bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissemination of Circulating Tumor Cell Clusters Occurs Early in Non‑metastatic Breast Cancer Patients
Authors: Reduzzi Carolina , Cosimo Serena Di , Gerratana Lorenzo , Motta Rosita , Martinetti Antonia , Vingiani Andrea , D'Amico Paolo , Zhang Youbin , Vismara Marta , Depretto Catherine , Scaperrotta Gianfranco , Folli Secondo , Pruneri Giancarlo , Cristofanilli Massimo , Daidone Maria Grazia , Cappelletti Vera
Published: January 2021

Background: Metastatic spreading is promoted by cancer cell seeding from the primary tumor into the bloodstream. In patients with metastatic breast cancer (MBC), the clinical relevance of circulating tumor cell clusters (CTC-clusters) has been extensively reported, while their study in earlier stages is limited. Several methods, besides the FDA-cleared CellSearch®, limited to the detection of epithelial-enriched clusters, can be used for the detection of CTC-clusters. We hypothesize that resorting to marker-independent approaches can improve CTC-cluster detection. Methods: Blood samples collected from healthy donors and spiked-in with tumor mammospheres, or from BC patients, were processed for CTC-cluster detection with 3 technologies: CellSearch®, CellSieve™ filters, ScreenCell® filters. The number of CTC-clusters was compared among the technologies and analyzed in relation to patient characteristics and outcome. Results: In spiked-in samples, the 3 technologies showed similar capability of recover epithelial mammospheres, whereas, in a series of 19 clinical samples processed in parallel with the CellSearch® and CellSieve™ filters (that allow the detection of both epithelial and non-epithelial clusters), CTC-clusters were detected in 53% of samples with the CellSearch®, versus 79% and 84% with the CellSieve™, when considering only epithelial or both epithelial and non-epithelial clusters, respectively. Next, blood samples from 37 non-metastatic breast cancer (NMBC) and 23 MBC patients were processed using ScreenCell® filters for attaining both unbiased enrichment and marker-independent identification of clusters based on cytomorphological criteria. At baseline, CTC-clusters were detected in 70% of NMBC cases and in 20% of MBC patients (median number= 2, range 0–20, versus 0, range 0‑15, P =0.0015). Among NMBC patients, clusters were slightly higher in women with node-positive than node‑negative status (0 versus 3, P =0.1110 ) and were more frequently observed in women with luminal‑like and triple-negative tumors than in patients with HER2-positive disease (median CTC-cluster number =4, 5, and 0 for luminal‑like, triple-negative, and HER2-positive BC, respectively, P =0.0467). Conclusions: We demonstrated that CTC-cluster detection can be improved by a marker-independent enrichment and identification, and we reported that CTC-clusters are more frequently detected in NMBC than in MBC patients, suggesting that dissemination of CTC-clusters is an early event in BC natural history.
Weld Defect Detection and Image Defect Recognition Using Deep Learning Technology
Authors: Cheng Yu , Deng HongGui , Feng YuXin , Xiang JunJiang
Published: January 2021

Welding defects not only bring several economic losses to enterprises and individuals but also threatens peoples lives. We propose a deep learning model, where the data-trained deep learning algorithm is employed to detect the weld defects, and the Convolutional Neural Networks (CNNs) are utilized to recognize the image features. The Transfer Learning (TL) is adopted to reduce the training time via simple adjustments and hyperparameter regulations. The designed deep learning-based model is compared with other classic models to prove its effectiveness in weld defect detection and image recognition further. The results show this model can accurately identify weld defects and eliminates the complexity of manually extracting features, reaching a recognition accuracy of 92.54%. Hence, the reliability and automation of detection and recognition is improved signifificantly. Actual application also verififies the effectiveness of TL in weld defect detection and image defect recognition. Therefore, our research results can provide theoretical and practical references for effificient automatic detection of steel plates, cost reduction, and the high-quality development of iron and steel enterprises.Index Terms - convolutional neural network, deep learning, image detect recognition, transfer learning, weld defect detection
Improving Early Diagnosis of Rare Diseases Using Natural Language Processing in Unstructured Medical Records: An Illustration From Dravet Syndrome 
Authors: Barco Tommaso Lo , Kuchenbuch Mathieu , Garcelon Nicolas , Neuraz Antoine , Nabbout Rima
Published: January 2021

BackgroundThe growing use of Electronic Health Records (EHRs) is promoting the application of data mining in health-care. A promising use of big data in this field is to develop models to support early diagnosis and to establish natural history. Dravet Syndrome (DS) is a rare Developmental and Epileptic Encephalopathy that commonly initiates in the first year of life with febrile seizures (FS). Age at diagnosis is often delayed after two years, as it is difficult to differentiate DS at onset from FS.We aimed to explore if some clinical terms (concepts) are significantly more used in the electronic narrative medical reports of individuals with DS before the age of two years compared to those of individuals with FS. These concepts would allow an earlier detection of patients with DS resulting in an earlier orientation toward expert centers that can provide early diagnosis and care.MethodsData were collected from the Necker Enfants Malades Hospital using a document-based data warehouse, Dr Warehouse, which employs Natural Language Processing, a computer technology consisting in processing written information. Using Unified Medical Language System Meta-thesaurus, phenotype concepts can be recognized in medical reports. We selected individuals with DS (DS Cohort) and individuals with FS (FS Cohort) with confirmed diagnosis after the age of four years. A phenome-wide analysis was performed evaluating the statistical associations between the phenotypes of DS and FS, based on concepts found in the reports produced before two years and using a series of logistic regressions. ResultsWe found significative higher representation of concepts related to seizures’ phenotype distinguishing DS from FS in the first phases, namely the major recurrence of complex febrile convulsions (long-lasting and/or with focal signs) and other seizure-types. Some typical early onset non-seizure concepts also emerged, in relation to neurodevelopment and gait disorders. ConclusionsNarrative medical reports of individuals younger than two years with FS contain specific concepts linked to DS diagnosis, which can be automatically detected by software exploiting NLP. This approach could represent an innovative and sustainable methodology to decrease time of diagnosis of DS and could be transposed to other rare diseases.
The DISCO App: Evaluating an Electronic Patient Intervention to Reduce The Financial Burden of Cancer Through Improved Cost Communication In A Non-Randomized Pilot Trial
Authors: Hamel Lauren M. , Dougherty David W. , Hastert Theresa A. , Seymour Erlene K. , Kim Seongho , Assad Hadeel , Phalore Jasminder , Soulliere Roger , Eggly Susan
Published: January 2021

