bluuebunny/crossref_metadata_2025 huggingface dataset:
Primarily Treated Patients versus Referred Patients in the Treatment of Native Septic Arthritis of Digits: A Retrospective Comparative Study
Authors: Kwak Sang Ho , Bae Jung Yun , Oh Youngkwang , Jang Hyo Seok , Ahn Tae Young , Lee Sang Hyun
Published: September 2020

Background
Septic arthritis of digits needs urgent treatment. When treatments delayed or insufficient, patients may be referred to the upper-level hospital due to uncontrolled infection. We reviewed the treatment history of referred patients and compared the microorganisms and the clinical course of both primary and referred patients as relevant studies are rare.

Methods
In this retrospective review of consecutive case series, 45 patients (primary, n =11; referred, n =34) were treated with multiple irrigation and debridement. Cefazolin was used as empiric antibiotics, then changed according to microbiologic study. Previously used antibiotics, treatment delay, surgical history of the referred patients were reviewed. Identified microorganisms, required surgical intervention, hospital stay, radiologic outcome, functional outcomes were compared between both groups.

Results
In the referred patients, methicillin-resistant Staphylococcus aureus (MRSA) was commonly found and cefazolin was susceptible in only 15% of the cases. Longer hospital stay, prolonged antibiotic therapy, more surgical intervention including flap surgery was required to treat the referred patients. Postoperative pain was not severe in daily activities, but the final range of motion was significantly less in the referred patients compared to the primary patients.

Conclusions
This study suggests that in the treatment of uncontrolled septic arthritis of the digits, antibiotic agents covering MRSA may shorten the duration of antibiotic therapy in areas of high MRSA incidence. Besides, more number of I & D including flap surgery may be required for the referred patients compared with the primary patients. These findings can help the surgeon in setting up a treatment plan or in counseling of referred patients with uncontrolled septic arthritis of the digits.
Compositional and functional comparisons of the microbiota in the colostrum and mature milk of dairy goats
Authors: Niyazbekova Zhannur , Yao Xiao-Ting , Liu Ming-Jie , Bold Nomin , Tong Juan-Zhen , Chang Jian-Jun , Wen Ying , Li Li , Wang Yong , Chen De-Kun , Ma Wen-Tao
Published: September 2020

The authors have withdrawn this preprint due to erroneous posting.
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: September 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.
Transcriptome analysis reveals underlying immune response mechanism of fungal (Penicillium oxalicum) disease in Gastrodia elata Bl. f. glauca S. Chow (Orchidaceae)
Authors: Wang Yanhua , Gao Yugang , Zang Pu , Xu Yue
Published: September 2020

Background: Gastrodia elata Bl. f. glauca S. Chow is a medicinal plant. G. elata f. glauca is unavoidably infected by pathogens in their growth process. In previous work, we have successfully isolated and identified Penicillium oxalicum from fungal diseased tubers of G. elata f. glauca . As a widespread epidemic, this fungal disease seriously affected the yield and quality of G. elata f. glauca . We speculate that the healthy G. elata f. glauca might carry resistance genes , which can resist against fungal disease. In this study, healthy and fungal diseased mature tubers of G. elata f. glauca from Changbai Mountain area were used as experimental materials to help us find the potential resistance genes against fungal disease. Results: A total of 7540 differentially expressed Unigenes (DEGs) were identified (FDR<0.01, log2FC>2). The current study screened 10 potential resistance genes. They were attached to transcription factors (TFs) in plant hormone signal transduction pathway and plant pathogen interaction pathway, including WRKY22, GH3, TIFY/JAZ, ERF1, WRKY33, TGA. In addition, four of these genes were closely related to jasmonic acid signaling pathway. Conclusions: The immune response mechanism of fungal disease in G. elata f. glauca is a complex biological process, involving plant hormones such as ethylene, jasmonic acid, salicylic acid and disease-resistant transcription factors such as WRKY, TGA.
HKDC1 promotes the tumorigenesis and glycolysis in lung adenocarcinoma via regulating AMPK/mTOR signaling pathway2
Authors: Wang Xinyu , Shi Bowen , Zhao Yue , Lu Qijue , Fei Xiang , Lu Chaojing , Li Chunguang , Chen Hezhong
Published: September 2020

Background: Hexokinase domain component 1 (HKDC1) plays an oncogenic role in certain types of cancer, such as lymphoma, liver cancer, and breast cancer. Previous bioinformatics study revealed that HKDC1 was significantly upregulated in lung adenocarcinoma (LUAD). However, its biological functions and potential mechanism in LUAD have not been studied.Methods: We performed bioinformatics analysis, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and a series of functional assays in vitro and in vivo to investigate the roles of HKDC1 in LUAD.Results: We discovered that HKDC1 was highly expressed in LUAD tissues and cell lines, and the positive expression of HKDC1 was correlated with aberrant clinicopathological characteristics in LUAD patients. Furthermore, HKDC1 could serve as a prognostic predictor for LUAD patients. Overexpression of HKDC1 promoted proliferation, migration, invasion, glycolysis, EMT and tumorigenicity, whereas knockdown of HKDC1 produced the opposite functional effects. Mechanistically, HKDC1 could regulate the AMPK/mTOR signaling pathway to perform its biological function.Conclusions: Our findings suggest that HKDC1 plays an oncogenic role in LUAD. Targeting this gene may provide a promising therapeutic target to delay LUAD progression.
Model for Utilizing Distance Learning post COVID-19 using (PACT)™ A Cross Sectional Qualitative Study
Authors: Ahmed Samar A , Hegazy Nagwa Nashat , Malak Hany W. Abdel , Kayser Cliff W. , Elrafie Noha M , Hassanien Mohammed , Al-Hayani Abdulmonem A , Saadany Sherif A El , AI-Youbi Abdulrahman O , Shehata Mohamed Hany Kamel
Published: September 2020

