bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and methodology of algorithm for the enhancement of breast tumor images
Authors: Shwetha S V , Dharmanna L , Basavaraj Anami S
Published: December 2020

Breast cancer is the second largest disease in the world having high mortality rate among ladies. Breast image enhancement is required for the foundation of high accuracy segmentation. Several features are extracted from the ROI of mammogram in order to detect the cancer tumor in the early stage. Ultrasound breast images have the speckle noise during the capturing of image. In mammogram images also, the noises like Guassian, Normal and Poisson are introduced. There are no proper enhancements algorithms are designed to enhance the images for the preprocessing of the images. The image enhancement is broadly categorized into two different domains such as spatial and frequency. The spatial domain algorithms will smoothen the image quality and frequency domain algorithms will sharpen the image. Till today there is no concrete work on suitable algorithm methods using different domains of enhancement. The research work has been implemented in two stages. In the first stage we are identifying various noises in the mammogram and ultrasound images. In second stage the algorithms like mean, median, Homomorphic, Weiner, Modified Gabor, Anisoid diffusion filter, Contrast limited Adaptive Histogram equalization (CLAHE), Bilateral filter and Guided filter are worked out. Among all these filters we modified Gabor filter that clearly highlights the portion of the tumor. For all these filters Mean Square Error (MSE), RMSE, PSNR, VAR, SSIM, SD are computed. The best PSNR is obtained for the modified Gabor filter.
Design and Simulation of MIMO Antennas for Mobile Communication
Authors: Bhargava D. S. , Padmavathy T. V. , Reddy Yadhamuri Vinitha , Kavitha Neelapareddy , Hema Vuppalapati
Published: December 2020

A MIMO based antenna structure for next generation mobile communication is proposed. The antenna structure consists of 4 symmetric F-shaped elements placed at the centre of the FR_4 substrate with dielectric constant of 4.4 and loss tangent value of 0.001. The thickness of the substrate is 1.6 mm and the overall dimensions of the proposed structure are 122 x 147 x 0.8 mm3. The designed antenna works in the frequency range of 3.4-3.6 GHz (LTE band 42) with impedance bandwidth of 125MHz. The antenna is designed using CST 3D simulation software and antenna parameters namely Return Loss, Voltage Standing Wave Ratio, Gain, Directivity and Efficiency are analysed. Simulated results show better antenna performance in the desired frequency range.
Efficient Communication Routing Through WiMax Network During Disaster
Authors: Vanitha U , Sivaramakrishnan S , Karthika S , Babukarthik R G
Published: December 2020

During emergency situation like flood, Volcano, tsunami etc., the communication has to reach all the people in that area within a short span of time ensuring the necessary quality of service (QoS). The time at which the information is conveyed save a lot of life. In this paper we propose a communication through a Wi-max technology which broadcast information to all the nodes within the location. The node cooperates among them so that the information is conveyed to all the nodes within the coverage range of the Wi-max. Many cities are affected by some natural disaster where many lives are lots. The implementation of this technology cannot prevent the natural disturbance and certainly give warnings to people and save the valuable human lives. The WiMax network is implemented in Qualnet and various network parameters are measured when the node is mobile and non-mobile.
Multi-sensor optical profilometer for measurement of large freeforms at nm-level uncertainty
Authors: Heikkinen Ville , Nysten Johan , Byman Ville , Hemming Björn , Lassila Antti
Published: December 2020

Optical measurement of large freeform samples is often limited by the resolution, size and slope limits of measurement devices. This trade-off can be solved using stitching—which, however, creates several difficulties often linked to accuracy of movement of the sample or objective. We present a stitching multisensor freeform topography instrument based on scanning white light interferometer, confocal sensor and accurate movements of the sample tracked using laser interferometers. The interferometers track the sample in 2D at an accuracy of a few nm over a 10 cm × 10 cm area. The instrument is thoroughly characterized and uncertainty is estimated to ensure traceable results. Based on the characterization results the instrument allows topography measurement of freeform sample with 54 nm standard uncertainty for datasets of a few hundred sub-images.
Germline Cancer Predisposition Variants in Pediatric Rhabdomyosarcoma: A Report From the Children’s Oncology Group
Authors: Li He , Sisoudiya Saumya D , Martin-Giacalone Bailey A , Khayat Michael M , Dugan-Perez Shannon , Marquez-Do Deborah A , Scheurer Michael E , Muzny Donna , Boerwinkle Eric , Gibbs Richard A , Chi Yueh-Yun , Barkauskas Donald A , Lo Tammy , Hall David , Stewart Douglas R , Schiffman Joshua D , Skapek Stephen X , Hawkins Douglas S , Plon Sharon E , Sabo Aniko , Lupo Philip J
Published: December 2020

Background

Several cancer-susceptibility syndromes are reported to underlie pediatric rhabdomyosarcoma (RMS); however, to our knowledge there have been no systematic efforts to characterize the heterogeneous genetic etiologies of this often-fatal malignancy.

Methods

We performed exome-sequencing on germline DNA from 615 patients with newly diagnosed RMS consented through the Children’s Oncology Group. We compared the prevalence of cancer predisposition variants in 63 autosomal-dominant cancer predisposition genes in these patients with population controls (n = 9963). All statistical tests were 2-sided.

