bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geographic disparities in Saskatchewan prostate cancer incidence and its association with physician density: analysis using Bayesian models
Authors: Andkhoie Mustafa , Szafron Michael 
Published: August 2021

Abstract
Background
Saskatchewan has one of the highest incidence of prostate cancer (PCa) in Canada. This study assesses if geographic factors in Saskatchewan, including location of where patients live and physician density are affecting the PCa incidence. First, the objective of this study is to estimate the PCa standardized incidence ratio (SIRs) in Saskatchewan stratified by PCa risk-level. Second, this study identifies clusters of higher than and lower than expected PCa SIRs in Saskatchewan. Lastly, this study identifies the association (if any) between family physician density and estimated PCa SIRs in Saskatchewan.

Methods
First, using Global Moran’s I, Local Moran’s I, and the Kuldorff’s Spatial Scan Statistic, the study identifies clusters of PCa stratified by risk-levels. Then this study estimates the SIRs of PCa and its association with family physician density in Saskatchewan using the Besag, York, and Mollie (BYM) Bayesian method.

Results
Higher than expected clusters of crude estimated SIR for metastatic PCa were identified in north-east Saskatchewan and lower than expected clusters were identified in south-east Saskatchewan. Areas in north-west Saskatchewan have lower than expected crude estimated SIRs for both intermediate-risk and low-risk PCa. Family physician density was negatively associated with SIRs of metastatic PCa (IRR: 0.935 [CrI: 0.880 to 0.998]) and SIRs of high-risk PCa (IRR: 0.927 [CrI: 0.880 to 0.975]).

Conclusions
This study identifies the geographical disparities in risk-stratified PCa incidence in Saskatchewan. The study identifies areas with a lower family physician density have a higher-than-expected incidences of metastatic and high-risk PCa. Hence policies to increase the number of physicians should ensure an equitable geographic distribution of primary care physicians to support early detection of diseases, including PCa.
A case report: pseudoxanthoma elasticum diagnosed based on ocular angioid streaks and the curative effect of Conbercept treatment
Authors: Cui Chaoxiong , Zhou Zhanyu , Zhang Yi , Sun Ding 
Published: August 2021

Abstract
Background
This article is a case report of pseudoxanthoma elasticum (PXE) which was diagnosed based on significant angioid streaks (AS) with choroidal neovascularization (CNV) and regain normal visual function by intravitreal injection with Conbercept.

Case presentation
A 51-year-old woman was referred to the Ophthalmology Department of Qingdao Municipal Hospital (Qingdao, China) on September 14, 2020 for metamorphopsia and loss of vision in the left eye in the preceding three days. Past history: high myopia for more than 30 years, best corrected visual acuity (BCVA) of both eyes was 1.0 (5 m Standard Logarithm Visual Acuity chart in decimal notations), hypertension for six years, and cerebral infarction two years ago, no history of ocular trauma or surgeries or similar patients in family was documented. We used methods for observation, including fundus examination, optical coherence tomography (OCT), fluorescein angiography combined with indocyanine green angiography (FFA + ICGA). Due to her symptoms and manifestations, along with the appearance of her neck skin, which resembled ‘chicken skin’, we speculated that she should be further examined at the Department of Dermatology by tissue paraffin section and molecular pathology analyses, and the diagnosis of PXE was then confirmed. After intravitreal injection with Conbercept (10 mg/ml, 0.2 ml, Chengdu Kanghong Biotechnologies Co., Ltd.; Chengdu, Sichuan, China) she regained her BCVA.

Conclusions
This patient regained her best corrected visual acuity through intravitreal injection with Conbercept. To the best of our knowledge, no publications are available on cases in which a vision loss and the normal visual function can be reverted by intravitreal injection with Conbercept. Although PXE is a disease with low incidence and thus no effective cure established, targeted symptomatic treatment can effectively retard the disease progression and improve visual function, such as intravitreal injection with Conbercept.
Health ambassadors in the workplace: a health promotion intervention mobilizing middle managers and RE-AIM evaluation of outcomes
Authors: Greenberg Keren L. , Donchin Milka , Leiter Elisheva , Zwas Donna R. 
Published: August 2021

Abstract
Background
The workplace provides an ideal setting for health promotion, as adults spend most of their day at work. Middle managers hold a strategic position to lead workplace health promotion. This study evaluates the outcomes of an intensive intervention training middle managers to promote health in the workplace.

