bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR)
Authors:   the AVENIR Study Group, O’Brien Kieran S. , Arzika Ahmed M. , Amza Abdou , Maliki Ramatou , Ousmane Sani , Kadri Boubacar , Nassirou Beido , Mankara Alio Karamba , Harouna Abdoul Naser , Colby Emily , Lebas Elodie , Liu Zijun , Le Victoria , Nguyen William , Keenan Jeremy D. , Oldenburg Catherine E. , Porco Travis C. , Doan Thuy , Arnold Benjamin F. , Lietman Thomas M. 
Published: April 2021

AbstractBackgroundBiannual distribution of azithromycin to children 1–59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1–11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance.MethodsAVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1–11: biannual azithromycin to children 1–11 months old with placebo to children 12–59 months old, 2) azithromycin 1–59: biannual azithromycin to children 1–59 months old, or 3) placebo: biannual placebo to children 1–59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1–59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1–59 months old comparing the azithromycin 1–59 and placebo arms, 2) children 1–11 months old comparing the azithromycin 1–11 and placebo arm, and 3) children 12–59 months in the azithromycin 1–11 and azithromycin 1–59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1–59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1–59 months old.DiscussionAs high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival.Trial registrationThis trial was registered on January 13, 2020 (clinicaltrials.gov:NCT04224987).
Combination therapies with thiazolidinediones are associated with a lower risk of acute exacerbations in new-onset COPD patients with advanced diabetic mellitus: a cohort-based case–control study
Authors: Chen Kuan-Yuan , Wu Sheng-Ming , Tseng Chien-Hua , Lee Kang-Yun , Lin Yu-Huei , Liu Hung-Yi , Chien Li-Nien 
Published: April 2021

AbstractBackgroundThe effects of oral antihyperglycaemic drugs (OADs) for type 2 diabetes mellitus (T2DM) on the outcomes of co-existing chronic obstructive pulmonary disease (COPD) patients are not well studied. We examined the association of combinational OADs and the risk of acute exacerbations of COPD (AECOPD) in T2DM patients with co-existing COPD.MethodsA cohort-based case–control study was conducted using data from the National Health Insurance Research Database of Taiwan. Among new-onset COPD-T2DM patients, 65,370 were prescribed metformin and 2nd-line OADs before the date of COPD onset. Each AECOPD case was matched to 4 randomly selected controls according to the propensity score estimated by the patient’s baseline characteristics. Conditional logistic regression analysis was performed to estimate the association between AECOPD risk and OAD use.ResultsAmong COPD-T2DM patients, 3355 AECOPD cases and 13,420 matched controls were selected. Of the patients treated with a double combination of oral OADs (n = 12,916), those treated with sulfonylurea (SU) and thiazolidinediones (TZD) had a lower AECOPD risk than the patients who received metformin (MET) and SU, with an adjusted odds ratio (OR) of 0.69 (95% confidence interval [CI] 0.51–0.94,P = 0.02). Of the patients with a triple combination of oral OADs (n = 3859), we found that those treated with MET, SU and TZD had a lower risk of AECOPD (adjusted OR 0.81 (0.68–0.96,P = 0.01) than a combination of MET, SU and α-glucosidase inhibitors (AGIs) regardless of the level of COPD complexity.ConclusionCombination therapies with TZD were associated with a reduced risk of AECOPD in advanced T2DM patients with co-existing COPD.
Esophageal leiomyoma and simultaneous overlying squamous cell carcinoma: a case report and review of the literature
Authors: Mehrabi Saadat , Yavari Barhaghtalab Mohammad Javad , Hejazinia Safoora , Saedi Hossein 
Published: April 2021

Abstract
Background
Squamous cell carcinoma is the most common epithelial tumor of the esophagus. Upper endoscopy with multiple minimally invasive biopsies should be performed to confirm the diagnosis. Leiomyoma of esophagus is rare, but it’s the most common benign submucosal mesenchymal tumor of the esophagus. The simultaneous occurrence of an overlying epithelial lesion and a mesenchymal lesion is very rare. This study aims to show a case operated due to squamous cell carcinoma of esophagus that was postoperatively diagnosed with coexistent esophageal leiomyoma and give a clear overview of the existing literature on it.

