bluuebunny/crossref_metadata_2025_split huggingface dataset:
The French paediatric cohort of Castleman disease: a retrospective report of 23 patients
Authors: Borocco Charlotte , Ballot-Schmit Claire , Ackermann Oanez , Aladjidi Nathalie , Delaleu Jeremie , Giacobbi-Milet Vannina , Jannier Sarah , Jeziorski Eric , Maurier François , Perel Yves , Piguet Christophe , Oksenhendler Eric , Koné-Paut Isabelle , Galeotti Caroline 
Published: April 2020

Abstract
Background
Castleman disease (CD) is a rare non-malignant lymphoproliferation of undetermined origin. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis confirmation is based on histopathological findings in a lymph node. We attempted to survey all cases of paediatric CD identified to date in France to set up a national registry aiming to improve CD early recognition, treatment and follow-up, within the context of a new national reference center (http://www.castleman.fr).

Methods
In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the paediatric rheumatology society and the Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory.

Results
We identified 23 patients (12 girls) with a diagnosis of UCD (n = 17) and MCD (n = 6) between 1994 and 2018. The mean age at first symptoms was 11.47 ± 4.23 years for UCD and 8.3 ± 3.4 years for MCD. The mean diagnosis delay was 8.16 ± 10.32 months for UCD and 5.16 ± 5.81 years for MCD. In UCD, the initial symptoms were isolated lymph nodes (n = 10) or lymph node associated with other symptoms (n = 7); fever was present in 3 patients. Five patients with MCD presented fever. No patients had HIV or human herpesvirus 8 infection. Autoinflammatory gene mutations were investigated in five patients. One patient with MCD carried a K695R heterozygous mutation in MEFV, another patient with MCD and Duchenne myopathy carried two variants in TNFRSF1A and one patient with UCD and fever episodes carried two heterozygous mutations, in IL10RA and IL36RN, respectively. Treatment of UCD was mainly surgical resection, steroids, and radiotherapy. Treatment of MCD included tocilizumab, rituximab, anakinra, steroids, chemotherapy, and splenectomy. Overall survival after a mean of 6.1 ± 6.4 years of follow-up, was 100% for both forms.

Conclusion
Paediatric CD still seems underdiagnosed, with a significant diagnosis delay, especially for MCD, but new international criteria will help in the future. Unlike adult CD, which is strongly associated with HIV and human herpesvirus 8 infection, paediatric CD could be favored by primary activation of innate immunity and may affect life expectancy less.
HVEM/HIF-1α promoted proliferation and inhibited apoptosis of ovarian cancer cells under hypoxic microenvironment conditions
Authors: Duan Liyan , Tao Jie , Yang Xiaoqian , Ye Lei , Wu Yueqian , He Qizhi , Duan Yingchun , Chen Li , Zhu Jianlong 
Published: April 2020

Abstract
Background
Our previous studies showed the expression of herpes virus entry mediator (HVEM) is high in ovarian cancer samples and correlated to the patient clinic pathological features. As we all know, the hypoxic environment is the main feature of tumor. In this work, we explored the role of HVEM in hypoxic ovarian cancer cells and its effects on HIF-1α, a transcription factor responding to hypoxia.

Methods
The expression of HVEM, HIF-1α and apoptosis-related genes was detected by qRT-PCR and western blot. The proliferation and apoptosis of the ovarian cancer cells were determined with the Cell Counting Kit-8 assay and AnnexinV-FITC/PI-stained flow cytometry assay, respectively.

Results
The expression of HVEM was positively correlated to that of HIF-1α. The expression of HVEM and HIF-1α under hypoxic conditions was higher than that under normoxic conditions, which suggested that the level of HVEM and HIF-1α correlates with prolonged periods of hypoxia in ovarian cancer. The overexpression of HVEM promoted cell proliferation and inhibited cell apoptosis under hypoxic condition. HVEM overexpression elevated the expression of HIF-1α and Bcl-2 (anti-apoptotic protein), and reduced the expression of Bax (pro-apoptotic protein). In addition, overexpression of HVEM activated the AKT/mTOR signaling. Moreover, knockdown of HVEM had the completely opposite effects.