Results

We identified germline cancer predisposition variants in 45 RMS patients (7.3%; all FOXO1 fusion negative) across 15 autosomal dominant genes, which was statistically significantly enriched compared with controls (1.4%, P = 1.3 × 10–22). Specifically, 73.3% of the predisposition variants were found in predisposition syndrome genes previously associated with pediatric RMS risk, such as Li-Fraumeni syndrome (TP53) and neurofibromatosis type I (NF1). Notably, 5 patients had well-described oncogenic missense variants in HRAS (p.G12V and p.G12S) associated with Costello syndrome. Also, genetic etiology differed with histology, as germline variants were more frequent in embryonal vs alveolar RMS patients (10.0% vs 3.0%, P = .02). Although patients with a cancer predisposition variant tended to be younger at diagnosis (P = 9.9 × 10–4), 40.0% of germline variants were identified in those older than 3 years of age, which is in contrast to current genetic testing recommendations based on early age at diagnosis.

Conclusions

These findings demonstrate that genetic risk of RMS results from germline predisposition variants associated with a wide spectrum of cancer susceptibility syndromes. Germline genetic testing for children with RMS should be informed by RMS subtypes and not be limited to only young patients.
Cell-surface antigen profiling of pediatric brain tumors: B7-H3 is consistently expressed and can be targeted via local or systemic CAR T-cell delivery
Authors: Haydar Dalia , Houke Haley , Chiang Jason , Yi Zhongzhen , Odé Zelda , Caldwell Kenneth , Zhu Xiaoyan , Mercer Kimberly S , Stripay Jennifer L , Shaw Timothy I , Vogel Peter , DeRenzo Christopher , Baker Suzanne J , Roussel Martine F , Gottschalk Stephen , Krenciute Giedre
Published: December 2020

Background

Immunotherapy with chimeric antigen receptor (CAR) T cells is actively being explored for pediatric brain tumors in preclinical models and early phase clinical studies. At present, it is unclear which CAR target antigens are consistently expressed across different pediatric brain tumor types. In addition, the extent of HLA class I expression is unknown, which is critical for tumor recognition by conventional αβTCR T cells.

Methods

We profiled 49 low- and high-grade pediatric brain tumor patient-derived orthotopic xenografts (PDOX) by flow analysis for the expression of 5 CAR targets (B7-H3, GD2, IL-13Rα2, EphA2, and HER2), and HLA class I. In addition, we generated B7-H3-CAR T cells and evaluated their antitumor activity in vitro and in vivo.

Results

We established an expression hierarchy for the analyzed antigens (B7-H3 = GD2 >> IL-13Rα2 > HER2 = EphA2) and demonstrated that antigen expression is heterogenous. All high-grade gliomas expressed HLA class I, but only 57.1% of other tumor subtypes had detectable expression. We then selected B7-H3 as a target for CAR T-cell therapy. B7-H3-CAR T cells recognized tumor cells in an antigen-dependent fashion. Local or systemic administration of B7-H3-CAR T cells induced tumor regression in PDOX and immunocompetent murine glioma models resulting in a significant survival advantage.

Conclusions

Our study highlights the importance of studying target antigen and HLA class I expression in PDOX samples for the future design of immunotherapies. In addition, our results support active preclinical and clinical exploration of B7-H3-targeted CAR T-cell therapies for a broad spectrum of pediatric brain tumors.
Baseline Sensitivities of Major Citrus, Pome, and Stone Fruits Postharvest Pathogens to Natamycin and Estimation of the Resistance Potential in Penicillium digitatum
Authors: Chen Daniel , Fӧrster Helga , Adaskaveg James E.
Published: December 2020

Natamycin is a biofungicide that was registered in the United States in 2016 and approved in California in 2017 for postharvest use on citrus and stone fruits. It has been used as a food preservative for many decades, with no resistance ever observed to date. The objective of this study was to determine baseline sensitivities for mycelial growth of 43 to 72 isolates of seven postharvest pathogens to natamycin and the resistance potential of Penicillium digitatum. Mean effective concentrations to inhibit mycelial growth by 50% (EC50 values), as determined by the spiral gradient method, were 0.90 μg/ml for Alternaria alternata, 0.76 μg/ml for Botrytis cinerea, 3.20 μg/ml for Geotrichum citri-aurantii, 0.17 μg/ml for Monilinia fructicola, 1.54 μg/ml for P. digitatum, 1.14 μg/ml for P. expansum, and 0.48 μg/ml for Rhizopus stolonifer. Distributions of EC50 values for each pathogen were unimodal and mostly normal with no outliers detected. Natamycin was also inhibitory to spore germination with values for five of the species similar to those for mycelial growth. Microscopically, natamycin generally arrested spores at the pregermination swelling stage. Mass platings of a conidial mixture of 10 isolates of P. digitatum were inoculated on agar media with 2.5-log radial concentration gradients of natamycin or fludioxonil, and a conidial mixture of 10 isolates of G. citri-aurantii were plated on media amended with natamycin or propiconazole. No resistant isolates were observed for both species to natamycin or for G. citri-aurantii to propiconazole, whereas a resistance frequency of 4.5 × 10−6 to 3.1 × 10−6 was calculated for P. digitatum to fludioxonil. The wide spectrum of activity against different fungal pathogens and a low resistance potential support the registration of natamycin as a postharvest treatment and its integration into an integrated pest management program with other practices including sanitation and rotation of other fungicides with different modes of action.
Operational Definitions for Chronic Liver Disease Manifestations and Recurring Clinical Events in Biliary Atresia
Authors: Shiau Henry , Schraw Jeremy M. , Cavallo Laurel , Leung Daniel H. , Harpavat Sanjiv , Lupo Philip J. , Shneider Benjamin L.
Published: December 2020

Background:

The disease course of biliary atresia (BA) may be complicated by development of chronic liver disease (CLD) manifestations (eg, ascites) and recurring clinical events (eg, cholangitis). Most pediatric CLD‐manifestations/events lack standardized operational definitions, leading to inconsistent identification in clinical research. This study aimed to develop operational research definitions of CLD‐manifestations/events in BA for application in retrospective analysis.

