bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre‐clinical pharmacological profile of QF‐036, a potent HIV‐1 maturation inhibitor
Authors: Zhao Li , He Hong‐Hong , Ou‐Yang Ting , Liu Di‐Fa , Jiang Chun‐Hong , Yang He‐Ping , Wang Pei , Xie Ning , Yan Shou‐Sheng
Published: October 2020

QF‐036 is an HIV‐1 maturation inhibitor in pre‐clinical development, and its antiviral activity against a laboratory HIV‐1 strain and two drug‐resistant strains was determined in the C8166 line. QF‐036 was also subjected to absorption, distribution and metabolism (ADM) assessment in vitro, and pharmacokinetic profiles were evaluated in rats and monkeys. The 50% effective concentrations (EC50) of QF‐036 against the three strains were 20.36 nM, 0.39 μM and 2.11 nM, respectively, demonstrating better antiviral potential than the first‐generation antiviral maturation inhibitor bevirimat. QF‐036 demonstrated moderate cell permeability, high plasma protein binding ability and good metabolic stability in vitro. After oral QF‐036 administration to rats and monkeys, both species exhibited moderate bioavailability, and the plasma drug exposure increased in an approximately dose‐proportional manner. When administered orally (30 mg/kg) to monkeys, the QF‐036 plasma concentration (Cmax) peaked at 3671 ng/mL (4.82 μM), 12 to 2410 times higher than the EC50 of laboratory or resistant HIV‐1 strains. Moreover, the plasma concentration of QF‐036 at 12 hours after administration was 263 ng/mL (0.35 μM), which approximately matched the highest EC50 value of the three test strains. The favourable viral inhibitory activity and pharmacokinetic properties provide critical support for QF‐036 as a promising anti‐HIV therapeutic candidate.
Species distribution models predict the geographic expansion of an enzootic amphibian pathogen
Authors: Zumbado‐Ulate Héctor , García‐Rodríguez Adrián , Searle Catherine L.
Published: October 2020

Globally, numerous amphibian species have declined due to the introduction of the chytrid fungus Batrachochytrium dendrobatidis (Bd). However, the understanding of the spatiotemporal dynamics remains incomplete. Therefore, estimating the current geographic distribution of Bd is urgently needed, especially in countries like Costa Rica, where susceptible species are still recovering from Bd‐driven declines. We conducted model tuning and spatial analysis to compare the habitat suitability for epizootic and enzootic Bd in Costa Rica and to identify data‐deficient regions, opportunistic sampling, and Bd hotspots. Our dataset combined two methods of detection (histology and PCR methods) for a total of 451 Bd‐positive records from 34 localities. We found that the distribution of enzootic Bd in Costa Rica increased 60% since previous estimates in the early 2000s and extended to highlands and dry lowlands that were considered unsuitable for Bd. We also found that Bd is common across protected lands (80%) and within the herpetological provinces containing the highest amphibian richness and endemism in Costa Rica. Opportunistic sampling of Bd has focused on sites where epizootics occurred with the strongest intensity, leading to deficient or absent sampling across the Talamanca Range, the Nicoya Peninsula, and the northern lowlands. Our results showed that PCR increased the power of Bd detection in lowlands and favored the identification of Bd hotspots across the Caribbean side of Costa Rica. Our results add to the understanding of disease spread during enzootics and can be used to identify new hotspots for disease to mitigate future outbreaks of this pathogen.

Abstract in Spanish is available with online material
Microwave ablation of symptomatic benign thyroid nodules: Short‐ and long‐term effects on thyroid function tests, thyroglobulin and thyroid autoantibodies
Authors: Erturk Mehmet Sercan , Cekic Bulent , Celik Mehmet , Ucar Havva
Published: October 2020

Objective

Microwave ablation therapy has been attracting great attention due to its advantages such as low complication rate, good cosmetic results and effective nodule shrinking. Although the effect of thermal ablation therapy on the nodule volume reduction rate has been shown several studies, a limited number of papers have been reported for the effects of microwave ablation (MWA) on thyroid function tests. The aim of this study was to investigate the short‐ and long‐term effects of MWA therapy on thyroid function tests (TFTs), thyroglobulin (Tg) and thyroid autoantibodies in euthyroid patients.

Design, patients and measurements

Demographic data of the patients, TFTs, Tg, thyroid autoantibodies and thyroid volume of the nodules were recorded before the procedure and follow‐up. Any differences in serum thyroid hormone levels were investigated in pre‐, post‐ and 6‐month follow‐up periods before and after MWA.

Results

The difference between all thyroid hormone levels at pre MWA and 24 h after MWA was statistically significant (p < .001). FT3 (4.62) pmol/L and FT4 (10.81) pmol/L median levels increased significantly (p < .001), while thyrotropin (TSH) levels decreased at 24 h after MWA (p < .001). Thyroid antibodies levels were not statistically different at 6‐month (p > .05), whereas Tg levels decreased (p < .001) compared to pre MWA.

Conclusions

While no significant effect was observed at 6 month, the effect of MWA on thyroid function tests was prominent at 24 h.
Identifying factors associated with spontaneous restoration of hearing in children with otitis media with effusion
Authors: Edwards Lowri , Cannings‐John Rebecca , Butler Christopher , Francis Nick
Published: October 2020

Objectives

To identify predictors of acceptable hearing at 5 weeks, 6 and 12 months in children with bilateral otitis media with effusion (OME).

