bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dimethyl-2-oxoglutarate improves redox balance and mitochondrial function in muscle pericytes of individuals with diabetes mellitus
Authors: Faulkner Ashton , Tamiato Anita , Cathery William , Rampin Andrea , Caravaggi Carlo Maria , Jover Eva , Allen Steve , Mellor Harry , Hauton David , Heather Lisa C. , Spinetti Gaia , Madeddu Paolo 
Published: July 2020

Abstract
Aims/hypothesis
Treatment of vascular complications of diabetes remains inadequate. We reported that muscle pericytes (MPs) from limb muscles of vascular patients with diabetes mellitus display elevated levels of oxidative stress causing a dysfunctional phenotype. Here, we investigated whether treatment with dimethyl-2-oxoglutarate (DM-2OG), a tricarboxylic acid cycle metabolite with antioxidant properties, can restore a healthy metabolic and functional phenotype.

Methods
MPs were isolated from limb muscles of diabetes patients with vascular disease (D-MPs) and from non-diabetic control participants (ND-MPs). Metabolic status was assessed in untreated and DM-2OG-treated (1 mmol/l) cells using an extracellular flux analyser and anion-exchange chromatography–mass spectrometry (IC-MS/MS). Redox status was measured using commercial kits and IC-MS/MS, with antioxidant and metabolic enzyme expression assessed by quantitative RT-PCR and western blotting. Myogenic differentiation and proliferation and pericyte–endothelial interaction were assessed as functional readouts.

Results
D-MPs showed mitochondrial dysfunction, suppressed glycolytic activity and reduced reactive oxygen species-buffering capacity, but no suppression of antioxidant systems when compared with ND-MP controls. DM-2OG supplementation improved redox balance and mitochondrial function, without affecting glycolysis or antioxidant systems. Nonetheless, this was not enough for treated D-MPs to regain the level of proliferation and myogenic differentiation of ND-MPs. Interestingly, DM-2OG exerted a positive effect on pericyte–endothelial cell interaction in the co-culture angiogenesis assay, independent of the diabetic status.

Conclusions/interpretation
These novel findings support the concept of using DM-2OG supplementation to improve pericyte redox balance and mitochondrial function, while concurrently allowing for enhanced pericyte–endothelial crosstalk. Such effects may help to prevent or slow down vasculopathy in skeletal muscles of people with diabetes.
Topology optimization accounting for surface layer effects
Authors: Suresh Shyam , Thore Carl-Johan , Torstenfelt Bo , Klarbring Anders 
Published: July 2020

AbstractMetal AM (additive manufacturing) components are generally inhomogeneous and have different microstructure in the bulk compared with (contour) regions near the surface. This, as well as rough as-built surfaces, affects mechanical properties. In this paper, we develop a topology optimization method that considers such inhomogeneities. The method is a direct extension of standard density-based methods using linear filtering for regularization, and a second filtering of the design variables is used to identify a surface layer, the thickness of which is given by the filter radius. Domain extension is used in order to properly identify such layers at the boundary of the design domain. The method is generally applicable but is demonstrated for stiffness optimization. Both two- and three-dimensional problems are treated. A general property of the method is that the topological complexity is reduced, i.e. the optimized designs get fewer and thicker structural members as the width of the surface layer is increased.
Reaction time and brake pedal force after total knee replacement: timeframe for return to car driving
Authors: Kirschbaum Stephanie , Fuchs Michael , Otto Marion , Gwinner Clemens , Perka Carsten , Sentürk Ufuk , Pfitzner Tilman 
Published: July 2020

Abstract
Purpose
This prospective cohort study aimed to examine objective and subjective parameters in patients who underwent total knee replacement (TKR) to assess from when on driving a car can be deemed safe again.

Methods
Thirty patients (16 women, 14 men, age 66 ± 11 years) who received TKR of the right knee and 45 healthy controls (26 women, 19 men, age 32 ± 9 years) were asked to perform an emergency braking manoeuvre using a driving simulator. Brake pedal force (BPF), neuronal reaction time (NRT), brake reaction time (BRT), and subjective parameters (pain, subjective driving ability) were measured preoperatively as well as 5 days, 3–4, and 6 weeks after TKR.

