bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance Evaluation of a Novel Ultrafast Molecular Diagnostic Device Integrated With Microfluidic Chips and Dual Temperature Modules
Authors: Lin Shan , Song Xiaojun , Zhu Kun , Shao Quanyu , Chen Yinhang , Cheng Wei , Lei Zhijing , Chen Yu , Luo Yun , Jin Dazhi 
Published: May 2022

Ultrafast, portable, and inexpensive molecular diagnostic platforms are critical for clinical diagnosis and on-site detection. There are currently no available real-time polymerase chain reaction (PCR) devices able to meet the demands of point-of-care testing, as the heating and cooling processes cannot be avoided. In this study, the dual temperature modules were first designed to process microfluidic chips automatically circulating between them. Thus, a novel ultrafast molecular diagnostic real-time PCR device (approximately 18 and 23 min for DNA and RNA detection, respectively) with two channels (FAM and Cy5) for the detection of 12 targets was developed. The device contained three core functional components, including temperature control, optics, and motion, which were integrated into a portable compact box. The temperature modules accurately control temperature in rapid thermal cycles with less than ±0.1 °C, ±1 °C and ±0.5 °C for the temperature fluctuation, uniformity, and error of indication, respectively. The average coefficient of variation (CV) of the fluorescence intensity (FI) for all 12 wells was 2.3% for FAM and 2.7% for Cy5. There was a good linear relationship between the concentrations of fluorescent dye and the FIs of FAM and Cy5(R2 = 0.9990 and 0.9937), and the average CVs of the Ct values calculated by the embedded software were 1.4% for FAM and Cy5, respectively. The 100 double-blind mocked sputum and 249 clinical stool samples were analyzed by the ultrafast real-time PCR device in comparison with the DAAN Gene SARS-CoV-2 kit run on the ABI 7500 instrument and Xpert C. difficile/Epi, respectively. Among the 249 stool samples, the ultrafast real-time PCR device detected toxigenic C. difficile in 54 samples (54/249, 21.7%) with a specificity and positive predictive values of 99.0 and 96.3%, which were higher than the Xpert C. difficile/Epi values of 94.4 and 88.1% (p &gt; 0.05). The ultrafast real-time PCR device detected 15 SARS-CoV-2 positive samples, which has a 100% concordance with that obtained by the DAAN Gene SARS-CoV-2 kit. This study demonstrated that the ultrafast real-time PCR device integrated with microfluidic chips and dual temperature modules is an ultrafast, reliable, easy-to-use, and cost-effective molecular diagnostic platform for clinical diagnosis and on-site testing, especially in resource-limited settings.
Characteristics of the Intestinal Flora of TPOAb-Positive Women With Subclinical Hypothyroidism in the Second Trimester of Pregnancy: A Single-Center Prospective Cohort Study
Authors: Wu Min , Yang Yuxi , Fan Yali , Guo Shan , Li Tianhe , Gu Muqing , Zhang Tingting , Gao Huimin , Liu Ruixia , Yin Chenghong 
Published: May 2022

Pregnant women are at high risk of developing subclinical hypothyroidism (SCH), and anti-thyroid peroxidase antibody (TPOAb) positivity can further inhibit thyroxine synthesis. Emerging evidence indicates that intestinal flora can modulate metabolic and immune homeostasis. The characteristics of intestinal flora of TPOAb-positive women with SCH in their second trimester of pregnancy have not been reported. This single-center prospective observational cohort study investigated gut microbial composition and metabolic function using sequencing of the 16S rRNA gene in fecal samples from 75 TPOAb-positive women with SCH and 90 TPOAb-negative women with SCH during their second trimester of pregnancy. Women were treated with no levothyroxine (LT4), low-dose LT4 (≤50ug/d), or high-dose LT4 (&gt;50ug/d). Taxonomic analysis showed Firmicutes and Bacteroidetes were the dominant phyla, followed by Actinobacteria and Proteobacteria. Faecalibacterium, Bacteroides, Prevotella 9, Bifidobacterium, Subdoligranulum, Lachnospira, and Megamonas were the predominant genera. The intestinal flora of TPOAb-positive women with SCH who received no LT4 was characterized by bacterial amplicon sequence variants (ASVs)/operational taxonomic units (OTUs) enriched in the genus Subdoligranulum. The intestinal flora of TPOAb-positive women with SCH who received low-dose or high-dose LT4 were characterized by bacterial ASVs/OTUs depleted of the species Ruminococcus sp._or Bacteroides massiliensis, respectively. A total of 19 metabolic functions of intestinal flora, mainly involving lipid and amino acid metabolism, discriminated TPOAb-positive and TPOAb-negative women with SCH. Our study suggests that there are differences in the composition and metabolic function of intestinal flora of TPOAb-positive and TPOAb-negative women with SCH treated with different doses of LT4 in the second trimester of pregnancy. The findings provide insight into intestinal flora as novel targets for the treatment of TPOAb-positive women with SCH during pregnancy.
Rapid Detection of Klebsiella pneumoniae Carrying Virulence Gene rmpA2 by Recombinase Polymerase Amplification Combined With Lateral Flow Strips
Authors: Li Na , Wang Lei , Wang Fang , Chen Huimin , Tao Shuan , Zhu Qing , Liu Liping , Liang Wei , Ma Fang 
Published: May 2022

