bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal Health Policy Priorities in Pakistan: A Content Analysis of Policy Documents
Authors: Sadaat Pakeezah , Zain Shahzadi , Jameel Bismah , Shaikh Rida , Bowen Brittany , Majid Umair
Published: November 2020

Background: Despite numerous improvements in the health care system of Pakistan in the past few decades, many disparities continue to persist between health care policies and practices in comparison to developed nations, particularly in the area of maternal health. Despite a 181% increase in expenditure, Pakistan did not meet its target to reduce child mortality and improve maternal health by 2015, causing these disparities to further widen. Methods: We sought to investigate the policymaking process of Pakistan by conducting a content analysis of 34 policy documents pertaining to maternal health service delivery. Results: We found a number of gaps, priorities, and determinants for health policymaking. The most commonly discussed themes were the following: Measures of Burden, System and Organizational Capacity, Access and Availability of Health Services, Policy and Planning, Gaps and Needs, and Socioeconomic Factors. Integrated care and opioid use were seldom mentioned in included policy documents. Conclusions: We discuss the reasons that might explain why Pakistan has not observed an improvement in maternal health outcomes despite significant investment. We use path dependency to explain that drawbacks of health care priority-setting processes in Pakistan. We suggest a refocus on identifying and improving health disparities between communities. We also suggest research and policy attention on integrated care and opioid use in Pakistan.
Genomic Differences Between Carbapenem-susceptible and Carbapenem-resistant Escherichia Coli Analyzed by Whole-genome Sequencing
Authors: Wu Qiong , Hu Jun , Wang Jianqiang , Li Yungai , Pan Yunqi , Chen Rong , Tang Jin
Published: November 2020

Background The widespread resistance to carbapenem via Enterobacteriaceae is a major public health concern. To investigate the reason for the change of Escherichia coli from carbapenem-susceptible to carbapenem-resistant status after antibiotic therapy, whole-genome sequencing was applied for the analysis of genetic difference between the two isolates. The genome of the two isolates of Escherichia coli with distinct resistant phenotypes recovered from one patient was sequenced and compared. Single-nucleotide polymorphisms and insertions/deletions were analyzed using software MUMmer (http://mummer.sourceforge.net/). Results The homology of chromosomes, plasmid 1, and plasmid 2 between the two isolates was very high (>99.5%). However, the coverage ratio of plasmid 3 was only 7.13%. This plasmid harbored the IMP-4 carbapenemase-coding gene. The upstream of blaIMP-4 was the plasmid mobilization relaxosome protein Mobe gene and the downstream were class 1 integrom integrase IntI1 and IS6 family transposase IS15DIV, which may be related to carbapenemase gene capture. Conclusions Single-nucleotide mutation, insertion, and deletion could not result in the development of resistance to carbapenem, whereas acquisition of the IMP-4-encoding gene may be the reason for changes in resistance to carbapenem.
Seasonal Changes of the Airborne Microbiome in a Large Urban Area
Authors: Núñez Andrés , Moreno Diego A , García Ana M , Guantes Raul
Published: November 2020

Background Compared to soil or aquatic ecosystems, the atmosphere is still an underexplored environment for microbial diversity. Besides its ecological importance, the spatial and temporal characterization of aerosolized microorganisms is relevant for understanding allergy and disease outbreaks, especially in highly populated cities. Results In this study, we surveyed the composition, variability and sources of microbes (bacteria and fungi) in the near surface atmosphere of a highly populated area, spanning ~ 4,000 Km 2 around the city center of Madrid (Spain), in different seasonal periods along two years. We found a core of abundant bacterial genera robust across space and time, most of soil origin, while fungi were more sensitive to environmental conditions. Microbial communities showed clear seasonal patterns driven by variability of environmental factors, mainly temperature and accumulated rain, while local sources played a minor role. We also identified taxa in both kingdoms characteristic of seasonal periods, but not of specific sampling sites or plant coverage. Conclusions The present study suggests that the near surface atmosphere of urban environments constitutes a stable ecosystem, with a relatively homogenous composition, modulated by climatic variations. As such, it contributes to our understanding of the long-term changes associated to the human exposome in the air of highly populated areas.
Efficacy of Pediatric Integrative Manual Therapy in Positional Plagiocephaly: A Randomized Controlled Trial.
Authors: Pastor-Pons Iñaki , López María Orosia Lucha , Barrau-Lalmolda Marta , Rodes-Pastor Iñaki , Rodríguez-Fernández Ángel Luis , Hidalgo-García César , Tricás-Moreno José Miguel
Published: November 2020

