bluuebunny/crossref_metadata_2025 huggingface dataset:
OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized open label trial.
Authors: Algara Manuel , Rodríguez Elvira , Beato Inmaculada , Martínez Francisco José , Salinas Juan , Rodrígez Jose Reyes , Sanz Xavier , Soler Ana , Juan Germán , Flaquer Amanda
Published: July 2020

Background: Conservative surgery followed by breast and nodal irradiation is the standard loco-regional early breast cancer (BC) treatment for patients with four or more involved lymph nodes (LN). However, the treatment strategy when fewer nodes are involved remains unclear, especially when lymphadenectomy has not been performed. Sensitive nodal status assessment molecular techniques as the OSNA (One-Step Nucleic Acid Amplification) assay can contribute to the definition and standardization of the treatment strategy. Therefore, the OPTIMAL study aims to demonstrate the feasibility of incidental irradiation of axillary nodes in patients with early-stage BC and limited involvement of the SLN. Methods: BC patients who underwent conservative surgery and whose SLN total tumour load assessed with OSNA ranged between 250–15,000 copies/µL will be eligible. Patients will be randomized to receive irradiation on the breast, tumour bed, axillary and supraclavicular lymph node areas (intentional arm) or only on the breast and tumour bed (incidental arm). All areas, including the internal mammary chain, will be contoured. The mean, median, D5% and D95% doses received in all volumes will be calculated. The primary endpoint is the non-inferiority of the incidental irradiation of axillary nodes compared to the intentional irradiation in terms of 5-year disease free survival. Secondary endpoints comprise the comparison of acute and chronic toxicity and loco-regional and distant disease recurrence rates.Discussion: Standardizing the treatment and diagnosis of BC patients with few nodes affected is crucial due to the lack of consensus. Hence, the quantitative score for the metastatic burden of SLN provided by OSNA can contribute by improving the discrimination of which BC patients with limited nodal involvement can benefit from incidental radiation as an adjuvant treatment strategy. Trial registration: ClinicalTrial.gov, NCT02335957; https://clinicaltrials.gov/ct2/show/NCT02335957
Searching for Programme Theories for a realist evaluation: A case study comparing an academic database search and a simple Google search
Authors: Coleman Susanne , WRIGHT Judith M , NIXON Jane , SCHOONHOVEN Lisette , TWIDDY Maureen , GREENHALGH Joanne
Published: July 2020

BackgroundRealist methodologies are increasingly being used to evaluate complex interventions in health and social care. Programme theory (ideas and assumptions of how a particular intervention works) development is the first step in a realist evaluation or a realist synthesis, with literature reviews providing important evidence to support this. Deciding how to search for programme theories is challenging and there is limited guidance available. Using an example of identifying programme theories for a realist evaluation of Pressure Ulcer Risk Assessment Instruments in clinical practice, the authors explore and compare several different approaches to literature searching and highlight important methodological considerations for those embarking on a programme theory review.MethodsWe compared the performance of an academic database search with a simple Google search and developed an optimised search strategy for the identification primary references (i.e. documents providing the clearest examples of programme theories) associated with the use of Pressure Ulcer Risk Assessment Instruments (PU-RAIs). We identified the number of primary references and the total number of references retrieved per source. We then calculated the number needed to read (NNR) expressed as the total number of titles and abstracts screened to identify one relevant reference from each source.ResultsThe academic database search (comprising CINAHL, The Cochrane Library, EMBASE, HMIC, Medline) identified 2 /10 primary references with a NNR of 1395.The Google search identified 7/10 primary references with a NNR of 10.1. The combined NNR was 286.3. The optimised search combining Google and CINAHL identified 10/10 primary references with a NNR of 40.2. ConclusionThe striking difference between the efficiency of the review’s academic database and Google searches in finding relevant references prompted an in-depth comparison of the two types of search. The findings indicate the importance of including grey literature sources such as Google in this particular programme theory search, while acknowledging the need for transparency of methods. Further research is needed to facilitate improved guidance for programme theory searches to enhance practice in the realist field and to save researcher time and therefore resource.
Stakeholder perceptions about the establishment of medical simulation-based learning at a university in a low resource setting: A qualitative study in Uganda
Authors: Najjuma Josephine Nambi , Bajunirwe Francis , Twine Margaret , Namata Tamara , Kyakwera Catherine , Cherop Moses , Data Santorino
Published: July 2020