Background: Financial toxicity affects 30-50% of people with cancer in the US. Although experts recommend patients and oncologists discuss treatment cost, cost discussions occur infrequently. Using a non-randomized pre-test post-test design, we pilot-tested the feasibility, acceptability and preliminary effectiveness of the DIScussions of COst (DISCO) App, a patient communication intervention designed to improve the frequency of cost discussions and related outcomes. Methods: While waiting to see their oncologist, patients (n=32) used the DISCO App on a tablet. Clinic visits were video recorded and patients completed pre- and post-intervention measures of self-efficacy for managing treatment costs, self-efficacy for interacting with oncologists, cost-related distress, and perceptions of the DISCO App. Coders observed the recordings to determine the presence of cost discussions, initiators, and topics. Results: Most patients (84%) reported needing <15 minutes to use the DISCO App. Patients reported the DISCO App made it easier to ask cost-related questions. Findings showed increased self-efficacy for managing treatment costs (p=.02) and for interacting with oncologists (p=.001). All clinic visits included a cost discussion. Conclusion: The DISCO App is feasible, acceptable, and effective in prompting cost discussions and improving outcomes. Prompting patients to discuss costs before meeting with an oncologist may improve treatment cost discussions and related outcomes.Trial registration: Clinical Trials.gov registration number: NCT03676920 (September 19, 2018)
Tracing Sources of PM10 in Central Taiwan by using Chemical Characteristics and Pb Isotope Ratios: Local Versus Long-range Transport
Authors: Wu Po-Chao , Huang Kuo-Fang
Published: January 2021

Central Taiwan is among the most heavily polluted regions in Taiwan because of a complex mixing of local emissions from intense anthropogenic activities with natural dust. Long-range transport (LRT) of pollutants from outside Taiwan also contributes critically to the deterioration of air quality, especially during the northeast monsoon season. To identify the sources of particulate matter <10 μm (PM10) in central Taiwan, this study performed several sampling campaigns, including three local events, one LRT event, and one dust storm event, during the northeast monsoon season of 2018/2019. The PM10 samples were analyzed for water-soluble ion and trace metal concentrations as well as Pb isotope ratios. Local river sand/soil samples were also collected and analyzed to constrain chemical/isotopic signatures of natural sources. The Pb isotope data were interpreted together with the enrichment factors of trace metals in PM10, and reanalysis data sets were used to delineate the sources of PM10 in central Taiwan. Our results suggested that PM10 was predominantly contributed by oil combustion and oil refineries during the local events (48%–88%), whereas the lowest contributions were from coal combustion (<21%). During periods of high wind speed, the contribution from natural sources increased significantly from 7% to 31%. Moreover, the Pb isotopic signals of PM10 collected during the LRT event confirmed the impact of LRT from Mainland China, and the chemical characteristics of the PM10 significantly differed from those of the PM10 collected during local events. This study demonstrates the robustness of using a combination of Pb isotopic compositions and enrichment factors in PM10 for source apportionment in complex and heavily polluted areas.
Hsa_circ_0013401 Accelerates the Growth, Metastasis and Prevents Apoptosis Autophagy of Neuroblastoma Cells by Sponging miR-195 to Release PAK2 
Authors: Zhu Shibo , Tang Xiangliang , Gao Xiaofeng , Zhang Jingqi , Cui Yanhong , Li Dian , Jia Wei
Published: January 2021

