bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized synthesis of isocyanate microcapsules for self-healing application in epoxy composites
Authors: Sun Yong , Wang Shugang , Dong Xiaosu , Liang Yuntao , Lu Wei , He Zhenglong , Qi Guansheng
Published: January 2020

Microcapsules containing isophorone diisocyanate were fabricated in oil-in-water emulsion. The emulsification effect of different emulsifiers during the capsule synthesis was systematically investigated by optical microscope. Three kinds of shell materials were discussed to obtain the high core content, smooth-surfaced, and robust capsule by scanning electronic microscope and Fourier transform infrared spectroscopy. Self-healing performance of corresponding self-healing epoxy composites was fully evaluated by accelerated corrosion test and mechanical test. The results demonstrated that high core content and smooth-surfaced capsules with dense composite shell could be synthesized in polyvinyl alcohol emulsion, and the core content of the optimized capsules was determined as 71.3–84.6 wt% at the capsule size from 35 µm to 154 µm. In addition, the optimized capsules had good processing properties and the corresponding self-healing epoxy composites exhibited excellent core release and self-healing performance.
Effectiveness, Safety, and Costs of Dolutegravir/Abacavir/Lamivudine Single-Tablet Regimen in a Real-Life Cohort of HIV-1 Adult Infected Patients
Authors: Rodriguez-Gonzalez Carmen Guadalupe , Chamorro-de-Vega Esther , Ortega-Navarro Cristina , Alonso Roberto , Herranz-Alonso Ana , Sanjurjo-Saez Maria
Published: January 2020

Background: Real-life data on single-tablet regimen (STR) dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) is scarce, and concerns about DTG neuropsychiatric adverse events (NP-AEs) have recently arisen. Objective: To explore the effectiveness and safety, in particular NP-AEs, of DTG/ABC/3TC in a cohort of HIV-1 adult infected patients. Pill burden, adherence to this STR, and the impact of switching on costs were also evaluated. Methods: This was an observational, retrospective study. The study population included antiretroviral therapy (ART)-naive and treatment-experienced (TE) patients who started DTG/ABC/3TC between February 1, 2016, and October 31, 2016. Effectiveness and safety were analyzed at week 48 (W48) by intention-to-treat analysis. The Cox regression model was used to investigate predictors of DTG/ABC/3TC discontinuation. Results: A total of 253 patients were included (44 ART naïve, 209 TE). At W48, the proportion of patients with virological suppression was 72.7% (95% CI = 58.4-87.0) in ART-naive patients, 85.6% (95% CI = 80.3-90.9) in previously suppressed TE patients, and 86.4% (95% CI = 65.1-97.1) in previously not suppressed TE patients. The rate of protocol-defined virological failure was 4.3%. The incidence of AEs was higher in the subgroup of ART-naive patients (56.1% vs 39.0%), with a rate of interruptions for this reason of 13.6% and 7.6%, respectively. The incidence of NP-AEs was 20.6%, with 3.9% of patients requiring discontinuation. Patients who had switched from a raltegravir-containing regimen discontinued DTG/ABC/3TC because of AEs more frequently (relative risk = 2.83; 95% CI = 1.04-7.72; P = 0.041) in the multivariate analysis. After switching to DTG/ABC/3TC, the median pill burden was reduced from 3 to 1 and the proportion of patients with an adherence <90%, from 20.1% to 12.0%. The annual per-patient ART costs increased by €48 (0.6% increase). Conclusion and Relevance: DTG/ABC/3TC is an effective strategy as first-line and switching ART. Our data suggest a worse tolerance in ART-naive patients, although the rate of discontinuation resulting from NP-AEs was relatively low. In the short-term, the adherence was slightly improved without significant changes in costs.
Preliminary clinical outcomes of a short-term low-intensity Early Start Denver Model implemented in the Taiwanese public health system
Authors: Lin Tzu-Ling , Chiang Chung-Hsin , Ho Suk Yin , Wu Hsin-Chi , Wong Ching-Ching
Published: January 2020

The Early Start Denver Model is an evidence-based, comprehensive naturalistic developmental behavioral intervention. Randomized controlled studies indicate that long-term, high-intensity Early Start Denver Model in home-based settings can positively impact the clinical outcomes of young children with autism spectrum disorder. However, it is difficult to deliver high-intensity early intervention in an under-resourced country such as Taiwan. This study evaluated the effects of implementing the Early Start Denver Model with adaptations (including low intensity, shorter duration, and delivery in general hospitals by multidisciplinary professionals) within the Taiwanese public health system. A pre- and post-intervention study was conducted. Sixteen children with autism spectrum disorder (mean age of 33.5 months) received 6 months of one-on-one Early Start Denver Model intervention (approximately 8 h per week). The children showed significant post-intervention improvements in language and overall cognitive functioning and reduced symptom severity in communication and play. This study suggests that delivering the Early Start Denver Model in community-based hospitals may be an effective intervention, with a wider reach, for young children with autism spectrum disorder in Taiwan. The next steps in Taiwan are to incorporate a control group and assess the long-term effects of the adapted Taiwanese Early Start Denver Model program.