BackgroundCOVID -19 pandemic pressured medical schools globally to shift to Distance learning (DL) as an alternative way to ensure that the content delivered is satisfactory for student progression.Aim of the workThis work aims at mapping priorities for post-COVID planning for better balance between distance learning and face to face learning.MethodsThis qualitative study aimed to develop a model for utilizing DL using The Polarity Approach for Continuity and Transformation (PACT)™. A virtual mapping session was held with 79 faculty from 19 countries. They worked in small groups to determine upsides and downsides of face-to-face and DL subsequently. An initial polarity map was generated identifying five tension areas; Faculty, Students, Curriculum, Social aspects and Logistics. A 63-item assessment tool was generated based on this map, piloted and then distributed as a self-administered assessment. The outcomes of this assessment were utilized for another mapping session to discuss warning signs and action steps to maintain upsides and avoid downsides of each pole.ResultsParticipants agreed that face-to-face teaching allows them to inspire students and have meaningful connections with them. They also agreed that DL provides a good environment for most students. However, students with financial challenges and special needs may not have equal opportunities to access technology. As regards social issues, participants agreed that face-to-face learning provides a better chance for professionalism through enhanced team-work. Cognitive, communication and clinical skills are best achieved in face-to-face. Participants agreed that logistics for conducting DL are much more complicated when compared to face-to-face learning. Participants identified around 10 warning signs for each method that need to be continuously monitored in order to minimize the drawbacks of over focusing on one pole at the expense of the other. Action steps were determined to ensure optimized use of in either method.ConclusionIn order to plan for the future, we need to understand the dynamics of education within the context of polarities. Educators need to understand that the choice of DL, although was imposed as a no-alternative solution during the COVID era, yet it has always existed as a possible alternative and will continue to exist after this era. The value of polarity mapping and leveraging allows us to maximize the benefit of each method and guide educators' decisions to minimize the downsides for the good of the learning process.
Deficits in Skilled Motor and Auditory Learning in a Rat Model of Rett Syndrome
Authors: Adcock Katherine S. , Blount Abigail E. , Morrison Robert A. , Alvarez-Dieppa Amanda , Kilgard Michael P. , Engineer Crystal T. , Hays Seth A.
Published: September 2020

Background: Rett Syndrome is an X-linked neurodevelopmental disorder caused by a mutation in the gene MECP2. Individuals with Rett Syndrome display developmental regression at an early age, and develop a range of motor, auditory, cognitive and social impairments. Several studies have successfully modeled some aspects of dysfunction and Rett Syndrome-like phenotypes in transgenic mouse and rat models bearing mutations in the MECP2 gene. Here, we sought to extend these findings and characterize skilled learning, a more complex behavior known to be altered in Rett syndrome. Methods: We evaluated the acquisition and performance of auditory and motor function on two complex tasks in heterozygous female Mecp2 rats. Animals were trained to perform a speech discrimination task or a skilled forelimb reaching task. Results: Our results reveal that Mecp2 rats display slower acquisition and reduced performance on an auditory discrimination task than wild-type (WT) littermates. Similarly, Mecp2 rats exhibit impaired learning rates and worse performance on a skilled forelimb motor task compared to WT. Conclusions: Together, these findings illustrate novel deficits in skilled learning consistent with clinical manifestation of Rett syndrome and provide a framework for development of therapeutic strategies to improve these complex behaviors.
What is the role of locoregional anesthesia in breast surgery? A systematic literature review focused on pain intensity, opioid consumption, adverse events, and patient satisfaction.
Authors: Sansone Pasquale , Giaccari Luca Gregorio , Faenza Mario , Costanzo Pasquale Di , Izzo Sara , Aurilio Caterina , Coppolino Francesco , Passavanti Maria Beatrice , Pota Vincenzo , Pace Maria Caterina
Published: September 2020

