bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual visits at the Helsinki Head and Neck Center during the COVID-19 pandemic: patient safety incidents and the experiences of patients and staff
Authors: Tolvi Morag , Oksanen Lotta-Maria , Lehtonen Lasse , Geneid Ahmed , Männikkö Pia , Ruokonen Hellevi , Majander Anna , Arminen Susan , Aaltonen Leena-Maija 
Published: May 2023

Abstract
Background
During the COVID-19 pandemic, health care had to find new ways to care for patients while reducing infection transmission. The role of telemedicine role has grown exponentially.

Methods
A questionnaire on experiences and satisfaction was sent to the staff of the Head and Neck Center of Helsinki University Hospital and to otorhinolaryngology patients treated remotely between March and June 2020. Additionally, patient safety incident reports were examined for incidents involving virtual visits.

Results
Staff (response rate 30.6%, (n = 116)) opinions seemed to be quite polarized. In general, staff felt virtual visits were useful for select groups of patients and certain situations, and beneficial in addition to face-to-face visits, not instead of them. Patients (response rate 11.7%, (n = 77)) gave positive feedback on virtual visits, with savings in time (average 89 min), distance travelled (average 31.4 km) and travel expenses (average 13.84€).

Conclusions
While telemedicine was implemented during the COVID-19 pandemic to ensure patient treatment, its usefulness after the pandemic must be examined. Evaluation of treatment pathways is critical to ensure that quality of care is upheld while new treatment protocols are introduced. Telemedicine offers the opportunity to save environmental, temporal, and monetary resources. Nonetheless, the appropriate use of telemedicine is essential, and clinicians must be offered the option to examine and treat patients face-to-face.
Accuracy of minimal residual disease detection by circulating tumor DNA profiling in lung cancer: a meta-analysis
Authors: Zhong Ran , Gao Rui , Fu Wenhai , Li Caichen , Huo Zhenyu , Gao Yuewen , Lu Yi , Li Feng , Ge Fan , Tu Hengjia , You Zhixuan , He Jianxing , Liang Wenhua 
Published: May 2023

Abstract

Background

The sensitivity and specificity of minimal residual disease detected by circulating tumor DNA profiling (ctDNA MRD) in lung cancer, with particular attention to the distinction between landmark strategy and surveillance strategy, for predicting relapse in lung cancer patients after definitive therapy has yet to be determined.

Methods
The prognostic value of ctDNA MRD by landmark strategy and surveillance strategy was evaluated in a large cohort of patients with lung cancer who received definitive therapy using a systemic literature review and meta-analysis. Recurrence status stratified by ctDNA MRD result (positive or negative) was extracted as the clinical endpoint. We calculated the area under the summary receiver operating characteristic curves, and pooled sensitivities and specificities. Subgroup analyses were conducted based on histological type and stage of lung cancer, types of definitive therapy, and ctDNA MRD detection methods (detection technology and strategy such as tumor-informed or tumor-agnostic).

Results
This systematic review and meta-analysis of 16 unique studies includes 1251 patients with lung cancer treated with definitive therapy. The specificity of ctDNA MRD in predicting recurrence is high (0.86–0.95) with moderate sensitivity (0.41–0.76), whether shortly after treatment or during the surveillance. The landmark strategy appears to be more specific but less sensitive than the surveillance strategy.

Conclusions
Our study suggests that ctDNA MRD is a relatively promising biomarker for relapse prediction among lung cancer patients after definitive therapy, with a high specificity but suboptimal sensitivity, whether in landmark strategy or surveillance strategy. Although surveillance ctDNA MRD analysis decreases specificity compared with the landmark strategy, the decrease is minimal compared to the increase in sensitivity for relapse prediction of lung cancer.
Post-malarial neurological syndrome in a Gambian adult residing in the Gambia: a case report and a review of literature
Authors: Ekeh Bertha C. , Bah Ebrima , Jobe Ya Fatou B M , Daboer Aji F. , Gomez Mariama , Lanlokun Ridhwan A. 
Published: May 2023