Methods:

Operational definitions of CLD‐manifestations/events were developed by literature review and revised by a panel of experienced pediatric hepatologists. Definitions were applied to a single‐center review of infants with BA post‐Kasai. Manifestations/events were captured until last clinical visit with native liver (SNL), liver transplantation (LT), or death. Native liver survival and event‐free survival were estimated by Kaplan‐Meier method. Cluster analysis was performed to identify similar patterns of manifestation/event development.

Results:

Of 65 infants with BA post‐Kasai (2006–18; median Kasai 56.8 days; 65% girls), 29 underwent LT (median 12.9 months) and 4 died without LT (median 6.9 months). Seventy‐six percent of CLD‐manifestations/events presented within the first year. Presence of definite clinically evident portal hypertension, thrombocytopenia, and dCE ascites were associated with poor transplant‐free survival (P < 0.01). Similar pattern developments of CLD‐manifestations/events identified 3 outcome groups: poor outcomes (87.8% LT/death), SNL with manifestations/events, and SNL with few/no events.

Conclusions:

Operational definitions can provide a timely description of the disease course progression in infants with BA. Research definitions may provide better consistency in future pediatric CLD studies. Furthermore, definitions may serve as endpoints in therapeutic trials or used as variables for disease pattern identification in potential multicenter studies.
ADAPTED SERVQUAL: A Health Service Quality Scale Incorporating Indicators of Sanitation and Hygiene
Authors: Asiamah Nestor , Frimpong Opuni Frank , Aggrey Mavis , Adu-Gyamfi Kwame
Published: December 2020

Background and Objectives:

Many scales have been developed to measure health care quality over the years, but no scale available today incorporates all important indicators of sanitation and hygiene in health care. This study therefore assessed the psychometric properties of an adapted scale, hereby called ADAPTED SERVQUAL, in an attempt to provide a scale that includes relevant indicators of hospital hygiene and sanitation.

Methods:

The setting of the study was low- and medium-capacity hospitals in the Greater Accra Region of Ghana. Patients in wards and outpatient departments in the hospitals participated in the study. We used relevant statistical tools to estimate the psychometric properties of ADAPTED SERVQUAL. To understand the relative importance of the new scale, we compared and related it to a recent scale, HEALTHQUAL.

Results:

Principal component analysis yielded 6 factors: “tangibles,” “reliability,” “responsiveness,” “assurance,” “empathy,” and “sanitation and hygiene,” which explained 84% of the total variance. ADAPTED SERVQUAL has a good internal consistency (Cronbach α = 0.96). Confirmatory factor analysis confirmed the 6-factor solution and produced satisfactory discriminant validity and convergent validity indicators. The adapted scale was highly correlated with all dimensions of HEALTHQUAL, including continuous quality improvement (r ≥0.75, P < .001). In multiple linear regression, the 5 domains of HEALTHQUAL explained 59% of the variance in ADAPTED SERVQUAL (P < .001).

Conclusions:

The study concluded that 8 items that make up a single factor (ie, sanitation and hygiene) and contribute most of the total variance satisfactorily fit into the SERVQUAL scale as additional indicators of health care quality.
Antihelical Auricular Reconstruction With Adipoperichondrial Turnover Flap and Full-thickness Skin Graft
Authors: Baek Sang Oon , Kim Jae Won , Rha Eun Young
Published: December 2020

Reconstruction of the antihelical area can be challenging because the cartilage can be easily exposed due to the thin overlying soft tissue, and it has a lack of tissue mobility. Skin graft can be hesitant to perform in antihelical defects where the bare cartilage is exposed.

A 70-year-old male with squamous cell carcinoma of the antihelix of the left ear was referred to our department for surgical excision. Wide excision with tumor-free margins resulted in a defect of 2.0 × 1.0 cm with exposed bare cartilage. The authors covered the defect using adipoperichondrial turnover flap from cephalic portion of the earlobe followed by full thickness skin graft. The skin graft took well with no complication. Aesthetic result was satisfactory with no auricular deformity.

This adipoperichondrial turnover flap is simple, easy, can be performed in one stage, and produces good esthetic results with no disfiguration of the ear shape.
Dominance of the Leptoprosopic Face and Mesorrhine Nose Types: Does Stature and Facial Types Matter in Northern Nigerian Adults?
Authors: Obaje Sunday Godwin , Ibegbu Austine Oseloka
Published: December 2020

Introduction:

World scientists are using facial morphometry as a reconstructive option in the treatment of patients and ethnic differentiations. Hence, the authors aimed to study the naso-facial dimensions of northern population in Nigeria.

Materials and Methods:

About 500 subjects (Igede, n = 260 and Idoma, n = 240) were recruited from schools in the Benue-Plateau valley in 2014–2015 academic session. Notable parameters measured using vernier caliper were upper facial length, lower facial length, total facial indices, nasal length, nasal width, and nasal indices. Also, stature was measured to the nearest centimeters with stadiometer.