Background: positional plagiocephaly frequently affects healthy babies. It is hypothesized that manual therapy tailored to pediatrics is more effective in improving plagiocephalic cranial asymmetry than just repositioning and sensory and motor stimulation. Methods: 34 neurologically healthy subjects aged less than 28 weeks old with a difference of at least 5 mm between cranial diagonal diameters were randomly distributed into 2 groups. For 10 weeks, the pediatric integrative manual therapy (PIMT) group received manual therapy plus a caregiver education program, while the controls received the same education program exclusively. Cranial shape was evaluated using anthropometry; cranial index (CI) and cranial vault asymmetry index (CVAI) were calculated. Parental perception of change was assessed using a visual analogue scale (-10 cm to +10 cm). Results: CVAI presented a greater decrease in PIMT group: 3.72 ± 1.40 % compared with 0.34 ± 1.72% in the controls (p=0.000). CI changes did not present any significant differences between the 2 groups. Manual therapy increased positive parental perception of cranial changes (manual therapy: 6.66 ± 2.07 cm; control: 4.25 ± 2.31 cm; p= 0.004). Conclusion: manual therapy plus caregiver education program improved cranial symmetry and parents’ satisfaction more effectively than solely caregiver education program.Trial registration: trial registration number: NCT03659032; registration date: September 1, 2018. Retrospectively registered.https://clinicaltrials.gov/ct2/show/NCT03659032?term=NCT03659032&cond=Plagiocephaly&draw=2&rank=1
ADHD Symptoms and School Impairment History in Parents of ADHD Children are a Fundamental Diagnostic and Therapeutic Clue.
Authors: Wiel Luisa Cortellazzo , Rispoli Francesco , Peccolo Giulia , Rosolen Valentina , Barbi Egidio , Skabar Aldo
Published: November 2020

Background: Attention Deficit and Hyperactivity Disorder (ADHD) is a multi-factorial condition, with inheritance playing a major role. Recognizing parents’ ADHD represents a clue not only for an earlier diagnosis of the disease in their children, but also to optimize psycho-educational therapy outcome, by addressing the impairment of parenting related to untreated ADHD. This study aimed to assess the frequency of features suggestive of ADHD during childhood among parents of affected children, and the presence of school and emotional impairment.Methods: We administered the Wender Utah Rating Scale-25, a self-assessment tool for the retrospective identification of symptoms consistent with ADHD during childhood, to a cohort of 120 parents of 60 children diagnosed with ADHD, and to a consistent number of “controls”.Results: The WURS-25 proved positive in 49.1% of fathers and 30.0% of mothers of ADHD patients, compared to 1.7% of fathers and 1.7% of mothers of non-ADHD patients (p < 0.0001). The questions addressing learning and emotional impairment provided significantly higher scores in parents with an overall positive test compared to those with negative test (p < 0.0001).Conclusions: This study demonstrates a remarkably high rate of symptoms consistent with ADHD during childhood in parents of affected children. Physicians should be aware that this is a relevant anamnestic clue and, given the relevance of parents’ role in the management of children with ADHD, an important issue in order to improve patients’ treatment.
Case Report of Severe Lactic Acidosis and Persistent Diastolic Hypotension After Standard Dose Intermittent Salbutamol Nebulization in a Child: Rare Adverse Effects for Common Treatment.
Authors: Colombo Marco , Plebani Anna , Bosco Annalisa , Agosti Massimo
Published: November 2020

BackgroundSalbutamol is a selective β2 receptor agonist widely used to treat asthma and other conditions and it often represents the treatment of choice for reversing airflow obstruction both in emergency and domiciliary settings. However, it can be associated to a broad spectrum of side effects and even paradox effects, if administered intravenously, at high doses continuous nebulized treatment and even at standard doses intermittent nebulized treatment, the latter being the most hazardous due to its infrequency. Lactic acidosis and persistent diastolic hypotension secondary to intermittent salbutamol nebulization are rare in children, moreover at standard therapeutic doses during asthma exacerbations.Case presentation We present a case of a 12 year-old boy, 34 Kg, who experienced a serious drug reaction during a moderate asthma attack, after intermittent inhaled (0.2 mg in 3 hours interval – overall 1.4 mg in 24 hours before arrival) and nebulized treatment (3.25 mg in 20 minutes interval in 60 minutes, overall 11.25 mg in our ED). He began experiencing symptoms of toxicity (tremor) in the emergency department few minutes after administration of the second dose of nebulized salbutamol, without reporting that to health care providers. Few minutes after the end of the third nebulized dose, clinical conditions worsened showing hyperglycemia (highest value 222 mg/dl), hypokalemia (lowest value 2.6 mEq/L), electrocardiogram alterations, decreased blood pressure (lowest value 87/33 mm/Hg), increased lactate serum level (highest value 8.1 mmol/L). The patient fully recovered after discontinuation of salbutamol and was discharged after 24 hours of staying in the intensive brief observation unit of our pediatric emergency department.ConclusionsWe reinforce the message that not only intravenous administration or continuous nebulization of salbutamol can lead to severe complication in children, but also intermittent therapy given at standard doses. Then, health care providers should pay attention not only in emergency settings in order to achieve prompt recognition and proper management of this adverse reaction.
Breast Adipose Tissue Macrophages (BATMs) have a Stronger Correlation with Breast Cancer Survival than Breast Tumor Stroma Macrophages (BTSMs)
Authors: Lin Lili , Kuhn Christina , Ditsch Nina , Kolben Thomas , Czogalla Bastian , Beyer Susanne , Trillsch Fabian , Schmoeckel Elisa , Mayr Doris , Mahner Sven , Jeschke Udo , Hester Anna
Published: November 2020