Methods
A workshop was designed and conducted to train female middle management employees to construct, implement, and evaluate a health promotion program in their workplace. Semi-structured interviews were carried out post-intervention to assess workplace health promotion outcomes according to the RE-AIM framework, and identify variables contributing to success. Additionally, questionnaires were distributed pre and post-program assessing personal health and self-efficacy changes.

Results
Eighteen participants from 13 government offices, who serve 19,560 employees, completed the training course. Nine workplaces had workplace health promotion programs in progress 12 months after the course had ended, of which 8 made health promotion changes in organizational policy. Workplace RE-AIM scores showed that 8 workplaces were high or partial performers, and 5 were low or non-performers. Factors that increased the likelihood of successful interventions included management support, steering committee, comprehensive programming, conducting a needs assessment and flexibility in program implementation in the presence of challenges. Post course, participants reported increased health knowledge related to workplace health promotion (p < 0.001), and increased health promotion self-efficacy (p < 0.05).

Conclusions
Training and continued guidance of middle managers resulted in the design and successful implementation of workplace health promotion interventions. A RE-AIM based assessment was found to be an effective method for evaluating multi-content workplace health promotion programs.
Registered at ClinicalTrials.gov, https://www.clinicaltrials.gov, registration number:
NCT03295136, registration date: 24/09/2017.
Paradoxical effects of cigarette smoke and COPD on SARS-CoV-2 infection and disease
Authors: Tomchaney M. , Contoli M. , Mayo J. , Baraldo S. , Li S. , Cabel C. R. , Bull D. A. , Lick S. , Malo J. , Knoper S. , Kim S. S. , Tram J. , Rojas-Quintero J. , Kraft M. , Ledford J. G. , Tesfaigzi Y. , Martinez F. D. , Thorne C. A. , Kheradmand F. , Campos S. K. , Papi A. , Polverino F. 
Published: August 2021

Abstract
Background
How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro.

Methods
We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively.

Results
ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR.

Conclusions
ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.
Lung "holes" after cryobiopsy: a case report
Authors: Piro Roberto , Taddei Sofia , Fontana Matteo , Scelfo Chiara , Casalini Eleonora , Facciolongo Nicola 
Published: August 2021

Abstract
Background
Transbronchial lung cryobiopsy is a safe technique increasingly used in the study of lung diseases. Until now, only a case of pneumatocele was described but this interesting condition is probably underestimated because CT scan is routinely not performed after transbronchial lung cryobiopsies.

Case presentation
We report a case of a woman presenting two pneumatoceles after lung cryobiopsies performed for the study of an interstitial lung disease. The finding was obtained with a CT scan performed because of the appearance of hemoptysis, four days after the biopsies.

Conclusions
Small cavitations could develop after cryobiopsies in the absence of an active infection. Studies that prospectively perform CT scan of the chest in patients who have undergone these samplings could be useful to know the incidence of iatrogenic lesions.
The Elk1/MMP-9 axis regulates E-cadherin and occludin in ventilator-induced lung injury
Authors: Tao Zhao , Jie Yan , Mingru Zhang , Changping Gu , Fan Yang , Haifeng Wu , Yuelan Wang 
Published: August 2021

Abstract
Background
Ventilator-induced lung injury (VILI) is a common complication in the treatment of respiratory diseases with high morbidity and mortality. ETS-domain containing protein (Elk1) and Matrix metalloproteinase (MMP) 9 are involved in VILI, but the roles have not been fully elucidated. This study examined the mechanisms of the activation of MMP-9 and Elk1 regulating barrier function in VILI in vitro and in vivo.