Conclusion
These data indicated that HVEM signaling might promote HIF-1α activity via AKT/mTOR signaling pathway and thus to regulate tumor growth in ovarian cancer under the hypoxic conditions. Furthermore, these findings indicate that this molecular mechanism could represent a therapeutic target for ovarian cancer.
Lifestyle changes and glycemic control in type 1 diabetes mellitus: a trial protocol with factorial design approach
Authors: Sawani Sobiya , Siddiqui Amna Rehana , Azam Syed Iqbal , Humayun Khadija , Ahmed Asma , Habib Aysha , Naz Sabahat , Tufail Mayera , Iqbal Romaina 
Published: April 2020

AbstractBackgroundType 1 diabetes (T1D) has been increasing globally over the past three decades. Self-monitoring of blood glucose is a challenge in both developed as well as developing countries. Self-management guidelines include maintaining logbooks for blood glucose, physical activity, and dietary intake that affect glycated hemoglobin (HbA1c) and a multitude of life-threatening acute complications. Innovative, cost-effective interventions along with beneficial lifestyle modifications can improve home-based self-monitoring of blood glucose in T1D patients. The overall objective of this study is to evaluate the relationship between maintaining log books for blood glucose levels, reinforcement by e-messages, and/or daily step count and changes in HbA1c.Methods/designA randomized controlled trial will enroll participants aged 15 years and above in four groups. Each group of 30 participants will be working with a newly designed standard log book for documenting their blood glucose. The first group will be entirely on routine clinical care, the second group will be on routine care and will receive an additional e-device for recording step count (fit bit), the third group will receive routine care and daily motivational e-messages to maintain the log book, and the fourth group along with routine care will receive an e-device for measuring step count (fit bit) and e-messages about maintaining the log book. Patients will be enrolled from pediatric and endocrine clinics of a tertiary care hospital in Karachi. All groups will be followed up for a period of 6 months to evaluate outcomes. Log book data will be obtained every 3 months electronically or during a patient’s clinic visit. HbA1c as a main outcome will be measured at baseline and will be evaluated twice every 3 months. A baseline questionnaire will determine the socio-demographic, nutritional, and physical activity profile of patients. Clinical information for T1D and other co-morbidities for age of onset, duration, complications, hospitalizations, habits for managing T1D, and other lifestyle characteristics will be ascertained. Behavioral modifications for maintaining daily log books as a routine, following e-messages alone, fit bit alone, or e-messages plus using fit bit will be assessed for changes in HbA1c using a generalized estimated equation.DiscussionThe proposed interventions will help identify whether maintaining log books for blood glucose, motivational e-messages, and/or daily step count will reduce HbA1c levels.Trial registrationClinicalTrials.gov,NCT03864991. March 6, 2019.
Synthesis of new 2-amino-1,3,4-oxadiazole derivatives with anti-salmonella typhi activity evaluation
Authors: Salama Eid E. 
Published: April 2020

AbstractReaction of phenyl acetic acid derivatives with thiosemicarbazide in the presence of POCl3 afforded 5-(4-bromobenzyl)-1,3,4-oxadiazole-2-amine 1 and 5-(3-nitrophenyl)-1,3,4-oxadiazole -2-amine 2. Acylation of the amino group of oxadiazoles 1 and 2 with some acid chlorides such as methyl 4-(chlorocarbonyl) benzoate, 3-nitrobenzoyl chloride, 4-methoxy-benzoyl chloride, 4-isobutylbenzoyl chloride and chloroacetyl chloride yielded the acylated compounds 3–8. Cyclization of acetamides 7 and 8 by reaction with ammonium thiocyanate gave the thiazolidinones 9 and 10. Coupling of chloroacetamide 7 with two mercaptothiazoles gave coupled heterocyclic derivatives 11 and 12. Coupling of amino-oxadiazole 1 with N-Boc-glycine and N-Boc-phenylalanine lead to the formation of 16 and 17 respectively. All compounds were screened for their antibacterial activity against Salmonella typhi where compounds 3, 4, 10, 11 and 15 showed significant activity. Structures of the new synthesized compounds were confirmed using the spectral analysis such as IR, 1H NMR and 13C NMR and mass spectrometry.
Phlebotomine sand flies in Southwest Germany: an update with records in new locations
Authors: Oerther Sandra , Jöst Hanna , Heitmann Anna , Lühken Renke , Krüger Andreas , Steinhausen Irmgard , Brinker Christine , Lorentz Susanne , Marx Michael , Schmidt-Chanasit Jonas , Naucke Torsten , Becker Norbert 
Published: April 2020