Background: An abundance of tumor-associated macrophages has been shown to be an independent prognostic factor for a poor prognosis of human breast cancer (BC). Adipose tissue accounts for the largest proportion of the breast and has also been identified as an independent indicator of poor survival in BC. This study aims to elucidate, if the influence of adipose tissue in BC might be mediated by macrophages. The roles of macrophages in the breast tumor-stroma (breast tumor stroma macrophages, BTSM) and macrophages in the surrounding adipose tissue (breast adipose tissue macrophages, BATM) were explored separately.Methods: 298 BC tissue samples were analyzed immunohistochemically. The number of macrophages was detected by CD68+ staining. The quantity of BATMs and BTSMs was correlated to clinical and pathological parameters as well as to disease free survival (DFS) and overall survival (OS). Results: The amounts of BATMs and BTSMs strongly correlated with each other (r = 0.5, p < 0.001). The quantity of BTSMs, but not of BATMs, was significantly associated with the BC molecular subtype (p < 0.001) and all triple negative BC tumors contained high amounts of BTSMs. BATMs were negatively associated with DFS (p = 0.0332). Both BATMs (p < 0.001) and BTSMs (p = 0.021) were negatively associated with OS in the Kaplan-Meier analysis, but only BATMs remained an independent factor in the multivariate Cox-regression analysis (HR = 4.464, p = 0.004). Combining prostaglandin E2 receptor 3 (EP3)-expression and the quantity of BATMs, a subgroup with an extremely poor prognosis could be identified (median OS 2.31 years in the “high BATMs/low EP3” subgroup compared to 11.42 years in the most favorable “low BATMs/high EP3” subgroup, p < 0.001).Conclusion: Our findings suggest that BTSMs and BATMs seem to be involved differently in BC. Breast adipose tissue might contribute to the aggressiveness of BC via BATMs, which were independently associated with BC survival. BATMs’ role and occurrence might be functionally dependent on EP3, as a combination of both factors was strongly associated with survival. Targeting BATMs – eventually in combination with targeting the EP3-pathway – might be promising for future therapies.
Effects of Combining Diaphragm Training with Electrical Stimulation on Balance, Pain, and Function in Athletes with Chronic Low Back Pain : A Randomized Clinical Trial
Authors: Otadi Khadijeh , Ansari Noureddin Nakhostin , Sharify Shahriar , Fakhari Zahra , Sarafraz Hadi , Aria Amir , Rasouli Omid
Published: November 2020

Background: It is unknown how diaphragm training combined with electrical stimulation affect balance, core stability, pain, and function in athletes with chronic low back pain (CLBP). This study aimed to explore the effects of combining diaphragm training with electrical stimulation on core stability, dynamic balance, pain, and function in young athletes with nonspecific CLBP.Methods: The design was a randomized clinical trial A total of 24 young adult athletes (12 women, 12 men) with non-specific CLBP were randomly allocated into experimental and control group. The experimental group received diaphragm training plus Transcutaneous Electrical Nerve Stimulation (TENS), while the control group received only TENS. Both groups underwent 12 sessions over a 4-week period. Static stability, dynamic balance, pain, and function were measured pre- and post-intervention.Results: Significant improvements in pain and function scores were found in both groups after completing the interventions. However, only the experimental group showed significant improvements in the static stability and dynamic balance post-intervention. The experimental group showed greater improvements in pain and static stability. No significant differences in function or dynamic balance were observed between the groups. Conclusions: The present study indicates that diaphragm training plus TENS can improve static stability, dynamic balance, function, and pain in young athletes with non-specific CLBP. It seems beneficial to add diaphragm training to rehabilitation programs for athletes with CLBP.Trial registration: The trial was retrospectively registered at the Iranian Registry of Clinical Trials on www.irct.ir (Identification number: IRCT20090228001719N8).
The Role of Pruriceptors in Enhancing Sensitivity to Pruritogens in a Murine Chronic Compression Model of Dorsal Root Ganglion
Authors: Wang Tao , Tao Jin , Fang Yehong , Ma Chao
Published: November 2020

Chronic pruritus is a symptom that commonly observed in neurological diseases. It has been hypothesized that the chronic pruritus may result from sensitization of itch-signaling pathways but the mechanisms remain obscure. In this study, we established a mouse model of chronic compression of dorsal root ganglion (CCD) and injected various pruritogenic and algogenic agents intradermally to the calf skin ipsilateral to the compressed dorsal root ganglion (DRG). Compared to the naïve mice, a significant increase in itch-related behaviors was observed in the CCD mice after the injection of pruritogens including histamine and BAM8-22, but not after the injection of capsaicin, although all the above agents evoked enhanced pain-related behaviors toward the injected site. In addition, we investigated if pruritogen-evoked activities of DRG neurons are enhanced in this model. In vivo calcium imaging revealed that compressed DRG neurons exhibited significant enhanced responses to histamine and BAM8-22. Immunoflorescent staining also showed that the histamine receptor H1 and the capsaicin receptor TRPV1 were significantly upregulated in DRG neurons. Our findings indicated that in mice modeling the sensitization of primary pruriceptive neurons may underlie the enhanced itch sensation after chronic compression of DRG neurons, and may play a role in chronic pruritus in neurological diseases.
High Lymphocyte Population-related Predictive Factors for a Long-term Response in Non-small Cell Lung Cancer Patients Treated with Pemetrexed: A Retrospective Observational Study
Authors: Sumiyoshi Issei , Okabe Takahiro , Togo Shinsaku , Takagi Haruhi , Motomura Hiroaki , Ochi Yusuke , Shimada Naoko , Haraguchi Mizuki , Shibayama Rina , Fujimoto Yuichi , Watanabe Junko , Iwai Moe , Kadoya Kotaro , Iwakami Shin-ichiro , Takahashi Kazuhisa
Published: November 2020