AbstractBackgroundPost malarial neurological syndrome (PMNS) occurs as a sequel of cerebral malaria which is the most deadly form of severe malaria. In holo-endemic regions (areas of high malarial transmission) all forms of severe malaria as well as cerebral malaria usually occur in children and those who are semi or non-immune like pregnant women, migrants as well as tourists. It also occurs in hypo-endemic regions (areas of limited malarial transmission with low immunity) and malaria- free zones. Survivors however may have neurologic complications after recovery. PMNS has been reported in many parts of the world. Being a sequel to cerebral malaria, it is uncommon in adults who were born and reside in a holo-endemic region all their lives.Case reportThis is the case of an 18 year old Gambian who has lived in The Gambia all his life that had PMNS five days after recovery from cerebral malaria.MethodsThis was a predominantly web based literature search. The search comprise all case reports, original articles and reviews on PMNS or neurological deficits associated with malaria or noted after malaria infection. The search engines used were Google, Yahoo and Google scholar.ResultsA total of 62 papers were found. These were used for this review of the literature.ConclusionCerebral malaria also occurs in adults in holo-endemic areas though rare and some of the survivors may develop PMNS. It is commoner in the youth age group. There is need for further studies since the youth may be a possible new ‘vulnerable group’ in holoendemic areas. This may lead to the widening the targeted group for malaria control in the regions of high malarial transmission.
Radio-resistance of hypoxic tumors: exploring the effects of oxygen and X-ray radiation on non-small lung cancer cell lines
Authors: Hanley Rachel , Pagliari Francesca , Garcia-Calderón Daniel , Fernandes Guerreiro Joana , Genard Géraldine , Jansen Jeannette , Nisticò Clelia , Marafioti Maria Grazia , Tirinato Luca , Seco Joao 
Published: May 2023

Abstract
Background
Solid tumors are often riddled with hypoxic areas, which develops as a result of high proliferation. Cancer cells willingly adapt and thrive in hypoxia by activating complex changes which contributes to survival and enhanced resistance to treatments, such as photon radiation. Photon radiation primarily relies on oxygen for the production of reactive oxygen species to induce DNA damage. The present in-vitro study aimed at investigating the biochemical responses of hypoxic non-small cell lung cancer (NSCLC) cells, particularly the effects on the DNA damage repair systems contributing to more radioresistant phenotypes and their pro- and anti-oxidant potential, within the first 24 h post-IR.

Methods
NSCLC cell lines (H460, A549, Calu-1) were irradiated using varying X-ray doses under normoxia (21% O2) and hypoxia (0.1% O2). The overall cell survival was assessed by clonogenic assays. The extent of irradiation (IR)-induced DNA damage was evaluated by analyzing γ-H2AX foci induction and the altered expression of repair genes involved in non-homologous end joining and homologous recombination pathways. Moreover, cell-altered responses were investigated, including the nuclear and cytosolic hydrogen peroxide (H2O2) production, as well as the associated anti-oxidant potential, in particular some components related to the glutathione system.

Results
Analysis of clonogenic survival revealed an enhanced radioresistance of the hypoxic NSCLC cells associated with reduced DNA damage and a downregulation of DNA repair genes. Moreover, nuclear H2O2 levels were IR-induced in a dose-dependent manner only under normoxia, and directly correlated with the DNA double-strand breaks. However, the observed nuclear H2O2 reduction in hypoxia appeared to be unaffected by IR, thus highlighting a possible reason for the enhanced radioresistance of the hypoxic NSCLC cells. The cellular antioxidant capacity was upregulated by IR in both oxygen conditions most likely helping to counteract the radiation effect on the cytosolic H2O2.

Conclusions
In conclusion, our data provide insight into the adaptive behavior of radiation-resistant hypoxic NSCLC cells, in particular their DNA repair and oxidative stress responses, which could contribute to lower DNA damage and higher cell survival rates following X-ray exposure. These findings may therefore help to identify potential targets for improving cancer treatment outcomes.
Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome
Authors: Wang Yue , Cai Mengru , Jiang Xianliang , Lv Guangyu , Hu Daiju , Zhang Guofeng , Liu Jinli , Wei Wei , Xiao Jun , Shen Bing , Ryu Jay H. , Hu Xiaowen 
Published: May 2023

Abstract
Background
The pathogenic variants responsible for Birt-Hogg-Dubé syndrome (BHDS) in folliculin (FLCN) gene mostly consist of point mutations. Although large intragenic deletions/duplications have been reported in several case reports, the relationship between large intragenic deletions/duplications and phenotype in BHDS remains unclear.

