bluuebunny/crossref_metadata_2025_split huggingface dataset:
C/N ratio and carbon source-dependent lipid production profiling in Rhodotorula toruloides
Authors: Lopes Helberth Júnnior Santos , Bonturi Nemailla , Kerkhoven Eduard Johannes , Miranda Everson Alves , Lahtvee Petri-Jaan 
Published: January 2020

AbstractMicrobial oils are lipids produced by oleaginous microorganisms, which can be used as a potential feedstock for oleochemical production. The oleaginous yeast Rhodotorula toruloides can co-produce microbial oils and high-value compounds from low-cost substrates, such as xylose and acetic acid (from hemicellulosic hydrolysates) and raw glycerol (a byproduct of biodiesel production). One step towards economic viability is identifying the best conditions for lipid production, primarily the most suitable carbon-to-nitrogen ratio (C/N). Here, we aimed to identify the best conditions and cultivation mode for lipid production by R. toruloides using various low-cost substrates and a range of C/N ratios (60, 80, 100, and 120). Turbidostat mode was used to achieve a steady state at the maximal specific growth rate and to avoid continuously changing environmental conditions (i.e., C/N ratio) that inherently occur in batch mode. Regardless of the carbon source, higher C/N ratios increased lipid yields (up to 60% on xylose at a C/N of 120) but decreased the specific growth rate. Growth on glycerol resulted in the highest specific growth and lipid production (0.085 g lipids/gDW*h) rates at C/Ns between 60 and 100. We went on to study lipid production using glycerol in both batch and fed-batch modes, which resulted in lower specific lipid production rates compared with turbisdostat, however, fed batch is superior in terms of biomass production and lipid titers. By combining the data we obtained in these experiments with a genome-scale metabolic model of R. toruloides, we identified targets for improvements in lipid production that could be carried out either by metabolic engineering or process optimization.
Evaluation of baseline fracture risk in younger postmenopausal women with breast cancer using different risk assessment methods
Authors: Schaffler-Schaden Dagmar , Kneidinger Christoph , Schweighofer-Zwink Gregor , Flamm Maria , Iglseder Bernhard , Pirich Christian 
Published: January 2020

Abstract
Objective
Controversy exists about the impact of bone mineral density (BMD) and fracture risk in newly diagnosed patients with breast cancer (BC). It is presumed that there are differences in BMD between women with BC and healthy controls. BMD is therefore considered as a potential marker to predict BC risk. This study was conducted to investigate the association of BMD, trabecular bone score (TBS) and fracture risk in younger postmenopausal women with hormone responsive BC.

Methods
Overall, 343 women were examined. Women with BC were matched to a control group of the general population. Forty-nine women and fifty-nine controls were included in the final analysis. All subjects underwent dual energy x-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and the total hip to evaluate bone mineral density. The 10-year fracture risk for a major osteoporotic fracture was assessed using the FRAX-score and the TBS-adjusted FRAX-Score, respectively.

Results
Lumbar and femoral neck BMD were similar in BC patients and controls. No difference was found for TBS of the spine (1.38 ± 0.1 vs.1.36 ± 0.09) in the BC and the control group, respectively (p = 0.19). The 10- year probability for a major osteoporotic fracture (MoF) or femoral neck (FN) fracture was 6.1 (± 2.6%) and 0.9 (± 1.2%) in the BC group vs. 6.7 (± 3.5%) (p = 0.33) and 0.9 (± 1.1%) (p = 0.73) in the control group.

Conclusion
Postmenopausal women younger than 60 years with breast cancer do not show any differences in baseline BMD, TBS, or TBS adjusted FRAX in comparison to controls.
Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors
Authors: de Ruiter Emma J. , de Roest Reinout H. , Brakenhoff Ruud H. , Leemans C. René , de Bree Remco , Terhaard Chris H. J. , Willems Stefan M. 
Published: January 2020

Abstract
Aim
This study aimed to evaluate the presence and prognostic value of tumor-infiltrating T cells in the tumor epithelium in advanced stage, HPV-negative head and neck squamous cell carcinoma (HNSCC) patients treated with primary chemoradiotherapy using digital pathology.

