bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orotracheal treprostinil administration attenuates bleomycin‐induced lung injury, vascular remodeling, and fibrosis in mice
Authors: Nikitopoulou Ioanna , Manitsopoulos Nikolaos , Kotanidou Anastasia , Tian Xia , Petrovic Aleksandar , Magkou Christina , Ninou Ioanna , Aidinis Vassilis , Schermuly Ralph T. , Kosanovic Djuro , Orfanos Stylianos E. 
Published: September 2019

Pulmonary fibrosis is a progressive disease characterized by disruption of lung architecture and deregulation of the pulmonary function. Prostacyclin, a metabolite of arachidonic acid, is a potential disease mediator since it exerts anti‐inflammatory and anti‐fibrotic actions. We investigated the effect of treprostinil, a prostacyclin analogue, in bleomycin‐induced experimental pulmonary fibrosis. Bleomycin sulfate or saline was administrated intratracheally to mice (n = 9–10/group) at day 0. Orotracheal aspiration of treprostinil or vehicle was administered daily and started 24 h prior to bleomycin challenge. Evaluation of lung pathology was performed in tissue samples and bronchoalveolar lavage fluid collected 7, 14 and 21 days after bleomycin exposure. Lung injury was achieved due to bleomycin exposure at all time points as indicated by impaired lung mechanics, pathologic lung architecture (from day 14), and cellular and protein accumulation in the alveolar space accompanied by a minor decrease in lung tissue VE‐cadherin at day 14. Treprostinil preserved lung mechanics, and reduced lung inflammation, fibrosis, and vascular remodeling (day 21); reduced cellularity and protein content of bronchoalveolar lavage fluid were additionally observed with no significant effect on VE‐cadherin expression. Bleomycin‐induced collagen deposition was attenuated by treprostinil from day 14, while treprostinil involvement in regulating inflammatory processes appears mediated by NF‐κB signaling. Overall, prophylactic administration of treprostinil, a stable prostacyclin analogue, maintained lung function, and prevented bleomycin‐induced lung injury, and fibrosis, as well as vascular remodeling, a hallmark of pulmonary hypertension. This suggests potential therapeutic efficacy of treprostinil in pulmonary fibrosis and possibly in pulmonary hypertension related to chronic lung diseases.
Enemies and friends in high-tech places: the development and validation of the Online Social Experiences Measure
Authors: Kent de Grey Robert G , Uchino Bert N , Baucom Brian RW , Smith Timothy W , Holton Avery E , Diener Edward F 
Published: September 2019

Background Interpersonal positivity and negativity are separable dimensions both recognized as having important effects on health. Though online social interactions and research examining them are increasingly common, no validated instrument has heretofore been developed to examine social support and social negativity specifically in online contexts. The present studies describe the development and validation of the Online Social Experiences Measure (OSEM) to allow for assessment of online social positivity and negativity simultaneously. Methods and results In Study I, responses to a potential item pool were collected from participants ( N = 557), who were then subdivided into two groups for the purposes of cross-validation via exploratory and confirmatory factor analyses. Results suggested the emergence of two factors: online social support (OSEM+ subscale) and online social negativity (OSEM− subscale). Across Studies I and II ( N = 139), the OSEM showed good convergent and discriminant validity, and both subscales had high internal consistency. Study II included an ambulatory cardiovascular assessment and found the OSEM− subscale to be predictive of elevated diastolic blood pressure and heart rate. The OSEM+ subscale was predictive of more favorable cardiovascular readings for some types of participants (e.g. those with a greater number of online-only social ties). Conclusions Overall, results suggest online social positivity and negativity may have implications for physical health, and that the OSEM may be a useful tool in understanding online social processes.
Experiences of Patient Incivility: A Qualitative Study
Authors: Vargas Emily A , Mahalingam Ramaswami 
Published: September 2019