Lay Abstract

The Early Start Denver Model is a comprehensive naturalistic developmental behavioral intervention for young children with autism spectrum disorder. Rigorous studies indicate that long-term, high-intensity Early Start Denver Model in home-based settings can help young children with autism spectrum disorder have great progress in language, cognitive development, and adaptive skills and reduce overall symptom severity. In accordance with the current limitations in resourcing for early intervention in Taiwan, this study evaluated the effects of implementing the Early Start Denver Model in the Taiwanese public health system with some adaptations, including lower intensity, shorter duration, and delivery in general hospitals. A total of 16 children with autism spectrum disorder, aged between 25 and 46 months, received approximately 8 h per week one-on-one Early Start Denver Model intervention. After 6 months of intervention, the children showed great improvements in language and overall cognitive functioning and reduced symptom severity in communication and play. This study suggests that directly delivering the Early Start Denver Model in community-based hospitals may be an effective intervention, which can make more young children with autism spectrum disorder in Taiwan access the Early Start Denver Model service.
Prevalence of coexisting autoimmune thyroidal diseases in coeliac disease is decreasing
Authors: Castro Patricia Dominguez , Harkin Grace , Hussey Mary , Christopher Brian , Kiat Clifford , Chin Jun Liong , Trimble Valerie , McNamara Deirdre , MacMathuna Padraic , Egan Brian , Ryan Barbara , Kevans David , Abuzakouk Mohamed , Farrell Richard , Feighery Con , Byrnes Valerie , Mahmud Nasir , McManus Ross
Published: January 2020

Background

Coeliac disease (CD) is associated with an increased risk of other immune‐mediated conditions.

Aim : To investigate the prevalence of coexistent immune‐mediated diseases in CD patients, and changes in the prevalence of autoimmune thyroidal diseases over the last 50 years.

Methods

Medical record data were collected retrospectively from 749 CD patients in Ireland. Prevalence of autoimmune diseases was compared with previously published results from general populations. Patients were divided into four groups based on the year of diagnosis to analyse changes in the prevalence of autoimmune thyroidal disease over time.

Results

Median age at the time of CD diagnosis was 56 years (range 18–91 years). A total of 233 (31.1%) patients had a coexistent immune‐mediated condition (IMC). Autoimmune thyroidal diseases were seen in 149 (19.9%) patients, hypothyroidism in 110 (14.7%), type 1 diabetes in 27 (3.6%), psoriasis in 20 (2.7%), inflammatory bowel disease in 14 (1.9%) and rheumatoid arthritis in 12 (1.6%). All conditions were more common in CD patients than in the general population. Type 1 diabetes was diagnosed mainly before CD, whereas there was no such trend in other conditions. Autoimmune thyroidal diseases became less common in female CD patients over time.

Conclusions

Prevalence of autoimmune diseases is increased in adult CD patients compared with the general population. However, concomitant autoimmune thyroidal diseases became less common over time in women.
Ticagrelor causes false-negative functional tests for heparin-induced thrombocytopenia
Authors: Eekels Julia J. M. , Pachler Christoph , Krause Nora , Muhr Tina , Waltl Gert , Greinacher Andreas
Published: January 2020

Heparin-induced thrombocytopenia (HIT) occurs in 1-2% of patients with acute coronary events or cardiac surgery. Eekels and colleagues report that ticagrelor comedication must be taken into account by laboratory physicians for interpretation of functional tests for HIT, as the presence of the drug can cause false-negative results.
Applying evidence-based medicine in general practice: a video-stimulated interview study on workplace-based observation
Authors: Welink Lisanne S. , Van Roy Kaatje , Damoiseaux Roger A. M. J. , Suijker Hilde A. , Pype Peter , de Groot Esther , Bartelink Marie-Louise E. L.
Published: January 2020

Background

Evidence-based medicine (EBM) in general practice involves applying a complex combination of best-available evidence, the patient’s preferences and the general practitioner’s (GP) clinical expertise in decision-making. GPs and GP trainees learn how to apply EBM informally by observing each other’s consultations, as well as through more deliberative forms of workplace-based learning. This study aims to gain insight into workplace-based EBM learning by investigating the extent to which GP supervisors and trainees recognise each other’s EBM behaviour through observation, and by identifying aspects that influence their recognition.

Methods

We conducted a qualitative multicentre study based on video-stimulated recall interviews (VSI) of paired GP supervisors and GP trainees affiliated with GP training institutes in Belgium and the Netherlands. The GP pairs (n = 22) were shown fragments of their own and their partner’s consultations and were asked to elucidate their own EBM considerations and the ones they recognised in their partner’s actions. The interview recordings were transcribed verbatim and analysed with NVivo. By comparing pairs who recognised each other’s considerations well with those who did not, we developed a model describing the aspects that influence the observer’s recognition of an actor’s EBM behaviour.

Results

Overall, there was moderate similarity between an actor’s EBM behaviour and the observer’s recognition of it. Aspects that negatively influence recognition are often observer-related. Observers tend to be judgemental, give unsolicited comments on how they would act themselves and are more concerned with the trainee-supervisor relationship than objective observation. There was less recognition when actors used implicit reasoning, such as mindlines (internalised, collectively reinforced tacit guidelines). Pair-related aspects also played a role: previous discussion of a specific topic or EBM decision-making generally enhanced recognition. Consultation-specific aspects played only a marginal role.