Background: Breast surgery in the United States is common. Pain affects up to 50% of women undergoing breast surgery and can interfere with postoperative outcomes. General anesthesia is the conventional, most frequently used anaesthetic technique. Various locoregional anesthetic techniques are also used for breast surgeries. A systematic review of the use of locoregional anesthesia for postoperative pain in breast surgery is needed to clarify its role in pain management.Objectives: To systematically review literature to establish the efficacy and the safety of locoregional anesthesia used in the treatment of pain after breast surgery.Methods: Embase, MEDLINE, Google Scholar and Cochrane Central Trials Register were systematically searched in Mars 2020 for studies examining locoregional anesthesia for management of pain in adults after breast surgery. The methodological quality of the studies and their results were appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and specific measurement properties criteria, respectively.Results: Nineteen studies evaluating locoregional anesthesia were included: 1058 patients underwent lumpectomy/mastectomy, 142 breast augmentation and 79 breast reduction. Locoregional anesthesia provides effective anesthesia and analgesia in the perioperative setting. After mastectomy, the use of locoregional anesthesia techniques seems to reduce pain, especially in the first hour after the end of the surgery. Other potentially beneficial effects of locoregional anesthesia emerged from our review include decreased need for opioids, decreased postoperative nausea and vomiting, fewer complications and increased patient satisfaction. All this improves postoperative recovery and shortens hospitalization stay.Conclusion: The results of this study support the technique of locoregional anesthesia for breast surgery.
Effect of the Electrode Array-Retina Gap Distance on Visual Function in Patients with the Argus II Retinal Prosthesis
Authors: Naidu Abhishek , Ghani Nimra , Yazdanie Mohammad Saad , Chaudhary Khurram
Published: September 2020

Background: Post-implantation visual outcomes in patients with the Argus II Retinal Prosthesis is dependent on a multitude of factors including the positioning of the electrode array on the retina. The purpose of this study is to determine whether the average electrode array-retina gap distance correlates with objective visual function outcomes and sensitivity detection thresholds in patients implanted with the Argus II Retinal Prosthesis.Methods: 5 patients with implantation of the Argus II Retinal Prosthesis were enrolled in this single-institution retrospective study. Patient demographics were collected from medical records. Visual function data (Square Localization [SL] and Direction of Motion [DOM]) and Optical Coherence Tomography (Cirrus HD-OCT) images were extracted retrospectively from the Argus II Retinal Prosthesis Post-Approval study. Visual function tests were performed with the device OFF and ON at each study visit. Electrode array-retina gap distances were measured at each of the array’s 60 electrodes using the Cirrus HD-OCT software in both the nasotemporal and superoinferior planes. Data was obtained at baseline, and post-operative month 1, month 3, month 6, and year 1. Sensitivity detection thresholds were obtained at the initial programming visit and each reprogramming session. Results: 3 patients performed significantly better in SL visual function testing with the device ON. Patients that worsened in visual function testing with the device ON in both SL and DOM testing had a statistically significant decrease in performance. The electrode array-retina gap distance was found to effect performance in SL testing in a patient-dependent manner. No effect was found between the electrode-array gap distance and DOM testing or sensitivity detection threshold. Conclusion: Our results demonstrate that the electrode array-retina gap distance may affect visual function outcomes in SL testing in certain patients with the Argus II Retinal Prosthesis, and the direction and magnitude of this effect is likely patient-dependent. Furthermore, complete apposition between the electrode array and retina may not always be necessary to achieve optimal visual outcomes.
Postoperative incidence of seizure and cerebral infarction in pediatric patients with epileptic type moyamoya disease: a meta-analysis of single rate
Authors: LIU JINGJING , Xu Qinlan , Niu Hongchuan , Wang Rong , Ye Xun , Liu Xianzeng
Published: September 2020

Background: Surgery is a conventional mature treatment for moyamoya disease (MMD). However, whether surgery is also an effective therapy for epileptic type MMD has seldom been investigated systematically. The study aims to summarize the pooled postoperative incidence of seizure and cerebral infarction in pediatric patients with epileptic type moyamoya disease. Method: The study was a systematic review and critical appraisal with a meta-analysis of cohort studies, both prospective and retrospective. Studies were identified by a computerized search of Pubmed, EMBASE, Web of Science, Wanfang, and CNKI databases. In a literature search, a total of 7 cohort studies were identified. The I2statistic was used to quantify heterogeneity. A fixed-effect model was used to synthesize the results. The linear regression test of funnel plot asymmetry was used to estimate the potential publication bias.Results: The pooled estimated postoperative incidence of seizure in pediatric patients with epileptic type moyamoya disease was 23.44%. The pooled estimated postoperative incidence of cerebral infarction in pediatric patients with epileptic type moyamoya disease was 9.12%. Low substantial heterogeneity and potential publication bias were present.Conclusion: Evidence from this study suggests that the postoperative incidence of seizure and cerebral infarction is relatively low. Surgery is an effective and secure therapy for pediatric patients with epileptic type moyamoya disease.
Long non-coding RNA BCYRN1 exerts an oncogenic role in colorectal cancer through regulating miR-204-3p/KRAS axis
Authors: Yang Liu , Zhang Yinan , Bao Jun , Feng Ji-Feng
Published: September 2020