BackgroundRegimens combining pemetrexed (PEM) and immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed death-ligand 1 (PD-L1) are widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSq-NSCLC). Recently, PEM was shown to induce immunogenic cell death (ICD) and to enhance immune-regulatory genes. Some patients demonstrate an extremely long-term response to PEM. It is possible that the continued response in these patients is dependent on not only the pharmacological induction of cytotoxic cell death but also antitumor immunity. However, factors that can predict outcomes associated with long-term PEM administration using blood test results have not yet been elucidated. We investigated the clinical characteristics and predictive factors in patients with advanced NSq-NSCLC who underwent long-term PEM maintenance therapy.MethodsIn total, 504 patients with advanced NSq-NSCLC who received PEM combination therapy/monotherapy (n=414) or paclitaxel (PTX) combination therapy (n=90) between January 2010 and November 2019 were recruited; 381 patients were retained for the final analysis. Patients treated with PEM (n=301) were divided into subgroups according to the total cycles of PEM (≥17 [n=25] for the long-term administration group and ≤16 [n=276] for the intermediate/short-term group) and compared with another population (n=80) treated with PTX combination regimen. We investigated clinical features and predictive biomarkers, focusing on immune-regulatory factors, absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), and PD-1 and PD-L1 expression, to predict long-term response to PEM. ResultsThe long-term PEM administration group exhibited a higher ALC and a lower NLR than the shorter-term group did. Both these markers displayed greater association with progression-free survival and overall survival in the PEM combination therapy group than in the PTX combination therapy group. Increased PD-1 lymphocytes were associated with the long-term PEM response group, as PD-L1 expression in tumors was associated with a high incidence of immune-related adverse effects following ICI administration.ConclusionsALC, NLR, and PD-1 expression are PEM-mediated predictive biomarkers that are indirectly related to tumor immunity and can provide useful predictive information on the long-term response to PEM in patients with NSq-NSCLC.
Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Pancreatic Ductal Adenocarcinoma
Authors: Xu Qianhui , Wang Yuxin , Huang Wen
Published: November 2020

Background: An increasing body of evidence has suggested that long non-coding RNAs (lncRNAs) can serve as essential regulators in cancer immunity. We aimed to establish a robust immune-associated lncRNA signature for pancreatic ductal adenocarcinoma (PDAC) outcome prediction to enhance prognostic accuracy.Methods: Pancreatic cancer samples were obtained from the The Cancer Genome Atlas (TCGA) project. Immune‐related lncRNAs displaying significant association with overall survival (OS) were screened through univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. The prediction reliability was further estimated in the internal validation set and combination set. Gene set enrichment analysis (GSEA) of the lncRNA model risk score was performed for functional annotation. The correlation between immune checkpoint inhibitors and this signature was examined. Results: 5 immune-related lncRNAs were confirmed to establish five‐immune-related lncRNAs prognostic signature. The constructed risk model showed significant correlation with PDAC OS. The area under the curve (AUC) for this lncRNA model was up to 0.747. This immune‐related lncRNA signature was correlated with disease progression and worse survival and was an independent prognostic biomarker. Our signature mediated chondrocyte development, laminin binding and so forth. This risk score model was associated with immune cell infiltration (i.e., CD4 T cells, etc.,) and immune checkpoint blockade (ICB) immunotherapy‐related molecules (i.e., PDCD1 and CTLA4).Conclusion: The immune‐related lncRNA signature we established possesses latent prognostic value for patients with PDAC and may have the potential to measure the response to ICB immunotherapy, which could guide for immunological treatment in PDAC.
MiRNA Profiling: Mouse Blastocyst Extracellular Microvesicles Inhibit Melanoma Cell Invasion
Authors: Duan Ruxia , Liu Qing , Wang Yiting , Wei Zixin , Ba Xiaoyun , Fang Liaoqiong
Published: November 2020

Background: Microvesicles (MVs) mediate the transmission of information between cells through the miRNAs, proteins, lipids and mRNAs carried by MVs, which inhibit/promote the function of receptor cells. This study confirmed that blastocyst MVs inhibited the invasion of melanoma cells and showed a complex miRNA pedigree. Functional miRNAs were found, and the mechanism of inhibiting invasiveness was analyzed based on the miRNA lineage characteristics of mouse blastocyst MVs, combined with the miRNA bioinformatics information of miRBase, microRNA.org, NCBI and other databases.Methods: MVs derived from D3.5 mouse blastocysts were isolated and the miRNA gene expression of MV was detected by fluorescence quantitative polymerase chain reaction (qPCR). The dynamic changes in tumor cell invasiveness in the co-culture system of blastocyst MVs and melanoma B16-F10 cells were monitored in real time. The MV miRNAs expression profile of blastocyst was identified using the qPCR array. Bioinformatics tools were used to analyze the characteristics of miRNA pedigree in blastocyst MV to screen functional miRNAs, which reduce tumor cell invasiveness and to predict functional miRNA target genes. The target genes were analyzed by KEGG and GO pathway enrichment analyses using David and FunRich software.Results: The average diameter of round MVs extracted from mouse blastocysts was 196.4 ±7.8 nm. When B16-F10 melanoma cells were co-cultured with mouse blastocyst MVs, no significant difference in invasive ability was found between the two groups before 72 h, but increased significantly after 72 h (P < 0.05, P < 0.01). A total of 336 miRNAs were analyzed in mouse blastocyst MVs. Further analysis showed that 224 miRNAs were associated with invasion. Also, 32 invasion-related miRNAs with the strongest differential expression were verified by real-time quantitative polymerase chain reaction (qPCR). The GO analysis of the target genes showed that the 32 functional miRNAs were mainly related to 8 biological processes, including DNA binding, sequence-specific DNA binding, metal ion binding, chromatin binding, nucleotide binding, sequence specificity, DNA binding transcription factor activity and ubiquitin-protein ligase activity. The KEGG pathway analysis showed that the 32 functional miRNAs were mainly related to the PI3K-Akt signaling pathway.Conclusion: Blastocyst MVs carrying miRNAs regulated the decrease in the invasive ability of melanoma cells through the PI3K-Akt signaling pathway.
LncRNA ACTA2-AS1 Suppress Colon Adenocarcinoma Progression by Sponging miR-4428 Upregulation BCL2L11
Authors: Pan Qingyun , Huang Ying , Wang Yirui , Li Deke , Lei Changjiang
Published: November 2020