Design and setting

Secondary analysis of OSTRICH data, conducted in hospital ear, nose and throat (ENT) and paediatric audiology and audiovestibular medicine departments across Wales and England.

Participants

The OSTRICH study included 389 children aged 2‐8 years with bilateral hearing loss attributable toOME for at least 3 months.

Main outcome measures

Baseline, 5‐week, 6‐ and 12‐month audiology measurements were collected and logistic regression models used to identify pre‐randomisation baseline variables that predicted return of acceptable hearing, which was defined as less than or equal to 20 dB hearing loss averaged within the frequencies of 0.5, 1, 2 and 4 kHz in at least one ear in children assessed by pure tone audiometry, ear‐specific insert visual reinforcement audiometry or ear‐specific play audiometry less than or equal to 25 dB hearing loss averaged within the frequencies of 0.5, 1, 2 and 4 kHz in children assessed by sound‐field visual reinforcement audiometry or sound‐field performance/play audiometry, based on national guidelines.

Results

Less severe baseline hearing loss across both ears most consistently predicted acceptable hearing at 5 weeks (adjusted odds ratio [aOR] 0.91, 95% CI 0.87‐0.95), 6 months (0.94 [0.90‐0.98]) and 12 months (0.93 [0.89‐0.97]). Negative history of atopy (2.05 [1.16‐3.61]), never using hearing aids (aOR 2.16 [1.04‐4.48]), and being male (1.75 [1.02‐2.99]) were significant at 6 months, but not at 12 months. Symptom duration was a predictor at 5 weeks, but not at 6 or 12 months.

Conclusions

Milder baseline hearing loss most consistently predicts acceptable hearing at 5 weeks, 6 and 12 months in children with chronic OME. Negative history of atopy, never using hearing aids, and male gender are associated with better prognosis. These predictors can be used to identify children that may not require treatment.
Can a brief assessment of social support predict outcomes after bariatric surgery?
Authors: Hilgendorf William , Monfared Sara , Monfared Sina Hassan Beygi , Athanasiadis Dimitrios I. , Selzer Don , Choi Jennifer N. , Banerjee Ambar , Stefanidis Dimitrios
Published: October 2020

Social support is important to optimize bariatric surgery outcomes, but limited tools exist for brief and effective assessment preoperatively. The aims of the study were to determine the extent to which two ratings of social support can predict bariatric surgery outcomes, and to examine any associations between these two methods.In this retrospective study, patients were included for whom the Cleveland clinic behavioral rating system (CCBRS) and Flanagan quality of life scale (FQoLS) scores were obtained as part of their preoperative psychosocial evaluation. They were followed up for 6 to 24 months after bariatric surgery. Linear and logistic regressions were performed with patients' CCBRS and FQoLS scores as independent variables, and percent excess weight loss (%EWL), length of stay (LOS), complications, readmissions and loss to follow‐up as dependent variables. The prediction of CCBRS ratings from FQoLS social support items was also evaluated. A total of 415 patients were included in the analysis. There were significant associations between the CCBRS and three of the four relevant FQoLS self‐ratings. As CCBRS and FQoLS scores increased, complications decreased significantly. The CCBRS alone additionally predicted decreased length of hospital stay and approached significance for predicting decreased readmission rates. There were no associations between %EWL and behavior ratings. The degree of patients' social support is associated with important bariatric surgery outcomes. It is possible to obtain this valuable information via the administration of brief assessments prior to bariatric surgery.
Combination of endosonography‐guided fine‐needle aspiration and conventional endoscopic techniques in sarcoidosis diagnosis. Optimal strategy to achieve high diagnostic yield
Authors: Kasper Lukasz , Andrychiewicz Anna , Gross‐Sondej Iwona , Soja Jerzy , Kasper Marta , Tomaszewska Romana , Urbanczyk Katarzyna , Sladek Krzysztof
Published: October 2020

Introduction

Diagnosis of sarcoidosis is based on clinical status and radiologic specific findings. Tissue confirmation of noncaseating granulomas is crucial. Pathological confirmation of pulmonary sarcoidosis is most commonly accomplished by bronchoscopy, which has a diagnostic yield of approximately 60%–70%.

Objectives

In this prospective study, we analysed potential benefit of EBUS‐TBNA and EBB combination, application of cell blocks and smears with puncturing more than one station of lymph nodes in order to determine optimal strategy in diagnosis of sarcoidosis.

Methods

About 133 patients with suspicion of sarcoidosis (stage I and stage II) were included in this study. Each patient underwent conventional bronchoscopy with endobronchial biopsy (EBB) followed by the EBUS and puncturing at least two different lymph node stations.

Results

Positive cytopathological verification of sarcoidosis in our study was obtained in 123 patients (92.5%). EBUS‐TBNA was diagnostic in 116 patients (87.2%). EBB was positive in 26 patients (19.55%). Combination of EBUS‐TBNA and EBB statistically increased diagnostic yield of sarcoidosis to 92.5%. Sensitivity of EBUS‐TBNA with EBB was 93.9%, specificity 100%, PPV 100% and NPV 20%.