Result:

Taller Idoma males than Igede males (169.25 ± 8.92, 167.13 ± 8.99), and taller Igede females than Idoma females (164.57 ± 8.77, 163.45 ± 8.94). The mean facial indices of Idoma subjects showed 97.89 ± 8.53 and 97.82 ± 8.11 with nasal indices of 77.77 ± 7.34 and 80.42 ± 7.53, whereas Igede subjects showed 96.88 ± 8.61: 97.83 ± 8.36 with nasal indices of 75.59 ± 7.45 and 77.55 ± 0.21. Both ethnic groups showed dominance of the leptoprosopic face type and mesorrhine nose type. All R2 values appeared to be above 0.5% (P < 0.05), where Igede males and females were 0.72, 0.71: 0.82, 0.81, and 0.69, 0.65 and 0.72, 0.73 for stature with total facial indices, and nasal indices respectively.

Conclusions:

Facial and nasal types serve as good predictors of stature, important for dimorphic and ethnic classifications in time of forensic needs.
Neurological Disorders associated with COVID-19 Hospital Admissions : Experience of a Single Tertiary Healthcare Centre
Authors: Dhillon Permesh Singh , Dineen Robert A. , Morris Haley , Tanasescu Radu , Nikfekr Esmaeil , Evans Jonathan , Constantinescu Cris S. , Hosseini Akram A.
Published: December 2020

Background

Early reports have detailed a range of neurological symptoms in patients with the SARS-CoV-2 infection. However, there is a lack of detailed description and incidence of the neurological disorders amongst hospitalized COVID-19 patients. We describe a range of neurological disorders (other than non-specific neurological symptoms), including their clinical, radiological and laboratory findings, encountered in our cohort of COVID-19 patients admitted to a large tertiary institution.

Methods

We reviewed our prospectively collated database of all adult Neurology referrals, Neurology and Stroke admissions and Neurological multi-disciplinary team meetings for all hospitalized patients with suspected or proven COVID-19 from 17 March 2020 to 31 August 2020.

Results

Twenty-nine of 1243 COVID-19 inpatients (2.3%) presented with COVID-19-related neurological disorders. The mean age was 68.9 +/- 13.5(SD) years, age range of 34-97 years, and there were 16 males. 22 patients had confirmed, 5 were probable and 2 had suspected COVID-19 infection according to the WHO case classification. Eight patients (27%) required critical care admission. Neurological symptoms at presentation included acute confusion and delirium, seizures, and new focal neurological deficits. Based on the pre-defined neurological phenotype, COVID-19 patients were grouped into four main categories. 16 patients had cerebrovascular events (13 with acute ischaemic stroke and 3 had haemorrhagic features), 7 patients were found to have inflammatory, non-inflammatory and autoimmune encephalopathy (including 2 with known Multiple Sclerosis), whilst disorders of movement and peripheral nervous system were diagnosed in 3 patients each.

Conclusion

Although the exact prevalence and aetiology remain unclear, new onset of neurological disorders, in addition to anosmia, is non-sporadic during the acute COVID-19-infection. Longitudinal follow-up of these patients is required to determine the clinical and functional outcome, treatment response and long-term effects of the SARS-CoV-2 infection.
AYUSH medicine as add-on therapy for mild category COVID-19; an open label randomised, controlled clinical trial
Authors: Rao Anusha , Ranganatha R , Vikneswaran G , Sagar C , Mathu R , Sherin M , sigamani Alben , Reddy M. Ravi Kumar
Published: December 2020

Background

AYUSH formulations have a potential role in symptomatic treatment, preventing disease progression and improving quality of life in COVID-19 patients.

Objective

To study the effect of AYUSH formulation (Kabasura Kudineer tablets, Shakti drops and Turmeric plus) as an add-on treatment in patients with mild COVID - 19

Methodology

Single centre, two arms, open labelled randomized controlled trial with a total of 30 patients (15 in the intervention arm and 15 in the standard care arm). Intervention arm received a combination of 3 AYUSH formulation along with the standard of care treatment for 21 days. All patients were followed for 28 days. Symptom severity (using Modified Jackson scale), negative conversion of SARS-CoV-2 RNA (using RTPCR) and quality of life (WHOWOL BREF questionnaire) was assessed.

Results

Fifteen patients (93.8%) in the intervention group and twelve patients (92.3%) in the standard care arm had complete resolution of symptoms (P value= 0.36). Negative conversion for SARS-CoV-2 was seen in thirteen patients (92.9%) in intervention arm and eleven patients (100%) in standard care arm at day 28 (P value = 0.56). There was no difference in the quality of life scores between the 2 groups.

Conclusion

The use of Ayush interventions as add-on therapy did not negatively impact the clinical outcomes in COVID-19. This trial confirmed the safety and tolerability of Kabasura Kudineer tablets, Shakti drops and Turmeric plus tablets when used use among mild to moderate symptom category, of COVID-19. There were no serious adverse events in the treated group. There was no clinical progression of disease from baseline status and all trial participants recovered fully by day 28. A longer follow up and a larger sample size is recommended for future definitive trials with this alternative medicine (AYUSH) combination.
Management of the Covid-19 Health Crisis: A Survey in Swiss Hospital Pharmacies
Authors: Schumacher Laurence , Dhif Yassine , Bonnabry Pascal , Widmer Nicolas
Published: December 2020

Background

The COVID-19 pandemic has put a lot of strain on health systems since 2020. A review of the Swiss hospital pharmacies responses during the first wave was performed to improve the quality of the pharmaceutical management of future health crises.