Case presentation
The patient was a 41-year-old woman who underwent three field esophagectomy (McKeown). Pathological evaluation was done, and the patient had poorly differentiated squamous cell carcinoma and multiple leiomyomas. A leiomyoma was found with an invading overlying squamous cell carcinoma.

Conclusion
It is concluded that esophageal carcinomas may coexist with leiomyomas; preexisting benign tumors may have played an important role in the development of the carcinoma by inducing constant stimulation of the overlying mucosa; endoscopic ultrasonography is recommended to avoid overestimating the extent of tumor invasion and the resultant aggressive radical surgery. As the developing countries had limited equipment, esophageal resection could be the modality of choice in the treatment.
Association of hypertension and incident diabetes in Chinese adults: a retrospective cohort study using propensity-score matching
Authors: Wu Yang , Hu Haofei , Cai Jinlin , Chen Runtian , Zuo Xin , Cheng Heng , Yan Dewen 
Published: April 2021

Abstract
Background
Reliable quantification of the relationship between hypertension and diabetes risk is limited, especially among Chinese people. We aimed to investigate the association between hypertension and the risk of diabetes in a large cohort of the Chinese population.

Methods
This was a retrospective propensity score-matched cohort study among 211,809 Chinese adults without diabetes at baseline between 2010 and 2016. The target independent and dependent variable were hypertension at baseline and incident diabetes during follow-up respectively. The propensity score matching using a non-parsimonious multivariable logistic regression was conducted to balance the confounders between 28,711 hypertensive patients and 28,711 non-hypertensive participants. The doubly robust estimation method was used to investigate the association between hypertension and diabetes.

Results
In the propensity-score matching cohort, diabetes risk increased by 11.0% among hypertensive patients (HR = 1.110, 95% confidence interval (CI): 1.031–1.195, P = 0.00539). And diabetes risk dropped to 8.3% among hypertensive subjects after adjusting for the propensity score (HR = 1.083, 95%CI: 1.006–1.166, P = 0.03367). Compared to non-hypertensive participants with low propensity score, the risk of incident diabetes increased by 2.646 times among hypertensive patients with high propensity score (HR = 3.646, 95%CI: 2.635–5.045, P < 0.0001).

Conclusion
Hypertension was associated with an 11.0% increase in the risk of developing diabetes in Chinese adults. And the figure dropped to 8.3% after adjusting the propensity score. Additionally, compared to non-hypertensive participants with low propensity scores, the risk of incident diabetes increased by 2.646 times among hypertensive patients with high propensity scores.
Effects of Green cardamom (Elettaria cardamomum Maton) and its combination with cyclophosphamide on Ehrlich solid tumors
Authors: Almeer Rafa S. , Alnasser Meshael , Aljarba Nada , AlBasher Gadah I. 
Published: April 2021

Abstract
Background
Cardamom (Elettaria cardamomum) is a spice and exhibits potent antioxidant and biological activities through distinct molecular mechanisms. However, the anticancer effect of cardamom was not explored yet in Ehrlich solid tumor (EST)-bearing mice.

Objectives
This investigation was aimed to evaluate the anti-cancer effects of green cardamom (GCar) alone or combined with the anti-cancer drug cyclophosphamide in an in vivo model to explore its mechanistic role in tumor cell death in EST-bearing mice.

Methods
Ehrlich ascites tumor cells were injected in the mice and 5 days later the animals treated with GCar and/or cyclophosphamide for 10 days. Twenty-four hours from the last treatment, animals were sacrificed for the different measurements.

Results
Data recorded for tumor size, percentage of tumor growth inhibition, tumor growth delay and mean survival time of EST-bearing mice demonstrated the effective role of GCar alone or combined with CPO as a promising anti-cancer agent because it reduced tumor size. GCar elevated the mean survival time of EST-bearing mice compared to that of untreated EST and EST + CPO groups. Analysis of qPCR mRNA gene and protein expression revealed that GCar alone or combined with CPO were promising anticancer agents. After the treatment of EST with GCar, the apoptotic-related genes and proteins were significantly modulated. GCar induced markedly significant decreases in oxidative stress biomarkers and a significant increment in glutathione levels and that of antioxidant enzymes. With a marked diminish in liver and kidney function biomarkers.

