bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inclusion of diabetic retinopathy screening strategies in national-level diabetes care planning in low-income and middle-income settings: protocol for a scoping review
Authors: Curran Katie , Piyasena Prabhath , Congdon Nathan , Duke Lisa , Malanda Belma , Peto Tunde 
Published: September 2020

IntroductionThe diabetes mellitus (DM) epidemic is a major public health concern globally, with the highest-burden in low-income and middle-income countries (LMICs). Diabetic retinopathy (DR) is a microvascular complication of diabetes, and if left untreated can lead to visual impairment and blindness. Epidemiological studies suggest that the incidence of sight-threatening DR is decreasing in high-income countries due to improved treatments and management of DM; however, these trends are not replicated in LMICs. In this paper, we outline a scoping review protocol that aims to identify which LMICs have included DR in their national DM, non-communicable disease or prevention of blindness plans. The scoping review also aims to assess gaps when implementing national DR screening programmes in LMICs.Methods and analysisThis scoping review will follow the Arksey and O’Malley (2005) methodology and the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Review guidelines. A comprehensive search of peer-reviewed and grey literature will be conducted from October 1989 (St. Vincent Declaration) to February 2020. Studies will be identified from electronic databases; Medline, Embase and CENTRAL (Cochrane Library). To identify further relevant articles, a hand search will be conducted using the reference lists of included studies. Two reviewers will independently screen records for relevant data and disagreements about eligibility will be resolved through consensus or arbitration by a third reviewer. A quantitative analysis will be performed to highlight key findings and thematic analysis will be used to identify emerging themes and subthemes from included studies. The key themes will highlight countries progress in terms of national-level DR service planning and screening implementation.Ethics and disseminationNo ethical approval is required because the scoping review methodology aims to synthesise information from publicly available resources. The results will be disseminated through conference presentations and peer-reviewed publication.
History of coronary heart disease increased the mortality rate of patients with COVID-19: a nested case–control study
Authors: Gu Tian , Chu Qiao , Yu Zhangsheng , Fa Botao , Li Anqi , Xu Lei , Wu Ruijun , He Yaping 
Published: September 2020

ObjectiveEvaluate the risk of pre-existing comorbidities on COVID-19 mortality, and provide clinical suggestions accordingly.SettingA nested case–control design using confirmed case reports released from the news or the national/provincial/municipal health commissions of China between 18 December 2019 and 8 March 2020.ParticipantsPatients with confirmed SARS-CoV-2 infection, excluding asymptomatic patients, in mainland China outside of Hubei Province.Outcome measuresPatient demographics, survival time and status, and history of comorbidities.MethodA total of 94 publicly reported deaths in locations outside of Hubei Province, mainland China, were included as cases. Each case was matched with up to three controls, based on gender and age ±1 year old (94 cases and 181 controls). The inverse probability-weighted Cox proportional hazard model was performed, controlling for age, gender and the early period of the outbreak.ResultsOf the 94 cases, the median age was 72.5 years old (IQR=16), and 59.6% were men, while in the control group the median age was 67 years old (IQR=22), and 64.6% were men. Adjusting for age, gender and the early period of the outbreak, poor health conditions were associated with a higher risk of COVID-19 mortality (HR of comorbidity score, 1.31 [95% CI 1.11 to 1.54]; p=0.001). The estimated mortality risk in patients with pre-existing coronary heart disease (CHD) was three times that of those without CHD (p<0.001). The estimated 30-day survival probability for a profile patient with pre-existing CHD (65-year-old woman with no other comorbidities) was 0.53 (95% CI 0.34 to 0.82), while it was 0.85 (95% CI 0.79 to 0.91) for those without CHD. Older age was also associated with increased mortality risk: every 1-year increase in age was associated with a 4% increased risk of mortality (p<0.001).ConclusionExtra care and early medical interventions are needed for patients with pre-existing comorbidities, especially CHD.
What do double-check routines actually detect? An observational assessment and qualitative analysis of identified inconsistencies
Authors: Pfeiffer Yvonne , Zimmermann Chantal , Schwappach David L. B. 
Published: September 2020

