bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct and indirect costs and cost-driving factors in adults with tuberous sclerosis complex: a multicenter cohort study and a review of the literature
Authors: Zöllner Johann Philipp , Grau Janina , Rosenow Felix , Sauter Matthias , Knuf Markus , Kurlemann Gerhard , Mayer Thomas , Hertzberg Christoph , Bertsche Astrid , Immisch Ilka , Klein Karl Martin , Knake Susanne , Marquard Klaus , Meyer Sascha , Noda Anna H. , von Podewils Felix , Schäfer Hannah , Thiels Charlotte , Willems Laurent M. , Zukunft Bianca , Schubert-Bast Susanne , Strzelczyk Adam 
Published: June 2021

Abstract
Background
Tuberous sclerosis complex (TSC) is a monogenetic, multisystem disorder characterized by benign growths due to TSC1 or TSC2 mutations. This German multicenter study estimated the costs and related cost drivers associated with organ manifestations in adults with TSC.

Methods
A validated, three-month, retrospective questionnaire assessed the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket (OOP), and nursing care-level costs among adult individuals with TSC throughout Germany from a societal perspective (costing year: 2019).

Results
We enrolled 192 adults with TSC (mean age: 33.4 ± 12.7 years; range: 18–78 years, 51.6% [n = 99] women). Reported TSC disease manifestations included skin (94.8%) and kidney and urinary tract (74%) disorders, epilepsy (72.9%), structural brain defects (67.2%), psychiatric disorders (50.5%), heart and circulatory system disorders (50.5%), and lymphangioleiomyomatosis (11.5%). TSC1 and TSC2 mutations were reported in 16.7% and 25% of respondents, respectively. Mean direct health care costs totaled EUR 6452 (median EUR 1920; 95% confidence interval [CI] EUR 5533–7422) per patient over three months. Medication costs represented the major direct cost category (77% of total direct costs; mean EUR 4953), and mechanistic target of rapamycin (mTOR) inhibitors represented the largest share (68%, EUR 4358). Mean antiseizure drug (ASD) costs were only EUR 415 (6%). Inpatient costs (8%, EUR 518) and outpatient treatment costs (7%; EUR 467) were important further direct cost components. The mean care grade allowance as an approximator of informal nursing care costs was EUR 929 (median EUR 0; 95% CI EUR 780–1083) over three months. Mean indirect costs totaled EUR 3174 (median EUR 0; 95% CI EUR 2503–3840) among working-age individuals (< 67 years in Germany). Multiple regression analyses revealed mTOR inhibitor use and persistent seizures as independent cost-driving factors for total direct costs. Older age and disability were independent cost-driving factors for total indirect costs, whereas epilepsy, psychiatric disease, and disability were independent cost-driving factors for nursing care costs.

Conclusions
This three-month study revealed substantial direct healthcare, indirect healthcare, and medication costs associated with TSC in Germany. This study highlights the spectrum of organ manifestations and their associated treatment needs in the German healthcare setting. Trial registration: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.
Diabetes outbreak during COVID19 lock-down in a prediabetic patient with cystic fibrosis long treated with glargine
Authors: Rosanio Francesco Maria , Mozzillo Enza , Cimbalo Chiara , Casertano Alberto , Sepe Angela , Raia Valeria , Franzese Adriana , Tosco Antonella 
Published: June 2021

Abstract
Background
Cystic Fibrosis Related Diabetes (CFRD) is a frequent comorbidity of patients with Cystic Fibrosis (CF). A worsening of clinical conditions appears before CFRD. It has been demonstrated a decline in pulmonary function and nutritional status also in patients with prediabetes. Few trials show that insulin may be beneficial in prediabetic CF patients, to date guidelines do not recommend for this condition.

Case presentation
We report a case of a patient treated with insulin glargine at 13 years, due to glycemic intolerance, and with Lumacaftor/Ivacaftor at 15 years. A reduction of pulmonary exacerbations was observed after glargine therapy, also confirmed after the starting of Lumacaftor/ Ivacaftor in this patient. Pulmonary function improved only after the first year of glargine therapy, then a deterioration appeared due to the natural history of CF lung damage. During the COVID-19 lockdown, poor adherence to care contributed to diabetes mellitus onset needing high insulin requirements. After two weeks the patient returned to prediabetic condition and his previous dose of glargine.