Methods
Pre-treatment biopsies from 80 oropharyngeal, 52 hypopharyngeal, and 29 laryngeal cancer patients were collected in a tissue microarray (TMA) and immunohistochemically stained for T-cell markers CD3, CD4, CD8, FoxP3, and PD1, and for immune checkpoint PD-L1. For each marker, the number of positive tumor-infiltrating lymphocytes (TILs) per mm2 tumor epithelium was digitally quantified and correlated to overall survival (OS), disease-free survival (DFS), and locoregional control (LRC), as well as to clinicopathological characteristics. Differences in clinical outcome were estimated using Cox proportional hazard analysis and visualized using Kaplan–Meier curves.

Results
The patient cohort had a 3-year OS of 58%, with a median follow-up of 53 months. None of the T-cell markers showed a correlation with OS, DFS or LRC. A low N stage was correlated to a better prognosis (OS: HR 0.39, p = 0.0028, DFS: HR 0.34, p =  < 0.001, LRC: HR 0.24, p = 0.008). High TIL counts were more often observed in PD-L1-positive tumors (p < 0.05).

Conclusion
This study showed an objective, digital pathology-aided method to assess TILs in the tumor epithelium. However, it did not provide evidence for a prognostic role of the presence of CD3 + , CD4 + , CD8 + , FoxP3 + , and PD1 + TILs in the tumor epithelium of advanced stage, HPV-negative HNSCC patients treated with primary chemoradiotherapy.
First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors
Authors: Ishihara Mikiya , Tono Yasutaka , Miyahara Yoshihiro , Muraoka Daisuke , Harada Naozumi , Kageyama Shinichi , Sasaki Takeshi , Hori Yasuhide , Soga Norihito , Uchida Katsunori , Shiraishi Taizo , Sato Eiichi , Kanda Hideki , Mizuno Toshiro , Webster Gill A. , Ikeda Hiroaki , Katayama Naoyuki , Sugimura Yoshiki , Shiku Hiroshi 
Published: January 2020

AbstractCholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (μg/μg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4–5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.
FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction
Authors: Veith Christine , Neghabian Dariusch , Luitel Himal , Wilhelm Jochen , Egemnazarov Bakytbek , Muntanjohl Caja , Fischer Jan-Hendrik , Dahal Bhola Kumar , Schermuly Ralph Theo , Ghofrani Hossein Ardeschir , Grimminger Friedrich , Fink Ludger , Kwapiszewska Grazyna , Weissmann Norbert , Sydykov Akylbek 
Published: January 2020

Abstract
Aims
The cytoskeletal signaling protein four and-a-half LIM domains 1 (FHL-1) has recently been identified as a novel key player in pulmonary hypertension as well as in left heart diseases. In this regard, FHL-1 has been implicated in dysregulated hypertrophic signaling in pulmonary arterial smooth muscle cells leading to pulmonary hypertension. In mice, FHL-1-deficiency (FHL-1−/−) led to an attenuated hypertrophic signaling associated with a blunted hypertrophic response of the pressure-overloaded left ventricle (LV). However, the role of FHL-1 in right heart hypertrophy has not yet been addressed.

Methods and results
We investigated FHL-1 expression in C57Bl/6 mice subjected to chronic biomechanical stress and found it to be enhanced in the right ventricle (RV). Next, we subjected FHL-1−/− and corresponding wild-type mice to pressure overload of the RV by pulmonary arterial banding for various time points. However, in contrast to the previously published study in LV-pressure overload, which was confirmed here, RV hypertrophy and hypertrophic signaling was not diminished in FHL-1−/− mice. In detail, right ventricular pressure overload led to hypertrophy, dilatation and fibrosis of the RV from both FHL-1−/− and wild-type mice. RV remodeling was associated with impaired RV function as evidenced by reduced tricuspid annular plane systolic excursion. Additionally, PAB induced upregulation of natriuretic peptides and slight downregulation of phospholamban and ryanodine receptor 2 in the RV. However, there was no difference between genotypes in the degree of expression change.