Methods
For the in vitro study, Mouse lung epithelial cells (MLE-12) were pre-treated with Elk1 siRNA or MMP-9 siRNA for 48 h prior to cyclic stretch at 20% for 4 h. For the in vivo study, C57BL/6 mice were pre-treated with Elk1 siRNA or MMP-9 siRNA for 72 h prior to 4 h of mechanical ventilation. The expressions of Elk1, MMP-9, Tissue inhibitor of metalloproteinase 1 (TIMP-1), E-cadherin, and occludin were measured by Western blotting. The intracellular distribution of E-cadherin and occludin was shown by immunofluorescence. The degree of pulmonary edema and lung injury were evaluated by Hematoxylin–eosin (HE) staining, lung injury scores, Wet/Dry (W/D) weight ratio, total cell counts, and Evans blue dye.

Results
20% cyclic stretch and high tidal volume increases the expressions of Elk1, MMP-9, and TIMP-1, increases the ratio of MMP-9/TIMP-1, decreases the E-cadherin and occludin level. Elk1 siRNA or MMP-9 siRNA reverses the degradations of E-cadherin, occludin, and the ratio of MMP-9/TIMP-1 caused by cyclic stretch. Elk1 siRNA decreases the MMP-9 level with or not 20% cyclic stretch and high tidal volume.

Conclusions
The results demonstrate mechanical stretch damages the tight junctions and aggravates the permeability in VILI, Elk1 plays an important role in affecting the tight junctions and permeability by regulating the balance of MMP-9 and TIMP-1, thus indicating the therapeutic potential of Elk1 to treat VILI.
Entomological baseline data collection and power analyses in preparation of a mosquito swarm-killing intervention in south-western Burkina Faso
Authors: Niang Abdoulaye , Sawadogo Simon P. , Millogo Abdoul A. , Akpodiete Nwamaka O. , Dabiré Roch K. , Tripet Frederic , Diabaté Abdoulaye 
Published: August 2021

Abstract
Background
Insecticides are currently the main tools used to reduce the transmission of malaria; therefore, the development of resistance to insecticides in malaria vectors is of major concern for malaria control. The resistance level to pyrethroids is particularly high in the Western region of Burkina Faso and may affect the efficacy of insecticidal bed nets and indoor residual spraying. Adult mosquito swarming and other nocturnal behaviours exhibit spatial and temporal patterns that suggest potential vulnerability to targeted space spraying with effective insecticides. Indeed, targeted space-spraying against adult mosquito swarms has been used to crash mosquito populations and disrupt malaria transmission.

Methods
Prior to impact assessment of swarm killing, a baseline data collection was conducted from June to November 2016 in 10 villages divided into two areas in western Burkina Faso. The data considered both ecological and demographic characteristics to monitor the key entomological parameters.

Results
The mean number of swarms observed was 35 per village, ranging from 25 to 70 swarms according to the village. Female density in both areas varied significantly as a function of the village and the period of collection. The human biting rate was significantly affected by the period of collection and depended upon whether the collection was carried out indoors or outdoors. Averages of parity rate were high in both areas for all periods of collection, ranging from 60 to 90%. These values ranged from 80 to 100% for inseminated females. Sporozoite rates ranged between 1.6 and 7.2% depending upon the village. The molecular identification of resting and swarming mosquitoes showed the presence of the three major malaria vectors in Burkina Faso, but in different proportions for each village.

Conclusions
The distribution of the potential swarm markers and swarms in villages suggested that swarms are clustered across space, making intervention easier. Power simulations showed that the direct sampling of swarms provides the highest statistical power, thereby reducing the number of villages needed for a trial.
Cardiac amyloidosis screening using a relative apical sparing pattern in patients with left ventricular hypertrophy
Authors: Nakao Yasuhisa , Saito Makoto , Inoue Katsuji , Higaki Rieko , Yokomoto Yuki , Ogimoto Akiyoshi , Suzuki Moeko , Kawakami Hideo , Hiasa Go , Okayama Hideki , Ikeda Shuntaro , Yamaguchi Osamu 
Published: August 2021