Background: It has been well documented that long non-coding RNAs (lncRNAs) regulate numerous characteristics of cancer, including proliferation, migration, metastasis, apoptosis, and even metabolism. LncRNA BCYRN1 (BCYRN1) is a newly identified brain cytoplasmic lncRNA with 200 nucleotides that was discovered to be highly expressed in tumour tissues, including those of hepatocellular carcinoma, gastric cancer and lung cancer. However, the roles of BCYRN1 in colorectal cancer (CRC) remain obscure. This study was designed to reveal the role of BCYRN1 in the occurrence and progression of CRC.Methods: RT-PCR was used to detect the expression level of BCYRN1 in tumour tissues and CRC cell lines. BCYRN1 was knocked down in CRC cells, and cell proliferation changes were evaluated by cell counting kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), and Ki-67 and proliferating cell nuclear antigen (PCNA) expression assays. Cell migration and invasion changes were evaluated by wound healing, Transwell and invasion-related protein expression assays. Flow cytometry analysis was used to assess whether BCYRN1 regulates the apoptosis of CRC cells. The dual luciferase reporter gene detects the competitive binding of BCYRN1 to miR-204-3p. In vivo experiments were performed to evaluate the effect of BCYRN1 on tumour development. TargetScan analysis and dual luciferase reporter gene assays were applied to detect the target gene of miR-204-3p. Rescue experiments verified that BCYRN1 affects CRC by regulating the effect of miR-204-3p on KRAS.Results: We found that compared with normal tissues and human intestinal epithelial cells (HIECs), CRC tumour tissues and cell lines had significantly increased BCYRN1 levels. We further determined that knockdown of BCYRN1 inhibited the proliferation, migration, and invasion and promoted the apoptosis of CRC cells. In addition, bioinformatics analysis and dual luciferase reporter assay showed that BCYRN1 served as a competitive endogenous RNA (ceRNA) to regulate the development of CRC through competitively binding to miR-204-3p. Further studies proved that overexpression of miR-204-3p reversed the effects of BCYRN1 on CRC. Next, TargetScan analysis and dual luciferase reporter assay indicated that KRAS is a target gene of miR-204-3p and is negatively regulated by miR-204-3p. A series of rescue experiments showed that BCYRN1 affected the occurrence and development of CRC by regulating the effects of miR-204-3p on KRAS. In addition, tumorigenesis experiments in a CRC mouse model confirmed that BCYRN1 downregulation effectively inhibited tumour growth.Conclusions: Our findings suggest that BCYRN1 plays a carcinogenic role in CRC by regulating the miR-204-3p/KRAS axis.
Optimal preparation of high-entropy boride-silicon carbide ceramics
Authors: Zhang Yan , Sun Shi-Kuan , Guo Wei-Ming , Xu Liang , Zhang Wei , Lin Hua-Tay
Published: September 2020

High-entropy boride-silicon carbide (HEB-SiC) ceramics were fabricated by using boride-based powders prepared from borothermal and boro/carbothermal reduction methods. The effects of processing routes (borothermal reduction and boro/carbothermal reduction) of HEB powders were examined. HEB-SiC ceramics with nearly relatively full density (>98%) were prepared by spark plasma sintering at 2000 °C. It was demonstrated that the addition of SiC led to slightly coarsening of the microstructure. The HEB-SiC ceramics prepared from boro/carbothermal reduction powders showed the fine-grained microstructure and higher Vickers’ hardness but lower fracture toughness values as compared with the same composition prepared from borothermal reduction powders. These results indicated that the selection of the powder processing method and the addition of SiC phase could contribute to the optimal preparation of high-entropy boride-based ceramics.
Patients’ experiences with the advanced practice nurse role in Swiss family practices: a qualitative study
Authors: Schönenberger Nicole , Sottas Beat , Merlo Christoph , Essig Stefan , Gysin Stefan
Published: September 2020

Background: Considering shortages of general practitioners (GP) and strategies for improving the quality of health care provision, many countries have implemented interprofessional care models with advanced practice nurses (APN). International evidence suggests that APN care results in high patient satisfaction. In Switzerland, the role is still new, and the patient perspective has not yet been researched. Our aim was therefore to explore patients’ experiences with the APN role in Swiss family practices.Methods: We conducted 22 semi-structured interviews in four different family practices with patients aged 18 to 97 suffering from minor acute to multiple chronic diseases, and who had at least one consultation with an APN. All interviews were audiotaped, transcribed verbatim, and analysed using qualitative content analysis.Results: The analysis resulted in five themes: Despite the unfamiliarity, all patients were willing to be consulted by an APN because it was recommended by their GP (1); after several encounters, most participants perceived differences between the APN and the GP consultation in terms of the length and approach of the consultations as well as the complexity of their tasks (2); the interviewees emphasised coaching, guidance, care coordination, and GP-assisting tasks as APN core competencies and attributed the characteristics empathetic, trustworthy, and competent to the APN role (3); most patients especially valued home visits and the holistic approach of the APNs, but they also noticed that in certain cases GP supervision was required (4); and due to the close collaboration between the APN and the GP, patients felt safe, well cared for and experienced improvements in physical and psychological well-being as well as in daily activities (5). Conclusion: Our results suggest that patients value the APNs’ competencies, despite their initial lack of role knowledge. Trust in the GP seems to be the most important factor for patients’ receptiveness toward the APN role. Overall, patients perceived an added value due to the enlargement of the scope of practice offered by APNs. The patient perspective might provide valuable insights for further APN role implementation in Swiss family practices.
Prevalence and determinants of intimate partner violence against mothers of children under-five years in central Malawi
Authors: Chilanga Emmanuel , Collin-Vezina Delphine , Khan Mohammad Nuruzzaman , Riley Liam
Published: September 2020