Highly virulent Klebsiella pneumoniae often causes invasive infections with high morbidity and mortality rates, posing an immense clinical challenge. Rapid and accurate detection of pathogenic bacteria is of great significance for treatment and preventive control. Conventional detection by polymerase chain reaction (PCR) is limited by a dependence on laboratory equipment and professional staff. Recombinase polymerase amplification (RPA) combined with a lateral flow strip (LFS) can rapidly amplify and visualize target genes in a short period of time. The aim of this study was to develop an RPA-LFS technique for detection of the K. pneumoniae virulence gene rmpA2. Primers were designed against conserved sequences specific to the virulence gene, and primer probe design was optimized by introducing base substitution to obtain a specific and sensitive primer-probe combination for clinical detection. We tested 65 actual samples collected from clinics to evaluate the performance of the newly established RPA-LFS system in comparison with conventional PCR methods and qPCR methods. The RPA-LFS assay was performed at for 25 min a constant temperature of 37°C, and results could be observed without instrumentation. The system could specifically identify highly virulent K. pneumoniae carrying the virulence gene rmpA2 with a minimum detection limit of 10−1 ng/μL and 10 copies/μL. For the 65 clinical samples tested, The RPA-LFS assay results were in complete agreement with the qPCR results and PCR results. The RPA-LFS assay provides a rapid, accurate, and simple method for identification of highly virulent K. pneumoniae carrying rmpA2.
INSC Is Down-Regulated in Colon Cancer and Correlated to Immune Infiltration
Authors: Yu Tao , Li Dan , Zeng Zhi , Xu Xu , Zhang Haiming , Wu Jie , Song Wei , Zhu Hua 
Published: May 2022

Background: Previous studies have verified that Inscuteable Spindle Orientation Adaptor Protein (INSC) can regulate cell proliferation and differentiation in the developing nervous system. It also plays an important role in spindle orientation during mitosis and asymmetric division of fibroblasts and participates in the process of stratification of the squamous epithelium. The role and potential mechanism of INSC in the development of colonic adenocarcinoma (COAD) have not been fully understood. This study aimed at exploring the prognostic value of INSC in COAD and the correlation of its expression with immune infiltration.Methods: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) project, Gene Expression Profiling Interactive Analysis (GEPIA), and Gene Expression Omnibus (GEO) database were used to analyze the expression of INSC in COAD. The INSC protein expression level was analyzed by immunohistochemistry staining and the Human Protein Atlas (HPA) database. The diagnostic and prognostic values of INSC in COAD patients were analyzed using receiver operating characteristic (ROC) and Kaplan–Meier (KM) survival curves. In order to understand whether INSC is an independent prognostic factor, we used univariable and multivariate Cox analyses to analyze INSC expression and several clinical characteristics with survival. We use STRING analysis to find INSC-related proteins and related biological events analyzed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. At last, GEPIA and the Tumor Immune Estimation Resource (TIMER) were employed to explore the relationship between INSC and immune infiltrates and its marker gene set.Results: INSC was lower expressed in COAD tissues than in normal colon tissues, which was correlated with tumor stage. Patients with lower expression of INSC had shorter overall survival (OS). Moreover, univariable Cox analysis demonstrated that high expression of INSC was an independent prognostic factor for COAD. ROC analysis showed INSC was an accurate marker for identifying tumors from normal colon tissue, and the AUC of the curve was 0.923. Significant GO term analysis by GSEA showed that genes correlated with INSC were found to be enriched in several immune-related pathways. Specifically, INSC expression showed significant negative correlations with infiltration levels of B cells, CD4+ T cells, macrophages, DCs, and their marker sets in COAD.Conclusion: INSC was provided with prognostic value in COAD and related to immune invasion.
Anti-Mitochondrial Antibody Titers Decrease Over Time in Primary Biliary Cholangitis Patients With Ursodeoxycholic Acid Therapeutic Response: A Cohort Study Followed Up to 28 Years
Authors: Chang Ming-Ling , Chen Wei-Ting , Chan Tien-Ming , Lin Cheng-Yu , Chang Ming-Yu , Chen Shiang-Chi , Chien Rong-Nan 
Published: May 2022