AbstractBackgroundCardiac amyloidosis (CA) mimics left ventricular hypertrophy (LVH). It is treatable, but its prognosis is poor. A simple screening tool for CA would be valuable. CA is more precisely diagnosed with echocardiographic deformation parameters (e.g., relative apical sparing pattern [RASP]) than with conventional parameters. We aimed to 1) investigate incremental benefits of echocardiographic deformation parameters over established parameters for CA screening; 2) determine the resultant risk score for CA screening; and 3) externally validate the score in LVH patients.MethodsWe retrospectively studied 295 consecutive non-ischemic LVH patients who underwent detailed diagnostic tests. CA was diagnosed with biopsy or99mTc-PYP scintigraphy. The base model comprised age (≥65 years [men], ≥70 years [women]), low voltage on the electrocardiogram, and posterior wall thickness ≥ 14 mm in reference to the literature. The incremental benefit of each binarized echocardiographic parameter over the base model was assessed using receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC).ResultsFifty-four (18%) patients had CA. RASP showed the most incremental benefit for CA screening over the base model. After conducting multiple logistic regression analysis for CA screening using four variables (RASP and base model components), a score was determined (range, 0–4 points). The score demonstrated adequate discrimination ability for CA (AUC = 0.86). This result was confirmed in another validation cohort (178 patients, AUC = 0.88).ConclusionsWe developed a score incorporating RASP for CA screening. This score is potentially useful in the risk stratification and management of LVH patients.
Efficacy of radiotherapy for gastric bleeding associated with advanced gastric cancer
Authors: Lee Joongyo , Byun Hwa Kyung , Koom Woong Sub , Lee Yong Chan , Seong Jinsil 
Published: August 2021

Abstract
Background
Gastric bleeding negatively impacts the quality of life of patients with unresectable advanced gastric cancer and is frequently lethal. We investigated the efficacy of RT for palliation of gastric bleeding from gastric cancer and identified an optimal radiotherapy (RT) strategy.

Methods
The study analyzed 57 patients submitted to palliative RT for gastric bleeding associated with gastric cancer between January 2009 and February 2019. Changes in hemoglobin (Hb) levels were analyzed based on measurements taken before and immediately, 1 month, and 2 months after RT. Re-bleeding after RT was identified as either Hb level dropping to < 7.0 g/dL or the administration of a blood transfusion after RT.

Results
The median biologically effective dose (α/β = 10) was 37.5 Gy (range 23.6–58.5). The most common regimen was 25 Gy in five fractions. The mean Hb levels before, immediately after, 1 month, and 2 months after RT (6.6, 9.7, 10.3, and 9.7 g/dL, respectively) were significantly higher than that before RT (all p < 0.001). No significant differences in re-bleeding rates were observed according to total dose, fractional dose, and fraction number. Gastric tumor response evaluated by computed tomography within 2 months after RT showed partial responses were more frequent in patients achieving bleeding control (25.0% vs. 10.8%, p = 0.023) and overall survival was significantly improved for bleeding control within 3 months after RT (median, 15.4 vs. 10.0 weeks, p = 0.048).

Conclusions
RT was an effective modality for gastric bleeding control in gastric cancer, which can be achieved with a short course scheme with five fractions.
iGlioSub: an integrative transcriptomic and epigenomic classifier for glioblastoma molecular subtypes
Authors: Ensenyat-Mendez Miquel , Íñiguez-Muñoz Sandra , Sesé Borja , Marzese Diego M. 
Published: August 2021

Abstract
Background
Glioblastoma (GBM) is the most aggressive and prevalent primary brain tumor, with a median survival of 15 months. Advancements in multi-omics profiling combined with computational algorithms have unraveled the existence of three GBM molecular subtypes (Classical, Mesenchymal, and Proneural) with clinical relevance. However, due to the costs of high-throughput profiling techniques, GBM molecular subtyping is not currently employed in clinical settings.

Methods
Using Random Forest and Nearest Shrunken Centroid algorithms, we constructed transcriptomic, epigenomic, and integrative GBM subtype-specific classifiers. We included gene expression and DNA methylation (DNAm) profiles from 304 GBM patients profiled in the Cancer Genome Atlas (TCGA), the Human Glioblastoma Cell Culture resource (HGCC), and other publicly available databases.

