRG neuron and microglia, but not the dorsal spinal cord, contributed to SNI-induced neuronal sensitization. Inhibiting GPER expression in the DRG alleviated SNI-induced pain behaviours and neuroinflammation by simultaneously downregulating iNOS, IL-1β and IL-6 expression and restoring GABAα2 expression. Additionally, the positive interaction between GPER and β-alanine and subsequent β-alanine accumulation enhances pain sensation and promotes chronic pain development.

Conclusion
GPER activation in the DRG induces a positive association between β-alanine with iNOS, IL-1β and IL-6 expression and represses GABAα2 involved in post-SNI neuropathic pain development. Blocking GPER and eliminating β-alanine in the DRG neurons and microglia may prevent neuropathic pain development.
Ethnobotany of medicinal plants used by the Yao people in Gongcheng County, Guangxi, China
Authors: Lu Zhaocen , Chen Hailing , Lin Chunrui , Ou Gui , Li Junsheng , Xu Weibin 
Published: June 2022

Abstract
Background
Gongcheng Yao Autonomous County (Gongcheng) is typical for the Yao people in northeastern Guangxi, southern China. The Yao people have a long history of using medicinal plants. In this study, we used ethnobotanical methods to collect traditional knowledge regarding herbal medicines in Gongcheng. Our study provides fundamental data for developing and applying local ethnic medicines and their protection.

Methods
Ethnobotanical data were collected from 103 villages in nine townships from 2014 to 2018 in Gongcheng. A total of 352 informants (279 male and 73 female) were interviewed through semi-structured interviews, key informant interviews, and guided field walks. All the informants were local inhabitants aged between 28 and 101 years of age, of which 40 key informants were selected based on the recommendations of knowledgeable elders and local medical institutions. The informant consensus factor (ICF) was used to evaluate the degree and importance of differences in medicinal plant species and calculated the relative frequencies of citation (RFC) for the recorded medicinal plants.

Results
Data from 352 local healers were collected for the study. The Guanyin and Sanjiang townships had the highest distribution of per capita healers (Pch), while the Gongcheng, Lianhua, and Ping'an townships were relatively lower. Of the 352 local healers, more than half were older than 60 years of age and therefore faced the problem of suitable successors and potential loss of traditional medicinal knowledge. There are 12 types of diseases treated by local healers in the study area, and most of the types had a high ICF value. The highest ICF (0.80) was reported for digestive system disease, followed by urinary system disease (0.78) and nervous system disease (0.77). Traumatic injury and orthopedics, digestive system, and rheumatic disease are the most common ailments. The RFC value calculated in 33 medicinal plant species (with an FC of more than 5) ranged from 0.024 to 0.056. The higher RFC values included Kadsura longipedunculata, Schefflera heptaphylla, Plantago asiatica, etc. The most commonly used medicinal method was decoction; plasters, creams, and some form of moxibustion and cupping skills were locally practiced, but only rarely. The local healers used 306 medicinal plant species (116 families and 255 genera). Herbal plants were most commonly used among these, with whole plants and roots being favored.

Conclusion
The Yao people are highly skilled at using medicinal plants to treat various diseases in Gongcheng. Their treatment methods are varied, convenient, and efficient. Due to the impact of urbanization and economic development, knowledge of traditional medicine is under threat, with declining numbers of local healers and a lack of suitable successors. In order to protect and inherit Yao's traditional medicinal knowledge, it is necessary to educate young healers and to protect biodiversity.
Urgent need to expand syringe services programs in South Carolina and beyond
Authors: Pham Quang , Burrows Marc , Litwin Alain 
Published: June 2022

AbstractOpioid related overdose deaths in the United States claimed over 100,000 thousand lives during the 12-month period ending in April 2021, an increase of 28.5% from the previous period. Syringe services programs (SSPs) are an evidence-based harm reduction strategy that have been shown to be effective in reducing opioid overdose deaths and infectious complications and increasing rates of entry into recovery programs. Ignoring this evidence, South Carolina (SC) and several states have yet to legalize SSPs. In the absence of full legalization, the operation of SSPs in SC faces many barriers. Despite these barriers, Challenges Inc. has been successful in playing a critical role in preventing opioid overdoses through naloxone and fentanyl test strip distribution, reducing infectious complications by providing clean needles, treating individuals with hepatitis C and HIV, and helping patients remain in sustained recovery from opioids. In order for SSPs to function at their full potential to curb the rising tides of opioid overdose deaths and related health complications, policymakers in SC and similar states need to urgently legalize them.