Background: Circular RNA (circRNA) is a newly discovered non-coding RNA with a covalently closed loop structure. Recently, the increased circRNAs have been identified in a variety of cancers. While, the specific functions and mechanisms of some circRNAs in neuroblastoma (NB) are still largely unexplored.Materials and Methods: The levels of hsa_circ_0045997, hsa_circ_0080307, hsa_circ_0013401, hsa_circ_0077578 and microRNA-195 (miR-195) were confirmed by RT-qPCR assay in NB. Functionally, gain- and loss-of-function assays and the rescued experiment were conducted to determine the influences of hsa_circ_0013401, miR-195 and P21-activated kinase 2 (PAK2) on the proliferation, apoptosis, autophagy, migration and invasion of NB cells. Luciferase reporter gene assay was also applied to examine the relationships between hsa_circ_0013401 and miR-195, miR-195 and PAK2. Hsa_circ_0013401/miR-195/PAK2 axis was also identified by in vivo experiment study.Results: Hsa_circ_0013401 was highly expressed, miR-195 was lowly expressed, and there was a negative correlation between hsa_circ_0013401 and miR-195 in NB. Hsa_circ_0013401 significantly suppressed the proliferation, migration and invasion, and induced apoptosis and autophagy of NB. In mechanism, miR-195 was a direct target of hsa_circ_0013401, and PAK2 was the downstream target gene of miR-195. And the inhibitory effects of hsa_circ_0013401 knockdown on the malignant biological properties of NB can be achieved by targeting miR-195 to upregulated PAK2. Besides, in vivo evidences also revealed that hsa_circ_0013401 promotes tumor formation, and regulated miR-195 and PAK2. Conclusions: Hsa_circ_0013401 induced NB progression through miR-195 to enhance PAK2. Therefore, we might highlight a novel regulatory axis (hsa_circ_0013401/miR-195/PAK2) in NB.
Total Health Expenditure and Its Driving Factors in China: A Gray Theory Analysis
Authors: Jia Huanhuan , Jiang Hairui , Yu Jianxing , Zhang Jingru , Cao Peng , Yu Xihe
Published: January 2021

Background: The continuous growth in total health expenditure (THE) has become a social issue of common concern in most countries. In China, THE is maintaining a rapid growth trend that is faster than that of the economy, and this trend has become increasingly obvious in the 21st century and has placed a heavy burden on the government and residents. Therefore, the aims of this paper are to analyze the main driving factors and establish a predictive model of the growth of THE in China in the 21st century.Methods: Gray system theory was employed to explore the correlation degree between THE and 9 hot topics in the areas of the economy, population, health service utilization, and policy using national data for China from 2000 to 2018. Additionally, a New Structure of the Multivariate Gray (NSGM) prediction model of health expenditure was established and compared with the traditional grey model and widely used Back Propagation (BP) neural network.Results: General government expenditures on health, the economy, and out-of-pocket health expenditures were highly correlated with THE, with all correlation degrees greater than 0.8. The correlation degrees between health institutions, population and THE were 0.6-0.8, whereas infant mortality rate and THE was only 0.573. The average of the residual percentage of the training data of the NSGM(1,10) model is 0.36%, and that of the test data is 1.85%, which is better than the results of the other models.Conclusion: The Chinese government and society have played a crucial role in reducing residents’ medical burden, whereas the improved economy and aging population have increased the demand for health services, leading to the continual increase in THE. The improved NSGM(1,N) model achieved good prediction accuracy and has unique advantages in simulating and predicting THE, which can provide a basis for policy formulation.
Prognostic Factors of Fluid-gas Exchange Outcomes in Patients with Failed Primary Surgery for Idiopathic Macular Hole
Authors: Lee You Hyun , Jang Ji Hye , Lee Soo Jin , Kim Yu Cheol
Published: January 2021

This retrospective study aimed to evaluate prognostic factors associated with the success of fluid-gas exchange in patients with failed primary idiopathic macular hole (IMH) surgery. Outcomes of the fluid-gas exchange were categorised as unclosed, or U-type, V-type, or W-type closure. Patients were divided into the successful and unsuccessful groups according to the absence or presence of bare retinal pigment epithelium, respectively, following fluid-gas exchange. Demographics, baseline characteristics, and pre-procedure characteristics were assessed. A total of 19 eyes in 19 patients that had failed IMH surgery and then underwent fluid-gas exchange were included. Of those, 18 eyes had MH closure (successful, 15 eyes; unsuccessful, three eyes). One eye was unclosed after fluid-gas exchange; therefore, the patient underwent additional vitrectomy for MH closure (unsuccessful). The successful group showed significantly lower pre-procedure base diameters; higher baseline and pre-procedure macular hole index, hole form factor, and tractional hole index values; and lower baseline and pre-procedure minimum diameter and diameter hole index values. Moreover, a better visual prognosis was observed in the successful group. These results suggest that indices predicting favourable results of primary surgery for IMH are useful to predict the success of fluid-gas exchange in patients with failed primary MH surgery.
The effect of physical exercise on fundamental movement skills and physical fitness among preschool children: study protocol for a cluster-randomized controlled trial
Authors: Wang Guangxu , Zi Yahua , Li Bo , Su Shan , Sun Lei , Wang Fei , Ren Chener , Liu Yang
Published: January 2021

Background Previous evidence has proven that physical exercise is positively related to preschoolers’ fundamental movement skills (FMS) and physical fitness (PF). However, studies to assess the effectiveness of different physical exercise interventions aiming at improving FMS and PF in preschool children are still scarce. To explore and compare the effectiveness of different physical exercise on FMS and PF; ball games (BG), rhythm activities (RA), basic movements (BM) and a combination of all related activities (multiple activities, MA) interventions were conducted among preschoolers.Methods A single-blind, 5-arm, cluster-randomized trial will be conducted in kindergarten in Shanghai, China. Three hundred healthy preschoolers, aged 4 to 5 years, will be randomized to four intervention groups (BG group, RA group, BM group or MA group) and one control group (unorganized physical activities). Four intervention groups will receive three 30-minute lessons weekly for 16 weeks. At the baseline, the end of 16-week intervention, and 6-month follow-up after the end of intervention, the primary outcomes (FMS and PF) and the secondary outcome (physical activity, PA) will be assessed, as well as sociodemographic and anthropometric data.Discussion This study will provide vital information regarding the effect of different physical exercise interventions on preschool children’s FMS and PF, PA, and the potential interactions between these domains. If the results of this trial are positive, the most effective intervention strategy can be generalized to kindergarten and other preschool educational institutions in practice to promote preschooler’s development of FMS and PF.Trial registration Chictr.org.cn ChiCTR2000029333.
Antibiotic accumulation, growth performance, physiologic status and intestinal flora diversification of Nile tilapia (Oreochromis niloticus) feed by diets supplemented with different dose of sulfamethoxazole
Authors: Fang Longxiang , Chen Xi , Shan Xiangbao , Qiu Liping , Fan Limin , Meng Shunlong , Song Chao
Published: January 2021

