bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma
Authors: Glutsch Valerie , Kneitz Hermann , Gesierich Anja , Goebeler Matthias , Haferkamp Sebastian , Becker Jürgen C. , Ugurel Selma , Schilling Bastian 
Published: January 2021

Abstract
Background
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cutaneous malignancy with poor prognosis. In Europe, approved systemic therapies are limited to the PD-L1 inhibitor avelumab. For avelumab-refractory patients, efficient and safe treatment options are lacking.

Methods
At three different sites in Germany, clinical and molecular data of patients with metastatic MCC being refractory to the PD-L1 inhibitor avelumab and who were later on treated with combined IPI/NIVO were retrospectively collected and evaluated.

Results
Five patients treated at three different academic sites in Germany were enrolled. Three out of five patients investigated for this report responded to combined IPI/NIVO according to RECIST 1.1. Combined immunotherapy was well tolerated without any grade II or III immune-related adverse events. Two out of three responders to IPI/NIVO received platinum-based chemotherapy in between avelumab and combined immunotherapy.

Conclusion
In this small retrospective study, we observed a high response rate and durable responses to subsequent combined immunotherapy with IPI/NIVO in avelumab-refractory metastatic MCC patients. In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC.
Influence of the Cu substitution on magnetic properties of Ni–Mn–Sn–B shape memory ribbons
Authors: Kirat G. , Aksan M. A. 
Published: January 2021

AbstractThe Heusler alloy Ni50-xCuxMn38Sn12 + By (x = 0, 1, 3 and 5) was successfully produced in ribbon form using melt spinning technique. The magnetic properties of the obtained ribbons were analyzed in detail. In all ribbons, it was detected that the ferromagnetic austenite phase transformed into the weak magnetic martensite phase. A separation between FC and ZFC curves at lower temperatures was found. An increase in the magnetization in FC mode can be attributed to the coexistence of ferromagnetic (FM)/antiferromagnetic (AFM) at martensitic phase. It was found that the transition temperatures shifted to low temperatures with increasing the Cu content. The magnetization results under high magnetic field (10 kOe and 50 kOe) showed a thermal hysteresis between the cooling and heating cycles, which is clear evidence for a first-order transformation in the ribbons. From M–H data, all the ribbons exhibited ferromagnetic behavior at low temperatures below the martensitic transition temperature and paramagnetic behavior at high temperatures above the transition temperature. The results provide us a comprehensive view to reveal the effect of the Cu substitution on the magnetic properties of Ni–Mn-based shape memory ribbons.
The use of Lactobacillus casei DG® prevents symptomatic episodes and reduces the antibiotic use in patients affected by chronic bacterial prostatitis: results from a phase IV study
Authors: Cai Tommaso , Gallelli Luca , Cione Erika , Perletti Gianpaolo , Ciarleglio Francesco , Malossini Gianni , De Pretis Giovanni , Palmieri Alessandro , Mirone Vincenzo , Bartoletti Riccardo , Johansen Truls E. Bjerklund 
Published: January 2021

Abstract
Purpose
To evaluate the efficacy of Lactobacillus paracasei CNCM I-1572 (L. casei DG®) in both prevention of symptomatic recurrences and improvement of quality of life in patients with chronic bacterial prostatitis (CBP).

Methods
Patients with CBP attending a single Urological Institution were enrolled in this phase IV study. At enrollment, all patients were treated with antibiotics in agreement with EAU guidelines and then were treated with L. casei DG® (2 capsules/day for 3 months). Clinical and microbiological analyses were carried out before (enrollment, T0) and 6 months (T2) after the treatment. Both safety and adherence to the treatment were evaluated 3 months (T1) after the enrollment. NIH Chronic Prostatitis Symptom Index (CPSI), International Prostate Symptom Score (IPSS) and Quality of Well-Being (QoL) questionnaires were used. The outcome measures were the rate of symptomatic recurrence, changes in questionnaire symptom scores and the reduction of antibiotic use.

Results
Eighty-four patients were included. At T2, 61 patients (72.6%) reported a clinical improvement of symptoms with a return to their clinical status before symptoms. A time dependent improvement in clinical symptoms with significant changes in NIH-CPSI, IPSS and QoL (mean difference T2 vs T0: 16.5 ± 3.58; − 11.0 ± 4.32; + 0.3 ± 0.09; p < 0.001), was reported. We recorded that L. casei DG® treatment induced a statistically significant decrease in both (p < 0.001) symptomatic recurrence [1.9/3 months vs 0.5/3 months] and antibiotic use [− 7938 UDD]. No clinically relevant adverse effects were reported.