Methods
We retrospectively identified and reviewed patients with a large intragenic deletion spanning exons 1–3 and analyzed their phenotypic features to compare with those of point mutation carriers in our hospital from January 1, 2017 to August 31, 2022.

Results
Twenty unique point mutations (including 4 novel mutations) were detected in 62 patients from 45 families (90%). Exons 1–3 deletion were identified in 8 patients from 5 families (10%) that resided in the same region, Feidong County of Anhui Province, China. Breakpoint analysis indicated that all the deletion breakpoints were flanked by Alu repeats. The prevalence of exons 1–3 deletion carriers in Feidong County was 8.1-times higher than that for BHDS in Anhui Province, suggesting a clustered phenomenon of exons 1–3 deletion. Significantly increased risk of pneumothorax was observed in those with exons 1–3 deletion compared with point mutations (91% vs. 58%, p value 0.047). The risk of renal cancer may be higher in those with exons 1–3 deletion than for those with point mutations (18% vs. 4%, p > 0.05).

Conclusions
Large intragenic deletion of exons 1–3 in FLCN was identified as a local aggregation phenomenon in Feidong County, China, and was associated with a significantly higher risk of pneumothorax compared to those with point mutations.
Exploring circular MET RNA as a potential biomarker in tumors exhibiting high MET activity
Authors: Bersani Francesca , Picca Francesca , Morena Deborah , Righi Luisella , Napoli Francesca , Russo Mariangela , Oddo Daniele , Rospo Giuseppe , Negrino Carola , Castella Barbara , Volante Marco , Listì Angela , Zambelli Vanessa , Benso Federica , Tabbò Fabrizio , Bironzo Paolo , Monteleone Emanuele , Poli Valeria , Pietrantonio Filippo , Di Nicolantonio Federica , Bardelli Alberto , Ponzetto Carola , Novello Silvia , Scagliotti Giorgio V. , Taulli Riccardo 
Published: May 2023

Abstract
Background
MET-driven acquired resistance is emerging with unanticipated frequency in patients relapsing upon molecular therapy treatments. However, the determination of MET amplification remains challenging using both standard and next-generation sequencing-based methodologies. Liquid biopsy is an effective, non-invasive approach to define cancer genomic profiles, track tumor evolution over time, monitor treatment response and detect molecular resistance in advance. Circular RNAs (circRNAs), a family of RNA molecules that originate from a process of back-splicing, are attracting growing interest as potential novel biomarkers for their stability in body fluids.

Methods
We identified a circRNA encoded by the MET gene (circMET) and exploited blood-derived cell-free RNA (cfRNA) and matched tumor tissues to identify, stratify and monitor advanced cancer patients molecularly characterized by high MET activity, generally associated with genomic amplification.

Results
Using publicly available bioinformatic tools, we discovered that the MET locus transcribes several circRNA molecules, but only one candidate, circMET, was particularly abundant. Deeper molecular analysis revealed that circMET levels positively correlated with MET expression and activity, especially in MET-amplified cells. We developed a circMET-detection strategy and, in parallel, we performed standard FISH and IHC analyses in the same specimens to assess whether circMET quantification could identify patients displaying high MET activity. Longitudinal monitoring of circMET levels in the plasma of selected patients revealed the early emergence of MET amplification as a mechanism of acquired resistance to molecular therapies.

Conclusions
We found that measurement of circMET levels allows identification and tracking of patients characterized by high MET activity. Circulating circMET (ccMET) detection and analysis could be a simple, cost-effective, non-invasive approach to better implement patient stratification based on MET expression, as well as to dynamically monitor over time both therapy response and clonal evolution during treatment.
Predicting the outcome of plantar heel pain in adults: a systematic review of prognostic factors
Authors: Gulle Halime , Morrissey Dylan , Tan Xiang Li , Cotchett Matthew , Miller Stuart Charles , Jeffrey Aleksandra Birn , Prior Trevor 
Published: May 2023

