bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of clinical and laboratory characteristics of patients with cutaneous sarcoidosis: A single-center retrospective cohort study
Authors: Boch Katharina , Langan Ewan A. , Zillikens Detlef , Ludwig Ralf J. , Kridin Khalaf 
Published: October 2022

BackgroundCutaneous sarcoidosis is a relatively rare disease whose clinical manifestations include red-brown macules, plaques, papules and subcutaneous nodules. The skin changes may also be restricted to pre-existing scars. Cutaneous sarcoidosis can be associated with systemic organ involvement.ObjectivesAim of this retrospective study was to longitudinally investigate clinical and laboratory findings in patients with cutaneous sarcoidosis.MethodsPatients (&gt;18 years) with histologically confirmed cutaneous sarcoidosis between January 2014 and December 2020 were included. Patient demographics, clinical features, laboratory and radiological findings, management, clinical outcomes and co-morbidities associated with cutaneous sarcoidosis were analyzed.ResultsThirty-seven patients with cutaneous sarcoidosis were identified, of whom 57% were female. The most common clinical phenotype of cutaneous sarcoidosis was papular sarcoidosis (n = 16), while plaques and nodules were present in 9 patients. In contrast, subcutaneous (n = 1) and scar-associated sarcoidosis (n = 1) were rare. Of patients with systemic disease, the cutaneous disease followed, preceded, and coincided with the development of systemic sarcoidosis in 2, 9, and 12 patients, respectively. Levels of soluble interleukin (IL)-2 receptor, angiotensin converting enzyme (ACE), and C-reactive protein (CRP) were elevated, in 76%, 21%, and 50% of the tested patients respectively and predicted systemic involvement. Hypercalcemia was present in 6% of patients. Female sex and younger age (&lt;54 years) were significantly associated with systemic manifestations.ConlcusionsCutaneous sarcoidosis was frequently associated with additional systemic involvement, particularly when present in young females. 24 % of patients with cutaneous sarcoidosis developed additional organ involvement during follow-up.
Challenges related to data protection in clinical research before and during the COVID-19 pandemic: An exploratory study
Authors: Lalova-Spinks Teodora , De Sutter Evelien , Valcke Peggy , Kindt Els , Lejeune Stephane , Negrouk Anastassia , Verhenneman Griet , Derèze Jean-Jacques , Storme Ruth , Borry Pascal , Meszaros Janos , Huys Isabelle 
Published: October 2022

BackgroundThe COVID-19 pandemic brought global disruption to health, society and economy, including to the conduct of clinical research. In the European Union (EU), the legal and ethical framework for research is complex and divergent. Many challenges exist in relation to the interplay of the various applicable rules, particularly with respect to compliance with the General Data Protection Regulation (GDPR). This study aimed to gain insights into the experience of key clinical research stakeholders [investigators, ethics committees (ECs), and data protection officers (DPOs)/legal experts working with clinical research sponsors] across the EU and the UK on the main challenges related to data protection in clinical research before and during the pandemic.Materials and methodsThe study consisted of an online survey and follow-up semi-structured interviews. Data collection occurred between April and December 2021. Survey data was analyzed descriptively, and the interviews underwent a framework analysis.Results and conclusionIn total, 191 respondents filled in the survey, of whom fourteen participated in the follow-up interviews. Out of the targeted 28 countries (EU and UK), 25 were represented in the survey. The majority of stakeholders were based in Western Europe. This study empirically elucidated numerous key legal and ethical issues related to GDPR compliance in the context of (cross-border) clinical research. It showed that the lack of legal harmonization remains the biggest challenge in the field, and that it is present not only at the level of the interplay of key EU legislative acts and national implementation of the GDPR, but also when it comes to interpretation at local, regional and institutional levels. Moreover, the role of ECs in data protection was further explored and possible ways forward for its normative delineation were discussed. According to the participants, the pandemic did not bring additional legal challenges. Although practical challenges (for instance, mainly related to the provision of information to patients) were high due to the globally enacted crisis measures, the key problematic issues on (cross-border) health research, interpretations of the legal texts and compliance strategies remained largely the same.
Safety and efficacy of unilateral and bilateral pedicle screw fixation for lumbar degenerative diseases by transforaminal lumbar interbody fusion: An updated systematic review and meta-analysis
Authors: Zhong Rui , Xue Xiali , Wang Runsheng , Dan Jing , Wang Chuanen , Liu Daode 
Published: October 2022