Conclusions

GP trainees and supervisors do not fully recognise EBM behaviour through observing each other’s consultations. To improve recognition of EBM behaviour and thus benefit from informal observational learning, observers need to be aware of automatic judgements that they make. Creating explicit learning moments in which EBM decision-making is discussed, can improve shared knowledge and can also be useful to unveil tacit knowledge derived from mindlines.
Novel deep intronic mutation in the coagulation factor XIII a chain gene leading to unexpected RNA splicing in a patient with factor XIII deficiency
Authors: Deng Jun , Li Dan , Mei Heng , Tang Liang , Wang Hua-fang , Hu Yu
Published: January 2020

Background

Coagulation factor XIII (FXIII) plays an essential role in maintaining hemostasis by crosslinking fibrin. Deficiency in FXIII affects clot stability and increases the risk of severe bleeding. Congenital FXIII deficiency is a rare disease. Recently, we identified a Chinese family with FXIII deficiency and investigated the pathogenesis of congenital FXIII deficiency, contributing non-coding pathogenic variants.

Methods

We performed common tests, coding sequencing by targeted next-generation sequencing (NGS), whole-genome sequencing and splice-sites prediction algorithms. The pathogenesis was investigated via minigene and nonsense-mediated mRNA decay (NMD) by experiments in vitro.

Results

The proband is homozygote for a novel deep intronic c.799-12G > A mutation in the F13A1 gene. Through direct sequencing of the minigenes mRNA, we found 10 bases of intron 6 insert in the mRNA of mutant minigenes mRNA. The relative expression of EGFP-F13A1 was higher by suppression of NMD in vitro. Furthermore, we found the proband with enhanced thrombin generation (TG).

Conclusion

We reported a novel deep intronic c.799-12G > A mutation of F13A1 which produced a new acceptor site and frame shifting during translation introducing a premature termination codon. Our results support the premature termination codon triggered NMD. We need to pay attention to the position of potential alterable splicing sites while counselling and genetic test. The finding of enhanced TG indicated that we should be aware of the risk of thrombosis in patients with FXIII deficiency during replacement therapy.
Chromatin remodeling dysfunction extends the etiological spectrum of schizophrenia: a case report
Authors: Poisson Alice , Chatron Nicolas , Labalme Audrey , Fourneret Pierre , Ville Dorothée , Mathieu Marie Laure , Sanlaville Damien , Demily Caroline , Lesca Gaëtan
Published: January 2020

Background

The role of deleterious copy number variations in schizophrenia is well established while data regarding pathogenic variations remain scarce. We report for the first time a case of schizophrenia in a child with a pathogenic mutation of the chromodomain helicase DNA binding protein 2 (CHD2) gene.

Case presentation

The proband was the second child of unrelated parents. Anxiety and sleep disorders appeared at the age of 10 months. He presented febrile seizures and, at the age of 8, two generalized tonic-clonic seizures. At the age of 10, emotional withdrawal emerged, along with a flat affect, disorganization and paranoid ideation, without seizures. He began to talk and giggle with self. Eventually, the patient presented daily auditory and visual hallucinations. The diagnosis of childhood onset schizophrenia (DSM V) was then evoked. Brain imaging was unremarkable. Wakefulness electroencephalography showed a normal background and some bilateral spike-wave discharges that did not explain the psychosis features. A comparative genomic hybridization array (180 K, Agilent, Santa Clara, CA, USA) revealed an 867-kb 16p13.3 duplication, interpreted as a variant of unknown significance confirmed by a quantitative PCR that also showed its maternal inheritance. Risperidone (1,5 mg per day), led to clinical improvement. At the age of 11, an explosive relapse of epilepsy occurred with daily seizures of various types. The sequencing of a panel for monogenic epileptic disorders and Sanger sequencing revealed a de novo pathogenic heterozygous transition in CHD2 (NM_001271.3: c.4003G > T).

Conclusions

This case underlines that schizophrenia may be, sometimes, underpinned by a Mendelian disease. It addresses the question of systematic genetic investigations in the presence of warning signs such as a childhood onset of the schizophrenia or a resistant epilepsy. It points that, in the absence of pathogenic copy number variation, the investigations should also include a search for pathogenic variations, which means that some of the patients with schizophrenia should benefit from Next Generation Sequencing tools. Last but not least, CHD2 encodes a member of the chromodomain helicase DNA-binding (CHD) family involved in chromatin remodeling. This observation adds schizophrenia to the phenotypic spectrum of chromodomain remodeling disorders, which may lead to innovative therapeutic approaches.
Comparing healthcare cost associated with the use of enzyme-inducing and non-enzyme active antiepileptic drugs in elderly patients with epilepsy in the UK: a long-term retrospective, matched cohort study
Authors: Borghs Simon , Byram Laura , Chan Jane , Dedeken Peter , Logan John , Kiri Victor , Noack-Rink Matthias , Patsalos Philip N. , Thieffry Solène
Published: January 2020

Background

In elderly patients (≥65 years of age) with epilepsy who take medications for comorbid conditions, some antiepileptic drugs (AEDs) may alter the metabolism of other treatments and increase the risk of adverse consequences and healthcare utilisation. This analysis compares healthcare costs associated with enzyme-inducing AEDs (EIAEDs) and non-enzyme active AEDs (nEAAEDs) use in elderly patients with epilepsy.