Conclusions
L. casei DG® prevents symptomatic recurrences and improves the quality of life in patients with CBP, reducing the antibiotic use.
Limitation of current probe design for oligo-cross-FISH, exemplified by chromosome evolution studies in duckweeds
Authors: Hoang Phuong T. N. , Rouillard Jean-Marie , Macas Jiří , Kubalová Ivona , Schubert Veit , Schubert Ingo 
Published: January 2021

AbstractDuckweeds represent a small, free-floating aquatic family (Lemnaceae) of the monocot order Alismatales with the fastest growth rate among flowering plants. They comprise five genera (Spirodela, Landoltia, Lemna, Wolffiella, and Wolffia) varying in genome size and chromosome number. Spirodela polyrhiza had the first sequenced duckweed genome. Cytogenetic maps are available for both species of the genus Spirodela (S. polyrhiza and S. intermedia). However, elucidation of chromosome homeology and evolutionary chromosome rearrangements by cross-FISH using Spirodela BAC probes to species of other duckweed genera has not been successful so far. We investigated the potential of chromosome-specific oligo-FISH probes to address these topics. We designed oligo-FISH probes specific for one S. intermedia and one S. polyrhiza chromosome (Fig. 1a). Our results show that these oligo-probes cross-hybridize with the homeologous regions of the other congeneric species, but are not suitable to uncover chromosomal homeology across duckweeds genera. This is most likely due to too low sequence similarity between the investigated genera and/or too low probe density on the target genomes. Finally, we suggest genus-specific design of oligo-probes to elucidate chromosome evolution across duckweed genera.
Decreased inflammatory cytokine production of antigen-specific CD4+ T cells in NMDA receptor encephalitis
Authors: Dao Le-Minh , Machule Marie-Luise , Bacher Petra , Hoffmann Julius , Ly Lam-Thanh , Wegner Florian , Scheffold Alexander , Prüss Harald 
Published: January 2021

AbstractAnti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is the most common autoimmune encephalitis with psychosis, amnesia, seizures and dyskinesias. The disease is mediated by pathogenic autoantibodies against the NR1 subunit that disrupt NMDAR function. Antibody infusion into mouse brains can recapitulate encephalitis symptoms, while active immunization resulted also in strong T cell infiltration into the hippocampus. However, whether T cells react against NMDAR and their specific contribution to disease development are poorly understood. Here we characterized the ex vivo frequency and phenotype of circulating CD4+ T helper (TH) cells reactive to NR1 protein using antigen-reactive T cell enrichment (ARTE) in 24 patients with NMDAR encephalitis, 13 patients with LGI1 encephalitis and 51 matched controls. Unexpectedly, patients with NMDAR encephalitis had lower frequencies of CD154-expressing NR1-reactive TH cells than healthy controls and produced significantly less inflammatory cytokines. No difference was seen in T cells reactive to the synaptic target LGI1 (Leucine-rich glioma-inactivated 1), ubiquitous Candida antigens or neoantigens, suggesting that the findings are disease-specific and not related to therapeutic immunosuppression. Also, patients with LGI1 encephalitis showed unaltered numbers of LGI1 antigen-reactive T cells. The data reveal disease-specific functional alterations of circulating NMDAR-reactive TH cells in patients with NMDAR encephalitis and challenge the idea that increased pro-inflammatory NMDAR-reactive T cells contribute to disease pathogenesis.
NF-κB, iNOS, IL-6, and collagen 1 and 5 expression in healthy and keratoconus corneal fibroblasts after 0.1% riboflavin UV-A illumination
Authors: Berger Tim , Szentmáry Nóra , Latta Lorenz , Seitz Berthold , Stachon Tanja 
Published: January 2021

Abstract
Purpose
To analyze the effect of riboflavin UV-A illumination on mRNA and protein expression of healthy (HCFs) and keratoconus human corneal fibroblasts (KC-HCFs), concerning the inflammatory markers NF-κB, iNOS, IL-6, and collagen 1 and 5 (Col 1/Col 5).