BackgroundThe purpose of this study was to compare the safety and efficacy of unilateral vs. bilateral pedicle screw fixation (BPSF) for lumbar degenerative diseases.MethodsElectronic databases including PubMed, Web of science, the Cochrane Library, Scopus, MEDLINE, EMBASE, EBSCO were searched by computer. The deadline was set for June 1, 2022. This study included all high-quality randomized controlled trials (RCTs), prospective clinical controlled studies (PRO), and retrospective studies (Retro) that compared unilateral and bilateral pedicle screw fixation in the treatment of lumbar degenerative diseases. Revman5.3 software was used for meta-analysis after two researchers independently screened the literature, extracted data, and assessed the risk of bias in the study.ResultsFourteen studies with a total of 1,086 patients were included. Compared with BPSF, unilateral pedicle screw fixation (UPSF) has shorter operation time and hospital time, and less blood loss and operation cost, operation time [SMD = −1.75, 95% CI (−2.46 to −1.03), P &lt; 0.00001], hospital time [SMD = −1.10, 95% CI (−1.97 to −0.22), P = 0.01], Blood loss [SMD = −1.62, 95% CI (−2.42 to −0.82), P &lt; 0.0001], operation cost [SMD = −14.03, 95% CI (−20.08 to −7.98), P &lt; 0.00001], the ODI after bilateral pedicle screw fixation was lower, and the degree of lumbar dysfunction was lighter, [SMD = 0.19, 95% CI (0.05–0.33), P = 0.007], better fusion effect, fusion rate [RR=0.95, 95% CI (0.91–1.00), P = 0.04]. VAS-Low back pain [SMD = 0.07, 95% CI (−0.07–0.20), P = 0.35], VAS-Leg pain [SMD = 0.18, 95% CI (−0.00–0.36), P = 0.05], SF-36 [SMD = 0.00, 95% CI (−0.30–0.30), P = 1.00], complications rate [RR = 0.94, 95% CI (0.9154–1.63), P = 0.82], the overall difference was not statistically significant.ConclusionsCurrently limited evidence suggests that UPSF significantly reduces blood loss, significantly shortens the operative time and hospital stay, and reduces blood loss and costs. After BPSF, the ODI was lower, the degree of lumbar spine dysfunction was lower, and the fusion rate was significantly higher. The VAS, SF-36, and complications scores of the two groups were comparable, and there was no significant clinical difference.
MDFI is a novel biomarker for poor prognosis in LUAD
Authors: Chen Pengyu , Quan Zhen , Song Xueyu , Gao Zhaojia , Yuan Kai 
Published: October 2022

BackgroundApproximately 80% of lung cancers are non-small cell lung cancers (NSCLC). Lung adenocarcinoma (LUAD) is the main subtype of NSCLC. The incidence and mortality of lung cancer are also increasing yearly. Myogenic differentiation family inhibitor (MDFI) as a transcription factor, its role in lung cancer has not yet been clarified.MethodsLUAD data were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO), analyzed and plotted using the R language. Associations between Clinical information and MDFI expression were assessed using logistic regression analyses to explore the effects of MDFI on LUAD. Two sets of tissue microarrays (TMAs) further confirmed the overexpression of MDFI in LUAD and its impact on prognosis. In addition, we examined the correlation between MDFI and immune infiltration. To investigate the effect of MDFI on the biological behavior of LUAD tumor cells by GSEA and GO/KEGG analysis. The survival status and somatic mutational characteristics of patients according to MDFI levels were depicted and analyzed.ResultsExpression of high MDFI in LUAD tissues via analyzing TCGA dataset (P &lt;0.001). Kaplan-Meier survival analysis indicated a poor prognosis for those patients with LUAD who had upregulated MDFI expression levels (P &lt;0.001). This was also verified by two groups of TMAs (P=0.024). Using logistic statistics analysis, MDFI was identified as an independent predictive factor and was associated with poor prognosis in LUAD (P &lt;0.001, P =0.021). Assessment of clinical characteristics, tumor mutation burden (TMB), and tumor microenvironment (TME) between high- and low-expression score groups showed lower TMB, richer immune cell infiltration, and better prognosis in the low-risk group.ConclusionThis study showed that MDFI was overexpressed in LUAD and was significantly associated with poor prognosis, indicating that MDFI may be used as a potential novel biomarker for the diagnosis and prognosis of LUAD. MDFI is associated with immune infiltration of LUAD and it is reasonable to speculate that it plays an important role in tumor proliferation and spread. In view of the significant differences in MDFI expression between different biological activities, LUAD patients with MDFI overexpression may obtain more precise treatment strategies in the clinic.
Detection of axillary lymph node metastasis in breast cancer using dual-layer spectral computed tomography
Authors: Li Huijun , Wang Huan , Chen Fangfang , Gao Lei , Zhou Yurong , Zhou Zhou , Huang Jinbai , Xu Liying 
Published: October 2022