Methods

This retrospective matched cohort study used the Clinical Practice Research Datalink (CPRD) of UK primary care medical records, linked to the Hospital Episode Statistics (HES) database. Selected patients with epilepsy were ≥ 65 years and prescribed an EIAED or nEAAED between 2001 and 2010 (index) after ≥1 year without AEDs (baseline) and followed until the first occurrence of the following: end of HES data coverage, end of GP registration, or death; practice’s up-to-standard status or addition of an AED belonging to another cohort or discontinuation of the last AED of that cohort. Propensity score matching reduced confounding factor effects between cohorts. Key outcomes included time to cohort treatment failure, time to index AED treatment failure, and direct healthcare costs in 2014 Pound Sterling (£) values.

Results

Overall, 1425 elderly patients were included: 964 with EIAEDs and 461 with nEAAEDs. At baseline, the EIAED cohort was older (mean age, 76.2 vs. 75.1 years) and a higher proportion were male. Baseline direct healthcare costs were similar. After matching (n = 210 each), and over the entire follow-up period, median monthly direct healthcare costs were higher for patients taking EIAEDs than nEAAEDs (£403 vs. £317; p = 0.0150, Mann-Whitney U). Costs were higher for patients remaining in the EIAED cohort after 3 follow-up years. The median time to cohort treatment failure for the EIAED cohort was 1110 days vs. 1175 days for the nEAAED cohort.

Conclusion

Newly treated elderly patients with epilepsy were more likely to be prescribed EIAEDs than nEAAEDs. In matched cohorts, elderly patients with epilepsy treated with EIAEDs had higher average total direct and epilepsy-related healthcare costs than nEAAED-treated patients; this difference was greater than previously reported in the overall adult population. Changing treatment practices could improve patient care and reduce costs.
Venous sinus stenting improves cerebral autoregulation in a patient with venous sinus stenosis: a case report
Authors: Jia Meiyan , Guo Zhen-Ni , Jin Hang , Yan Xiuli , Shi Mingchao , Sun Xin , Ma Hongyin , Lv Shan , Yang Yi
Published: January 2020

Background

Venous sinus stenosis (VSS) is a type of cerebral venous vascular disease. Cerebral autoregulation is an indicator of cerebral arterial function. The cerebral circulatory system is composed of the venous system and arterial system. Impaired venous function may affect arterial function. Thus, cerebral venous stenosis may influence cerebral autoregulation.

Case presentation

In this case, a 50-year-old woman with transient blindness and headache was admitted to the hospital. The patient was diagnosed with VSS. A stent was placed at the stenosis. The stent released the intravenous pressure and remitted the patient’s symptoms. Measurements of dynamic cerebral autoregulation (dCA) were performed at 3 time points: before stenting, after stenting, and 3 months later. The dCA gradually improved after stenting.

Conclusion

VSS may have an influence on cerebral autoregulation, and effective treatment improves cerebral autoregulation in patients with VSS.
Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells
Authors: Yoshida Kazushige , Okamoto Masanori , Sasaki Jun , Kuroda Chika , Ishida Haruka , Ueda Katsuya , Ideta Hirokazu , Kamanaka Takayuki , Sobajima Atsushi , Takizawa Takashi , Tanaka Manabu , Aoki Kaoru , Uemura Takeshi , Kato Hiroyuki , Haniu Hisao , Saito Naoto
Published: January 2020

Background

There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear.

Methods

In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFNγ for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry.

Results

We discovered that IFNγ increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes.

Conclusions

Here we clarify for the first time an additional mechanism of anti-tumour effect—as exerted by anti-PD-1 antibody decreasing Treg— we anticipate that our findings will lead to the development of new methods for cancer treatment.
Macular vessel density versus ganglion cell complex thickness for detection of early primary open-angle glaucoma
Authors: Wang Yiwei , Xin Chen , Li Meng , Swain David L. , Cao Kai , Wang Huaizhou , Wang Ningli
Published: January 2020

Background

To evaluate the macular vessel density (VD) and ganglion cell complex (GCC) thickness in pre-perimetric (PPG) and early perimetric primary open-angle glaucoma (PG) eyes, and to compare the diagnostic ability of the two measurements to discriminate PPG and early PG eyes from healthy eyes.

Methods

Seventy-nine eyes in 72 subjects (31 normal, 26 PPG, and 22 early PG eyes) were included in the consecutive case series. Macular VD and GCC thickness were acquired simultaneously using the 6 × 6 mm2 high-density AngioRetina scanning mode. Diagnostic abilities were assessed using the area under the receiver operating characteristic curve (AUROC).

Results

Compared to healthy eyes, whole image VD (wiVD) and GCC thickness were significantly lower in PPG and early PG eyes (all P < 0.025). The percent reduction of wiVD was lower than that of GCC thickness in early PG eyes (P < 0.05), while they were similar in PPG eyes (P > 0.05). Regionally, greater VD attenuation and GCC thinning were identified in the perifovea than in the parafovea in both groups (all P < 0.05). Moreover, the percent reduction of VD was less than that of GCC thickness in the perifoveal region in PPG eyes (P < 0.05). The AUROCs for wiVD and GCC thickness were 0.824 and 0.881, respectively, in PPG eyes (P > 0.05), and 0.918 and 0.977, respectively, in early PG eyes (P > 0.05).

