bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic implications of alcohol dehydrogenases in hepatocellular carcinoma
Authors: Liu Xiangye , Li Tingting , Kong Delong , You Hongjuan , Kong Fanyun , Tang Renxian
Published: December 2020

Background: Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates worldwide. Alcohol dehydrogenases (ADHs) are huge family of dehydrogenase enzymes and associated with the prognosis of various cancers. However, comprehensive analysis of prognostic implications related to ADHs in HCC is still lacking and largely unknown. Methods: The expression profiles and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test was employed to evaluate the expression of ADHs. Cox regression and Kaplan-Meier analyses were used to investigate the association between clinicopathological characteristics and survival. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed and visualized using R/BiocManager package. Results: We found that the expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly downregulated in HCC samples compared to normal liver samples. Our univariate and multivariate Cox regression analyses results showed that high expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was considered as an independent factor with an improved prognosis for the survival of HCC patients. Moreover, our Kaplan-Meier analysis results also revealed that high expression of AHD1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly associated with good survival rate in HCC patients. In addition, GO, KEGG, and GSEA analyses unveiled several oncogenic signaling pathways were negatively associated high expression of ADHs in HCC. Conclusion: In the present study, our results provide the potential prognostic biomarkers or molecular targets for the patients with HCC.
Community health workers for non-communicable diseases prevention and control in Bangladesh: a qualitative study
Authors: Rawal Lal , Jubayer Shamim , Choudhury Shohel R , Islam Sheikh Mohammad Shariful , Abdullah Abu
Published: December 2020

Background: The increasing burden of Non-Communicable Diseases (NCDs) in Bangladesh underscores the importance of strengthening primary health care systems. In this study, we examined the barriers and facilitators to engaging Community Health Workers (CHWs) for NCDs prevention and control in Bangladesh.Methods: We used multipronged approaches, including a. Situation analyses using a literature review, key personnel and stakeholders’ consultative meetings, and exploratory studies. A grounded theory approach was used for qualitative data collection from health facilities across three districts in Bangladesh. We conducted in-depth interviews with CHWs (Health Inspector; Community Health Care Provider; Health Assistant and Health Supervisor) (n=4); key informant interviews with central level health policymakers/ managers (n=15) and focus group discussions with CHWs (4 FGDs; total n=29). Participants in a stakeholder consultative meeting included members from the government (n=4), non-government organisations (n=2), private sector (n=1) and universities (n=2). Coding of the qualitative data and identification of themes from the transcripts were carried out and thematic approach was used for data analyses.Results: The CHWs in Bangladesh deliver a wide range of public health programs. They also provide several NCDs specific services, including screening, provisional diagnosis, and health education and counselling for common NCDs, dispensing basic medications, and referral to relevant health facilities. These services are being delivered from the sub-district health facility, community clinics and urban health clinics. The participants identified key challenges and barriers, which include lack of NCD specific guidelines, inadequate training, excessive workload, inadequate systems-level support, and lack of logistics supplies and drugs. Yet, the facilitating factors to engaging CHWs included government commitment and program priority, development of NCD related policies and strategies, establishment of NCD corners, community support systems, social recognition of health care staff and their motivation.Conclusion: Engaging CHWs has been a key driver to NCDs services delivery in Bangladesh. However, there is a need for building capacity of CHWs, maximizing CHWs engagement to NCD services delivery, facilitating systems-level support and strengthening partnerships with non-state sectors would be effective in prevention and control efforts of NCDs in Bangladesh.
KK-LC-1 may be an effective prognostic biomarker for gastric cancer
Authors: Ji Jun , Chen Jiahui , Wang Anqiang , Zhang Wei , Ju Hongge , Liu Yang , Li Leping
Published: December 2020

Background: To detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyze the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods: A total of 94 patients with GC who underwent surgical resection were enrolled in this study. The expression of KK-LC-1 in GC tissues was detected by immunohistochemistry. The assessment of KK-LC-1 expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of KK-LC-1 in the cytoplasm and was scored to achieve respective H-score values. The correlations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. Results: In the cytoplasm, the expression of KK-LC-1 in tumor tissues was significantly higher than that in normal tissues (P < 0.001, respectively). Using the median H-score as the cutoff value, it was discovered that, GC patients with higher levels of KK-LC-1expression in the cytoplasm, had favorable overall survival (P =0.016), and it was still statistically meaningful in Cox regression analysis. At the same time, the study found that there was a negative correlation between KK-LC-1’s protein expression and the pathological grade of the tumor (P = 0.036). Conclusions: Our research data shows that KK-LC-1’s expression in GC is higher than that of normal tissues, which is associated with a longer overall survival in GC. KK-LC-1 can be used as a biomarker for GC patients with good prognosis.
Altered striatal dopamine levels in Parkinson’s disease VPS35 D620N mutant transgenic aged mice
Authors: Vanan Sarivin , Zeng Xiaoxia , Chia Sook Yoong , Varnäs Katarina , Jiang Mei , Zhang Ke , Saw Wuan Ting , Padmanabhan Parasuraman , Yu Wei-Ping , Zhou Zhi-Dong , Halldin Christer , Gulyás Balázs , Tan Eng-King , Zeng Li
Published: December 2020

Vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex that mediates the retrograde transport of cargo proteins from endosomes to the trans-Golgi network. Mutations such as D620N in the VPS35 gene have been identified in patients with autosomal dominant Parkinson’s disease (PD). However, it remains poorly understood whether and how VPS35 deficiency or mutation contributes to PD pathogenesis; specifically, the studies that have examined VPS35 thus far have differed in results and methodologies. We generated a VPS35 D620N mouse model using a Rosa26-based transgene expression platform to allow expression in a spatial manner, so as to better address these discrepancies. Here, aged (20-months-old) mice were first subjected to behavioral tests. Subsequently, DAB staining analysis of substantia nigra (SN) dopaminergic neurons with the marker for tyrosine hydroxylase (TH) was performed. Next, HPLC was used to determine dopamine levels, along with levels of its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum. Western blotting was also performed to study the levels of key proteins associated with PD. Lastly, autoradiography (ARG) evaluation of [3H]FE-PE2I binding to the striatal dopamine transporter DAT was carried out. We found that VPS35 D620N Tg mice displayed a significantly higher dopamine level than NTg counterparts. All results were then compared with that of current VPS35 studies to shed light on the disease pathogenesis. Our model allows future studies to explicitly control spatial expression of the transgene which would generate a more reliable PD phenotype.
Parents' and medical staff's experience of adolescents with suicide-related behaviors admitted to a general hospital in China: qualitative study
Authors: Fu Xi , Yang Jiaxin , Liao Xiaoli , Shen Yidong , Ou Jianjun , Li Yamin , Chen Runsen
Published: December 2020

Background: Currently, there is increasing awareness of suicide-related behaviors. Mental health services are a key location for assisting people with suicide-related behaviors. However, few studies focused on the evaluation and experience of the mental health care system from families and the medical staff’s perspective in China. The study aims to explore parents' and the front-line medical staff's experience of an adolescent with suicide-related behaviors admitted to the psychiatry department of a general hospital in China. Design: Qualitative study was employed in the study. Participants were recruited from a general hospital in China characterized by high levels in the Chinese mental health system. Methods: Semi-structured in-depth interviews were conducted exploring their experience and perceptions when an adolescent was admitted to the hospital. The theme analysis method is used for data analysis. Results: Participants expressed dissatisfaction in the psychiatric department. Other barriers in their work were identified, such as the shortage of staff and difficulties in caring or communicating with patients. Besides, the imperfect treatment system also contributes to the low satisfaction of patients and their families. Two themes and six subthemes were identified: 1) staff perceive patients with SRBs as difficult to engage (feelings of helplessness, the need for compassion, challenges of professional self-efficacy, the recommendations to the health care service); 2) parents not satisfied with the existing hospital services (doubt the hospitalization treatment and the advice to the health care service). Conclusion: This study found that insufficient staffing and lacking of systematic professional treatment models are the major challenges. We suggest increasing the input of mental health resources to expand and train the mental health service team and establish a complete set of a treatment model for SRBs.
Hypoxia-induced Tie1 drives stemness and cisplatin resistance in non-small cell lung carcinoma cells
Authors: Li Chaojie , Yang Nannan , Chen Zhijin , Xia Ning , Shan Qungang , Wang Ziyin , Lu Jian , Shang Mingyi , Wang Zhongmin
Published: December 2020

Background: Drug resistance and metastasis involving hypoxic tumor environments and persistent stem cell populations are detrimental to the survival of patients with non-small cell lung carcinoma (NSCLC). Tie1 is upregulated in hypoxia and is believed to counteract the effectiveness of platinum agents by promoting the stemness properties in cells. We have investigated the association of Tie1 with HIF-1α and cisplatin resistance in NSCLC cell lines.Methods: The expression of Tie1 in a pulmonary microvascular endothelial cell line (HPMEC) and NSCLC cell lines was detected using qRT-PCR and western blotting. The effect of Tie1 on cell stemness and migration was examined by sphere-forming and transwell assays in NSCLC cells with Tie1 silenced. The regulation of Tie1 by HIF-1α was evaluated by a dual-luciferase reporter assay and chromatin immunoprecipitation.Results: We found that hypoxia could induce stemness and cisplatin resistance in vitro. Tie1 was expressed at low levels in NSCLC cells when compared with human pulmonary microvascular endothelial cells, however, its expression was increased by hypoxia. Additionally, Tie1 knockdown could reduce stemness properties and increase sensitivity to cisplatin in vitro and in a xenograft mouse model. The promoter of Tie1 contains two predicted hypoxia-response elements (HREs). We mutated both HRE sites and conducted chromatin immune-precipitation and promoter luciferase reporter assays and were able to conclude that the induction of Tie1 by hypoxia was HIF-1α-dependent.Conclusions: Our findings indicated that Tie1 is upregulated in a hypoxic environment by HIF-1α and contributes to tumorigenesis and cisplatin resistance through the promotion of stemness in NSCLC cells.
Comparison of lumbar endoscopic unilateral laminotomy bilateral decompression and minimally invasive surgery transforaminal lumbar interbody fusion for one-level lumbar spinal stenosis
Authors: Hua Wenbin , Wang Bingjin , Ke Wencan , Wu Xinghuo , Zhang Yukun , Li Shuai , Yang Shuhua , Yang Cao
Published: December 2020