Conclusion
The results revealed that GCar could serve as an apoptotic stimulator agent, presenting a novel and potentially curative approach for cancer treatment, inducing fewer side effects than those of the commercially used anti-cancer drugs, such as CPO.
Ethical and procedural issues for applying researcher-driven multi-national paediatric clinical trials in and outside the European Union: the challenging experience of the DEEP project
Authors: Giannuzzi Viviana , Felisi Mariagrazia , Bonifazi Donato , Devlieger Hugo , Papanikolaou George , Ragab Lamis , Fattoum Slaheddine , Tempesta Bianca , Reggiardo Giorgio , Ceci Adriana 
Published: April 2021

Abstract
Background
We describe our experience from a multi-national application of a European Union-funded research-driven paediatric trial (DEEP-2, EudraCT 2012-000353-31; NCT01825512). This paper aims to evaluate the impact of the local and national rules on the trial authorisation process in European and non-European countries. National/local provisions and procedures, number of Ethics Committees and Competent Authorities to be addressed, documentation required, special provisions for the paediatric population, timelines for completing the authorisation process and queries received were collected; compliance with the European provisions were evaluated. Descriptive analysis, Wilcoxon Rank-Sum test and General Linear Model analysis were used to determine factors potentially influencing the timelines. The Cluster Analysis procedure was used to identify homogenous groups of cases.

Result
The authorisation process was completed in 7.7 to 53.8 months in European countries and in 17.1 to 27.1 months in non-European countries. The main factors influencing these timelines were the requests for changes/clarifications in European countries and the different national legislations in non-European countries.

Conclusion
This work confirms that the procedures and requirements for the clinical trial application of a paediatric trial are different. In the European Union, the timeframes for submission were generally harmonised but longer. In non-European countries, delays were caused by national dispositions but the entire authorisation process resulted faster with less requests from ECs/CAs. The upcoming application of Regulation (EU) 536/2014 is expected to harmonise practices in Europe and possibly outside. Networks on paediatric research acting at international level will be crucial in this effort.
“From experts to locals hands” healthcare service planning in sub-Saharan Africa: an insight from the integrated community case management of Ghana
Authors: Annobil Isaac , Dakyaga Francis , Sillim Mavis Lepiinlia 
Published: April 2021

Abstract
Background
Although community participation remains an essential component globally in healthcare service planning, evidence of how rural communities participate in the planning of rural-based healthcare programs has less been explored in Sub-Saharan Africa.

Objective
We explored communities’ participation in health care planning in hard-to-reach communities, within the context of Integrated Community Case Management (iCCM), a community-based health program implemented in Ghana.

Methods
Qualitative data were collected from eleven (11) hard-to-reach communities through Focus Group Discussions (FGDs), Key Informant Interviews (KIIs) as well as district-level studies (Nadowli-Kaleo, and WA East districts of Ghana). The Rifkin’s spider-gram, framework, for measuring and evaluating community participation in healthcare planning was adapted for the study.

The results
The study found that community participation was superficially conducted by the CHOs. A holistic community needs assessment to create awareness, foster a common understanding of health situations, collaboration, acceptance and ownership of the program were indiscernible. Rather, it took the form of an event, expert-led-definition, devoid of coherence to build locals understanding to gain their support as beneficiaries of the program. Consequently, some of the key requirements of the program, such as resource mobilization by rural residents, Community-based monitoring of the program and the act of leadership towards sustainability of the program were not explicitly found in the beneficiaries’ communities.

Conclusion and recommendation
The study concludes that there is a need to expand the concept of community involvement in iCCM to facilitate communities’ contribution to their healthcare. Also, a transdisciplinary approach is required for engineering and scaling up community-based health programs, empowering VHCs, CBHVs and CHAs to realize success.
Upper eyelid blepharoplasty following hyaluronic acid injection with improved facial aesthetics and eye symptoms: a case report
Authors: Maione Luca , Vinci Valeriano , Costanzo Domenico , Battistini Andrea , Lisa Andrea , Di Maria Alessandra 
Published: April 2021

Abstract
Background
Dermatochalasis of the upper eyelids (blepharochalasis) is a typical age-related change in the upper third of the face and a major concern for facial aesthetics. Nowadays both surgical and nonsurgical interventions are available for patients complaining of upper eyelid dermatochalasis. Although nonsurgical treatments are often easier to perform, if they are not performed correctly, complications may ensue and worsen the condition.