Conclusions

Combining EBUS‐TBNA from at least two lymph node stations and EBB increased diagnostic yield of sarcoidosis. Such diagnostic strategy had almost 93% of diagnostic yield in stage I and stage II of sarcoidosis. Taking into account the safety of the whole procedure with endobronchial ultrasonography combined with conventional endoscopy with EBB and its cost effectiveness, TBLB can be intended to diagnose stage III or IV of pulmonary sarcoidosis.
Shielding method for the endoscopic procedures during the COVID‐19 pandemic
Authors: Kikuchi Daisuke , Suzuki Yugo , Hoteya Shu
Published: October 2020

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Absent pulmonary valve or pulmonary atresia with intact ventricular septum: Which is it?
Authors: Nealon Erin , Berman Darren , Rowland Daniel , Boe Brian , Lloyd Eric , Cua Clifford L.
Published: October 2020

A fetal echocardiogram noted valvar pulmonary atresia vs critical pulmonary valve stenosis, confluent pulmonary arteries, patent ductus arteriosus, and an apical muscular ventricular septal defect vs coronary sinusoid. Postnatal echocardiogram documented an absent pulmonary valve, coronary artery fistula to the right ventricle, confluent pulmonary arteries, and a patent ductus arteriosus. Catheterization confirmed the postnatal echocardiographic findings except there was no antegrade flow from the right ventricle to the pulmonary arteries. Close evaluation of all imaging modalities revealed the final diagnosis of absent pulmonary valve with a double‐chambered right ventricle with no egress from the right ventricle to pulmonary artery.
Isolated papillary muscle rupture with nonobstructive coronary artery disease, minimal myocardial infarction, and normal wall motion
Authors: Nakou Eleni S. , Theodoropoulos Konstantinos C. , Shaikh Hizbullah , Amin‐Youssef George , Monaghan Mark J. , Papachristidis Alexandros
Published: October 2020

Papillary muscle (PM) rupture can usually complicate inferior or posterior myocardial infarctions, but selective PM infarction is extremely rare, and the exact underlying pathophysiological mechanism is not entirely clear. We present a case of PM rupture due to isolated PM infarction in a patient with unobstructed coronary arteries, which could be misdiagnosed as a vegetation or other mass given the absence of regional wall motion abnormalities (RWMAs) on transthoracic echocardiogram. Our case highlights that in patients with severe mitral regurgitation and associated mitral valve mass, the absence of RWMAs should not exclude ischemic PM rupture from differential diagnosis.
Spatio‐temporal responses of butterflies to global warming on a Mediterranean island over two decades
Authors: Colom Pau , Traveset Anna , Carreras David , Stefanescu Constantí
Published: October 2020

1. One very conspicuous sign that warming is affecting the ecology of butterflies are the phenological advances occurring in many species. Moreover, rising temperatures are having a notable impact – both negative and positive – on population abundances. To date, patterns have generally been analysed at species level without taking into account possible differences between populations, which, when they are noted, are mostly attributed to large‐scale climate differences across a latitudinal gradient.

2. We use a long‐term database (18 years) of butterflies from five sites of the island of Menorca (Balearic Islands, Spain) to investigate how phenology and population dynamics have been affected by climate warming during the past two decades.

3. Both species' phenology and abundance respond differently to warming at a local scale depending on the season. Rising temperatures in spring give rise to greater advancement of the phenology, whereas warming affects population abundance negatively in summer. Additional variability of responses among sites suggests that habitats are involved in the modulation of the aforementioned seasonal effect.

4. We discuss how the effects of temperature could be partially offset in more inland habitats such as forests or deep ravines, especially the latter which represent particularly fresh and humid environments. The positive effect of temperature on ravine populations during the summer suggests that butterflies disperse across habitats as a response to rising temperatures during the season. This dispersal behaviour as a response to warming could be especially important in island ecosystems where the possibilities of modifying altitudinal or latitudinal distributions are often severely limited.
Students’ views on the sustained impact of a learning approach developed by blending pedagogy to prepare for professional practice: Introducing “Daybook”
Authors: Hanks Sally J. , Coelho Catherine S.
Published: October 2020

Introduction

Daybook is an enquiry‐based teaching and learning approach that blends various adult learning theories. It is designed to equip and prepare a new graduate to do a designated job in the workplace. It supports the safe beginner to undertake high‐level thinking that permits adaptation to unfamiliar challenges of the job, as well as use of continuous learning strategies to do the job better. Its aim is to support four main pedagogic pillars of learning: preparing for practice, educating for employability, enhancing capability over competence and lifelong learning.

Methods

A study using three successive student cohorts evaluated the perceived sustained impact of Daybook on learners’ clinical practice following graduation and entry into the workplace. Using a questionnaire with open‐ended, opinion and closed questions, descriptive quantitative analysis was used on numerical data, and qualitative data underwent a deductive thematic analysis.

Results

Quantitative and qualitative results supported one another to identify that the four pedagogic pillars of learning were all impacted positively by use of Daybook. Enhancing capability was the most influenced area. Each of the four areas, although discrete academic entities, demonstrated overlap and commonality.

Conclusions

Although an academic exercise, Daybook is perceived to support users’ undergraduate learning across the four domains of educating for employability, preparing for practice, enhancing capability and lifelong learning, and this impact sustains through the transition from student to independent practitioner when they qualify.
Students´ preparedness, learning habits and the greatest difficulties in studying Histology in the digital era: A comparison between students of general and dental schools
Authors: Tauber Zdenek , Lacey Helena , Lichnovska Radka , Erdosova Bela , Zizka Radovan , Sedy Jiri , Cizkova Katerina
Published: October 2020

Introduction

There are only sporadic references in literature regarding general medicine and dentistry student´s preparedness for Histology, study resources and how students might use them in the era of virtual microscopy.

