bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropeptide S-initiated sequential cascade mediated by OX1, NK1, mGlu5 and CB1 receptors: a pivotal role in stress-induced analgesia
Authors: Lee Ming Tatt , Chiu Yu-Ting , Chiu Yu-Chun , Hor Chia Chun , Lee Hsin-Jung , Guerrini Remo , Calo Girolamo , Chiou Lih-Chu 
Published: January 2020

Abstract
Background
Stress-induced analgesia (SIA) is an evolutionarily conserved phenomenon during stress. Neuropeptide S (NPS), orexins, substance P, glutamate and endocannabinoids are known to be involved in stress and/or SIA, however their causal links remain unclear. Here, we reveal an unprecedented sequential cascade involving these mediators in the lateral hypothalamus (LH) and ventrolateral periaqueductal gray (vlPAG) using a restraint stress-induced SIA model.

Methods
Male C57BL/6 mice of 8–12 week-old were subjected to intra-cerebroventricular (i.c.v.) and/or intra-vlPAG (i.pag.) microinjection of NPS, orexin-A or substance P alone or in combination with selective antagonists of NPS receptors (NPSRs), OX1 receptors (OX1Rs), NK1 receptors (NK1Rs), mGlu5 receptors (mGlu5Rs) and CB1 receptors (CB1Rs), respectively. Antinociceptive effects of these mediators were evaluated via the hot-plate test. SIA in mice was induced by a 30-min restraint stress. NPS levels in the LH and substance P levels in vlPAG homogenates were compared in restrained and unrestrained mice.

Results
NPS (i.c.v., but not i.pag.) induced antinociception. This effect was prevented by i.c.v. blockade of NPSRs. Substance P (i.pag.) and orexin-A (i.pag.) also induced antinociception. Substance P (i.pag.)-induced antinociception was prevented by i.pag. Blockade of NK1Rs, mGlu5Rs or CB1Rs. Orexin-A (i.pag.)-induced antinociception has been shown previously to be prevented by i.pag. blockade of OX1Rs or CB1Rs, and here was prevented by NK1R or mGlu5R antagonist (i.pag.). NPS (i.c.v.)-induced antinociception was prevented by i.pag. blockade of OX1Rs, NK1Rs, mGlu5Rs or CB1Rs. SIA has been previously shown to be prevented by i.pag. blockade of OX1Rs or CB1Rs. Here, we found that SIA was also prevented by i.c.v. blockade of NPSRs or i.pag. blockade of NK1Rs or mGlu5Rs. Restrained mice had higher levels of NPS in the LH and substance P in the vlPAG than unrestrained mice.

Conclusions
These results suggest that, during stress, NPS is released and activates LH orexin neurons via NPSRs, releasing orexins in the vlPAG. Orexins then activate OX1Rs on substance P-containing neurons in the vlPAG to release substance P that subsequently. Activates NK1Rs on glutamatergic neurons to release glutamate. Glutamate then activates perisynaptic mGlu5Rs to initiate the endocannabinoid retrograde inhibition of GABAergic transmission in the vlPAG, leading to analgesia.
Comorbidities and survival in patients with chronic hypersensitivity pneumonitis
Authors: Wälscher Julia , Gross Benjamin , Morisset Julie , Johannson Kerri A. , Vasakova Martina , Bruhwyler Jacques , Kreuter Michael 
Published: January 2020

Abstract
Introduction
Chronic Hypersensitivity Pneumonitis (cHP) is a fibrotic interstitial lung disease (ILD) resulting from repeated exposure to an offending antigen. Prognostication in cHP remains challenging, and the relationship between comorbidities and survival has yet to be characterized. The aim of this study was to describe the relationship between comorbid conditions and survival in patients with cHP.

Methods
The prospective database from a tertiary referral centre for ILD was reviewed for patient-reported comorbidities, their frequency, and relationship with survival in cHP patients. Comorbidities were assessed by direct questioning of the patient at the baseline visit and by a standardized questionnaire for the diagnosis of interstitial lung diseases. During the follow-up examinations, patients were asked about newly diagnosed comorbidities.

