bluuebunny/crossref_metadata_2025_split huggingface dataset:
LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice
Authors: Gavini Chaitanya K. , Elshareif Nadia , Aubert Gregory , Germanwala Anand V. , Calcutt Nigel A. , Mansuy-Aubert Virginie 
Published: February 2022

Abstract
Background
Peripheral neuropathy is a common and progressive disorder in the elderly that interferes with daily activities. It is of importance to find efficient treatments to treat or delay this age-related neurodegeneration. Silencing macrophages by reducing foamy macrophages showed significant improvement of age-related degenerative changes in peripheral nerves of aged mice. We previously demonstrated that activation of the cholesterol sensor Liver X receptor (LXR) with the potent agonist, GW3965, alleviates pain in a diet-induced obesity model. We sought to test whether LXR activation may improve neuropathy in aged mice.

Methods
21-month-old mice were treated with GW3965 (25 mg/Kg body weight) for 3 months while testing for mechanical allodynia and thermal hyperalgesia. At termination, flow cytometry was used to profile dorsal root ganglia and sciatic nerve cells. Immune cells were sorted and analyzed for cholesterol and gene expression. Nerve fibers of the skin from the paws were analyzed. Some human sural nerves were also evaluated. Comparisons were made using either t test or one-way ANOVA.

Results
Treatment with GW3965 prevented the development of mechanical hypersensitivity and thermal hyperalgesia over time in aged mice. We also observed change in polarization and cholesterol content of sciatic nerve macrophages accompanied by a significant increase in nerve fibers of the skin.

Conclusions
These results suggest that activation of the LXR may delay the PNS aging by modifying nerve-immune cell lipid content. Our study provides new potential targets to treat or delay neuropathy during aging.
Frequency of osteoradionecrosis of the lower jaw after radiotherapy of oral cancer patients correlated with dosimetric parameters and other risk factors
Authors: Lang Kristin , Held Thomas , Meixner Eva , Tonndorf-Martini Eric , Ristow Oliver , Moratin Julius , Bougatf Nina , Freudlsperger Christian , Debus Jürgen , Adeberg Sebastian 
Published: February 2022

Abstract
Objectives
Osteoradionecrosis (ORN) of the lower jaw is a serious late complication after radiotherapy in patients with oral cavity cancer. The aim of this study is to generate more insight into which patient- and treatment-related factors are associated with the development of ORN in oral cavity cancer patients undergoing postoperative radiotherapy.

Material and methods
Retrospective evaluation and comparison of 44 patients with ORN (event group 1) matched according to 45 patients without ORN (control group 2) who received postoperative radiotherapy of oral cavity squamous cell carcinoma at our institution between 2012 and 2020. Dosimetric factors that favor the occurrence of ORN should be detected. The cumulative occurrence rate of ORN was calculated according to the Kaplan–Meier method and analyzed by Cox regression and log-rank test.

Results
The median time to develop ORN was 18 months (3–93 months) after radiotherapy. Dental status before radiotherapy (RT) treatment (HR 4.5; 1.8–11.5) and dosimetric parameters including Dmean > 45 Gy (HR 2.4; 1.0–5.7), Dmax > 60 Gy (HR 1.3; 1.1–2.8) and planning target volume (PTV) proportion > 40% intersection with the lower jaw (HR 1.1; 1.0–1.1) were significantly associated with ORN.

Conclusion
The results of this retrospective study reveal that oral cavity cancer patients who underwent pre-RT dental surgery as well as dosimetric parameters using Dmax > 60 Gy, higher mean doses > 45 Gy and more than 40% PTV intersection with the lower jaw bone are independent risk factors for ORN. These findings can assist in the management of patients undergoing RT for head and neck cancer regarding ORN prevention.

Clinical relevance
Poor oral hygiene and desolate dental status as well as high radiation doses to the mandibular bone significantly increase the risk of developing osteoradionecrosis. Before irradiating a patient with oral cavity cancer, an appointment with the dentist should be made and teeth sanitized if necessary. Likewise, maximum radiation doses to the lower jaw should be minimized.
Application of a novel microscopic technique for quantifying CA125 binding to circulating mononuclear cells in longitudinal specimens during treatment for ovarian cancer
Authors: Lakatos Kornél , González Germán , Hoballah Jawad , Brooker Jeff , Jeong Sinyoung , Evans Conor , Krauledat Petra , Hansen W. Peter , Elias Kevin M. , Patankar Manish , Fülöp Vilmos , Konstantinopoulos Panagiotis A. , Cramer Daniel W. 
Published: February 2022

Abstract
Background
Measurement of serum CA125, an antigenic fragment of human mucin 16 (MUC16), is used to monitor the clinical progression of epithelial ovarian cancer (EOC). However, rather than simply a passive marker reflecting tumor burden, MUC16 may have a more active role by binding to immune cells and altering their tumor response. We developed a research tool to measure MUC16-binding to the surfaces of peripheral blood mononuclear cell (PBMC) subtypes and tested its research value using specimens collected serially from a woman being treated for high grade serous EOC.