Background: Incivility is one of the most prevalent forms of interpersonal mistreatment. Although studies have examined the full range of experiences of incivility against nurses and other hospital personnel, very few studies examined the forms of incivility that patients face in a hospital. Objective: To empirically investigate the range of uncivil experiences targeted against patients. Our study furthers our understanding of the phenomenology of incivility from the patients’ perspective. Method: We used interpretative phenomenological analysis to analyze participant’s (n = 173) experiences of incivility in a hospital. Results: We identified 6 major themes of incivility, namely Insensitivity, Identity Stigma, Gaslighting, Infantilization, Poor Communication, and Ignored. Conclusion: The findings highlight that instances of incivility are present in almost all aspects of the patient experience and take on unique forms, given the patient’s role in the hospital. Implications for health consequences are discussed.
Prognostic impact of platelet-to-lymphocyte ratio on diffuse large B-cell lymphoma: a meta-analysis
Authors: Chen Ying , Zhang Zongxin , Fang Qiu , Jian Huiqin 
Published: September 2019

Abstract

Background
Recently, some studies reported the prognostic value of platelet-to-lymphocyte ratio (PLR) in patients with diffuse large B-cell lymphoma (DLBCL), however, the results varied from different studies. Therefore, we performed a meta-analysis to explore the prognostic value of PLR in DLBCL.

Methods
A comprehensive literature retrieval was conducted by using PubMed, Embase, Web of Science, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), and Wanfang. Pooled hazard ratio (HR) and 95% confidence interval (CI) were used to evaluate the association of PLR and overall survival (OS) and progression-free survival (PFS). Odd ratios (ORs) and 95% CIs for clinicopathological characteristics were statistically analyzed.

Results
Eight studies with 1931 patients were included for meta-analysis. The pooled analysis indicated that elevated PLR was significantly associated with poor OS (HR = 1.73, 95% CI 1.29–2.31, p < 0.001), but not PFS (HR = 0.85, 95% CI 0.57–1.27, p = 0.438). Furthermore, elevated PLR was significantly associated with presentation of B symptoms (OR = 2.27, 95% CI 1.29–3.98, p = 0.004), elevated lactate dehydrogenase (LDH) (OR = 2.76, 95% CI 2.05–3.72, p < 0.001), higher tumor stage (OR = 2.22, 95% CI 1.66–2.98, p < 0.001), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2 (OR = 1.71, 95% CI 1.09–2.69, p = 0.019). However, elevated PLR was not significantly correlated with gender, age or cell of origin.

Conclusion
This meta-analysis revealed that PLR may be an effective and noninvasive biomarker for poor prognosis and aggressive disease characteristics for patients with DLBCL.
Health care providers’ perceptions regarding antimicrobial stewardship programs (AMS) implementation—facilitators and challenges: a cross-sectional study in the Eastern province of Saudi Arabia
Authors: Baraka Mohamed A. , Alsultan Hassan , Alsalman Taha , Alaithan Hussain , Islam Md. Ashraful , Alasseri Abdulsalam A. 
Published: September 2019

AbstractBackgroundInfections result from invasions of an organism into body tissues leading to diseases and complications that might eventually lead to death. Inappropriate use of antimicrobials has led to development of antimicrobial resistance (AMR) which has been associated with increased mortality, morbidity and health costs. Antimicrobial stewardship (AMS) programs are designed to ensure appropriate selections of an effective antimicrobial drugs and optimizing antibiotic use to minimize antibiotic resistance by implementing certain policies, strategies and guidelines. The aim of this study was to investigate practitioners’ perceptions regarding AMS implementation and to identify challenges and facilitators of these programs execution.MethodsCross-sectional study among health care providers in Eastern province of Saudi Arabia Hospitals. The data was collected using a survey including questions about demographic data and information about clinicians’ (physicians, pharmacists and nurses) previous experience with AMS and prescribing of antibiotics, the level of knowledge and attitudes regarding AMS programs’ implementation.ResultsMore than 50% of clinicians (N = 184) reported lack of awareness of AMS programs and their components, whereas 71.2% do not have previous AMS experience. The majority of clinicians (72.3%) noticed increasing number of AMR infections over the past 5 years and (69.6%) were involved in care of patients with an antibiotic-resistant infection. Around 77.2% of respondents reported that formulary management can be helpful for AMS practice and majority of respondents (79.9%) reported that the availability of pathogens and antimicrobial susceptibility testing can be helpful for AMS. Major barriers to AMS implementation identified were lack of internal policy/guidelines and specialized AMS information resources. Lack of administrative awareness about AMS programs; lack of personnel, time limitation, limited training opportunities, lack of confidence, financial issue or limited funding and lack of specialized AMS information resources were also reported 65.8%, 62.5%, 60.9%, 73.9%, 50%, 54.3 and 74.5%, respectively.ConclusionOur study identified comprehensive education and training needs for health care providers about AMS programs. Furthermore, it appears that internal policy and guidelines need revision to ensure that the health care providers work consistently with AMS. Future research must focus on the benefit of implementing AMS as many hospitals are not implementing AMS as revealed by the clinicians. We recommend policy makers and concerned health authorities to consider the study findings into account to optimize AMS implementation.
The development of an herbal material quality control strategy considering the effects of manufacturing processes
Authors: Pan Jingjing , He Siyuan , Zheng Jiayao , Shao Jingyuan , Li Ning , Gong Yunqi , Gong Xingchu 
Published: September 2019