Results
Preoperative NRT was 506 ± 162 ms, BRT 985 ± 356 ms, and BPF 614 ± 292 N. NRT increased to 561 ± 218 ms, BRT to 1091 ± 404 ms and BPF decreased to 411 ± 191 N 5 days after TKR. Three weeks after surgery, NRT was 581 ± 164 ms and BRT 1013 ± 260 ms, while BPF increased to 555 ± 200 N. Only BPF showed significant differences (p < 0.01). In week 6, all parameters were restored to baseline levels; patients showed significant pain decrease and evaluated their driving ability as “good” again.

Conclusion
BPF was the only parameter displaying a significant postoperative decrease. However, preoperative patients’ baseline levels and subjective confidence in driving ability were only reached 6 weeks after the operation. These results indicate that a minimum waiting period of 6 weeks should be considered before patients can safely participate in road traffic at their individual preoperative safety level again.

Level of evidence
II.
Identification of bacteria and fungi inhabiting fruiting bodies of Burgundy truffle (Tuber aestivum Vittad.)
Authors: Perlińska-Lenart Urszula , Piłsyk Sebastian , Gryz Elżbieta , Turło Jadwiga , Hilszczańska Dorota , Kruszewska Joanna S. 
Published: July 2020

AbstractTuber species may be regarded as complex microhabitats hosting diverse microorganisms inside their fruiting bodies. Here, we investigated the structure of microbial communities inhabiting the gleba of wild growing (in stands) T. aestivum, using Illumina sequencing and culture-based methods. The two methods used in combination allowed to extract more information on complex microbiota of Tuber aestivum gleba. Analysis of the V3–V4 region of 16S rDNA identified nine phyla of bacteria present in the gleba of T. aestivum ascomata, mostly Proteobacteria from the family Bradyrhizobiaceae. Our results ideally match the earlier data for other Tuber species where the family Bradyrhizobiaceae was the most represented. The ITS1 region of fungal rDNA represented six alien fungal species belonging to three phyla. To complement the metagenomic analysis, cultivable fungi and bacteria were obtained from the gleba of the same T. aestivum fruiting bodies. The identified fungi mostly belong to the phylum Basidiomycota and same to Ascomycota. Analysis of cultivable bacteria revealed that all the specimens were colonized by different strains of Bacillus. Fungal community inhabiting T. aestivum fruiting bodies was never shown before.
68Ga-labelled desferrioxamine-B for bacterial infection imaging
Authors: Petrik Milos , Umlaufova Eva , Raclavsky Vladislav , Palyzova Andrea , Havlicek Vladimir , Pfister Joachim , Mair Christian , Novy Zbynek , Popper Miroslav , Hajduch Marian , Decristoforo Clemens 
Published: July 2020

AbstractPurposeWith the increase of especially hospital-acquired infections, timely and accurate diagnosis of bacterial infections is crucial for effective patient care. Molecular imaging has the potential for specific and sensitive detection of infections. Siderophores are iron-specific chelators recognized by specific bacterial transporters, representing one of few fundamental differences between bacterial and mammalian cells. Replacing iron by gallium-68 without loss of bioactivity is possible allowing molecular imaging by positron emission tomography (PET). Here, we report on the preclinical evaluation of the clinically used siderophore, desferrioxamine-B (Desferal®, DFO-B), radiolabelled with68Ga for imaging of bacterial infections.MethodsIn vitro characterization of [68Ga]Ga-DFO-B included partition coefficient, protein binding and stability determination. Specific uptake of [68Ga]Ga-DFO-B was tested in vitro in different microbial cultures. In vivo biodistribution was studied in healthy mice and dosimetric estimation for human setting performed. PET/CT imaging was carried out in animal infection models, representing the most common pathogens.ResultsDFO-B was labelled with68Ga with high radiochemical purity and displayed hydrophilic properties, low protein binding and high stability in human serum and PBS. The high in vitro uptake of [68Ga]Ga-DFO-B in selected strains ofPseudomonas aeruginosa,Staphylococcus aureusandStreptococcus agalactiaecould be blocked with an excess of iron-DFO-B. [68Ga]Ga-DFO-B showed rapid renal excretion and minimal retention in blood and other organs in healthy mice. Estimated human absorbed dose was 0.02 mSv/MBq. PET/CT images of animal infection models displayed high and specific accumulation of [68Ga]Ga-DFO-B in bothP. aeruginosaandS. aureusinfections with excellent image contrast. No uptake was found in sterile inflammation, heat-inactivatedP. aeruginosaorS. aureusandEscherichia colilacking DFO-B transporters.ConclusionDFO-B can be easily radiolabelled with68Ga and displayed suitable in vitro characteristics and excellent pharmacokinetics in mice. The high and specific uptake of [68Ga]Ga-DFO-B byP. aeruginosaandS. aureuswas confirmed both in vitro and in vivo, proving the potential of [68Ga]Ga-DFO-B for specific imaging of bacterial infections. As DFO-B is used in clinic for many years and the estimated radiation dose is lower than for other68Ga-labelled radiopharmaceuticals, we believe that [68Ga]Ga-DFO-B has a great potential for clinical translation.
Open reduction and internal fixation of acetabular fractures in patients of old age
Authors: Rommens Pol Maria , Schwab Roland , Handrich Kristin , Arand Charlotte , Wagner Daniel , Hofmann Alexander 
Published: July 2020