Background: Simulation based learning (SBL) is a technique where teachers recreate “real life” clinical experiences for health care teams for purposes of gaining clinical skills in a safe environment. There is evidence that SBL is superior to the traditional clinical teaching methods for acquisition of clinical skills. Although it is well established in resource rich settings, there is limited experience in resource limited settings and there is uncertainty regarding how SBL will be perceived among the stakeholders in medical education. As part of the steps leading to implementation of a SBL program at a university in Uganda, we sought to describe the perceptions of various stakeholders regarding the introduction of SBL methodology into learning at a medical school in Uganda. Methods: We conducted a formative qualitative assessment using key informant interviews (KIIs) among faculty members and university administrators and focus group discussions (FGDs) among medical and nursing students at Mbarara University of Science and Technology. Data were collected till saturation point and were transcribed and analyzed manually using open and axial coding approaches to develop themes. Results: We conducted 7 KIIs and 3 FGDs. Overall, findings were categorized into five broad themes: 1. Motivation to adopt simulation based learning 2. Prior experience and understanding of medical simulation 3. Outcomes arising from introduction of medical simulation 4. Drawbacks to establishment of medical simulation; and 5. remedies to the drawbacks. Overall, our data show there was significant buy-in from the institution for SBL, stakeholders were optimistic about the prospects of having a new method of teaching, which they perceived as modern to complement the traditional methods. There was significant knowledge but very limited prior experience of medical simulation. Also, there was some concern regarding how students and faculty would embrace training on lifeless objects, the human resources needed and sustainability of simulation-based learning in the absence of external funding. Conclusion: Stakeholders perceive SBL positively and are likely to embrace the learning methods. Concerns about human resource needs and sustainability need to be addressed to ensure acceptability.
Relationship of metabolic syndrome defined by IDF or revised NCEP ATP III with glycemic control among Malaysians with Type 2 Diabetes
Authors: Saif-Ali Riyadh , Kamaruddin Nor Azmi , AL-Habori Molham , Al-Dubai Sami A , Ngah Wan Zurinah Wan
Published: July 2020

Background The chronic complications of Type 2 Diabetes (T2D) such as macrovascular disease is amplified with the increase in the number of metabolic syndrome (MetS) risk factors. This research aims to study the relationship of MetS, diagnosed by the International Diabetes Federation (IDF) or revised National Cholesterol Education Programs Adult Treatment Panel III (NCEP ATP III) criteria, with glycemic control, Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), C-peptide, and insulin resistance in T2D patients.Methods The study is a cross-sectional observational study which, involved 485 T2D patients who are receiving treatment at the University Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur, Malaysia. The MetS among the T2D patients was diagnosed based on IDF and revised NCEP ATP III criteria. C-peptide and HbA1c levels were determined by an automated quantitative immunoassay analyzer and high-performance liquid chromatography, respectively. The MetS factors; FBG, triglyceride, and high-density lipoprotein cholesterol were measured by spectrophotometer. Results Application of the IDF and revised NCEP ATP III criteria respectively resulted in 73% and 85% of the T2D subjects being diagnosed with MetS. The concordance of these criteria in diagnosing MetS among T2D patients was low (κ =0.33, P<0.001). Both IDF and revised NCEP ATP III criteria indicated that T2D patients with 5 MetS factors had higher insulin resistance (P=2.1×10-13;1.4×10-11), C-peptide (P=1.21×10-13; 4.1×10-11), FBG (P=0.01; 0.021), and HbA1c (P=0.039; 0.018) than those T2D patients without MetS, respectively. Conclusion Although there is a low concordance between IDF and revised NCEP ATP III criteria in the diagnosis of MetS among T2D patients, both criteria showed that T2D patients with 5 MetS factors had higher insulin resistance, C-peptide, FBG, and HbA1c.
Prediction of Treatment Failure and Compliance in Patients with Tuberculosis
Authors: Koo Hyeon-Kyoung , Min Jinsoo , Kim Hyung Woo , Lee Joosun , Kim Ju Sang , Park Jae Seuk , Lee Sung-Soon
Published: July 2020

Background: To improve treatment outcomes for tuberculosis (TB), efforts to reduce treatment failure are necessary. The aim of our study was to describe the characteristics of subjects who had failed treatment of tuberculosis and identify the risk factors for treatment failure and poor compliance using national data.Methods: A multicenter cross-sectional study was performed on tuberculosis subjects whose final outcome was reported as treatment failure during 2015-2017. The same number of subjects with treatment success during the same study period were randomly selected for comparison. Demographics, microbiological, radiographic, and clinical data were collected based on in-depth interviews by TB nurse specialists at all Public Private Mix (PPM) participating hospitals in South Korea. Results: A total of 52 tuberculosis patients with treatment failure were enrolled. In a multivariable analysis, the presence of diabetes, previous history of tuberculosis, and cavity were identified as risk factors for treatment failure; and Medicaid support was a favorable factor for treatment success (area under the curve [AUC]: 0.79). Age, low body mass index (BMI), presence of diabetes, preexisting lung disease, positive sputum acid-fast bacilli (AFB) smear result, and the presence of multidrug-resistant tuberculosis (MDR-TB) were significantly associated with presence of cavities. Younger age, lower BMI and previous history of TB were associated with poor compliance during treatment (AUC: 0.76). Conclusion: To reduce treatment failure, careful evaluation of the presence of diabetes, previous TB history, underlying lung disease, cavity, results of sputum AFB smears, and socioeconomic status are needed. To enhance treatment compliance, more attention should be paid to younger patients with lower BMIs during follow-up.
High burden of Self-reported Sexually Transmitted Infections among Key Populations in Mozambique: The Urgent Need for an Integrated Surveillance System
Authors: Boothe Makini A.S. , Comé Charlotte , Baltazar Cynthia Semá , Chicuecue Noela , Seleme Jessica , Langa Denise Chitsondzo , Sathane Isabel , Raymond Henry Fisher , Fazito Erika , Temmerman Marleen , Luchters Stanley
Published: July 2020