Methods
Cryopreserved PBMCs were mixed with anti-CA125 antibody-labeled plasmonic gold nanoparticles (PNPs) to detect cell surface MUC16-binding along with fluorescent stains to identify B cells, NK cells, NK-T cells, T cells, and monocytes. From 3D darkfield images, a computer algorithm was applied to enumerate PNP-binding and fluorescence microscopy to identify cell lineage. Average MUC16-binding was determined by fitting a Poisson distribution to PNP-counts across similar cell types. MUC16-binding to cell types was correlated with treatment details, CA125 levels, and complete blood count (CBC) data.

Results
Over a 21-month period, monocytes had the highest level of MUC16-binding which was positively correlated with serum CA125 and inversely correlated with circulating monocyte and lymphocyte counts. Fluctuations of PNP-binding to NK cells were associated temporally with types of chemotherapy and surgical events. Levels of MUC16 bound to NK cells were positively correlated with levels of MUC16 bound to T and NK-T cells and inversely correlated with circulating platelets.

Conclusions
Assessment of MUC16-binding among cryopreserved PBMC cell types can be accomplished using darkfield and fluorescence microscopy. Correlations observed between level of binding by cell type with serum CA125, CBC data, and treatment details suggest that the new techniques may offer novel insights into EOC’s clinical course.
Clinical features of gout in adult patients with type Ia glycogen storage disease: a single-centre retrospective study and a review of literature
Authors: Xu Na , Han Xinxin , Zhang Yun , Huang Xiaoming , Zhu Weiguo , Shen Min , Zhang Wen , Jialin Chen , Wei Min , Qiu Zhengqing , Zeng Xuejun 
Published: February 2022

Abstract
Background
This study aimed to explore the clinical features of gout in adult patients with glycogen storage disease type Ia (GSD Ia).

Methods
Ninety-five adult patients with GSD Ia admitted to Peking Union Medical College Hospital were retrospectively analysed. A clinical diagnosis of GSD Ia was confirmed in all patients through gene sequencing. All patients had hyperuricaemia; 31 patients complicated with gout were enrolled, and 64 adult GSD Ia patients with asymptomatic hyperuricaemia were selected as a control group during the same period. Clinical characteristics were analysed and compared between the two groups.

Results
Thirty-one of the 95 patients had complications of gout (median age, 25 years; 11 (35.5%) females). All 31 patients had hepatomegaly, abnormal liver function, fasting hypoglycaemia, hyperuricaemia, hyperlipaemia, and hyperlacticaemia. A protuberant abdomen, growth retardation, recurrent epistaxis, and diarrhoea were the most common clinical manifestations. Among these 31 patients, 10 patients (32.3%) had gout as the presenting manifestation and were diagnosed with GSD Ia at a median time of 5 years (range, 1–14) after the first gout flare. The median age of gout onset was 18 years (range, 10–29). Fifteen of the 31 GSD Ia-related gout patients were complicated with gouty tophi, which has an average incidence time of 2 years after the first gouty flare. The mean value of the maximum serum uric acid (SUA) was 800.5 μmol/L (range, 468–1068). The incidence of gout in adult GSD Ia patients was significantly associated with the initial age of regular treatment with raw corn starch, the proportion of urate-lowering therapy initiated during the asymptomatic hyperuricaemic stage, maximum SUA level, and mean cholesterol level.

Conclusions
Determination of GSD Ia should be performed for young-onset gout patients with an early occurrence of gouty tophi, especially in patients with hepatomegaly, recurrent hypoglycaemia, or growth retardation. Early detection and long-term regulatory management of hyperuricaemia, in addition to early raw corn starch and lifestyle intervention, should be emphasized for GSD Ia patients in order to maintain good metabolic control.

Trial registration
Retrospectively registered.
Sensitive and reproducible MEG resting-state metrics of functional connectivity in Alzheimer’s disease
Authors: Schoonhoven Deborah N. , Briels Casper T. , Hillebrand Arjan , Scheltens Philip , Stam Cornelis J. , Gouw Alida A. 
Published: February 2022