Results
Two hundred eleven patients with cHP were identified (mean age 63 years, 53% male, mean FVC 73%), with mean follow-up of 32 months. The mean number of comorbidities was 3 (10% had 0, 59% 1–3 and 31% ≥4 comorbidities). Most frequent comorbidities groups were cardiovascular (65%) and respiratory (26%), most common comorbidities were hypertension (56%), gastro-esophageal reflux disease (GERD) (24%), diabetes (20%) and coronary heart disease (18%). In general, deceased patients had more comorbidities than survivors (p = 0.005), yet there was no association between the absolute number of comorbidities and survival. Pulmonary hypertension (30.8% versus 5.7%, p = 0.001;), diastolic dysfunction (26.9% versus 6.4%, p = 0.004) and cerebrovascular disease were more frequent in non-survivors (23.1% versus 7.6%, p = 0.026). Lung cancer was not observed, and neither GERD nor antacid drugs were associated with outcome (p = 0.357 and p = 0.961, respectively).

Conclusions
Comorbidities are common in cHP are associated with survival. Further work should determine whether interventions for these specific comorbidities can positively affect survival.
Engineering of Streptomyces lividans for heterologous expression of secondary metabolite gene clusters
Authors: Ahmed Yousra , Rebets Yuriy , Estévez Marta Rodríguez , Zapp Josef , Myronovskyi Maksym , Luzhetskyy Andriy 
Published: January 2020

Abstract
Background
Heterologous expression of secondary metabolite gene clusters is used to achieve increased production of desired compounds, activate cryptic gene clusters, manipulate clusters from genetically unamenable strains, obtain natural products from uncultivable species, create new unnatural pathways, etc. Several Streptomyces species are genetically engineered for use as hosts for heterologous expression of gene clusters. S. lividans TK24 is one of the most studied and genetically tractable actinobacteria, which remain untapped. It was therefore important to generate S. lividans chassis strains with clean metabolic backgrounds.

Results
In this study, we generated a set of S. lividans chassis strains by deleting endogenous gene clusters and introducing additional φC31 attB loci for site-specific integration of foreign DNA. In addition to the simplified metabolic background, the engineered S. lividans strains had better growth characteristics than the parental strain in liquid production medium. The utility of the developed strains was validated by expressing four secondary metabolite gene clusters responsible for the production of different classes of natural products. Engineered strains were found to be superior to the parental strain in production of heterologous natural products. Furthermore, S. lividans-based strains were better producers of amino acid-based natural products than other tested common hosts. Expression of a Streptomyces albus subsp. chlorinus NRRL B-24108 genomic library in the modified S. lividans ΔYA9 and S. albus Del14 strains resulted in the production of 7 potentially new compounds, only one of which was produced in both strains.

Conclusion
The constructed S. lividans-based strains are a great complement to the panel of heterologous hosts for actinobacterial secondary metabolite gene expression. The expansion of the number of such engineered strains will contribute to an increased success rate in isolation of new natural products originating from the expression of genomic and metagenomic libraries, thus raising the chance to obtain novel biologically active compounds.
Klebsiella pneumoniae: an increasing threat to public health
Authors: Effah Clement Yaw , Sun Tongwen , Liu Shaohua , Wu Yongjun 
Published: January 2020

Abstract
Objectives
This review fills the paucity of information on K. pneumoniae as a nosocomial pathogen by providing pooled data on epidemiological risk factors, resistant trends and profiles and resistant and virulent genes of this organism in Asia.

Methods
Exhaustive search was conducted using PubMed, Web of Science, and Google scholar for most studies addressing the prevalence, risk factors, drug resistant-mediated genes and/or virulent factors of K. pneumoniae in Asia. Data extracted for meta-analysis were analyzed using comprehensive meta-analysis version 3. Trends data for the isolation rate and resistance rates were entered into Excel spread sheet and the results were presented in graphs.

Results
The prevalence rate of drug resistance in K. pneumoniae were; amikacin (40.8%) [95% CI 31.9–50.4], aztreonam (73.3%) [95% CI 59.9–83.4], ceftazidime (75.7%) [95% CI 65.4–83.6], ciprofloxacin (59.8%) [95% CI 48.6–70.1], colistin (2.9%) [95% CI 1.8–4.4], cefotaxime (79.2%) [95% CI 68.0–87.2], cefepime (72.6) [95% CI 57.7–83.8] and imipenem (65.6%) [95% CI 30.8–89.0]. TEM (39.5%) [95% CI 15.4–70.1], SHV-11 (41.8%) [95% CI 16.2–72.6] and KPC-2 (14.6%) [95% CI 6.0–31.4] were some of the resistance mediated genes observed in this study. The most virulent factors utilized by K. pneumoniae are; hypermucoviscous phenotype and mucoviscosity-related genes, genes for biosynthesis of lipopolysaccharide, iron uptake and transport genes and finally, adhesive genes.