Background: Key populations - men who have sex with men (MSM), female sex workers (FSW) and people who inject drugs (PWID) – are at high risk for sexually transmitted infections (STI) given their sexual risk behaviours along with social, legal and structural barriers to prevention, care and treatment services. The purpose of this secondary analysis is to assess the prevalence of self-reported STIs and to describe associated risk factors among participations of the first Biological Behavioural Surveillance (BBS) in Mozambique. Methods: Responses from the first BBS surveys conducted in 2011-2014 were aggregated across survey-cities to produce pooled estimates for each population. Aggregate weighted estimates were computed to analyse self-reported STI prevalence. Unweighted pooled estimates were used in multivariable logistic regression to identify risk factors associated with self-reported STI. Results: The prevalence of self-reported STI was 11.9% (95% CI: 7.8-16.0), 33.6% (95% CI: 29.0-41.3), and 22.0% (95% CI: 17.0-27.0) among MSM, FSW and PWID, respectively. MSM who were circumcised, had HIV, reported drug use, reported receptive anal sex, and non-condom use with their last male partner had greater odds of STI self-report. STI-self report among FSW was associated with living in Beira, being married, employment aside from sex work, physical violence, sexual violence, drug use, access to comprehensive HIV prevention services, non-condom use with last client, and sexual relationship with a non-client romantic partner. Among PWID, risk factors for self-reported STI included living in Nampula/Nacala, access to HIV prevention services, and sex work.Conclusion: The high-burden of STIs among survey participants requires integrated HIV and STI prevention, treatment, and harm reduction services that address overlapping risk behaviours, especially injection drug use and sex work. A robust public health response requires the creation of a national STI surveillance system for better screening and diagnostic procedures within these vulnerable populations.
Adjuvant instant preoperative renal artery embolization facilitates the radical nephrectomy and thrombectomy in locally advanced renal cancer with venous thrombus: A retrospective study of 54 cases
Authors: Tang Guangxin , chen xiaoxu , Wang Jianwei , He Wei , Niu Zhihong
Published: July 2020

Background: The role of renal artery embolization (RAE) in the therapeutic armamentarium is always controversial. The present study aimed to assess the safety and the surgical outcomes of the instant renal artery embolization (I-RAE) prior to nephrectomy and thrombectomy in patients with locally advanced renal cell carcinoma (RCC) with venous thrombus.Methods: We performed a retrospective analysis of 54 patients treated with nephrectomy and thrombectomy between January 2012 and January 2019. Twenty-four patients were treated with I-RAE before surgery. Thirty patients received surgery alone (non-RAE group). The patient demographics, operation time, blood loss, transfusion requirements, complications and other surgical parameters were analyzed between the two groups.Results: The mean tumor size in the I-RAE group was significantly larger than that in the non-RAE group (11.1 cm versus 7.9 cm; p = .001). The mean estimated blood loss was significantly lower in the I-RAE group compared to that in the non-RAE group (596 ml versus 827 ml; p = .015), and the patients in the Non-RAE group were more likely to receive blood transfusion (red blood cell, RBC units, 4 U versus 6 U, p = .025; plasma volume, 200 ml versus 400 ml, p = .01). No differences were found in operative duration, ICU stay, perioperative complications and length of postoperative hospitalization. Conclusions: Instant preoperative adjuvant renal artery embolization (I-RAE) is a safe technique. It facilitates nephrectomy and thrombectomy by reducing blood loss, transfusion requirements and complications of delayed operations, providing urologists with a reliable option for treatment of locally advanced RCC with tumor thrombus.
Genetic Analysis of Children with Congenital Ocular Anomalies in Three Ecological Regions of Nepal: A Phase II of Nepal Pediatric Ocular Diseases Study
Authors: Adhikari Srijana , Thakur Neelam , Shrestha Ujjowala , Shrestha Mohan , Shrestha Murari Man , Thapa Bijaya , Poudel Manish , Kunwar Ajay
Published: July 2020

Background: Genetic eye diseases constitute a large and heterogeneous group of childhood ocular morbidity. Individual diseases may cause multiple structural anomalies and developmental features. Nepal Pediatric Ocular Disease Study (NPODS) was a population-based epidemiological study conducted across three ecological regions of Nepal to determine the prevalence and etiology of childhood ocular morbidity and blindness. In Phase II of this study, genetic analysis was performed for children who were found to have congenital ocular anomalies. Method: It was a cross sectional descriptive study. A total of 10,270 children across three different ecological regions in Nepal (Low lands, hills, and mountains) underwent ocular examinations in NPODS. Out of 374 (3.6%) of children with ocular abnormalities, 30 were thought to be congenital in nature. Targeted genetic analysis, including genotyping for genes specific to presenting phenotype, was performed for 25 children using serum samples. Results: Out of 25 children, 18 had meaningful genetic results. Analysis revealed one missense alteration G12411T of Zinc Finger Homeobox 4 (ZFHX4) gene in one participant among 10 with congenital ptosis and another missense variation T>C P. Y374 C of Signaling Receptor and Transporter Retinol 6 (STRA6) gene in one participant among 3 with microphthalmos.Conclusion: The study is first of its kind from Nepal and mutant genes were unique to Nepalese Population. Further analysis of genetic factors is crucial to better understand genetic association with ocular diseases and conditions. This helps further in genetic counseling and probably gene therapy to prevent blindness from these conditions.
Impact of viral coinfection and macrolide-resistant mycoplasma infection in children with refractory Mycoplasma pneumoniae pneumonia
Authors: Zhou Yajuan , Wang Jing , Chen Wenjuan , Shen Nan , Tao Yue , Zhao Ruike , Luo Lijuan , Li Biru , Cao Qing
Published: July 2020