AbstractBackgroundPlantar Heel Pain (PHP) is a common disorder with many treatment pathways and is not self‐limiting, hence prognostic information concerning recovery or recalcitrance is needed to guide practice. In this systematic review, we investigate which prognostic factors are associated with favourable or unfavourable PHP outcomes.MethodsMEDLINE, Web of Science, EMBASE, Scopus and PubMed electronic bibliographic databases were searched for studies evaluating baseline patient characteristics associated with outcomes in prospective longitudinal cohorts or after specific interventions. Cohort, clinical prediction rule derivation and single arms of randomised controlled trials were included. Risk of bias was evaluated with method‐specific tools and evidence certainty with GRADE.ResultsThe review included five studies which evaluated 98 variables in 811 participants. Prognostic factors could be categorised as demographics, pain, physical and activity‐related. Three factors including sex and bilateral symptoms (HR: 0.49[0.30–0.80], 0.33[0.15–0.72], respectively) were associated with a poor outcome in a single cohort study. The remaining four studies reported twenty factors associated with a favourable outcome following shockwave therapy, anti‐pronation taping and orthoses. Heel spur (AUC = 0.88[0.82–0.93]), ankle plantar‐flexor strength (Likelihood ratio (LR): 2.17[1.20–3.95]) and response to taping (LR = 2.17[1.19–3.90]) were the strongest factors predicting medium‐term improvement. Overall, the study quality was low. A gap map analysis revealed an absence of research that included psychosocial factors.ConclusionsA limited number of biomedical factors predict favourable or unfavourable PHP outcomes. High quality, adequately powered, prospective studies are required to better understand PHP recovery and should evaluate the prognostic value of a wide range of variables, including psychosocial factors.
Citicoline in hypoxic ischemic encephalopathy in neonates: a randomized controlled trial
Authors: Salamah Abeer , El Amrousy Doaa , Elsheikh Mai , Mehrez Mostafa 
Published: May 2023

Abstract
Background
Hypoxic-ischemic encephalopathy (HIE) is one of the major complications that can lead to death or disability in neonates. We assessed the effect of citicoline as a neuroprotector in neonates with moderate and severe HIE.

Methods
This clinical trial was carried on 80 neonates with moderate to severe HIE who were not candidates for therapeutic cooling. They were subdivided randomly into two groups; citicoline treatment group which included 40 neonates who received citicoline 10 mg / kg /12 h IV for 4 weeks plus other supportive measures and the control group which included 40 neonates who were managed with placebo and the same supportive measures. All patients were evaluated for duration of mechanical ventilation (MV), need for inotropes, seizures (type, frequency, and duration), and duration of NICU. Cranial ultrasounds and brain magnetic resonance image (MRI) were performed for all included neonates after 4 weeks of treatment. Follow- ups of all neonates for the neurodevelopmental outcomes were done at 3, 6, 9, and 12 months.

Results
There was a significant reduction in the number of neonates having seizures after discharge in the citicoline-treated group (2 neonates) compared to the control group (11 neonates). Cranial ultrasound and MRI findings at 4 weeks were significantly better in the treatment group compared to the control group. Moreover, neurodevelopmental outcome showed significant improvement at 9 and 12 months in the citicoline treated neonates compared to the control group. There was statistically significant reduction in the duration of seizures, NICU stay, inotrope use, and MV in the treatment group compared to the control group. Citicoline was well tolerated with no remarkable side effects.

Conclusion
Citicoline could be a promising neuroprotector drug in neonates with HIE.

Trial registration
The study was registered at ClinicalTrials.gov (NCT03949049). Registered at 14 May 2019, https://clinicaltrials.gov/ct2/show/NCT03949049
Central venous stenosis after subclavian versus internal jugular dialysis catheter insertion (CITES) in adults in need of a temporary central dialysis catheter: study protocol for a two-arm, parallel-group, non-inferiority randomised controlled trial
Authors: Borgquist Ola , Naddi Leila , Božović Gracijela , Hellberg Matthias , Annborn Martin , Sjövall Fredrik , Adrian Maria , Hettinger Eva , Sjöberg Pia , Kander Thomas 
Published: May 2023

Abstract
Background
The right internal jugular vein is currently recommended for temporary central dialysis catheters (tCDC) based on results from previous studies showing a lower incidence of central vein stenosis compared to the subclavian vein. Data is however conflicting, and there are several advantages when the subclavian route is used for tCDCs. This prospective, controlled, randomised, non-inferiority study aims to compare the incidence of post-catheterisation central vein stenosis between the right subclavian and the right internal jugular routes.