Background

Sulfamethoxazole (SMZ) is an antibiotic used globally to treat fish disease in aquaculture, but the effects of exposure to legal aquaculture doses of SMZ in fish are still unclear. To comprehensively investigate the effects of exposure to legal doses of sulfamethoxazole (SMZ) in Nile tilapia (Oreochromis niloticus), fish were exposed to diets supplemented with different doses of SMZ (blank group, normal feed; LS, 0.67 g/kg; MS, 6.67 g/kg and HS, 33.33 g/kg) for 4 weeks. General SMZ accumulation, growth performance, physiologic status, intestinal and hepatic health were systemically evaluated.
Results

The exposure experiment indicated that the SMZ accumulation in O. niloticus muscles, intestinal and aquaculture environment were positively related to the exposure dose. And withdrawal of antibiotics feed after 4th week, the SMZ residual in fish muscles, aquaculture water and sediment gradually decreased to safe level. LS and MS amount of antibiotics promoted the growth of fish accompanied by reduced feed coefficient in treated groups, while the fish growth in HS group was retarded. Exposure of O. niloticus to SMZ also increased the content of TG, promoted liver hypertrophy, and increased number of fat particles in liver. Antibiotics changed the content of intestinal short-chain fatty acids (SCFAs), and the changes in acetic acid were the most obvious. SMZ exposure reduced the biological diversity of the intestinal flora subsequently induced microbiota dysbiosis, and the degree was positively related to the exposure doses, and the experimental mainly inhibiting the growth of Fusobacteria.
Conclusions

Overall, exposure to of fish to legal doses of SMZ impair general physiological functions, intestinal flora and provokes health risk in fish. This study highlights the importance of rational and regulated use of SMZ in aquaculture.
Efficacy of Bladder Ultrasound in Prediction of Resolution of Vesicoureteral Reflux after Endoscopic Subureteral Hyaluronic Acid/Dextranome (Deflux®) Injection
Authors: Aboutaleb Hamdy , Eldib Diaa , Omar Mohamed , Gharbawy Mohamed El , Zanaty Fouad
Published: January 2021

BACKGROUND: We evaluated the efficacy of bladder ultrasound to predict resolution of vesicoureteral reflux after subureteral endoscopic Hyaluronic acid/dextranome (Deflux) injection.METHODS: Between 2010 and 2018, 120 patients (220 ureters) underwent Subureteral Deflux injection for reflux in children. Male/female ratio was 1: 5. All patients had voiding cystourethrography and bladder ultrasound at 3 months and one year after surgery. Outcome analysis included: Success rates and presence/ absence of Deflux mount by bladder ultrasound. RESULTS: Mean follow-up was 48 months. Mean age at surgery 72 months. Grades of reflux were grade II in 100 ureters (45.4%), III in 90 ureters (41%) and IV-V in 30 ureters (13.6%). Bilateral surgery was performed in 40 patients. Single Deflux injection cured reflux (Success rate) in 85% (187 ureters) at 3 months which improved to 88.2% (194 ureters) at last follow-up. Ultrasound was able to detect Deflux mounts at the base of the bladder in 200 ureters (91%). Sensitivity and specificity of ultrasound was 92.68% and 20% of the correction of reflux at the last follow up. Positive Predictive Value of bladder ultrasound was 94 % and accuracy was 87.7 % at the last follow up. Ultrasound did not detect the mount in 20 ureters (9 %) and 8 of these ureters (3.6%) had persistence of their reflux. Ultrasound was able to detect bilateral mounts as well as unilateral mounts.CONCLUSION: Bladder-US was highly sensitive for detection of Deflux implants and can predict resolution of reflux in 82.7% of refluxing ureters. Postoperative bladder-US could be adjusted as a screening tool in the follow-up of patients with primary low-grade VUR patients treated by Deflux injection, while VCUG could be preserved for follow-up of high-grade VUR patients.
Trends in Prevalence of Extended-Spectrum Beta-Lactamase-Producing Escherichia Coli Isolated From Patients With Community- And Healthcare-Associated Bacteriuria: Results From 2014 To 2020 In An Urban Safety-Net Healthcare System
Authors: Raphael Eva , Glymour Maria , Chambers Henry F
Published: January 2021