Methods
Keratocytes were isolated from healthy (n = 3) and keratoconus (KC) corneas (n = 3) and were cultivated in basal medium with 5% fetal calf serum, which resulted in their transformation into human corneal fibroblasts (HCFs/KC-HCFs). Cells underwent 0.1% riboflavin UV-A illumination for 250 s (CXL). NF-κB, iNOS, IL-6, Col 1, and Col 5 expression was investigated by qPCR and Western blot analysis. IL-6 concentration of the cell culture supernatant and cell lysate was determined by ELISA.

Results
In untreated KC-HCFs, NF-κB (p = 0.0002), iNOS (p = 0.0019), Col 1 (p = 0.0286), and Col 5 (p = 0.0054) mRNA expression was higher and IL-6 expression was lower (p = 0.0057), than in healthy controls. In HCFs, CXL led to an increased NF-κB (p = 0.0286) and IL-6 (p = 0.0057) mRNA expression. The IL-6 concentration in the cell culture supernatant was increased in HCFs (p = 0.0485) and KC-HCFs (p = 0.0485) after CXL. CXL increased intracellular IL-6 concentration only in KC-HCFs (p = 0.0357). In the HCF group (p = 0.0286), an increased Col 1 mRNA expression after CXL could be observed.

Conclusion
Our study confirmed altered gene expression in untreated KC-HCFs compared to untreated HCFs. Riboflavin UV-A illumination affected gene expression only in HCFs. Increased IL-6 concentration in the cell culture supernatant and cell lysate indicate a secondary inflammatory response of HCFs and KC-HCFs to riboflavin UV-A illumination.
Performing newborn life support in advance of neonatal advanced life support course—back to basics?
Authors: Hundscheid Tim , Bruinenberg Jos , Dudink Jeroen , de Jonge Rogier , Hogeveen Marije 
Published: January 2021

AbstractIn this retrospective analysis, the Newborn Life Support (NLS) test scenario performance of participants of the Dutch Neonatal Advanced Life Support (NALS) course was assessed. Characteristics of participants and total amount of failures were collected. Failures were subdivided in (1) errors of omission; (2) errors of commission; and (3) unspecified if data was missing. Pearson’s chi-squared test was used to assess differences between participant groups. In total, 23 out of 86 participants (27%) failed their NLS test scenario. Life support course instructors in general (20/21) passed their test scenario more often compared to other participants (43/65) (p = 0.008). In total 110 fail items were recorded; the most common errors being not assessing heart rate (error of omission) (n = 47) and inadequate performance of airway management (error of commission) (n = 24).Conclusion: A substantial part of NALS participants failed their NLS test scenario. Errors of omission could be reduced by the availability of a checklist/NLS algorithm. Life support course instructors possibly make less errors of commission due to retention of skills by teaching these skills at least twice a year. Therefore, our study suggests that neonatal basic life support skills should be retained by local assurance of training programmes.

What is Known:• Retention of skills after life support courses decreases after three months.• Adherence to newborn life support guidelines is suboptimal.

What is New:• NLS performance is suboptimal in participants for advanced neonatal life support.• Most common failures are not assessing heart rate and inadequate airway management.
Combination of mesenchymal stromal cells and machine perfusion is a novel strategy for organ preservation in solid organ transplantation
Authors: Zhao Lingfei , Hu Chenxia , Han Fei , Chen Dajin , Ma Yanhong , Cai Fanghao , Chen Jianghua 
Published: January 2021

AbstractOrgan preservation is a prerequisite for an urgent increase in the availability of organs for solid organ transplantation (SOT). An increasing amount of expanded criteria donor (ECD) organs are used clinically. Currently, the paradigm of organ preservation is shifting from simple reduction of cellular metabolic activity to maximal simulation of an ex vivo physiological microenvironment. An ideal organ preservation technique should not only preserve isolated organs but also offer the possibility of rehabilitation and evaluation of organ function prior to transplantation. Based on the fact that mesenchymal stromal cells (MSCs) possess strong regeneration properties, the combination of MSCs with machine perfusion (MP) is expected to be superior to conventional preservation methods. In recent years, several studies have attempted to use this strategy for SOT showing promising outcomes. With better organ function during ex vivo preservation and the potential of utilization of organs previously deemed untransplantable, this strategy is meaningful for patients with organ failure to help overcome organ shortage in the field of SOT.
What is the recommended procedure for recurrent rectal prolapse? A retrospective cohort study in a single Japanese institution
Authors: Funahashi Kimihiko , Kurihara Akiharu , Miura Yasuyuki , Ushigome Mitsunori , Kaneko Tomoaki , Kagami Satoru , Yoshino Yu , Koda Takamaru , Nagashima Yasuo , Yoshida Kimihiko , Sakai Yu 
Published: January 2021

Abstract
Purpose
The choice of surgical procedure for rectal prolapse (RP) is challenging because of the high recurrence and morbidity rates. We aimed to clarify whether laparoscopic suture rectopexy (lap-rectopexy) is suitable for Japanese patients with recurrent RP.