ObjectivesDouble checking is used in oncology to detect medication errors before administering chemotherapy. The objectives of the study were to determine the frequency of detected potential medication errors, i.e., mismatching information, and to better understand the nature of these inconsistencies.DesignIn observing checking procedures, field noteswere taken of all inconsistencies that nurses identified during double checking the order against the prepared chemotherapy.SettingOncological wards and ambulatory infusion centres of three Swiss hospitals.ParticipantsNurses’ double checking was observed.Outcome measuresIn a qualitative analysis, (1) a category system for the inconsistencies was developed and (2) independently applied by two researchers.ResultsIn 22 (3.2%) of 690 observed double checks, 28 chemotherapy-related inconsistencies were detected. Half of them related to non-matching information between order and drug label, while the other half was identified because the nurses used their own knowledge. 75% of the inconsistencies could be traced back to inappropriate orders, and the inconsistencies led to 33 subsequent or corrective actions.ConclusionsIn double check situations, the plausibility of the medication is often reviewed. Additionally, they serve as a correction for errors and that are made much earlier in the medication process, during order. Both results open up new opportunities for improving the medication process.
Community knowledge, perceptions and practices around COVID-19 in Sierra Leone: a nationwide, cross-sectional survey
Authors: Sengeh Paul , Jalloh Mohammad B , Webber Nance , Ngobeh Ibrahim , Samba Thomas , Thomas Harold , Nordenstedt Helena , Winters Maike 
Published: September 2020

ObjectivesTo assess the public’s knowledge, attitudes and practices about the novel coronavirus in Sierra Leone to inform an evidence-based communication strategy around COVID-19.DesignNationwide, cross-sectional Knowledge, Attitudes and Practices survey.Setting56 randomly selected communities in all 14 districts in Sierra Leone.Participants1253 adults aged 18 years and older of which 52% were men.Main outcome measuresWe calculated proportions of core indicators (awareness, knowledge, risk perception, practices). A composite variable for knowledge (based on seven variables) was created, and categorised into low (0–2 correct), medium (3–4) and high (5–7). Predictors of knowledge were analysed with multilevel ordinal regression models. Associations between information sources, knowledge and two practices (washing hands with soap and avoiding crowds) were analysed using multilevel logistic regression models.ResultsWe found that 75% of the respondents felt at moderate or great risk of contracting coronavirus. A majority (70%) of women did not know you can survive COVID-19, compared with 61% of men. 60% of men and 54% of women had already taken action to avoid infection with the coronavirus, mostly washing hands with soap and water (87%). Radio (73%) was the most used source for COVID-19 information, followed by social media (39%). Having a medium or high level of knowledge was associated with higher odds of washing hands with soap (medium knowledge: adjusted OR (AOR) 2.1, 95% CI 1.0 to 4.4; high knowledge: AOR 4.6, 95% CI 2.1 to 10.2) and avoiding crowds (medium knowledge: AOR 2.0, 95% CI 1.1 to 3.6; high knowledge: AOR 2.3, 95% CI 1.2 to 4.3).ConclusionsThis study shows that in the context of COVID-19 in Sierra Leone, there is a strong association between knowledge and practices. Because the knowledge gap differs between genders, regions, educational levels and age, it is important that messages are specifically targeted to these core audiences.
Efficacy, Tolerability, and Pharmacokinetics of Combined Targeted MEK and Dual mTORC1/2 Inhibition in a Preclinical Model of Mucosal Melanoma
Authors: Wei Bih-Rong , Hoover Shelley B. , Peer Cody J. , Dwyer Jennifer E. , Adissu Hibret A. , Shankarappa Priya , Yang Howard , Lee Maxwell , Peat Tyler J. , Figg William D. , Simpson R. Mark 
Published: September 2020