Abstract

Background
Quality by design (QbD) is an advanced drug quality control concept that has been gradually implemented in the optimization of manufacturing processes of Chinese medicines. However, the variation of Chinese medicinal material quality has rarely been considered in published works. Because manufacturing processes may lower the variation introduced through different batches of materials, a material quality control strategy should be developed considering the influences of manufacturing processes.

Methods
In this work, the processes of extraction, concentration, water precipitation, and chromatography for notoginseng total saponin (NTS) production were investigated while considering Panax notoginseng quality variation as a sample. Ten process parameters were studied simultaneously using a definitive screening design. After the process critical quality attributes (CQAs) were determined, critical process parameters (CPPs) and critical material attributes (CMAs) were identified simultaneously. Then, models utilizing the CMAs, CPPs, and process CQAs were developed. The design space was then calculated using a Monte Carlo simulation method with an acceptable probability of 0.90. A material quality control strategy considering the influences of manufacturing processes was proposed.

Results
The ginsenoside Rd purity and total saponin purity in the eluate were identified as process CQAs. The ethanol solution concentration used for extraction, the ethanol solution concentration used for elution, and elution time were identified as CPPs. The extractable dry matter content of Panax notoginseng was one of the CMAs. The extractable contents of notoginsenoside R1, ginsenoside Rg1, ginsenoside Rb1, and ginsenoside Rd were the other CMAs. The inequalities implemented to discriminate the high quality and low quality of Panax notoginseng were developed according to the NTS standard of the Xuesaitong injection. Low quality Panax notoginseng should not be released for NTS production. High quality Panax notoginseng can be treated with feasible manufacturing processing parameters. Verification experiments were carried out successfully for 2 batches of high quality Panax notoginseng.

Conclusions
In this work, a quality control strategy for herbal materials was developed considering the matching of process characteristics and material quality attributes. This strategy is promising for application to other Chinese medicines.
Borrelia spp. in small mammals in Romania
Authors: Kalmár Zsuzsa , Sándor Attila Dávid , Matei Ioana Adriana , Ionică Angela , D’Amico Gianluca , Gherman Călin Mircea , Mihalca Andrei Daniel 
Published: September 2019

Abstract

Background
Small mammals play an important role in the life-cycle of ticks and are reservoirs for several zoonotic pathogens. The aim of this study was to provide epidemiological data regarding the presence of Borrelia spp. in tissues of small mammals from Romania.

Methods
We examined 401 individuals belonging to 11 small mammal species collected in Romania. Collections cover the largest effort to survey these reservoirs in the country. Tissue samples were analyzed by multiplex qPCR targeting the ospA gene of Borrelia burgdorferi (s.l.) and a part of the flaB gene of B. miyamotoi. Positive samples were further analysed by conventional PCR and sequenced.