BackgroundThe prevalence of infections caused by extended-spectrum beta-lactamase producing Escherichia coli (ESBL-E. coli) is increasing worldwide, but the setting in which this increase is occurring is not well defined. We compared trends and risk factors for ESBL-E. coli bacteriuria in community vs healthcare settings.MethodsWe collected electronic health record data on all patients with E. coli isolated from urine cultures in a safety-net public healthcare system from January 2014 to March 2020. All analyses were stratified by healthcare-onset/associated (bacteriuria diagnosed > 48 hours after hospital admission or in an individual hospitalized in the past 90 days or in a skilled nursing facility resident, N=1,277) or community-onset bacteriuria (all other, N=7,751). We estimated marginal trends from logistic regressions to evaluate annual change in prevalence of ESBL-E. coli bacteriuria among all bacteriuria. We evaluated risk factors using logistic regression models.ResultsESBL-E. coli prevalence increased in both community-onset (0.91% per year, 95% CI: 0.56%, 1.26%) and healthcare-onset/associated (2.31% per year, CI: 1.01%, 3.62%) bacteriuria. In multivariate analyses, age >65 (RR 1.88, CI: 1.17, 3.05), male gender (RR 2.12, CI: 1.65, 2.73), and Latinx race/ethnicity (RR 1.52, CI: 0.99, 2.33) were associated with community-onset ESBL-E. coli. Only male gender (RR 1.53, CI: 1.03, 2.26) was associated with healthcare-onset/associated ESBL-E. coli.ConclusionsESBL-E. coli bacteriuria frequency increased at a faster rate in healthcare-associated settings than in the community between 2004 to 2020. Male gender was associated with ESBL-E. coli bacteriuria in both settings, but additional risks—age >65 and Latinx race/ethnicity—were observed only in the community.
Incidence of Microcarcinoma and Non-Microcarcinoma in Ultrasound-Found Thyroid Nodules
Authors: Chen Zhi , Mosha Singla Sethiel , Zhang Tong , Xu Ming , Li Yanli , Hu Zhuoqing , Liang Weiqiang , Deng Xiaoyi , Ou Tingting , Li Ling , Li Wangen
Published: January 2021

Backgrounds: The incidence of thyroid nodules is increasing year by year around the world. However, ultrasound is not recommended as a screening test for the general population or patients with a normal thyroid on palpation by the American Association of Clinical Endocrinologists (AACE). In practice, some individuals with normal thyroid palpation have nodules that can just be found out by ultrasound. No studies have directly described the risk of nodules found by ultrasound or by palpation up to now. More evidence is needed to carry out for helping us balance the over diagnosis and missed diagnosis of malignant lesions. Therefore, we carried out a retrospective study to investigate the incidence of malignant lesions in ultrasound-found nodules in a large cohort.Methods: We conducted a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation and fine-needle aspiration (FNA) between Jan 2013 and Dec 2019. The cytologic examinations were analyzed based on the Bethesda system. For nodules suspected to be follicular neoplasm or other malignant tumors by cytological tests, patients were recommended for surgery and histopathology examinations.Results: Compared with palpation-found nodules, ultrasound-found nodules were presenting less as purely cystic nodules (10.1% vs 39.9%, x2=355.69, p=0.000), smaller size (17.5±9.9 mm vs 28.0±12.5 mm, t=23.876 p=0.000), and higher TI-RADS score (5.5±2.9 vs 3.4±3.3, t=18.084, p=0.000), respectively. More ultrasound-found nodules were diagnosed as carcinoma by histology examinations [136 (11.2%) nodules found by ultrasound vs 68 (3.9%) by palpation, x2=59.737, p=0.000], and 88 (64.7%) nodules found by ultrasound were non-microcarcinoma. Among the malignant nodules confirmed by histopathology, a higher proportion of microcarcinoma was detected in ultrasound-found nodules [35.3% (48/136) vs 16.2% (11/68), x2=8.183, p=0.004]. Conclusions: In view of the results observed in our research that malignant nodules were more common screened out by ultrasound, and nearly two thirds of them were non-microcarcinoma. We recommend reassessment of the recommendations for thyroid nodule screening.
A Pseudomonas plant pathogen uses distinct modes of stationary phase persistence to survive bacteriocin and streptomycin treatments
Authors: Patel Ravikumar R. , Kandel Prem P. , Traverso Eboni , Hockett Kevin L. , Triplett Lindsay R.
Published: January 2021

Antimicrobial treatment of bacteria often results in a small population of surviving tolerant cells, or persisters, that may contribute to recurrent infection. Antibiotic persisters are metabolically dormant, but the basis of persistence to membrane-disrupting biological compounds is less well-understood. We previously found that the model plant pathogen Pseudomonas syringae pv. phaseolicola 1448A (Pph) exhibits persistence to tailocin, a membrane-disrupting biocontrol compound with potential for sustainable disease control. Here we compared physiological traits associated with persistence to tailocin and to the antibiotic streptomycin, and established that both treatments leave similar frequencies of persisters. Microscopic profiling of treated populations revealed that while tailocin rapidly permeabilizes most cells, streptomycin treatment results in a heterogeneous population of redox and membrane permeability states. Sorting cells according to redox reporter intensity identified streptomycin persisters among the low-redox fraction, but tailocin persisters were only cultured from the fraction with intermediate redox activity. Cells from culturable fractions were able to infect host plants, while nonculturable redox-active cells were not. Tailocin and streptomycin were effective in eliminating all persisters when applied sequentially, in addition to eliminating cells in other viable states. This study identifies distinct redox states associated with antibiotic persistence, tailocin persistence, and virulence, and demonstrates that tailocin is highly effective in eliminating dormant cells.
Effectiveness of Attachment-Based Family Therapy compared to Treatment as Usual for Depressed Adolescents in Community Mental Health Clinics
Authors: Waraan Luxsiya , Rognli Erling W. , Czajkowski Nikolai Olavi , Aalberg Marianne , Mehlum Lars
Published: January 2021