Case presentation
We describe the case of a Caucasian patient presenting with bilateral upper eyelid dermatochalasis, previously treated with multiple injections of hyaluronic acid filler. Following these procedures, the patient reported nonspecific eye symptoms (such as a sense of heaviness and asthenopia) and cosmetic concerns. We decided to perform an upper eyelid blepharoplasty. During the procedure we found a ribbon of hard, fibrous material, which was carefully removed. The patient reported resolution of functional eye symptoms owing to the reduction of upper lid heaviness, which also resulted in subjective improvement of the visual field. Patient satisfaction was assessed preoperatively and 3 months postoperatively using the Blepharoplasty Outcomes Evaluation (BOE), which showed an overall satisfaction rate of 95.8 %.

Conclusions
Blepharoplasty not only treated the patient’s blepharochalasis but also allowed us to correct the previous nonsurgical intervention by removing the excessive amount of injected hyaluronic acid. Both aesthetic and functional results were successfully achieved.
Local NF-κB Activation Promotes Parathyroid Hormone Synthesis and Secretion in Uremic Patients
Authors: Mao Jianping , Wang Mengjing , Ni Li , Gong Wen , Jiang Xinxin , Zhang Qian , Zhang Minmin , Wen Donghai , Chen Jing 
Published: April 2021

Abstract
Secondary hyperparathyroidism (SHPT) in uremic patients is characterized by parathyroid gland (PTG) hyperplasia and parathyroid hormone (PTH) elevation. Previously, we demonstrated that NF-κB activation contributed to parathyroid cell proliferation in rats with chronic kidney disease. Although vitamin D inhibits inflammation and ameliorates SHPT, the contribution of vitamin D deficiency to SHPT via local NF-κB activation remains to be clarified. PTGs collected from 10 uremic patients with advanced SHPT were used to test the expressions of vitamin D receptor (VDR), NF-κB, and proliferating cell nuclear antigen (PCNA). Freshly excised PTG tissues were incubated for 24 hours in vitro with VDR activator (VDRA) calcitriol or NF-κB inhibitor pyrrolidine thiocarbamate (PDTC). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate the regulation of PTH transcription by NF-κB. We found higher levels of activated NF-κB and lower expression of VDR in nodular hyperplastic PTGs than in diffuse hyperplasia. In cultured PTG tissues, treatment with VDRA or PDTC inhibited NF-κB activation and PCNA expression, and downregulated preproPTH mRNA and intact PTH levels. ChIP assays demonstrated the presence of NF-κB binding sites in PTH promoter. Furthermore, in luciferase reporter assays, addition of exogenous p65 significantly increased PTH luciferase activity by 2.4-fold (P &lt; 0.01), while mutation of NF-κB binding site at position −908 of the PTH promoter suppressed p65-induced PTH reporter activity (P &lt; 0.01). In summary, local NF-κB activation contributes to SHPT and mediates the transcriptional activation of PTH directly in uremic patients. Vitamin D deficiency may be involved in SHPT via the activation of NF-κB pathway.
The Black Aquatic
Authors: Walcott Rinaldo 
Published: April 2021

Abstract
This essay argues that thinking through black diasporic life as birthed through a unique and ongoing relationship with bodies of water (sea, oceans, rivers, creeks) can and does aid in analyses of contemporary art and its engagement with black subjectivity. I am concerned with how bodies of water are foundationally formative of blackness. And secondarily I pursue how this foundational aspect of blackness is both an act of representation worth engaging contemporary art and also a limit on what some representations of contemporary art can do to undo the brutal history of the aquatic birth of blackness and its perpetuation.
Special report of the RSNA COVID-19 task force: systematic review of outcomes associated with COVID-19 neuroimaging findings in hospitalized patients
Authors: Mogensen Monique A. , Wangaryattawanich Pattana , Hartman Jason , Filippi Christopher G. , Hippe Daniel S. , Cross Nathan M. ,   RSNA COVID-19 task force
Published: April 2021

