bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiological and Clinical Characteristics of 26 Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Carriers
Authors: Pan Yanfeng , Yu Xue , Du Xinwei , Li Qingqing , Li Xianyang , Qin Tao , Wang Miaomiao , Jiang Minlin , Li Jie , Li Weiguo , Zhang Qian , Xu Zhiwei , Zhang Lu 
Published: April 2020

Abstract

Background
We retrospectively analyzed 26 persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carriers.

Methods
Epidemiological and clinical characteristics from the 26 asymptomatic patients with positive results for SARS-CoV-2 ribonucleic acid testing were obtained.

Results
Twenty-two patients (84.6%) correlated with clustering occurrence. The median period from contact to diagnosis and the last positive nucleic acid test was 19 (8–24 days) and 21.5 days (10–36 days), respectively. The median period from diagnosis to negative nucleic acid test was significantly different between patients with normal or atypical chest computed tomography (CT) findings (n = 16, 61.5%; 7.5 days [2–20 days]) and patients with typical ground-glass or patchy opacities on CT (n = 10, 38.5%; 12.5 days [8–22 days]; P &lt; .01). Seven patients (70.0%) with initial positive nucleic acid test results had a negative result simultaneously with improved CT findings. Obvious improvement in CT findings was observed in 3 patients (30.0%) despite positive nucleic acid test results.

Conclusions
In asymptomatic patients, changes in biochemical and inflammatory variables are small and changes on chest CT can occur. It is worth noting that the long existence of SARS-CoV-2 in some asymptomatic patients and false-negative results need to be considered in SARS-CoV-2 nucleic acid test.
Diet complexity and l-threonine supplementation: effects on growth performance, immune response, intestinal barrier function, and microbial metabolites in nursery pigs
Authors: Koo Bonjin , Choi Janghan , Yang Chengbo , Nyachoti Charles Martin 
Published: April 2020

AbstractThe aim of this study was to investigate the effects of diet complexity and l-Thr supplementation level on the growth performance, immune response, intestinal barrier function, and microbial metabolites in nursery pigs. Thirty-two weaned pigs (body weight 7.23 ± 0.48 kg) were randomly assigned to dietary treatments in a 2 × 2 factorial arrangement based on diet complexity (complex or simple) and dietary Thr content. The complex diet contained fish meal, plasma protein, and dried whey to mimic a conventional nursery diet. The simple diet was formulated with corn, wheat, and soybean meal and did not contain any animal products. l-Thr was supplemented to each diet to supply either 100% (STD Thr) or 115% (SUP Thr) of the NRC (2012) requirement for standardized ileal digestible Thr. Pigs were individually housed and fed experimental diets ad libitum for 14 d. Diet complexity, dietary Thr content, and their interactions were considered the main effects. Pigs fed the simple diet had greater (P &lt; 0.05) plasma interleukin (IL)-10 and IL-6 concentrations compared with those fed the complex diet on days 7 and 14, respectively. Simple diet-fed pigs tended to show greater (P &lt; 0.10) expression of genes encoding for tumor necrosis factor-α, claudin-1, and zonula occludens-1 in the jejunum compared with complex diet-fed pigs. The simple diet-fed pigs had greater (P &lt; 0.05) concentrations of NH3-N in the jejunum digesta than did complex diet-fed pigs. The SUP Thr increased (P &lt; 0.05) villus height and goblet cell (GC) density in villi and crypts in the jejunum and deepened (P &lt; 0.05) crypts in the proximal colon. The SUP Thr resulted in the upregulation (P &lt; 0.05) of occludin gene expression and a tendency toward the downregulation (P = 0.10) of IL-6 gene expression in the jejunum. Interactions (P &lt; 0.05) between diet complexity and l-Thr supplementation level were observed in GC density in the crypt, NH3-N concentration in the jejunum, and the contents of acetate, propionate, and total volatile fatty acids in the colon. In conclusion, feeding a simple diet to nursery pigs resulted in systemic and intestinal inflammation. The SUP Thr diet did not normalize the simple diet-induced inflammation but improved gut integrity. SUP Thr seems to have greater benefits with a simple diet than with a complex diet. Therefore, SUP Thr in a simple diet could be a beneficial nutritional strategy for enhancing gut health.
Synchronous Teledermoscopy in Military Treatment Facilities
Authors: Day William G , Shrivastava Vikas , Roman John W 
Published: April 2020