PurposeTo investigate the value of contrast-enhanced dual-layer spectral computed tomography (DLCT) in the detection of axillary lymph node (ALN) metastasis in breast cancer.Materials and MethodsIn this prospective study, 31 females with breast cancer underwent contrast-enhanced DLCT from August 2019 to June 2020. All ALNs were confirmed by postoperative histology. Spectral quantitative parameters, including λHU (in Hounsfield units per kiloelectron-volt), nIC (normalized iodine concentration), and Zeff (Z-effective value) in both arterial and delay phases, were calculated and contrasted between metastatic and nonmetastatic ALNs using the McNemar test. Discriminating performance from metastatic and nonmetastatic ALNs was analyzed using receiver operating characteristic curves.ResultsIn total, 132 ALNs (52 metastatic and 80 nonmetastatic) were successfully matched between surgical labels and preoperative labels on DLCT images. All spectral quantitative parameters (λHu, nIC, and Zeff) derived from both arterial and delayed phases were greater in metastatic ALNs than in nonmetastatic SLNs (all p &lt; 0.001). Logistic regression analyses showed that λHu in the delayed phase was the best single parameter for the detection of metastatic ALNs on a per-lymph node basis, with an area under the curve of 0.93, accuracy of 86.4% (114/132), sensitivity of 92.3% (48/52), and specificity of 87.5% (70/80).ConclusionThe spectral quantitative parameters derived from contrast-enhanced DLCT, such as λHu, can be applied for the preoperative detection of ALN metastasis in breast cancer.
Changes to intraocular pressure and its correlation with corneal diameter in infants aged from 0 to 36 months
Authors: Wang Jian-Cang , Du Fei-Fan , Meng Shuo-Shuo , Wei Yun-Shuo , Guo Xi-Ting 
Published: October 2022

ObjectiveThis study examines the distribution and development of intraocular pressure (IOP) in infants aged from 0 to 36 months and analyzes its correlation with corneal diameter.MethodsThe study used a retrospective case analysis methodology. Healthy infants treated in the ophthalmology department of Hebei Children's Hospital from December 2012 to December 2020 were included in the study. Among these infants, 385 had their IOP measured, and 432 had their corneal diameters measured. Furthermore, information such as birth history, growth and development, IOP, and corneal diameter were collected. Their IOPs were measured with an iCare portable rebound tonometer when the child was awake and calm, and the corneal diameter was measured with a Castroviejo caliper under chloral hydrate sedation. The infants were divided into five groups according to age, and SPSS statistical software was used to analyze, compare, and correlate IOP and corneal diameter variations.ResultsThe mean IOP values of 0–1 month, 1–6 months, 6–12 months, 12–24 months and 24–36 months groups were 7.42 ± 1.92, 9.10 ± 2.85, 12.00 ± 3.15, 13.72 ± 3.09, and 15.14 ± 2.67 mmHg, respectively. The differences in IOP of the 0–1 month old infants and the 1–6 months old infants with the other three groups were statistically significant; the difference in IOP between the 6–12 months group and the 24–36 months group was statistically significant. In the studied groups, the horizontal corneal diameters were 9.78 ± 0.14, 10.50 ± 0.29, 10.86 ± 0.23, 11.38 ± 0.07, and 11.72 ± 0.04 mm, respectively, and the vertical diameters of the cornea were 9.28 ± 0.26, 10.07 ± 0.18, 10.28 ± 0.14, 10.56 ± 0.24, and 10.85 ± 0.03 mm, respectively. The differences in the vertical and horizontal diameters of the cornea among the groups were statistically significant.ConclusionInfants' IOP and corneal diameter positively correlate with age, and they peak in the first 12 months.
Predicting vaccine hesitancy among parents towards COVID-19 vaccination for their children in Singapore
Authors: Low Jia Ming , Soo Chloe Wen Ting , Phuong TA , Zhong Youjia , Lee Le Ye 
Published: October 2022