Methods

An electronic survey was sent to all head of hospital pharmacies in Switzerland. The questionnaire was organized into eleven clusters of questions and covered many topics regarding the management of the first wave of COVID-19. Data collection was conducted from May to June, 2020.

Results

Analyses were performed with 43 responses (66%) out of 65 questionnaires sent (at least one answer per questionnaire). 41% (17/41) of pharmacies had existing standard operating procedures or pandemic plans and 95% of them (39/41) created a steering committee to manage the crisis. 67% (29/43) created new activities to respond to the specific needs of the crisis. 67% (26/39) created new drug lists for: COVID-19-specific treatments (85% of pharmacies; 22/26), sedatives (81%; 21/26), anaesthetics (77%; 20/26) and antibiotics (73%; 19/26). Drug availability in COVID-19 wards was managed by increasing existing stocks (54% of pharmacies; 22/41) and creating extra storage space (51%; 21/41). Two drugs generated the most concern about shortages: propofol (49% of pharmacies; 19/39) and midazolam (44%; 17/39). Remdesivir stocks even ran out in 26% of pharmacies (10/39). Specific new documents were drafted to respond to medical needs with regards to drug administration (28% of pharmacies; 12/43), drug preparation (28%; 12/43) and treatment choices (23%; 10/43).

Conclusions

Swiss hospital pharmacies encountered many challenges related to the COVID-19 crisis and had to find solutions quickly, effectively and safely. The survey highlights the key role played by Hospital Pharmacy’s in many aspects during the pandemic by providing logistical and clinical support to medical and care teams. The lessons and experiences outlined could be used to improve the quality of the preparation for similar future events.

KEY POINTS

▸

The COVID-19 pandemic generated unprecedented global demand for specific drugs, hand sanitizer solution, and other therapeutic products, particularly in critical care settings, highlighting the essential role of hospital pharmacists in such crises.

▸

Key COVID-19 responses at the hospital pharmacy level included staff flexibility with regards to changes in roles and procedures, communication, teamwork and solidarity, and the need to prepare business continuity plans and management dashboards ▸ Managing and facing complex pandemic response reveals the importance of involving hospital pharmacists in pandemic response steering committees at many levels. The lived experiences during the pandemic could have been reviewed and evaluated to raise awareness and guide future policy responses for when the next crisis occurs.
Multimodal Data Acquisition at SARS-CoV-2 Drive Through Screening Centers: Setup Description and Experiences in Saarland, Germany
Authors: Flotho Philipp , Bhamborae Mayur J. , Grün Tobias , Trenado Carlos , Thinnes David , Limbach Dominik , Strauss Daniel J.
Published: December 2020

SARS-CoV-2 drive through screening centers (DTSC) have been implemented worldwide as a fast and secure way of mass screening. We use DTSCs as a platform for the acquisition of multimodal datasets that are needed for the development of remote screening methods. Our acquisition setup consists of an array of thermal, infrared and RGB cameras as well as microphones and we apply methods from computer vision and computer audition for the contactless estimation of physiological parameters. We have recorded a multimodal dataset of DTSC participants in Germany for the development of remote screening methods and symptom identification. Acquisition in the early stages of a pandemic and in regions with high infection rates can facilitate and speed up the identification of infection specific symptoms and large scale data acquisition at DTSC is possible without disturbing the flow of operation.
Declining HIV incidence in sub-Saharan Africa: a systematic review and meta-analysis of empiric data
Authors: Joshi Keya , Lessler Justin , Olawore Oluwasolape , Loevinsohn Gideon , Bushey Sophrena , Tobian Aaron A.R. , Grabowski M. Kate
Published: December 2020

Background

UNAIDS models suggest HIV incidence is declining in sub-Saharan Africa; however, it is unclear whether modeled trends are supported by empirical evidence.

Methods

We conducted a systematic review and meta-analysis of adult HIV incidence data from sub-Saharan Africa by searching Embase, Scopus, PubMed, and OVID databases and technical reports published between January 1, 2010 and July 23, 2019. We included studies that directly measured incidence from blood samples. Incidence data were abstracted according to population risk group, geographic location, sex, intervention arm, and calendar period. Weighted regression models were used to assess incidence trends across general population studies by sex. We also identified studies reporting ≥3 incidence measurements since 2010 and assessed trends within them.

Findings

292 studies met inclusion criteria. Most studies were conducted in South Africa (n=102), Uganda (n=46), and Kenya (n=41); there were 27 countries with no published incidence data, most in western and central Africa. Across general population studies, average annual incidence declines since 2010 were 0.16/1000 person-years (95%CI:0.06-0.26;p=0.004) among men and 0.16/1000 person-years (95%CI: −0.01-0.33;p=0.060) among women in eastern Africa, and 0.25/1000 person-years (95%CI:0.17-034;p<0.0001) among men and 0.42/1000 person-years (95%CI:0.23-0.62;p=0.0002) among women in southern Africa. In 9/10 studies with multiple measurements, incidence declined over time. Incidence was typically higher in women than men (median ratio=1.45, IQR: 1.12-1.83) with increasing sex disparity over time.