Conclusions
our case highlights firstly that insulin glargine has contributed to preserve him from further clinical worsening due to prediabetes in the years before pandemic, secondly the negative impact of COVID-19 lockdown on the clinical course of a chronic disease as CF.
A case report of a boy suffering from type 1 diabetes mellitus and familial Mediterranean fever
Authors: Gicchino Maria Francesca , Iafusco Dario , Zanfardino Angela , del Giudice Emanuele Miraglia , Olivieri Alma Nunzia 
Published: June 2021

Abstract
Background
Type 1 diabetes mellitus could be associated with other autoimmune diseases, such as autoimmune thyroid disease, celiac disease, but the association with Familial Mediterranean Fever is rare, we describe a case of a boy with type 1 Diabetes Mellitus associated with Familial Mediterranean Fever (FMF).

Case presentation
A 13 year old boy already suffering from Diabetes Mellitus type 1 since the age of 4 years, came to our attention because of periodic fever associated with abdominal pain, chest pain and arthralgia. The fever appeared every 15–30 days with peaks that reached 40 °C and lasted 24–48 h. Laboratory investigation, were normal between febrile episodes, but during the attacks revealed an increase in inflammatory markers. Suspecting Familial Mediterranean Fever molecular analysis of MEFV gene, was performed. The genetic analysis showed homozygous E148Q mutation. So Familial Mediterranean Fever was diagnosed and colchicine treatment was started with good response.

Conclusion
Familial Mediterranean Fever could be associated with other autoimmune diseases such as Ankylosing Spondylitis, Rheumatoid Arthritis, Polyarteritis Nodosa, Behcet disease, Systemic Lupus, Henoch-Schönlein Purpura, and Hashimoto’s Thyroiditis. Association of type 1 Diabetes Mellitus and Familial Mediterranean Fever has been newly reported in the medical literature, this is the third association of these two diseases described in the medical literature so far.
Endoscopic vacuum therapy versus stent treatment of esophageal anastomotic leaks (ESOLEAK): study protocol for a prospective randomized phase 2 trial
Authors: Tachezy Michael , Chon Seung-Hun , Rieck Isabel , Kantowski Marcus , Christ Hildegard , Karstens Karl , Gebauer Florian , Goeser Tobias , Rösch Thomas , Izbicki Jakob R. , Bruns Christiane J. 
Published: June 2021

Abstract
Background
Intrathoracic anastomotic leaks represent a major complication after Ivor Lewis esophagectomy. There are two promising endoscopic treatment strategies in the case of leaks: the placement of self-expanding metal stents (SEMS) or endoscopic vacuum therapy (EVT). Up to date, there is no prospective data concerning the optimal endoscopic treatment strategy. This is a protocol description for the ESOLEAK trial, which is a first small phase 2 randomized trial evaluating the quality of life after treatment of anastomotic leaks by either SEMS placement or EVT.

Methods
This phase 2 randomized trial will be conducted at two German tertiary medical centers and include a total of 40 patients within 2 years. Adult patients with histologically confirmed esophageal cancer, who have undergone Ivor Lewis esophagectomy and show an esophagogastric anastomotic leak on endoscopy or present with typical clinical signs linked to an anastomotic leak, will be included in our study taking into consideration the exclusion criteria. After endoscopic verification of the anastomotic leak, patients will be randomized in a 1:1 ratio into two treatment groups. The intervention group will receive EVT whereas the control group will be treated with SEMS. The primary endpoint of this study is the subjective quality of life assessed by the patient using a systematic and validated questionnaire (EORTC QLQ C30, EORTC QLQ-OES18 questionnaire). Important secondary endpoints are healing rate, period of hospitalization, treatment-related complications, and overall mortality.