Background: Major Depressive Disorder (MDD) is a disabling mood disorder, profoundly affecting a large number of adolescent’s quality of life. To date, no obvious treatment of choice for MDD in adolescents is available and progress in the treatment of depressed adolescents will have important public health implications. Attachment-Based Family Therapy (ABFT), as the only empirically supported family therapy model designed to treat adolescent depression, aims to repair interpersonal ruptures and rebuild an emotionally protective parent-child relationship. Objective: To study the effectiveness of ABFT compared with treatment as usual (TAU) delivered within child- and adolescent mental health services (CAMHS) to adolescents with MDD. Method: Sixty adolescents (86.7% girls), aged 13-18 years (M = 14.9, SD = 1.35), with MDD referred to two CAMHS were randomized to 16 weeks of ABFT or TAU. ABFT consisted of weekly therapy sessions (family/individual or both) according to the treatment manual. TAU was not monitored. Primary outcomes were assessed by blinded evaluators at baseline and post-treatment with the Hamilton Depression Scale (HAMD). Self-reported (Beck Depression Inventory-II, BDI-II) depressive symptoms were assessed at baseline, and after 4, 6, 8, 10,12, 14, and 16 weeks. Analyses were performed according to intent-to-treat principles. Results: At post-treatment, clinician-rated remission rates on the HAMD (5 % in ABFT and 3.33% in TAU, p =1, OR=1.54, Fisher’s exact test) and self-reported symptoms of depression on the BDI-II did not differ significantly between groups (X2[2, N = 60] =0.06 , p = 0.97). In both treatment groups participants reported significantly reduced depressive symptoms, but the majority (63.3 %) of adolescents were still in the clinical range after 16 weeks of treatment. Conclusion: ABFT was not superior to TAU. Remission and response rates were low in both groups, suggesting none of the treatments were effective in treating MDD in adolescents. Findings must be viewed in the context of the study’s small sample size, missing data, and implementation challenges. Continued efforts to improve treatment for MDD in outpatient clinics are warranted . Future research should examine moderators of and mechanisms for individual differences to treatment response, as well as the feasibility and cost-effectiveness of implementing treatment models which may require extensive training and expertise to yield clinically meaningful improvements in non-research settings. Trial Registration: Clinicaltrials.gov identifier: NCT01830088 https://clinicaltrials.gov/ct2/show/NCT01830088?term=Villab%C3%B8&draw=2&rank=1 Date of registration: April 12, 2013
The concept of a cementless isoelastic monoblock cup made of highly cross-linked polyethylene infused with vitamin E: Radiological analyses of migration and wear using EBRA and clinical outcomes at mid-term follow-up
Authors: Afghanyar Yama , Joser Sebastian , Tecle Jonas , Drees Philipp , Dargel Jens , Rehbein Philipp , Kutzner Karl Philipp
Published: January 2021

Background: The newest generation of cementless titanium-coated, isoelastic monoblock cup with vitamin E-blended highly cross-linked polyethylene (HXLPE) was introduced to the market in 2009. The aim of the present study was to obtain mid-term follow-up data including migration and wear analyses.Methods: This prospective study investigated 101 primary total hip arthroplasty (THA) cases in 96 patients treated at a single institution. Patients were allowed full weight-bearing on the first day postoperatively. Harris hip score (HHS) and pain and satisfication on a visual analogue scale (VAS) were assessed at a mean follow-up of 79.0 months. Migration and wear were assessed using Einzel-Bild-Roentgen-Analyse (EBRA) software. Radiological acetabular bone alterations and complications were documented.Results: At mid-term follow-up (mean 79.0 months, range: 51.8–101.7), 81 cases with complete clinical and radiological data were analyzed. Utilisable EBRA measurements were obtained for 42 hips. The mean HHS was 91.1 (range 38.0–100.0), VAS satisfaction was 9.6 (range 6.0–10.0), VAS rest pain was 0.2 (range 0.0–4.0), and VAS load pain was 0.6 (range 0.0–9.0). Mean migration was 0.86 mm (range: 0.0–2.56) at 24 months and 1.34 mm (range: 0.09–3.14) at 5 years, and the mean annual migration rate was 0.22 (range: -0.24–1.34). The mean total wear was 0.4 mm (range: 0.03–1.0), corresponding to a mean annual wear rate of 0.06 mm per year (range: 0.0–0.17). Radiographic analysis did not reveal any cases of osteolysis, and no revision surgeries had to be performed.Conclusions: After using vitamin-E blended HXLPE in cementless isoelastic monoblock cups, there were no obvious signs of osteolysis or aseptic loosening occurred. No patients required revision surgery after mid-term follow-up. Cup migration and wear values were well below the benchmarks considered predictive for potential future failure.
Prevalence of Metabolic Syndrome among Breast Cancer Survivors in East Coast of Peninsular Malaysia
Authors: Shahril Mohd Razif , Amirfaiz Syed , Lua Pei Lin , Nurnazahiah Ali , Zakarai Nor Syamimi , Kow Ving Lok , Ahmad Aryati , Sulaiman Suhaina
Published: January 2021