Abstract
Melanomas arising in the mucous membranes are a rare and aggressive subtype. New treatment approaches are needed, yet accumulating sufficient evidence to improve patient outcomes is difficult. Clinical and pathological correlates between human and canine mucosal melanomas are substantial, and the relatively greater incidence of spontaneous naturally occurring mucosal melanoma in dogs represents a promising opportunity for predictive modeling. The genomic landscapes of human and canine mucosal melanoma appear highly diverse and generally lack recurring hotspot mutations associated with cutaneous melanomas. Although much remains to be determined, evidence indicates that Ras/MAPK and/or PI3K/AKT/mTOR signaling pathway activations are common in both species and may represent targets for therapeutic intervention. Sapanisertib, an mTORC1/2 inhibitor, was selected from a PI3K/mTOR inhibitor library to collaborate with MEK inhibition; the latter preclinical efficacy was demonstrated previously for canine mucosal melanoma. Combined inhibition of MEK and mTORC1/2, using trametinib and sapanisertib, produced apoptosis and cell-cycle alteration, synergistically reducing cell survival in canine mucosal melanoma cell lines with varying basal signaling activation levels. Compared with individual inhibitors, a staggered sapanisertib dose, coupled with daily trametinib, was optimal for limiting primary mucosal melanoma xenograft growth in mice, and tumor dissemination in a metastasis model, while minimizing hematologic and renal side effects. Inhibitors downmodulated respective signaling targets and the combination additionally suppressed pathway reciprocal crosstalk. The combination did not significantly change plasma sapanisertib pharmacokinetics; however, trametinib area under the curve was increased in the presence of sapanisertib. Targeting Ras/MAPK and PI3K/AKT/mTOR signal transduction pathways appear rational therapies for canine and human mucosal melanoma.
Synthetic Lethal Metabolic Targeting of Androgen-Deprived Prostate Cancer Cells with Metformin
Authors: Yang Bing , Damodaran Shivashankar , Khemees Tariq A. , Filon Mikolaj J. , Schultz Adam , Gawdzik Joseph , Etheridge Tyler , Malin Dmitry , Richards Kyle A. , Cryns Vincent L. , Jarrard David F. 
Published: September 2020

Abstract
The initiation of androgen-deprivation therapy (ADT) induces susceptibilities in prostate cancer cells that make them vulnerable to synergistic treatment and enhanced cell death. Senescence results in cell-cycle arrest, but cells remain viable. In this study, we investigated the mechanisms by which prostate cancer cells undergo senescence in response to ADT, and determined whether an FDA-approved antidiabetic drug metformin has a synergistic effect with ADT in prostate cancer both in vitro and in vivo. Our results show that longer term exposure to ADT induced senescence associated with p16INK4a and/or p27kip2 induction. The activation of PI3K/AKT and inactivation of AMPK in senescent cells resulted in mTORC1 activation. In addition, the antiapoptotic protein XIAP expression was increased in response to ADT. The addition of metformin following ADT induced apoptosis, attenuated mTOR activation, reduced senescent cell number in vitro, and inhibited tumor growth in prostate cancer patient-derived xenograft models. This study suggests that combining ADT and metformin may be a feasible therapeutic approach to remove persistent prostate cancer cells after ADT.
Microparticle Encapsulation of a Prostate-targeted Biologic for the Treatment of Liver Metastases in a Preclinical Model of Castration-resistant Prostate Cancer
Authors: Rogers Oliver C. , Antony Lizamma , Levy Oren , Joshi Nitin , Simons Brian W. , Dalrymple Susan L. , Rosen D. Marc , Pickering Andrew , Lan Haoyue , Kuang Heidi , Ranganath Sudhir H. , Zheng Lei , Karp Jeffrey M. , Howard S. Peter , Denmeade Samuel R. , Isaacs John T. , Brennen W. Nathaniel 
Published: September 2020