Conclusions

Macular VD and GCC thickness significantly decreased in PPG and early PG eyes. The perifoveal region appeared to be more vulnerable to macular VD attenuation and GCC thinning in early glaucoma. Our results showed that macular VD measurements may be helpful for detecting and understanding early glaucomatous damage.
An outbreak of norovirus-related acute gastroenteritis associated with delivery food in Guangzhou, southern China
Authors: Lu Ying , Ma Mengmeng , Wang Hui , Wang Dahu , Chen Chun , Jing Qinlong , Geng Jinmei , Li Tiegang , Zhang Zhoubin , Yang Zhicong
Published: January 2020

Background

A large number of students at a school in Guangzhou city developed a sudden onset of symptoms of diarrhea and vomiting. To help control the outbreak, we conducted an epidemiological investigation to determine the causative agent, sources, role of transmission and risk factors of the infections.

Methods

The study population consisted of probable and confirmed cases. An active search was conducted for cases among all students, teachers and other school staff members. A case control study was carried out using standardized online questionnaires. Data were obtained regarding demographic characteristics, gastrointestinal symptoms, personal hygiene habits, history of contact with a person who had diarrhea and/or vomiting and dining locations during the past 3 days. Rectal swabs or stool samples of the cases and, food handlers, as well as environmental samples were collected to detect potential intestinal viruses and bacteria. We calculated odds ratios and 95% confidence intervals (CIs).

Results

A total of 157 individuals fit the definition of a probable case, including 46 with laboratory-confirmed norovirus infection between March 8 and March 22, 2018. The proportion of students who had eaten delivery food 3 days before the onset of illness in the case group was 2.69 times that in the control group (95%CI: 1.88–3.85). Intake of take-out food 3 days earlier, and exposure to similar cases 72 h before onset and case in the same dormitory were risk factors. A total of 20 rectal swab samples from students, 10 rectal swabs from food handlers and 2 environmental swab samples from the out-campus restauranttested positive for norovirus (GII, genogroup II strain).

Conclusions

We investigated an outbreak of norovirus infectious diarrhea. Food handling practices carry potential risk of acute gastroenteritis outbreaks owing to a lack of surveillance and supervision. Greater attention should be paid to the monitoring and supervision of food handlers in off campus restaurant to reduce the incidence of norovirus-related acute gastroenteritis associated with delivery food.
Cricopharyngeal myotomy for delayed Cricopharyngeal dysfunction after head and neck surgery – case report
Authors: Sung An , Lee Ka-Wo
Published: January 2020

Background

Head and neck surgeries can perturb normal structures of neck muscles and nerve innervations, which are supposed to function in harmony to allow complicated process like swallowing. It is still likely that cricopharyngal dysfunction emerges years after the head and neck surgeries.

Case presentation

We report a case with history of left unilateral vocal cord immobility and development of dysphagia and aspiration 2 years after radical thyroidectomy with neck lymph nodes dissection and medialization thyroplasty. Cricopharyngeal dysfunction was impressed and was confirmed with visualization of cricopharyngeal narrowing segment in radiographic contrast swallow examination. The patient was treated successfully by cricopharyngeal myotomy, achieving long-term relief in our 4 years of follow up.

Conclusions

Our case of delayed cricopharyngal dysfunction after radical thyroidectomy and medialization thyroplasty shows that it is important to follow up swallowing functions after patients with UVCI undergo medialization thyroplasty. In the event of delayed manifestation of cricopharyngeal function, it can still be treated successfully by cricoharyngeal myotomy, achieving long term relief of dysphagia.
Assessment of the half-life of cationic periodontal pocket irrigation
Authors: Kirtiloglu Tugrul , Keskiner Ilker , Sahin Murathan , Kirtiloglu Banu , Aygul Safak , Sakallioglu Umur , Acikgoz Gokhan
Published: January 2020

Background

The concentration and persisting time of antimicrobial agents in the periodontal pockets are important factors for their antimicrobial efficacy. Increased clearance time in the periodontal pocket is a significant criterion for the selection of intrapocket irrigants. The aim of this study was to estimate the clearance time of a cationic agent from the periodontal pocket.

Methods

Thallium-201(Tl-201) was chosen as a tracer to simulate the clearance of cationic substance because of its electrical activity. Twenty patients with periodontitis and probing depths 6 to 9 mm were included in this study. In each patient, 3 Mega Becquerel (MBq) of Tl-201 were inserted into the periodontal pocket. Dynamic imaging was performed and clearance of radioactivity was measured.

Results

Clearance of radioactivity was 67.1 ± 16.9, 83.1 ± 13.9, 90.4 ± 10.4, 93.39 ± 8.0% at 30, 60, 90 and 120 min, respectively. Half-life of wash-out was determined as 20.3 ± 10.2 min.

Conclusion

The results of this study demonstrate that the half-life of the cationic solution applied subgingivally was approximately 20 min and labelling of oral irrigants with radiotracers may be used to determine their clearance in further research.
Bevacizumab treatment of meningeal melanoma metastases
Authors: Simonsen Trude G. , Gaustad Jon-Vidar , Rofstad Einar K.
Published: January 2020

Background

Melanoma patients with metastatic growth in the meninges have poor prognosis and few treatment options. Although treatment with BRAF inhibitors or immune checkpoint inhibitors has provided promising results, most patients with advanced melanoma are resistant to these treatments and develop severe side effects. Novel treatment strategies are needed for patients with meningeal melanoma metastases, and the potential of antiangiogenic therapy was investigated in this preclinical study.