Interpretation

Empirical incidence data show the rate of new HIV infections is declining in eastern and southern Africa. However, recent incidence data are non-existent or very limited for many countries, particularly in western and central Africa.

Funding

National Institute of Allergy and Infectious Diseases
The impact of the COVID-19 pandemic on college students’ health and financial stability in New York City: Findings from a population-based sample of City University of New York (CUNY) students
Authors: Jones Heidi E. , Manze Meredith , Ngo Victoria , Lamberson Patricia , Freudenberg Nicholas
Published: December 2020

Understanding the effect of the coronavirus disease 2019 (COVID-19) pandemic on students’ health and financial stability is important to establish effective interventions to mitigate these effects, which may have long-term consequences on their health and wellbeing. Public universities in urban centers represent a substantial proportion of college students in the United States. We implemented a cross-sectional population-based online survey of 2,282 students in a large, public university in New York City in April 2020. We created weights to account for non-response and used Poisson regression with robust standard errors to estimate adjusted prevalence ratios (aPR) for factors associated with mental health outcomes. Students experienced high rates of anxiety/depression and financial instability due to the pandemic. Half of the students reported anxiety/depression (54.5%) and an increased need for mental health services (49.0%) as a result of the COVID-19 pandemic. The majority (81.1%) reported loss of household income, and half (49.8%) reported worries about losing housing. High levels of food (aPR=1.4, 95% CI 1.2, 1.6) and housing (aPR=1.3, 95% CI 1.2, 1.4) insecurity were the strongest predictors of anxiety/depression. Household and personal experiences with possible COVID-19 symptoms were also associated with anxiety/depression or the need for increased mental health services. Addressing student needs at public urban universities requires an integrated holistic approach that targets urgent mental health and economic needs related to the impact of COVID-19. Students who become infected need mental health services as well as health monitoring.
Multivariate Analysis Of Histopathological And Immunohistochemical Prognostic Factors In Endometrial Carcinoma. A Retrospective Pilot Study Of An Italian Regional Referral Center
Authors: Paudice Michele , Scaglione Giulia , Biatta Chiara Maria , Barra Fabio , Riva Marianna , Spina Bruno , Gaggero Gabriele , Fulcheri Ezio , Ferrero Simone , Vellone Valerio Gaetano ,   Gyn DMT
Published: December 2020

Background

to investigate endometrial carcinoma prognostic value of some histopathological and immunohistochemical factors, fairly easily accessible in every routinely pathology lab set.

Methods

we considered patients affected by endometrial carcinoma with available clinical and radiological follow-up data after radical hysterectomy (S. Martino Polyclinic Hospital, Genoa, Italy, period 1/1/2013 - 1/7/2016). We analyzed the following histopathological items: histotype, stage (FIGO), type of infiltration (infiltrative/espansive), desmoplasia, intratumoral necrosis, tumor infiltrating lymphocytes and lymph vascular spaces invasion. Moreover, each case has been investigated with a panel of immunohistochemistry including estrogen receptor α, progesteron receptor, Ki67, p53, β-catenin, e-cadherin, bcl-2 and cyclin D1. Primary endpoints were disease free survival and overall survival.

Results

out of 99 cases eligible for our purpose, we found 69 low-grade endometrioid, 8 high-grade endometrioid and 22 other high-grade endometrial carcinomas. Disease free survival multivariate analysis showed a strong significant correlation between poor prognosis and advanced stage (p=0.0042). Advanced stage (p=0.0003) and presence of desmoplasia (p=0.04) resulted significantly correlated to a worse prognosis in overall survival multivariate analysis. In univariate model, the non-endometrioid histotype was significantly correlated with an unfavorable prognosis when compared to the endometriod type. Same for progesteron receptor low expression.

Conclusion

the multivariate analysis confirmed the central prognostic role of stage in endometrial carcinoma. Moreover, other immunohistochemical markers in univariate analysis, have confirmed their easily reproducible usefulness, well integrating the recent TGCA molecular classification.
Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome
Authors: Roberts Ivayla , Muelas Marina Wright , Taylor Joseph M. , Davison Andrew S. , Xu Yun , Grixti Justine M. , Gotts Nigel , Sorokin Anatolii , Goodacre Royston , Kell Douglas B.
Published: December 2020

The diagnosis of COVID-19 is normally based on the qualitative detection of viral nucleic acid sequences. Properties of the host response are not measured but are key in determining outcome. Although metabolic profiles are well suited to capture host state, most metabolomics studies are either underpowered, measure only a restricted subset of metabolites, compare infected individuals against uninfected control cohorts that are not suitably matched, or do not provide a compact predictive model.

Here we provide a well-powered, untargeted metabolomics assessment of 120 COVID-19 patient samples acquired at hospital admission. The study aims to predict the patient’s infection severity (i.e., mild or severe) and potential outcome (i.e., discharged or deceased).

High resolution untargeted LC-MS/MS analysis was performed on patient serum using both positive and negative ionization modes. A subset of 20 intermediary metabolites predictive of severity or outcome were selected based on univariate statistical significance and a multiple predictor Bayesian logistic regression model was created. The predictors were selected for their relevant biological function and include cytosine and ureidopropionate (indirectly reflecting viral load), kynurenine (reflecting host inflammatory response), and multiple short chain acylcarnitines (energy metabolism) among others.