Background: To date, limited data are available on metabolic syndrome prevalence among breast cancer survivors in Malaysia. Therefore, this study was conducted to determine the prevalence of metabolic syndrome and abnormal metabolic syndrome components among breast cancer survivors in East Coast of Peninsular Malaysia. Methods: This cross-sectional study included 95 breast cancer survivors (age 53.7±7.6 years) who have completed main cancer treatments for ≥6 months. Cancer survivors were recruited from two main government hospitals in Kelantan and Terengganu using a purposive sampling method. Results: According to the Harmonized criteria, the metabolic syndrome prevalence was 50.5%. Among those with metabolic syndrome, the most prevalent abnormal metabolic components were triglycerides (91.2%), fasting blood glucose (79.6%) and HDL-c level (78.4%). Except for total cholesterol and LDL-c, all other metabolic syndrome components were significantly different (p<0.05) between those with and without metabolic syndrome. Significant differences between metabolic syndrome and non-metabolic syndrome groups were found for weight, BMI, waist circumference, body fat percentage and cancer stages (p<0.05). However, no significant relationship was reported between sociodemographic, clinical parameters and metabolic syndrome among breast cancer survivors in this study. Conclusions: Metabolic syndrome was highly prevalent among breast cancer survivors. It is recommended for health care professionals to closely monitor and improve the triglycerides, blood glucose and HDL-c level of the breast cancer survivors under their care to control the detrimental effect of metabolic syndrome.
A method for evaluation of patient-specific lean body mass from limited-coverage CT images and its application in PERCIST: comparison with predictive equation
Authors: Shang Jingjie , Tan Zhiqiang , Cheng Yong , Tang Yongjin , Guo Bin , Gong Jian , Ling Xueying , Wang Lu , Xu Hao
Published: January 2021

Background: Standardized uptake value (SUV) normalized by lean body mass ([LBM] SUL) is recommended as metric by PERCIST 1.0. The James predictive equation (PE) is a frequently used formula for LBM estimation, but may cause substantial error for an individual. The purpose of this study was to introduce a novel and reliable method for estimating LBM by limited-coverage (LC) CT images from PET/CT examinations and test its validity, then to analyse whether SUV normalised by LC-based LBM could change the PERCIST 1.0 response classifications, based on LBM estimated by the James PE. Methods: First, 199 patients who received whole-body PET/CT examinations were retrospectively retrieved. A patient-specific LBM equation was developed based on the relationship between LC fat volumes (FVLC) and whole-body fat mass (FMWB). This equation was cross-validated with an independent sample of 97 patients who also received whole-body PET/CT examinations. Its results were compared with the measurement of LBM from whole-body CT (reference standard) and the results of the James PE. Then, 241 patients with solid tumours who underwent PET/CT examinations before and after treatment were retrospectively retrieved. The treatment responses were evaluated according to the PE-based and LC-based PERCIST 1.0. Concordance between them was assessed using Cohen’s κ coefficient and Wilcoxon’s signed-ranks test. The impact of differing LBM algorithms on PERCIST 1.0 classification was evaluated.Results: The FVLC were significantly correlated with the FMWB (r=0.977). Furthermore, the results of LBM measurement evaluated with LC images were much closer to the reference standard than those obtained by the James PE. The PE-based and LC-based PERCIST 1.0 classifications were discordant in 27 patients (11.2 %; κ = 0.823, P=0.837). These discordant patients’ percentage changes of peak SUL (SULpeak) were all in the interval above or below 10 % from the threshold (± 30 %), accounting for 43.5 % (27/62) of total patients in this region. The degree of variability is related to changes in LBM before and after treatment. Conclusions: LBM algorithm-dependent variability in PERCIST 1.0 classification is a notable issue. SUV normalised by LC-based LBM could change PERCIST 1.0 response classifications based on LBM estimated by the James PE, especially for patients with a percentage variation of SULpeak close to the threshold.
Opioid use disorder in pregnancy: Leveraging provider perceptions to inform comprehensive treatment
Authors: Titus-Glover Doris , Shaya Fadia T , Welsh Christopher , Qato Danya M , Shah Savyasachi , Gressler Laura E , Vivrette Rebecca
Published: January 2021

Background: Medications for opioid use disorder (MOUD) are recommended with adjuvant behavioral therapies, counseling, and other services for comprehensive treatment of maternal opioid use disorder. Inadequate access to treatment, lack of prescribing providers and complex delivery models are among known barriers to care. Multi-disciplinary provider input can be leveraged to comprehend factors that facilitate or inhibit treatment. The objective of this study is to explore provider perceptions of MOUD and factors critical to comprehensive treatment delivery to improve the care of pregnant women with opioid use disorder. ﻿Methods: A qualitative research approach was used to gather data from individual provider and group semi-structured interviews. Providers (n=12) responded to questions in several domains related to perceptions of MOUD, treatment delivery, access to resources, and challenges/barriers. Data were collected, transcribed, coded (by consensus) and emerging themes were analyzed using grounded theory methodology. Results: Emerging themes revealed persistent gaps in treatment and challenges in provider, health systems and patient factors. Providers perceived MOUD to be a “lifeline” to women. Conclusions: Inconsistencies in treatment provision, access and uptake can be improved by leveraging provider perceptions, direct experiences and recommendations for an integrated team-based, patient-centered approach to guide the care of pregnant women with opioid use disorder.
The Efficacy and Safety of Indocyanine green- hyaluronic acid mixture (LuminoMarkTM) for Localization in Patients with Non-palpable Breast Lesions: A Multi-center Open-label Parallel Phase-2 Clinical trial
Authors: kim isaac , Choi Hee Jun , Ryu Jai Min , Lee Se Kyung , Yu Jong Han , Lee Jeong Eon , Nam Seok Jin , Shin Hyuk Jai , Kim Seok Won
Published: January 2021