Discussion
The latest meta-analysis comparing implantation of SEMS with EVT in the treatment of esophageal anastomotic leaks suggested a higher success rate for EVT. The ESOLEAK trial is the first study comparing both treatments in a prospective manner. The aim of the trial is to find suitable endpoints for the treatment of anastomotic leaks as well as to enable an adequate sample size calculation and evaluate the feasibility of future interventional trials. Due to the exploratory design of this pilot study, the sample size is too small to answer the question, whether EVT or SEMS implantation represents the superior treatment strategy.

Trial registration
ClinicalTrials.gov NCT03962244. Registered on May 23, 2019.
DRKS-ID DRKS00007941
Evaluation of sleep quality and anxiety in Italian pediatric healthcare workers during the first wave of COVID-19 pandemic
Authors: Di Filippo Paola , Attanasi Marina , Dodi Giulia , Porreca Annamaria , Raso Massimiliano , Di Pillo Sabrina , Chiarelli Francesco 
Published: June 2021

AbstractObjectiveThe aim of this study was to evaluate sleep quality and psychological effects on pediatric healthcare workers during the first wave of COVID-19 epidemic in Italy and to evaluate differences between primary and secondary care operators. Pediatric healthcare workers were involved in an online survey to assess sleep quality, stress and anxiety level, self-efficacy and social support in Italian pediatric healthcare workers during COVID-19 pandemic.ResultsWe found that 67.4% of our sample suffered from sleep disturbance and 19.4% of subjects suffered from anxiety. Lower values of anxiety and social support were found in primary care staff compared to secondary care one. The associations between healthcare professional figures (being primary or secondary care operators) and mental health outcomes were not statistically significant. However, sex, age and having a SARS-CoV-2 infected relative/friend had an independent effect on mental health outcomes. It is crucial to provide social and psychological support to pediatric healthcare workers. A tailored psychological screening would be desirable for female healthcare workers and for those who have a SARS-CoV-2 infected relative/friend.
Management of a spontaneous supra-aortic arterial dissection: a case report
Authors: Sharaf Omar M. , Martin Tomas D. , Jeng Eric I. 
Published: June 2021

Abstract
Background
Acute DeBakey type I and type II aortic dissections are indications for emergent surgical repair; however, there are currently no standard protocols in the management of isolated supra-aortic dissections. Prompt diagnosis and management of an isolated innominate artery dissection are necessary to prevent distal malperfusion and thromboembolic sequelae.

Case presentation
A 50-year-old Caucasian gentleman presented with chest pain radiating to his jaw and right arm. He had no recent history of trauma. On physical exam, he was neurologically intact and malignantly hypertensive. Computed tomographic angiography of the chest and neck confirmed a spontaneous isolated innominate artery dissection without ascending aorta involvement. Given the lack of evidence for rupture, distal emboli, and/or end-organ malperfusion, the decision was made for initial non-operative management—anti-impulse regimen, antiplatelet therapy, and close follow-up.

Conclusions
Medical management of a spontaneous isolated innominate artery dissection is appropriate for short-term and potentially long-term therapy. This not only spares the patient from a potentially unnecessary surgical operation but also provides the surgeon and the patient the time to plan for a surgical approach if it becomes necessary.
Holobiont nitrogen control and its potential for eutrophication resistance in an obligate photosymbiotic jellyfish
Authors: Röthig Till , Puntin Giulia , Wong Jane C. Y. , Burian Alfred , McLeod Wendy , Baker David M. 
Published: June 2021

Abstract
Background
Marine holobionts depend on microbial members for health and nutrient cycling. This is particularly evident in cnidarian-algae symbioses that facilitate energy and nutrient acquisition. However, this partnership is highly sensitive to environmental change—including eutrophication—that causes dysbiosis and contributes to global coral reef decline. Yet, some holobionts exhibit resistance to dysbiosis in eutrophic environments, including the obligate photosymbiotic scyphomedusa Cassiopea xamachana.

Methods
Our aim was to assess the mechanisms in C. xamachana that stabilize symbiotic relationships. We combined labelled bicarbonate (13C) and nitrate (15N) with metabarcoding approaches to evaluate nutrient cycling and microbial community composition in symbiotic and aposymbiotic medusae.