BackgroundLong non-coding RNA is considered to be essential to modulate the development and progression of human malignant cancers. And long non-coding RNA can act as crucial modulators by sponging the corresponding microRNA in tumorigenesis. We aimed to elucidate the function of ACTA2-AS1 and its molecular mechanism in colon adenocarcinoma. Materials and MethodsThe expression of ACTA2-AS1, miR-4428 and BCL2L11 in colon adenocarcinoma tissues were detected via qRT-PCR. SW480 and HT29 cells were transfected with shRNA ACTA2-AS1, OE ACTA2-AS1, miRNA mimics of miR-4428, miR-4428 inhibitor, si-BCL2L11 and over-expression of si-BCL2L11. Cell proliferation, colony formation and apoptosis were respectively assessed using CCK-8 assay, colony assay and flow cytometry. Luciferase reporter assay was performed to verify the targets of ACTA2-AS1 and miR-4428. Tumor subcutaneous xenograft mode was constructed to explore tumor growth in vivo. ResultsACTA2-AS1 was obviously downregulated in human colon adenocarcinoma tissues and colon adenocarcinoma cell lines. Silence or over-expression of ACTA2-AS1 promoted or inhibited cell proliferation and colony formation abilities, and regulated apoptosis. The silence of ACTA2-AS1 resulted in the decrease of Bax and increase of Bal2, while restored in OE ACTA2-AS1 group when compared with the control transfected cells. In addition, luciferase reporter assay revealed that ACTA2-AS1 interacted with miR-4428 and suppressed its expression. miR-4428 could bind to 3ʹ untranslated region of BCL2L11 and modulated the expression of BCL2L11 negatively. Knockdown of ACTA2-AS1 and over-expression of BCL2L11 reversed the biological function that ACTA2-AS1 mediated by knockdown ACTA2-AS1 alone. ConclusionOur data demonstrated that ACTA2-AS1 could suppress colon adenocarcinoma progression via sponging miR-4428 to regulate BCL2L11 expression.
Identification of Four Key Prognostic Genes and Three Potential Drugs in Human Papillomavirus Negative Head and Neck Squamous Cell Carcinoma
Authors: Tian Guocai , Fu You , Zhang Dahe , Li Jiang , Zhang Zhiyuan , Yang Xi
Published: November 2020

BackgroundHead and neck squamous cell carcinoma (HNSCC) is a common tumor worldwide with poor prognosis. The pathogenesis of human papillomavirus (HPV)-positive and HPV-negative HNSCCs differs. However, few studies have considered the HPV status when identifying biomarkers for HNSCC. Thus, the identification of biomarkers for HPV-positive and HPV-negative HNSCCs is urgently needed.MethodsThree microarray datasets from Gene Expression Omnibus (GEO) were analyzed, and the differentially expressed genes (DEGs) were obtained. Then, functional enrichment pathway analysis was performed and protein-protein interaction (PPI) networks were constructed. The expression of hub genes at both the mRNA and protein level was determined in Oncomine, The Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA). In addition, survival analysis of the patient stratified by HPV status and the expression levels of key genes were performed based on TCGA data. The role of AREG, STAG3, CAV1 and C19orf57 in cancer were analyzed through Gene set enrichment analysis (GSEA). Finally, the top ten small molecule drugs were identified and the therapeutic value of zonisamide, NVP-AUY922, PP-2 and fostamatinib was further evaluated in six HPV-negative HNSCC cell lines.ResultsIn total, 47 DEGs were obtained, 11 of which were identified as hub genes. Biological process analysis indicated that the hub genes were associated with the G1/S transition of the mitotic cell cycle. Survival analysis uncovered that the prognostic value of AREG, STAG3, C19orf57 and CAV1 differed between HPV-positive and HPV-negative patients. Gene set enrichment analysis (GSEA) showed the role of AREG, STAG3 and CAV1 in dysregulated pathways of tumor. Ten small molecules were identified as potential drugs specifically for HPV-positive or HPV-negative patients; three—NVP-AUY922, fostamatinib and PP-2—greatly inhibited the proliferation of six HPV-negative HNSCC cell lines in vitro, and NVP-AUY922 inhibited three HPV-negative HNSCC xenografts in vivo.ConclusionsIn conclusion, AREG, STAG3, C19orf57 and CAV1 are key prognostic factors and potential therapeutic targets in HPV-negative HNSCC. NVP-AUY922, fostamatinib and PP-2 may be effective drugs for HPV-negative HNSCC.
Impact of Covid-19 pandemic for patient care in an Interventional Radiology Unit
Authors: Veiga José , Amante Sofia , Costa Nuno Vasco , Luz José Hugo , Gomes Filipe Veloso , Coimbra Élia , Bilhim Tiago
Published: November 2020