Background: Cases of refractory Mycoplasma pneumoniae pneumonia have been increasing recently; however, whether viral coinfection or macrolide-resistant M. infection contribute to the development of refractory M. pneumoniae pneumonia remains unclear. This study aimed to investigate the impacts of viral coinfection and macrolide-resistant M. pneumoniae infection on M. pneumoniae pneumonia in hospitalized children and build a model to predict a severe disease course. Methods: Nasopharyngeal swabs or sputum specimens were collected from patients with community-acquired pneumonia meeting our protocol who were admitted to Shanghai Children’s Medical Center from December 1, 2016, to May 31, 2019. The specimens were tested with the FilmArray Respiratory Panel, a multiplex polymerase chain reaction assay that detects 16 viruses, Bordetella pertussis, M. pneumoniae, and Chlamydophila pneumoniae. Univariate and multivariate logistic regression models were used to identify the risk factors for adenovirus coinfection and macrolide-resistant mycoplasma infection.Results: Among the 107 M. pneumoniae pneumonia patients, the coinfection rate was 56.07%, and 60 (60/107, 56.07%) patients were infected by drug-resistant M. pneumoniae. Adenovirus was the most prevalent coinfecting organism, accounting for 22.43% (24/107). The classification tree confirmed that viral coinfection was more common in patients younger than 3 years old. Adenovirus coinfection and drug-resistant M. pneumoniae infection occurred more commonly in patients with refractory M. pneumoniae pneumonia (P=0.019; P=0.001). A prediction model including wheezing, lung consolidation and extrapulmonary complications was used to predict adenovirus coinfection. The area under the receiver operating characteristic curve of the prediction model was 0.795 (95% CI 0.679-0.893, P<0.001). A prolonged fever duration after the application of macrolides for 48 hours was found more commonly in patients infected by drug-resistant M. pneumoniae (P=0.002). A fever duration longer than 7 days was an independent risk factor for drug-resistant Mycoplasma infection (OR=3.500, 95% CI=1.310-9.353, P=0.012).Conclusions: The occurrence of refractory M. pneumoniae pneumonia is associated with adenovirus coinfection and infection by drug-resistant M. pneumoniae. A prediction model combining wheezing, extrapulmonary complications and lung consolidation can be used to predict adenovirus coinfection in children with M. pneumoniae pneumonia. A prolonged fever duration indicates drug-resistant M. pneumoniae infection, and a reasonable change in antibiotics is necessary.
Relationship Between the Levels of Inflammatory Cytokines in the Aqueous Humor and Cataract in Fuchs Uveitis Syndrome-A Case Control Study
Authors: Wang Hui , Tao Yong
Published: July 2020

Background This study aims to compare the levels of intraocular cytokines between Fuchs uveitis syndrome (FUS) eyes and the senile cataract eyes. The association between inflammatory cytokine levels and cataract severity in FUS is evaluated to find the possible mechanism of cataract in FUS eyes.Methods A retrospective study of 28 eyes with FUS was performed. Auxiliary examinations were performed, including ophthalmic examinations, laser flare-cell photometry, and levels of inflammatory cytokines in the aqueous humor were measured. The control group included 25 eyes with senile cataract. Data on the aqueous humor inflammatory cytokines were compared between the two groups. The association between the aqueous humor cytokine levels and severity of posterior subcapsular cataract was assessed.Results There were 28 eyes with FUS in 27 patients. Unilateral involvement was noted in 26 patients (96.30%). Stellate keratic precipitates (KPs) were noted in 16 eyes (57.14%). Heterochromia was observed in 21.43% of affected eyes. Posterior subcapsular cataract was observed in 16 of the 28 eyes. Eyes with FUS had significantly higher aqueous humor (AH) cytokine levels (VEGF, bFGF, IL-6, IL-8 and IL-10) compared with the control eyes (P<0.05). There was a statistically significant positive correlation between the severity of cataract and IL-6 and IL-8 levels in the AH (τ = 0.675 and 0.793, respectively; P = 0.001, P<0.001, respectively).Conclusions Expression of VEGF, bFGF, IL-6, IL-8 and IL-10 in the AH of FUS patients was significantly higher than in senile cataract eyes, and the aqueous humor levels of IL-6 and IL-8 were significantly positively associated with the severity of posterior subcapsular cataract. Our results imply that an inflammation mechanism may be involved in the early development of cataract in FUS.
A New Postural Stability-Indicator to Predict the Level of Fear of Falling in Parkinson’s Disease Patients
Authors: Pourghayoomi Ehsan , Behzadipour Saeed , Ramezani Mehdi , Joghataei Mohammad Taghi , Shahidi Gholamali
Published: July 2020