Methods

Two GFP-transfected melanoma models (A-07 and D-12) differing substantially in VEGF-A expression were included in the study, and the anti-VEGF-A antibody bevacizumab was used as therapeutic agent. Meningeal metastases were initiated in BALB/c nu/nu mice by intracranial inoculation of melanoma cells, and bevacizumab treatment was given twice a week in i.p. doses of 10 mg/kg until the mice became moribund. Therapeutic effects were evaluated by determining tumor host survival time, assessing tumor growth and angiogenic activity by quantitative analyses of histological preparations, and measuring the expression of angiogenesis-related genes by quantitative PCR.

Results

Meningeal A-07 melanomas showed higher expression of VEGF-A than meningeal D-12 melanomas, whereas the expression of ANGPT2 and IL8, two important angiogenesis drivers in melanoma, was much higher in D-12 than in A-07 tumors. Bevacizumab treatment inhibited tumor angiogenesis and prolonged host survival in mice with A-07 tumors but not in mice with D-12 tumors. Meningeal A-07 tumors in bevacizumab-treated mice compensated for the reduced VEGF-A activity by up-regulating a large number of angiogenesis-related genes, including ANGPT2 and its receptors TIE1 and TIE2. Melanoma cells migrated from meningeal tumors into the cerebrum, where they initiated metastatic growth by vessel co-option. In the A-07 model, the density of cerebral micrometastases was higher in bevacizumab-treated than in untreated mice, either because bevacizumab treatment increased mouse survival or induced increased tumor gene expression.

Conclusions

The development of antiangiogenic strategies for the treatment of meningeal melanoma metastases is a challenging task because the outcome of treatment will depend on the angiogenic signature of the tumor tissue, treatment-induced alterations of the angiogenic signature, and the treatment sensitivity of metastatic lesions in other intracranial sites.
Atraumatic bleeding of the subclavian artery 20 years after surgical treatment of pneumothorax
Authors: Miura Kentaro , Kobayashi Nobutaka
Published: January 2020

Background

Bleeding of the subclavian artery is a fatal condition. Adhesion between the pleura and staple line may develop after surgical treatment of pneumothorax, and collateral arteries often develop from the subclavian artery toward the adhesion at the lung apex; however, atraumatic tearing and bleeding of these collateral arteries into the extrapleural and intrathoracic cavities is rare.

Case presentation

A 70-year-old man visited the hospital for evaluation of left chest pain. Contrast-enhanced chest computed tomography showed a huge tumor in the left apex of the lung. It was suspected to be an extrapleural huge hematoma, and it ruptured into the thoracic cavity. Bleeding from the left subclavian artery was suspected; therefore, emergency angiography was performed. Angiography showed some collateral circulation from the left subclavian artery to the apex of the left lung. Distal and proximal bleeding points were identified. The distal bleeding point was embolized using coils. The proximal bleeding point was blown out, and stents were placed in the left subclavian artery. He had undergone pneumothorax surgery 20 years previously, and the present bleeding episode was strongly suspected to be associated with that surgery. The collateral circulation from the subclavian artery could have developed because of post-pneumothorax inflammation, eventually rupturing and bleeding into the extrapleural space.

Conclusions

This report described an important case of atraumatic subclavian artery bleeding considered to have been caused by surgical treatment of pneumothorax 20 years previously. Emergency angiography and percutaneous stent placement or coil embolization should be considered first in such cases.
Neuropeptide Y regulates proliferation and apoptosis in granulosa cells in a follicular stage-dependent manner
Authors: Urata Yoko , Salehi Reza , Lima Patricia D. A. , Osuga Yutaka , Tsang Benjamin K.
Published: January 2020

Background

The complex regulatory mechanism involved in ovarian follicular development is not completely understood. Neuronal neuropeptide Y (NPY) is involved in the regulation of feeding behavior, energy homeostasis, and reproduction behavior, while its function in ovarian follicular development is not clear. The objective of this study was to investigate if and how NPY regulates follicle development in the ovary.

Methods

All experiments were performed using Sprague Dawley rats. To understand NPY expression pattern at different stages of follicular development, NPY content was assessed using immunohistochemistry in individual follicles. NPY and its receptors expression pattern were evaluated in granulosa cells isolated from preantral (PA), early antral (EA) and late antral follicles (LAF). The influence of NPY on granulosa cell proliferation and apoptosis were further assessed in vitro, using Ki67- and TUNEL-positivity assays. To investigate whether NPY induced-proliferation in EA granulosa cells is mediated through the activation of NPY receptor Y5 (NPY5R) and Mitogen-activated protein kinase (MEK) signal pathway, EA granulosa cells were treated with NPY5R antagonist (CGP71683) and MEK inhibitors (PD98059 and U0126), and Ki67-positive cells were assessed.

Results

NPY protein expression was follicular stage-dependent and cell type-specific. NPY signal intensity in EA was higher than those in PA and LAF. Antral granulosa cells showed the highest signal intensity compared to mural granulosa cells, cumulus cells and theca cells. Granulosa cells NPY protein content and mRNA abundance were higher in EA than in LAF. NPY receptor contents in granulosa cells were follicular stage-dependent. While NPY reduced apoptosis of EA granulosa cells, it increased the proliferation through NPY5R and MEK pathway. In contrast, in LAF granulosa cells, NPY reduced proliferation and increased the number of apoptotic cells, with no significant effects on PA granulosa cells.