Objective: We reviewed the literature to describe outcomes associated with abnormal neuroimaging findings among adult COVID-19 patients. Methods: We performed a systematic literature review using PubMed and Embase databases. We included all studies reporting abnormal neuroimaging findings among hospitalized patients with confirmed COVID-19 and outcomes. Data elements including patient demographics, neuroimaging findings, acuity of neurological symptoms and/or imaging findings relative to COVID-19 onset (acute, subacute, chronic), and patient outcomes were recorded and summarized. Results: After review of 775 unique articles, a total of 39 studies comprising 884 COVID-19 patients ≥ 18 years of age with abnormal neuroimaging findings and reported outcomes were included in our analysis. Ischemic stroke was the most common neuroimaging finding reported (49.3%, 436/884) among patients with mortality outcomes data. Patients with intracranial hemorrhage (ICH) had the highest all-cause mortality (49.7%, 71/143), followed by patients with imaging features consistent with leukoencephalopathy (38.5%, 5/13), and ischemic stroke (30%, 131/436). There was no mortality reported among COVID-19 patients with acute disseminated encephalomyelitis without necrosis (0%, 0/8) and leptomeningeal enhancement alone (0%, 0/12). Stroke was a common acute or subacute neuroimaging finding, while leukoencephalopathy was a common chronic finding. Conclusion: Among hospitalized COVID-19 patients with abnormal neuroimaging findings, those with ICH had the highest all-cause mortality; however, high mortality rates were also seen among COVID-19 patients with ischemic stroke in the acute/subacute period and leukoencephalopathy in the chronic period. Advances in knowledge: Specific abnormal neuroimaging findings may portend differential mortality outcomes, providing a potential prognostic marker for hospitalized COVID-19 patients.
Metal artefact reduction in the oral cavity using deep learning reconstruction algorithm in ultra-high-resolution computed tomography: a phantom study
Authors: Sakai Yuki , Kitamoto Erina , Okamura Kazutoshi , Tatsumi Masato , Shirasaka Takashi , Mikayama Ryoji , Kondo Masatoshi , Hamasaki Hiroshi , Kato Toyoyuki , Yoshiura Kazunori 
Published: April 2021

Objectives: This study aimed to improve the impact of the metal artefact reduction (MAR) algorithm for the oral cavity by assessing the effect of acquisition and reconstruction parameters on an ultra-high-resolution CT (UHRCT) scanner. Methods: The mandible tooth phantom with and without the lesion was scanned using super-high-resolution, high-resolution (HR), and normal-resolution (NR) modes. Images were reconstructed with deep learning-based reconstruction (DLR) and hybrid iterative reconstruction (HIR) using the MAR algorithm. Two dental radiologists independently graded the degree of metal artefact (1, very severe; 5, minimum) and lesion shape reproducibility (1, slight; 5, almost perfect). The signal-to-artefact ratio (SAR), accuracy of the CT number of the lesion, and image noise were calculated quantitatively. The Tukey-Kramer method with a p-value of less than 0.05 was used to determine statistical significance. Results: The HRDLR visual score was better than the NRHIR score in terms of degree of metal artefact (4.6 ± 0.5 and 2.6 ± 0.5, p < 0.0001) and lesion shape reproducibility (4.5 ± 0.5 and 2.9 ± 1.1, p = 0.0005). The SAR of HRDLR was significantly better than that of NRHIR (4.9 ± 0.4 and 2.1 ± 0.2, p < 0.0001), and the absolute percentage error of the CT number in HRDLR was lower than that in NRHIR (0.8% in HRDLR and 23.8% in NRIR). The image noise of HRDLR was lower than that of NRHIR (15.7 ± 1.4 and 51.6 ± 15.3, p < 0.0001). Conclusions: Our study demonstrated that the combination of HR mode and DLR in UHRCT scanner improved the impact of the MAR algorithm in the oral cavity.