Background: Fear of falling (FoF) is defined as a lasting concern about falling that causes a person to limit or even stop the daily activities that he/she is capable of. Seventy percent of Parkinson’s disease (PD) patients report activity limitations due to FoF. Timely identification of FoF is critical to prevent its additional adverse effects on the quality of life. Self-report questionnaires are commonly used to evaluate the FoF, which may be prone to human error.Objectives: In this study, we attempted to identify a new postural stability-indicator to objectively predict the intensity of FoF and its related behavior(s) in PD patients. Methods: Thirty-eight PD patients participated in the study (mean age, 61.2 years), among whom 10 (26.32%) were identified with low FoF and the rest (73.68%) with high FoF, based on Falls Efficacy Scale-International (FES-I). We used a limit of stability task calibrated to each individual and investigated the postural strategies to predict the intensity of FoF. New parameters (FTRi’s; functional time ratio) were extracted based on the center of pressure presence pattern in different rectangular areas (i = 1, 2, and 3). The task was performed on two heights to investigate FoF related behavior(s). Results: FTR1/2 (the ratio between FTR1 and FTR2) was strongly correlated with the FES-I (r = −0.63, P < 0.001), Pull Test (r = −0.65, P < 0.001), Timed Up and Go test (r = −0.57, P < 0.001), and Berg Balance Scale (r = 0.62, P < 0.001). The model of FTR1/2 was identified as a best-fitting model to predicting the intensity of FoF in PD participants (sensitivity = 96.43%, specificity = 80%), using a threshold level of ≤ 2.83. Conclusions: Using the proposed assessment technique we can accurately predict the intensity of FoF in PD patients. Also, The FTR1/2 index can be potentially considered as a mechanical biomarker to sense the FoF-related postural instability in PD patients.
Discontinuation of hydroxychloroquine in older patients with Systemic Lupus Erythematosus: A multicenter retrospective study
Authors: Ruiz Ruth Fernandez , Bornkamp Nicole , Kim Mimi Y. , Askanase Anca D. , Zezon Anna , Tseng Chung-E , Belmont H. Michael , Saxena Amit , Salmon Jane E. , Lockshin Michael , Buyon Jill P. , Izmirly Peter M.
Published: July 2020

Background: Although hydroxychloroquine (HCQ) is a mainstay of treatment for patients with Systemic Lupus Erythematosus (SLE), ocular toxicity can result from accumulated exposure. As the longevity of patients with SLE improves, data are needed to balance the risk of ocular toxicity and the risk of disease flare, especially in older patients with quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients.
Methods: Data were obtained by retrospective chart review at three major lupus centers in New York City. Twenty-six patients who discontinued HCQ, and thirty-two patients on HCQ matched for gender, race/ethnicity and age were included in this study. The primary outcome was the occurrence of a lupus flare classified by the revised version of the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare composite index, within one year of HCQ withdrawal or matched time of continuation.
Results: Five patients (19.2%) in the HCQ withdrawal group compared to five (15.6%) in the HCQ continuation group experienced a flare of any severity (odds ratio [OR]=1.28; 95% CI: 0.31, 5.30; p=0.73). There were no severe flares in either group. The results were similar after adjusting for length of SLE, number of American College of Rheumatology criteria, low complement levels, and SELENA-SLEDAI score, and in a propensity score analysis (OR=1.18; 95% CI: 0.23, 6.16, p=0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log rank p=0.67). Most flares were in the cutaneous and musculoskeletal systems, but one patient in the continuation group developed pericarditis. The most common reason for HCQ withdrawal was retinal toxicity (42.3%), followed by patient’s preference (34.6%), other confirmed or suspected adverse effects (15.4%), ophthalmologist recommendation for macular degeneration (3.8%), and rheumatologist recommendation for quiescent SLE (3.8%).
Conclusions: In this retrospective study of older stable patients with SLE on long-term HCQ, withdrawal did not significantly increase the risk of flares.
Comparison of visual field progression in new-diagnosed primary open-angle and exfoliation glaucoma patients in Sweden.
Authors: Ayala Marcelo
Published: July 2020

Background: The present study aimed to compare visual field progression in new-diagnosed exfoliation versus open-angle glaucoma patients. Methods: Retrospective study. The study included patients with new-diagnosed primary open-angle and exfoliation glaucoma. All patients were followed for three years with reliable visual fields. At least five reliable fields were needed for inclusion. Exfoliation and open-angle glaucoma were defined based on the European Glaucoma Society guidelines. Visual field evaluation was performed using the software threshold 24-2 of the Humphrey Field Analysis. Outcomes: Visual field progression. For visual field progression, three different strategies were used: mean deviation (MD), visual field index (VFI), and the guided progression analysis (GPA). Results: The study included 128 subjects, of the 54 in the open-angle and 74 in the exfoliation glaucoma group. The MD difference values were higher in the exfoliation (-3.17 dB) than in the primary open-angle (-1.25 dB) glaucoma group in the three-year follow-up period. The difference between groups was significant (t-test, p=<0.001). The difference in VFI was calculated for the three years follow-up period. The difference was higher in the exfoliation (-7.65%) than in the primary open (-1.90%) glaucoma group (t-test, p=<0.001). The GPA showed progression in 58% of cases in exfoliation, and 13% in primary open glaucoma group (Chi-square, p=<0.001). Conclusion: The present study found a more frequent and faster visual field progression in exfoliation than in primary open-angle glaucoma patients. New-diagnosed exfoliation glaucoma patients must be controlled and treated more strictly than primary open-angle glaucoma patients to avoid visual field deterioration.
Knockdown of lncRNA LINC01234 suppresses the tumorigenesis of liver cancer via sponging miR-513a-5p
Authors: Xu Wen , Li Kesang , Song Changfeng , Wang Xiaotong , Li Yueqi , Bai Xue , Liang Xin , Deng Wanli , Wang Junqing , Liu Jianwen
Published: July 2020