Abstract
PRX302 is a highly potent, mutant bacterial pore-forming biologic protoxin engineered for selective activation by PSA, a serine protease expressed by benign and malignant prostate epithelial cells. Although being developed as a local therapy for benign prostatic hyperplasia and localized prostate cancer, PRX302 cannot be administered systemically as a treatment for metastatic disease due to binding to ubiquitously expressed glycosylphosphatidylinositol (GPI)-anchored proteins, which leads to poor accumulation within the tumor microenvironment. To overcome this limitation, poly-lactic-co-glycolic acid (PLGA) microparticles encapsulating the protoxin were developed, which are known to accumulate in the liver, a major site of metastasis for prostate cancer and other solid tumors. A highly sensitive and reproducible sandwich ELISA to quantify PRX302 released from microparticles was developed. Utilizing this assay, PRX302 release from different microparticle formulations was assessed over multiple days. Hemolysis assays documented PSA-dependent pore formation and lytic potential (i.e., function) of the released protoxin. MTT assays demonstrated that conditioned supernatant from PRX302-loaded, but not blank (i.e., unloaded), PLGA microparticles was highly cytotoxic to PC3 and DU145 human prostate cancer cells in the presence of exogenous PSA. Microparticle encapsulation prevented PRX302 from immediately interacting with GPI-anchored proteins as demonstrated in a competition assay, which resulted in an increased therapeutic index and significant antitumor efficacy following a single dose of PRX302-loaded microparticles in a preclinical model of prostate cancer liver metastasis with no obvious toxicity. These results document that PRX302 released from PLGA microparticles demonstrate in vivo antitumor efficacy in a clinically relevant preclinical model of metastatic prostate cancer.
The feasibility of obstacle awareness forwarding scheme in a visible light communication vehicular network
Authors: Kristiana Lisa , Darlis Arsyad Ramadhan , Dewi Irma Amelia 
Published: September 2020

A vehicular-to-vehicular (V2V) communication is a part of a vehicular ad-hoc network (VANET) that emerges recently due to the heavy traffic environment. V2V is a frequently changing network since it implements vehicles as mobile nodes. The challenges in implementing V2V are the relatively short duration of possible communication and the uneven city environment caused by high rise buildings or other objects that distract
the signal transmission. The limited transmitting duration between vehicles requires efficient coordination and communication. This work focuses on the utility of visible light communication in vehicular network (VLC-VN) in data transmitting and the obstacle awareness in the forwarding scheme based on our knowledge in previous researches. The result of evaluating the feasibility of VLC-VN forwarding in a freeway environment the transmission delay is lower than 1 second in 500 byte data transmission, however it reaches to only about 4% in throughput as a drawback.
Differential diagnosis for suspected cases of coronavirus disease 2019: a retrospective study
Authors: Chi Qiong , Dai Xinjian , Jiang Xiangao , Zhu Lefei , Du Junyan , Chen Yuxi , Zheng Jiyang , Huang Jianping 
Published: September 2020

Abstract
Background
Since December 2019, the coronavirus disease 2019 (COVID-19) has infected more than 12,322,000 people and killed over 556,000 people worldwide. However, Differential diagnosis remains difficult for suspected cases of COVID-19 and need to be improved to reduce misdiagnosis.

Methods
Sixty-eight cases of suspected COVID-19 treated in Wenzhou Central Hospital from January 21 to February 20, 2020 were divided into confirmed and COVID-19-negative groups based on the results of real-time reverse transcriptase polymerase chain reaction (RT-PCR) nucleic acid testing of the novel coronavirus in throat swab specimens to compare the clinical symptoms and laboratory and imaging results between the groups.

Results
Among suspected patients, 17 were confirmed to COVID-19-positive group and 51 were distinguished to COVID-19-negative group. Patients with reduced white blood cell (WBC) count were more common in the COVID-19-positive group than in the COVID-19-negative group (29.4% vs 3.9%, P = 0.003). Subsequently, correlation analysis indicated that there was a significant inverse correlation existed between WBC count and temperature in the COVID-19-positive patients (r = − 0.587, P = 0.003), instead of the COVID-19-negative group. But reduced lymphocyte count was no different between the two groups (47.1% vs 25.5%, P = 0.096). More common chest imaging characteristics of the confirmed COVID-19 cases by high-resolution computed tomography (HRCT) included ground-glass opacities (GGOs), multiple patchy shadows, and consolidation with bilateral involvement than COVID-19-negative group (82.4% vs 31.4%, P = 0.0002; 41.2% vs 17.6% vs P = 0.048; 76.5% vs 43.1%, P = 0.017; respectively). The rate of clustered infection was higher in COVID-19-positive group than COVID-19-negative group (64.7% vs 7.8%, P = 0.001). Through multiplex PCR nucleic acid testing, 2 cases of influenza A, 3 cases of influenza B, 2 cases of adenovirus, 2 cases of Chlamydia pneumonia, and 7 cases of Mycoplasma pneumoniae were diagnosed in the COVID-19-negative group.