Results
The overall prevalence of infection with Borrelia spp. in small mammal tissues was 4.9%. The most commonly detected species were B. afzelii, followed by B. garinii/B. bavariensis, B. miyamotoi and B. burgdorferi (s.s.). To our knowledge, we report for the first time the detection of Borrelia spp. in Crocidura leucodon and C. suaveolens, and B. miyamotoi in the liver of Myodes glareolus.

Conclusions
To our knowledge, our study evaluates for the first time the occurrence of Borrelia spp. in small mammals in Romania, contributing to a better knowledge of the distribution of these bacteria. This survey upgrades previous data on the spatial distribution of the pathogens and reveals the importance of animal surveillance regarding Lyme borreliosis and relapsing fever caused by B. miyamotoi.
Apolipoprotein E promoter genotypes are not associated with white matter hyperintensity development in high-altitude careers
Authors: Chapleau Richard R. , Martin CharLee A. , Hughes Summer R. , Baldwin James C. , Sladky John , Sherman Paul M. , Grinkemeyer Michael 
Published: September 2019

Abstract

Objective
This study sought to determine if there is an association between variants in the apolipoprotein E (ApoE) promoter regions and development of white matter hyperintensities (WMH) in military subjects who have been exposed to high altitude. In an earlier study, we found that ApoE status did not correlate with WMH development, and here we hypothesized that regulation of APOE protein expression may be protective.

Results
Our cohort of 92 subjects encountered altitude exposures above 25,000 feet mean sea level through their occupations as pilots or altitude chamber technicians. Using Taqman-style polymerase chain reaction genotyping and t-tests and two-way analyses of variance we found no significant association between ApoE promoter genotypes and the presence, volume, or quantity of WMHs after high altitude exposure. Taken together, the observations that neither ApoE genotype status nor promoter status are associated with WMH properties, we believe that the mechanism of action for developing WMH does not derive from ApoE, nor would therapies for ApoE-mediated neurodegeneration likely benefit high altitude operators.
A general approach for retrosynthetic molecular core analysis
Authors: Naveja J. Jesús , Pilón-Jiménez B. Angélica , Bajorath Jürgen , Medina-Franco José L. 
Published: September 2019

Abstract
Scaffold analysis of compound data sets has reemerged as a chemically interpretable alternative to machine learning for chemical space and structure–activity relationships analysis. In this context, analog series-based scaffolds (ASBS) are synthetically relevant core structures that represent individual series of analogs. As an extension to ASBS, we herein introduce the development of a general conceptual framework that considers all putative cores of molecules in a compound data set, thus softening the often applied “single molecule–single scaffold” correspondence. A putative core is here defined as any substructure of a molecule complying with two basic rules: (a) the size of the core is a significant proportion of the whole molecule size and (b) the substructure can be reached from the original molecule through a succession of retrosynthesis rules. Thereafter, a bipartite network consisting of molecules and cores can be constructed for a database of chemical structures. Compounds linked to the same cores are considered analogs. We present case studies illustrating the potential of the general framework. The applications range from inter- and intra-core diversity analysis of compound data sets, structure–property relationships, and identification of analog series and ASBS. The molecule–core network herein presented is a general methodology with multiple applications in scaffold analysis. New statistical methods are envisioned that will be able to draw quantitative conclusions from these data. The code to use the method presented in this work is freely available as an additional file. Follow-up applications include analog searching and core structure–property relationships analyses.
Identification of Actionable Genomic Alterations Using Circulating Cell-Free DNA
Authors: Sánchez Nora S. , Kahle Michael P. , Bailey Ann Marie , Wathoo Chetna , Balaji Kavitha , Demirhan Mehmet Esat , Yang Dong , Javle Milind , Kaseb Ahmed , Eng Cathy , Subbiah Vivek , Janku Filip , Raymond Victoria M. , Lanman Richard B. , Mills Shaw Kenna R. , Meric-Bernstam Funda 
Published: September 2019