Background: Liver cancer is a frequent malignancy with poor prognosis. It has been reported that many lncRNAs could regulate the progression of liver cancer. To identify potential therapeutic targets for liver cancer, we conducted bioinformatics analysis of lncRNAs in tumor tissues and adjacent normal tissues.
Methods: The differential expression of lncRNAs between liver cancer tissues and adjacent normal tissues were examined by bioinformatics analysis. Cell proliferation was tested by CCK-8. Cell apoptosis in liver cancer was detected by flow cytometry. Gene and protein expression in liver cancer cells were measured by q-PCR and Western-blot, respectively. Xenograft tumor model was established to verify the function of LINC01234 on liver cancer in vivo .
Results: LINC01234 was found to be notably upregulated in liver cancer tissues. In addition, knockdown of LINC01234 significantly inhibited the proliferation, invasion and induced the apoptosis of liver cancer cells. Meanwhile, miR-513a-5p was a downstream target of LINC01234 and USP4 was a direct target of miR-513a-5p. Moreover, downregulation of LINC01234 inhibited the tumorigenesis of liver cancer via inactivating TGF-β signaling.
Conclusion: Downregulation of LINC01234 could inhibit the progression of liver cancer. Thus, LINC01234 may serve as a potential novel target for treatment of liver cancer.
Use of Community-based Interventions to Promote Family Planning Use Among Pastoralist Women in Ethiopia: Cluster Randomized Controlled Trial
Authors: Alemayehu Mussie , Medhanyie Araya Abrha , Reed Elizabeth , Bezabih Afework Mulugeta
Published: July 2020

Background- Afar region is one of the pastoralists dominated regions in Ethiopia. The region is characterized by a low contraceptive prevalence rate (CPR) with 5.4%. Lack of awareness, husband objection, and religious influence was the reasons attributed to low CPR in the region. As objective we assessed the effect of a community-based interventions for promoting FP use among pastoralist communities of Afar region state, Ethiopia.MethodsThe design was parallel, cluster randomized controlled trial (CRT) recruiting married women. It had three arms: 1) women’s education on FP, 2) male involvement in FP education and 3) control with one to one ratio. A total of 33 kebeles (lowest administrative structure) were randomized and allocated. Women’s FP education and male involvement in FP education were the interventions. It was implemented using 1) health education on FP to married women and men by faema leaders (a traditional community-based structure that serves as a social support group) 2) Video-assisted message on FP, and 3) Assisting the faema leader using health workers. The intervention was given for a total of 9 months. FP use and intentions were measured as outcome variables based on woman’s perspectives. Cluster level summaries considering a cluster effect analysis was performed. The result was presented with adjusted risks and 95% CI. A p-value < 0.05 was used to declare statistically significant.ResultsThere was a positive change in the proportion of married women who use FP in the women’s FP education arm, absolute risk (AR) of 0.13(95% CI,0.08,0.17) and male involvement arm with AR of 0.29 (95% CI, 0.23,0.34) as compared to the control arm. In the control arm, the proportion of FP use was 4.3%, whereas it was 17.5% with women who receive FP education and 34% in the male involvement arm. Furthermore, the proportion of married women who had high intention to use FP was high in arms of women’s FP education and male involvement with AR = 3.4(95% CI: 2.48,4.91) and AR = 2.1 (95% CI: 1.5,2.95), respectively as compared with the control arm.ConclusionThe community-based interventions brings a significant change in increasing FP users and intention to use FP.Trial registration : NCT03450564
Carbon ion reirradiation compared to intensity-modulated re-radiotherapy for recurrent head and neck cancer (CARE): a randomized controlled trial
Authors: Held Thomas , Lang Kristin , Regnery Sebastian , Weusthof Katharina , Hommertgen Adriane , Jäkel Cornelia , Tonndorf-Martini Eric , Krisam Johannes , Plinkert Peter , Zaoui Karim , Freudlsperger Christian , Moratin Julius , Krauss Jürgen , Harrabi Semi B. , Herfarth Klaus , Debus Jürgen , Adeberg Sebastian
Published: July 2020