Background: The aim of the present study is to compare the clinical outcomes and postoperative complications of lumbar endoscopic unilateral laminotomy bilateral decompression (LE-ULBD) and minimally invasive surgery transforaminal lumbar interbody fusion (MIS-TLIF) to treat one-level lumbar spinal stenosis (LSS) without degenerative spondylolisthesis or deformity. Methods: A retrospective analysis of 112 consecutive patients of one-level LSS undergoing either LE-ULBD or MIS-TLIF was performed. Patient demographics, operation time, estimated blood loss, time to ambulation, length of hospitalization, intraoperative and postoperative complications were recorded. The visual analog scale (VAS) score for leg and back pain, the Oswestry Disability Index (ODI) score, and the Macnab criteria were used to evaluate the clinical outcomes. The healthcare cost was also recorded.Results: The operation time, estimated blood loss, time to ambulation and length of hospitalization of LE-ULBD group were shorter than MIS-TLIF group. The postoperative mean VAS and ODI scores decreased significantly in both groups. According to the modified Macnab criteria, the outcomes rated as excellent/good rate were 90.6% and 93.8% in the two groups. The mean VAS scores, ODI scores and outcomes of the modified Macnab criteria of both groups were of no significant difference. The healthcare cost of LE-ULBD group was lower than MIS-TLIF group. Two cases of intraoperative epineurium injury were observed in the LE-ULBD group. One case of cauda equina injury was observed in the LE-ULBD group. No nerve injury, dural injury or cauda equina syndrome was observed in MIS-TLIF group. However, one case with transient urinary retention, one case with pleural effusion, one case with incision infection and one case with implant dislodgement were observed in MIS-TLIF group. Conclusions: Both LE-ULBD and MIS-TLIF are safe and effective to treat one-level LSS without degenerative spondylolisthesis or deformity. LE-ULBD is a more minimally invasive option and of less economic burden compared with MIS-TLIF. Decompression plus instrumented fusion may be not necessary for one-level LSS without degenerative spondylolisthesis or deformity.
The association between retinal vessel abnormalities and H-type hypertension
Authors: Huang Kuankuan , Zhang Zhixiang , Huang Shan , Jia Yanwen , Zhang Min , Yun Wenwei
Published: December 2020

Background: This study aimed to investigate the relationship between H-type hypertension and retinal vessel abnormalities. Methods: Hypertensive patients were retrospectively enrolled in this study. According to plasma homocysteine (HCY), patients were divided into isolated hypertension and H-type hypertension groups. The diameter of retinal vessels and retinopathy were evaluated using retinal fundus photography. The differences of retinal vessel abnormalities between H-type hypertension and isolated hypertension were investigated by univariate and multivariate regression. Results: A total of 191 hypertensive patients were included, of which 86 were with isolated hypertension and 105 with H-type hypertension. The H-type hypertension group had a higher ratio of retinopathy(P=0.004) and higher degree of retinal arteriosclerosis (P=0.005) than the isolated hypertension group. CRAE (107.47±13.99mm v 113.49±11.72mm, P=0.002) and AVR (0.55±0.06 v 0.58±0.06, P=0.001) were smaller in H-type hypertension group than those in isolated hypertension group. Multivariate analysis showed that after adjusting for age, sex, course of hypertension and diabetes, H-type hypertension was an independent risk factor of retinopathy(OR, 2.259; 95%CI, 1.165—4.378; P=0.016), CRAE (B=-5.669; 95%CI, -9.452—-1.886; P=0.004), and AVR (B=-0.023; 95%CI,-0.039—-0.007; P=0.005). Conclusion: H-type hypertension is closely related to more retinal vessel abnormalities than isolated hypertension. Controlling H-type hypertension may reduce the risk of small vascular damage.
Effect of the Versatile Bifunctional Chelator AAZTA5 on the Radiometal Labelling properties and the in vitro performance of a Gastrin Releasing Peptide Receptor Antagonist
Authors: Hofstetter Michael , Moon Euy Sung , D'Angelo Fabio , Geissbühler Lucien , Alberts Ian , Afshar-Oromieh Ali , Rösch Frank , Rominger Axel , Gourni Eleni
Published: December 2020