AbstractBackgroundAnalysis of functional brain networks in Alzheimer’s disease (AD) has been hampered by a lack of reproducible, yet valid metrics of functional connectivity (FC). This study aimed to assess both the sensitivity and reproducibility of the corrected amplitude envelope correlation (AEC-c) and phase lag index (PLI), two metrics of FC that are insensitive to the effects of volume conduction and field spread, in two separate cohorts of patients with dementia due to AD versus healthy elderly controls.MethodsSubjects with a clinical diagnosis of AD dementia with biomarker proof, and a control group of subjective cognitive decline (SCD), underwent two 5-min resting-state MEG recordings. Data consisted of a test (AD = 28; SCD = 29) and validation (AD = 29; SCD = 27) cohort. Time-series were estimated for 90 regions of interest (ROIs) in the automated anatomical labelling (AAL) atlas. For each of five canonical frequency bands, the AEC-c and PLI were calculated between all 90 ROIs, and connections were averaged per ROI. General linear models were constructed to compare the global FC differences between the groups, assess the reproducibility, and evaluate the effects of age and relative power. Reproducibility of the regional FC differences was assessed using the Mann-WhitneyUtests, with correction for multiple testing using the false discovery rate (FDR).ResultsThe AEC-c showed significantly and reproducibly lower global FC for the AD group compared to SCD, in the alpha (8–13 Hz) and beta (13–30 Hz) bands, while the PLI revealed reproducibly lower FC for the AD group in the delta (0.5–4 Hz) band and higher FC for the theta (4–8 Hz) band. Regionally, the beta band AEC-c showed reproducibility for almost all ROIs (except for 13 ROIs in the frontal and temporal lobes). For the other bands, the AEC-c and PLI did not show regional reproducibility after FDR correction. The theta band PLI was susceptible to the effect of relative power.ConclusionFor MEG, the AEC-c is a sensitive and reproducible metric, able to distinguish FC differences between patients with AD dementia and cognitively healthy controls. These two measures likely reflect different aspects of neural activity and show differential sensitivity to changes in neural dynamics.
Rituximab and dupilumab improve eosinophilic granulomatosis with polyangiitis with multiple pulmonary thrombi
Authors: Adachi Sei , Oshikata Chiyako , Kaneko Takeshi , Tsurikisawa Naomi 
Published: February 2022

Abstract
Background
Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by a necrotizing vasculitis with tissue and peripheral blood eosinophilia affecting small and medium-sized arteries, capillaries, and veins. Venous thromboembolic events are uncommon in EGPA. Moreover, there are only a few reported cases of EGPA complicated by pulmonary embolism or infarction.

Case presentation
We report the case of a 43-year-old woman with eosinophilic granulomatosis with polyangiitis and acute respiratory and heart failure due to bilateral pulmonary artery thrombosis and left femoral vein thrombosis 12 years after disease onset. She also had cardiac involvement (myocarditis, pericardial effusion, and diastolic dysfunction), gastrointestinal symptoms, and peripheral neuropathy. The condition was refractory to treatment with systemic corticosteroids, intravenous cyclophosphamide, and mepolizumab, but the thrombosis and associated acute cardiac failure, as well as the cardiac and gastrointestinal symptoms and multiple polyneuropathy, improved after a switch to rituximab. However, the heart failure did not improve sufficiently and the patient continued to need inhaled oxygen at 1 L/min and asthma exacerbations occurred. We then swapped the patient’s mepolizumab treatment for dupilumab. Not only did she have no further asthma attacks after switching to dupilumab, but also her vasculitis symptoms improved. Oxygen therapy was discontinued as the heart failure improved 5 months after starting the dupilumab.

Conclusions
This may be the first case report of the successful treatment by rituximab of pulmonary thromboembolism associated with EGPA. In addition, in this patient, treatment with dupilumab was effective not only for the asthma symptoms but also for the symptoms of vasculitis and heart failure.
Cost-effectiveness of a photopethysmographic procedure for screening for atrial fibrillation in 6 European countries
Authors: Wahler Steffen , Birkemeyer Ralf , Alexopoulos Dimitrios , Siudak Zbigniew , Müller Alfred , von der Schulenburg Johann-Matthias 
Published: February 2022

Abstract
Background
Strokes cause an estimated annual health care burden of 170 billion euros across Europe. Atrial fibrillation is one of the major risk factors for stroke and increases the individual risk 4.2-fold. But prevention with anticoagulants may reduce this risk by 70%. Screening methods are employed to detect previously undetected atrial fibrillation. Screening studies in various European countries show a high degree of undetected atrial fibrillation. This study aims to assess the cost-effectiveness of systematic screening with a smartphone application, named Preventicus Heartbeats. It is a hands-on screening tool for use on smartphone to diagnose AF with high sensitivity and specificity.

Methods
A previously published model for calculating screening cost-effectiveness was extended to 6 European countries covering a wide range in terms of treatment costs and epidemiologic parameters.