Background: Intensity-modulated re-radiotherapy (reIMRT) has been established as a standard local treatment option in patients with non-resectable, recurrent head and neck cancer (rHNC). However, the clinical outcome is unfavorable and severe toxicities (≥grade III) occurred in 30–40% of patients. The primary aim of the current trial is to investigate carbon ion reirradiation (reCIRT) compared to reIMRT in patients with rHNC regarding safety/toxicity as well as local control, overall survival (OS), and quality of life (QoL). Methods: The present trial will be performed as a single center, two-armed, prospective phase II study. A maximum of 72 patients will be treated with either reIMRT or reCIRT to evaluate severe (≥grade III) treatment-related toxicities (randomization ratio 1:1). The primary target value is to generate less than 35% acute/subacute severe toxicity (≥grade III), according to the Common Terminology Criteria for Adverse Events v5.0, within 6 months after study treatment. The total dose of reirradiation will range between 51–60 Gy or Gy (RBE), depending primarily on the radiotherapy interval and the cumulative dose to organs at risk. Individual dose prescription will be at the discretion of the treating radiation oncologist. The local and distant progression-free survival 12 months after reirradiation, the OS, and the QoL are the secondary endpoints of the trial. Explorative trial objectives are the longitudinal investigation of clinical patient-related parameters, tumor parameters on radiological imaging, and blood-based tumor analytics.Discussion: Recent retrospective studies suggested that reCIRT could represent a feasible and effective treatment modality for rHNC. This current randomized prospective trial is the first to investigate the toxicity and clinical outcome of reCIRT compared to reIMRT in patients with rHNC.Trial registration: ClinicalTrials.gov; NCT04185974; December 4th 2019; https://clinicaltrials.gov/ct2/show/record/NCT04185974.
Mutation screening of the UBE3A gene in Chinese Han population with autism
Authors: Zhao Xue , Zhang Ran , Yu Shunying
Published: July 2020

Background
15q11-13 region is one of the most complex chromosomal regions in the human genome. UBE3A is an important candidate gene of autism spectrum disorder (ASD), which located at the 15q11-13 region and encodes ubiquitin-protein ligase E3A. Previous studies about UBE3A gene and ASD have shown inconsistent results and few studies were performed in Chinese population. This study aimed to detect the genetic variation of UBE3A gene in Chinese Han population with ASD and analyze the genetic association between these variations and ASD.
Methods
The samples consisted of 192 patients with clinical diagnosis of autism according to the DSM-IV diagnostic criteria and 192 healthy controls. We searched for mutations at coding sequence (CDS) regions and their adjacent non-coding regions of UBE3A gene using the high resolution melting (HRM) and Sanger sequencing methods. We further increased sample size to validate the detected variants using HRM and analyzed the difference of allele and genotype frequencies between case and control groups.
Results
A known single nucleotide polymorphism (T > C, rs150331504) located at the CDS4 and a known 5 bp insertion/deletion variation (AACTC+/-, rs71127053) located at the intron region of the upstream 288 bp of the CDS2 of UBE3A gene were detected using Sanger sequencing method. The association analysis suggested that there were no significant difference about the allele and genotype frequencies of rs71127053 and rs150331504 between case and control groups after extending the sample size. Besides, rs150331504 is a synonymous mutation and we analyzed the minimum free energy (MFE) of mRNA coded by the different alleles of rs150331504. The result showed that MFE values of the allele T and allele C of rs150331504 were different and indicated that the variant might alter the mRNA secondary structure. We did not detect mutations in other coding regions of UBE3A gene.
Conclusions
These findings showed that UBE3A gene might not be a major disease gene in Chinese ASD cases.
Serology profile and effects of influenza vaccination on COVID-19-positive symptomatic and asymptomatic patients
Authors: Grossberg Allison N. , Koza Lilia A. , Ledreux Aurelie , Prusmack Chad , Krishnamurthy Hari Krishnan , Jayaraman Vasanth , Granholm Ann-Charlotte , Linseman Daniel A.
Published: July 2020

The COVID-19 pandemic has affected more than 6.6 million people worldwide. As the population returns to work, it is critical to develop tests that can reliably detect SARS-CoV-2-specific antibodies. Here, we present the results of a novel multiplex serology test to assess the immune response to COVID-19 in an outpatient cohort consisting of adults and children in Colorado. The IgG response was more robust in positive/symptomatic participants than in positive/asymptomatic participants. The IgM response in symptomatic participants was transient and largely fell below the detection limit 30 days after symptom onset. Influenza vaccination gave rise to milder symptomology, but did not protect against contagion. These results provide novel insight into serology profiling and the immune response to COVID-19.
Susceptibility to South African cassava mosaic virus is Associated with a RING Finger E3 Ubiquitin Ligase
Authors: Chatukuta Patience , Rey Marie Emma Christine
Published: July 2020

BackgroundThe ubiquitylation of proteins is reprogrammed by plant geminiviruses which alter the ubiquitin proteasome system (UPS) to fully infect the host. A RING Finger E3 Ubiquitin Ligase (MeE3L) is located on a major cassava mosaic disease resistance-associated quantitative trait locus. Here, we examine the genetic structure and relative expression of MeE3L (native and gene-edited mutant), and determine how MeE3L affects geminivirus South African cassava mosaic virus (SACMV) DNA accumulation. MethodsCassava protoplasts of model, susceptible and tolerant genotypes were transformed with SACMV infectious clones and/or a CRISPR-editing construct targeting the MeE3L using PEG4000-mediated transfection. DNA and RNA were extracted from transformed protoplasts at 24 hours post-transfection. Relative SACMV load quantitation was determined using DpnI-digested total DNA via qPCR and MeE3L relative expression was determined via reverse transcriptase qPCR, and results were analysed using the 2-ΔΔ method. The MeE3L exonic region was sequenced on the ABI 3500XL Genetic Analyzer platform; and sequences were analysed for mutations and for construction of a phylogenetic tree using the Maximum Likelihood method and Tamura-Nei model.ResultsResults show that SACMV DNA accumulation is cassava genotype-dependent. The study also reveals that native and mutant MeE3L is differentially expressed during SACMV infection in protoplasts of susceptible and tolerant cassava landraces. The susceptible cassava landrace encodes a RINGless MeE3L and the MeE3L base sequence is a determinant of cassava’s response to SACMV. Results further show that SACMV silences the MeE3L RING domain in the susceptible and tolerant landraces; and specifically targets the tolerant MeE3L gene homolog for silencing. ConclusionsThese findings suggest that MeE3L is a target of SACMV, contributing to susceptibility in cassava. The MeE3L base sequence is a determinant of cassava’s response to SACMV. The MeE3L RING domain is actively silenced by SACMV and therefore may be essential for host defence against geminiviruses. The study provides further evidence, in addition to existing literature, that plant E3 ligases are exploited by geminiviruses to enhance pathogenicity.
Eye gaze differences in school scenes between preschool children and adolescents with high-functioning autism spectrum disorder and those with typical development
Authors: Ishizaki Yuko , Higuchi Takahiro , Yanagimoto Yoshitoki , Kobayashi Hodaka , Noritake Atsushi , Nakamura Kae , Kaneko Kazunari
Published: July 2020