Abstract
Sustained demand for dermatologic care throughout military medicine, in conjunction with increasing dermatologic provider shortages, has led to increase use of teledermatology in military treatment facilities (MTFs). Initially used to aid in the differentiation of suspicious melanocytic lesions, dermoscopy has found increasing clinical utility in an expanding realm of general dermatologic conditions. We demonstrate the use of synchronous teledermoscopy within a remote MTF by repurposing webcam technology already available at most MTFs. Two patients were seen in clinic at a remote naval primary care clinic with limited subspecialties. Once written consent was retrieved, an on-site dermatologist evaluated each patient and performed a history and skin exam with dermoscopy. Synchronous consultations were conducted with the Global Med Cart (GlobalMed(R) Clinical Access Station with TotalExam(R) 3 HDUSB camera), and Cisco webcam video jabber (Cisco TelePresence PrecisionHD USB Camera part number TTC8-03). The patients then underwent individual synchronous teledermatology consultations with an off-site U.S. Navy dermatologist located in the continental United States. The methodology for the consultation involved the use of a standard dermatoscope and jabber webcam. Two synchronous teledermatology consultations were completed successfully on patients in MTFs with limited subspecialty capabilities. Both cases, with two lesions of concern per case, had 100% concordance between the on-site and teleconsulted dermatologist. Through observing inter-rater agreements between the on-site and remote dermatologists, this small study demonstrates a novel application of technology readily available at most MTFs.
Needlestack: an ultra-sensitive variant caller for multi-sample next generation sequencing data
Authors: Delhomme Tiffany M , Avogbe Patrice H , Gabriel Aurélie A G , Alcala Nicolas , Leblay Noemie , Voegele Catherine , Vallée Maxime , Chopard Priscilia , Chabrier Amélie , Abedi-Ardekani Behnoush , Gaborieau Valérie , Holcatova Ivana , Janout Vladimir , Foretová Lenka , Milosavljevic Sasa , Zaridze David , Mukeriya Anush , Brambilla Elisabeth , Brennan Paul , Scelo Ghislaine , Fernandez-Cuesta Lynnette , Byrnes Graham , Calvez-Kelm Florence L , McKay James D , Foll Matthieu 
Published: April 2020

AbstractThe emergence of next-generation sequencing (NGS) has revolutionized the way of reaching a genome sequence, with the promise of potentially providing a comprehensive characterization of DNA variations. Nevertheless, detecting somatic mutations is still a difficult problem, in particular when trying to identify low abundance mutations, such as subclonal mutations, tumour-derived alterations in body fluids or somatic mutations from histological normal tissue. The main challenge is to precisely distinguish between sequencing artefacts and true mutations, particularly when the latter are so rare they reach similar abundance levels as artefacts. Here, we present needlestack, a highly sensitive variant caller, which directly learns from the data the level of systematic sequencing errors to accurately call mutations. Needlestack is based on the idea that the sequencing error rate can be dynamically estimated from analysing multiple samples together. We show that the sequencing error rate varies across alterations, illustrating the need to precisely estimate it. We evaluate the performance of needlestack for various types of variations, and we show that needlestack is robust among positions and outperforms existing state-of-the-art method for low abundance mutations. Needlestack, along with its source code is freely available on the GitHub platform: https://github.com/IARCbioinfo/needlestack.
Single-Cell Virtual Cytometer allows user-friendly and versatile analysis and visualization of multimodal single cell RNAseq datasets
Authors: Pont Frédéric , Tosolini Marie , Gao Qing , Perrier Marion , Madrid-Mencía Miguel , Huang Tse Shun , Neuvial Pierre , Ayyoub Maha , Nazor Kristopher , Fournié Jean-Jacques 
Published: April 2020