Currently, this approach predicts outcome and severity with a Monte Carlo cross validated area under the ROC curve of 0.792 (SD 0.09) and 0.793 (SD 0.08), respectively. A blind validation study on an additional 90 patients predicted outcome and severity at ROC AUC of 0.83 (CI 0.74 – 0.91) and 0.76 (CI 0.67 – 0.86). Prognostic tests based on the markers discussed in this paper could allow improvement in the planning of COVID-19 patient treatment.
GOLIATH regulates LDLR availability and plasma LDL cholesterol levels
Authors: Clifford Bethan L. , Jarrett Kelsey E. , Cheng Joan , Cheng Angela , Seldin Marcus , Morand Pauline , Lee Richard , Baldan Angel , de Aguiar Vallim Thomas Q. , Tarling Elizabeth J.
Published: December 2020

Increasing the availability of hepatic low-density lipoprotein receptors (LDLR) remains a major clinical target for reducing circulating plasma LDL cholesterol (LDL-C) levels. Here, we identify the molecular mechanism underlying genome-wide significant associations in theGOLIATHlocus with plasma LDL-C levels. We demonstrate that GOLIATH is an E3 ubiquitin ligase that ubiquitinates the LDL Receptor resulting in redistribution away from the plasma membrane. Overexpression of GOLIATH decreases hepatic LDLR and increases plasma LDL-C levels. Silencing ofGoliathusing antisense oligonucleotides, germline deletion, or AAV-CRISPRin vivostrategies increases hepatic LDLR abundance and availability, thus decreasing plasma LDL-C.In vitroubiquitination assays demonstrate RING-dependent regulation of LDLR abundance at the plasma membrane. Our studies identify GOLIATH as a novel post-translational regulator of LDL-C levels via modulation of LDLR availability, which is likely important for understanding the complex regulation of hepatic LDLR.
A novelRLIM/RNF12variant disrupts protein stability and function to cause severe Tonne-Kalscheuer syndrome
Authors: Bustos Francisco , Espejo-Serrano Carmen , Segarra-Fas Anna , Eaton Alison J. , Kernohan Kristin D. , Wilson Meredith J. , Riley Lisa G. , Findlay Greg M.
Published: December 2020

Tonne-Kalscheuer syndrome (TOKAS) is an X-linked intellectual disability syndrome associated with variable clinical features including craniofacial abnormalities, hypogenitalism and diaphragmatic hernia. TOKAS is caused exclusively by variants in the gene encoding the E3 ubiquitin ligase geneRLIM, also known as. Here we report identification of a novelRLIMmissense variant, c.1262A>G p.(Tyr421Cys) adjacent to the regulatory basic region, which causes a severe form of TOKAS resulting in perinatal lethality by diaphragmatic hernia. Inheritance and X-chromosome inactivation patterns implicateRLIMp.(Tyr421Cys) as the likely pathogenic variant in the affected individual and within the kindred. We show that the RLIM p.(Tyr421Cys) variant disrupts both expression and function of the protein in an embryonic stem cell model. RLIM p.(Tyr421Cys) is correctly localised to the nucleus, but is readily degraded by the proteasome. The RLIM p.(Tyr421Cys) variant also displays significantly impaired E3 ubiquitin ligase activity, which interferes with RLIM function inXistlong-non-coding RNA induction that initiates imprinted X-chromosome inactivation. Our data uncover a highly disruptive missense variant inRLIMthat causes a severe form of TOKAS, thereby expanding our understanding of the molecular and phenotypic spectrum of disease severity.
A non-invasive radar system for automated behavioural tracking: application to sheep
Authors: Dore Alexandre , Pasquaretta Cristian , henry Dominique , Ricard Edmond , Bompard Jean-François , Bonneau Mathieu , Boissy Alain , Hazard Dominique , Aubert Hervé , Lihoreau Mathieu
Published: December 2020

Automated quantification of the behaviour of freely moving animals is increasingly needed in ethology, ecology, genetics and evolution. State-of-the-art approaches often require tags to identify animals, high computational power for data collection and processing, and are sensitive to environmental conditions, which limits their large-scale utilisation. Here we introduce a new automated tracking system based on millimetre-wave radars for real time robust and high precision monitoring of untagged animals. To validate our system, we tracked 64 sheep in a standard indoor behavioural test used for genetic selection. First, we show that the proposed radar application is faster and more accurate than conventional video and infrared tracking systems. Next, we illustrate how new behavioural estimators can be derived from the radar data to assess personality traits in sheep for behavioural phenotyping. Finally, we demonstrate that radars can be used for movement tracking at larger spatial scales, in the field, by adjusting operating frequency and radiated electromagnetic power. Millimetre-wave radars thus hold considerable promises for high-throughput recording of the behaviour of animals with various sizes and locomotor modes, in different types of environments.
An IDH-independent mechanism of DNA hypermethylation upon VHL inactivation in cancer
Authors: Artemov Artem V. , Zhenilo Svetlana , Kaplun Daria , Starshin Alexey , Sokolov Alexey , Mazur Alexander M. , Szpotan Justyna , Gawronski Maciej , Modrzejewska Martyna , Gackowski Daniel , Prokhortchouk Egor B.
Published: December 2020

Hypermethylation of tumor suppressors and other aberrations of DNA methylation in tumors play a significant role in cancer progression. DNA methylation can be affected by various environmental conditions including hypoxia. The response to hypoxia is mainly achieved through activation of the transcription program associated with HIF1a transcription factor. VHL inactivation by genetic or epigenetic events, which also induces aberrant activation of HIF1a, is the most common driver event for renal cancer. With whole-genome bisulfite sequencing and LC-MS, we demonstrated that VHL inactivation induced global genome hypermethylation in human kidney cancer cells under normoxic conditions. This effect was reverted by exogenous expression of wild-type VHL. We show that global genome hypermethylation in VHL mutants can be explained by transcriptional changes in MDH and L2HGDH genes that cause the accumulation of 2-hydroxyglutarate—a metabolite that inhibits DNA demethylation by Tet enzymes. Unlike the known cases of DNA hypermethylation in cancer, 2-hydroxyglutarate was accumulated in IDH wild type cells.