Abstract
Material and methods
There is an ongoing debate on which treatment for acetabular fractures in elderly patients is the most appropriate. This study was set up to identify the role of open reduction and internal fixation of acetabular fractures in persons of old age.
We retrospectively reviewed the medical charts and radiological data of all patients older than 65 years, who suffered an isolated acetabular fracture and were admitted in our Department between 2010 and 2014 (5-year period). Complications, outcome and mortality were recorded. Of all surviving patients, quality of life (QoL), mobility and independence were graded with European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L), European Quality of Life 5 Dimensions Visual Analogue Scale (EQ-5D-VAS), Numeric Rating Scale (NRS), Elderly Mobility Scale (EMS) and Tinetti Mobility Test (TMT).

Results
Seventy patients could be identified. There were 52 men (74%) and 18 women (26%) with a median age of 79.0 years (range: 65–104 years). Forty-six patients (66%) had been treated with open reduction and internal fixation (ORIF), 24 (34%) conservatively. There were negative predictive factors—subchondral impaction, damage to the femoral head and multiple fragments—in 54% of the operative group. With ORIF, an anatomical reduction could be achieved in 27 patients (59%), an acceptable in 18 (39%) and a poor in one (2%). At follow-up, 18 patients (26%) had died and 23 (33%) were not able to participate. The follow-up rate of the surviving operatively treated patients was 77%. Eleven of 46 operated patients (24%) needed a conversion to a total hip arthroplasty (THA). All patients undergoing conversion had imperfect reduction after surgery. No patient in the non-operative group underwent conversion to THA during follow-up. The median follow-up time of operatively treated patients without conversion (n = 17) was 30 months (range, 16–73 months), of patients with THA (n = 9) 30 months after conversion (range, 17–55 months). Quality of reduction correlated to QoL, mobility and independence in all recorded parameters. Patients with secondary THA had similar good outcomes as patients after ORIF without later conversion. Men had better outcome than women.

Conclusion
ORIF of acetabular fractures in patients of old age results in excellent outcomes at short-term follow-up when anatomical reduction can be achieved. In case of negative predictive factors, ORIF cannot be regarded as a definitive solution, rather as the construction of a stable socket for secondary THA. The decision of therapy should be made dependent on pre-operative radiographic parameters.
A simplified diagnostic work-up for the detection of gestational diabetes mellitus in low resources settings: achievements and challenges
Authors: Putoto Giovanni , Somigliana Edgardo , Olivo Federico , Ponte Simona , Koroma Michael Momoh , Citterio Federica , Orsi Michele , Pisani Enzo , Pilon Marica , Manenti Fabio , Segafredo Giulia 
Published: July 2020

Abstract
Purpose
Modern strategies for the screening and diagnosis of Gestational Diabetes Mellitus (GDM) rely on universal Oral Glucose Tolerance Test (OGTT). However, they are unsustainable in low-income countries. In this study, we aimed at assessing the feasibility of a simplified diagnostic policy.

Methods
The study took place in an urban referral hospital in Freetown, Sierra Leone. During an 11-month period, pregnant women were offered capillary blood test for glucose assessment. They could be screened at any time during pregnancy. GDM was diagnosed if fasting glucose was ≥ 92 mg/dl or if the OGTT was positive. The latter was prescribed only to women presenting after 24 weeks’ gestation with at least one risk factor for GDM and fasting capillary glucose between 85 and 91 mg/dl. A definitive diagnosis required confirmation to this aim, women with values above the thresholds were invited to refer the next working day for repeating the test after fasting overnight.