Methods
We retrospectively evaluated 77 recurrent RP patients who had been treated on average 1.5 times between June 2008 and April 2016. Forty-one patients underwent lap-rectopexy and 36 underwent perineal procedures. We compared surgical outcomes and recurrence rate following surgery between the two groups. The multivariable logistic regression analysis was performed to determine risk factors of recurrent RP.

Results
In patients’ characteristics, significant differences were observed in the type of anesthesia (p < 0.01) and length of recurrent RP (p = 0.030). The mean operative time was significantly longer in the lap-rectopexy group (p < 0.001). Blood loss, length of hospitalization, and postoperative complications were similar. The recurrence rate was significantly lower in the lap-rectopexy group (17.1% vs. 38.9%, p = 0.032). Multivariate analysis showed that only the laparoscopic approach was significantly associated with a low recurrence following surgery (odds ratio 0.273, 95% CI − 2.568 to − 0.032).

Conclusion
Lap-rectopexy is recommended for recurrent RP because its low recurrence rate and safety profile are similar to those of perineal procedures.
Promise and challenges of dystonia brain banking: establishing a human tissue repository for studies of X-Linked Dystonia-Parkinsonism
Authors: Fernandez-Cerado Cara , Legarda G. Paul , Velasco-Andrada M. Salvie , Aguil Abegail , Ganza-Bautista Niecy G. , Lagarde J. Benedict B. , Soria Jasmin , Jamora Roland Dominic G. , Acuña Patrick J. , Vanderburg Charles , Sapp Ellen , DiFiglia Marian , Murcar Micaela G. , Campion Lindsey , Ozelius Laurie J. , Alessi Amy K. , Singh-Bains Malvindar K. , Waldvogel Henry J. , Faull Richard L. M. , Macalintal-Canlas Regina , Muñoz Edwin L. , Penney Ellen B. , Ang Mark A. , Diesta Cid Czarina E. , Bragg D. Cristopher , Acuña-Sunshine Geraldine 
Published: January 2021

AbstractX-Linked Dystonia-Parkinsonism (XDP) is a neurodegenerative disease affecting individuals with ancestry to the island of Panay in the Philippines. In recent years there has been considerable progress at elucidating the genetic basis of XDP and candidate disease mechanisms in patient-derived cellular models, but the neural substrates that give rise to XDP in vivo are still poorly understood. Previous studies of limited XDP postmortem brain samples have reported a selective dropout of medium spiny neurons within the striatum, although neuroimaging of XDP patients has detected additional abnormalities in multiple brain regions beyond the basal ganglia. Given the need to fully define the CNS structures that are affected in this disease, we created a brain bank in Panay to serve as a tissue resource for detailed studies of XDP-related neuropathology. Here we describe this platform, from donor recruitment and consent to tissue collection, processing, and storage, that was assembled within a predominantly rural region of the Philippines with limited access to medical and laboratory facilities. Thirty-six brains from XDP individuals have been collected over an initial 4 years period. Tissue quality was assessed based on histologic staining of cortex, RNA integrity scores, detection of neuronal transcripts in situ by fluorescent hybridization chain reaction, and western blotting of neuronal and glial proteins. The results indicate that this pipeline preserves tissue integrity to an extent compatible with a range of morphologic, molecular, and biochemical analyses. Thus the algorithms that we developed for working in rural communities may serve as a guide for establishing similar brain banks for other rare diseases in indigenous populations.
Can the intermittent low-speed function of left ventricular assist device prevent aortic insufficiency?
Authors: Kohno Hiroki , Matsumiya Goro , Sawa Yoshiki , Fukushima Norihide , Saiki Yoshikatsu , Shiose Akira , Ono Minoru 
Published: January 2021