Results
C-fixation and cycling by algal Symbiodiniaceae was essential for C. xamachana as even at high heterotrophic feeding rates aposymbiotic medusae continuously lost weight. Heterotrophically acquired C and N were readily shared among host and algae. This was in sharp contrast to nitrate assimilation by Symbiodiniaceae, which appeared to be strongly restricted. Instead, the bacterial microbiome seemed to play a major role in the holobiont’s DIN assimilation as uptake rates showed a significant positive relationship with phylogenetic diversity of medusa-associated bacteria. This is corroborated by inferred functional capacity that links the dominant bacterial taxa (~90 %) to nitrogen cycling. Observed bacterial community structure differed between apo- and symbiotic C. xamachana putatively highlighting enrichment of ammonium oxidizers and nitrite reducers and depletion of nitrogen-fixers in symbiotic medusae.

Conclusion
Host, algal symbionts, and bacterial associates contribute to regulated nutrient assimilation and cycling in C. xamachana. We found that the bacterial microbiome of symbiotic medusae was seemingly structured to increase DIN removal and enforce algal N-limitation—a mechanism that would help to stabilize the host-algae relationship even under eutrophic conditions.
High precision 3-D coordinates for JSATS tagged fish in an acoustically noisy environment
Authors: Nebiolo Kevin P. , Meyer Thomas H. 
Published: June 2021

Abstract
Background
Acoustic tagging methods have been used to track fish for some time. Multiple systems have been developed, including those that give researchers the ability to position fish in three dimensions and time. However, proprietary positioning methods have suffered from a lack of transparency. The U.S. Department of Energy and the U.S. Army Corps of Engineers developed the Juvenile Salmon Acoustic Telemetry System (JSATS) to monitor the survivability of juvenile salmonids as they migrate downstream. With much smaller tags and high ping rates, JSATS positioning studies should be more prevalent, but implementation is difficult and often out of reach for small budget-minded studies. This study implemented a small scale JSATS positioning study using relatively inexpensive, autonomous, independent receivers. We will show that proper synchronization of the transmissions and elimination of multipath allows the positions of a smolt to be determined in three spatial dimensions over time with high precision.

Results
Tracking of 172 tagged smolts produced a total of nearly 2,00,000 positions. We compared the performance of four different supervised machine learning classifiers (Support Vector Classifier (SVC), Gaussian Naïve Bayes (NB), Classification Tree (CART), and K-Nearest Neighbor (KNN). All algorithms performed well with high accuracy and precision, but recall rates decreased with distance from the source. The SVC and KNN were least restrictive in practice. Overall, the SVC had the longest time to solve.

Conclusion
Positions determined from fish outside of the convex hull of the hydrophones were effectively being extrapolated, while positions determined from within the convex hull nearly always met or exceeded 1-m precision. Having stationary submerged hydrophones was necessary to produce three-dimensional positions. The main technical advances presented are the hydrophone-clock synchronization scheme and the multipath rejection scheme, which found the best multipath classifier to be the K-Nearest Neighbor. Neither algorithm was capable of alleviating close proximity detection interference (CPDI), suggesting the need to reposition receivers from reflective surfaces or install baffling.
How do you feel during the COVID-19 pandemic? A survey using psychological and linguistic self-report measures, and machine learning to investigate mental health, subjective experience, personality, and behaviour during the COVID-19 pandemic among university students
Authors: Herbert Cornelia , El Bolock Alia , Abdennadher Slim 
Published: June 2021

Abstract
Background
The WHO has raised concerns about the psychological consequences of the current COVID-19 pandemic, negatively affecting health across societies, cultures and age-groups.

Methods
This online survey study investigated mental health, subjective experience, and behaviour (health, learning/teaching) among university students studying in Egypt or Germany shortly after the first pandemic lockdown in May 2020. Psychological assessment included stable personality traits, self-concept and state-like psychological variables related to (a) mental health (depression, anxiety), (b) pandemic threat perception (feelings during the pandemic, perceived difficulties in describing, identifying, expressing emotions), (c) health (e.g., worries about health, bodily symptoms) and behaviour including perceived difficulties in learning. Assessment methods comprised self-report questions, standardized psychological scales, psychological questionnaires, and linguistic self-report measures. Data analysis comprised descriptive analysis of mental health, linguistic analysis of self-concept, personality and feelings, as well as correlational analysis and machine learning. N = 220 (107 women, 112 men, 1 = other) studying in Egypt or Germany provided answers to all psychological questionnaires and survey items.