AbstractThe development of single-cell transcriptomic technologies yields large datasets comprising multimodal informations, such as transcriptomes and immunophenotypes. Despite the current explosion of methods for pre-processing and integrating multimodal single-cell data, there is currently no user-friendly software to display easily and simultaneously both immunophenotype and transcriptome-based UMAP/t-SNE plots from the pre-processed data. Here, we introduce Single-Cell Virtual Cytometer, an open-source software for flow cytometry-like visualization and exploration of pre-processed multi-omics single cell datasets. Using an original CITE-seq dataset of PBMC from an healthy donor, we illustrate its use for the integrated analysis of transcriptomes and epitopes of functional maturation in human peripheral T lymphocytes. So this free and open-source algorithm constitutes a unique resource for biologists seeking for a user-friendly analytic tool for multimodal single cell datasets.
A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01)
Authors: Balana Carmen , Vaz Maria Angeles , Manuel Sepúlveda Juan , Mesia Carlos , del Barco Sonia , Pineda Estela , Muñoz-Langa Jose , Estival Anna , de las Peñas Ramón , Fuster Jose , Gironés Regina , Navarro Luis Miguel , Gil-Gil Miguel , Alonso Miriam , Herrero Ana , Peralta Sergio , Olier Clara , Perez-Segura Pedro , Covela Maria , Martinez-García Maria , Berrocal Alfonso , Gallego Oscar , Luque Raquel , Perez-Martín Franciso Javier , Esteve Anna , Munne Nuria , Domenech Marta , Villa Salvador , Sanz Carolina , Carrato Cristina 
Published: April 2020

Abstract

Background
Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for 6 cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized trial investigating whether extending adjuvant temozolomide for more than 6 cycles improved outcome.

Methods
Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after 6 cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of 12 cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and safety (Clinicaltrials.gov NCT02209948).

Results
From August 2014 to November 2018, 166 patients were screened, 7 of whom were ineligible. Seventy-nine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P &lt; 0.001), thrombocytopenia (P &lt; 0.001), and nausea and vomiting (P = 0.001).

Conclusions
Continuing temozolomide after 6 adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS.

Key Points
1. Extending adjuvant temozolomide to 12 cycles did not improve 6-month PFS.
2. Extending adjuvant temozolomide did not improve PFS or OS in any patient subset.
3. Extending adjuvant temozolomide was linked to increased toxicities.
EP01 Audit of the monitoring and documentation of DAS28 score in patients prescribed high cost DMARDs for rheumatoid arthritis every 6 months according to British Society for Rheumatology guidelines
Authors: Tsoi Kevin F. W , Sahni Amit , Selvanayagam Bianka , Memon Muhammad 
Published: April 2020

Abstract

Background
DAS28 is a measure of disease activity in rheumatoid arthritis (RA) which is comprised of the number of tender and swollen joints, inflammatory markers and visual analogue score. Both NICE and British Society of Rheumatology recommend DAS28 is recorded at least every 6 months in patients with RA, to monitor disease activity and ensure adequate response to treatment. CCG mandate 6 monthly DAS28 scores for patients on high cost DMARDs in order to secure funding. Absence of DAS28 scores results in CCGs refusing to fund treatment at the expense of the Trust.

Methods
Our aim was to review whether a DAS28 was documented in every consultation and if it meets the audit standard of a review every 6 months. If the 6 month target is not met, to understand the reason for this and to suggest ways to meet the standard. Blueteq is the software used to identify all patients with a diagnosis of RA between January 2014 and January 2019 at Royal Surrey County Hospital (RSCH). Clinic letters were reviewed to identify whether a DAS28 score was recorded, the date it was recorded and whether this was done within 6 months.

Results
In total, 207 patients are prescribed high cost DMARDs for RA at RSCH. 166 (80%) patients have a documented DAS28, but 41 (20%) patients did not have a documented DAS28. 14 (7%) patients have a documented DAS28 at least 6 monthly. 152 (73%) patients did not meet the audit standard.