Conclusion
It can be concluded that, antimicrobial resistant in K. pneumoniae is a clear and present danger in Asia which needs strong surveillance to curb this menace. It is very important for public healthcare departments to monitor and report changes in antimicrobial-resistant isolates.
Insights into the angiogenic effects of nanomaterials: mechanisms involved and potential applications
Authors: Liu Wenjing , Zhang Guilan , Wu Junrong , Zhang Yanli , Liu Jia , Luo Haiyun , Shao Longquan 
Published: January 2020

AbstractThe vascular system, which transports oxygen and nutrients, plays an important role in wound healing, cardiovascular disease treatment and bone tissue engineering. Angiogenesis is a complex and delicate regulatory process. Vascular cells, the extracellular matrix (ECM) and angiogenic factors are indispensable in the promotion of lumen formation and vascular maturation to support blood flow. However, the addition of growth factors or proteins involved in proangiogenic effects is not effective for regulating angiogenesis in different microenvironments. The construction of biomaterial scaffolds to achieve optimal growth conditions and earlier vascularization is undoubtedly one of the most important considerations and major challenges among engineering strategies. Nanomaterials have attracted much attention in biomedical applications due to their structure and unique photoelectric and catalytic properties. Nanomaterials not only serve as carriers that effectively deliver factors such as angiogenesis-related proteins and mRNA but also simulate the nano-topological structure of the primary ECM of blood vessels and stimulate the gene expression of angiogenic effects facilitating angiogenesis. Therefore, the introduction of nanomaterials to promote angiogenesis is a great helpful to the success of tissue regeneration and some ischaemic diseases. This review focuses on the angiogenic effects of nanoscaffolds in different types of tissue regeneration and discusses the influencing factors as well as possible related mechanisms of nanomaterials in endothelial neovascularization. It contributes novel insights into the design and development of novel nanomaterials for vascularization and therapeutic applications.
Modified facelift incision and superficial musculoaponeurotic system flap in parotid malignancy: a retrospective study and review of the literature
Authors: Giotakis Evangelos I. , Giotakis Aris I. 
Published: January 2020

AbstractBackgroundData reporting the use of modified facelift incision (MFI) approach with or without superficial musculoaponeurotic system (SMAS) reconstruction in parotid malignancy are limited. To enhance the limited knowledge in this subject, the authors of the current study report quality data of MFI in patients with parotid malignancy with or without SMAS reconstruction.MethodsWe performed a retrospective review of parotid malignancy patients treated with the MFI over a 5-year period (2015–2019) in the 1st ENT University Department, University of Athens, Greece.ResultsWe identified five patients with parotid malignancy. We performed MFI parotidectomy in 5/5 patients and SMAS reconstruction in 2/5 patients. All tumors were classified as T1N0M0. After a mean follow-up of 43.6 months (minimum, 36; maximum, 55), we noted no recurrence. The patients reported no Frey’s syndrome.ConclusionsThe authors of the current study suggest consideration of the MFI approach in parotid malignancy. A MFI approach should at least favor small parotid tumors without neck metastatic disease (T1cN0). Surgeons could also address larger tumors with a MFI approach. Surgeons should reconstruct the parotid lodge with a SMAS advancement flap in tumors not in proximity with the SMAS.
Understanding the implications of the Sustainable Development Goals for health policy and systems research: results of a research priority setting exercise
Authors: Bennett Sara , Jessani Nasreen , Glandon Douglas , Qiu Mary , Scott Kerry , Meghani Ankita , El-Jardali Fadi , Maceira Daniel , Javadi Dena , Ghaffar Abdul 
Published: January 2020

Abstract
Background
Given the paradigmatic shift represented by the Sustainable Development Goals (SDGs) as compared to the Millennium Development Goals - in particular their broad and interconnected nature - a new set of health policy and systems research (HPSR) priorities are needed to inform strategies to address these interconnected goals.

Objectives
To identify high priority HPSR questions linked to the achievement of the Sustainable Development Goals.