BackgroundThere was a considerably slower uptake among children despite the high COVID-19 vaccination uptake amongst adults and adolescents in Singapore. This was concerning as unvaccinated children are at risk of severe COVID-19 infections and a source and reservoir of infections. We sought to understand the impact of social media on parental vaccine hesitancy and to determine the risk factors associated with vaccine hesitancy.MethodsAn electronic survey conducted from November 2021 to March 2022. Data on the demographic profiles of respondents and to classify them based on their vaccine hesitancy status. Data including the choice of social media used to obtain information on the COVID-19 pandemic, frequency of use were collected. Statistical significance was defined as p &lt; 0.05.ResultsSix hundred and twenty-eight parents participated. 66.9% of parents were not vaccine hesitant. About a third (27.2%) considered themselves somewhat vaccine hesitant. Fathers were more vaccine hesitant than mothers. Vaccine hesitancy was also associated with having a lower household income, unvaccinated parents, knowing someone with an adverse reaction to the Covid 19 vaccine and having a low level of trust in their child's doctor. There was no significant difference with high usage of social media between parents who were not vaccine hesitant vs. those who were vaccine hesitant. Despite high usage of social media, about two thirds (62.7%) of parents preferred print material to obtain COVID-19 related information. Parental trust in their child's doctor was the most significant factor in determining vaccine hesitancy amongst parents. When the variables of gender, household income status, vaccine status were further analysed with a multinomial logistic regression model, vaccine hesitancy in a parent could be predicted with a 70% accuracy, and non-vaccine hesitancy with a 92.4% accuracy.ConclusionNewspapers and print media were the primary sources used in obtaining information on COVID-19 vaccine safety and efficacy, especially amongst parents with a higher household income. Healthcare providers should continue to establish rapport amongst parents, in particular the group with a lower household income to encourage higher paediatric COVID-19 vaccine uptake as well as correct COVID-19 related vaccine misconceptions or vaccine hesitancy, if present.
Predictors of inappropriate antimicrobial prescription: Eight-year point prevalence surveys experience in a third level hospital in Spain
Authors: Núñez-Núñez María , Perez-Galera Salvador , Girón-Ortega José Antonio , Sandoval Fernández-Del-Castillo Santiago , Beltrán-García Margarita , De Cueto Marina , Suárez-Barrenechea Ana Isabel , Palacios-Baena Zaira R. , Terol-Barrero Pedro , Oltra-Hostalet Fernando , Arenzana-Seisdedos Ángel , Rodriguez-Baño Jesús , Retamar-Gentil Pilar 
Published: October 2022

Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. We aimed to describe the Point Prevalence Surveys (PPS) methodology implemented in our hospital as an efficient tool to guide ASP strategies. Annually repeated PPS were conducted from 2012 to 2019 at a 750-bed university hospital in South Spain. Key quality indicators and inappropriateness of antimicrobial treatment, defined strictly according to local guidelines, were described. Variables associated with inappropriate treatment were identified by bi/multivariable analysis. A total of 1,600 patients were included. We found that 49% of the prescriptions were inappropriate due to unnecessary treatment (14%), not first line drug recommended (14%), inadequate drug according to microbiological results (9%), unsuitable doses (8%), route (3%) or duration (7%). Samples collection presented a significant protective effect together with sepsis presentation at onset and intensive care unit admission. However, age, receiving an empirical treatment and an unknown or urinary source of the infections treated were independent risk factors for inappropriateness. Site and severity of infection were documented in medical charts by prescribers (75 and 61% respectively). PPS may allow identifying the main risk factors for inappropriateness. This simple methodology may be useful for ASP to select modifiable factors to be prioritized for targeted interventions.
HAS 1: A natural product from soil-isolated Streptomyces species with potent activity against cutaneous leishmaniasis caused by Leishmania tropica
Authors: Awada Bassel , Hamie Maguy , El Hajj Rana , Derbaj Ghada , Najm Rania , Makhoul Perla , Ali Dima Hajj , Abou Fayad Antoine G. , El Hajj Hiba 
Published: October 2022