BackgroundHow anti-mitochondrial antibody (AMA) and liver biochemistry levels change in primary biliary cholangitis (PBC) patients treated with ursodeoxycholic acid (UDCA) remains unclear.MethodsA 28-year cohort of 157 PBC patients was conducted. Patients with alkaline phosphatase (Alk-p) levels &gt;1.67 × upper limit of normal after 1 year of UDCA treatment were considered nonresponders.ResultsAt baseline, of 157 (mean age: 54.41 years), 136 (86.6%) were female, 51 (32.5%) had cirrhosis, and 128 (81.5%) had detectable AMAs (immunoglobulin G). UDCA nonresponders (n=61) were younger and had higher Alk-p and total bilirubin levels and cirrhosis rates than UDCA responders (n=84). Alk-p levels and cirrhosis were negatively associated with UDCA response. Regardless of cirrhosis and UDCA response, most PBC patients had decreased Alk-p and γ-glutamyltransferase levels at last follow-up (up to 28.73 years) compared with baseline levels. Patients with baseline cirrhosis (2.78 ± 2.56 vs. 6.84 ± 9.00 mg/dL, p=0.024) and UDCA nonresponders (2.54 ± 2.19 vs. 4.51 ± 6.99 mg/dL, p=0.006) had increased total bilirubin levels while patients without cirrhosis (AST: 91.5 ± 84.5 vs. 58.9 ± 43.7 U/L, p&lt;0.001; ALT: 107.3 ± 122.5 vs. 50.7 ± 36.8 U/L, p&lt;0.001) and UDCA responders (AST: 83.8 ± 101.3 vs. 45.58 ± 38.42 U/L, p=0.014; ALT: 95.10 ± 144.6 vs. 39.12 ± 30.65 U/L, p=0.009) had decreased aminotransferase levels. Only UDCA responders had decreased AMA titers from 1 year after UDCA treatment (p=0.028) until the last follow-up (p&lt;0.001).ConclusionsUDCA responders exhibited decreased AMA titers 1 year after treatment. Regardless of UDCA response, PBC patients showed improved cholestatic features, but only UDCA responders and patients without baseline cirrhosis exhibited attenuated hepatobiliary damage following UDCA treatment.
Informed Consent in Clinical Studies Involving Human Participants: Ethical Insights of Medical Researchers in Germany and Poland
Authors: Timmermann Cristian , Orzechowski Marcin , Kosenko Oxana , Woniak Katarzyna , Steger Florian 
Published: May 2022

BackgroundThe internationalization of clinical studies requires a shared understanding of the fundamental ethical values guiding clinical studies. It is important that these values are not only embraced at the legal level but also adopted by clinicians themselves during clinical studies.ObjectiveOur goal is to provide an insight on how clinicians in Germany and Poland perceive and identify the different ethical issues regarding informed consent in clinical studies.MethodsTo gain an understanding of how clinicians view clinical studies in the countries they work in, we carried out semi-structured problem-centered interviews per telephone in Poland (n = 6) and Germany (n = 6). Our interviewees concentrated on three main topics: an appraisal of the normative framework, challenges in the information process and the protection of all participants in clinical studies.ResultsClinicians generally supported the normative framework, even though they considered it quite complex. In the two study countries, a widely noted dilemma in the information process was whether to overburden participants with extensive information or risking leaving out important facts. Clinicians were ready to exclude larger population groups from participating in clinical studies when the information process could not be carried out with standard procedures or when their inclusion was ethically sensitive.ConclusionClinicians need to gain a better understanding of the consequences of excluding larger population groups form participating in clinical studies. They should seek assistance in improving the information process for the inclusion of underrepresented groups in clinical studies.
Sex Differences in the Association Between Poor Sleep Quality and Alcohol-Related Problems Among Heavy Drinkers With Insomnia
Authors: Verlinden Justin J. , Moloney Mairead E. , Whitehurst Lauren N. , Weafer Jessica 
Published: May 2022