Conclusion

This study is the first to evaluate the intraovarian role of NPY in granulosa cells at various stage of follicular development. These results indicate that NPY regulates granulosa cells proliferation and apoptosis in a follicular stage-dependent and autocrine manner. NPY may play a role in pathogenesis of ovarian follicular disorders.
Is there an interest in repeating the vaginal administration of dinoprostone (Propess®), to promote induction of labor of pregnant women at term? (RE-DINO): study protocol for a randomized controlled trial
Authors: Coste Mazeau P. , Hessas M. , Martin R. , Eyraud J.-L. , Margueritte F. , Aubard Y. , Sallee C. , Sire F. , Gauthier T.
Published: January 2020

Background

Labor is induced in over 20% of women in France. Prostaglandins, especially intravaginal dinoprostone (Propess®), are widely used to initiate cervical ripening. If labor does not start within 24 h, there is uncertainty about whether to administer a second dinoprostone pessary or to use oxytocin to induce labor in order to achieve a vaginal delivery.

Methods

RE-DINO is a prospective, open-label, multicenter, randomized superiority trial with two parallel arms running in six French hospitals. A total of 360 patients ≥ 18 years of age at > 37 weeks of gestation who exhibit unfavorable cervical conditions (Bishop score < 6) 24 h after placement of the first Propess®, with fetuses in cephalic presentation, will be included. Patients with premature membrane rupture, uterine scars, or multiple pregnancies will be excluded. Our principal objective is to determine whether placement of a second Propess® (followed by oxytocin [Syntocinon®], if necessary) in women for whom the first Propess® failed to induce cervical ripening increases the vaginal delivery rate compared to direct oxytocin injection. The vaginal delivery rate is therefore the primary outcome. The secondary outcomes are the induction failure rates and maternofetal morbidity and mortality.

Discussion

This study may help in determining the optimal way to induce labor after failure of a first Propess®, an unresolved problem to date. This trial explores the effectiveness and safety of placing a second Propess® and may contribute to development of an obstetric consensus.

Trial registration

Registered on 2 September 2016 at clinicaltrials.gov (identification number NCT02888041).
SINE Retrotransposon variation drives Ecotypic disparity in natural populations of Coilia nasus
Authors: Liu Dong , Yang Jinquan , Tang Wenqiao , Zhang Xing , Royster Clay Matthew , Zhang Ming
Published: January 2020

Background

SINEs are a type of nonautonomous retrotransposon that can transpose from one site to be integrated elsewhere in an organism genome. SINE insertion can give rise to genetic variants and regulate gene expression, allowing organisms to acquire new adaptive capacity. Studies on this subject have focused on the impacts of SINEs on genes. However, ecological disparities in fish have not yet been explained by SINEs.

Results

New SINEs were isolated fromCoilia nasus,which has two ecotypes—migratory and resident—that differ in their spawning and migration behaviors. The SINEs possess two structures that resemble a tRNA gene and a LINE retrotransposon tail. Comparison of olfactory tissue transcriptomes, intact SINE transcript copies were detected in only the migratory fish at the initial retrotransposition stage. The SINE DNA copy numbers were higher in the resident type than in the migratory type, while the frequency of SINE insertion was higher in the migratory type than in the resident type. Furthermore, SINE insertions can lead to new repeats of short DNA fragments in the genome, along with target site duplications. SINEs in the resident type have undergone excision via a mechanism in which predicted cleavage sites are formed by mutations, resulting in gaps that are then filled by microsatellites via microhomology-induced replication.

Conclusions

Notably, SINEs in the resident type have undergone strong natural selection, causing genomic heteroplasmy and driving ecological diversity ofC. nasus. Our results reveal possible evolutionary mechanisms underlying the ecological diversity at the interface between SINE mobilization and organism defense.
Correction to: Nested plant LTR retrotransposons target specific regions of other elements, while all LTR retrotransposons often target palindromes and nucleosome-occupied regions: in silico study
Authors: Jedlicka Pavel , Lexa Matej , Vanat Ivan , Hobza Roman , Kejnovsky Eduard
Published: January 2020

Following publication of the original article [1], the authors spotted an error in Table 2.
Biophysical classification of a CACNA1D de novo mutation as a high-risk mutation for a severe neurodevelopmental disorder
Authors: Hofer Nadja T. , Tuluc Petronel , Ortner Nadine J. , Nikonishyna Yuliia V. , Fernándes-Quintero Monica L. , Liedl Klaus R. , Flucher Bernhard E. , Cox Helen , Striessnig Jörg
Published: January 2020

Background

There is increasing evidence that de novo CACNA1D missense mutations inducing increased Cav1.3 L-type Ca2+-channel-function confer a high risk for neurodevelopmental disorders (autism spectrum disorder with and without neurological and endocrine symptoms). Electrophysiological studies demonstrating the presence or absence of typical gain-of-function gating changes could therefore serve as a tool to distinguish likely disease-causing from non-pathogenic de novo CACNA1D variants in affected individuals. We tested this hypothesis for mutation S652L, which has previously been reported in twins with a severe neurodevelopmental disorder in the Deciphering Developmental Disorder Study, but has not been classified as a novel disease mutation.