Conclusion
FHL-1 pathway is not involved in the control of adverse remodeling in the pressure overloaded RV.
Murine sca1/flk1-positive cells are not endothelial progenitor cells, but B2 lymphocytes
Authors: Steffen Eva , Mayer von Wittgenstein Wolfgang Bernd Edziu , Hennig Marie , Niepmann Sven Thomas , Zietzer Andreas , Werner Nikos , Rassaf Tienush , Nickenig Georg , Wassmann Sven , Zimmer Sebastian , Steinmetz Martin 
Published: January 2020

AbstractCirculating sca1+/flk1+ cells are hypothesized to be endothelial progenitor cells (EPCs) in mice that contribute to atheroprotection by replacing dysfunctional endothelial cells. Decreased numbers of circulating sca1+/flk1+ cells correlate with increased atherosclerotic lesions and impaired reendothelialization upon electric injury of the common carotid artery. However, legitimate doubts remain about the identity of the putative EPCs and their contribution to endothelial restoration. Hence, our study aimed to establish a phenotype for sca1+/flk1+ cells to gain a better understanding of their role in atherosclerotic disease. In wild-type mice, sca1+/flk1+ cells were mobilized into the peripheral circulation by granulocyte-colony stimulating factor (G-CSF) treatment and this movement correlated with improved endothelial regeneration upon carotid artery injury. Multicolor flow cytometry analysis revealed that sca1+/flk1+ cells predominantly co-expressed surface markers of conventional B cells (B2 cells). In RAG2-deficient mice and upon B2 cell depletion, sca1+/flk1+ cells were fully depleted. In the absence of monocytes, sca1+/flk1+ cell levels were unchanged. A PCR array focused on cell surface markers and next-generation sequencing (NGS) of purified sca1+/flk1+ cells confirmed their phenotype to be predominantly that of B cells. Finally, the depletion of B2 cells, including sca1+/flk1+ cells, in G-CSF-treated wild-type mice partly abolished the endothelial regenerating effect of G-CSF, indicating an atheroprotective role for sca1+/flk1+ B2 cells. In summary, we characterized sca1+/flk1+ cells as a subset of predominantly B2 cells, which are apparently involved in endothelial regeneration.
The single-suture technique for anterior cruciate ligament graft preparation provides similar stability as a three-suture technique: a biomechanical in vitro study in a porcine model
Authors: Theopold Jan , Schleifenbaum Stefan , Georgi Alexander , Schmidt Michael , Henkelmann Ralf , Osterhoff Georg , Hepp Pierre 
Published: January 2020

Abstract
Purpose
Numerous techniques have been described for the tibial-sided graft preparation in anterior cruciate ligament (ACL) reconstruction. The use of less suture material for graft preparation is thought to improve ingrowth and to reduce the risk for infection. At the same time, the suture construct should be strong enough to resist the surgeon’s pull during tensioning of the transplant.

Methods
In total, 39 fresh-frozen procine deep flexor tendons were used and prepared as four-strand grafts. In the three-suture group (n = 19), graft preparation was performed using three tibial-sided sutures, with each tendon end sutured separately. In the one-suture group (n = 20), a modified graft preparation using only one tibial-sided suture was applied. Each sample underwent load-to-failure testing (Nmax) after cyclic pre-loading. To estimate intraoperative tension forces acting on the tibial-sided suture constructs, the maximal tension force of 26 volunteers on such a construct was measured using a load cell.

Results
The biomechanical testing of the two different suture constructs showed a significantly higher load-to-failure for the three-suture group (711 N ± 91 N) compared to the one-suture group (347 N ± 24 N) (p = 0.0001). In both groups, the mode of failure was a tear of the suture in all samples. A failure of the suture–tendon interface was not observed in any case. The median maximal tension force on the construct applied by the 26 volunteers was 134 N (range 73–182 N).