BackgroundAlcohol Use Disorder (AUD) and insomnia are highly comorbid; at least 40% of individuals with AUD suffer from insomnia. Women are more likely to report insomnia than men and have seen a concerning rise in rates of AUD in recent years. As such, the association between AUD and insomnia could be particularly pronounced in women. However, currently little is known regarding sex differences in this association. Here we examined the degree to which relationships between alcohol use and sleep quality differ between women and men.MethodsHeavy drinking women (n = 66) and men (n = 45) completed the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality and the Alcohol Use Disorders Identification Test (AUDIT) to assess alcohol use and alcohol-related problems. Hierarchical regression analyses were conducted to determine sex differences in the association between poor sleep quality and alcohol-related problems.ResultsAfter controlling for age, global subjective stress, and depression, sex significantly moderated the positive association between poor sleep quality and alcohol-related problems. Further analyses of the simple slopes for each sex revealed that poorer sleep quality (i.e., higher scores on the PSQI) were associated with greater alcohol-related problems (i.e., higher scores on the AUDIT) in women, but not in men.ConclusionThese results suggest that in heavy drinkers with insomnia, poor sleep is more strongly associated with drinking problems in women than in men. Future research is needed to investigate potential mechanisms underlying this relationship. Specifically, it will be important to determine whether sleep problems in heavy drinking women are a cause or consequence, or both, of heavy drinking.
Sequential Prefrontal and Temporoparietal Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment of Tinnitus With and Without Comorbid Depression: A Case Series and Systematic Review
Authors: Marder Katharine G. , Cho Janice , Chincanchan Ruth , Wilson Andrew C. , Corlier Juliana , Krantz David E. , Ginder Nathaniel D. , Lee Jonathan C. , Wilke Scott A. , Tadayonnejad Reza , Levitt Jennifer , Ishiyama Akira , Leuchter Michael K. , Leuchter Andrew F. 
Published: May 2022

BackgroundTinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems may better alleviate tinnitus distress than approaches targeting the auditory system alone.Materials and MethodsTen subjects with chronic tinnitus received sequential rTMS treatment involving: 1) excitatory stimulation administered to the left dorsolateral prefrontal cortex (DLPFC) or inhibitory stimulation administered to the right DLPFC, followed by 2) inhibitory stimulation administered to primary auditory cortex (Heschel's gyrus or HG). A systematic literature review was performed to evaluate the existing literature on sequential repetitive Transcranial Magnetic Stimulation (rTMS) treatment approaches for tinnitus. Results of the case series are interpreted in the context of tinnitus neurobiology and the extant literature.ResultsSubjects experienced a significant decrease (average 21.7%) in symptoms on the Tinnitus Functional Index (TFI). Those with tinnitus alone experienced a greater mean symptom reduction than those with comorbid MDD (27.7 vs. 17.0%, respectively). Adverse effects were transient and minor. Literature review confirmed that sequential approaches had some advantages compared to single site rTMS; in general, the addition of 1 Hz treatment at DLPFC was superior to single site rTMS in the short term (1–12 weeks), while the addition of 20 Hz treatment at DLPFC appeared superior in the long term (90–180 days).ConclusionsSequential rTMS approaches for the treatment of tinnitus—particularly those administering low-frequency treatment at left DLPFC—merit further investigation.
Machine Learning Classifiers to Evaluate Data From Gait Analysis With Depth Cameras in Patients With Parkinson’s Disease
Authors: Muñoz-Ospina Beatriz , Alvarez-Garcia Daniela , Clavijo-Moran Hugo Juan Camilo , Valderrama-Chaparro Jaime Andrés , García-Peña Melisa , Herrán Carlos Alfonso , Urcuqui Christian Camilo , Navarro-Cadavid Andrés , Orozco Jorge 
Published: May 2022