PURPOSE Cell-free DNA (cfDNA) next-generation sequencing is a noninvasive approach for genomic testing. We report the frequency of identifying alterations and their clinical actionability in patients with advanced/metastatic cancer. PATIENTS AND METHODS Prospectively consented patients had cfDNA testing performed. Alterations were assessed for therapeutic implications. RESULTS We enrolled 575 patients with 37 tumor types. Of these patients, 438 (76.2%) had at least one alteration detected, and 205 (35.7%) had one or more alterations of high potential for clinical action. In diseases with 10 or more patients enrolled, 50% or more had at least one alteration deemed of high potential for clinical action. Trials were identified in 80% of patients (286 of 357) with any alteration and in 92% of patients (188 of 205) with one or more alterations of high potential for clinical action of whom 57.6% (118 of 205) had 6 or more months of follow-up available. Of these patients, 10% (12 of 118) had received genomically matched therapy through enrollment in clinical trials (n = 8), off-label drug use (n = 3), or standard of care (n = 1). Although 88.6% of all patients had a performance status of 0 or 1 upon enrollment, the primary reason for not acting on alterations was poor performance status at next treatment change (28.1%; 27 of 96). CONCLUSION cfDNA testing represents a readily accessible method for genomic testing and allows for detection of genomic alterations in most patients with advanced disease. Utility may be higher in patients interested in investigational therapeutics with adequate performance status. Additional study is needed to determine whether utility is enhanced by testing earlier in the treatment course.
Noninvasive Prenatal Diagnosis for Cystic Fibrosis: Implementation, Uptake, Outcome, and Implications
Authors: Chandler Natalie J , Ahlfors Helena , Drury Suzanne , Mellis Rhiannon , Hill Melissa , McKay Fiona J , Collinson Claire , Hayward Jane , Jenkins Lucy , Chitty Lyn S 
Published: September 2019

Abstract

BACKGROUND
Noninvasive prenatal diagnosis (NIPD) for monogenic disorders has a high uptake by families. Since 2013, our accredited public health service laboratory has offered NIPD for monogenic disorders, predominantly for de novo or paternally dominantly inherited mutations. Here we describe the extension of this service to include definitive NIPD for a recessive condition, cystic fibrosis (CF).

METHODS
Definitive NIPD for CF was developed using next-generation sequencing. Validation was performed on 13 cases from 10 families before implementation. All cases referred for CF NIPD were reviewed to determine turnaround times, genotyping results, and pregnancy outcomes.

RESULTS
Of 38 referrals, 36 received a result with a mean turnaround of 5.75 days (range, 3–11 days). Nine cases were initially inconclusive, with 3 reported unaffected because the low-risk paternal allele was inherited and 4 cases in which the high-risk paternal allele was inherited, receiving conclusive results following repeat testing. One case was inconclusive owing to a paternal recombination around the mutation site, and one case was uninformative because of no heterozygosity. Before 2016, 3 invasive referrals for CF were received annually compared with 38 for NIPD in the 24 months since offering a definitive NIPD service.

CONCLUSIONS
Timely and accurate NIPD for definitive prenatal diagnosis of CF is possible in a public health service laboratory. The method detects recombinations, and the service is well-received as evidenced by the significant increase in referrals. The bioinformatic approach is gene agnostic and will be used to expand the range of conditions tested for.
The business capacity of broiler farmers in the partnership business pattern
Authors: Suryanti R. , Sumardjo S. , Syahyuti S. , Tjitropranoto P. 
Published: September 2019

The present study was conducted to analyze the broiler farmers’ capacity level in the partnership pattern and to analyze the factors which affect it. The current study was conducted in Bogor and Sukabumi, West Java Province using a survey approach on 247 farmers who ran farm businesses with the partnership pattern. Data were collected through questionnaire filling by farmers and in-depth interviews with key informants. The data were collected from July to October 2018. The data were analyzed descriptively and with inferential analysis (regression). The results of the study revealed that the farmers’ business capacity was weak. This was evident in the managerial and partnership capability which was categorized as low, the entrepreneurship and problem-solving capability which was categorized as medium, and only the technical capability which was categorized as high. The regression results demonstrated that business capacity was influenced positively by the formal education level, social environment characteristics (organizational support, access to experts), and the role of private extension agents (their role as educators, communicators, consultants, dynamizators, and organizers).