Background: Gastrin Releasing Peptide receptor (GRPr)-based radioligands have shown great promise for diagnostic imaging of GRPr-positive cancers, such as prostate and breast.The present study aims at developing and evaluating a versatile GRPr-based probe for both PET/SPECT imaging as well as intraoperative and therapeutic applications. The influence of the versatile chelator AAZTA5 on the radiometal labelling properties and the in vitro performance of the generated radiotracers were thoroughly investigated.The GRPr-based antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 was functionalized with the chelator 6-[Bis(carboxymethyl)amino]-1,4-bis(carboyxmethyl)-6-methyl-1,4-diazepane (AAZTA5) through the spacer 4-amino-1-carboxymethyl-piperidine (Pip) to obtain AAZTA5-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (LF1). LF1 was radiolabelled with gallium-68 (PET), indium-111 (SPECT, intraoperative applications) and lutetium-177 (therapy, SPECT). In vitro evaluation included stability studies, determination of lipophilicity, protein-binding studies, determination of Kd and Bmax as well as internalization studies using the epithelial human prostate cancer cell line PC3. In vitro monotherapy as well as combination therapy studies were further performed to assess its applicability as a theranostic compound.Results: LF1 was labelled with gallium-68, indium-111 and lutetium-177 within 5 min at room temperature (RT). The apparent molar activities (Am) were ranging between 50-60 GBq/µmol for the 68Ga-labelled LF1, 10-20 GBq/µmol for the 111In- and 177Lu-labelled LF1. The radiotracers were stable for a period of 4 h post labeling exhibiting a hydrophilic profile with an average of a LogDoctanol/PBS of -3, while the bound activity to the human serum protein was approximately 10%. 68/natGa-LF1, 177/natLu-LF1 and 111/natIn-LF1 exhibited high affinity for the PC3 cells, with Kd values of 16.3±2.4 nM, 10.3±2.73 nM and 5.2±1.9 nM, respectively, and the required concentration of the radiotracers to saturate the receptors (Bmax) was between 0.5 and 0.8 nM which corresponds to approximately 4 x 105 receptors per cell. Low specific internalization rate was found in cell culture, while the total specific cell surface bound uptake always exceeded the internalized activity. In vitro therapy studies showed that inhibition of PC3 cells growth is somewhat more efficient when combination of 177Lu-labelled LF1 with rapamycin is applied compared to 177Lu-laballed LF1 alone.Conclusion: Encouraged by these promising in vitro data, preclinical evaluation of the LF1 precursor are planned in tumour models in vivo.
Post-trial Perceptions of a Symptom-based TB Screening Intervention in South Africa: Implementation Insights and Future Directions for TB Preventative Healthcare Services
Authors: Salazar-Austin Nicole , Milovanovic Minja , West Nora S , Tladi Molefi , Barnes Grace Link , Variava Ebrahim , Martinson Neil , Chaisson Richard E , Kerrigan Deanna
Published: December 2020

Background: Tuberculosis is a top-10 cause of under-5 mortality, despite policies promoting tuberculosis preventive therapy (TPT). We previously conducted a cluster randomized trial to evaluate the effectiveness of symptom-based versus tuberculin skin-based screening on child TPT uptake. Symptom-based screening did not improve TPT uptake and nearly two-thirds of child contacts were not identified or not linked to care. Here we qualitatively explored healthcare provider perceptions of factors that impacted TPT uptake among child contacts. Methods: Sixteen in-depth interviews were conducted with key informants including healthcare providers and administrators who participated in the trial in Matlosana, South Africa. The participants’ experience with symptom-based screening, study implementation strategies, and ongoing challenges with child contact identification and linkage to care were explored. Interviews were systematically coded and thematic content analysis was conducted. Results: Participants’ had mixed opinions about symptom-based screening and high acceptability of the study implementation strategies. A key barrier to optimizing child contact screening and evaluation was the supervision and training of community health workers. Conclusions: Symptom screening is a simple and effective strategy to evaluate child contacts, but additional pediatric training is needed to provide comfort with decision making. New clinic-based child contact files were highly valued by providers who continued to use them after trial completion. Future interventions to improve child contact management will need to address how to best utilize community health workers in identifying and linking child contacts to care. Trial Registration: The results presented here were from research related to NCT03074799, retrospectively registered on 9 March 2017.
MiR-489-3p reduced pancreatic cancer proliferation and metastasis by targeting PKM2 and LDHA involving glycolysis
Authors: Zhang Dan , He zhiwei , Shen Yiyi , wang Jie , Liu Tao , Jiang Jianxin
Published: December 2020

Background: Malignant proliferation and chemotherapy resistance are some of the causes of high mortality in pancreatic cancer. MicroRNAs have for a long period been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. miR-489-3p is involved in the inhibition of the growth of many tumors. However, its relationship with the growth and metabolism of pancreatic cancer is not clear.Methods：We used RNA in situ hybridization to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues. The qRT-PCR experiment detected the content of miR-489-3p in pancreatic cancer cell lines and ordinary pancreatic ductal epithelial cells. Then we did experiments in vivo (subcutaneous tumor formation in nude mice) and in vitro (plate cloning, transwell, glycolysis related experiments) experiments to verify that miR-489-3p can continue the invasion and metastasis of pancreatic cancer and glucose metabolism. Furthermore, we confirmed that LDHA and PKM2 are the two targets of miR-489-3p through dual luciferase reporter gene experiments. Finally, several reply experiments were done to verify the regulation mechanism of miR-489-3p.Results: We determined that miR-489-3p was under-expressed in pancreatic cancer tissues by RNA in situ hybridization. The function acquisition and deletion and glycolysis experiments confirmed that miR-489-3p could inhibit the proliferation and invasion of Glycolysis. On the analysis of the website, we found that miR-489-3p could target LDHA and PKM, a finding that we verified through the luciferase report experiment. Therefore, we proceeded with recovery experiments on LDHA and PKM2 and concluded that miR-489-3p performed its function by targeting LDHA and PKM2. Finally, in vivo experiments confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer.Conclusion: In short, this study has identified miR-489-3p as a novel chemotherapy target for pancreatic cancer, but its diagnostic value deserves further study.
Common Causes and Characteristics of Adverse Drug Reactions in Older Adults: A Retrospective Study
Authors: Woo Seong-Dae , Yoon Jiwon , Doo Go-Eun , Park Youjin , Lee Youngsoo , Lee So-Hee , Lee Young-Hee , Ye Young-Min
Published: December 2020