Background Intimate partner violence (IPV) against women is a global human rights violation and a public health problem. The phenomenon is linked to adverse health effects for women and children. Mothers of young children in Malawi can be particularly at risk because of gender-based power imbalances. The objectives of this study were to examine the prevalence and the risk factors of IPV against mothers of children under-five years of age in rural Malawi.Methods A multistage, cross-sectional study design was used. A sample of 538 mothers of young children was randomly selected from postnatal clinics in Dowa district. The WHO's Violence against women screening instrument was used to collect data. Logistic regressions were used to determine risk factors that were associated with IPV against mothers. Results Overall prevalence of all four forms of IPV against mothers of under-five children was 60.2%. The prevalence of IPV controlling behavior, psychological, physical, and sexual violence were 74.7%, 49.4%, 43.7% and 73.2% respectively. In multivariate analyses, mothers whose partners had extra marital affairs were more likely to experience controlling behavior (AOR: 4.97, 95% CI: 2.59-8.55, P = 0.001), psychological (AOR: 2.14, 95% CI: 1.486-3.472, P = 0.001) and physical (AOR: 2.29, 95% CI: 1.48-3.94, P = 0.001) violence than mothers whose partners did not have extra marital affairs. Mothers whose partners consume alcohol were more likely to experience sexual violence (AOR: 2.00, 95% CI: 1.17-3.41, P = 0.001) than mothers whose partners did not drink. Finally, mothers who spent more than 30 minutes drawing water were at greater risk of experiencing IPV than mothers who spent less than 30 minutes. Conclusion This study found a significantly higher prevalence of IPV against mothers of under-five children in rural Malawi compared to women in the general population. Micro and macro-level programs aimed at mitigating the partners’ potential risk behaviors identified in this study are suggested. Public health programs that support increased household access to safe water are also recommended to help undermine IPV against mothers.
The impact of COL1A1 and COL6A1 expressions on hypospadias and penile curvature severity
Authors: Yuri Prahara , Gunadi . , Lestari Rahmadani Puji , Fardilla Firly Putri , Setyaningsih Wiwit Ananda Wahyu , Arfian Nur , Dachlan Ishandono
Published: September 2020

Background : Hypospadias, the most frequent congenital male external genitalia abnormality, is usually associated with curvature of the ventral penis, i.e. chordee. Abnormality of dartos tissue has been suggested as the pathophysiology of chordee. Collagen is one of the most abundant fibrous proteins within the extracellular matrix. In this study, we determined the expressions of collagen 1 (COL1A1) and COL6A1 in patients with hypospadias and associated them with the severity of penile curvature. Methods : We involved 60 children <18 years old, consisting of 20 distal hypospadias, 20 proximal hypospadias patients, and 20 controls in our institution from 2017 – 2020. The expressions of COL1A1 and COL6A1 from dartos tissue were determined by reverse-transcriptase polymerase chain reaction (qPCR). The penile curvature severity was classified as mild (<30 degree), moderate (30-60 degree), and severe (>60 degree). Results : qPCR showed that the COL1A1 and COL6A1 expressions were significantly downregulated in distal (0.88 (0.38-2.53) and 0.54 (0.16-4.35), respectively) and proximal 0.76 (0.33-2.57) and 0.57 (0.18-1.38), respectively) hypospadias groups compared to controls (1.85 (0.24-4.61) and 0.93 (0.17-4.06), respectively) with p -values of 0.024 and 0.018, respectively. Furthermore, there was a moderate correlation between COL1A1 and COL6A1 expressions ( r= 0.458, p< 0.0001). Interestingly, the COL1A1 and COL6A1 were also significantly downregulated in the moderate and severe compared to the mild chordee groups with p -values of 0.003 and 0.037, respectively. Conclusions : Aberrant COL1A1 and COL6A1 expressions might affect the abnormality of dartos tissue and penile curvature severity in hypospadias patients.
Older age and frailty are the chief predictors of mortality in COVID-19 patients admitted to an acute medical unit in a secondary care setting- A cohort study
Authors: Chinnadurai Rajkumar , Ogedengbe Onesi , Agarwal Priya , Money-Coomes Sally , Abdurrahman Ahmad Z , Mohammed Sajeel , Kalra Philip A , Rothwell Nicola , Pradhan Sweta
Published: September 2020

Background There is a need for more observational studies across different clinical settings to better understand the epidemiology of the novel COVID-19 infection. Evidence on clinical characteristics of COVID-19 infection is scarce in secondary care settings in Western populations.Methods We describe the clinical characteristics of all consecutive COVID-19 positive patients (n=215) admitted to the acute medical unit at Fairfield General Hospital (secondary care setting) between 23 March 2020 and 30 April 2020 based on the outcome at discharge (group 1: alive or group 2: deceased). We investigated the risk factors that were associated with mortality using binary logistic regression analysis. Kaplan-Meir (KM) curves were generated by following the outcome in all patients until 12 May 2020. Results The median age of our cohort was 74 years with a predominance of Caucasians (87.4%) and males (62%). Of the 215 patients, 86 (40%) died. A higher proportion of patients who died were frail (group 2: 63 vs group 1: 37%, p<0.001), with a higher prevalence of cardiovascular disease (group 2: 58 vs group 1: 33%, p<0.001) and respiratory diseases (group 2: 38 vs group 1: 25 %, p=0.03). In the multivariate logistic regression models, older age (odds ratio (OR) 1.03; p=0.03), frailty (OR 5.1; p<0.001) and lower estimated glomerular filtration rate (eGFR) on admission (OR 0.98; p=0.01) were significant predictors of inpatient mortality. KM curves showed a significantly shorter survival time in the frail older patients. Conclusion Older age and frailty are chief risk factors associated with mortality in COVID-19 patients hospitalised to an acute medical unit at secondary care level. A holistic approach by incorporating these factors is warranted in the management of patients with COVID-19 infection.
High-resolution habitat suitability model for Phlebotomus pedifer, the vector of cutaneous leishmaniasis in southwestern Ethiopia
Authors: Pareyn Myrthe , Rutten Anneleen , Merdekios Behailu , Wedegärtner Ronja Elisabeth Magdalene , Girma Nigatu , Regelbrugge Leo , Shibru Simon , Leirs Herwig
Published: September 2020