Background: Children with autism spectrum disorder (ASD) sometimes find it difficult to adapt to the daily life in a nursery or at school and are likely to develop psychosomatic symptoms. For a better understanding on the difficulties that preschool children and adolescents with ASD face in their daily lives, this study aimed to identify the differences in eye gaze behavior in the classroom environment between children with ASD and those with typical development (TD). Methods: A total of 30 children with ASD and 49 children with TD were included. We presented images of a human face and a classroom setting and used eye tracking with an iView X system in evaluating and comparing how long the two groups gazed at specific regions of the visual stimuli. Results: Compared to children with TD, children with ASD spent less time gazing at the eyes of the human face and the object pointed by the teacher in the school classroom scene. Preschool children with no classroom experience and adolescents with TD spent the same amount of time looking at the eyes and the object pointed by the teacher in the school classroom scene. Conclusion: Children with ASD did not look at the eyes in the facial image or the object pointed at in the classroom image, which might indicate their inability to analyze situations, understand instruction in a classroom, or act appropriately in a group. It is suggested that these gaze behavior of the children with ASD cause maladaptation and psychosomatic symptoms. A therapeutic approach that focuses on joint attention is desirable for the improvement of their adaptation to the society for children with ASD.
Assessment of soil microbial and enzyme activity in the rhizosphere zone under different land use/cover of a semi-arid ecosystem, India
Authors: Meena Archana , Rao K.S.
Published: July 2020

Background Land use/cover changes and management practices are widely known to influence SOM quality and quantity. The present study investigated the effect of different land uses i.e. forests viz. mixed forest cover (MFC), Prosopis juliflora (Sw.) DC dominated forest cover (PFC), and cultivated viz. agriculture field (AF), vegetable filed (VF), respectively, on soil parameter, microbial activity, and enzymes involved in soil nutrient cycle in a semi-arid ecosystem.Results The results showed a significant reduction (P < 0.05) in soil carbon (SC), soil nitrogen (SN) content (~ 30–80%) and consequently the soil microbial biomass carbon (SMBC) (~ 70–80%), soil basal respiration (SBR), soil substrate induced-respiration (SSIR), and soil enzyme activities (β-glucosidase, acid phosphatase, and dehydrogenase) under cultivated sites in comparison to forest analogs due to land use management practices. Pearson’s correlation showed a positive correlation of SC with SMBC, SBR, and SSIR (P < 0.01) and enzymatic activities i.e. β-glucosidase, dehydrogenase (P < 0.05) suggesting the critical role of SC in regulating microbial and enzymatic activity. Also, a positive correlation of SM with urease (P < 0.01) was observed indicating the importance of soil abiotic factors in controlling enzymatic activities. Additionally, based on the PCA analysis, we observed the clustering of SMBC/SC ratio and qCO2 nearby AF.Conclusion Our study suggested that degraded sites are more sensitive to the land management practices and land use changes and needed immediate attention in future studies related to SC dynamics in semi-arid ecosystems.
Biomass equations for 24 understory species in a temperate forest in Northeastern China
Authors: Wang Libin , Zhang Zhonghui , He Huaijiang , Luo Ye
Published: July 2020

Background: Understory plants are important components of forest ecosystem productivity and diversity. Compared to biomass models of overstory canopy trees, few are available for understory saplings and shrubs and therefore their contributions to forest carbon pools are often ignored.Methods: We harvested 24 understory species including 4 saplings, 9 tree-like shrubs and 11 typical shrubs in coniferous and broadleaved mixed forest in north-eastern China. We developed the species-specific or multispecies best fit allometric equations of total, above- and below-ground biomass using morphological measurements of basal diameter, height and crown area as independent variables.Results: Single basal diameter, height or crown area had good explanatory power for both species-specific and multispecies equations (p<0.001). The best-fit models included only basal diameter in sapling and tree-like shrubs, and combinations of crown area, height, and basal diameter in typical shrubs. The logarithmic model was most desired among the 4 model forms of linear, quadratic, multiple linear and logarithmic, for species-specific and multispecies equations.Conclusion: The models we developed should help the estimation of forest ecosystem carbon stocks, especially for the belowground component, and provide tools for quantification of individual species biomass of understory plants.