Background: Aging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (≥65 years) in comparison to younger individuals (<65 years).

Methods: Of 37,523 cases reported at a Korean pharmacovigilance center from 2011 to 2018, we reviewed 18,842 ADRs of certain or probable causality on the basis of WHO-UMC criteria. We estimated the number of ADRs per 1,000 patients exposed to the major culprit drugs, and incidence rate ratios were obtained to assess high- and low-risk medications in older adults.

Results: In total, 4,152 (22.0%) ADRs were reported for 3,437 older adults (mean age, 74.6 years and 57.3% female). Tramadol (rate ratio, 1.32; 95% confidence interval [CI], 1.21-1.44; P <0.001) and fentanyl (1.49, 1.16-1.92, P =0.002) posed higher risks of ADRs in the older adults, whereas nonsteroidal anti-inflammatory drugs (NSAIDs) (0.35, 0.30-0.40, P <0.001) and iodinated contrast media (ICM) (0.82, 0.76-0.89, P <0.001) posed lower risks. Ratios of serious ADRs to NSAIDs (odds ratio, 2.16; 95% CI, 1.48-3.15; P <0.001) and ICM (2.09, 1.36-3.21, P= 0.001) were higher in the older adults than in the younger patients. Analgesics primarily elicited cutaneous ADRs in the younger patients and gastrointestinal reactions in the older adults. ICM more commonly led to anaphylaxis in the older adults than the younger patients (3.0% vs. 1.6%, P =0.019).

Conclusion: For early detection of ADRs in older adults, better understanding of differences in the causes and characteristics thereof in comparison to the general population is needed.
Coincidence Analysis: A New Method for Causal Inference in Implementation Science
Authors: Whitaker Rebecca Garr , Sperber Nina , Baumgartner Michael , Thiem Alrik , Cragun Deborah , Damschroder Laura , Miech Edward J. , Slade Alecia , Birken Sarah A.
Published: December 2020

Background: Implementation of multifaceted interventions typically involves many diverse elements working together in interrelated ways, including intervention components, implementation strategies, and features of local context. Given this real-world complexity, implementation researchers may be interested in a new mathematical, cross-case method called Coincidence Analysis (CNA) that has been designed explicitly to support causal inference, answer research questions about combinations of conditions that are minimally necessary or sufficient for an outcome, and identify the possible presence of multiple causal paths to an outcome. CNA can be applied as a standalone method or in conjunction with other approaches, and can reveal new empirical findings related to implementation that might otherwise have gone undetected. Methods: We applied CNA to a publicly available dataset from Sweden with county-level data on human papillomavirus (HPV) vaccination campaigns and vaccination uptake in 2012 and 2014 and then compared CNA results to the published regression findings. Results: The original regression analysis found vaccination uptake was positively associated only with the availability of vaccines in schools. CNA produced different findings and uncovered an additional solution path: high vaccination rates were achieved by either (1) offering the vaccine in all schools or (2) a combination of offering the vaccine in some schools and media coverage. Conclusions. CNA offers a new comparative approach for researchers seeking to understand how implementation conditions work together and link to outcomes.
Perioperative risk factors of psychological distress in patients undergoing treatment for esophageal cancer
Authors: Ohkura Yu , Shindoh Junichi , Ichikura Kanako , Udagawa Harushi , Ueno Masaki , Matsushima Eisuke
Published: December 2020

Background:Esophageal cancer patients often feel depressed and are fearful of metastasis and death. The objective of this study was to clarify the characteristics of patients with psychological distress at all 5time points compared with patients with no psychological distress especially from standpoints of personal coping styles and QOL.Methods:In total, 102 of 152 consecutive patients who attended the outpatient clinic at Toranomon Hospital between April 2017 and April 2019 met eligibility criteria for inclusion in this study. Questionnaires designed to identify psychological distress(HADS-scores) and assess QOL(EORTC QLQ C-30/OES18) were administered at 5 time points from the time of the first outpatient consultation to 3 months after esophagectomy. The questionnaire of coping strategies(MAC-scales) was administered at only Time1 point.Results:Based on the trends of HADS-scores, we defined two groups:“persistent high-HAD scores” and “persistent low-HADS scores”. There are strong relationships between psychological distress and coping strategy, and psychological distress and QOL. The possibility that there are relationships between stress coping strategies and some QOL status depending on some point of treatment.Conclusions:The psychological distress during treatment course of esophageal cancer is significantly associated with the coping strategies and QOL influenced by esophagectomy. This study can provide baseline information for identifying patients in need of psychological management and paves the way for larger clinical studies in the future.
Discussing Personalized Prognosis in Amyotrophic Lateral Sclerosis: Development of a Communication Guide
Authors: Eenennaam Remko M. van , Kruithof Willeke J. , Es Michael A. van , Reenen Esther T. Kruitwagen-van , Westeneng Henk-Jan , Visser-Meily Johanna M.A. , Berg Leonard H. van den , Beelen Anita
Published: December 2020