Background: Phlebotomus pedifer is the vector for Leishmania aethiopica causing cutaneous leishmaniasis (CL) in southwestern Ethiopia. Previous research on the transmission dynamics of CL resulted in recommendations for vector control. In order to target these interventions towards affected areas, a comprehensive understanding of the spatial distribution of P. pedifer at high spatial resolution is required. Therefore, this study determined the environmental predictors that facilitate the distribution of P. pedifer and created a map indicating the areas where conditions are suitable for survival of the vector in southwestern Ethiopia with high spatial resolution.Methods: Phlebotomus pedifer presence points were collected during two entomological surveys. Climate, vegetation and topographic variables were assembled. Climate variables were interpolated with variables derived from high-resolution digital elevation models to generate topoclimatic layers representing the climate conditions in the highlands. A Maximum Entropy model was run with the presence points, predicting variables and background points, which were selected based on a bias file.Results: Phlebotomus pedifer was the only captured Phlebotomus species in the study area and was collected at altitudes ranging between 1685 and 2892 m. Model projections indicated areas with suitable conditions in a ‘belt’ surrounding the high mountain peaks. Model performance was high, with test and train AUC values being 0.93 and 0.90, respectively. A multivariate environmental similarity surface (MESS) analysis showed that the model projection was only slightly extrapolated for some of the variables. The mean annual temperature was the environmental variable, which contributed most to the model predictions (60.0%) followed by the seasonality in rainfall (13.2%). Variables representing steep slopes showed very low importance to model predictions.Conclusions: Our findings indicate that the suitable habitats for P. pedifer correspond well with the altitudes at which CL was reported previously, but the predictions are more widely distributed, in contrast with the description of CL to occur in particular foci. Moreover, we confirm that vector distribution is driven by climate factors, suggesting inclusion of topoclimate in sand fly distribution models. Overall, our model provides a map with a high spatial resolution that can be used to target sand fly control measures in southwestern Ethiopia.
Determinants of early sexual initiation among female youth in Ethiopia: A multilevel analysis of 2016 Ethiopian Demographic and Health Survey
Authors: Arefaynie Mastewal , Yalew Melaku , Damtie Yitayish , Kefale Bereket
Published: September 2020

Background: Evidences on determinants of early sexual initiation among female youth is still limited especially; community-level factors are not investigated in Ethiopia. Therefore, the aim of this study was to assess individual and community-level factors associated with early sexual initiation among female youth in Ethiopia.Methods: The 2016 Ethiopian Demographic and Health Survey (EDHS) dataset were used and a total of 6,143 participants (female youth) were included. Multi-level mixed-effect logistic regression was done to identify individual and community-level factors. Adjusted odds ratio along with 95% confidence interval was used to show the strength and direction of the association. Finally, the level of statistical significance was declared at P value less than 0.05.Results: Individual-level factors significantly associated with early sexual initiation among female youth were; age group from 19-24 years [AOR=5.8, 95% CI= (4.6, 7.3)], not attending school [AOR=14.1, 95% CI= (8.1, 24.7)], ever chewing Chat [AOR= 2.0, 95% CI= (1.3, 3.0)]. From community-level factors: living in Addis Ababa [AOR= 0.3, 95% CI= (0.2, 0.5)], living in Gambella [AOR=2.7, 95% CI= (1.7, 4.3)] and live in a low proportion of poor communities [AOR= 0.7, 95% CI= (0.5, 0.9)] were significantly associated with early sexual initiation among female youth in Ethiopia.Conclusions: Age, low educational status, ever chewing Chat, region and live in a high proportion of poor community had a statistical association with early sexual initiation among female youth in Ethiopia. Improving educational coverage and community-level of wealth status are important intervention areas to delay the age of early sexual initiation.
Cancer Associated Macrophage-Like Cells and Prognosis of Esophageal Cancer after Chemoradiation Therapy
Authors: Gironda Daniel Joseph , Adams Daniel Lee , He Jianzhong , Xu Ting , Gao Hui , Qiao Yawei , Komaki Ritsuko , Reuben James M. , Liao Zhongxing , Blum-Murphy Mariela , Hofstetter Wayne L. , Tang Cha-Mei , Lin Steven H.
Published: September 2020