Conclusion
Documentation of DAS28 in clinic letters at RSCH does not meet the audit standard. However, these scores have been recorded on Blueteq in order to satisfy CCG requirements. There needs to be consistency in where DAS28 is recorded. Factors contributing to an absence of a documented DAS28 in clinic letters include: no recent inflammatory markers, patients not receiving clinic appointments scheduled at the correct interval, patients not attending clinic, limited follow-up clinic capacity. DAS28 documentation can be improved by incorporating a table into each rheumatology clinic letter template. On initiation of a high cost therapy, the importance of regular blood monitoring and clinic attendance should be reiterated to patients as well as to the appointments booking team. An early arthritis pathway already exists, which can be extended to incorporate a high cost DMARD pathway detailing how to achieve target documentation.
Disclosures: K.F.W. Tsoi: None. A. Sahni: None. B. Selvanayagam: None. M. Memon: None.
EP04 Hypercalcaemia of sarcoidosis in a patient with severe renal impairment successfully treated with denosumab
Authors: Alshakh Randa , Gendi Nagui 
Published: April 2020

Abstract

Background
Denosumab has been used for the management of hypercalcaemia of malignancy where bisphosphonates are contraindicated (e.g. due to severe renal impairment). Unlike bisphosphonates, denosumab is not cleared by the kidneys. In one case report of a patient with multiple myeloma and severe renal impairment, denosumab therapy was associated with improvement in renal function. There are limited data for its use in the management of resorption related hypercalcaemia due to other causes including sarcoidosis.

Methods
We present the case of a 60 year old female with background chronic kidney disease (CKD), diabetes mellitus with severe retinopathy, non-alcoholic fatty liver disease, hypertension, and previous stroke. She was diagnosed with biopsy-proven sarcoidosis after she was admitted with hypercalcaemia of 3.7mmol/L. Her parathyroid hormone (PTH) was suppressed and total 25 vitamin D was low at 35 nmol/L. CT scan showed splenomegaly and multiple enlarged lymph nodes in the chest and abdomen. Lungs were clear. A CT guided para-aortic lymph node biopsy revealed non-caseating epithelioid granulomas with multinucleated giant cells. Her hypercalcaemia initially responded to intravenous hydration, high doses of oral and intravenous glucocorticoids, and pamidronate. Azathioprine was later started and the dose gradually titrated. However on reducing the dose of oral prednisolone, serum calcium started to rise reaching 2.9mmol/L in February 2019. Her eGFR was 22mL/min. Using FRAX, her 10 year probability of major osteoporotic and hip fracture was 13% and 1.1% respectively.

Results
The patient was given denosumab 60mg via subcutaneous route in March 2019 and her calcium has been normal since (see table). This is associated with improvement in renal function. Her PTH which was suppressed at presentation (0.7) was raised at 21.3 (normal range 1.3 - 9.3) pmol/L when last checked in September 2019, as would be expected in CKD. She is currently on 7mg of prednisolone and gradually weaning off. She remains on azathioprine 100mg BD.

Conclusion
We conclude that denosumab could be an option for the management of hypercalcaemia of sarcoidosis if bisphosphonates are contraindicated. More data are required to establish safety at variable degrees of renal impairment and to identify an optimal dose for this indication.

Disclosures
R. Alshakh None. N. Gendi None.
EP18 Use of anakinra for haemophagocytic lymphohistiocytosis in adults
Authors: Sammut Luke , Murryam Saerrah , Vincent Natalie , Davidson Brian , Edwards Christopher J 
Published: April 2020

Abstract

Background
Haemophagocytic lymphohistiocytosis (HLH) is a rare, life threatening syndrome characterised by severe immune activation. The primary form occurs in early childhood and is fatal without treatment. Secondary HLH can occur at any age, usually in the setting of autoimmune disease, malignancy and infections. Macrophage activation syndrome is a form of HLH occurring in patients with juvenile idiopathic arthritis or other rheumatological conditions. The 2004 paediatric HLH treatment protocol is an established regime of etoposide, dexamethasone and ciclosporin. In recent years, studies have suggested a role for Anakinra in paediatric patients with HLH. We describe our recent experience with Anakinra in adult patients with secondary HLH.

Methods
We performed a retrospective case review study of four adults diagnosed with HLH and treated with anakinra between 2014 and 2018.