Methods

A structured questionnaire was used to evaluate students´ opinion, with 192 students of general medicine and 82 students of dentistry responding.

Results

The dentistry students evaluate their previous knowledge of basic high school disciplines as less helpful when compared to their general medicine colleagues, but this difference diminishes during the first year of medical school studies. Students of dentistry display a better orientation in the amount of study resources (electronic vs printed) and also the ways of their use (practical vs theoretical preparation). The main problems surfacing in the study of Histology have been: the lack of time due to the high demands of Anatomy, problems with correct identification of structures in specimens and correct orientation in a large number of available study resources. Students indicate that they would appreciate the introduction of interactive exercise tests to verify practical and theoretical knowledge.

Conclusion

We revealed significant differences between students of general medicine and dentistry in terms of student´s preparedness and learning habits. According to our findings, it is still necessary to further develop teaching methods utilising virtual microscopy, taking into account the needs of both general medicine and dental school students.
STEM colonization: Applying hard sciences' socio‐organisational patterns and evaluation procedures to the soft sciences in Croatia
Authors: Brajdić Vuković Marija , Vignjević Korotaj Bojana , Ćulum Ilić Bojana
Published: October 2020

Academic systems are undergoing changes in which the social organisation of research as well as patterns of scientific productivity in the humanities and social sciences progressively resemble those in hard sciences. The hard and soft sciences are increasingly converging. This development can be observed in (a) publishing patterns, (b) the division of research, and (c) the internationalisation of research. This study explored the extent to which these changes occurring in academic systems in terms of a transformation of disciplinary practices are also becoming a trend in transitional post‐socialist countries. We used Croatia as a case of a post socialist transitional context and compared it to Slovenia, a country with a similar past but somewhat different science policies and strategies. The results point to increasing convergence in some soft disciplines, visible in projectification and internationalisation of academic work as well as a significant change in the publishing patterns.
Identifying key factors for improving ICA‐based decomposition of EEG data in mobile and stationary experiments
Authors: Klug Marius , Gramann Klaus
Published: October 2020

Recent developments in EEG hardware and analyses approaches allow for recordings in both stationary and mobile settings. Irrespective of the experimental setting, EEG recordings are contaminated with noise that has to be removed before the data can be functionally interpreted. Independent component analysis (ICA) is a commonly used tool to remove artifacts such as eye movement, muscle activity, and external noise from the data and to analyze activity on the level of EEG effective brain sources. The effectiveness of filtering the data is one key preprocessing step to improve the decomposition that has been investigated previously. However, no study thus far compared the different requirements of mobile and stationary experiments regarding the preprocessing for ICA decomposition. We thus evaluated how movement in EEG experiments, the number of channels, and the high‐pass filter cutoff during preprocessing influence the ICA decomposition. We found that for commonly used settings (stationary experiment, 64 channels, 0.5 Hz filter), the ICA results are acceptable. However, high‐pass filters of up to 2 Hz cut‐off frequency should be used in mobile experiments, and more channels require a higher filter to reach an optimal decomposition. Fewer brain ICs were found in mobile experiments, but cleaning the data with ICA has been proved to be important and functional even with low‐density channel setups. Based on the results, we provide guidelines for different experimental settings that improve the ICA decomposition.
Peripheral nerve regeneration following injury is altered in mice lacking P2X7 receptor
Authors: Magnaghi Valerio , Martin Sarah , Smith Patrick , Allen Luke , Conte Vincenzo , Reid Adam J. , Faroni Alessandro
Published: October 2020

Peripheral nerve injuries are debilitating, and current clinical management is limited to surgical intervention, which often leads to poor functional outcomes. Development of pharmacological interventions aimed at enhancing regeneration may improve this. One potential pharmacological target is the P2X purinergic receptor 7 (P2X7R) expressed in Schwann cells, which is known to play a role during the development of the peripheral nerves. Herein, we analysed differences in regeneration between genetically engineered P2X7 knockout mice and wild‐type controls, using in vivo and ex vivo models of peripheral nerve regeneration. We have found that the speed of axonal regeneration is unaltered in P2X7 knockout mice, nevertheless regenerated P2X7 knockout nerves are morphologically different to wild‐type nerves following transection and immediate repair. Indeed, the detailed morphometric analysis at 4 and 8 weeks after injury showed evidence of delayed remyelination in P2X7 knockout mice, compared to the wild‐type controls. Furthermore, the Wallerian degeneration phase was unaltered between the two experimental groups. We also analysed gene expression changes in the dorsal root ganglia neurones as a result of the peripheral nerve injury, and found changes in pathways related to pain, inflammation and cell death. We conclude that P2X7 receptors in Schwann cells may be a putative pharmacological target to control cell fate following injury, thus enhancing nerve re‐myelination.
Thalamohippocampal atrophy in focal epilepsy of unknown cause at the time of diagnosis
Authors: Leek N. J. , Neason M. , Kreilkamp B. A. K. , de Bezenac C. , Ziso B. , Elkommos S. , Das K. , Marson A. G. , Keller S. S.
Published: October 2020

Background and purpose

Patients with chronic focal epilepsy may have atrophy of brain structures important for the generation and maintenance of seizures. However, little research has been conducted in patients with newly diagnosed focal epilepsy (NDfE), despite it being a crucial point in time for understanding the underlying biology of the disorder. We aimed to determine whether patients with NDfE show evidence of volumetric abnormalities of subcortical structures.