Results
Overall, 7827 women were referred for screening, of whom 6872 (87%) underwent at least one capillary glucose assessment. However, 895 of those who had a positive test did not return for confirmation. Overall, a definite assessment could be done in 5799 subjects corresponding to 76% (95% CI 75–77%) of those eligible. GDM was diagnosed in 128 women (1.9%, 95% CI 1.6–2.2%). Based on an expected confirmation rate of 22% (calculated from those who referred for confirmation) in the 895 women who did not come back, one could infer that GDM would have been diagnosed in additional 197 women, raising the prevalence to 4.7% (95% CI 4.2–5.3%).

Conclusion
Three quarters of subjects could be assessed with our approach. Data also suggest that GDM is not rare even if identification of affected cases remains challenging.
Sex and freezing of gait in Parkinson’s disease: a systematic review and meta-analysis
Authors: Tosserams Anouk , Mazaheri Masood , Vart Priya , Bloem Bastiaan R. , Nonnekes Jorik 
Published: July 2020

Abstract
Objective
It is unknown how sex affects the prevalence of freezing of gait (FOG). We conducted a systematic review and meta-analysis to establish the sex-specific prevalence of FOG in persons with Parkinson’s disease (PD). In addition, we investigated whether men and women were represented accurately in intervention trials targeting FOG.

Methods
We queried the EMBASE and PubMed databases and identified 2637 articles. Of these, 16 epidemiological studies were included in the meta-analysis, and 51 intervention studies were included in the comparative analysis.

Results
In total, 5702 persons were included in the final meta-analysis of epidemiological studies. The pooled estimate of overall FOG prevalence was 43% [95% CI 33–53%]. We found no difference in FOG prevalence between men [44% (34–54%)] and women [42% (31–52%)] with PD. However, women were markedly underrepresented in intervention trials targeting FOG, with an average proportion of only 29.6% of women in trial populations. The percentage of women included in trials was similar across intervention types but differed greatly across geographical regions.

Conclusion
Sex is not a predictor of FOG. This could aid clinicians in counseling persons with PD about FOG. Importantly, a global effort is needed to include more women into clinical trials. Given the skewed distribution of men and women included in intervention trials targeting FOG, caution might be warranted when extrapolating results from FOG trials to women.
Prevalence and phenology of fine root endophyte colonization across populations of Lycopodiella inundata
Authors: Kowal Jill , Arrigoni Elena , Serra Jordi , Bidartondo Martin 
Published: July 2020

AbstractMycorrhizal fungi are critical components of terrestrial habitats and agroecosystems. Recently, Mucoromycotina fine root endophyte fungi (MucFRE) were found to engage in nutritional mutualism with Lycopodiella inundata, which belongs to one of the earliest vascular plant lineages known to associate with MucFRE. The extent to which this mutualism plays a role in resilient plant populations can only be understood by examining its occurrence rate and phenological patterns. To test for prevalence and seasonality in colonization, we examined 1305 individual L. inundata roots from 275 plants collected during spring and autumn 2019 across 11 semi-natural heathlands in Britain and the Netherlands. We quantified presence/absence of fine root endophyte (FRE) hyphae and vesicles and explored possible relationships between temperature and precipitation in the months immediately before sampling. Fine root endophyte hyphae were dominant in all of the examined heathlands, and every colonized root had FRE in both cortical cells and root hairs. However, we found significant differences in colonization between the two seasons at every site. Overall, 14% of L. inundata roots were colonized in spring (2.4% with vesicles) compared with 86% in autumn (7.6% with vesicles). Colonization levels between populations were also significantly different, correlating with temperature and precipitation, suggesting some local environments may be more conducive to root and related hyphal growth. These marked seasonal differences in host-plant colonization suggest that results about FRE from single time point collections should be carefully interpreted. Our findings are relevant to habitat restoration, species conservation plans, agricultural bio-inoculation treatments, and microbial diversity studies.
Botulinum toxin therapy in the SARS-CoV-2 pandemic: patient perceptions from a German cohort
Authors: Dressler Dirk , Adib Saberi Fereshte 
Published: July 2020