Key points

Inactivation of VHL gene leads to genome hypermethylation in kidney cancer cells. The DNA methylation phenotype can be rescued by endogenous expression of wild-type VHL.

DNA hypermethylation can be attributed to the accumulation of a Tet inhibitor 2-hydroxyglutarate

The accumulation of 2-hydroxyglutarate in IDH wild-type cells is explained by gene expression changes in key metabolic enzymes (malate dehydrogenase MDH and 2-hydroxyglutrarate dehydrogenase L2HGDH).
Conundrum of re-positives COVID-19 cases: A Systematic review of Case reports and Case series
Authors: Yadav Arun Kumar , Ghosh Subhadeep , Dubey Sudhir
Published: December 2020

Introduction

There have been case reports and case series published for RT PCR positive COVID - 19 cases that became RT PCR negative but subsequently became RT PCR positive after a symptom free interval following a negative RT PCR test. These cases may include re-positive, reactivated and re-infection cases. Hence, the systematic review to summarize and synthesize evidence from all available case series and case reports published was undertaken.

Methodology

The systematic review of case series and case reports was registered with Prospero with registration number CRD42020210446. PRISMA guidelines were followed for conducting the systematic review. Studies published in English language only were considered for the Systematic Review. Inclusion criteria for studies included case reports and case series which have documented cases of positive RT-PCR after a period of improvement or negative RT PCR. Reviews, opinions and animal studies were excluded. Case reports which described clinical presentation or manifestations of COVID-19 cases were also excluded from the studies. Methodological quality was assessed using modified Murad scale.

Results

A total of 30 case reports/case series were included in the study, wherein a total of 219 cases were included. In re-positive cases, the age range varied from 10 months to 91 years. The pooled proportion using random effects was 12% with 95% CI from 09% to 15%. Among the re-positives, a total of 57 cases (26%) of the cases had co-morbidities. A total of 51 (23.3%) and 17 (7.8%) re-positive cases had been treated with antivirals and corticosteroids respectively. Among the symptomatic cases, the disease severity was lesser as compared to the initial episode of illness. Only a few studies have confirmed the presence of antibodies after the first episode. The few studies that had done contact tracing of re-positives did not find any positive cases among those in contact with re-positives.

Conclusion

This systematic review presents the review of all the case reports and case series on recurrence of COVID 19 disease. Although limited evidence has been generated due to paucity of such studies and shortcomings in the study designs of case reports and case-series, nonetheless, the evidence generated can still be used in making clinical decisions and framing policy guidelines
Airborne magnetic nanoparticles: environmental risk factors for the transmission of SARS-CoV-2
Authors: Martinez-Boubeta C. , Simeonidis K.
Published: December 2020

Objectives

To examine the impact of concentrations of ambient fine particulate matter (PM2.5) air pollution on the incidence of COVID-19.

Methods

Publicly available data of COVID-19 deaths in March/October 2020 were compared with concentrations of PM2.5 measured in previous years at urban and suburban areas in Thessaloniki. Similar publicly available data of PM2.5 concentrations from Tehran were gathered for comparison. Cross-correlation and Granger causality analysis were performed in order to assess linkage.

Results

On the one hand, the mean PM2.5 concentrations in Thessaloniki were significantly higher in the winter, however the magnetic fraction of particulate matter in the autumn is twice its annual average, suggesting that traffic-related emissions alone may not explain the entire variability of PM2.5. On the other hand, it is implied that changes in coronavirus-related deaths follow changes in airborne magnetite, with the correlation between the two data sets being maximized at the lag time of one-month. Further insight is provided by the monthly pattern of PM2.5 mass concentrations in Tehran. We find that air pollution Granger causes COVID-19 deaths (p<0.05).

Conclusions

A significant association has been found between PM2.5 values and the impact of the COVID-19 pandemic on a bunch of regions. Reported links between pollution levels, climate conditions and other factors affecting vulnerability to COVID-19 may instead reflect inhalation exposure to magnetic nanoparticles. A hypothesis has been set that ubiquitous airborne magnetite pollution, together with certain climatic conditions, may promote a longer permanence of the viral particles in the air, thus favoring transmission.

Key messages

What is already known about this subject?

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Due to their small dimensions, airborne particles are able to penetrate through inhalation into many human organs, from the lungs to the cardiovascular system and the brain, which can threaten our health. Research has shown that air pollution is an important cofactor increasing the risk of mortality from coronaviruses.

What are the new findings?

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Evidence exists that the magnetic fraction of PM has modulated the transmission of SARS-CoV-2 in Thessaloniki, and potentially in any other region in the world.

How might this impact on policy or clinical practice in the foreseeable future?

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Policymakers should take care not to overestimate the effect of social distancing interventions and should consider the impact of air pollution in current or future epidemic waves.