AbstractAortic insufficiency (AI) is known to associate with a persistently closed aortic valve during continuous-flow ventricular assist device support. Some devices carry an intermittent low-speed (ILS) function, which facilitates aortic valve opening, but whether this function prevents AI is unknown. In this study, the Jarvik 2000 device, which is programmed to reduce the pump speed each minute for 8 s, was chosen to examine this potential effect. Prospectively collected data of 85 heart transplant-eligible Jarvik 2000 recipients who met the study criteria (no pre-existing AI and aortic valve surgery) were retrospectively analyzed for the incidence, correlating factors, and clinical outcomes of de novo AI. All data were provided by the Japanese Registry for Mechanically Assisted Circulatory Support. De novo AI occurred in 58 patients, 23 of whom developed at least moderate AI during a median support duration of 23.5 months. Freedom from moderate or greater AI was 84.4%, 66.1% and 60.2% at 1, 2 and 3 years, respectively. Multivariate analyses revealed that progressive AI was correlated with decreased pulse pressure after implantation (hazard ratio 1.060, 95% confidence interval 1.001–1.127, p = 0.045). No correlation was found for mortality or other adverse events, including stroke, bleeding, infection, pump failure, hemolysis, and readmission. The benefit of the Jarvik 2000′s current ILS mode against AI appears to be minimal. However, in this limited cohort where all recipients underwent implantation as a bridge to transplantation, the impact of de novo progressive AI on other clinical adversities was also minimal.
Language-independent look-ahead for checking multi-perspective declarative process models
Authors: Käppel Martin , Ackermann Lars , Schönig Stefan , Jablonski Stefan 
Published: January 2021

AbstractDeclarative process modelling languages focus on describing a process by restrictions over the behaviour, which must be satisfied throughout the whole process execution. Hence, they are well suited for modelling knowledge-intensive processes with many decision points. However, such models can be hard to read and understand, which affect the modelling and maintenance of the process models tremendously as well as their execution. When executing such declarative (multi-perspective) process models, it may happen that the execution of activities or the change of data values may result in the non-executability of crucial activities. Hence, it would be beneficial to know all consequences of decisions to give recommendations to the process participants. A look-ahead attempts to predict the effects of executing an activity towards possible consequences within an a priori defined time window. The prediction is based on the current state of the process execution, the intended next event and the underlying process model. While execution engines for single-perspective imperative process models already implement such functionality, execution approaches, for multi-perspective declarative process models that involve constraints on data and resources, are less mature. In this paper, we introduce a simulation-based look-ahead approach for multi-perspective declarative process models. This approach transforms the problem of a context-aware process simulation into a SAT problem, by translating a declarative multi-perspective process model and the current state of a process execution into a specification of the logic language Alloy. Via a SAT solver, process trajectories are generated that either satisfy or violate this specification. The simulated process trajectories are used to derive consequences and effects of certain decisions at any time of process execution. We evaluate our approach by means of three examples and give some advice for further optimizations.
Improving Numerical Dispersion Modelling in Built Environments with Data Assimilation Using the Iterative Ensemble Kalman Smoother
Authors: Defforge Cécile L. , Carissimo Bertrand , Bocquet Marc , Bresson Raphaël , Armand Patrick 
Published: January 2021

AbstractAir-pollution modelling at the local scale requires accurate meteorological inputs such as from the velocity field. These meteorological fields are generally simulated with microscale models (here Code_Saturne), which are forced with boundary conditions provided by larger scale models or observations. Local atmospheric simulations are very sensitive to the boundary conditions, whose accurate estimation is difficult but crucial. When observations of the wind speed and turbulence or pollutant concentration are available inside the domain, they provide supplementary information via data assimilation, to enhance the simulation accuracy by modifying the boundary conditions. Among the existing data assimilation methods, the iterative ensemble Kalman smoother (IEnKS) is adapted to urban-scale simulations. This method has already been found to increase the accuracy of wind-resource assessment. Here we assess the ability of the IEnKS method to improve scalar-dispersion modelling—an important component of air-quality modelling—by assimilating perturbed measurements inside the urban canopy. To test the data assimilation method in urban conditions, we use the observations provided by the Mock Urban Setting Test field campaign and consider cases with neutral and stable conditions, and the boundary conditions consisting of the horizontal velocity components and turbulence. We prove the capacity of the IEnKS method to assimilate observations of velocity as well as pollutant concentration. In both cases, the accuracy of pollutant concentration estimates is enhanced by 40–60%. We also show that assimilating both types of observations allows further improvements of turbulence predictions by the model.