Results
Three males and one female with mean age of 35 (18-53) fulfilled the 2004 HLH diagnostic criteria. Three patients had confirmed secondary HLH with the primary trigger being CMV infection, a connective tissue disease (CTD) & T-cell lymphoma and adult-onset Still’s disease. The aetiology of the fourth patient was uncertain although viral infection was likely. Common presenting features were fever, hyperferritinaemia and anaemia. Three patients were neutropaenic and two pancytopaenic. The peak mean ferritin level was 50358µg/L, (10052 - 126808). All patients were treated with anakinra 100mg subcutaneously per day. Ferritin fell rapidly, and at day 7 following treatment, the mean was 3688µg/L (645 - 8957). Three patients achieved initial clinical remission. The first stopped anakinra after 14 days of treatment and has done well, the second has remained on treatment. The third achieved initial clinical remission, stopped anakinra after two months but relapsed and died from atypical pneumonia. The fourth with CTD and T-cell lymphoma had a large drop in ferritin but did not achieve remission and died (Table 1).

Conclusion
HLH is a rare life threatening disorder. Similar to paediatric studies, anakinra appears to reduce ferritin rapidly in adults with secondary HLH. Anakinra may be effective in improving the clinical outcome in adults with non-malignancy associated secondary HLH. However, consistent with previous reports, patients with malignancy associated HLH had a worse survival.

Disclosures
L. Sammut None. S. Murryam None. N. Vincent None. B. Davidson None. C.J. Edwards Honoraria; C.J.E has received support to attend meetings and received honoraria from Amgen.
EP20 Long term safety and efficacy of denosumab and zoledronate
Authors: Alkutobi Ziad , Laila Deena , Tariq Mohammad 
Published: April 2020

Abstract

Background
Denosumab and zoledronate are increasingly prescribed for primary and secondary osteoporosis long-term management.

Methods
A retrospective audit was conducted at Basildon Hospital during 2012-2019 using the NICE guidelines standards to evaluate the long term safety and efficacy of denosumab and zoledronate. Number of patients was 84, diagnosed with osteoporosis or osteopenia, 34 of them received 10 or more denosumab injections and 50 patients planned to receive 5 zoledronate infusions (9 patients received 5 and 38 patients received 4).

Results
Forty percent of the patients were at their 8th decade followed by 28.57% and 21.42 % at their 9th and 7th decades respectively. More than 90% were Caucasian females. Primary prevention was in 39.28% and secondary prevention in 60.71%. The commonest sites of fracture were the wrist and vertebrae at 34.37% for each; followed by the neck of femur and humerous at 12.5% for each. Denosumab was the 1st, 2nd, 3rd or 4th line of treatment in 9.52%, 13.09%, 16.66% and 1.19% respectively; whereas zoledronate was the 1st, 2nd or 3rd line of treatment in 13.09%, 40.47% and 5.95% respectively. The commonest reason for choosing denosumab as the first line was chronic kidney disease, whereas the reason for choosing it as the 2nd or 3rd line was inefficacy of bisphosphonate in 69% or gastrointestinal side effects in 14%. Zoledronate was chosen in all cases because of intolerability to oral bisphosphonate or gastrointestinal side effects. Repeat DXA scan was performed after the 5th, 10th denosumab injections and the 3rd zoledronate infusions. After the 5th Denosumab, DXA scan showed improvement or stability in 100% and 85.29% at the spine and hip respectively whilst deterioration was seen in 14.7% at the hip. After the 10th denosumab, the rate of improvement or stability at the spine was reduced to 88.23% and decline was seen in 2.94%. At the hip area, 73.52% continued to show improvement or stability, whilst 17.66 % showed deterioration. After the 3rd zoledronate, 98% and 88% showed improvement or stability at the spine and hip respectively whilst deterioration seen in 2% and 12% at the spine and hip respectively. One patient on zoledronate experienced dental issues after the 4th injection and stopped treatment. There were no jaw osteonecrosis, no new fractures and no significant side effects with either denosumab or zoledronate. Ninety percent of patients who completed 10 denosumab injections were planned to continue for another 5 injections.

Conclusion
After the period of 3-5 years, denosumab and zoledronate were well tolerated and BMD was either stable or improved at both spinal and hip sites. There were few cases of deterioration mainly at the hip area with both zoledronate and denosumab. Future researches are needed to stratify guidelines on discontinuation of denosumab.

Disclosures
Z. Alkutobi None. D. Laila None. M. Tariq None. A. Nandagudi None.