Purpose: Assess the impact of Covid-19 pandemic in work volume in an Interventional Radiology Unit during the “State of Emergency” (16th March - 30th April) in 2020 and to analyse the short-term consequences for oncology patients.Materials and Methods: Single-centre retrospective analysis. The number and type of procedures performed during the “State of Emergency” was compared with the homologous period in 2019. The second analysis compared the impact on disease progression for oncology patients after the “State of Emergency”. All patients that had a scheduled loco-regional treatment (LRT) (74 hepatocellular carcinoma (HCC); 10 liver metastases) between 2nd May - 16th July 2020 were compared with the homologous period in 2019 (68 HCC; 11 liver metastases). The compared outcome measures included: baseline data, time from diagnostic imaging to LRT, LRT performed as planned, change in LRT.Results: There was a 55.2% reduction of procedures during the “State of Emergency” (n=77 in 2020; n=172 in 2019) with a significant increase in urgent procedures (48.1% in 2020; 33.1% in 2019; p=0.0120). Post-“State of Emergency”, in 2020, HCC patients had higher model of end-stage liver disease (MELD) scores (p=0.0124) and larger tumours (mean difference of 8.7 mm, p=0.0071). Mean time from diagnostic imaging to LRT increased 14.1 days (p=0.0439). More patients received different or no LRT due to disease progression (15.5% in 2020; 3.8% in 2019; p=0.0061).Conclusion: There was a reduction in interventional oncology treatments during the “State of Emergency” with more patients experiencing disease progression precluding LRTs in the following months.
Differential kinetics of T cell and antibody responses delineate dominant T cell epitopes in long-term immunity after COVID-19
Authors: Bilich Tatjana , Nelde Annika , Heitmann Jonas S. , Maringer Yacine , Roerden Malte , Bauer Jens , Rieth Jonas , Wacker Marcel , Peter Andreas , Hörber Sebastian , Rachfalski David , Märklin Melanie , Stevanović Stefan , Rammensee Hans-Georg , Salih Helmut R. , Walz Juliane S.
Published: November 2020

Long-term immunity to SARS-CoV-2 is crucial for the development of herd immunity and the aim of vaccination approaches. Reports on rapidly decreasing antibody titers question the efficacy of humoral immunity. The relevance of T cell memory after COVID-19 is yet unclear. Longitudinal analysis of SARS-CoV-2 immunity in convalescents up to six months post-infection revealed decreasing and stable spike and nucleocapsid antibody responses, respectively. In contrast, T cell responses remained robust and even increased in frequency and intensity. Single epitope mapping of T cell diversity over time identified ORF-independent, dominant T cell epitopes mediating long-term SARS-CoV-2 T cell responses and may be fundamental for vaccine design.
Web-based, rapid and contactless management of ambulatory patients for SARS-CoV-2-testing
Authors: Stemler Jannik , Cornely Oliver A. , Noack-Schönborn Torsten , Forholz Corinna , Schumacher Sofie , Poluschkin Leonard , Binder Bernd , Lehmann Clara , Langebartels Georg
Published: November 2020

BackgroundDuring the SARS-CoV-2 pandemic a mass casualty incident of ambulatory patients occurred at the COVID-19 rapid response infrastructure (CRRI) facility at the University Hospital of Cologne (UHC). We report the development of a patient-centred mobile-device solution to support efficient management of the facility, triage of patients and rapid delivery of test results.MethodsThe UHC-Corona Web Tool (CWT) was developed as a web-based application useable on each patient's smartphone. It provides, among others, a self-reported medical history including type and duration of symptoms and potential risk contacts and links all retrieved information to the digital patient chart via a QR code. It provides scheduling of outpatient appointments and automated transmission of SARS-CoV-2 test results.ResultsThe UHC-CWT was launched on April 9th, 2020. It was used by 28652 patients until August 31st,2020. Of those, 15245 (53,2%) consulted the CRRI, representing 43,1% of all CRRI patients during the observed period.There were 8304 (29,0%) specifications concerning travel history and 17145 (59,8%) indications of ≥1 symptom of SARS-CoV-2 infection. The most frequently indicated symptoms were sore throat (60,0%), headache (50,7%), common cold (45,1%) and cough (42,6%) while 11057 (40,2%) patients did not report any symptoms. After implementation of the UHC-CWT, the number of patient contacts per physician rose from 38 to 98,7 per day. The personnel for communication of test results was reduced from four on seven days to one on five days.ConclusionThe UHC-CWT is an effective digital solution for management of large numbers of outpatients for SARS-CoV-2 testing.
Altered Gut Microbiota Associated with Hemorrhage in Chronic Radiation Proctitis
Authors: Liu Liangzhe , Chen Chaoyun , Ding Chen , Chen Bingcheng , Liang Jinjun
Published: November 2020