Methods

For functional characterization, wild-type and mutant Cav1.3 channel complexes were expressed in tsA-201 cells and tested for typical gain-of-function gating changes using the whole-cell patch-clamp technique.

Results

Mutation S652L significantly shifted the voltage-dependence of activation and steady-state inactivation to more negative potentials (~ 13–17 mV) and increased window currents at subthreshold voltages. Moreover, it slowed tail currents and increased Ca2+-levels during action potential-like stimulations, characteristic for gain-of-function changes. To provide evidence that only gain-of-function variants confer high disease risk, we also studied missense variant S652W reported in apparently healthy individuals. S652W shifted activation and inactivation to more positive voltages, compatible with a loss-of-function phenotype. Mutation S652L increased the sensitivity of Cav1.3 for inhibition by the dihydropyridine L-type Ca2+-channel blocker isradipine by 3–4-fold.

Conclusions and limitations

Our data provide evidence that gain-of-function CACNA1D mutations, such as S652L, but not loss-of-function mutations, such as S652W, cause high risk for neurodevelopmental disorders including autism. This adds CACNA1D to the list of novel disease genes identified in the Deciphering Developmental Disorder Study. Although our study does not provide insight into the cellular mechanisms of pathological Cav1.3 signaling in neurons, we provide a unifying mechanism of gain-of-function CACNA1D mutations as a predictor for disease risk, which may allow the establishment of a more reliable diagnosis of affected individuals. Moreover, the increased sensitivity of S652L to isradipine encourages a therapeutic trial in the two affected individuals. This can address the important question to which extent symptoms are responsive to therapy with Ca2+-channel blockers.
Building attention and edge message passing neural networks for bioactivity and physical–chemical property prediction
Authors: Withnall M. , Lindelöf E. , Engkvist O. , Chen H.
Published: January 2020

Neural Message Passing for graphs is a promising and relatively recent approach for applying Machine Learning to networked data. As molecules can be described intrinsically as a molecular graph, it makes sense to apply these techniques to improve molecular property prediction in the field of cheminformatics. We introduce Attention and Edge Memory schemes to the existing message passing neural network framework, and benchmark our approaches against eight different physical–chemical and bioactivity datasets from the literature. We remove the need to introduce a priori knowledge of the task and chemical descriptor calculation by using only fundamental graph-derived properties. Our results consistently perform on-par with other state-of-the-art machine learning approaches, and set a new standard on sparse multi-task virtual screening targets. We also investigate model performance as a function of dataset preprocessing, and make some suggestions regarding hyperparameter selection.
Co-composting of chicken manure with organic wastes: characterization of gases emissions and compost quality
Authors: Hwang Hyun Young , Kim Seong Heon , Kim Myung Sook , Park Seong Jin , Lee Chang Hoon
Published: January 2020

Co-composting of organic wastes is globally recognized to be effective method to dispose two or more wastes at once and minimize drawbacks of composting such as gases emissions and nutrient reduction. In this study, pilot-scale experiments were conducted to characterize the co-composting process of chicken manure with cow manure (CC), swine manure (CS), plant residues plus mushroom media (CRM), on emissions of greenhouse gas, and ammonia, compost quality, maturity and their correlations. The results showed that cumulative flux of carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O) and ammonia (NH3) widely ranged like 38,211–50,830, 172–417, 98–142 and 118–927 g kg dm−1 day−1 respectively. It indicated the importance of selection for co-composting material. The NH3 emission was significantly increased by 4.3–7.9 times in CS and CRM, compared to OC and CC. Both of CS and CRM also showed longer thermophilic phase and later maturation were also observed in both treatments. Temperature was positively correlated with gases (P < 0.001) except CH4, and nitrogen content, C/N ratio and nitrate nitrogen significantly affected emission of carbon and nitrogen (P < 0.001). In conclusion, for chicken manure composting, sole chicken manure or combination with cow manure could be suitable composting method to improve compost quality and minimize gases losses.
A sustainable process for biodiesel production using Zn/Mg oxidic species as active, selective and reusable heterogeneous catalysts
Authors: Navas Marisa B. , Ruggera José F. , Lick Ileana D. , Casella Mónica L.
Published: January 2020

This paper describes the preparation and characterization of MgO and ZnO-based catalysts, pure and mixed in different proportions, supported on γ-Al2O3. Their catalytic performance was studied in the transesterification of soybean oil and castor oil with methanol and butanol, attempting to produce biodiesel. XRD (X-ray diffraction), SEM–EDS (scanning electron microscopy–energy dispersive X-ray spectroscopy), CO2-adsorption and N2-adsorption allowed characterizing the prepared catalysts. The characterization results were in all cases consistent with mesoporous solids with high specific surface area. All the catalysts exhibited good results, especially in the transesterification of castor oil using butanol. For this reaction, the reuse was tested, maintaining high FABE (fatty acid butyl esters) yields after four cycles. This good performance can be attributed to the basic properties of the Mg species, and simultaneously, to the amphoteric properties of ZnO, which allow both triglycerides and free fatty acids to be converted into esters. Using these catalysts, it is possible to obtain second-generation biodiesel, employing castor oil, a raw material that does not compete with the food industry. In addition, butanol can be produced from renewable biomass.