AbstractThe SARS-CoV-2 virus pandemic has provoked drastic countermeasures including shutdowns of public services. We wanted to describe the effects of a 6 week shutdown of a large German botulinum toxin (BT) outpatient clinics on patients and their well-being. 45 patients (age 61.9 ± 9.8 years, 29 females, 16 males) receiving BT therapy (319.3 ± 201.9MU-equivalent, treatment duration 8.3 ± 5.5 years) were surveyed with a standardised questionnaire. The shutdown delayed BT therapy by 6.6 ± 2.3 weeks. 93% of the patients noticed increased muscle cramps and 82% increased pain reducing their quality of life by 40.2 ± 19.5%. For 23 patients with cervical dystonia this reduction was 41.1 ± 18.3%, for 3 patients with blepharospasm 33.3 ± 15.3%, for 9 patients with spasticity 37.8 ± 15.6%, for 4 patients with pain conditions 37.4 ± 35.7% and for 3 patients with hemifacial spasm 27.5 ± 17.1%. After the shutdown 66% of patients perceived BT therapy as more important than before, 32% perceived it as unchanged. For all patients long-term availability of BT therapy was very important or important. 98% of the patients perceived the shutdown as inadequate and felt their patient rights not respected. The shutdown confirmed the considerable burden of disease caused by dystonia, spasticity, hemifacial spasm and various pain conditions and the importance of BT therapy to treat them. Any shutdown severely affects these patients and needs to be avoided.
Economic Evaluations of Public Health Interventions to Improve Mental Health and Prevent Suicidal Thoughts and Behaviours: A Systematic Literature Review
Authors: Feldman Inna , Gebreslassie Mihretab , Sampaio Filipa , Nystrand Camilla , Ssegonja Richard 
Published: July 2020

AbstractTo review the literature on economic evaluations of public health interventions targeting prevention of mental health problems and suicide, to support evidence based societal resource allocation. A systematic review of economic evaluations within mental health and suicide prevention was conducted including studies published between January 2000 and November 2018. The studies were identified through Medline, PsychINFO, Web of Science, the National Health Service Economic Evaluation Database and Health Technology Assessment. The quality of relevant studies and the transferability of their results were assessed using a criterion set out by the Swedish Agency for Health Technology Assessment. Nineteen studies of moderate to high quality were included in this review, which evaluated 18 interventions in mental health and four interventions in suicide prevention. Fourteen (63%) of all interventions were cost-effective based on the conclusions from original papers. None of the studies that evaluated suicide prevention was of high quality. The interventions largely focused on psychological interventions at school, the workplace and within elderly care as well as screening and brief interventions in primary care. Nine studies (around 50% of included articles) had a high potential for transferability to the Swedish context. Public health interventions aiming to improve mental health have a high potential to be economically beneficial to society, but high-quality evidence on the cost-effectiveness of suicide prevention is limited.
Identification of candidate mediators of chemoresponse in breast cancer through therapy-driven selection of somatic variants
Authors: Al Amri Waleed S. , Baxter Diana E. , Hanby Andrew M. , Stead Lucy F. , Verghese Eldo T. , Thorne James L. , Hughes Thomas A. 
Published: July 2020

Abstract
Purpose
More than a third of primary breast cancer patients are treated with cytotoxic chemotherapy, typically without guidance from predictive markers. Increased use of neoadjuvant chemotherapy provides opportunities for identification of molecules associated with treatment response, by comparing matched tumour samples before and after therapy. Our hypothesis was that somatic variants of increased prevalence after therapy promote resistance, while variants with reduced prevalence cause sensitivity.

Methods
We performed systematic analyses of matched pairs of cancer exomes from primary oestrogen receptor-positive/HER2-negative breast cancers (n = 6) treated with neoadjuvant epirubicin/cyclophosphamide. We identified candidate genes as mediators of chemotherapy response by consistent subclonal changes in somatic variant prevalence through therapy, predicted variant impact on gene function, and enrichment of specific functional pathways. Influence of candidate genes on breast cancer outcome was tested using publicly available breast cancer expression data (n = 1903).

Results
We identified 14 genes as the strongest candidate mediators of chemoresponse: TCHH, MUC17, ARAP2, FLG2, ABL1, CENPF, COL6A3, DMBT1, ITGA7, PLXNA1, S100PBP, SYNE1, ZFHX4, and CACNA1C. Genes contained somatic variants showing prevalence changes in up to 4 patients, with up to 3 being predicted as damaging. Genes coding for extra-cellular matrix components or related signalling pathways were significantly over-represented among variants showing prevalence changes. Expression of 5 genes (TCHH, ABL1, CENPF, S100PBP, and ZFHX4) was significantly associated with patient survival.

Conclusions
Genomic analysis of paired pre- and post-therapy samples resulting from neoadjuvant therapy provides a powerful method for identification of mediators of response. Genes we identified should be assessed as predictive markers or targets in chemo-sensitization.