Cutaneous Leishmaniasis (CL) is a neglected tropical disease, classified by the World Health Organization (WHO) as one of the most unrestrained diseases. The Syrian war and the significant displacement of refugees aggravated the spread of this ailment into several neighboring countries in the Eastern Mediterranean Region (EMR). In Syria, Leishmania tropica is identified as one of the most aggressive and endemic identified species, causing localized or generalized lesions, often chronic or relapsing. Pentavalent antimonial drugs are currently used as first line treatment against CL. Nonetheless, these drugs exhibit several limitations, including the repetitive painful injections, high cost, poor availability, and mainly systemic toxicity. Besides, the emergence of acquired parasitic resistance hinders their potency, stressing the need for new therapies to combat CL. Natural products (NPs) epitomize a valuable source in drug discovery. NPs are secondary metabolites (SMs) produced by plants, sponges, or a wide variety of organisms, including environmental microorganisms. The EMR is characterized by its immense biodiversity, yet it remains a relatively untapped area in drug discovery. NPs of the region were explored over the last 2 decades, but their discoveries lack biogeographical diversity and are limited to the Red Sea. Here, we isolated previously uncultured environmental soil-dwelling Streptomyces sp. HAS1, from Hasbaya region in southeast Lebanon. When fermented in one of our production media named INA, HAS1 produced a crude extract with significant potency against a clinical Leishmania tropica isolate. Using bio-guided fractionation, the bioactive compound was purified and the structure was elucidated by NMR and LC-HRMS. Our findings establish NPs as strong candidates for treating Leishmania tropica and further dwells on the importance of these natural sources to combat microbial infections.
Use of modeling and simulation to predict the influence of triazole antifungal agents on the pharmacokinetics of zanubrutinib and acalabrutinib
Authors: Chen Lu , Li Chao , Bai Hao , Li Lixian , Chen Wanyi 
Published: October 2022

Background: Bruton’s tyrosine kinase (BTK) inhibitors are commonly used in the targeted therapy of B-cell malignancies. It is reported that myelosuppression and fungal infections might occur during antitumor therapy of BTK inhibitors, therefore a combination therapy with triazole antifungals is usually required.Objective: To evaluate the influence of different triazoles (voriconazole, fluconazole, itraconazole) on the pharmacokinetics of BTK inhibitors (zanubrutinib, acalabrutinib) and to quantify the drug-drug interactions (DDIs) between them.Methods: The physiologically-based pharmacokinetic (PBPK) models were developed based on pharmacokinetic parameters and physicochemical data using Simcyp® software. These models were validated using clinically observed plasma concentrations data which based on existing published studies. The successfully validated PBPK models were used to evaluate and predict potential DDIs between BTK inhibitors and different triazoles. BTK inhibitors and triazole antifungal agents were simulated by oral administration.Results: Simulated plasma concentration-time profiles of the zanubrutinib, acalabrutinib, voriconazole, fluconazole, and itraconazole are consistent with the clinically observed profiles which based on existing published studies, respectively. The exposures of BTK inhibitors increase by varying degrees when co-administered with different triazole antifungals. At multiple doses regimen, voriconazole, fluconazole and itraconazole may increase the area under plasma concentration-time curve (AUC) of zanubrutinib by 127%, 81%, and 48%, respectively, and may increase the AUC of acalabrutinib by 326%, 119%, and 264%, respectively.Conclusion: The PBPK models sufficiently characterized the pharmacokinetics of BTK inhibitors and triazole antifungals, and were used to predict untested clinical scenarios. Voriconazole exhibited the greatest influence on the exposures of BTK inhibitors. The dosage of zanubrutinib or acalabrutinib need to be reduced when co-administered with moderate CYP3A inhibitors.