Background: Pelvic cancer radiotherapy may cause chronic radiation proctitis (CRP) that adversely affects patient’s quality of life, especially in patients with prolonged hematochezia. However, previous studies of radiation enteropathy mainly focused on acute irradiation hazards, and the detail pathogenesis process and mechanism of prolonged hematochezia associated with radiation-induce toxicity remain unclear. Methods: The 16S DNA of gut microbiota of 32 CRP patients with or without hematochezia were sequenced. The diversities and densities of gut microbiota were analyzed. Findings: Differential patterns of dysbiosis were observed. The abundance of Peptostreptococcaceae, Eubacterium and Allisonella were significantly higher in CRP patients with hematochezia, while the compositions of the Lachnospiraceae, Megasphera, Megamonas and Ruminococcaceae were lower in the microbiota of non-hematochezia patients. Functional prediction suggested significant difference in the expression of mineral absorption and the Arachidonic Acid metabolism proteins between hematochezia and non-hematochezia patients, possibly interdependent on radiation-induced inflammation. Interpretation: This study provides new insight to the function of gut microbiota in hemorrhage symptom of CRP patients. Further study is required to select probiotics and prebiotics to improve intestinal homoeostasis and relief prolonged hematochezia in CRP patients.
How do parents deal with their children's chronic kidney disease? A qualitative study for identifying factors related to parent's adaptation
Authors: Khorsandi Fatemeh , Parizad Naser , Feizi Aram , maslakpak Masumeh Hemmati
Published: November 2020

Background: Parents’ adaptation affects the health outcomes of children with chronic kidney diseases (CKD). Identifying factors that affect parents’ adaptation is necessary to understand their adaptation status. This study aims to explore factors related to the adaptation of parents who have children with CKD.Methods: This was a qualitative study with a content analysis approach. Seventeen parents of children with CKD were selected by using purposive sampling. The leading researcher performed semi-structured, in-depth, face-to-face interviews to collect data. Conventional content analysis was used to analyze data.Results: Two main categories extracted from the data were “adaptation facilitators” and “adaptation barriers.” Adaptation facilitators were supported by three sub-categories: "social support", "family capability" and "spiritual beliefs". Four sub-categories of “adaptation barriers” were revealed as: “family-related barriers,” “mental stress by others,” “the chronic nature of the disease,” and “unfavorable treatment conditions.”Conclusions: Identifying the factors influencing parental adaptation helps the medical staff to make the necessary interventions to support the parents. According to this study, increasing parent access to the required information, supporting them financially and emotionally, and helping them identify support resources can facilitate their adaptation to their child's chronic illness. Also, identifying and eliminating adaptation barriers can help parents deal better with their child’s chronic disease.
Hydroxysafflor yellow A promotes osteogenesis and bone development via epigenetically regulating β-catenin and prevents ovariectomy-induced bone loss
Authors: Wang Peng , Min Wang , Zhuo Tingling , Li Ying , Weiping Lin , Lingli Ding , Zhang Meng , Zhou Chi , Zhang Jinfang , Li Gang , Wang Haibin , Xu Liangliang
Published: November 2020

In clinical treatment, there is increasingly prevalent that traditional Chinese medicine treats common bone diseases including osteoporosis. Hydroxy safflor yellow A (HSYA), one of the essential compounds of Safflower, has strong effects to scavenge oxidative stress and inhibit apoptosis. It has been used as the therapy for thrombus, myocardial ischemia, and inflammation, but its effect on osteoporosis has not been explored. In this study, we found HSYA could enhance the cell viability and promote osteogenesis of hBMSC in vitro. Mechanistically, HSYA could increase the expression of β-catenin leading to its accumulation in the nucleus and activation of down-stream targets to promote osteogenesis. In addition, RNAseq and quantitative RT-PCR showed KDM7A was significantly increased by HSYA.The occupancy of H3K27me2 on β-catenin promoter was significantly decreased by HSYA, which could be reversed by silencing endogenous KDM7A. More importantly, HSYA could promote bone development in chick embryos and prevent ovariectomy(OVX)-induced bone loss in SD rats. Taken together, our study has shown convincing evidence that HSYA can promote osteogenesis and bone development via epigenetically regulating β-catenin and prevents ovariectomy-induced bone loss. HSYA might be used to treat some skeletal diseases such as osteoporosis.
Abnormal rich club organization in end-stage renal disease patients before dialysis initiation and undergoing maintenance hemodialysis
Authors: Ma Shaohui , Zhang Ming , Liu Yang , Ding Dun , Li Peng , Ma Xueying , Liu Hongjuan , Mu Junya
Published: November 2020

Background: End-stage renal disease (ESRD) patients are at a substantially higher risk for developing cognitive impairment compared with the healthy population. Dialysis is an essential way to maintain the life of ESRD patients. Based on previous research, there isn’t an uncontested result whether cognition was improved or worsened during dialysis.Methods: To explore the impact of dialysis treatment on cognitive performance, we recruited healthy controls (HCs), predialysis ESRD patients (predialysis group), and maintenance hemodialysis ESRD patients (HD group). All ESRD patients performed six blood biochemistry tests (hemoglobin, urea, cystatin C, Na+, K+, and parathyroid hormone). Neuropsychological tests were used to measure cognitive function. By using diffusion tensor imaging and graph-theory approaches, the topological organization of the whole-brain structural network was investigated. Generalized linear models (GLMs) were performed to investigate blood biochemistry predictors of the neuropsychological tests and the results of graph analyses in the HD group and predialysis group. Results: Neuropsychological analysis showed the HD group exhibited better cognitive function than the predialysis group, but both were worse than HCs. Whole-brain graph analyses revealed that increased global efficiency and normalized shortest path length remained in the predialysis group and HD group than the HCs. Besides, a lower normalized clustering coefficient was found in the predialysis group relative to the HCs and HD group. For the GLM analysis, only the Cystatin C level was significantly associated with the average fiber length of rich club connections in the predialysis group. Conclusions: Our study revealed that dialysis had a limited effect on cognitive improvement.
Association between Chronic Kidney Disease and the Most Common Corneal Ectasia Disease (Keratoconus): a Nationwide Cohort Study
Authors: Jan Ren-Long , Weng Shih-Feng , Wang Jhi-Joung , Chang Yuh-Shin
Published: November 2020