Methods

Eighty‐two patients with NDfE and 40 healthy controls underwent magnetic resonance imaging scanning using a standard clinical protocol. Volume estimation of the left and right hippocampus, thalamus, caudate nucleus, putamen and cerebral hemisphere was performed for all participants and normalised to whole brain volume. Volumes lower than two standard deviations below the control mean were considered abnormal. Volumes were analysed with respect to patient clinical characteristics, including treatment outcome 12 months after diagnosis.

Results

Volume of the left hippocampus (p(FDR‐corr) = 0.04) and left (p(FDR‐corr) = 0.002) and right (p(FDR‐corr) = 0.04) thalamus was significantly smaller in patients relative to controls. Relative to the normal volume limits in controls, 11% patients had left hippocampal atrophy, 17% had left thalamic atrophy and 9% had right thalamic atrophy. We did not find evidence of a relationship between volumes and future seizure control or with other clinical characteristics of epilepsy.

Conclusions

Volumetric abnormalities of structures known to be important for the generation and maintenance of focal seizures are established at the time of epilepsy diagnosis and are not necessarily a result of the chronicity of the disorder.
Sometimes they come back: New and old spinal muscular atrophy adults in the era of nusinersen
Authors: Sansone V. A. , Coratti G. , Pera M. C. , Pane M. , Messina S. , Salmin F. , Albamonte E. , De Sanctis R. , Sframeli M. , Di Bella V. , Morando S. , d’Amico A. , Frongia A. L. , Antonaci L. , Pirola A. , Pedemonte M. , Bertini E. , Bruno C. , Mercuri E. ,   the Italian ISMAC group
Published: October 2020

Background and purpose

Following the commercial availability of nusinersen, there have been a number of new referrals of adults with spinal muscular atrophy (SMA) not regularly followed in tertiary‐care centers or enrolled in any disease registry.

Methods

We compared demographics and disease characteristics, including assessment of motor and respiratory function, in regularly followed patients and newcomers subdivided according to the SMA type.

Results

The cohort included 166 adult patients (mean age: 37.09 years): one type I, 65 type II, 99 type III, and one type IV. Of these 166, there were 67 newcomers. There was no significant difference between newcomers and regularly followed patients in relation to age and disease duration. The Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module scores were higher in the regularly followed patients compared to newcomers in the whole cohort and in both SMA II and II. A difference was also found on ventilatory status (p = 0.013) and Cobb’s angle >50° (p = 0.039) between the two subgroups. No difference was found in scoliosis surgery prevalence (p > 0.05).

Conclusions

Our results showed differences between the two subgroups, even if less marked in the type III patients. In the type II patients, there was a higher proportion of newcomers who were in the severe end of the spectrum. Of the newcomers, only approximately a third initiated treatment, as opposed to the 51% in the regularly followed patients. The identification of patients who were not part of the registries will help to redefine the overall prevalence of SMA and the occurrence of different phenotypes.
Humoral antibody response of 10 horses after vaccination against African horse sickness with an inactivated vaccine containing all 9 serotypes in one injection
Authors: Wernery Ulrich , Rodriguez Marina , Raghavan Rekha , Syriac Ginu , Miriam Thomas M Shruti , Elizabeth Shyna K. , Federico Ronchi Gaetano , Muhammed Rubeena , Patteril Nissy A. , Joseph Sunitha
Published: October 2020

Background

African horse sickness (AHS) is a devastating viral disease of equids that was first recorded in 1327. Currently, prevention and control of the disease are based on attenuated vaccines and midge control. It has been shown that attenuated Orbivirus vaccines are not always safe as they may reverse to virulence.

Objectives

In the Emirate of Dubai, a vaccination experiment was carried out with an inactivated AHS vaccine produced at the Central Veterinary Research Laboratory (CVRL), Dubai, UAE to investigate the humoral antibody response of AHS‐naïve horses to this vaccine. Our vaccination experiment was performed to establish an AHS vaccine bank in the UAE to protect horses from the disease in case of an outbreak. Therefore, CVRL established an inactivated AHS vaccine containing all nine serotypes which induce high neutralising antibodies.

Study design

A total of 10 horses kept in a desert isolation area were subcutaneously and intramuscularly vaccinated with an inactivated vaccine containing all nine AHS serotypes previously isolated from Kenyan horse fatalities. Primary immunisation was followed by two booster immunisations 4 weeks and 6 months apart. After 13 months, an annual booster was administered.

Methods

Blood samples were regularly withdrawn for ELISA and virus neutralisation testing. Additionally, EDTA blood was tested every second day for 14 days post each vaccination for the presence of AHS virus or its RNA.

Results

Results show that ELISA and virus neutralising antibodies appeared after the first booster, declined after 4‐6 months and therefore three vaccinations and an annual vaccination are necessary to achieve high protective virus neutralising antibodies.

Main limitations

No challenge infection was carried out due to the lack of a safe facility in the UAE.