Results
The use of screening lowers the cost per case in countries with comparatively high levels of health care costs (Switzerland: -€75; UK: -€7). Moderate higher costs per case were observed in 4 countries (Greece: €6; Netherlands: €15). Low levels of health care costs result in less or no potential for further cost reduction (Poland: €20; Serbia: €33). In all countries considered, the model showed an increase in effectiveness measures both in the number of strokes avoided and the quality adjusted life years. The number of strokes avoided per 1000 participants ranged from 2.52 (Switzerland) to 4.44 (Poland). Quality-adjusted life-years per case gained from screening ranged from 0.0105 (Switzerland) to 0.0187 (Poland). The screening procedure dominated in two countries (Switzerland, UK). For the remaining countries, the incremental cost effectiveness ratio ranged from €489/QALY (Greece) to €2548/QALY (Serbia).

Conclusion
The model results showed a strong dependence of the results on the country-specific costs for stroke treatment. The use of the investigated screening method is close to cost-neutral or cost-reducing in the Western European countries and Greece. In countries with low price levels, higher cost increases due to AF screening are to be expected. Lower costs of anticoagulation, which are expected due to the upcoming patent expiry of direct anticoagulants, have a positive effect on the cost result.
Adolescent smoking, alcohol use, inebriation, and use of narcotics during the Covid-19 pandemic
Authors: Kapetanovic Sabina , Ander Birgitta , Gurdal Sevtap , Sorbring Emma 
Published: February 2022

AbstractBackgroundThe aim of the study was to investigate how general family relations, reported changes in family interaction and involvement with peers during the Covid-19 pandemic, and following rules and recommendations during the pandemic relate to adolescent smoking, alcohol use, inebriation, and use of narcotics during Covid-19.MethodsAn online national survey of Swedish adolescents (n = 1818) aged 15–19 years was conducted in June 2020. Hierarchical regression analysis was used to predict adolescents’ reported change in substance use during the pandemic. Person-oriented analyses, were used to identify clusters of participants characterized by similar patterns of substance use following ANOVA analysis with Scheffe post hoc tests testing differences between clusters in terms of family relations, reported changes in family interaction and involvement with peers during the Covid-19 pandemic, and following rules and recommendations during the pandemic.ResultsHigher general family conflict, increased involvement with peers, a strained relationship with parents, and less compliance with rules and restrictions during the pandemic predicted a reported increase in adolescent substance use during this period. The grouping of scores for adolescent smoking, alcohol use, inebriation, and use of narcotics resulted in a six-cluster solution. One cluster (n = 767) either did not use or had decreased use of substances during the Covid-19 pandemic. Five other clusters, thus risk clusters, had retained or increased use of substances during the pandemic. Poor general family relations, increased peer involvement, and difficulties to conform to the rules and restrictions during the covid-19 pandemic were characteristics of risk clusters.ConclusionsMost of adolescents in our study did not increase their substance use during the pandemic. However, adolescents with poor family relations who turn to peers during stressful times and who have difficulty following the government’s rules and restrictions, are at risk of increased substance use during the pandemic. This is a potential threat both to adolescents themselves and others in their surroundings which is why at-risk adolescents and their families need more attention from public health and social services during this time of crisis.
Study progress, recreational activities, and loneliness in young adult carers: a national student survey
Authors: Haugland Bente Storm Mowatt , Hysing Mari , Sivertsen Børge 
Published: February 2022

Abstract
Background
Young adults (18–25 years) with informal care responsibilities have received limited attention in the research literature, and little is known on how caring responsibilities are related to functioning across different life domains. In the present study we examine associations between care responsibilities and study progress, recreational life, and loneliness in young adults in higher education.

Methods
A national survey was conducted among Norwegian students in higher education (the SHoT2018-study). The response rate was 30.8%. The current sample is a subsample of the respondents, including young adults 18 to 25 years old, comprising 40.205 participants (70.2% women, mean age 22.0 years, SD = 1.7). Participants reported whether they had regular care responsibility for someone with physical or mental illness, disabilities, or substance misuse. They also answered questions on study progress, number of hours studying, physical exercise, involvement in organized volunteer student activities, number of close friends, and feelings of loneliness. Data were analyzed by Chi-square tests and logistic regression analyses, adjusting for age, sex, and chronic illness.

Results
Compared to students without care responsibility, young adult carers (n = 2228, 5.5% of study sample) were more likely to report delayed study progress (OR 1.20, p < .001), higher average number of failed exams (e.g., having failed three times or more, OR 1.31, p = .002), more feelings of loneliness (OR 1.26, p < .001), and slightly fewer friends. Those with limited care responsibility (≤ 1 h daily) were more likely to participate in organized volunteer student activities, whereas students with 2 h or more of caring per day were less likely to participate in leisure student activities. Both study progress and feelings of loneliness were related to care responsibility in a response-dose pattern, with worse outcomes for those with 2 h or more of daily caring responsibility. All comparisons were adjusted for age, sex, and chronic illness.

Conclusions
Study progress, recreational activities, and loneliness among young adults are associated with informal caring responsibilities. Professionals in the educational system as well as health personnel should be sensitized to the needs of young adult carers and necessary support made available.