Methods
We focused on three themes that we considered to be central to achieving the health related SDGs: (i) Protecting and promoting access to health services through systems of social protection (ii) Strengthening multisectoral collaborations for health and (iii) Developing more participatory and accountable institutions. We conducted 54 semi-structured interviews and two focus group discussions to investigate policy-maker perspectives on evidence needs. We also conducted an overview of literature reviews in each theme. Information from these sub-studies was extracted into a matrix of possible research questions and developed into three domain-specific lists of 30–36 potential priority questions. Topic experts from the global research community then refined and ranked the proposed questions through an online platform. A final webinar on each theme sought feedback on findings.

Results
Policy-makers continue to demand HPSR for many well-established issues such as health financing, human resources for health, and service delivery. In terms of service delivery, policy-makers wanted to know how best to strengthen primary health care and community-based systems. In the themes of social protection and multisectoral collaboration, prioritized questions had a strong emphasis on issues of practical implementation. For participatory and accountable institutions, the two priority questions focused on political factors affecting the adoption of accountability measures, as well as health worker reactions to such measures.

Conclusions
To achieve the SDGs, there is a continuing need for research in some already well established areas of HPSR as well as key areas highlighted by decision-makers. Identifying appropriate conceptual frameworks as well as typologies of examples may be a prerequisite for answering some of the substantive policymaker questions. In addition, implementation research engaging non-traditional stakeholders outside of the health sector will be critical.
Predictors of historical change in drug treatment coverage among people who inject drugs in 90 large metropolitan areas in the USA, 1993–2007
Authors: Tempalski Barbara , Williams Leslie D. , West Brooke S. , Cooper Hannah L. F. , Beane Stephanie , Ibragimov Umedjon , Friedman Samuel R. 
Published: January 2020

AbstractBackgroundAdequate access to effective treatment and medication assisted therapies for opioid dependence has led to improved antiretroviral therapy adherence and decreases in morbidity among people who inject drugs (PWID), and can also address a broad range of social and public health problems. However, even with the success of syringe service programs and opioid substitution programs in European countries (and others) the US remains historically low in terms of coverage and access with regard to these programs. This manuscript investigates predictors of historical change in drug treatment coverage for PWID in 90 US metropolitan statistical areas (MSAs) during 1993–2007, a period in which, overall coverage did not change.MethodsDrug treatment coverage was measured as the number of PWID in drug treatment, as calculated by treatment entry and census data, divided by numbers of PWID in each MSA. Variables suggested by the Theory of Community Action (i.e., need, resource availability, institutional opposition, organized support, and service symbiosis) were analyzed using mixed-effects multivariate models within dependent variables lagged in time to study predictors of later change in coverage.ResultsMean coverage was low in 1993 (6.7%; SD 3.7), and did not increase by 2007 (6.4%; SD 4.5). Multivariate results indicate that increases in baseline unemployment rate (β = 0.312;pseudo-p < 0.0002) predict significantly higher treatment coverage; baseline poverty rate (β = − 0.486;pseudo-p < 0.0001), and baseline size of public health and social work workforce (β = 0.425;pseudo-p < 0.0001) were predictors of later mean coverage levels, and baseline HIV prevalence among PWID predicted variation in treatment coverage trajectories over time (baseline HIV * Time: β = 0.039;pseudo-p < 0.001). Finally, increases in black/white poverty disparity from baseline predicted significantly higher treatment coverage in MSAs (β = 1.269;pseudo-p < 0.0001).ConclusionsWhile harm reduction programs have historically been contested and difficult to implement in many US communities, and despite efforts to increase treatment coverage for PWID, coverage has not increased. Contrary to our hypothesis, epidemiologic need, seems not to be associated with change in treatment coverage over time. Resource availability and institutional opposition are important predictors of change over time in coverage. These findings suggest that new ways have to be found to increase drug treatment coverage in spite of economic changes and belt-tightening policy changes that will make this difficult.
A brief transdiagnostic psychological intervention for Afghan asylum seekers and refugees in Austria: a randomized controlled trial
Authors: Knefel Matthias , Kantor Viktoria , Nicholson Andrew A. , Schiess-Jokanovic Jennifer , Weindl Dina , Schäfer Ingo , Lueger-Schuster Brigitte 
Published: January 2020

Abstract
Background
Asylum seekers and refugees are at great risk for developing mental disorders. Afghan refugees are a particularly vulnerable group with a low average education and mental health literacy level. Traumatic experiences and hardship before and during migration are predictive of mental health problems. However, post-migration living difficulties (PMLDs) also account for a large proportion of mental distress in such populations, which, critically, are not sufficiently considered in treatment protocols and research investigations. Indeed, the evidence base for the treatment of refugees and asylum seekers is sparse and limited mainly to trauma-specific treatments, where refugees may likely suffer from other mental health problems such as depression or anxiety.