Background: Personalized ENCALS survival prediction model reliably estimates the personalized prognosis of patients with amyotrophic lateral sclerosis. Concerns were raised on discussing personalized prognosis without causing anxiety and destroying hope. Tailoring communication to patient readiness and patient needs mediates the impact of prognostic disclosure. We developed a communication guide to support physicians in discussing personalized prognosis tailored to individual needs and preferences of people with ALS and their families.Methods: A multidisciplinary working group of neurologists, rehabilitation physicians, and healthcare researchers A) identified relevant topics for guidance, B) conducted a systematic review on needs of patients regarding prognostic discussion in life-limiting disease, C) drafted recommendations based on evidence and expert opinion, and refined and finalized these recommendations in consensus rounds, based on feedback of an expert advisory panel (patients, family member, ethicist and spiritual counsellor).Results: A) Topics identified for guidance were 1) filling in the ENCALS survival model, and interpreting outcomes and uncertainty, and 2) tailoring discussion to individual needs and preferences of patients (information needs, role and needs of family, severe cognitive impairment or frontotemporal dementia, and non-western patients). B) 17 studies were included in the systematic review. C) Consensus procedures on drafted recommendations focused on selection of outcomes, uncertainty about estimated survival, culturally sensitive communication, and lack of decisional capacity.Recommendations for discussing the prognosis include the following: discuss prognosis based on the prognostic groups and their median survival, or, if more precise information is desired, on the interquartile range of the survival probability. Investigate needs and preferences of the patients and their families for prognostic disclosure, regardless of cultural background. If the patient does not want to know their prognosis, with patient permission discuss the prognosis with their family. If the patient is judged to lack decisional capacity, ask the family if they want to discuss the prognosis. Tailor prognostic disclosure step by step, discuss it in terms of time range, and emphasize uncertainty of individual survival time.Conclusion: This communication guide supports physicians in tailoring discussion of personalized prognosis to the individual needs and preferences of people with ALS and their families.
Screening of the College Students at Clinical High Risk for Psychosis in China: A Multicenter Epidemiological Study
Authors: Wu JiaXin , Long XiangYun , Liu Fei , Qi AnSi , Chen Qi , Guan XiaoFeng , Zhang Qiong , Yao YuHong , Shi JingYu , Xie ShiPing , Yan Wei , Hu MaoRong , Yuan Xin , Tang Jun , Wu SiLiang , Zhang TianHong , Wang JiJun , Lu Zheng
Published: December 2020

Background: To investigate a 3-stage screening procedure and explore the clinical features of subjects at Clinical High Risk (CHR) for psychosis in a representative sample of Chinese college students. Methods: An epidemiological survey of the prevalence of CHR syndrome in Chinese college students that was selected by stratified random sampling from Shanghai, Nanjing and Nanchang cities was done followed a 3-stage procedure. Participants was initially screened with the Prodromal Questionnaire-brief version (PQ-B), and whose distress score of PQ-B exceeded 24 would be invited to a telephone assessment using the subscale for positive symptoms of the Scale of Prodromal Symptoms (SOPS)/Structured Interview for Prodromal Syndromes (SIPS). Lastly, participants who scored 3 or higher in any item of the subscale would be administered with the SIPS interview conducted by trained researchers to confirm the diagnosis of CHR syndrome. Results: 23 063 college students completed the survey during September 2017 to October 2018. 72 students were diagnosed as CHR subjects, and the detection rate in the total sample was 0.3%. The peak age range for the first diagnosis of CHR was 17 to 20 years. 13 and 46 were set as the cut-off points of PQ-B total score and distress score to balance the greatest sensitivity and specificity. Binary logistic regression revealed that 8 items in PQ-B showed significant distinction for detecting CHR subjects. Conclusions: The 3-stage screening method can be utilized in the detection of CHR subjects for psychosis in general population, during which delusional ideas, perceptual abnormalities and suspiciousness deserve great attention.
Respiratory microbiome profiles differ by recent hospitalization and nursing home residence in patients on mechanical ventilation
Authors: Baek Min-gyung , Woo Seong Ji , Kim Nam-Eun , Baek Chaeyun , Won Sungho , Kim Youngmi , Lee Jae Jun , Yi Hana , Hong Ji Young
Published: December 2020