Methods
Adult patients needing a tCDC will be included from several hospitals and randomised to either subclavian or internal jugular vein catheterisation with a silicone tCDC. Inclusion continues until 50 patients in each group have undergone a follow-up CT venography. The primary outcome is the incidence of post-catheterisation central vein stenosis detected by a CT venography performed 1.5 to 3 months after removal of the tCDC. Secondary outcomes include between-group comparisons of (I) the patients’ experience of discomfort and pain, (II) any dysfunction of the tCDC during use, (III) catheterisation success rate and (IV) the number of mechanical complications. Furthermore, the ability to detect central vein stenosis by a focused ultrasound examination will be evaluated using the CT venography as golden standard.

Discussion
The use of the subclavian route for tCDC placement has largely been abandoned due to older studies with various methodological issues. However, the subclavian route offers several advantages for the patient. This trial is designed to provide robust data on the incidence of central vein stenosis after silicone tCDC insertion in the era of ultrasound-guided catheterisations.

Trial registration
Clinicaltrials.gov; NCT04871568. Prospectively registered on May 4, 2021.
Diagnostic value of IL-6 for patients with asthma: a meta-analysis
Authors: Pan Ruilin , Kuai Shougang , Li Qingqing , Zhu Xuming , Wang Tingting , Cui Yubao 
Published: May 2023

Abstract
Background
IL-6 is a pleotropic cytokine that acts as a pro-inflammatory mediator and acute-phase response inducer, but has also been reported to possess anti-inflammatory properties. The objective of this study was to assess the validity of serum IL-6 test for diagnosis of asthma.

Methods
A literature search was conducted using PubMed, Embase, and Cochrane library from January 2007 to March 2021 to identify relevant studies. Eleven studies were included in this analysis, involving 1977 patients with asthma and 1591 healthy non-asthmatic controls. The meta-analysis was performed using Review Manager 5.3 software and Stata 16.0. Random effect model or fixed effect model (FEM) was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs).

Results
The meta-analysis results revealed that the serum IL-6 levels were higher in asthmatic patients than healthy non-asthmatic controls (SMD 1.31, 95% CI 0.82–1.81, P < 0.00001). IL-6 levels are significantly elevated in pediatric patients with asthma (SMD 1.58, 95% CI 0.75–2.41, P = 0.0002) and mildly elevated in adult patients with asthma (SMD 1.08, 95% CI 0.27–1.90, P = 0.009). In addition, a subgroup analysis of asthma disease status showed that IL-6 levels were increased in stable (SMD 0.69, 95% CI 0.28–1.09, P = 0.009) and exacerbation asthma (SMD 2.15, 95% CI 1.79–2.52, P < 0.00001) patients.

Conclusion
The results of this meta-analysis suggest that serum IL-6 levels were significantly elevated in asthmatic patients as compared to normal population. IL-6 levels can be used as an auxiliary indicator to distinguish individuals with asthma from healthy non-asthmatic controls.
Insight into muscle stem cell regeneration and mechanobiology
Authors: Pang Kuin Tian , Loo Larry Sai Weng , Chia Sean , Ong Francesca Yi Teng , Yu Hanry , Walsh Ian 
Published: May 2023

AbstractStem cells possess the unique ability to differentiate into specialized cell types. These specialized cell types can be used for regenerative medicine purposes such as cell therapy. Myosatellite cells, also known as skeletal muscle stem cells (MuSCs), play important roles in the growth, repair, and regeneration of skeletal muscle tissues. However, despite its therapeutic potential, the successful differentiation, proliferation, and expansion processes of MuSCs remain a significant challenge due to a variety of factors. For example, the growth and differentiation of MuSCs can be greatly influenced by actively replicating the MuSCs microenvironment (known as the niche) using mechanical forces. However, the molecular role of mechanobiology in MuSC growth, proliferation, and differentiation for regenerative medicine is still poorly understood. In this present review, we comprehensively summarize, compare, and critically analyze how different mechanical cues shape stem cell growth, proliferation, differentiation, and their potential role in disease development (Fig. 1). The insights developed from the mechanobiology of stem cells will also contribute to how these applications can be used for regenerative purposes using MuSCs.