Abstract
Background
Vector-borne diseases (VBD) are of growing global importance. Sand flies are potential vectors for phleboviruses (family Phenuiviridae) including Toscana virus (TOSV), Sicilian virus, Sandfly fever, Naples virus, and Leishmania parasites in Europe. To date, only two phlebotomine species have been recorded for Germany: Phlebotomus perniciosus and Phlebotomus mascittii. This study updates the distribution and abundance of the two occurring species.

Methods
An entomological field study was carried out during 2015–2018 to assess the abundance of sand flies in Southwest Germany within the federal states Baden-Wuerttemberg (BW) and Rhineland-Palatinate (RLP). A total of 176 collection sites were examined using CDC light traps.

Results
A total of 149 individuals of P. mascittii were collected. During 2015–2018, P. mascittii was found at all sites known positive from previous studies and was detected at 15 additional sites previously unknown for the presence of sand flies. Although the environment has changed considerably in 30 years, no significant difference in sand fly dynamics and distribution was found. Phlebotomus perniciosus has only been trapped once since 2001.

Conclusions
This study showed that sand flies occur in different areas in Southern Germany where they had not been recorded previously. Therefore, it can be assumed that they are more widespread than expected. In addition, sand flies could be found over several years at the same trapping sites, indicating population stability. This supports the need for continued surveillance of possible vector populations and urgent clarification of the vector competence of P. mascittii.
Don’t let sleeping dogs lie: unravelling the identity and taxonomy of Babesia canis, Babesia rossi and Babesia vogeli
Authors: Penzhorn Barend L. 
Published: April 2020

AbstractFor most of the 20th century the causative agent of canine babesiosis, wherever it occurred in the world, was commonly referred to as Babesia canis. Early research, from the 1890s to the 1930s, had shown that there were three distinctly different vector-specific parasite entities occurring in specific geographical regions, that host response to infection ranged from subclinical to acute, and that immunity to one stock of the parasite did not necessarily protect against infection with other stocks. This substantial body of knowledge was overlooked or ignored for 50 years. In this review the first records and descriptions of the disease in four geographical regions were traced: sub-Saharan Africa, Europe, North Africa and Asia. Research leading to identification of the specific tick vector species involved is documented. Evidence is given of the growing realisation that there were substantial biological differences between stocks originating from different geographical regions. Etymological provenance for Babesia vogeli is proposed.
Pro-fibrinolytic potential of the third larval stage of Ascaris suum as a possible mechanism facilitating its migration through the host tissues
Authors: Diosdado Alicia , Simón Fernando , Morchón Rodrigo , González-Miguel Javier 
Published: April 2020

Abstract
Background
Ascaris roundworms are the parasitic nematodes responsible for causing human and porcine ascariasis. Whereas A. lumbricoides is the most common soil-transmitted helminth infecting humans in the world, A. suum causes important economic losses in the porcine industry. The latter has been proposed as a model for the study of A. lumbricoides since both species are closely related. The third larval stage of these parasites carries out an intriguing and complex hepatopulmonary route through the bloodstream of its hosts. This allows the interaction between larvae and the physiological mechanisms of the hosts circulatory system, such as the fibrinolytic system. Parasite migration has been widely linked to the activation of this system by pathogens that are able to bind plasminogen and enhance plasmin generation. Therefore, the aim of this study was to examine the interaction between the infective third larval stage of A. suum and the host fibrinolytic system as a model of the host-Ascaris spp. relationships.

Methods
Infective larvae were obtained after incubating and hatching fertile eggs of A. suum in order to extract their cuticle and excretory/secretory antigens. The ability of both extracts to bind and activate plasminogen, as well as promote plasmin generation were assayed by ELISA and western blot. The location of plasminogen binding on the larval surface was revealed by immunofluorescence. The plasminogen-binding proteins from both antigenic extracts were revealed by two-dimensional electrophoresis and plasminogen-ligand blotting, and identified by mass spectrometry.