Background: Cancer Associated Macrophage-Like cells (CAMLs) are polynucleated circulating stromal cells found in the bloodstream of numerous solid-tumor malignancies. Variations within CAML size have been associated with poorer progression free survival (PFS) and overall survival (OS) in a variety of cancers; however, no study has evaluated their clinical significance in esophageal cancer (EC). Methods: To examine this significance, we ran a two-year prospective pilot study consisting of newly diagnosed stage I-III EC patients (n=32) receiving chemoradiotherapy (CRT). CAML sizes were sequentially monitored prior to CRT (BL), ~2 weeks into treatment (T1), and at the first available sample after the completion of CRT (T2). Results: We found CAMLs in 88% (n=28/32) of all patient samples throughout the trial, with a sensitivity of 76% (n=22/29) in pre-treatment screening samples. Improved 2 year PFS and OS was found in patients with CAMLs <50μm by the completion of CRT over patients with CAMLs ≥50μm; PFS (HR=12.0, 95%CI=2.7-54.1, p=0.004) and OS (HR=9.0, 95%CI=1.9-43.5, p=0.019). Conclusions: Tracking CAML sizes throughout CRT as a minimally invasive biomarker may serve as a prognostic tool in mapping EC progression, and high prevalence of these cells prior to treatment suggest diagnostic value for at-risk populations.
A phase 2 study of combined chemo-immunotherapy with cisplatin-pembrolizumab and radiation for unresectable vulvar squamous cell carcinoma
Authors: Yeku Oladapo , Russo Andrea L , Lee Hang , Spriggs David
Published: September 2020

Background: Unresectable or metastatic vulvar cancer has relatively poor outcomes despite chemotherapy-sensitized radiation therapy and combination cytotoxic therapy. Despite the virus-associated and immunogenic nature of this disease, novel immunotherapy options that exploit this advantage are currently lacking. Platinum agents such as cisplatin have been shown to prime dendritic cells for T-cell costimulation, promote downregulation of inhibitory checkpoint molecules, and sensitize tumor cells to cytotoxic T-cell killing. Radiation therapy has also been shown to promote immunogenetic cell death as monotherapy and in combination with cisplatin. In combination with pembrolizumab, cisplatin-sensitized radiation is hypothesized to increase overall response rates and recurrence-free survival in patients with vulvar cancer, via induction of an anti-tumor inflammatory response. Methods: We propose a single-arm phase II clinical trial of pembrolizumab combined with cisplatin-sensitized radiation therapy for women with unresectable, locally advanced, or metastatic vulvar cancer. The first three patients with locally advanced or unresectable disease will receive cycle 1 of pembrolizumab followed by a break and resumption of pembrolizumab at cycle 4 and as part of a safety cohort. All other patients, including the fourth patient with locally advanced/unresectable disease, will receive weekly cisplatin and pembrolizumab every 3 weeks, concurrently with daily radiation therapy. Following the completion of Cis-RT, patients will continue pembrolizumab maintenance for a total of 12 cycles. Archived tissue will be used for HPV status, MSI status, PD-L1, and TIL stratification post-hoc. Imaging will be performed at baseline and every 3 cycles (21-day cycles) as per standard-of-care. Laboratory analysis will occur on the first day of each cycle. Discussion: The combination of cisplatin-sensitized radiation and immune checkpoint blockade has not been evaluated in the upfront setting for vulvar cancer. In this rare malignancy, there are limited interventional clinical trials. This trial is designed to be as accessible as possible by allowing patients to receive cisplatin and radiation locally according to accepted standard-of-care while receiving pembrolizumab and adverse event monitoring at a centralized site. A robust suite of translational correlative studies has also been built into the trial to evaluate tumor-directed immune activation. Trial registration: NCT04430699
Timing for Closed Reduction Procedure for Developmental Dysplasia of the Hip and its Failure Analysis
Authors: Zhang Zhiqiang , Li Hao , Li Hai , Zhang Ziming
Published: September 2020

Background It remains controversial whether the older age to perform closed reduction (CR) procedure for developmental dysplasia of the hip (DDH), the higher incidence of complications. The aim of this study is to evaluate the midterm outcome of CR for DDH among difference age groups, and to analyze and identify risk factors for the failure of this procedure. Methods Clinical data of 107 DDH patients, who received CR, were retrospectively reviewed. Data were divided into three groups according to initial treatment age (Group I: younger than 12 months; Group II: 12 months to less or equal to18 months; Group III: older than 18 months). The presence of avascular necrosis (AVN), residual acetabular dysplasia (RAD), re-dislocation, and further surgeries (FS) were observed. The risk factors were identified for those outcomes aforementioned using univariable logistic regression models. For identified risk factor age, pre-op acetabular index (AI) and post-op AI, their prediction of CR failure were evaluated by receiver operating characteristics curve (ROC).Results A total of 107 patients (156 hips) undergoing CR procedure were evaluated with a median age at initial reduction of 13.0±5.4 months (range, 4 to 28 mo). Mean follow-up time in this study was 6.7±0.8 years (range, 3-8 years). The incidence of AVN, RAD and re-dislocation was 15.4% (24/156), 17.3% (27/156) and 14.7% (23/156) respectively. For AVN, RAD and re-dislocation, the significant risk factors are pre-op IHDI IV (p=0.033), age≥18 months (p=0.012), and pre-op IHDI IV (p=0.004) and walking (p=0.011), respectively. The areas under the ROC curve of each type of failures were 0.841 (post-op AI), 0.688 (pre-op AI) and 0.650 (age).Conclusions Severe DDH patients older than 18 months with CR procedure may result in a high risk of RAD complication. Re-dislocation is significantly associated with pre-op IHDI IV and walking. Patients, who are older than 12.5 months or have a pre-op AI of 38.7° or a post-op AI of 26.4°, are also more likely to fail of CR procedure.
High NEMO score values in nailfold videocapillaroscopy are associated with the subsequent development of ischemic digital ulcers in patients with systemic sclerosis.
Authors: Papa Nicoletta Del , Pignataro Francesca , Maglione Wanda , Minniti Antonina , Sambataro Domenico , Sambataro Gianluca , Valentini Gabriele , Caporali Roberto , Vitali Claudio
Published: September 2020