Conclusion

Before more advanced AHS vaccines become a reality, inactivated vaccines containing all nine serotypes should be used as they produce high ELISA and neutralising antibodies.
Interactions of galeterone and its 3‐keto‐Δ4 metabolite (D4G) with one of the key enzymes of corticosteroid biosynthesis – steroid 21‐monooxygenase (CYP21A2)
Authors: Masamrekh Rami A. , Filippova Tatiana A. , Sherbakov Kirill A. , Veselovsky Alexander V. , Shumyantseva Victoria V. , Kuzikov Alexey V.
Published: October 2020

We have investigated interactions of galeterone and its pharmacologically active metabolite – 3‐keto‐Δ4‐galeterone (D4G) – with one of the key enzymes of corticosteroid biosynthesis – steroid 21‐monooxygenase (CYP21A2). It was shown by absorption spectroscopy that both compounds induce type I spectral changes of CYP21A2. Spectral dissociation constants (KS) of complexes of CYP21A2 with galeterone or D4G were calculated as 3.1 ± 0.7 μm and 4.6 ± 0.4 μm, respectively. It was predicted by molecular docking that both ligands similarly bind to the active site of CYP21A2. We have revealed using reconstituted monooxygenase system that galeterone is a competitive inhibitor of CYP21A2 with the inhibition constant (Ki) value of 12 ± 3 μm, while D4G at the concentrations of 10 and 25 μm does not inhibit the enzyme. Summarizing, based on the in vitro analyses we detected inhibition of CYP21A2 by galeterone and lack of the influence of D4G on this enzyme.
Oil content, fatty acid composition and biodiesel properties among natural provenances of Siberian apricot (Prunus sibirica L.) from China
Authors: Ma Yunxia , Wang Shaoxiong , Liu Xiaojuan , Yu Haiyan , Yu Dan , Li Gangtie , Wang Libing
Published: October 2020

Siberian apricot (Prunus sibirica L.), an excellent woody oil plant unique to Asia, is well known for its ability to produce high‐oil seeds for use as a promising feedstock of biodiesel. Based on the investigation of natural Siberian apricot resources in China in the early stage, seeds of Siberian apricot from 74 geographic provenances which can fully reflect the overall information were collected. In this research, seeds oil content, fatty acid composition and biodiesel properties were evaluated, and the key environmental factors that caused the variation of these in different geographic provenance were analyzed. The oil content of Siberian apricot seeds is 45.48%–61.07%, and the average was 50.95% for all provenances. The characteristics of oil can identify and quantify eight fatty acids. The most abundant fatty acids were oleic acid (C18:1; 54.02%–76.54%), followed by linoleic acid (C18:2; 16.78%–38.49%) and erucic acid (C16:0; from 3.27% to 6.12%). Monounsaturated fatty acids are the most abundant in 54.75%–77.03% compared with saturated fatty acids and polyunsaturated fatty acids. The biodiesel properties of most provenance seeds meet the standards of the ASTM D6751 and GB/T 20828, and a few meet the standards of the EN14214. Through the clustering of oil content and fatty acid composition and the analysis of biodiesel properties indexes, it is concluded that KSK provenance is the most suitable for biodiesel production. The XBZ, HHE, AES, ZLQ and LD provenances may be preserved as potential biodiesel. RDA and VPA showed that the effects of environmental factors on the oil properties of Siberian apricot were ranked as terrain factor > climate factor > soil factor, among which longitude, latitude and altitude are the main terrain indicators. These evaluations can provide reference for the effective utilization and further development of Siberian apricot as a bioenergy feedstock.
Evolution of soil carbon stocks under Miscanthus × giganteus and Miscanthus sinensis across contrasting environmental conditions
Authors: Ouattara Malick S. , Laurent Anabelle , Ferchaud Fabien , Berthou Magali , Borujerdi Elsa , Butier Arnaud , Malvoisin Pierre , Romelot Dominique , Loyce Chantal
Published: October 2020

Miscanthus is a C4 bioenergy perennial crop characterized by its high potential yield. Our study aimed to compare the carbon storage capacities of Miscanthus sinensis (M. sinensis) with that of Miscanthus × giganteus (M. × giganteus) in field conditions in different types of soils in France. We set up a multi‐environment experimental network. On each trial, we tested two treatments: M. × giganteus established from rhizomes (Gr) and M. sinensis transplanted seedlings (Sp). We quantified the soil organic carbon (SOC) stock at equivalent soil mass for both genotypes in 2014 and 2019 and for two sampling depths: L1 (ca. 0–5 cm) and L1‐2 (ca. 0–30 cm). We also calculated the total and annual variation of the SOC stock and investigated factors that could explain the variation and the initial state of the SOC stock. ANOVAs were performed to compare the SOC stock, as well as the SOC stock variation rates across treatments and soil layers. Results showed that the soil bulk density did not vary significantly between 2014 and 2019 for both treatments (Gr and Sp). The SOC concentration (i.e. SOC expressed in g/kg) increased significantly between 2014 and 2019 in L1, whereas no significant evolution was found in L2 (ca. 5–30 cm). The SOC stock (i.e. SOC expressed in t/ha) increased significantly in the superficial layer L1 for M. × giganteus and M. sinensis, by 0.48 ± 0.41 and 0.54 ± 0.25 t ha−1 year−1 on average, respectively, although no significant change was detected in the layer L1‐2 for both genotypes. Moreover, SOC stocks in 2019 did not differ significantly between M. × giganteus and M. sinensis in the soil layers L1 and L1‐2. Lastly, our results showed that the initial SOC stock was significantly higher when miscanthus was grown after set‐aside than after annual crops.
Miscanthus: A fast‐growing crop for environmental remediation and biofuel production
Authors: Wang Congpeng , Kong Yingzhen , Hu Ruibo , Zhou Gongke
Published: October 2020