Background: Both keratoconus (KCN) and chronic kidney disease (CKD) are multifactorial conditions with multiple aetiologies and share several common pathophysiologies. However, the few studies that have described the relationship between KCN and CKD are limited to case reports and small case series. This study aimed to evaluate the association between KCN and CKD.Methods: The study cohort included 4,609 new-onset keratoconus patients ≥ 12 years identified by the International Classification of Diseases, Ninth Revision, Clinical Modification, code 371.6 and recruited between 2004 and 2011 from the Taiwan National Health Insurance Research Database. The age- , sex- , and comorbidity-matched control group included 27,654 non-KCN patients, selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information for each patient was collected and tracked from the index date until December 2013. The incidence and risk of CKD were compared between the two groups. The adjusted hazard ratios (HRs) for CKD were calculated with Cox proportional hazard regression analysis. Kaplan–Meier analysis was used to calculate the cumulative CKD incidence rate. Results: The incidence rate of CKD was 1.36 times higher in KCN patients than in controls without statistically significant difference (95% confidence interval [CI] = 0.99–1.86, p = 0.06). In total, 29 male KCN patients and 90 male controls developed CKD during the follow-up period. The incidence rate of CKD was 1.92 times (95% [CI] = 1.26–2.91; p = 0.002) higher in male KCN patients than in controls. After adjusting for potential confounders, including age, hypertension, hyperlipidaemia, and diabetes mellitus, male KCN patients were 1.75 times (adjusted HR = 1.75, 95% [CI] = 1.14–2.68, p < 0.05) more likely to develop CKD. Conclusions: We found that male KCN patients have an increased risk of CKD. Therefore, it is recommended that male KCN patients should be aware of CKD.
DASSI: Differential Architecture Search for Splice Identification from DNA Sequences
Authors: Moosa Shabir , Amira Abbes , Boughorbel Sabri
Published: November 2020

Background: The data explosion caused by unprecedented advancements in the field of genomics is constantly challenging the conventional methods used in the interpretation of the human genome. The demand for robust algorithms over the recent years has brought huge success in the field of Deep Learning (DL) in solving many difficult tasks in image, speech and natural language processing by automating the manual process of architecture design. This has been fueled through the development of new DL architectures. Yet genomics possesses unique challenges that requires customization and development of new DL models. Methods: We proposed a new model, DASSI, by adapting a differential architecture search method and applying it to the Splice Site (SS) recognition task on DNA sequences to discover new high-performance convolutional architectures in an automated manner. We evaluated the discovered model against state-of-the-art tools to classify true and false SS in Homo sapiens (Human), Arabidopsis thaliana (Plant), Caenorhabditis elegans (Worm) and Drosophila melanogaster (Fly). Results: Our experimental evaluation demonstrated that the discovered architecture outperformed baseline models and fixed architectures and showed competitive results against state-of-the-art models used in classification of splice sites. The proposed model - DASSI has a compact architecture and showed very good results on a transfer learning task. The benchmarking experiments of execution time and precision on architecture search and evaluation process showed better performance on recently available GPUs making it feasible to adopt architecture search based methods on large datasets. Conclusions: We proposed the use of differential architecture search method (DASSI) to perform SS classification on raw DNA sequences, and discovered new neural network models with low number of tunable parameters and competitive performance compared with manually engineered architectures. We have extensively benchmarked DASSI model with other state-of-the-art models and assessed its computational efficiency. The results have shown a high potential of using automated architecture search mechanism for solving various problems in the field of genomics.
Overhydration and low serum prealbumin predict peritoneal dialysis-related peritonitis in continuous ambulatory peritoneal dialysis patients
Authors: Quy Quyen Dao Bui , Huy Tuan Pham Ngoc , Duc Loc Nguyen , Van My Pham , Huu Dung Nguyen , Duy Toan Nguyen , Viet Tien Tran , Do Quyet , Viet Thang Le
Published: November 2020

Background: In this study, we focused on the role of overhydration (OH) and low serum prealbumin concentration in predicting peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients over a 3-year period.Methods: We measured serum prealbumin concentration and OH by body composition monitor in 278 CAPD patients (159 males and 119 females) with a mean age of 46 years and a median peritoneal dialysis (PD) duration of 21 months. Cases of PD-related peritonitis were collected over 3 years. Results: After the 3-year follow-up, 44 patients were diagnosed with PD-related peritonitis (15.8%). Low education, serum glucose, prealbumin, and OH were independent risk factors for predicting peritonitis over 36 months in CAPD patients. Based on the ROC curve model and Kaplan-Meier analysis, we realized that low prealbumin and high OH were independent predictors of 3-year peritonitis in CAPD patients (Prealbumin: AUC = 0.838, cut-off value = 32.5 mg/dL, Se= 90.9%, Sp = 32.9%; OH: AUC = 0.851, cut-off value = 1.33 L, Se = 79.5%, Sp = 85.5%; and log-rank test p < 0.001, respectively). Conclusion: Overhydration and low serum prealbumin were the independent predictors of PD-related peritonitis in CAPD patients.