Conclusion
The presented single-suture tendon graft preparation resisted to smaller failure loads than the conventional three-suture technique. However, no failures in the suture–tendon interface were seen and the failure loads observed were far beyond the tension forces that can be expected intraoperatively. Hence, the single-suture graft preparation technique may be a valuable alternative to the conventional technique.
Effect of voice therapy with or without transcutaneous electrical stimulation on recovery of injured macroscopically intact recurrent laryngeal nerve after thyroid surgery
Authors: Formánek Martin , Walderová Radana , Baníková Šárka , Chmelová Irina , Formánková Debora , Zeleník Karol , Komínek Pavel 
Published: January 2020

AbstractPurposeElectrical stimulation-supported therapy is an often used modality. However, it still belongs to experimental methods in the human larynx. Data are lacking with which to evaluate the real effect in recurrent laryngeal nerve injury. The aim of this study was to investigate whether transcutaneous electrical stimulation added to voice therapy has a beneficial effect compared to voice therapy alone on vocal fold movement recovery in the case of an injured macroscopically intact recurrent laryngeal nerve.MethodsAdults with unilateral vocal fold paralysis after thyroidectomy, in which the recurrent laryngeal nerve was left macroscopically intact, were included in this case–control study performed in tertiary referral hospital between September 2006 and June 2018. Among 175 eligible participants, 158 were included. Compliance with 6 months follow-up was 94.3%. Interventions: medicament therapy and voice therapy (group 1) vs. medicament therapy and voice therapy and transcutaneous electrical stimulation (group 2). Main outcome: vocal fold movement.ResultsA total of 149 patients were included in the analysis (group 1, 89 patients; group 2, 60 patients). The groups were homogenous. In groups 1 and 2, 64% and 60% of vocal folds, respectively, were improved after 6 months (P = 0.617). No difference was found between patients who improved and patients who did not improve.ConclusionsAdding transcutaneous electrical stimulation to voice therapy provided no beneficial effect on the recovery of vocal fold movement. Therefore, its indications should be re-evaluated; it is questionable whether stimulation should be routinely recommended.
Tolerability of facial electrostimulation in healthy adults and patients with facial synkinesis
Authors: Volk Gerd Fabian , Thielker Jovanna , Möller Martin Christian , Majcher Daniela , Mastryukova Valeria , Altmann Carolin Susann , Dobel Christian , Guntinas-Lichius Orlando 
Published: January 2020

Abstract
Purpose
To evaluate optimal stimulation parameters with regard to discomfort and tolerability for transcutaneous electrostimulation of facial muscles in healthy participants and patients with postparetic facial synkinesis.

Methods
Two prospective studies were performed. First, single pulse monophasic stimulation with rectangular pulses was compared to triangular pulses in 48 healthy controls. Second, 30 healthy controls were compared to 30 patients with postparetic facial synkinesis with rectangular pulse form. Motor twitch threshold, tolerability threshold, and discomfort were assessed using a numeric rating scale at both thresholds.

Results
Discomfort at motor threshold was significantly lower for rectangular than for triangular pulses. Average motor and tolerability thresholds were higher for patients than for healthy participants. Discomfort at motor threshold was significantly lower for healthy controls compared to patients. Major side effects were not seen.

Conclusions
Surface electrostimulation for selective functional and tolerable facial muscle contractions in patients with postparetic facial synkinesis is feasible.
Hippocampal subfield and amygdala nuclei volumes in schizophrenia patients with a history of violence
Authors: Tesli Natalia , van der Meer Dennis , Rokicki Jaroslav , Storvestre Guttorm , Røsæg Cato , Jensen Arvid , Hjell Gabriela , Bell Christina , Fischer-Vieler Thomas , Tesli Martin , Andreassen Ole A. , Melle Ingrid , Agartz Ingrid , Haukvik Unn K. 
Published: January 2020