Background: Healthcare-associated pneumonia (HCAP) is a heterogeneous disease. We redefined nursing-home- and hospital-associated infections (NHAI) group by revising existing HCAP risk factors. The NHAI group comprised nursing home residents with a poor functional status, or recent (past 90 days) hospitalization or recent (past 180 days) antibiotic therapy. Our aim was to determine whether respiratory microbiota profiles are related to newly defined NHAI group in critically ill patients on mechanical ventilation.Methods: The 180 endotracheal aspirates (ETAs) from 60 mechanically ventilated ICU patients (NHAI group, n = 24; non-NHAI group, n = 36) were prospectively collected on days 1, 3 and 7 in a university hospital. The bacterial community profiles of the ETAs were explored by 16S rRNA gene sequencing. A phylogenetic-tree-based microbiome association test (TMAT), generalized linear mixed models (GLMMs), the Wilcoxon test and the reference frame method were used to analyze the association between microbiome abundance and disease phenotype.Results: The relative abundance of the genus Corynebacterium was significantly higher in the pneumonia than in the non-pneumonia group. The microbiome analysis revealed significantly lower α-diversity in the NHAI group than in the non-NHAI group. In the analysis of β-diversity, the structure of the microbiome also differed significantly between the two groups (weighted UniFrac distance, Adonis, P <0.001). The abundance of Corynebacterium was significantly higher, and the relative abundances of Granulicatella, Staphylococcus, Streptococcus and Veillonella were significantly lower, in the NHAI group than in the non-NHAI group.Conclusions: The microbiota signature of the ETAs distinguished between patients with and without risk factors for NHAI. The lung microbiome may serve as a therapeutic target for NHAI group.
COVID-19 detection in Chest X-ray Images using Deep Learning
Authors: Erdem Ebru , Aydın Tolga
Published: December 2020

COVID-19 is an important threat worldwide. This disease is caused by the novel SARS-CoV-2. CXR and CT images reveal specific information about the disease. However, when interpreting these images, experiencing an overlap with other lung infections complicates the detection of the disease. Due to this situation, the need for computer-aided systems is increasing day by day. In this study, solutions were developed with proposed models based on deep neural networks (DNN). All the analyses were performed on a publicly available CXR dataset. This study offers a comparison of the deep learning models (SqueezeNet, Inception-V3, VGG16, MobileNet, Xception, VGG19+MobileNet (Concatenated)) that results in the detection and classification of a disease. Empirical evaluation demonstrates that the Inception-V3 model gives 90% accuracy with 100% precision for the COVID-19 infection. This model has been provided with better results compared to other models. In addition to the studies in the literature, it has been observed that the proposed pre-trained-based concatenated model gives very similar successful results to the other models.
KVarPredDB: A database for predicting pathogenicity of missense sequence variants of keratin genes associated with genodermatoses
Authors: Ying Yuyi , Lu Lu , Banerjee Santasree , Xu Lizhen , Zhao Qiang , Wu Hao , Li Ruiqi , Xu Xiao , Yu Hua , Neculai Dante , Xi Yongmei , Yang Fan , Qin Jiale , Li Chen
Published: December 2020

Background: Germline variants of ten keratin genes (K1, K2, K5, K6A, K6B, K9, K10, K14, K16 and K17) have been reported for causing different types of genodermatoses with an autosomal dominant mode of inheritance. Among all the variants of these ten keratin genes, most of them are missense variants. Unlike pathogenic and likely pathogenic variants, understanding the clinical importance of novel missense variants or variants of uncertain significance (VUS) is the biggest challenge for clinicians or medical geneticists. Functional characterization is the only way to understand the clinical association of novel missense variants or VUS but it is time-consuming, costly and depends on the availability of patient’s samples. Existing databases report the pathogenic variants of the keratin genes, but never emphasize the systematic effects of these variants on keratin protein structure and genotype-phenotype correlation. Results: To address this need, we developed a comprehensive database KVarPredDB, which contains information of all ten keratin genes associated with genodermatoses. We integrated and curated 400 reported pathogenic missense variants as well as 4629 missense VUS. KVarPredDB predicts the pathogenicity of novel missense variants as well as to understand the severity of disease phenotype, based on four criteria; firstly, difference in physico-chemical properties between the wild-type and substituted amino acids, secondly, the loss of inter/intra-chain interactions, thirdly, evolutionary conservation of the wild type amino acids and lastly, the effect of the substituted amino acids in the heptad repeat. Molecular docking simulations based on resolved crystal structures were adopted to predict stability changes and get the binding energy to compare the wild type protein with the mutated one. We use this basic information to determine the structural and functional impact of novel missense variants on the keratin coiled-coil heterodimer. KVarPredDB was built under the integrative web application development framework SSM (SpringBoot, Spring MVC, MyBatis) and implemented in Java, Bootstrap, React-mutation-mapper, MySQL, Tomcat. The website can be accessed through http://bioinfo.zju.edu.cn/KVarPredDB. The genomic variants and analysis results are freely available under the Creative Commons license.Conclusions: KVarPredDB provides an intuitive and user-friendly interface with computational analytical investigation for each missense variant of the keratin genes associated with genodermatoses.
Redox-Sensitive Polymeric Micelles with Aggregation-Induced Emission for Bioimaging and Delivery of Anticancer Drugs
Authors: Sun Changzhen , Lu Ji , Wang Jun , Hao Ping , Li Chunhong , Qi Lu , Yang Lin , He Bin , Zhong Zhirong , Hao Na
Published: December 2020