IntroductionThe assessments of the motor symptoms in Parkinson’s disease (PD) are usually limited to clinical rating scales (MDS UPDRS III), and it depends on the clinician’s experience. This study aims to propose a machine learning technique algorithm using the variables from upper and lower limbs, to classify people with PD from healthy people, using data from a portable low-cost device (RGB-D camera). And can be used to support the diagnosis and follow-up of patients in developing countries and remote areas.MethodsWe used Kinect®eMotion system to capture the spatiotemporal gait data from 30 patients with PD and 30 healthy age-matched controls in three walking trials. First, a correlation matrix was made using the variables of upper and lower limbs. After this, we applied a backward feature selection model using R and Python to determine the most relevant variables. Three further analyses were done using variables selected from backward feature selection model (Dataset A), movement disorders specialist (Dataset B), and all the variables from the dataset (Dataset C). We ran seven machine learning models for each model. Dataset was divided 80% for algorithm training and 20% for evaluation. Finally, a causal inference model (CIM) using the DoWhy library was performed on Dataset B due to its accuracy and simplicity.ResultsThe Random Forest model is the most accurate for all three variable Datasets (Dataset A: 81.8%; Dataset B: 83.6%; Dataset C: 84.5%) followed by the support vector machine. The CIM shows a relation between leg variables and the arms swing asymmetry (ASA) and a proportional relationship between ASA and the diagnosis of PD with a robust estimator (1,537).ConclusionsMachine learning techniques based on objective measures using portable low-cost devices (Kinect®eMotion) are useful and accurate to classify patients with Parkinson’s disease. This method can be used to evaluate patients remotely and help clinicians make decisions regarding follow-up and treatment.
Changes in Neutrophil to Lymphocyte Ratio, Lymphocyte to Monocyte Ratio, and Platelet to Lymphocyte Ratio During Palliative Radiotherapy May Predict Efficacy of Immune Checkpoint Inhibitor as Re-Challenge Treatment in Advanced Gastric Cancer: A Case Report
Authors: Chen Jianxin , Wu Xilin , Zhu Shijian , Wang Junhui 
Published: May 2022

IntroductionImmunotherapy with programmed death-1 (PD-1) inhibitors has emerged as frontline option in patients with advanced or metastatic gastric cancer. However, two-thirds of patients who received PD-1 inhibitors treatment still had disease progression in 1 year. Subsequent treatment strategies as salvage options always lead to limited efficacy.Case DescriptionHerein, we presented a case of recurrent metastatic gastric adenocarcinoma that had progressed on first-line treatment with nivolumab, in which systematic inflammation parameters with neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) were significantly changed by palliative radiotherapy on metastatic lymph nodes. The patient achieved persistent response to the re-challenge of immune checkpoint inhibitor, which resulted in survival time reaching 52 months, and is still in extension.ConclusionsWe supposed that the palliative radiotherapy may lead to the correction of NLR, LMR, and PLR and finally contribute to the efficacy of the re-challenge treatment by PD-1 inhibitor.
Risk Prediction of Second Primary Malignancies in Primary Early-Stage Ovarian Cancer Survivors: A SEER-Based National Population-Based Cohort Study
Authors: Xu Jiaqin , Huang Chen , Wu Zhenyu , Xu Huilin , Li Jiong , Chen Yuntao , Wang Ce , Zhu Jingjing , Qin Guoyou , Zheng Xueying , Yu Yongfu 
Published: May 2022

PurposeThis study aimed to characterize the clinical features of early-stage ovarian cancer (OC) survivors with second primary malignancies (SPMs) and provided a prediction tool for individualized risk of developing SPMs.MethodsData were obtained from the Surveillance, Epidemiology and End Results (SEER) database during 1998–2013. Considering non-SPM death as a competing event, the Fine and Gray model and the corresponding nomogram were used to identify the risk factors for SPMs and predict the SPM probabilities after the initial OC diagnosis. The decision curve analysis (DCA) was performed to evaluate the clinical utility of our proposed model.ResultsA total of 14,314 qualified patients were enrolled. The diagnosis rate and the cumulative incidence of SPMs were 7.9% and 13.6% [95% confidence interval (CI) = 13.5% to 13.6%], respectively, during the median follow-up of 8.6 years. The multivariable competing risk analysis suggested that older age at initial cancer diagnosis, white race, epithelial histologic subtypes of OC (serous, endometrioid, mucinous, and Brenner tumor), number of lymph nodes examined (&lt;12), and radiotherapy were significantly associated with an elevated SPM risk. The DCA revealed that the net benefit obtained by our proposed model was higher than the all-screening or no-screening scenarios within a wide range of risk thresholds (1% to 23%).ConclusionThe competing risk nomogram can be potentially helpful for assisting physicians in identifying patients with different risks of SPMs and scheduling risk-adapted clinical management. More comprehensive data on treatment regimens and patient characteristics may help improve the predictability of the risk model for SPMs.