AbstractSchizophrenia (SCZ) is associated with an increased risk of violence compared to the general population. Previous studies have indicated smaller hippocampal and amygdala volumes in violent than non-violent psychotic patients. However, little is known about volumetric differences at the subdivision level of these structures. In the present study, hippocampal subfields and amygdala nuclei volumes were estimated with FreeSurfer from 3 T MRI of SCZ patients with (SCZ-V, n = 24) and without (SCZ-NV, n = 51) a history of severe violence and 90 healthy controls (HC). Volumetric differences between groups were explored with a general linear model covarying for confounders, in addition to follow-up analyses in patient groups controlling for clinical characteristics such as antipsychotic medication, duration of illness and illicit substance use. SCZ-V had smaller total hippocampal volume and smaller CA1, HATA, fimbria, and molecular layer of DG volumes compared to HC. Total amygdala volume together with basal nucleus, accessory basal nucleus, CTA, and paralaminar nucleus volumes were smaller in SCZ-V compared to HC. In SCZ-NV, compared to HC, the observed smaller volumes were limited to basal and paralaminar nucleus. There were no significant differences in hippocampal subfield and amygdala nuclei volumes between SCZ-V and SCZ-NV. Follow-up analyses showed that the results in patient groups were not affected by clinical characteristics. The results suggest that smaller hippocampal subfield and amygdala nuclei volumes may be relevant to violence risk in SCZ. However, the neurobiological signature of violence in SCZ should be further investigated in larger cohorts.
Microalbuminuria: a sentinel of neurocognitive impairment in HIV-infected individuals?
Authors:   The ALCOVE Study Group, Moulignier Antoine , Viret-Vilayphon Anne-Claire , Lescure François-Xavier , Plaisier Emmanuelle , Salomon Laurence , Lamirel Cédric , Pialoux Gilles 
Published: January 2020

Abstract
Background
According to population-based studies, microalbuminuria is associated with subsequent cognitive decline over a 4–6-year period, because of cerebral small-vessel disease (CSVD). This prospective cross-sectional study (NCT02852772) was designed to evaluate whether a history of microalbuminuria is associated with subsequent cognitive decline in combined antiretroviral therapy (cART)-treated persons living with human immunodeficiency virus (PLHIVs).

Methods
From our computerized medical database, we identified 30 PLHIVs (median age 52 years), immunovirologically controlled on cART, who had microalbuminuria in 2008 and had undergone, between 2013 and 2015, a comprehensive neuropsychological assessment (NPA) including seven domains (cases): information-processing speed, motor skills, executive functions, attention/working memory, learning/memory, reasoning and verbal fluency. Forty-nine PLHIVs matched for age (median age 48 years; p = 0.19), sex, and year of first HIV-seropositivity without microalbuminuria in 2008 were identified and underwent the same NPA between 2013 and 2015 (controls).

Results
Cases performed less well than controls for information-processing speed (p = 0.01) and motor skills (p = 0.02), but no differences were found for the other cognitive domains and global z-scores. A multivariable linear-regression model adjusted for confounding factors confirmed the microalbuminuria effect for the information-processing-speed z score.

Conclusion
cART-treated PLHIVs with a history of microalbuminuria subsequently had worse cognitive performances for the information-processing-speed domain, possibly because of CSVD. Our observations should be considered preliminary findings of a temporal link between microalbuminuria, CSVD, and subsequent cognitive impairment.
Staged implant placement after defect regeneration using biphasic calcium phosphate materials with different surface topographies in a minipig model
Authors: Mihatovic I. , Schwarz F. , Obreja K. , Becker J. , Sader R. , Dard M. , John G. 
Published: January 2020

Abstract
Objective
To assess the influence of biphasic calcium phosphate materials with different surface topographies on bone formation and osseointegration of titanium implants in standardized alveolar ridge defects.

Materials and methods
Standardized alveolar ridge defects (6 × 6 mm) were created in the mandible of 8 minipigs and filled with three biphasic calcium phosphate materials (BCP1–3, 90% tricalcium phosphate/10% hydroxyapatite) with different surface properties (micro- and macroporosities) as well as a bovine-derived natural bone mineral (NBM) as a control. At 12 weeks, implants were placed into the augmented defects. After further 8 weeks of healing, dissected blocks were processed for histological analysis (e.g., mineralized (MT), residual bone graft material (BS), bone-to-implant contact (BIC)).

Results
All four biomaterials showed well-integrated graft particles and new bone formation within the defect area. MT values were comparable in all groups. BS values were highest in the NBM group (21.25 ± 13.52%) and markedly reduced in the different BCP groups, reaching statistical significance at BCP1-treated sites (9.2 ± 3.28%). All test and control groups investigated revealed comparable and statistically not significant different BIC values, ranging from 73.38 ± 20.5% (BCP2) to 84.11 ± 7.84% (BCP1), respectively.

Conclusion
All bone graft materials facilitated new bone formation and osseointegration after 12 + 8 weeks of healing.