As an herbaceous perennial, Miscanthus has attracted extensive attention in bioenergy refinery and ecological remediation due to its high yield and superior environmental adaptability. This review summarizes current research advances of Miscanthus in several aspects including biological properties, biofuels production, and phytoremediation of contaminated soil. Miscanthus has relatively high biomass yield, calorific value, and cellulose content compared with other lignocellulosic bioenergy crops, which make it one of the most promising feedstocks for the production of second‐generation biofuels. Moreover, Miscanthus can endure soil pollutions caused by various heavy metals and survive in a variety of adverse environmental conditions. Therefore, it also has potential applications in ecological remediation of contaminated soil, and reclamation of polluted soil and water resources. Nevertheless, more endeavors are still needed in the genetic improvement and elite cultivar breeding, large‐scale cultivation on marginal land, and efficient conversion to biofuels, when utilizing Miscanthus as a bioenergy crop. Furthermore, more efforts should also be undertaken to translate Miscanthus into a bioenergy crop with the phytoremediation potential.
Enhancement of leukemia‐like phenotypes in Drosophila mxc mutant larvae due to activation of the RAS‐MAP kinase cascade possibly via down‐regulation of DE‐cadherin
Authors: Kurihara Masanori , Takarada Kazuki , Inoue Yoshihiro H.
Published: October 2020

Loss of mxc gene function in mature hemocytes of Drosophila mxcmbn1 mutant results in malignant hyperplasia in larval hematopoietic tissues termed lymph glands (LGs) owing to over‐proliferation of immature cells. This is a useful model for genetic analyses of leukemia progression. To identify other mutations that deteriorate the hyperplasia, we aimed to investigate whether hyper‐activation of common signaling cascade enabled to enhance the phenotypes. Ectopic expression of the constitutively active forms of MAPK signaling factors in the mutant increased the hyperplasia and the number of circulating hemocytes, resulting in the production of LG fragments. The LG phenotype was related to the reduced DE‐cadherin level in the mutants. Depletion of Drosophila MCRIP, involved in MAPK‐induced silencing of cadherin gene expression, exhibited a similar enhancement of the mxcmbn1 phenotypes. Furthermore, expression of MMP1 proteinase that cleaves the extracellular matrix proteins increased in the mutant larvae harboring MAPK cascade activation. Depletion of Mmp1 and that of pnt (required for Mmp1 expression) suppressed the LG hyperplasia. Hence, we speculated that reduction in DE‐cadherin level by either down‐regulation of MCRIP or up‐regulation of MMP1 was involved in the progression of the tumor phenotype. Our findings can contribute to understanding the mechanism underlying human leukemia progression.
Real‐world data demonstrate improved bleed control and extended dosing intervals for patients with haemophilia B after switching to recombinant factor IX Fc fusion protein (rFIXFc) for up to 5 years
Authors: Shapiro Amy , Chaudhury Ateefa , Wang Michael , Escobar Miguel , Tsao Elisa , Barnowski Christopher , Feng Jing , Jain Nisha , Quon Doris V.
Published: October 2020

Introduction

In clinical trials, recombinant factor IX fusion protein (rFIXFc) has demonstrated safety, efficacy and prolonged activity with extended dosing intervals for treatment of haemophilia B.

Aim

To assess the real‐world clinical utility of rFIXFc in a variable patient population and routine clinical practice.

Methods

A multicentre, retrospective chart review was conducted of patients with haemophilia B who had received rFIXFc prophylaxis or on‐demand treatment for ≥6 months across six sites in the United States.

Results

Sixty‐four eligible patients were identified who had a median (range) duration on rFIXFc of 2.7 (0.5‐5.0) years. Of 32 patients on rFIXFc prophylaxis who switched from prophylaxis with another factor treatment (ie pre‐rFIXFc) and had a known pre‐rFIXFc dosing interval, the initial dosing interval was lengthened for 26 (81%) patients and maintained for the remaining 6 (19%) patients. Most (n = 48 [91%]) patients who received rFIXFc prophylaxis from the beginning to the end of the chart review period (n = 53) maintained or lengthened the dosing interval from first through last dose of rFIXFc. For patients receiving rFIXFc prophylaxis, there was an approximate 50% reduction in weekly factor consumption compared with pre‐rFIXFc prophylaxis. Overall annualized bleed rates, annualized spontaneous bleed rates and annualized joint bleed rates decreased after switching to rFIXFc prophylaxis (n = 24 with bleed data). Compliance to recommended treatment improved or remained stable in most patients with available data (30/31).

Conclusion

Recombinant factor IX fusion protein prophylaxis improved bleed control, reduced overall consumption, reduced frequency of infusion and improved compliance for patients with haemophilia B in a real‐world setting.
Associations of marijuana with markers of chronic lung disease in people living with HIV
Authors: Wenger DS , Triplette M , Shahrir S , Akgun KM , Wongtrakool C , Brown ST , Kim JW , Soo Hoo GW , Rodriguez‐Barradas MC , Huang L , Feemster LC , Zifodya J , Crothers K
Published: October 2020

Objectives

The relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood.