Results
Cuticle and excretory/secretory antigens from infective larvae of A. suum were able to bind plasminogen and promote plasmin generation in the presence of plasminogen activators. Plasminogen binding was located on the larval surface. Twelve plasminogen-binding proteins were identified in both antigenic extracts.

Conclusions
To the best of our knowledge, the present results showed for the first time, the pro-fibrinolytic potential of infective larvae of Ascaris spp., which suggests a novel parasite survival mechanism by facilitating the migration through host tissues.
Exploring the relationship between susceptibility to canine leishmaniosis and anti-Phlebotomus perniciosus saliva antibodies in Ibizan hounds and dogs of other breeds in Mallorca, Spain
Authors: Burnham Alexis C. , Ordeix Laura , Alcover M. Magdalena , Martínez-Orellana Pamela , Montserrat-Sangrà Sara , Willen Laura , Spitzova Tatiana , Volf Petr , Solano-Gallego Laia 
Published: April 2020

AbstractBackgroundCanine leishmaniosis caused byLeishmania infantumis a neglected zoonosis transmitted by sand flies likePhlebotomus perniciosus. Clinical signs and disease susceptibility vary according to various factors, including host immune response and breed. In particular, Ibizan hounds appear more resistant. This immunocompetence could be attributed to a more frequent exposure to uninfected sand flies, eliciting a stronger anti-sand fly saliva antibody response.MethodsThis study aimed to investigate the prevalence of anti-P. perniciosussaliva antibodies in Ibizan hounds and dogs of other breeds in theLeishmania-endemic area of Mallorca, Spain, and to correlate these antibody levels with clinical, immunological and parasitological parameters. Anti-sand fly saliva IgG was examined in 47 Ibizan hounds and 45 dogs of other breeds using three methods:P. perniciosuswhole salivary gland homogenate (SGH) ELISA; recombinant protein rSP03B ELISA; and rSP03B rapid tests (RT). Additionally, diagnostic performance was evaluated between methods.ResultsResults indicate significantly higher anti-SGH antibodies (P = 0.0061) and a trend for more positive SGH ELISA and RT results in Ibizan hounds compared to other breeds. General linear model analysis also found breed to be a significant factor in SGH ELISA units and a marginally significant factor in RT result. Although infection rates were similar between groups, Ibizan hounds included significantly more IFN-γ producers (P = 0.0122) and papular dermatitis cases (P< 0.0001). Older age andL. infantumseropositivity were also considered significant factors in sand fly saliva antibody levels according to at least one test. Fair agreement was found between all three tests, with the highest value between SGH and rSP03B RT.ConclusionsTo our knowledge, this is the first study elaborating the relationship between anti-P. perniciosussaliva antibodies and extensive clinical data in dogs in an endemic area. Our results suggest that Ibizan hounds experience a higher frequency of exposure to sand flies and have a stronger cellular immune response toL. infantuminfection than other breed dogs. Additional sampling is needed to confirm results, but anti-P. perniciosussaliva antibodies appear to negatively correlate with susceptibility toL. infantuminfection and could possibly contribute to the resistance observed in Ibizan hounds.
Fast multiplex real-time PCR assay for simultaneous detection of dog and human blood and Leishmania parasites in sand flies
Authors: Sales Kamila Gaudêncio da Silva , Miranda Débora Elienai de Oliveira , Paiva Marcelo Henrique Santos , Figueredo Luciana Aguiar , Otranto Domenico , Dantas-Torres Filipe 
Published: April 2020

Abstract
Background
The blood-feeding behaviour of female sand flies may increase their likelihood of acquiring and transmitting Leishmania parasites. Studies on the host usage by these insects may thus improve our understanding of the Leishmania transmission risk in leishmaniasis-endemic areas. Here, we developed a fast multiplex real-time PCR assay for simultaneous detection of dog, human and Leishmania DNA in sand flies.

Methods
Primers and TaqMan probes targeting the mitochondrial cytochrome c oxidase subunit 1 and cytochrome b genes of dog and human, respectively, were combined in a multiplex assay, which also includes primers and a TaqMan probe targeting the Leishmania minicircle kinetoplast DNA.