Results
The integrative Glioblastoma Subtype (iGlioSub) classifier shows better performance (mean AUC = 95.9%) stratifying patients than gene expression (mean AUC = 91.9%) and DNAm-based classifiers (AUC = 93.6%). Also, to expand the understanding of the molecular differences between the GBM subtypes, this study shows that each subtype presents unique DNAm patterns and gene pathway activation.

Conclusions
The iGlioSub classifier provides the basis to design cost-effective strategies to stratify GBM patients in routine pathology laboratories for clinical trials, which will significantly accelerate the discovery of more efficient GBM subtype-specific treatment approaches.
Synthetic lethality and synergetic effect: the effective strategies for therapy of IDH-mutated cancers
Authors: Yao Kun , Liu Hua , Yin Jiajun , Yuan Jianmin , Tao Hong 
Published: August 2021

AbstractMutant isocitrate dehydrogenase 1/2 (mIDH1/2) gain a novel function for the conversion of α-ketoglutarate (α-KG) to oncometabolite R-2-hydroxyglutarate (R-2-HG). Two molecular entities namely enasidenib (AG-221) and ivosidenib (AG-120) targeting mIDH2 and mIDH1 respectively, have already been approved by FDA for the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). However, the low responses, drug-related adverse effects, and most significantly, the clinically-acquired resistance of AG-221 and AG-120 has shown great influence on their clinical application. Therefore, searching for novel therapeutic strategies to enhance tumor sensitivity, reduce drug-related side effects, and overcome drug resistance have opened a new research field for defeating IDH-mutated cancers. As the effective methods, synthetic lethal interactions and synergetic therapies are extensively investigated in recent years for the cure of different cancers. In this review, the molecules displaying synergetic effects with mIDH1/2 inhibitors, as well as the targets showing relevant synthetic lethal interactions with mIDH1/2 are described emphatically. On these foundations, we discuss the opportunities and challenges for translating these strategies into clinic to combat the defects of existing IDH inhibitors.
GATA1-induced upregulation of LINC01503 promotes carboplatin resistance in ovarian carcinoma by upregulating PD-L1 via sponging miR-766-5p
Authors: Li Yao , Zhai Yan , Chen Yuxuan 
Published: August 2021

Abstract
Background
Ovarian Carcinoma (OCa) is a high-mortality malignancy derived from female reproductive system. Increasing evidence has identified long non-coding RNAs (lncRNAs) as important regulators in OCa chemoresistance. In this study, we intended to explore the role of LINC01503 in OCa resistance to carboplatin (CBP).

Methods
Gene expression was measured by reverse transcription-quantitative PCR (RT-qPCR) in OCa cells. Western blot was adopted to detect protein levels of GATA1, PD-L1, E-cadherin, N-cadherin, Vimentin, Bcl-2, Bax, cleaved caspase-3. To assess the effects of LINC01503 on the resistance of OCa cells to CBP, Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and flow cytometry experiments were performed to evaluate half-maximal inhibitory concentration (IC50), cell viability, migrative and invasive ability, as well as cell apoptosis. Dual-luciferase reporter assay was employed to assess the associations between the genes.

Results
LINC01503 was upregulated in CBP-resistant OCa cells. LINC01503 knockdown reduced CBP resistance in OCa cells. Besides, GATA-binding protein 1 (GATA1) activated LINC01503 transcription in CBP-resistant OCa cells. MiR-766-5p was lowly expressed in CBP-resistant cells and confirmed as a target for LINC01503. In addition, miR-766-5p overexpression increased CBP sensitivity in OCa cells. PD-L1 was verified as the target of miR-766-5p. Besides, LINC01503 upregulated PD-L1 level by regulating miR-766-5p. Furthermore, rescue experiments showed that PD-L1 overexpression abrogated the inhibited impacts of blocking LINC01503 on CBP resistance in OCa cells.

Conclusion
GATA1-induced LINC01503 expedited CBP resistance in OCa cells via the miR-766-5p/PD-L1 axis, providing a new target for improving the efficacy of OCa chemotherapy.

Graphical Abstract