Methods

We performed a cross‐sectional analysis of the Examinations of HIV‐Associated Lung Emphysema (EXHALE) study, including 162 HIV‐positive patients and 138 participants without HIV. We modelled marijuana exposure as: (i) current daily or weekly marijuana smoking vs. monthly or less often; or (ii) cumulative marijuana smoking (joint‐years). Linear and logistic regression estimated associations between marijuana exposure and markers of lung disease, adjusted for tobacco smoking and other factors.

Results

In PLWH, current daily or weekly marijuana use was associated with a larger forced vital capacity (FVC), larger total lung capacity and increased odds of radiographic emphysema compared with marijuana non‐smokers in adjusted models; these associations were not statistically significant in participants without HIV. Marijuana joint‐years were associated with higher forced expiratory volume in 1 s and FVC in PLWH but not with emphysema.

Conclusions

In PLWH, marijuana smoking was associated with higher lung volumes and potentially with radiographic emphysema. No consistently negative associations were observed between marijuana and measures of chronic lung health.
Scientometric analysis of vital pulp therapy studies
Authors: Kodonas K. , Fardi A. , Gogos C. , Economides N.
Published: October 2020

Aim

To present a scientometric analysis of the entire body of scientific publications in the field of vital pulp therapy (VPT) and analyse the research trends and popular topics.

Methodology

A comprehensive literature search was conducted in the Web of Science and Scopus databases on 21 August 2020 to identify all articles related to VPT. The publications were reviewed and basic research parameters were collected, including publication year, patterns of authorship, geographical distribution of scientific productions, journals, h‐index, study design and keyword analysis. Web of Science, Scopus and Google Scholar databases were used for the citation analysis of the ten top cited articles. The data were analysed using VOSviewer and visualized by tables and diagrams.

Results

In total, 1197 VPT‐associated items were identified from 64 countries in 176 journals. The majority of papers were published in the Journal of Endodontics. The United States of America was the leading country for number of publications, citations, h‐index and collaborations. The distribution of articles based on study design was as follows: basic science (35%), clinical (27%), observational studies (26%) and review publications (12%). The most frequently occurring keywords were pulpotomy, mineral trioxide aggregate, calcium hydroxide and direct pulp capping.

Conclusions

This scientometric analysis outlines the evolutionary trends and the productivity of researchers and countries in the field of vital pulp therapy. Research output is dominated by basic science articles involving innovative materials published in high impact factor dental journals.
A macroscopic and histological analysis of radiographically well‐defined deep and extremely deep carious lesions: carious lesion characteristics as indicators of the level of bacterial penetration and pulp response
Authors: Demant S. , Dabelsteen S. , Bjørndal L.
Published: October 2020

Aim

To investigate the relationship between radiographically and macroscopically well‐defined carious lesions and the dentine–pulp complex with regard to: (i) level of bacterial penetration; (ii) inflammatory status including the presence of hyperplastic pulp stroma; and (iii) formation of hard and/or ectopic connective tissue.

Methodology

The material comprised 68 untreated cavitated permanent teeth divided into well‐defined radiographic categories based on the lesion penetration depth: (i) deep lesions ( ≥3/4 of the dentine thickness with a radio‐dense zone separating the lesion from the pulp) and (ii) extremely deep lesions (the carious lesion penetrated the entire thickness of the dentine, without a radio‐dense zone). After extraction, the teeth were processed for histology. The material was scored with regard to coronal breakdown, macroscopic variables describing caries activity and histological variables describing the dentine–pulp complex (bacteria, inflammatory infiltrate, partial pulp necrosis, hyperplastic changes and hard tissue/ectopic presence of connective tissue). Interrater agreement was assessed using Cohen’s kappa. Associations between variables were assessed using Pearson’s chi‐squared or Fisher’s exact test. The effect size was reported by odds ratio (OR) and associated 95% confidence interval (CI). Level of significance was set to 5%.

Results

There were significant associations between a closed environment (1–2 surfaces involved) and the presence of biofilm, retrograde demineralization and light‐coloured demineralized dentine. Whereas radiographically defined deep lesions tended to have bacteria only in the primary dentine (P < 0.001, OR = 20.55, 95% CI [4.44, 107.89]), extremely deep carious lesions tended to have bacteria in contact with the pulpal tissue (P = 0.007, OR = 6.84, 95% CI [2.00, 62.83]), presence of an inflammatory infiltrate (Fisher’s exact; P < 0.001) and partial pulp necrosis. Hyperplastic pulps were seen only in extremely deep lesions.

Conclusions

Unlike deep lesions, extremely deep carious lesions were often associated with severe pulp inflammation and infection. A radiographic threshold between deep and extremely deep lesions is suggested as indicator of the bacterial penetration level and the severity of the pulpal response prior to intervention.
Properties of extruded corn snacks with common flax (Linum usitatissimum L.) and golden flax (Linum flavum L.) pomace
Authors: Tomaszewska‐Ciosk Ewa , Zdybel Ewa
Published: October 2020

An attempt was undertaken in this study to produce extruded snacks based on maize semolina with the addition of pomace from common flax (Linum usitatissimum L.) and golden flax (Linum flavum L.). Study results showed that increasing pomace content in the extrudates made their expansion ratio and colour lightness to decrease, and their mechanical properties to increase. The analysis of all sensory attributes demonstrated that the panellists did not notice any statistically significant differences between the snacks without pomace addition and those with 5% flax pomace. Flax pomace addition in the amount exceeding 10% made the product unacceptable by the panellists. No statistically significant difference was observed in most of the evaluated traits between the snacks containing of pomace from common flax and golden flax, except for the colour.