Background: Nano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject.Results: To construct a smart drug delivery system for simultaneous imaging and cancer chemotherapy, mPEG-ss-Tripp was prepared and self-assembled into redox-sensitive polymeric micelles with a diameter of 105 nm that were easily detected within cells using confocal laser scanning microscopy based on aggregation-induced emission. Doxorubicin-loaded micelles rapidly released the drug intracellularly when GSH reduced the disulfide bond. The drug-loaded micelles inhibited tumor xenografts in mice, while this efficacy was lower without the GSH-responsive disulfide bridge. These results establish an innovative multi-functional polymeric micelle for intracellular imaging and redox-triggered drug deliver to cancer cells.Conclusions: A novel redox-sensitive drug delivery system with AIE property was constructed for simultaneous cellular imaging and intelligent drug delivery and release. This smart drug delivery system opens up new possibilities for multifunctional drug delivery systems.
Synthetic Wavelength Holography: Snapshot Non-Line-of-Sight Imaging with High-Resolution and Wide Field of View
Authors: Willomitzer Florian , Rangarajan Prasanna , Li Fengqiang , Balaji Muralidhar , Christensen Marc , Cossairt Oliver
Published: December 2020

The presence of a scattering medium in the imaging path between an object and an observer is known to severely limit the visual acuity of the imaging system. We present an approach to circumvent the deleterious effects of scattering, by exploiting spectral correlations in scattered wavefronts. Our Synthetic Wavelength Holography (SWH) method is able to recover a holographic representation of hidden targets with high resolution over a wide field of view. The complete object field is recorded in a snapshot-fashion, by monitoring the scattered light return in a small probe area. This unique combination of attributes opens up a plethora of new Non-Line-of-Sight imaging applications ranging from medical imaging and forensics, to early-warning navigation systems and reconnaissance. Adapting the findings of this work to other wave phenomena will help unlock a wider gamut of applications beyond those envisioned in this paper.
Mathematical Model for COVID-19 Management in Crowded Settlements and High-Activity Areas
Authors: Ssematimba Amos , Nakakawa Juliet , Ssebuliba Joseph , Mugisha Joseph Y. T
Published: December 2020

This paper develops and analyses a population density-dependent mathematical model to study the transmission dynamics of COVID-19 in crowded settlements such as refugee camps, schools, markets and churches. The model quantifies the potential impact of physical/social distancing and population density on the disease burden. Results reveal that with no fatalities and no infected entrants, the reproduction numbers associated with asymptomatic and symptomatic cases are inversely proportional to; the habitat area size, and the efforts employed in tracing and hospitalising these cases. The critical habitat area below which the disease dies out is directly proportion to the time taken to identify and hospitalise infected individuals. Results also show that disease persistence in the community is guaranteed even with minimal admission of infected individuals. Our results further show that as the level of compliance to standard operating procedures (SOPs) increases, then the disease prevalence peaks are greatly reduced and delayed. Therefore, proper adherence to SOPs such as use of masks, physical distancing measures and effective contact tracing should be highly enforced in crowded settings if COVID-19 is to be mitigated.
Edible Coatings as Carriers of Antibrowning Compounds to Maintain Appealing Appearance of Fresh-cut Mango
Authors: Marín Anna , Baldwin Elizabeth A. , Bai Jinhe , Wood David , Ference Christopher , Sun Xiuxiu , Brecht Jeffrey K. , Plotto Anne
Published: December 2020

Fresh-cut mango (Mangifera indica) slices and chunks garner an exotic image and are highly appreciated for their unique flavor and nutritional value. However, processors tend to use firm unripe mangoes to achieve shelf life of 10 to 14 days, which compromises eating quality. The post-processing life of ripe fresh-cut mangoes is limited by tissue softening, translucency, and browning. The current study was undertaken to investigate whether edible coatings can extend the shelf life of fresh-cut mangoes processed at an eating-ripe stage. Three edible coatings, carboxymethylcellulose (1% w/v), aloe (Aloe vera) powder (2% w/v), and whey protein isolate (2% w/v), supplemented with calcium ascorbate 2% w/v (firming agent) and the antioxidants citric acid (0.8% w/v) and acetyl-N-cysteine (0.4% w/v), were used. The mixture of antibrowning agents, whether applied alone or with the edible coatings, was the most effective at reducing slice browning up to 10 and 11 days at 5 °C for ‘Tommy Atkins’ and ‘Kent’, respectively. In general, there were no differences in firmness and flavor among the three edible coatings. Calcium ascorbate alone did not suppress browning consistently, whereas citric acid appeared to be the ingredient having the greatest antibrowning effect on slice quality. Citric acid can easily be used by processors of fresh-cut mangoes to prevent browning.