Methods/design
This trial is the first evaluation of a short-term, transdiagnostic treatment protocol for treatment-seeking Afghan refugees which addresses mental health problems and PMLDs while using an adapted version of the Problem Management Plus (PM+) protocol. Here, we will investigate the efficacy of an intervention manual with a prospective, single-center, randomized, assessor-blind, two-group trial among refugees who are on a waiting list for professional mental health treatment. Furthermore, we will investigate participants’ subjective experiences with the intervention manual via in-depth interviews. One hundred twenty people will be assessed and randomly allocated to either the intervention arm or a treatment-as-usual arm. Clinical psychologists will conduct the treatment, and the sessions will take place with a Dari interpreter. The protocol consists of six 90-min sessions. The primary endpoint is the general symptom distress measure, assessed with the General Health Questionnaire 28 (GHQ-28). Secondary endpoints are the Post-Migration Living Difficulties Checklist (PMLDC), the International Trauma Questionnaire (ITQ), the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF), the Psychological Outcome Profile (PSYCHLOPS), service and health care use (assessed with several items), and the Immigrant Integration Index (IPL-12).

Discussion
This trial may provide substantial evidence for a brief transdiagnostic psychological intervention. Here, we intend to contribute to the treatment of mental health problems among Afghan refugees. The assessment of subjective experience with this treatment manual, as well as the evaluation of its clinical applicability, may optimize treatment acceptance and outcomes across a wide range of mental health problems among refugees.

Trial registration
German Clinical Trials Register (DRKS) registration number: DRKS00016538. Universal Trial Number: U1111-1226-3285. Registered on January 7, 2019. https://www.drks.de/drks_web/setLocale_EN.do
Bionomics and insecticide resistance of Aedes albopictus in Shandong, a high latitude and high-risk dengue transmission area in China
Authors: Liu Hongmei , Liu Luhong , Cheng Peng , Yang Linlin , Chen Junhu , Lu Yao , Wang Haifang , Chen Xiao-Guang , Gong Maoqing 
Published: January 2020

AbstractBackgroundDengue fever outbreaks tend to spread northward in China, and Jining is the northernmost region where local dengue fever cases have been detected. Therefore, it is important to investigate the density ofAedes albopictusand its resistance to deltamethrin.MethodsThe Breteau index (BI) and container index (CI) were calculated to assess the larval density ofAe. albopictusand human-baited double net trap (HDN) surveillance was performed in six subordinate counties (Rencheng, Yanzhou, Sishui, Liangshan, Zoucheng and Jiaxiang) of Jining City in 2017 and 2018. The resistance ofAe. albopictusadults to deltamethrin was evaluated using the World Health Organization (WHO) standard resistance bioassay. The mutations atVgsccodons 1532 and 1534 were also analysed to determine the association betweenkdrmutations and phenotypic resistance in adult mosquitoes.ResultsThe average BI, CI and biting rate at Jining were 45.30, 16.02 and 1.97 (female /man/hour) in 2017 and 15.95, 7.86 and 0.59 f/m/h in 2018, respectively. In August 26, 2017, when the first dengue fever case was diagnosed, the BI at Qianli village in Jiaxiang County was 107.27. The application of prevention and control measures by the government sharply decreased the BI to a value of 4.95 in September 3, 2017. The mortality of field-collectedAe. albopictusfemales from Jiaxiang was 41.98%. I1532T, F1534L and F1534S mutations were found in domain III of theVgscgene. This study provides the first demonstration that both I1532T and F1534S mutations are positively correlated with the deltamethrin-resistant phenotype.ConclusionsMosquito density surveillance, resistance monitoring and risk assessment should be strengthened in areas at risk for dengue to ensure the sustainable control ofAe. albopictusand thus the prevention and control of dengue transmission.