Results
Mean state and trait anxiety scores were significantly above the cut off scores that distinguish between high versus low anxious subjects. Depressive symptoms were reported by 51.82% of the student sample, the mean score was significantly above the screening cut off score for risk of depression. Worries about health (mental and physical health) and perceived difficulties in identifying feelings, and difficulties in learning behaviour relative to before the pandemic were also significant. No negative self-concept was found in the linguistic descriptions of the participants, whereas linguistic descriptions of feelings during the pandemic revealed a negativity bias in emotion perception. Machine learning (exploratory) predicted personality from the self-report data suggesting relations between personality and subjective experience that were not captured by descriptive or correlative data analytics alone.

Conclusion
Despite small sample sizes, this multimethod survey provides important insight into mental health of university students studying in Egypt or Germany and how they perceived the first COVID-19 pandemic lockdown in May 2020. The results should be continued with larger samples to help develop psychological interventions that support university students across countries and cultures to stay psychologically resilient during the pandemic.
Repetitive transcranial magnetic stimulation increases the brain’s drainage efficiency in a mouse model of Alzheimer’s disease
Authors: Lin Yangyang , Jin Jian , Lv Rongke , Luo Yuan , Dai Weiping , Li Wenchang , Tang Yamei , Wang Yuling , Ye Xiaojing , Lin Wei-Jye 
Published: June 2021

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disease with high prevalence rate among the elderly population. A large number of clinical studies have suggested repetitive transcranial magnetic stimulation (rTMS) as a promising non-invasive treatment for patients with mild to moderate AD. However, the underlying cellular and molecular mechanisms remain largely uninvestigated. In the current study, we examined the effect of high frequency rTMS treatment on the cognitive functions and pathological changes in the brains of 4- to 5-month old 5xFAD mice, an early pathological stage with pronounced amyloidopathy and cognitive deficit. Our results showed that rTMS treatment effectively prevented the decline of long-term memories of the 5xFAD mice for novel objects and locations. Importantly, rTMS treatment significantly increased the drainage efficiency of brain clearance pathways, including the glymphatic system in brain parenchyma and the meningeal lymphatics, in the 5xFAD mouse model. Significant reduction of Aβ deposits, suppression of microglia and astrocyte activation, and prevention of decline of neuronal activity as indicated by the elevated c-FOS expression, were observed in the prefrontal cortex and hippocampus of the rTMS-treated 5xFAD mice. Collectively, these findings provide a novel mechanistic insight of rTMS in regulating brain drainage system and β-amyloid clearance in the 5xFAD mouse model, and suggest the potential use of the clearance rate of contrast tracer in cerebrospinal fluid as a prognostic biomarker for the effectiveness of rTMS treatment in AD patients.
Big data insight on global mobility during the Covid-19 pandemic lockdown
Authors: Sadowski Adam , Galar Zbigniew , Walasek Robert , Zimon Grzegorz , Engelseth Per 
Published: June 2021

AbstractThe Covid-19 pandemic that began in the city of Wuhan in China has caused a huge number of deaths worldwide. Countries have introduced spatial restrictions on movement and social distancing in response to the rapid rate of SARS-Cov-2 transmission among its populations. Research originality lies in the taken global perspective revealing indication of significant relationships between changes in mobility and the number of Covid-19 cases. The study uncovers a time offset between the two applied databases, Google Mobility and John Hopkins University, influencing correlations between mobility and pandemic development. Analyses reveals a link between the introduction of lockdown and the number of new Covid-19 cases. Types of mobility with the most significant impact on the development of the pandemic are “retail and recreation areas", "transit stations", "workplaces" "groceries and pharmacies”. The difference in the correlation between the lockdown introduced and the number of SARS-COV-2 cases is 81%, when using a 14-day weighted average compared to the 7-day average. Moreover, the study reveals a strong geographical diversity in human mobility and its impact on the number of new Covid-19 cases.