Conclusions
WBC count inversely correlated with the severity of fever, GGOs, multiple patchy shadows, and consolidation in chest HRCT and clustered infection are common but not specific features in the confirmed COVID-19 group. Multiplex PCR nucleic acid testing helped differential diagnosis for suspected COVID-19 cases.
Comparisons of cardiovascular dysautonomia and cognitive impairment between de novo Parkinson’s disease and de novo dementia with Lewy bodies
Authors: Oka Hisayoshi , Umehara Tadashi , Nakahara Atsuo , Matsuno Hiromasa 
Published: September 2020

Abstract
Background
Cognitive impairment may be correlated with cardiovascular dysautonomia, including blood pressure (BP) dysregulation, in Parkinson’s disease (PD), but the association between these factors in dementia with Lewy bodies (DLB) is uncertain. This study aimed to clarify whether cardiovascular dysautonomia had an influence on cognitive function in Lewy body disease or not.

Methods
Ninty-nine patients with de novo PD (n = 75) and DLB (n = 24) were evaluated using the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). Cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, orthostatic hypotension (OH), supine hypertension (SH), postprandial hypotension (PPH), nocturnal BP fall in 24-h ambulatory blood pressure monitoring (ABPM) and constipation were estimated. Associations of these factors with cognitive and executive dysfunction were examined.

Results
In DLB, MIBG uptake was reduced and OH, PPH and SH were severely disturbed, compared to PD. The nocturnal BP fall in ABPM was lower in DLB, and the failure of nocturnal BP fall in PD was associated with MMSE, after adjustment for other clinical features. FAB was significantly associated nocturnal BP fall, age and SH in PD, but no significant correlations among factors were found for DLB.

Conclusion
The significant association between nocturnal BP dysregulation and cognitive or executive decline in PD might be due to impaired microvascular circulation or invasion of α-synuclein in the CNS. The lack of a correlation of BP insufficiency with cognitive impairment in DLB suggests initial involvement of Lewy body pathology in the neocortex, regardless of Lewy body invasion of the autonomic nervous system.
Long-term analysis of multimodality treatment outcomes and prognosis of esthesioneuroblastomas: a single center results of 138 patients
Authors: Sun Meng , Wang Kai , Qu Yuan , Zhang Jianghu , Zhang Shiping , Chen Xuesong , Wang Jingbo , Wu Runye , Zhang Ye , Yi Junlin , Xiao Jianping , Xu Guozhen , Huang Xiaodong , Luo Jingwei 
Published: September 2020

Abstract
Background
The aim of this study is to evaluate the efficacy of different treatment strategies and the potential prognostic factors of esthesioneuroblastoma (ENB).

Materials and methods
Between April 1984 and December 2018, 138 patients with non-metastatic ENB were retrospectively analyzed. The treatment modalities mainly included surgery alone (n = 7), radiotherapy alone (n = 33), concurrent chemoradiotherapy (n = 17), surgery combined with current chemoradiotherapy (n = 32), and surgery plus radiotherapy (n = 49).

Results
The median follow-up time for the entire cohort was 61 months (range, 4–231 months). The 5-year overall survival (OS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) rate were 69.6, 78.0 and 73.9%, respectively. Surgery combined with radiotherapy elicited superior survival results, and the combination of surgery and current chemoradiotherapy achieved the best prognoses for all patients, patients with advanced Kadish disease, patients receiving intensity modulated radiation therapy and those with positive surgical margin. Univariate analysis identified orbital invasion and treatment modalities were predictors for OS, LRFFS and DMFS. Lymph node metastasis was associated with OS and DMFS, but not LRFFS. Intracranial invasion, advanced Kadish stage and not receiving concurrent chemotherapy were also predictive of lower OS. Multivariate analyses indicated that lymph node metastasis was an independent prognostic factor affecting DMFS, whereas treatment modalities was independent prognostic factors for OS and LRFFS.

Conclusion
Orbital invasion, intracranial invasion, lymph node metastasis and advanced Kadish disease at initial diagnosis were significantly associated with inferior prognosis. Regarding the treatment modality, the optimal strategy remined surgery with radiotherapy-based multimodality treatment. The concurrent chemoradiotherapy may play a more beneficial role.