Results
The multiplex assay was 100% specific, with analytical sensitivities of 103 fg/reaction for dog and human and 1 fg for Leishmania. By testing field-collected engorged female sand flies (95 Migonemyia migonei and two Nyssomyia intermedia), 50 M. migonei were positive for one or two targets (positivity rates: 45.4% for human, 4.1% for dog and 12.4% for Leishmania DNA).

Conclusions
This multiplex real-time PCR assay represents a novel fast assay for detecting dog, human and Leishmania DNA in female sand flies and therefore a tool for assessing the risk of Leishmania transmission to these hosts in areas of active transmission.
Data quality predicts care quality: findings from a national clinical audit
Authors: Yates Mark , Bechman Katie , Dennison Elaine M. , MacGregor Alexander J. , Ledingham Jo , Norton Sam , Galloway James B. 
Published: April 2020

Abstract
Background
Missing clinical outcome data are a common occurrence in longitudinal studies. Data quality in clinical audit is a particular cause for concern. The relationship between departmental levels of missing clinical outcome data and care quality is not known. We hypothesise that completeness of key outcome data in a national audit predicts departmental performance.

Methods
The National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis (NCAREIA) collected data on care of patients with suspected rheumatoid arthritis (RA) from early 2014 to late 2015. This observational cohort study collected data on patient demographics, departmental variables, service quality measures including time to treatment, and the key RA clinical outcome measure, disease activity at baseline, and 3 months follow-up. A mixed effects model was conducted to identify departments with high/low proportions of missing baseline disease activity data with the results plotted on a caterpillar graph. A mixed effects model was conducted to assess if missing baseline disease activity predicted prompt treatment.

Results
Six thousand two hundred five patients with complete treatment time data and a diagnosis of RA were recruited from 136 departments. 34.3% had missing disease activity at baseline. Mixed effects modelling identified 13 departments with high levels of missing disease activity, with a cluster observed in the Northwest of England. Missing baseline disease activity was associated with not commencing treatment promptly in an adjusted mix effects model, odds ratio 0.50 (95% CI 0.41 to 0.61, p < 0.0001).

Conclusions
We have shown that poor engagement in a national audit program correlates with the quality of care provided. Our findings support the use of data completeness as an additional service quality indicator.
Correction to: Investigating psychometric properties of the Thai version of the Zarit Burden Interview using rasch model and confirmatory factor analysis
Authors: Pinyopornpanish Kanokporn , Pinyopornpanish Manee , Wongpakaran Nahathai , Wongpakaran Tinakon , Soontornpun Atiwat , Kuntawong Pimolpun 
Published: April 2020

Following the publication of the original article [1], the authors unfortunately became aware of the following errors in Table 3:
AutoGrow4: an open-source genetic algorithm for de novo drug design and lead optimization
Authors: Spiegel Jacob O. , Durrant Jacob D. 
Published: April 2020

AbstractWe here present AutoGrow4, an open-source program for semi-automated computer-aided drug discovery. AutoGrow4 uses a genetic algorithm to evolve predicted ligands on demand and so is not limited to a virtual library of pre-enumerated compounds. It is a useful tool for generating entirely novel drug-like molecules and for optimizing preexisting ligands. By leveraging recent computational and cheminformatics advancements, AutoGrow4 is faster, more stable, and more modular than previous versions. It implements new docking-program compatibility, chemical filters, multithreading options, and selection methods to support a wide range of user needs. To illustrate both de novo design and lead optimization, we here apply AutoGrow4 to the catalytic domain of poly(ADP-ribose) polymerase 1 (PARP-1), a well characterized DNA-damage-recognition protein. AutoGrow4 produces drug-like compounds with better predicted binding affinities than FDA-approved PARP-1 inhibitors (positive controls). The predicted binding modes of the AutoGrow4 compounds mimic those of the known inhibitors, even when AutoGrow4 is seeded with random small molecules. AutoGrow4 is available under the terms of the Apache License, Version 2.0. A copy can be downloaded free of charge from http://durrantlab.com/autogrow4.