Backgrounds With increasing screening for breast cancer, non-palpable breast lesions are detected more frequently. A preoperative localization is very important for a minimal but accurate excision of a non-palpable breast lesion. The purpose of this study was to evaluate the efficacy and safety of indocyanine green(ICG)-hyaluronic acid mixture injection as a novel material for localization. Methods We performed prospective clinical trial with female patients who underwent surgery for non-palpable breast lesion. All patients were sequentially assigned to the control group(localization with activated charcoal), test group 1(ICG-hyaluronic acid mixture 0.1ml), or test group 2(ICG-hyaluronic acid mixture 0.2ml) by 1:1:1 ratio. Results A total of 44 patients were eligible for this study (control group = 14, test 1 group = 15, test 2 group = 15 patients ). Among all patients, Fibroadenoma accounted for the largest share (38.6%, 17/44) and malignancy accounted for 11.4% (5/44). There was no difference in baseline characteristics in three groups. The marking rate was over 86% in all groups, and there was no difference. However, skin pigmentation was only in the control group and the accuracy of resection (the greatest length in cm of the excised specimen divided by the greatest length in cm on the pre-operation ultrasound image, the value closer to 1 meant resection as much as the size on ultrasound image) was different significantly. The average was 3.7 in control group and 2.2 in test 1 group and 2.1 in test 2 group. ( p-value was 0.037 between control and test 1 group, 0.744 between test 1 and test 2 group, 0.026 between control and test2 group respectively. ) Conclusion ICG-hyaluronic acid mixture injection is a new method for localization with non-palpable breast lesions, as well as a better method with higher accuracy of resection, lower skin pigmentation. Further research is required to apply this method to malignant breast lesions.Trial registration “A Multi-center Open-label Parallel Phase-2 Clinical trial to evaluate the efficacy and safety of LuminoMarkTM for Localization in Patients with Non-palpable Breast Lesions” was prospectively registered as a trial (ClinicalTrials. gov Identifier: NCT03743259, date of registration: May 29, 2018, https://clinicaltrials.gov/ct2/show/NCT03743259).
Introduction and Feeding Practices of Solid Food in Preterm Infants born in Salzburg!
Authors: Hofstätter Edda , Köttstorfer Verena , Stroicz Patricia , Schütz Sebastian , Hackenberg Lorenz Auer , Brandner Johannes , Wald Martin
Published: January 2021

Background: It is shown that meeting the increased nutritional demand of preterm infants from birth is not only important for survival but essentially contributes to the infants` overall development and long-term health. While there are established guidelines for weaning term infants, evidence regarding preterm infants is scarce and less precise. The aim of this study was to identify the current practices on introducing solids to preterm infants amongst caregivers in Salzburg and determine potential reasons for early weaning.Methods: Altogether 68 infants born between 24 0/7 and 36 6/7 weeks were recruited and detailed structured interviews with the caregivers were conducted at 17 weeks corrected age. Weight, height and head circumference were collected. Results: 52% of the study group received solids before the recommended 17 weeks corrected age. For this group the mean age being 13.77 ± 1.11 weeks corrected age. Premature introduction of solids significantly correlates with exclusively and early formula-feeding. 34% were weaned due to recommendation by their paediatrician. 23% of the preterm infants even received solids before 12 weeks corrected age, putting them at risks for developing obesity, celiac disease and diabetes. Conclusions: This study shows the necessity for clear guidelines regarding the introduction of complementary feeding in preterm infants as well as the importance of their implementation. Caregivers should receive information on this topic early enough and they should fully understand the difference between chronological and corrected age.
Inter-physician variability in strategies linked to treatment limitations after severe traumatic brain injury; proactivity or wait-and-see
Authors: Robertsen Annette , Helseth Eirik , Førde Reidun
Published: January 2021

Background Prognostic uncertainty is a challenge for physicians in the neuro intensive care field. Questions about whether continued life-sustaining treatment is in a patient’s best interests arise in different phases after a severe traumatic brain injury. In-depth information about how physicians deal with ethical issues in different contexts is lacking. The purpose of this study was to seek insight into clinicians’ strategies concerning unresolved prognostic uncertainty and their ethical reasoning on the issue of limitation of life-sustaining treatment in patients with minimal or no signs of neurological improvement after severe traumatic brain injury in the later trauma hospital phase. Methods Interviews with 18 physicians working in a neurointensive care unit in a large Norwegian trauma hospital, followed by a qualitative thematic analysis focused on physicians’ strategies related to treatment-limiting decision-making. Results A divide between proactive and wait-and-see strategies emerged. Notwithstanding the hospital’s strong team culture, inter-physician variability with regard to ethical reasoning and preferred strategies was exposed. All the physicians emphasized the importance of team – family interactions. Nevertheless, their strategies differed: (1) The proactive physicians were open to consider limitations of life-sustaining treatment when the prognosis was grim. They initiated ethical discussions, took leadership in clarification and deliberation processes regarding goals and options, saw themselves as guides for the families and believed in the necessity to prepare families for both best-case and worst-case scenarios. (2) The “wait-and-see” physicians preferred open-ended treatment (no limitations). Neurologically injured patients need time to uncover their true recovery potential, they argued. They often avoided talking to the family about dying or other worst-case scenarios during this phase. Conclusions Depending on the individual physician in charge, ethical issues may rest unresolved or not addressed in the later trauma hospital phase. Nevertheless, team collaboration serves to mitigate inter-physician variability. There are problems and pitfalls to be aware of related to both proactive and wait-and-see approaches. The timing of best-interest discussions and treatment-limiting decisions remain challenging after severe traumatic brain injury. Routines for timely and open discussions with families about the range of ethically reasonable options need to be strengthened.Trial registration: Not applicable