Background Nailfold videocapillaroscopy (NVC) is a feasible method that allows the observation of the microvascular changes that mark the course of systemic sclerosis (SSc). In previous studies we demonstrated that the NEMO score, i.e., the cumulative number of microhaemorrhages and microthromboses, is a good indicator of the steady state level and overtime changes of disease activity (DA) in SSc.Objectives To verify whether high NEMO scores, which mirror a very active microvascular derangement in the fingers, may be associated with the subsequent development of ischemic digital ulcers (IDUs).Methods The NEMO score was assessed at baseline (T0) in 98 patients with SSc, all classified according to the ACR-EULAR criteria. Of them, 90 were females, 48 had the limited and 50 the diffuse cutaneous variant of SSc. Afterwards, the patients were closely followed up for two years, and the appearance of new IDUs recorded at any time of the follow up.The T0-NEMO score values of patients who developed IDUs were compared to those of patients who did not. A receiver operating curve (ROC) was constructed, and the area under the curve (AUC) calculated by plotting the sensitivity and 1-specificity of the different NEMO score values in predicting the subsequent development of IDUs.Results During the follow-up 38 out of 98 patients developed one or more IDUs. The NEMO score at T0 was significantly higher in those who developed IDUs with respect to those who did not [median 14.5 (95%CI 11.0-21.5), and 4.5 (95%CI 4.0-6.0), respectively, p<.0001]. The ROC curve derived from different T0-NEMO score values had an AUC of 0.79 (95%CI 0.69-0.86, p<0.0001)]. A NEMO score of ≥12 had a sensitivity of 83.3% (95%CI 71.5-91.7), and a specificity of 63.2% (95%CI 46.0-78.2), with positive (P) and negative (N) predictive (PV) values of 58.9% (95%CI 44.7-72.2), and 85.6% (71.8-94.4), respectively. A NEMO score of ≥16 had a sensitivity of 95.0% (95%CI 86.1-99.0), and a NPV of 93.4% (77.5-99.2).Conclusions Being a valid tool to measure DA levels in SSc, the NEMO score also appears to be closely related to the subsequent development of IDUs in this disease.
Analysis of clinicopathological and molecular features of crawling-type gastric adenocarcinoma
Authors: Fujita Yasuko , Uesugi Noriyuki , Sugimoto Ryo , Eizuka Makoto , Toya Yosuke , Akasaka Risaburou , Matsumoto Takayuki , Sugai Tamotsu
Published: September 2020

Background: Crawling-type adenocarcinoma (CRA) is an important gastric cancer (GC) subtype that exhibits a specific histological pattern and has characteristic clinicopathological findings. Despite its characteristic histology, little is known about the molecular characteristics of CRA. Methods: We examined 254 GC cases, including 51 cases of CRA and 126 cases having conventional differentiated adenocarcinomas (CDAs). Results for immunohistochemistry (mucin phenotype; Muc5AC, Muc6, Muc2 and CD10, CDX-2, MLH-1, p53 and β-catenin), mutation analysis (TP53, KRAS and BRAF), microsatellite instability (BAT25, BAT26, D2S123, D5S346 and D17S250), DNA methylation status by a two-panel method (RUNX3, MINT31, LOX, NEUROG1, ELMO1 and THBD), MLH-1 promoter methylation, and allelic imbalance (AI; 1p, 3p, 4p, 5q, 8p, 9p, 13q, TP53, 18q and 22q) were examined. Results: CRAs were more likely to occur in the middle third of the stomach, in younger patients and to be macroscopically depressed. Nuclear accumulation of β-catenin and loss of MLH-1 expression were less frequent among CRA cases compared to CDA cases. At a molecular level, CRA is often characterized by the deletion mutation c.529_546 (18-base pair deletion at codon 177-182 in exon 5) in the TP53 gene (10 cases). Although the low methylation epigenotype was significantly more frequent for CRAs compared to CDAs, multiple AIs were more often seen in CRAs relative to CDAs. Conclusions: The results demonstrated that TP53 mutations, particularly c.529_546del, and multiple AIs are closely associated with CRA carcinogenesis. Our results suggest that CRA is an independent entity of GC in terms of clinicopathologic and molecular findings.